Aiims May 2015 Qa

AIIMS Q&A MAY 2015 By Dr Manish B Mandal Copyright 2015 Dr Manish B Mandal Smashwords Edition

AIIMS MAY 2015 Q&A

BY –Dr Manish B Mandal,MO(BHEL),ExHCMS-2,Ex-Resident AIIMS,SJH.NEWDELHI

1)Muscle not inserted on greater tuberosity a) Teres minor b) Supraspinatus c) Infraspinatus d) Subscapularis D The supraspinatus, infraspinatus, teres minor and subscapularis muscles comprise the rotator cuff muscle group. The main role of these muscles is stabilization of the humeral head in the glenoid fossa. Tendons of teres minor, supraspinatus, and infraspinatus insert on the greater tuberosity of the humerus, and subscapularis tendon inserts on lesser humeral tuberosity. Actions of these muscles are internal rotation (subscapularis), external rotation (teres minor and 7 infraspinatus) and early abduction from 0˚ to 30˚ (supraspinatus) . The subacromial bursa lies between supraspinatus tendon and the acromion.

http://morphopedics.wikidot.com/supraspinatus-tendinitis 2) Card test done for a) Lumbricals b) Palmar interossei c) Dorsal interossei d) Adductor pollicis B

Ulnar Nerve (C7,8,T1) injury : • M.C. site - Medial epicondyle, or a little more distally where the nerve enters the forearm b/w the two heads of flexor carpi ulnaris • Causes: - # of medial condyle - During anesthesia • S/S: - Radial deviation of wrist on flexion - Claw-hand deformity - Paresthesia and sensory loss on hand Page 21 21 A- Egawa’s Test – Dorsal Interossei B- Card Test – Palmer interossei C- Book Test - Adductor pollicis (Froment,s sign)

Page 22 22 :Median nerve (C5,6,7,8,T1) injury: • CAUSES - Crutch compression - Sleep paralysis - Penetrating trauma - Shoulder dislocation • S/S: - Atrophy of the thenar eminence - Simian or ape hand (d/t opponens pollicis) - Benediction hand Page 23 23 - Paresis of forearm pronation - Paresis of distal flexion of the thumb - Paresis of radial wrist flexion - Impaired opposition of the thumb - Paresis of flexion of the second and to a lesser extent, the third fingers Pen Test – For Abductor pollicis brevis http://www.aiimsnets.org/NeurosurgeryEducation/NeurosurgicalSpecialties/Peripheralnerve/Ner ve%20Injuries%20Diagnosis,%20Evaluation%20And%20Management_new/Nerve%20Injuries %20Diagnosis,%20Evaluation%20And%20Management.pdf

3) Which nerve doesn’t have a general visceral efferent a) Olfactory b) Facial c) Oculomotor d) Glossopharyngeal A It is possible to describe a cranial nerve in terms of its function and embryological origin, initially cranial nerves can be subdivided into being either: • •

Motor (efferent) Sensory (afferent)

And from there further categorization can occur. --------------------------------------------------------------------------------------------------Motor (efferent) Cranial nerves -Somatic motor (general somatic efferent) (III, IV, VI, XII) These cranial nerves are so called because they innervate muscles derived from the occipital somites, such as the extra ocular and extrinsic tongue muscles. -Branchial motor (special visceral efferent) (V, VII, IX, X, XI) These are described as branchial because they specifically innervate muscles which are derived from the branchial arches during development (muscles of mastication, larynx, facial expression, pharynx and middle ear) - Parasympatheic (general visceral efferent) (III, VII, IX, X) These nuclei do not innervate striated muscle like the branchial and somatic, they instead provide preganglionic parasympathetic fibers to innervate glands, smooth muscle and cardiac muscle within the head, heart, lungs and digestive tract above the splenic flexure. --------------------------------------------------------------------------------------------------Sensory (afferent) cranial nerves -Visceral sensory special visceral afferent- (VII, IX, X) general visceral afferent- (IX, X) The name is related to the fact that it detects sensation from visceral organs. They are divided into special visceral, referring to the rostral portion of the nucleus which contributes to the special sensation of taste. Whilst the general visceral portion is named as such due to this caudal portion receiving general sensory impulses such as cardiac, respiratory and GI inputs. - General somatic sensory (general somatic afferent) (V, VII, IX, X) These nuclei detect general sensation, such as touch, pain, vibration from the face, sinuses and meninges - Special somatic sensory (special somatic) (VIII) This carries information from the special sensation of hearing and balance.

http://www.fastbleep.com/medical-notes/neuro-and-psych/2/95/610 4) Cranial nerve nucleus lying beneath the facial colliculus is a) Facial b) Abducent c) Glossopharyngeal

d) Trigeminal B The abducent nucleus: This nucleus lies in the lower part of the pons, deep to the facial colliculus in the floor of the fourth ventricle. It is situated in the grey matter lining the floor of the fourth ventricle near the midline. The abducent nucleus is a motor nucleus and sends its attached nerve to supply the lateral rectus muscle. https://www.kenhub.com/en/library/anatomy/cranial-nerve-nuclei

Overview of the Brainstem

The brainstem consists (from superior to inferior) of the midbrain, pons and the medulla oblongata. The midbrain is continuous, above, with the cerebral hemispheres. The medulla is continuous, below, with the spinal cord. Posteriorly, the pons and medulla are separated from the cerebellum by the 4th ventricle. The brainstem has a ventral aspect (anterior surface) and a dorsal or posterior surface.

Posterior surface The posterior surface of the brainstem is formed by: •

the fasciculus gracilis (tracts from the posterior funiculus of the spinal cord) which

ends superiorly as a rounded elevation called gracile tubercle •

the fasciculus cuneatus (also tracts from the posterior funiculus of the spinal cord) which ends superiorly as a rounded elevation called cuneate tubercle These fasciculi and tubercles are at the lower half of the posterior surface of the medulla – thus the lowest portion of the brainstem (posteriorly).

At the midbrain level, the posterior surface of the brainstem is marked by four rounded swellings called the superior and inferior colliculi, with one pair (a superior- and an inferior colliculus) on each side of the midline, as well as a connecting ridge called the brachium. Most of the remaining part of the posterior surface of the brainstem, which includes the posterior surfaces of pons and the superior half of the medulla, is formed by the floor of the 4th ventricle. The 4th ventricle is continuous, below, with the central canal, which traverses the lower part of the medulla, and becomes continuous with the central canal of the spinal cord. Cranially, the 4th ventricle is continuous with the cerebral aqueduct (of Sylvius), which passes through the midbrain to connect the 3rd ventricle [which is a median cavity into which, the 1st and 2nd (lateral) ventricles open, through the interventricular foramen (of Monro). The fourth ventricle also has a tent-shaped roof, cavity and lateral walls. However, the floor is the most related part to the cranial nerve nuclei. The floor of the fourth ventricle, often called the rhomboid fossa because of its shape, is divisible into an upper triangular part formed by the posterior surface of the pons; a lower triangular part formed by the upper part of the posterior surface of the medulla; and an intermediate part at the junction of the pons and medulla. The intermediate part is prolonged laterally over the inferior cerebellar peduncle as the floor of the lateral recess. Its surface is marked by the presence of delicate bundles of transeversely running fibres. Those bundles are the striae medullares. The entire floor is divided into right and left halves by a median sulcus. Next to the middle line, there is a longitudinal elevation called the medial eminence. The eminence is bounded laterally by the sulcus limitans. The region lateral to the sulcus limitans is the vestibular area which overlies the vestibular nuclei (cranial nerve nuclei responsible for hearing and balance). The vestibular area lies partly in the pons and partly in the medulla. The pontine part of the floor shows some features of interest in close relation to the sulcus limitans and the median eminence. The uppermost part of the sulcus limitans overlies an area that is bluish in color and this area is called the locus coeruleus. Somewhat lower down, the sulcus limitans is marked by a depression, the superior fovea. At this level, the medial eminence shows a swelling, the facial colliculus. The medullary part of the floor also shows some features of interest in relation to the medial eminence and the sulcus limitans. The sulcus limitans is marked by a depression, theinferior fovea. Descending from the fovea, there is a sulcus that runs obliquely towards the middle line. That sulcus divides the medial eminence into two triangles – the hypoglossal trigone (which houses the cranial nerve nuclei called hypoglossal nuclei), medially; and thevagal trigone (housing the vagal nuclei), laterally. Between the vagal trigone, superiorly and the gracile tubercle, inferiorly, there is a small area called the area postrema. The lowest part of the floor of the fourth ventricle is called the calamus scriptorius, because of its resemblance to a nib. Each inferolateral margin of the ventricle is marked by a narrow

white ridge or taenia. The right and left taeniae meet at the inferior angle of the floor to form a small fold called the obex.

Ventral surface The anterior surface of the brainstem is mainly marked by the left and right crus cerebri at the midbrain, the middle cerebellar peduncle at the level of the pons, and rounded elevations called olive and pyramid at the level of the medulla. Within the brainstem, there is a remarkable number of tracts and grey matter. Along the entire length of the brainstem, there are areas not occupied by well-defined nuclei or nerve fibres, but consisted of a network of fibres within which scattered neurons are situated. Those areas are referred to as “the reticular formation of the brainstem”. These areas mainly occupy the dorsal part of the midbrain, pons and medulla. Such areas (reticular formation) are found at all levels of the central nervous system, and are functionally very important. At the level of the midbrain and medulla, there is a grey matter region called central grey matter which surrounds the cerebral aqueduct and gives origin to some cranial nerve nuclei including the mesencephalic nucleus of the trigeminal nerve. Most of the cranial nerve nuclei that migrated from their original position (in relation to the floor of fourth ventricle) during embryonic development are situated in this grey matter region (central grey matter).

Introduction The cranial nerve nuclei are aggregate of cells (collection of cell bodies). Attached to these cell bodies are fibres called cranial nerves (bundles of axons). These nuclei are either sensoryor motor but never both. However, cranial nerves can be sensory, motor or mixed nerves(when they have both sensory and motor functions). The cranial nerve motor nuclei are further grouped according to their targets, that is, where their axons (attached cranial nerves) are sent or structures they innervate. Hence the cranial nerve nuclei with motor functions can be grouped according to the following functional components to which their fibres belong: •

General Somatic Efferents (GSE)

•

Special Visceral Efferents (SVE)

•

General Visceral Efferents (GVE)

Similarly, the cranial nerve sensory nuclei are grouped according to the information they receive, which constitutes the functional components to which their attached nerves belong. These functional components are: •

General Somatic Afferents (GSA)

•

Special Somatic Afferents (SSA)

•

General Visceral Afferents (GVA)

•

Special Visceral Afferents (SVA)

The first cranial nerve (olfactory nerve – CN I) does not originate from a cranial nerve nucleus. CN 1 originates from the olfactory bulb, which is a structure located in the forebrain and controls olfaction. The second cranial nerve (optic nerve – CN II) originates from the lateral geniculate nucleus [(lateral geniculate body or lateral geniculate complex) – which is a relay centre in the thalamus for the visual pathway], the pulvinar, and the superior colliculus [the pulvinar and superior colliculus are also part of the primary visual centres, and from those three structures, fibres (CN II) connect the ganglionic cells of the retina to coordinate and interpret visual impulses]. In the brainstem, there are about 18 cranial nerve nuclei comprising of 10 motor cranial nerve nuclei and 8 sensory cranial nerve nuclei. The functions of those cranial nerves are suggestive of the functions of the parts of the brainstem they are located. For example, the midbrain is involved in eye movement control and houses the oculomotor and trochlear nuclei which also have these functions. The pons control breathing, signal relay, and contains the trigeminal, abducens and facial nuclei. In summary therefore, cranial nerve nuclei are either motor (efferent) or sensory (afferent), and both category can be somatic or visceral.

Development During embryonic development, the cranial nerve nuclei related to the various components – GSE, SVE, GVE, GSA, SSA, GVA and SVA, are arranged in vertical rows called columns in a definitive sequence in the grey matter related to the floor of the fourth ventricle. Each half (along the median sulcus) of the floor of the fourth ventricle is divided into a medial part called the basal lamina, and a lateral part called the alar lamina by the sulcus limitans. The Efferent nuclei (motor nuclei) lie in the medial part, while the Afferent nuclei (sensory nuclei) lie in the lateral part – alar lamina. In both the medial and lateral parts, the visceral nuclei [special visceral (branchial) effernt, general visceral efferent, general visceral afferent, and special visceral afferent] lie nearer to the sulcus limitans than the somatic nuclei [GSE, GSA, and SSA]. Therefore, from the midline (median sulcus of the fourth ventricle) to the lateral aspects, the sequence of nuclear column is: 1. GSE - lying closest to the median sulcus 2. SVE - lying next to the GSE 3. GVE - lying farthest from the median sulcus but next to the sulcus limitans All of the above listed three nuclear columns are in the medial part (basal lamina) of the floor of the 4th ventricle. On the other side of the sulcus limitans – that is the lateral part (alar lamina), the sequence is:

1. GVA - lying next to the sulcus limitans 2. SVA - lying next to GVA, laterally 3. GSA - lying next to the SVA and finally 4. SSA - lying farthest away from the sulcus limitans, laterally As development continues, parts of those columns disappear from their position in relation to the floor of the fourth ventricle, so that each of the no longer extends the whole length of the brainstem, but is represented by one or more discrete nuclei. Some nuclei retain their original positions in relation to the floor of the fourth ventricle, but some others migrate deeper into the brainstem. In the descriptions that follows, the cranial nerve nuclei originating from each of these columns, as well as their definitive positions in the brainstem are outlined.

Gross Anatomy General Somatic Efferent (Motor) Nuclei The general somatic efferent column consists of the following nuclei that supply striated (skeletal) muscles of somatic origin.

1. The oculomotor nucleus: This nucleus is located in the upper part of the midbrain at the level of the superior colliculus. The oculomotor nuclei (left and right sides) form a single complex that lies in the central grey matter, ventral to the cerebral aqueduct (of Sylvius). The oculomotor nucleus sends fibres (oculomotor nerve) to supply thesuperior, medial and inferior rectus, inferior oblique and levator palpebrae superioris muscles.

2. The trochlear nucleus: The trochlear nucleus is located in the lower part of the midbrain at the level of the inferior colliculus. The nucleus lies anterior to the cerebral aqueduct in the central grey matter. Since the trochlear nucleus is a motor nucleus, it sends fibres to innervate the superior oblique muscle.

3. The abducent nucleus: This nucleus lies in the lower part of the pons, deep to the facial colliculus in the floor of the fourth ventricle. It is situated in the grey matter lining the floor of the fourth ventricle near the midline. The abducent nucleus is a motor nucleus and sends its attached nerve to supply the lateral rectus muscle.

4. The hypoglossal nucleus: The hypoglossal nucleus is situated near the midline and below the hypoglossal trigone (or triangle) in the floor of the fourth ventricle of the upper medulla. It is an elongated column extending into both the open and closed parts of the medulla. Fibres from this nucleus are motor, and they innervate the muscles of the tongue.

Special Visceral Efferent (Motor) Nuclei These nuclei are also called Branchial Efferent or Branchiomotor nuclei. They supply striated (skeletal) muscles derived from the branchial arches.

1. The motor nucleus of the trigeminal nerve: This cranial nucleus lies in the upper part of the pons, in the pons' dorsal part. It is situated in the lateral part of the reticular formation, medial to the main sensory nucleus of the trigeminal nerve. The motor nucleus of trigeminal nerve innervates the mastication muscles, mylohyoid muscle and tensor palati.

2. The nucleus of the facial nerve: This nucleus lies in the lower part of the pons, deep and lateral to the facial colliculus, and occupies a position similar to that of the motor nucleus of the trigeminal nerve, because the spinal nucleus and tract of the trigeminal nerve lie lateral to it, as seen in figure 8 above. The facial nerve nucleus sends its nerve to the lacrimal gland for lacrimal secretion and salivary secretion.

3. The nucleus ambiguus: The nucleus ambiguus lies in the medulla. It forms an elongated collumn lying deep in the reticular formation, both in the open and closed parts of the medulla. Inferiorly, it is continuous with the spinal accessory nucleus. The nucleus ambiguus is a composite nucleus and contributes fibres to the glossopharyngeal, vagusand accessory nerves.

General Visceral Efferent (Motor) Nuclei The nuclei of this column gives origin to preganglionic fibres that contribute to the cranial parasympathetic outflow. These fibres end in peripheral ganglia. Postganglionic fibres arising in those ganglia (peripheral ganglia) supply the smooth muscles and glands. The nuclei from the GVE are as follows:

1. The Edinger-Westphal nucleus (Accessory Oculomotor nucleus): This nucleus lies in the midbrain. It is closely related to the oculomotor complex. Fibres arising in this nucleus pass through the oculomotor nerve, and relay in the ciliary ganglion to supply the sphincter pupillae and the ciliaris muscle (see the “Visual Pathway”).

2. The Salivary (salivatory) nuclei: The superior and inferior salivary nuclei lie in the dorsal part of the pons, just above its junction with the medulla. They are located a little above the upper end of the dorsal nucleus of the vagus nerve. The superior salivatory nucleus sends fibres into the facial nerve and these fibres relay in the submandibular ganglion to supply the submandibular and sublingual salivary glands. The inferior salivary nucleus sends fibres into the glossopharyngeal nerve. Those fibres relay in the otic ganglion to supply the parotid gland. The parotid gland may also receive some fibres from the superior salivatory nucleus, through the submandibular ganglion.

3. The dorsal or motor nucleus of the vagus nerve (dorsal vagal nucleus): This cranial nerve nucleus is long and it lies vertically in the medulla. Its upper end lies deep to the vagal

trigone in the floor of the fourth ventricle. When traced backwards, it extends into the closed part of the medulla where it lies in the lateral part of the central grey matter. Fibres arising fom this nucleus supply the heart, lungs, bronchi, oesophagus,stomach, small intestine and large intestine up to the right two-thirds of the transverse colon. Those fibres end in ganglion (nerve plexuses) closely related to those organs – heart, lungs, stomach, etc.

General and Special Visceral Afferent (Sensory) Nuclei The general and special visceral afferent collumns are represented by:

1. The nucleus of theSOLITARY tract 2. The commissural nucleus of vagus 3. The gustatory nucleus The nucleus of theSOLITARY tract is present in the medulla. Its cells (nucleus ofSOLITARY tract) form an elongated column lying deep in the reticular formation. The upper part of the nucleus of theSOLITARY tract lies ventrolateral to the dorsal nucleus of the vagus (dorsal vagal nucleus). When traced backwards, it extends into the closed part of the medulla. There it lies dorsomedial to the vagal nucleus. The lower ends of the nuclei of the two sides fuse to form the commissural nucleus of the vagus. The nucleus solitarius receives fibres carrying general visceral sensations through the vagus and glossopharyngeal nerves. Through those afferents, and through connections with the reticular formation, the nucleus of solitary tract plays an important role in reflex control of respiratory and cardiovascular functions. Fibres of taste – special visceral afferent, carried by facial, glossopharyngeal and vagus nerves end in the upper part of the nucleus of the solitary tract. This upper part of the nucleus is referred to as the gustatory nucleus.

General Somatic Afferent (Sensory) Nuclei These nuclei give rise to the following sensory nuclei:

1. The main or superior sensory nucleus: This nucleus lies in the upper part of the pons, in the lateral part of the reticular formation. It lies lateral to the motor nucleus of the trigeminal. The superior sensory nucleus is mainly concerned in mediation of proprioceptive impulses, touch and pressure.

2. The spinal nucleus: The spinal nucleus is another sensory cranial nerve nucleus which extends from the main nucleus (superior sensory nucleus) in the pons down into the medulla, and into the upper two segments of the spinal cord. The lower end of the spinal nucleus is continuous with the substantia gelatinosa of the spinal cord. The spinal nucleus receives general somatic sensations carried by the facial, glossopharyngeal and vagus nerves. Functions of the spinal nucleus includes mediation of pain and thermal sensibility. The spinal nucleus is divisible (craniocaudally) into three sub-nuclei, theoralis, interpolaris, and caudalis.

3. The mesencephalic nucleus: This is also called the mesencephalic nucleus of the trigeminal nerve. It extends cranially from the upper end of the main sensory nucleus in the pons into the midbrain. In the midbrain, the mesencephalic nucleus lies in the central grey matter lateral to the aqueduct. Functionally, this nucleus appears to be similar to sensory ganglia of the cranial nerves, and to the spinal ganglia, rather than to afferent nuclei. The processes (dendrites) of the neurons of this nucleus are believed to carry proprioceptive impulses from muscles of mastication, and possibly also from muscles of the eyeballs, face, tongue and teeth. The mesencephalic nucleus is the centre for jaw jerk.

Special Somatic Afferent (Sensory) Nuclei This column gives rise to: 1. The cochlear nucleus 2. The vestibular nucleus There are two cochlear nuclei – dorsal and ventral cochlear nucleus. They are respectively positioned dorsal and anterior to the inferior cerebellar peduncle at the level of the junction between the pons and medulla. The two nuclei are continuous with each other, being separated only by a layer of nerve fibres. The vestibular nucleus lies in the grey matter underlying the lateral part of the floor of the fourth ventricle. The vestibular nucleus is situated partly in the medulla and partly in the pons. Four distinct nuclei of the vestibular nucleus are recognized. These nuclei are themedial, lateral, inferior and superior vestibular nuclei. The lateral nucleus is also called theDeiter's nucleus.

Connections Of Some Cranial Nerve Nuclei Column of motor nucleus of the trigeminal nerve, nucleus of the facial nerve, nucleus ambiguus, and oculomotor, trochear, abducent, hypoglossal nuclei The nuclei of the GSE and SVE connect with the skeletal muscles, to which they send their nerves. Those nuclei (GSE and SVE) receive sensory fibres through which they also make connections with the cerebral cortex, the tectum (connections of vision and of hearing), vestibular nuclei (vestibular impulses), sensory cranial nuclei, the red nucleus and the reticular formation. Connections of the cochlear nuclei The dorsal and ventral cochlear nuclei are major parts of the partway of hearing. They receive fibres connecting them with the spiral ganglion and sends their attached fibres, some of which relay in the trapezoid body, before reaching the nucleus of trapezoid body and the superior olivary nucleus. Connections of the vestibular nuclei

The vestibular nuclei are connected to the cerebellum to which they send and receive fibres. These nuclei also have connections with the spinal cord, through fibres, mainly, originating in the medial vestibular nucleus. These fibres descend in the fasciculus. Connections of the nucleus of theSOLITARY tract The nucleus of theSOLITARY tract receives fibres from the sensory ganglia of the seventh, ninth, and tenth cranial nerves, and mainly send fibres to the hypothalamus (solitario-hypothalamic tract), the thalamus and cerebral cortex. Connections of the sensory nuclei of the trigeminal nerve The main sensory nucleus of the trigeminal nerve and the spinal nucleus of trigeminal nerve, both receive fibres, through which, they connect with the trigeminal ganglion. These nuclei (main sensory and spinal nucleus) send fibres to the thalamus and cerebral cortex.

Clinical Aspects Brain Death The combined developments of ventilatory machines and transplantation surgery have underlined the need for defining the criteria for making a correct diagnosis of brain death – the irreversible cessation of brainstem function. In comatose patients with irremediable structural brain damage due to a disorder that can lead to brain death, brainstem reflexes must be shown to be absent in order to establish brain death. The following are the criteria (anatomical basis) normally adopted: •

Fixed pupils, not reacting to light – testing midbrain function

•

No corneal reflexes – testing pontine connections between trigeminal and facial nerve

nuclei •

No vestibulo-ocular reflexes – testing the connections between the vestibular nerve

and eye muscle nerves •

No gag reflex or response to bronchial stimulation by a catheter passed down the trachea – testing vagal connections in the medulla •

No motor responses in any cranial nerves on adequate nociceptive stimulation of any

somatic area – testing for facial grimacing from pressure on the supraorbital margins (connections between trigeminal and facial nerve nuclei) or on the bases of fingernails (connections between cervical spinal cord and facial nerve nuclei)

5) Mesorectal fascia doesn’t contain which of the following

a) Inferior rectal vein b) Pararectal node c) Superior rectal vein A The mesorectum is an important surgical and radiological structure. It contains the superior rectal artery and vein, and numerous lymphatics as well as rectal branches of the inferior hypogastric plexus. It is bounded by the mesorectal fascia, a distinct layer which separates the rectal fat from other pelvic fat. http://ozradonc.wikidot.com/anatomy:rectum 6) Which of these is not a support of the uterus a) Urogenital diaphragm b) Pelvic diaphragm c) Perineal body d) Rectovaginal septum D 7) Reticular framework is present in all tissues except a) Thymus b) Bone marrow c) Spleen d) Lymph node A Ref= The Anatomical Record > Vol 190 Issue 3 > Abstract

• • •

Electron microscopy of the normal human thymus demonstrates a supporting framework of epithelial-reticular cells with long branching cytoplasmic processes joined by desmosomes. In the interstices of the epithelial-reticular cell processes lie lymphocytes, macrophages, and rare myoid cells. Both small and large lymphocytes are evident. No desmosomes are observed between the lymphocytes and the epithelial-reticular cells. Macrophages are most numerous in the cortex where they often contain phagocytized nuclear debris. The possible functional significance of the above-described fine structural features is discussed.

http://onlinelibrary.wiley.com/doi/10.1002/ar.1091900310/abstract 8) What is the stage present in the oogonia at birth a) Telophase I b) Prophase I B •

A wave of proliferation begins that lasts from the 15th week to the 7th

month: primary germ cells arise in the cortical zone via mitosis of oogonia clones, bound together in cellular bridges, that happens in rapid succession. The cell bridges are necessary for a synchronous onset of the subsequent meiosis.

•

With the onset of the meiosis (earliest onset in the prophase in the 12th week) the designation of the germ cells changes. They are now called primary oocytes. The primary oocytes become arrested in the diplotene stage of prophase I (the prophase of the first meiotic division). Shortly before birth, all the fetal oocytes in the female ovary have attained this stage. The meiotic resting phase that then begins is called the dictyotene and it lasts till puberty, during which each month (and in each month thereafter until menopause) a pair of primary oocytes complete the first meiosis. Only a few oocytes (secondary oocytes plus one polar body), though, reach the second meiosis and the subsequent ovulation. The remaining oocytes that mature each month become atretic. The primary oocytes that remain in the ovaries can stay in the dictyotene stage up to menopause, in the extreme case, without ever maturing during a menstrual cycle.

•

While the oogonia transform into primary oocytes, they become restructured so that at the end of prophase I (the time of the dictyotene) each one gets enveloped by a single layer of flat, follicular epithelial cells (descendents of the coelomic epithelium). (oocyte + follicular epithelium = primordial follicle).

http://www.embryology.ch/anglais/cgametogen/oogenese01.html 9) At which stage of maturation of the spermatocyte the assortment of maternal and paternal chromosomes takes place a) Spermatogonia to primary spermatocyte b) Primary to secondary spermatocyte c) Secondary spermatocyte to spermatids d) Spermatids to spermatozoa B 10) Not a branch of external carotid artery a) Transverse cervical A. b) Lingual A. c) Superior thyroid A. d) Ascending pharyngeal A. A 11) All are derived from Mesonephros except a) Glomerulus b) Paraoopharan c) Vas deferans d) Epididymis

A The urogenital system arises during the fourth week of development from urogenital ridges in the intermediate mesoderm on each side of the primitive aorta. The nephrogenic ridgeis the part of the urogenital ridge that forms the urinary system. Three sets of kidneys develop sequentially in the embryo: The pronephros is rudimentary and nonfunctional, and regresses completely. The mesonephros is functional for only a short period of time, and remains as the mesonephric (Wolffian) duct. The metanephros remains as the permanent adult kidney. It develops from the uteric bud, an outgrowth of the mesonephric duct, and the metanephric mesoderm, derived from the caudal part of the nephrogenic ridge. Urine excreted into the amniotic cavity by the fetus forms a major component of the amniotic fluid. Urine formation begins towards the end of the first trimester (weeks 11 to 12) and continues throughout fetal life. The kidneys develop in the pelvis and ascend during development to their adult anatomical location at T12-L3. This normally happens by the ninth week. Table 12 - Adult Derivatives of Embryonic Kidney Structures Embryonic Structure Adult Derivative Ureteric bud (metanephric Ureter diverticulum) Renal pelvis Major and minor calyces Collecting tubules Metanephric mesoderm Renal glomerulus + capillaries Bowman’s capsule Proximal convoluted tubule Loop of Henle Distal convoluted tubule Urinary Bladder

The urinary bladder develops from the upper end of the urogenital sinus, which is continuous with the allantois. It is lined with endoderm. The lower ends of the metanephric ducts are incorporated into the wall of the urogenital sinus and form the trigone of the bladder. The connective tissue and smooth muscle surrounding the bladder are derived from adjacent splanchnic mesoderm. The allantois degenerates and remains in the adult as a fibrous cord called the urachus (median umbilical ligament). http://www.med.umich.edu/lrc/coursepages/m1/embryology/embryo/11urinarysyste m.htm

12) Microvilli are not present in a) Duodenum b) Gall bladder c) PCT

d) Collecting duct D 13) In the following picture, wave B represents – [PICTURE] EEG shows high amplitude, low frequency waves as compared to waves A & C and EOG & EMG are nearly flat when compared to A. In C also they are flat. a) REM b) NREM c) Quiet wakefulness d) Awake

B EEG shows high amplitude, low frequency waves as compared to waves A & C and EOG & EMG are nearly flat when compared to A. In C also they are flat.

14) In the following diagram left ventricular pressure is nearly equal to diastolic BP at which number [PICTURE] a) A b) B c) C d) D (PIC NOT AVAILABLE) 15) If the interstitial hydrostatic pressure is 2 mm Hg, interstitial oncotic pressure is 7 mmHg and capillary hydrostatic pressure is 25mmHg, what should be the capillary oncotic pressure to allow a net filtration pressure of 3 mm Hg

a) 21 b) 27 B GFR If we disregard any oncotic pressure in the Bowman's capsule, we have in effect, three pressures to consider: glomerular hydrostatic pressure, glomerular oncotic pressure, and Bowman's capsule hydrostatic pressure. These can be expressed as a formula that will tell us the amount of hydrostatic pressure pushing fluid out of the glomerulus: Net glomerular pressure equals: Glomerular hydrostatic pressure minus [glomerular concotic pressure + Bowman's capsule hydrostatic pressure] In order to measure the glomerular filtration rate, we must add to this measurement an estimation of glomerular permeability, and surface area – that is, how many functioning nephrons are available in the body for filtration, and how effectively the glomeruli filter fluid. A normal glomerular filtration rate is around 125mls/min, and this measurement is used to determine, and to classify, kidney function.

http://www.nottingham.ac.uk/nmp/sonet/rlos/bioproc/gfr/6.html Net Filtration Pressure (NFP): NFP = HPg - (OPg + HPc) Glomerular Hydrostatic Pressure: (HPg) is essentially glomerular blood pressure (55 mm Hg) Filtration Opposing Forces: Colloid Osmotic Pressure (OPg) of glomerular blood (28 - 30 mm Hg) Capsular Hydrostatic Pressure (HPc) (15 mm Hg) NFP = 55 - (30+15) NFP = 10 mm Hg Glomerular Filtration Rate - the amount of filtrate formed per minute by the kidneys. There are generally three factors involved in the GFR: Page 2 1. total surface area for filtration 2. filtration membrane permeability 3. net filtration pressure Normal GFR for an adult is 120 - 125 ml/ min. Note a drop in glomerular pressure of 15% will stop filtration altogether. Note also that GFR is directly proportional to the net filtration rate. The GFR must be precisely regulated or many substances normally resorbed will be lost in the urine, OR wastes that should be expelled may be resorbed. There are three mechanisms that help to keep the GFR relatively constant: 1. Renal Autoregulation (intrinsic controls) 2. Neural controls 3. Renin-angiotensin system Renal Autoregulation - the kidney can maintain a relatively constant GFR regardless of fluctuations in systemic blood pressure. This is done by regulating the diameter of the afferent and efferent arterioles. This is done in one of two ways: 1. myogenic mechanisms - responds to changes in the pressure in the renal

vessels. 2. tubuloglomerular feedback mechanism - senses changes in the juxtaglomerular apparatus. Using the macula densa cells: these cells release a vasoconstrictor if the GFR is too high or permit vasodilation of afferent arterioles if the filtration rate is too low. This system can work in the range of 80 to 180 mm Hg. It cannot handle low systemic pressures. Below 45 mm Hg filtration stops. Neural Control - Sympathetic control. When the sympathetic nervous system is at rest renal vessels are maximally dilated. Sympathetic stimulation causes constriction of afferent arterioles thus decreasing filtration rate. This stimulation causes release of epinephrine from the adrenal medulla. The epinephrine in turn acts on alpha receptors on vascular smooth muscle. This indirectly starts the renin-angiotensin mechanism by stimulating macula densa cells. The sympathetic nervous system also directly stimulates the Juxtaglomerular cells (by binding NE to beta adrenergic receptors) to release renin, which begins the reninangiotensin mechanism. Renin-Angiotensin mechanism - begins when juxtaglomerular cells release renin. Renin acts on angiotensinogen (plasma protein made in the liver) to release angiotensin I which is then converted to angiotensin II by angiotensin converting enzyme. Resorption in the kidneys is active (requires ATP) or passive depending on the substance to be resorbed. Page 3 Sodium ions are the single most abundant cations in the filtrate. Sodium ion resorption is always active. Obligatory water reabsorption: sodium movement establishes a strong osmotic gradient, and water moves by osmosis into the peritubular capillaries. Here the water is “obliged” to follow the salt. As water leaves the tubules, the relative concentration of the substances still present in the filtrate increases dramatically and, if able, they will begin to follow their concentration gradients into the tubule cell. This is called Solvent Drag. Some substances are not resorbed or are resorbed incompletely. This happens because: 1. they lack carriers 2. they are not lipid soluble 3. they are too large to pass through the plasma membrane pores of the tubule cells. The most important of these substances are the nitrogenous end products of protein and nucleic acid metabolism: urea, creatinine, and uric acid. Absorptive capabilities of various regions of the renal tubules Proximal convoluted tubule: is the most active region for reabsorption All glucose , lactate, and amino acids 65 - 70% of Na+ (linked to cotransport of other solutes or Na+-H+ exchange) 65 - 70% of water 90% of bicarbonate 50% of chloride >90% of potassium Almost all uric acid is reabsorbed in the PCT but later is returned to the filtrate.

Of the 125 ml/min of fluid filtered at the glomerulus, only about 40 ml/min remains after the PCT. Loop of Henle Descending limb: Water moves out freely, K+ moves back in. Ascending limb: Na+, K+, Cl- move out, water cannot leave the ascending limb. Distal Convoulted Tubule: Page 4 Na+ and Cl- reabsorbed if needed by the body. This is under hormonal control. If needed almost ALL of the water and Na+ reaching this area can be reclaimed. Na+ resorption is under the control of Aldosterone from the adrenal cortex. When aldosterone is present almost no Na+ leaves the body via the urine. In addition the reninangiotensin mechanism stimulates the release of aldosterone. Aldosterone also promotes water reabsorption because water follows the Na+. ADH also plays a role here. Atrial Natriuretic Peptide: (ANP) is a hormone released from the atrial cardiac cells when blood volume and/or blood pressure is elevated. ANP inhibits Na+ absorption by closing Na+ channels. This reduces water reabsorption and therefore blood volume. Tubular Secretion: is essentially reabsorption in reverse. We see tubular secretion in the PCT, DCT and cortical collecting ducts, but not in the loop of Henle. This is important for: 1. disposing of substances that are not already in the filtrate (drugs) 2. eleminating undesirable substances such as urea and uric acid 3. getting rid of excess K+ 4. controlling blood pH Osmolality: the number of solute particles dissolved in one liter of water. This is reflected in the solutions ability to cause osmosis. The kidneys have the important job of keeping the body fluids at a constant 300 mosm (milliosmoles). This is done by using a countercurrent exchange system. Some common terms that apply to urinary physiology: Acidosis: A condition in which the pH of the blood is below 7.35 Alkalosis: A condition in which the pH of the blood is higher than 7.45 Compensation: the physiological response to an acid/base imbalance that acts to normalize the pH of arterial blood. Complete compensation: results if the arterial pH is brought to within normal limits Partial compensation: is only partially corrected but does not fall within the normal range Page 5 If a person has an altered blood pH due to metabolic causes, hyper/hypoventilation may bring the pH back into the normal range. This would be known as respiratory compensation. If a person has an altered blood pH due to respiratory causes then they must use renal

compensation to try to return to normal limits. Renal compensation works by changing the secretion of H+ and reabsorption of HCO3- by the kidneys. Metabolic acidosis/alkalosis results from changes in HCO3 - concentrations in the blood. The normal range for HCO3 - is 22 – 26 mEq/liter. Metabolic acidosis is defined as the arterial blood HCO3 - level dropping below 22 mEq/liter. This could result from actual loss of HCO3 - as may be seen with severe diarrhea or renal disease, or an accumulation of an acid other than HCO3 -, or failure of the kidneys to excrete H+. If this problem is not too severe we can use respiratory compensation (through hyperventilation) to bring the blood pH back into the normal range. Metabolic alkalosis is defined as an arterial blood HCO3 - level above 26 mEq/liter. A loss of acid or excessive intake of alkaline drugs can cause the blood pH to rise above 7.45. The most frequent cause is excessive vomiting which results in a substantial loss of HCl. Hypoventilation may provide respiratory compensation. There are basically 4 steps in diagnosing acid/base imbalances: 1. determine whether the pH is high (alkalosis) or low (acidosis). 2. determine which value (PCO2 or HCO3 -) is out of range 3. If the cause is a change in PCO2 the problem is respiratory. If the cause is HCO3 -, the problem is metabolic. 4. NOW, look at the value that doesn’t correspond with the observed pH change. If it is within its normal range there is no compensation occurring. If it is outside its normal range compensation is occurring and partially correct the problem. The partial pressure of carbon dioxide is the single most important indicator of respiratory function. When respiratory function is normal PCO2 ranges from 35 - 45 mm Hg. Respiratory acidosis and alkalosis are both disorders resulting form changes in the partial pressure of CO2 (PCO2) Values of PCO2 above 45 mm Hg indicate respiratory acidosis Values of PCO2 below 35 mm Hg indicate respiratory alkalosis Page 6 Respiratory acidosis is defined as an abnormally high PCO2 in arterial blood. Inadequate exhalation of CO2 causes the blood pH to drop. Respiratory acidosis can result from slow breathing or hampered gas exchange (pneumonia, cystic fibrosis, emphysema). Here CO2 accumulates in the blood. This causes a falling blood pH and rising PCO2. The kidneys may provide renal compensation by increasing the excretion of H+ and the reabsorption of HCO3 -.

The goal in treating respiratory acidosis is to increase the blow off (exhalation) of CO2. Respiratory alkalosis is defined as an abnormally low PCO2 in the arterial blood.. The cause of this condition is hyperventilation and CO2 is eliminated from the body faster than it is produced.. Hyperventilation may be caused by several factors such as oxygen deficiency due to high altitude, stroke, or sever anxiety. Renal compensation may bring the blood pH into the normal range if the kidneys are able to decrease the excretion of H+ and reabsorption of HCO3 -. Note that, unlike respiratory acidosis, respiratory alkalosis this is rarely caused by pathology,. • • •

h ttp://faculty.etsu.edu/forsman/UrinaryPhysiology.pdf

16) Physiological changes in laparoscopy include all except a) Increased ?PCWP b) Increased ICP c) Decreased FRC d) Increased pH D Summary of Haemodyanamic Changes due to Mechanical pressure of C02 insufflation Increased systemic vascular resistance (SVR) Increased Mean Arterial pressure (MAP) Minimal change in heart rate (HR) Increased cerebral blood flow (CBF) Increased intracranial pressure (ICP) Decreased renal blood flow (RBF) Decreased portal blood flow Decreased splanchnic blood flow Decreased pulmonary compliance C02 absorption Significant hypercapnia and acidosis may occur duringlaparoscopy due to C02 absorption. Hypercapnia may cause a decrease in myocardial contractility and lower arrhythmia threshold. The anticipated direct vascular effect ofhypercapnia, producing arteriolar dilation and decreased SVR,is modulated by mechanical and neurohumoral responses, including catecholamine release

http://iages.in/pdf/c_67_70.pdf 17) A 50 % increase in radius of vessel will cause rise in blood flow by a) 10 times b) 20 times c) 5 times d) 100 times C There are three primary factors that determine the resistance to blood flow within a single vessel: vessel diameter (or radius), vessel length, and viscosity of the blood. Of these three factors, the most important quantitatively and physiologically is vessel diameter. The reason for this is that vessel diameter changes because of contraction and relaxation of the vascular smooth muscle in the

wall of the blood vessel. Furthermore, as described below, very small changes in vessel diameter lead to large changes in resistance. Vessel length does not change significantly and blood viscosity normally stays within a small range (except when hematocrit changes). Vessel resistance (R) is directly proportional to the length (L) of the vessel and the viscosity (η) of the blood, and inversely proportional to the radius to the fourth power (r4). Because changes in diameter and radius are directly proportional to each other (D = 2r; therefore D∝r), diameter can be substituted for radius in the following expression.

Therefore, a vessel having twice the length of another vessel (and each having the same radius) will have twice the resistance to flow. Similarly, if the viscosity of the blood increases 2-fold, the resistance to flow will increase 2-fold. In contrast, an increase in radius will reduce resistance. Furthermore, the change in radius alters resistance to the fourth power of the change in radius. For example, a 2-fold increase in radius decreases resistance by 16-fold! Therefore, vessel resistance is exquisitely sensitive to changes in radius.

The relationship between flow and vessel radius to the fourth power (assuming constant ΔP, L, η and laminar flow conditions) is illustrated in the figure to the right. This figure shows how very small decreases in radius dramatically reduces flow. Vessel length does not change appreciably in vivo and, therefore, can generally be considered as a constant. Blood viscosity normally does not change very much; however, it can be significantly altered by changes in hematocrit, temperature, and by low flow states. If the above expression for resistance is combined with the equation describing the relationship between flow, pressure and resistance (F=ΔP/R), then

This relationship (Poiseuille's equation) was first described by the 19th century French physician Poiseuille. It is a description of how flow is related to perfusion pressure, radius, length, and viscosity. The full equation contains a constant of integration and pi, which are not included in the above proportionality. In the body, however, flow does not conform exactly to this relationship because this relationship assumes long, straight tubes (blood vessels), a Newtonian fluid (e.g., water, not blood which is non-

Newtonian), and steady, laminar flowconditions. Nevertheless, the relationship clearly shows the dominant influence of vessel radius on resistance and flow and therefore serves as an important concept to understand how physiological (e.g., vascular tone) and pathological (e.g., vascular stenosis) changes in vessel radius affect pressure and flow, and how changes in heart valve orifice size (e.g., in valvular stenosis) affect flow and pressure gradients across heart valves. Although the above discussion is directed toward blood vessels, the factors that determine resistance across a heart valve are the same as described above except that length becomes insignificant because path of blood flow across a valve is extremely short compared to a blood vessel. Therefore, when resistance to flow is described for heart valves, the primary factors considered are radius and blood viscosity.

http://www.cvphysiology.com/Hemodynamics/H003.htm

18) The clot formed is not stable unless extensive cross linking occurs. This is done by a) Plasmin b) Thrombin c) Factor XIII d) HMWK C 19) In a study mannitol 10g is injected iv and the concentration measured after some time is 50 mg/100ml. In this time 10% of mannitol is excreted. What is the volume of the ECF a) 18 L b) 42 L A Volume of ECF=amount/concentration

20) ABO blood group is an example of a) Co dominance A 21) What is true regarding alpha and gamma neurons during voluntary movements a) Alpha acts first b) Gamma acts first c) Both act together d) gamma 1st then aphla ANS=C

Motor neurons are divided into two groups. Alpha motor neurons innervate extrafusal fibers, the highly contracting fibers that supply the muscle with its power. Gamma motor neurons innervate intrafusal fibers, which contract only slightly. The function of intrafusal fiber contraction is not to provide force to the muscle; rather, gamma activation of the intrafusal fiber is necessary to keep the muscle spindle taut, and therefore sensitive to stretch, over a wide range of muscle lengths. This concept is illustrated in Figure 1.10. If a resting muscle is stretched, the muscle spindle becomes stretched in parallel, sending signals through the primary and secondary afferents. A subsequent contraction of the muscle, however, removes the pull on the spindle, and it becomes slack, causing the spindle afferents to cease firing. If the muscle were to be stretched again, the muscle spindle would not be able to signal this stretch. Thus, the spindle is rendered temporarily insensitive to stretch after the muscle has contracted. Activation of gamma motor neurons prevents this temporary insensitivity by causing a weak contraction of the intrafusal fibers, in parallel with the contraction of the muscle. This contraction keeps the spindle taut at all times and maintains its sensitivity to changes in the length of the muscle. Thus, when the CNS instructs a muscle to contract, it not only sends the appropriate signals to the alpha motor neurons, it also instructs gamma motor neurons to contract the intrafusal fibers appropriately; this coordinated process is referred to as alpha-gamma coactivation. http://neuroscience.uth.tmc.edu/s3/chapter01.html

22) Which of these is secreted by beta cells of pancreas along with insulin a) Amylin b) Glucagon like peptide A 23) Brown adipose tissue is present in all except a) Around blood vessels b) Subcutaneous tissue c) Adrenal cortex d) Scapula ANS=D

Visceral BAT includes the following: 1) Perivascular BAT around the aorta, common carotid artery, and brachiocephalic artery; in anterior mediastinum (paracardial) fat (Fig. 1); and around epicardial coronary artery and cardiac veins as well as mediumsized muscular arteries and veins including the internal mammary and the intercostal artery branches from the subclavian and aorta. The intercostal veins drain blood from the chest and abdominal walls into the azygous veins, the left joining the main right azygous vein in the latter’s thoracic cephalad course closely adjacent to the inferior vena cava before emptying into the superior vena cava (14). 2) Viscus BAT, defined as BAT surrounding a hollow muscular organ other than blood vessels, situated in variable amounts in the epicardium around the heart (Fig. 1) and in the esophago-tracheal groove, as well as greater omentum and transverse mesocolon in the peritoneal cavity. 3) BAT around solid organs, namely, kidney, adrenal, pancreas, liver, and splenic hilum including paravertebral fat, which was not examined in Heaton’s series (2) but can be seen on CT scans of the thorax adjacent to periaortic fat (Fig. 1). It lies next to the intercostal artery from which a spinal branch supplies the spinal cord (14). To our knowledge, BAT has not been described in the meninges covering the brain and spinal cord or in the subcutaneous tissue of the scalp. http://diabetes.diabetesjournals.org/content/62/6/1783.full --------------------------------------------------------------------------------Brown adipose tissue is sometimes mistaken for a type of gland, which it resembles more than white adipose tissue. It varies in color from dark red to tan, reflecting lipid content. Its lipid reserves are depleted when the animal is exposed to a cold environment, and the color darkens. In contrast to white fat, brown fat is richly vascularized and has numerous unmyelinated nerves which provide sympathetic

stimulation to the adipocytes. Brown fat is most prominent in newborn animals. In human infants it comprises up to 5% of body weight, then diminishes with age. Substantial quantities of brown adipose tissue can be detected in adult humans using positron-emission tomography, especially when the individuals are exposed to cold temperatures.* Most of this tissue in adults is located in the lower neck and supraclavicular region. Intriguingly, there is an inverse correlation between the amount of brown adipose tissue and body mass index, with obese individuals having significantly less of the tissue than lean individuals; this suggests that brown fat may be an important factor in maintaining a lean phenotype. A good place to observe brown fat is in mice, where it persists into adulthood.******* Dissection of a mouse will reveal two large, lobulated masses of brown fat on the dorsal aspect of the thorax, between the scapulae.********* Masses of brown fat are also to be found around the aorta and in the hilus of the kidney. Examination of sections of white and brown fat at low magnification reveal dramatic differences in structure, as seen below in images of mouse tissues. http://www.vivo.colostate.edu/…/p…/misc_topics/brownfat.html

24) 7 yr old boy with presents with severe abdominal pain. On examination he has xanthomas. Blood drawn for work up has milky appearance of plasma. Which lipoprotein is increased a) Chylomicron b) Chylomicron remnants c) LDL d) HDL ANS=A http://www.rxpgonline.com/modules.php?name=usertools&file=redirect&url=http:// usmle.biochemistryformedics.com/milky-plasma-your-diagnosis/

25) If in a person, Total Cholesterol= 300mg/dL, HDL= 25mg/dL and TAG=150mg/dL, find out the value of LDL. a) 245 b) 125 c) 95 d) 55 A Friedewald (1972) Formula: LDL = TC - HDL - TG/5.0 (mg/dL)

http://homepages.slingshot.co.nz/~geoff36/LDL_mg.htm

26) In a person, LDL is highly elevated but the level of LDL receptors is normal. What could be the cause a) Phosphorylation of LDL receptors b) ApoB100 mutation c) Lipoprotein lipase deficiency d) Cholesterol Acyl CoA transferased deficiency B 27) An infant at ?7months with history of vomiting and failure to thrive. Patient improved with iv glucose. After one month returns with same complaints. On evaluation found to have high glutamine and uracil. Which is the likely enzyme defect a) CPS1 b) Ornithine transcarbamoylase c) Arginase d) Arginosuccinase lyase A The liver is the only site of the complete urea cycle. Among the six enzymes in the cycle, N-acetylglutamate synthase (NAGS), carbamyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) are intramitochondrial whereas arginase, argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) are cytosolic. Unlike fats and carbohydrates, protein is not stored in the body but rather exists in a balanced state of anabolism (formation) and catabolism (breakdown). Protein excess beyond normal bodily requirements comes from either excess dietary protein intake or from protein breakdown through various catabolic processes (stress of the newborn period, infection, dehydration, injury, or surgery). Amino acids liberated from excess protein are broken down, releasing nitrogen which circulates in the body as ammonia (NH3). Ammonia is then converted into urea via the urea cycle and disposed of in the urine. An enzymatic block in the urea cycle defect results in the accumulation of excess ammonia which has toxic effects, most severe in the central nervous system causing cerebral edema. Ammonia also circulates in the body as free ammonia or within glutamine which functions as a temporary “repository” for ammonia. Consequently, in a urea cycle defect not only does free ammonia rise (hyperammonemia) but glutamine is also elevated. Alanine (Ala) is another amino acid that accumulates as a result of hyperammonemia due to a urea cycle defect. These two amino acid elevations (glutamine, alanine) may precede hyperammonemia and the onset of clinical symptoms and can serve as useful biochemical markers of decompensation in a patient with a urea cycle defect. Clinical Presentation of an Acute Hyperammonemic Episode Poor feeding Lethargy

Tachypnea Hypothermia Irritability Vomiting Ataxia Seizures Hepatomegaly Coma Hyperammonemic crises in neonates or infants with OTC deficiency are frequently precipitated by sepsis. Consequently, any neonate or infant with OTC deficiency who has clinical signs of a severe illness should be evaluated for a hyperammonemic crisis precipitated by infection or any other stressor. Clinical Assessment Assess cardiac, respiratory, neurologic, and hydration status. Identify potential precipitant(s) of metabolic decompensation such as infection (presence of fever) or any other physical stressor (e.g. injury, surgery). Initial laboratory tests to order: Plasma ammonia (1.5 ml blood in sodium-heparin tube sent STAT to lab on ice, run immediately) Plasma amino acid profile Urine orotic acid Liver function tests (AST,ALT, alakaline phospatase, bilirubin) Arterial or venous blood gas Serum electrolytes, bicarbonate, BUN, creatinine Blood glucose Blood, urine, and/or CSF cultures (as clinically indicated) Plasma ammonia level is a direct index of CNS toxicity and is important to follow in acute management. Plasma amino acids should be drawn at presentation and should be monitored frequently thereafter. Glutamine, as an ammonia buffer, reflects the direction of control of the hyperammonemia and, therefore, it is a useful marker for monitoring of ammonia status. Other amino acids, including glutamate, glycine, asparagine, aspartate and lysine, may be elevated when there is an excess in waste nitrogen burden. Please note that prolonged therapy with phenylacetate (phenylbutyrate) and/or benzoate may lead to a disproportionate decrease or only a modest elevation of glutamine and/or glycine. Laboratory Findings in OTC Deficiency High plasma ammonia level High plasma glutamine and alanine levels, low plasma citrulline level; low plasma arginine level Very high urine orotic acid level

Respiratory alkalosis (initially) Treatment Immediate treatment of hyperammonemia is crucial to prevent neurologic damage and avoid associated morbidity and mortality. Cognitive outcome is inversely related to the number of days of neonatal coma in the urea cycle disorders. Rapid control of the hyperammonemia is crucial in preventing or lessening the degree of mental retardation. Key steps of immediate treatment: Stop all protein intake (but do not withhold protein for longer than 36-48 hours as that can promote breakdown of endogenous proteins and hamper metabolic control). Provide intravenous fluids with dextrose and intralipids: 10%-25% IV dextrose at 1.5 times maintenance rate and intralipid at 1-3 g/kg/day to provide 120-130 kcal/kg/day. This will require a central line. Provide ammonia scavenger medications as detailed below. Prepare for probable hemodialysis by contacting the relevant renal and surgical specialists in anticipation of imminent need. The treatment of a hyperammonemic crisis in a patient with a urea cycle disorder rests on the principles which are detailed in the following sections: A. Promote waste nitrogen excretion B. Reverse catabolism/optimize caloric intake C. Treat the underlying precipitant A. Promote Waste Nitrogen Excretion There are two main ways to promote ammonia detoxification: hemodialysis and medications that facilitate ammonia excretion. Hemodialysis is the most effective way of rapidly disposing of excess ammonia and is far superior to other methods of dialysis (hemofiltration, peritoneal dialysis). Hemodialysis has the added benefit of removing amino acids such as glutamine and, in that way, disposing of additional waste nitrogen from the body. A newborn or young infant with a plasma ammonia greater than 300 μmol/L, should have hemodialysis ASAP, and administer IV Ammonul until hemodialysis is instituted. Central venous catheters should be placed in a critically ill patient in hyperammonemic crisis in anticipation of the potential for hemodialysis and the appropriate nephrology and surgical specialists should be alerted in advance for this potential need. The decision to hemodialyze is critical in preventing or minimizing irreversible CNS damage; when in doubt in the face of a markedly elevated ammonia level, the decision should be to hemodialyze as soon as possible. Ammonia scavenger medications include IV Ammonul® (sodium benzoate and sodium phenylacetate). Sodium benzoate conjugates with glycine to form hippuric acid and sodium phenylacetate conjugates with glutamine to form phenylacetylglutamine; both compounds are excreted in the urine, thereby removing the nitrogen (N) in glycine and glutamine which contribute to the hyperammonemia.

Sodium should not be provided in supplemental IV fluids when IV Ammonul® is given since this solution contains sufficient amounts of sodium. Otherwise, hypernatremia may result. Side effects of IV Ammonul® may occur in children, including nausea and vomiting. This may be controlled with antiemetic medications such as ondansetron, either prior to or during the infusion. Overdoses (3-5x the recommended dose) of IV Ammonul® can lead to agitation, confusion and hyperventilation. Caution should be exercised to avoid overdosing. IV Ammonul® dosing: 0-20 kg: 2.5 mL/kg (prior to mixture with dextrose solution) IV bolus over 90 min followed by the same dose as a 24-hour infusion. >20 kg: 55 mL/m2 (prior to mixture with dextrose solution) IV bolus over 90 min followed by the same dose as a 24-hour infusion. IV Arginine (600 mg/kg/day) – used to provide supplemental arginine which may be deficient due to early enzymatic blocks and to stimulate the urea cycle. After the diagnoses of citrullinemia and argininosuccinic aciduria have been ruled out, the dose may be reduced to 250 mg/kg/day. Citrulline – used in OTC deficiency when the child is able to have enteral feeding. Citrulline (by mouth, NG or gtube) may help pull aspartate into the urea cycle and, thus, increase nitrogen clearance. B. Reverse Catabolism/Optimize Caloric Intake *Diet should be planned in conjunction with a metabolic dietitian* The caloric intake for neonates and infants with OTC deficiency in hyperammonemic crisis should be kept at least at 120-130 kcal/kg/day to reverse catabolism. Strict intake and output records should be monitored. The caloric intake on day 1 is provided by intravenous dextrose and supplemented with intralipid to provide 120130 kcal/kg/day. Protein intake should ideally commence within 36-48 hours to avoid breakdown of endogenous proteins but may be delayed depending on clinical status. Start protein at 0.6 grams/kg/day, administered as essential amino acids. After 48 hours of this regimen and if patient tolerates this well, the protein concentration can be increased to 1.2 grams/kg/day, half in the form of essential amino acids and the other half in the form of a natural protein source (regular infant formula or breast milk) but, avoid elemental formulas as they are high in nitrogen content. Supplemental calories are added from a non-nitrogenous formula with vitamins and minerals (Ross formula Pro-Phree® or equivalent). Thereafter, the protein intake can be gradually increased by 0.25 – 0.5 gram/kg/day increments to a maximum of 2 grams /kg/day. Enteral feeds (oral or NG/NJ) should be started as soon as practical and that can even occur concomitant with IV nutrition and fluids if necessary. C. Treat the Underlying Precipitant A metabolic decompensation in a patient with a UCD is often precipitated by an underlying illness such as an

infection or dehydration which results in a state of catabolism. Diagnostic investigation and treatment aimed at this underlying precipitant is extremely important to optimize metabolic control of the decompensation and should be undertaken at the time of initial presentation and continued throughout the management phase of hyperammonemia. *Caution: Do not perform a lumbar puncture (LP) before evaluating for the presence of cerebral edema, which may contraindicate an LP. Monitoring Plasma ammonia levels do not always directly correlate with the presence or severity of clinical signs and symptoms and, thus, monitoring of clinical status and changes in that is crucial. Clinical decisions on appropriate treatments should be based on the combination of clinical assessment and plasma ammonia levels. Monitor ammonia levels every 4 hours, and electrolytes and arterial/venous blood gas as clinically indicated. Plasma amino acids should be monitored frequently depending on levels. If another IV is required, that solution should not contain sodium if given simultaneously with IV Ammonul® There may be a “rebound” hyperammonemia initially as stored glutamine is metabolized to glutamate and ammonia, and with the efflux of intracellular ammonia into the ‘relatively’ ammonia-depleted blood while on treatment and, thus, it is important to continue closely monitoring plasma ammonia levels until they remain stable in the normal range. On rare occasions it may be necessary to assess the magnitude of glutamine excess in brain tissue by performing brain magnetic resonance spectroscopy (MRS). Plasma glucose levels should be kept below 150 mg%. If hyperglycemia occurs while IV 10%-20% dextrose is supplied for added calories, an IV insulin drip at 0.01 units/kg/hour should be started to maintain plasma glucose between 100 and 150 mg%. Insulin may be increased by 0.01-0.03 units/kg/hour until desired effect is obtained. Please note that as the patient’s condition improves and anabolic homeostasis is restored, it may be necessary to rapidly eliminate or reduce the rate of the insulin infusion as hypoglycemia may develop. High IV dextrose solutions should not be decreased or stopped in the face of hyperglycemia. The goal is to keep the level from rising above 150 mg/ dl. Wide swings in glucose levels are not ideal and so plasma glucose should be kept within the above as best as possible. Cerebral edema: Oncotic agents such as albumin will increase the overall nitrogen load but may in selected cases be considered. Mannitol has been used but may not be as effective as hypertonic saline in alleviating cerebral edema due to hyperammonemia. Steroids should never be used in a patient with hyperammonemia. Hyperventilation is recommended, but only under close supervision. Neurologic status should be closely monitored for signs of CNS toxicity and cerebral edema while the patient is under treatment and in the recovery period. Caloric intake should be kept at a high level at all times to prevent catabolism. Close monitoring of the intake of calories is an essential part of treatment and monitoring of a patient with a urea cycle defect in crisis. Avoid certain medications, such as valproic acid, as it interferes with urea cycle function and accentuates hyperammonemia. Recovery Once the patient is stabilized and improving, oral diet has been established, and the plasma ammonia level is stable in an acceptable range, oral scavenger medications (sodium benzoate, sodium phenylbutyrate) and oral arginine can be provided in place of their IV forms.

The dose of sodium benzoate and sodium phenylbutyrate is determined based on either body weight or body surface area. The dose should be decided in conjunction with a metabolic physician if the patient does not have an up to date regimen.

http://newenglandconsortium.org/for-professionals/acute-illnessprotocols/urea-cycle-disorders/ornithine-transcarbamylase-deficiency-otc/ http://www.namrata.co/case-study-urea-cycle-disorders/

28) A child was found to have hypoglycemia, hepatomegaly and accumulation of highly branched glycogen called limit dextrins. He is likely to be suffering from a) Cori's Disease b) Von Gierke's D. c) Anderson’s D. d) McArdle’s D. A Glycogen storage disease type III GSD type III is also known as Forbes-Cori disease or limit dextrinosis. In contrast to GSD type I, liver and skeletal muscles are involved in GSD type III. Glycogen deposited in these organs has an abnormal structure. Differentiating patients with GSD type III from those with GSD type I solely on the basis of physical findings is not easy. http://emedicine.medscape.com/article/1116574-overview

29) A 48 yr old lady presented with … On examination of…crumpled tissue paper appearance is seen. Which is the product likely to have accumulated a) Glucocerebroside b) Sphingomylin c) Sulfatide d) Ganglioside A Clinical Features of Gaucher Disease The hallmark of Gaucher disease is the presence of lipid-engorged cells of the monocyte/macrophage lineage with a characteristic appearance in a variety of tissues. These distinctive cells contain one or more nuclei and their cytoplasm contains a striated tubular pattern described as "wrinkled tissue paper". These cells are called Gaucher cells. Clinically, Gaucher disease is classified into three major types. These types are determined by the absence or presence and severity of neurological involvement. Type 1 is the most commonly occurring form of Gaucher disease and is called the nonneuronopathic type (historically called the adult form). Both type 2 and type 3 Gaucher disease have

neuronopathic involvement. Type 2 disease is the acute neuronopathic form, exhibits early onset of severe central nervous system dysfunction and is usually fatal within the first 2 years of life. Type 3 Gaucher disease (subacute neuronopathic) patients have later onset neurological symptoms with a more chronic course than type 2 patients. Enlargement of the liver is characteristic in all Gaucher disease patients. In severe cases the liver can fill the entire abdomen. Splenomegaly is present in all but the most mildly affected individuals and even in asymptomatic individuals spleen enlargement can be found. In addition to hepatosplenomegaly, bleeding is a common presenting symptom in Gaucher disease. The most common cause of the bleeding is thrombocytopenia (deficient production of platelets). Type 1 (adult, nonneuronopathic): Type 1 Gaucher disease has a broad spectrum of severity from early onset of massive hepatosplenomegaly and extensive skeletal abnormalities to patients lacking symptoms until the eighth or ninth decade of life. The median age of appearance of symptoms in type 1 Gaucher disease is 30 years. Almost all mildly affected type 1 patients harbor the N370S mutation. The symptoms of type 1 Gaucher disease result from engorged macrophages that result in hepatosplenomegaly with resultant dysfunction of the liver and spleen. Type 2 (infantile, neuronopathic): Type 2 Gaucher disease is characterized by onset at an early age (hence being called the infantile form) and severe neurologic involvement. Extensive visceral involvement with heptosplenomegaly is characteristic of type 2 Gacuher disease. Abnormalities in oculomotor function is often the first manifesting symptom in type 2 disease. Patients often thrust their heads in an attempt to compensate when following a moving object. An ichthyosis-like (dry scaly skin) disorder has been suggested as a symptom to allow for the differentiation of type 2 Gaucher disease from types 1 and 3. Type 3 (juvenile, neuronopathic): Type 3 Gaucher disease is divided into three subclasses. Type 3a presents with progressive neurologic involvement dominated by dementia and myoclonus (involuntary muscleTWITCHING ). Type 3b presents with aggressive skeletal and visceral symptoms. The neurological symptoms are limited to horizontal supranuclear gaze palsy. Type 3c presents with neurological involvement limited to horizontal supranuclear gaze palsy, cardiac valve calcification and corneal opacities but with little visceral involvement.

http://themedicalbiochemistrypage.org/gaucherdisease.php

30) A child comes with coarse facial features, big tongue, hepatosplenomegaly, mucous discharge from nose. Diagnosis is a) Hurler’s syndrome b) Beckwith Weidemann S. c) Hypothyroidism d) Proteus syndrome ANS=A

Mucopolysaccharidoses The National Organization for Rare Disorders (NORD) web site, its databases, and the contents thereof are copyrighted by NORD. No part of the NORD web site, databases, or the contents may be copied in any way, including but not limited to the following: electronically downloading, storing in a retrieval system, or redistributing for any commercial purposes without

the express written permission of NORD. Permission is hereby granted to print one hard copy of the information on an individual disease for your personal use, provided that such content is in no way modified, and the credit for the source (NORD) and NORD’s copyright notice are included on the printed copy. Any other electronic reproduction or other printed versions is strictly prohibited. The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report. Copyright 1989, 1997, 2003, 2004, 2011 NORD is very grateful to Deborah Marsden, MD, Metabolism Program, Children's Hospital Boston, for assistance in the preparation of this report.

Synonyms of Mucopolysaccharidoses MPS MPS Disorder

Disorder Subdivisions MPS 1 H/S (Hurler/Scheie Syndrome) MPS I H (Hurler Disease) MPS II-(Hunter Syndrome) MPS III A, B, C, and D (Sanfillipo Syndrome) MPS I S (Scheie Syndrome) MPS IV A and B (Morquio Syndrome) MPS IX (Hyaluronidase Deficiency) MPS VII (Sly Syndrome) MPS VI (Maroteaux-Lamy Syndrome)

General Discussion The mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders. Lysosomes function as the primary digestive units within cells. Enzymes within lysosomes break Page 2 down or digest particular nutrients, such as certain carbohydrates and fats. In individuals with MPS disorders, deficiency or malfunction of specific lysosomal enzymes leads to an abnormal accumulation of certain complex carbohydrates (mucopolysaccharides or glycosaminoglycans) in the arteries, skeleton, eyes, joints, ears, skin, and/or teeth. These accumulations may also be found in the respiratory system, liver, spleen, central nervous system, blood, and bone marrow.

This accumulation eventually causes progressive damage to cells, tissues, and various organ systems of the body. There are several different types and subtypes of mucopolysaccharidosis. These disorders, with one exception, are inherited as autosomal recessive traits.

Symptoms Individuals with MPS disorders share many similar symptoms such as multiple organ involvement, distinctive "coarse" facial features, and abnormalities of the skeleton especially joint problems. Additional findings include short stature, heart abnormalities, breathing irregularities, liver and spleen enlargement (hepatosplenomegaly), and/or neurological abnormalities. The severity of the different MPS disorders varies greatly among affected individuals, even among those with the same type of MPS and even among individuals of the same family. In most cases of MPS, affected infants appear normal at birth and symptoms become apparent around the age of one or two. Initial symptoms may include frequent colds, runny nose, infections, growth delays, or mild developmental delays. Mild forms of these disorders may not become apparent until childhood or adolescence. In most cases, the mucopolysaccharidoses are chronic, progressive disorders and, depending upon the type of MPS and severity, affected individuals may experience a decline in physical and mental function, sometimes resulting in life-threatening complications. There are different types of mucopolysaccharides that are not broken down due to enzyme malfunction or deficiency. Specifically, the mucopolysaccharides known as dermatan sulfate, heparan sulfate, or keratan sulfate may be involved alone or in some combination. Disorder Subdivisions: Hurler syndrome (mucopolysaccharidosis type 1-H; MPS 1-H) is the most severe form of mucopolysaccharidosis. It is characterized by a deficiency of the enzyme alpha-L-iduronidase, which results in an accumulation of dermatan and heparan sulfates. Symptoms of the disorder first become evident at six months to two years of age. Affected infants may experience developmental delays, recurrent urinary and upper respiratory tract infections, noisy breathing and persistent nasal discharge. Additional physical problems may include clouding of the cornea of the eye, an unusually large tongue, severe deformity of the spine, and joint stiffness. Mental development begins to regress at about the age of two. Scheie syndrome (mucopolysaccharidosis type I-S; MPS 1-S) is the mildest form of mucopolysaccharidosis. As in Hurler syndrome, individuals with Scheie syndrome have a deficiency of the enzyme alpha-L-iduronidase. However, in Scheie syndrome the deficiency is specific for dermatan sulfate. Individuals with Scheie syndrome have normal intelligence, height, and life expectancy. Symptoms include stiff joints, carpal tunnel syndrome, backward flow of Page 3 blood into the heart (aortic regurgitation), and clouding of the cornea that may result in the loss of visual acuity. The onset of symptoms in individuals with Scheie syndrome usually occurs around the age of five. Hurler-Scheie syndrome (mucopolysaccharidosis type I-H/S; MPS-IH/S) is an extremely rare disorder that refers to individuals who have a less severe form of Hurler syndrome, but a more severe form than Scheie syndrome. Like Scheie syndrome, affected individuals have a deficiency of the alpha-L-iduronidase specific to dermatan sulfate. Hurler-Scheie syndrome is not as severe as Hurler syndrome, but more severe than Scheie syndrome. Affected individuals may develop coarse facial features, joint stiffness, short stature, clouding of the corneas, abnormally enlarged

liver and/spleen (hepatosplenomegaly), and skeletal and cardiac abnormalities. Intelligence may be normal or mild to moderate intellectual disability may develop. Symptoms usually become apparent between three and six years of age. Hunter syndrome (mucopolysaccharidosis type II; MPS II) is the only type of MPS disorder inherited as an X-linked trait. Initial symptoms and findings associated with Hunter syndrome usually become apparent between ages two to four years. Such abnormalities may include progressive growth delays, resulting in short stature; joint stiffness, with associated restriction of movements; and coarsening of facial features, including thickening of the lips, tongue, and nostrils. Affected children may also have an abnormally large head (macrocephaly), a short neck and broad chest, delayed tooth eruption, progressive hearing loss, and enlargement of the liver and spleen (hepatosplenomegaly). Accumulation of heparin sulfate may occur. Two relatively distinct clinical forms of Hunter syndrome have been recognized. In the mild form of the disease (MPS IIB), intelligence may be normal or only slightly impaired. However, in the more severe form (MPS IIA), profound intellectual disability may become apparent by late childhood. In addition, slower disease progression tends to occur in those with the mild form of the disorder. Sanfilippo syndrome (mucopolysaccharidosis type III; MPS III) has four subtypes (A, B, C, and D) that are distinguished by four different enzyme deficiencies. Initial symptoms of the four types of Sanfilippo syndrome include hyperactivity,SLEEP DISORDERS , and delays in attaining developmental milestones (e.g., crawling and walking). All forms of Sanfilippo syndrome are characterized by varying degrees of intellectual disability, progressive loss of previously acquired skills (e.g., language), and hearing loss. Affected individuals may experience seizures, unsteady gait, and aggressive behavior. Affected individuals may eventually lose the ability to walk. Accumulation of heparan sulfate may occur. Morquio syndrome (mucopolysaccharidosis type IV; MPS IV) exists in two forms (Morquio syndromes A and B) and occurs because of a deficiency of the enzyme N-acetyl-galactosamine6-sulfatase and beta-galactosidase, respectively, resulting in accumulation of keratan and chondroitin sulfate in type A and keratan sulfate in type B. A deficiency of either enzyme leads to the accumulation of mucopolysaccharides in the body, abnormal skeletal development, and additional symptoms. In most cases, individuals with Morquio syndrome have normal intelligence. The clinical features of MPS IV-B are usually fewer and milder than those associated with MPS IV-A. Symptoms may include growth retardation, a prominent lower face, an abnormally short neck, knees that are abnormally close together (knock knees or genu valgum), flat feet, abnormal sideways and front-to-back or side-to-side curvature of the spine Page 4 (kyphoscoliosis), abnormal development of the growing ends of the long bones (epiphyses), and/or a prominent breast bone (pectus carinatum). In some cases, hearing loss, weakness of the legs, and/or additional abnormalities also occur. Mucopolysaccharidosis type V is the former designation for Scheie syndrome. However when it was discovered that both Hurler and Scheie syndromes occur due to a deficiency of the same enzyme, Scheie syndrome was reclassified as a subtype of mucopolysaccharidosis type I. Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI; MPS VI) is characterized by a deficiency of the enzyme N-acetylgalactosamine-4-sulfatase, resulting in accumulation of dermatan sulfate. This form of MPS varies greatly among affected individuals. Some affected individuals only experience a few mild symptoms, other develop a more severe form of the

disorder. Possible symptoms of Maroteaux-Lamy syndrome include coarse facial features, umbilical hernia, a prominent breast bone (pectus carinatum), joint contractures, clouding of the corneas, an abnormal enlargement of the liver and/or spleen (heptasplenomegaly). Skeletal malformations and heart disease may occur in individuals with this form of MPS. In most cases, intelligence is normal. Sly syndrome (mucopolysaccharidosis type VII; MPS VII) is characterized by a deficiency of the enzyme beta-glucuronidase, resulting in the accumulation of three glycosaminoglycans: dermatan sulfate, heparan sulfate and chondroitin sulfate. The symptoms may vary greatly from case to case. Individuals may have normal intelligence or mild to moderate intellectual disability. Some skeletal abnormalities are often present. Hernias, clouding of the corneas, excessive accumulation of cerebrospinal fluid in the skull (hydrocephalus), short stature, heart disease, and coarse facial features have also been reported. In rare cases, some newborn infants with Sly syndrome may experience abnormal accumulation of fluid in various tissues of the body (hydrops fetalis). DiFerrante syndrome (mucopolysaccharidosis VIII; MPS VIII) is an obsolete term for a form of MPS described in a single individual with clinical and biochemical features of Morquio and Sanfilippo syndromes. The disorder had been reported to be due to a deficiency of glucosamine6-sulfate sulfatase. Subsequently, this disorder was called MPS VIII (DiFerrante syndrome). Dr. DiFerrante later found that the enzyme was normal in his patient, and the disorder had been misdiagnosed. Therefore, DiFerrante syndrome is not a valid medical disorder. Hyaluronidase deficiency (mucopolysaccharidosis IX; MPS IX) is an extremely rare form of MPS characterized by a deficiency of the enzyme hyaluronidase, which is needed to breakdown the mucopolysaccharides known as hyaluronan (hyaluronic acid). This form of MPS was first described in 1996. Symptoms may include mild short stature, cysts, frequent ear infections, cleft palate, and the development of soft-tissue masses. However, more cases of this form of MPS must be identified before a clear clinical picture can be established.

Causes All of the MPS disorders result from deficiency or malfunction of a specific lysosomal enzyme necessary in the breaking down of dermatan sulfate, heparan sulfate, or keratan sulfate, either Page 5 alone or together. Failure to breakdown these mucopolysaccharides results in their accumulation in cells, tissues and organs throughout the body. All of these disorders are inherited as autosomal recessive traits except for Hunter syndrome, which is an X-linked recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is "turned off" and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do

not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is turned off. Males have one X chromosome and if they inherit an X chromosome that contains a disease gene, they will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. Males cannot pass an X-linked gene to their sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% to have a son affected with the disease, and a 25% chance to have an unaffected son.

Affected Populations The prevalence of all forms of mucopolysaccharidosis is estimated to be one in 25,000 births. However, because mucopolysaccharidoses, especially the milder forms of the diseases, often go unrecognized, these disorders are under-diagnosed or misdiagnosed, making it difficult to determine their true frequency in the general population. Estimates for the specific types of mucopolysaccharidosis range from: one in 100,000 for Hurler syndrome; one in 500,000 for Scheie syndrome; one in 115,000 for Hurler-Scheie syndrome; one in 70,000 for Sanfilippo syndrome; one in 200,000 for Morquio syndrome; and fewer than one in 250,000 in Sly syndrome. Hunter syndrome occurs predominantly in males. In extremely rare cases, affected females have been reported. The incidence of Hunter syndrome is estimated at one in 100,000-150,000 male births. More than 40 distinct lysosomal storage diseases have been identified.

Related Disorders Symptoms of the following disorders can be similar to those of mucopolysaccharidosis. Comparisons may be useful for a differential diagnosis: Page 6 The mucolipidoses are another subgroup of lysosomal storage disorders and produce symptoms similar to those of the mucopolysaccharidoses. These disorders include I-cell disease, pseudohurler polydystrophy, and mucolipidosis (ML) type IV. I-cell disease (mucolipidosis type II) resembles Hurler syndrome and the two disorders are difficult to distinguish. I-cell disease has similar physical and mental deterioration as MPS I, but usually occurs earlier and is more severe. I-cell disease is characterized by diffused deficiency of lysosomal enzymes within the cell and is not associated with excretion of mucopolysaccharides in the urine. Pseudo-Hurler polydystrophy (mucolipidosis type III) is characterized by a deficiency of multiple lysosomal enzymes needed to break down mucopolysaccharides. ML III affects males more often than females, and can be identified by such symptoms as claw-like hands, somewhat coarse facial features, short stature and pain in the hands. Intelligence tends to be normal in most individuals, but mild intellectual disability is possible. ML type IV is thought to be caused by a deficiency of transport channel receptor protein. This deficiency may lead to the accumulation of certain fatty substances (mucolipids) and certain complex carbohydrates (mucopolysaccharides) within the cells of many tissues of the body. ML IV is characterized by intellectual disability; severe impairment in the acquisition of skills requiring the coordination of muscular and mental activities (psychomotor retardation); diminished muscle tone (hypotonia); clouding (opacity) of the clear portion of the eyes through which light passes (cornea); and/or degeneration of the nerve-rich membrane lining the eyes (retinal degeneration). (For more information on these disorders, choose "mucolipidosis" as your search term in the Rare Disease Database.) Lipid storage disorders are a group of disorders that include Fabry disease and Gaucher disease.

Fabry disease is characterized by a deficiency of the enzyme alpha-galactosidase A. Low levels or inactivity of this enzyme leads to the abnormal accumulation of a substance consisting of fatty material and carbohydrates (i.e., glycolipids such as glycosphingolipid) in various organs of the body, particularly blood vessels and the eyes. Symptoms of Fabry disease may include the appearance of clusters of wart-like discolorations on the skin (angiokeratomas), abdominal pain, and/or visual impairment. Later in the course of the disease, kidney failure, heart irregularities, and/or progressive neurological abnormalities may cause serious complications. Gaucher disease is rare disorder in which deficiency of the enzyme glucocerebrosidase results in the accumulation of harmful quantities of certain fats (lipids), specifically the glycolipid glucocerebroside, throughout the body especially within the bone marrow, spleen and liver. The symptoms and physical findings associated with Gaucher disease vary greatly from case to case. Some individuals will develop few or no symptoms (asymptomatic); others may have serious complications. Common symptoms associated with Gaucher disease include an abnormally enlarged liver and/or spleen (hepatosplenomegaly), low levels of circulating red blood cells (anemia), low levels of platelets (thrombocytopenia), and skeletal abnormalities. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.) Multiple sulfatase deficiency is a rare hereditary metabolic disorder characterized by impairment of all known sulfatase enzymes. Major symptoms include coarse facial features, deafness, and an enlarged liver and spleen (hepatosplenomegaly). Abnormalities of the skeleton may occur such as abnormal curvature of the spine (lumbar kyphosis). The skin is usually dry and scaly (ichthyosis). Before symptoms are noticeable, children with this disorder usually develop more Page 7 slowly than normal. They may not learn to walk or speak as quickly as other children (developmental delays). Multiple sulfatase deficiency is inherited as an autosomal recessive trait. (For more information on this disorder, choose "multiple sulfatase deficiency" as your search term in the Rare Disease Database.) Additional groups of disorders that have similar symptoms to the mucopolysaccharidoses include glycoprotein disorders (oligosaccharidoses), which include fucosidosis and mannosidosis; leukodystrophies, which include Krabbe's disease and metachromatic leukodystrophy; and gangliosidoses such as Tay-Sachs disease. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.) http://www.med.upenn.edu/orphandisease/docs/Mucopolysaccharidoses.pdf

31) Thiamine deficiency can cause lactic acidosis due to which enzyme dysfunction a) PEPcarboxykinase b) PDH c) Pyruvate carboxylase B

Lactic acidosis due to thiamine deficiency

Thiamine participates as a cofactor in oxidative phosphorylation, and its absence is sorely missed. Historically, this is a cause of lactic acidosis in the malnourished patient in who there is no other apparent cause of lactic acidosis.

Among its many uses, thiamine acts as a coenzyme with pyruvate dehydrogenase to form acetyl-CoA. So of course, if you completely abolish thiamine, there will be no entry for pyruvate into Krebs cycle. And even if it could enter, alpha-ketoglutarate dehydrogenase would also need thiamine as a coenzyme to convert alpha-ketoglutarate into succynyl coenzyme A. Thus, a deficiency of thiamine produces

an excess of lactate by preventing pyruvate from becoming a substrate for oxidative metabolism. It seems pretty difficult to become so thiamine deficient that it would produce a clinically relevant lactic acidosis. The case reports in the literature all seem to involve people on TPN in whom multivitamins are accidentally not administered.

Who gets thiamine deficient these days? One can easily envision a developing world environment where this sort of nutritional deficiency is commonplace. However, it seems this problem can also exist in the nutritionally competent West. Specifically, people on long-term frusemide (a huge proportion of the ICU population) seem to have a thiamine deficiency due to a constant urinary loss. And yes, it is a deficiency which is relevant to their outcome- the patients in that study all had an improvement in their systolic function once thiamine was replaced at 100g IV per day, for 7 days. In this way, one might argue that the hopelessly shocked cardiac patient could benefit from thiamine supplementation, and is unlikely to be harmed by it, which is a strong argument for supplementing everybody.

But of course these are occult thiamine deficits. Nobody expected those frusemide-intoxicated patients to develop a thiamine deficiency. The chronic alcoholic, on the other hand, is at risk of this every day; the term “wet beriberi” is used to describe the cardiovascular collapse which ensues, which is typically associated with a lactic acidosis.

Red cell transketolase is an enzyme of the pentose pathway which is affected by the presence of thiamine; its activity is decreased in the absence of thiamine (which it uses as a cofactor). Its increased activity with the addition of thiamine in the laboratory (measured by red cell NADH consumption) is used as an indirect evidence of thiamine deficiency. http://www.derangedphysiology.com/php/Acid-BaseDisturbance/lactic-acidosis-due-to-thiamine-deficiency.php

32) Enzyme used for both glycogenesis and glycogenolysis is a) Glycogen synthase b) Phosphoglucomutase c) Glycogen transferase B 33) In fasting states RBC use a) Glucose b) Alanine

c) Ketone body d) Fatty acid A FASTING STATE: •

RBC can ONLY use glucose for energy

•

exclusively anaerobic glycolysis produces lactate which gets sent to the liver for

glucoeogenesis http://my.ico.edu/document.doc?id=2729 34) RNAi can cause the following in a gene a) Knock in b) Knock out c) Knock down d) Knock up

C ANS=C Recent advances in technologies for genome editing-the use of TALEN or CRISPR to make targeted,permanent changes to genes-have revolutionized molecular genetics. They have also presented userswith a choice between these relatively new technologies and that of the more established method ofRNA interference (RNAi)-mediated knockdown using short hairpin RNA (shRNA) or short interfering RNA(siRNA). In this Technical Note, we explore the differences between the two methods for ablating genefunction, and situations where one technology is more appropriate than the other. RNAi-mediated gene silencing In higher eukaryotes, RNAi-mediated knockdown is the most common strategy for depleting cells of agene product of interest. However, RNAi usually does not completely shut off the gene. Essentially,short (approximately 20-25 nucleotides) double stranded RNA molecules are either generated fromhairpin-forming precursors (shRNAs) or introduced exogenously (siRNAs). After processing by Dicer, asingle stranded RNA base-pairs with a target mRNA (Ketting, 2013). Depending on the organism, RNAi-mediated gene silencing is carried out by Argonaute proteins via either mRNA degradation or translationinhibition (Figure 1). The end result is post transcriptional down-regulation of gene expression, withoutchanging the genetic code (Mittal, 2004). Some functional RNA or protein remains and is translated atlower levels. So, the RNAi strategy for reducing gene function is termed a “knockdown”. Gene functionis reduced, but not eliminated Genome editing for gene knockout By contrast, genome editing changes the genetic code, typically causing a “knockout”, or completeelimination of gene function. The process begins with creation of a double-strand break (DSB) in thechromosome (Bogdanove & Voytas, 2011). Recently, two tools have been developed for generatingDSBs with high efficiency: Transcription Activator-Like Effector Nucleases (TALENs), and Clustered,Regularly Interspaced Palindromic Repeat Associated (CRISPR-Cas) proteins (Bogdanove & Voytas, 2011;Jinek, et al., 2012; Shalem, et al., 2014; Wang, et al., 2014). Both these tools are adapted from bacterialsystems that either cause plant

pathogenesis (TALEN), or defend the genome from insertionalmutagenesis (CRISPR-Cas). TALENs are chimeric proteins consisting of site-specific DNA binding proteinsfused to the restriction endonuclease FokI. CRISPR-Cas uses a site-specific, 20 nucleotide single guideRNA (sgRNA) to bring the Cas9 nuclease to its target locus. For both TALEN and CRISPR-Cas, the nucleasecuts both DNA strands of the target. This break must be repaired or the cell will die, so eukaryotic cellsrespond by two major mechanisms (Figure 2). The first, non-homologous end joining (NHEJ), re-ligatesthe two free chromosome ends. However, NHEJ is error-prone, often resulting in small insertions ordeletions that can disrupt, or knock out, the gene. Alternatively, cells can repair DSBs throughhomologous recombination (HR), which provides researchers more options for gene knockout. Defineddeletions can be introduced, insertional mutations can be created, or single bases can be changed, toname a few

http://www.genesil.com/docs/Knockouts%20&%20RNAi.pdf http://www.genecopoeia.com/wpcontent/uploads/2014/02/Technotes_Knockdown_vs_knockout.pdf

35) Specific site to which the CRE recombinase binds a) RE site b) LoxP site ANS=B Cre-lox

P

Recombination

In the early 1990's a new method was developed to delete a specific portion of DNA. The procedure took advantage of the basic research performed on the bacteriophage called P1. In this virus, there is an enzyme called cre and particular DNA sequences called lox P sites. The lox P sites work in pairs and they flank a segment of DNA called a target When the cre enzyme binds to the lox P sites, it cuts the lox sites in half and then splices together the two halves after the target DNA has been removed Molecular biologists recognized the specificity and utility of this viral recombination system and put it to good use. Now if you want to excise a piece of DNA at a particular time, all you need to do is to flank the target DNA with a pair of lox P sites and introduce the cre enzyme when you want the target excised. Mike Snyder's group used this to added epitope tags onto yeast proteins (Proteomics Chapter). An additional twist is to express a Cre transgene under control of an inducible promoter so you can delete the target DNA inside selected cells of a transgenic organism when you want it deleted. http://www.bio.davidson.edu/genomics/method/CreLoxP.html

36) 10yrs old boy with muscle weakness and fatigue with increased lead in blood. Which of following enzyme production in the liver is increased a) ALA synthase b) Ferrochetalase c) PBG deaminase d) porphobilinogen ???? ANS=A Alterations in the activity of enzymes of haem biosynthesis in lead poisoning and acute hepatic prophyria. Campbell BC, Brodie MJ, Thompson GG, Meredith PA, Moore MR, Goldberg A. Abstract 1. The activities of six of the enzymes of haem biosynthesis have been assayed in peripheral blood from patients with lead poisoning, acute intermittent porphyria or hereditary coproprophyria. 2. Compared with normal subjects the lead-poisoned subjects had highly significant depression of delta-aminolaevulinate dehydratase, coproporphyrinogen oxidase and ferrochelatase. 3. Lead-poisoned subjects had highly significant elevation of delta-aminolaevulinate synthase activity. 4. deltaAminolaevulinate synthase activity was inversely related to the haemoglobin concentration. 5. Increased delta-aminolaevulinate synthase and decreased deltaaminolaevulinate dehydratase activity are also found in acute intermittent porphyria. 6. Increased delta-aminolaevulinate synthase, normal prophobilinogen deaminase and uroporphyrinogen decarboxylase and decreased coproporphyrinogen oxidase are found in both lead poisoning and hereditary coproporphyria. 7. These enzyme changes explain the recognized patterns of porphyrins and prophyrin precurosrs in blood and urine in these conditions. http://www.ncbi.nlm.nih.gov/pubmed/913057 37) In Granular dystrophy of cornea which stain is used a) Masson trichome b) Congo Red A &B Granular Corneal Dystrophy Type 1 [edit source] Also know as Corneal dystrophy Groenouw type I. Genetics & Inheritance[edit source] Autosomal dominant inheritance of the TGFBI gene on the 5q31 locus. Slit Lamp Examination[edit source] Discrete crumb-like opacities are seen in the central anterior stroma. These deposits may appear in

early childhood, and at first may appear as more subtle fine dots or lines before they develop into the more characteristic granules associated with this dystrophy. Early in life these granules are separated by clear cornea. The lesions do not extend typically to the limbus, and become more numerous over time. Late in the disease the lesions may coalesce and extend deep into posterior stroma. Granular Dystrophy Feldman Patient.jpeg Homozygotes for the dystrophy have a more severe course and presentation. Granular Dystrophy Photo--Feldman.jpg Pathology[edit source] Hyaline deposits that stain bright red with Masson Trichome and are weakly PAS positive. On EM, the deposits appearance trapezoidal or rod-shaped. Symptoms[edit source] While some visual symptoms may occur early in life, with problems of glare and light sensitivity, visual acuity is not usually affected until the 4th decade for most patients. Recurrent erosions may occur. There is wide variety in patient symptoms. Granular Corneal Dystrophy Type 2 [edit source] Also known as Granular-Lattice Dystrophy, because it displays findings of both diseases, and Avellino Dystrophy, because it was first described in families from Avellino, Italy. Genetics & Inheritance[edit source] Autosomal dominant inheritance of the TGFBI gene on the 5q31 locus. Slit Lamp Examination[edit source] Deposits begin to appear in early childhood (in homozygotes) or adolescence as tiny whitish dots in the anterior stromal. Over time, these lesions progress into larger stellate, ring, or snowflake-like opacities. Lattice lines are seen later than the granular lesions, and are usually found in deeper stroma. Some patients go on to develop near confluent anterior granular lesions, but not as frequently as in type 1 granular. Pathology[edit source] Mixed deposits of amyloid (as seen in Lattice dystrophy) and Hyaline (typical of Granular). The amyloid stains red with Congo red stain and the hyaline stains red with Masson Trichome. Symptoms[edit source] Vision loss may occur earlier than in Type 1 Granular, with many patients noting vision loss in adolescence. However, few patients drop below the 20/70 level, even late in the disease. Recurrent erosions and photophobia are also more common in Type 2 Granular than Type 1.

38) OIL red O stain is used for

a) Frozen specimen b) Glutaraldehyde fixed specimen c) Alcohol fixed specimen d) Formalin fixed specimen A Staining Methods: Connective Tissue, Muscle Fibers and Lipids Results OIL Red O Feature Visualization Fat Red Nuclei Blue

Sudan Black B Feature Visualization Fat Blue-black Nuclei Red

Technical Considerations ■

For demonstration of simple lipids, frozen sections must be used. ■

Frozen sections may be unfixed or post-fixed in 10% neutral buffered formalin or formol-calcium. ■

Tissue must not be exposed to fat solvents such as alcohols, acetone, xylene or paraffin. ■

Aqueous mounting media must be used when coverslipping finished slides. References 1. Sheehan DC, Hrapchak BB. Theory and practice of histotechnology. 2nd ed. Columbus, OH: Batelle Press; 1980. p. 180–213. 2. Carson FL. Histotechnology: a self-instructional text. 2nd ed. Chicago: American Society of Clinical Pathologists Press; 1996. p. 131–56. 3. Luna LG. Histopathologic methods and color atlas of special stains and tissue artifacts. Downer’s Grove, IL: Johnson Printers; 1992. p. 399–479. 4. Connective tissue and muscle morphology and staining. Bowie, MD: National Society for Histotechnology; 1990. 5. Bancroft J, Gamble M. Theory and practice of histological techniques. 5th ed. New York: Churchill Livingstone

http://www.lab.anhb.uwa.edu.au/hb313/main_pages/timetable/Tutorials/2008/DAKO.guide_to_s pecial_stains.pdf

39) In the following karyotype what is the abnormality seen. [PICTURE] Shows 2 Xchromosomes and 1 Y-chromosome. a) Gynecomastia with long thin limbs b) Short stature with polydactyly c) ? d) ?

A 40) [PICTURE] ?Immunofluorescence study. This photo was taken by attaching the camera to the microscope. What is the requirement for such a microscope a) Dark field condenser b) Phase shifter c) Dichroic mirror d) ??? ANS=C The basic principle of immunofluorescence To use a fluorescent compound (usually fluorescein) to detect the binding of antigen and antibody The Ab is labelled with the fluorescent compound Under a fluorescence microscope, fluorescein appears bright green wherever the binding occurs

Green fluorescence of FITC

Using the fluorescence microscope Select the correct filter block for the fluorescent compound Fluorescence fades quickly under UV light; try to limit the time of exposure to UV as much as possible Use high speed films for photography

Direct Immunofluorescence The aim is to identify the presence and location of an antigen by the use of a fluorescent labelled specific antibody

One step Direct Immunofluorescence

Two step Direct Immunofluorescence

Medical applications of direct IF

Renal diseases for evidence of immune deposition Skin diseases for evidence of immune deposition Detection of specific antigens, especially those of infective organisms

Application in renal diseases IgG

A section of kidney is placed on a slide; a fluorescein-labeled antiglobulin (specific for IgG, in this case) is added, then rinsed away The presence of fluorescence in the glomeruli indicates that IgG was deposited prior to the biopsy IgG is deposited in granular clumps along the capillary walls, enabling a diagnosis of membranous glomerulonephritis in this case

A section of kidney is placed on a slide; a fluorescein-labeled antiglobulin (specific for IgG, in this case) is added, then rinsed away The presence of fluorescence in the glomeruli indicates that IgG was deposited prior to the biopsy IgG is deposited in granular clumps along the capillary walls, enabling a diagnosis of membranous glomerulonephritis in this case

Direct Fluorescent Antibody Test for the Presence of Immunoglobulin Deposits in Skin IgG

A section of skin is placed on a slide; a fluorescein-labeled antiglobulin (specific for IgG, in this case) is added, then rinsed away The presence of fluorescence in the upper layers of the epithelium indicates that IgG was deposited in this skin (prior to the biopsy) The presence of immunoglobulins deposited around keratinocytes is consistent with a diagnosis of pemphigus

A section of skin is placed on a slide; a fluorescein-labeled antiglobulin (specific for IgG, in this case) is added, then rinsed away The presence of fluorescence in the upper layers of the epithelium indicates that IgG was deposited in this skin (prior to the biopsy) The presence of immunoglobulins deposited around keratinocytes is consistent with a diagnosis of pemphigus

Double labelling Lymphoid tissue: the two Ig light chains are separately labelled.

Indirect Immunofluorescence

Indirect Immunofluorescence The aim is to identify the presence of antigen specific antibodies in serum. The method is also be used to compare concentration of the antibodies in sera. Indirect Immunofluorescence A known antigen is placed on a slide; the patient's serum is added, then rinsed away. A fluorescein-labeled antiglobulin is added, then rinsed away. The presence of fluorescence over the antigen indicates the presence of antibodies to this antigen in the patient.

Diagnosis of Bacterial Diseases Clostridial diseases (direct) Brucella canis (indirect) Afipia catei, cat scratch disease (indirect) Borrelia burgdorferi (indirect) Coxiella burnetii, Q Fever (indirect) Rickettsia rickettsiae, Rocky Mountain Spotted Fever (indirect)

Diagnosis of Viral Diseases rabies virus (direct) bovine immunodeficiency-like virus (indirect) canine coronavirus (indirect) canine distemper (indirect) feline infectious peritonitis (corona-) virus (direct) porcine respiratory and reproductive syndrome (indirect)

Diagnosis of Protozoal Diseases

Babesia species (indirect) Ehrlichia species (indirect) Toxoplasma gondii (indirect) Trypanosoma cruzi (indirect) Cryptosporidia/Giardia (direct) Encephalitozoon cuniculi (indirect) Neosporum caninum (direct, indirect)

Some examples Indirect Immunofluorescence

Indirect Fluorescent Antibody Test for Antibodies to Toxoplasma gondii

Indirect Fluorescent Antibody Test for Antibodies to Toxoplasma gondii Toxoplasma organisms are killed and placed on the slide; the patient’s serum is added, then washed away. A fluorescein-labeled antiglobulin is added, then washed away. The presence of the green fluorescence outlining the T. gondii organisms indicates the presence of antibodies in the patient's serum.

Indirect Fluorescent Antibody Test for Antibodies to Toxoplasma gondii

Immune-Mediated Disorders antinuclear antibody (ANA) test (for diagnosis of systemic lupus erythematosus) Direct fluorescent antibody test for deposition of Abs in tissues, e.g. kidney, skin

Indirect Fluorescent Antibody Test for Antinuclear Antibodies

Indirect Fluorescent Antibody Test for Antinuclear Antibodies Cells from a cultured cell line are placed on a slide; the patient's serum is added, then rinsed away. A fluorescein-labeled antiglobulin is added, then rinsed away.

The presence of fluorescence in the nucleus of these cells indicates the presence of antibodies to nuclear antigens in the patient.

Indirect Fluorescent Antibody Test for Antinuclear Antibodies

Advantage over Immunoperoxidase Technically easier (fewer steps) More sensitive results

Drawbacks Microscope is more costly Frozen sections preferred Preparations need refrigeration Preparations cannot be kept for too long Quick fading of fluorescence under illumination (bleaching effect)

Part II: Confocal microscopy

Learning Objectives To understand the working principles of confocal scanning microscope To know the current use of confocal scanning microscopy in medical science

Principles of confocal microscopy a focused laser beam serves as a high intensity point source light reflected or fluorescence emitted by the specimen is allowed to pass through a pinhole that filters light coming from outside (above and below) of the focal plane

Principles of confocal microscopy a sensitive detector (photomultipler) behind a pinhole to measure the intensity of light the laser beam, the pinhole and detector scan through the specimen to build up an image on a monitor

The confocal concept

Modes of scanning Mechanical scanning stage Beam scanning (by means of mirror) Combined stage and beam scanning Slit may be used instead of a pinhole Shortens time for scanning an area Direct vision of real color image made possible At the expense of a lower resolution

Use of confocal microscope Performs optical sectioning of thick samples Three dimensional image reconstruction Detects very weak fluorescent signals Selective photobleaching Cell ablation

Image modalities Autofluorescence Single, double or treble fluorescent labeling: immunofluorescence, in-situ hybridization Image formed by reflectance intensified with metallic coating e.g. AgNOR, immunogold labeling

Application in biomedical science Growth of small organisms, cells, embryos Movement of intracellular structures Change in membrane permeability 3 dimensional reconstruction Image analysis

BIO-RAD MRC-1000 beam scanning LSM Zeiss "Axioskop" upright microscope for ordinary bright field transmitted light and epi-fluorescence

argon/krypton laser, 15 mW, wavelengths at 488 nm (e.g. FITC), 568 and 647 nm reflectance mode fluorescence mode: simultaneous recording of 2 channels, ie. For double labels

BIO-RAD MRC-1000 upgradable to 3 simultaneous channels in fluorescence mode computer-controlled stage motor for vertical motion at 0.5µm per step performs frame scan, line scan, vertical scan maximum image size 1024 x 1024 pixels scanning speed at maximum of 16 frames/s at 768 x 30 pixels, and 1 frame/s at 512 lines

BIO-RAD MRC-1000 beam park function for photobleaching, ablation computer programs for morphometric analysis, 3-D visualization IgG IgG Confocal Confocal microscope gives a clearer image and cleaner background over conventional fluorescent microscope Microphotography for weak signals is much easier with a confocal microscope Microphotography for weak signals

is much easier with a confocal microscope Excellent for picking up weak signals Immunofluorescence and Confocal Microscopy Dr. KW Chan

Learning Objectives To understand the working principles of immunofluorescence microscope To understand the difference between direct and indirect immunofluorescence To know the current use of immunofluorescence studies in medicine

Learning Objectives To understand the working principles of confocal scanning microscope To know the current use of confocal scanning microscopy in medical science

http://www.patho.hku.hk/docs/mmedsc/mms-ifcf.ppt

41) Platelet adhesion to vessel wall is due to a) Factor IX b) Fibrinogen c) vWF C 42) A10 yr old boy with mass in the abdomen. On imaging the paraaortic LN is enlarged. On biopsy starry sky appearance is seen. What is the underlying abnormality a) p53 gene mutation b) RB gene mutation c) Translocation involving BCR-ABL genes d) Translocation involving MYC gene D

43) A child with edema and decreased urine output. On evaluation, serum albumin is 2.5 g/dL, S.Creatinine is 0.5 mg/dL, urine protein is 3+ with no RBC casts. Pathological change expected is a) Minimal change disease b) Interstitial nephritis c) IgA nephropathy A 44) Most common nephropathy associated with malignancy a) Membranous b) MCD c) IgA d) FSGS A Membranous nephropathy: A frequent type of primary glomerular disease -- a disease affecting the glomerulus, the tiny ball-shaped structure in the kidney composed of capillary blood vessels that is actively involved in the filtration of the blood to form urine. The main sign of the disease is marked proteinuria (protein in the urine). The majority (about 2/3) of cases are primary (or idiopathic), meaning the cause is not known. The remaining cases are secondary to conditions such as cancer, infection, and drug side effects. Idiopathic MN is the most common cause of primary nephrotic syndrome in older (>60 years) Caucasian adults and is rare in children. It usually accounts for less than 5% of pediatric patient undergoing biopsy for nephrotic syndrome. About 30% of all biopsy specimens for primary nephrotic syndrome reveal membranous nephropathy in adults and about 50% in older Caucasian adults. A large number of agents appear to be capable of initiating membranous nephropathy in genetically susceptible individuals. More common agents include infections such as hepatitis B (less commonlyhepatitis C and syphilis), immune diseases such as lupus and diabetesmellitus (less commonly associated with rheumatoid arthritis and other connective tissue diseases), medications such asGOLD , penicillamine, non-steroidal anti-inflammatory agents, and captopril, and some tumors (the colon, kidney, and lung are the most common primary sites). Membranous nephropathy has been associated with the chronic immune response to renal transplants as well. Without intervention, about 40% of people with membranous nephropathy progress to end-stage renal failure after 10 years. Conversely, up to 30% of people with have a spontaneous remission and approximately 30% of people will have stable renal function. Female sex and lower grade (non-nephrotic) proteinuria at presentation are the only two features associated with a higher likelihood of spontaneous remission. Although the majority of membranous nephropathy patients do reasonably well long term, membranous nephropathy is still the second or third leading cause of end-stage renal failure among subjects with primary glomerulonephritis. Factors associated with worse renal survival in membranous nephropathy include older age at presentation, male sex, hypertension, decreased renal function (elevated creatinine and/or decreased GFR) at time of

presentation, higher level of proteinuria, and evidence of chronic features (scarring) on biopsy. Relapses after complete remission have occurred in approximately 25% to 40% of patients. Relapses have been reported up to 20 years after the primary remission. the great majority of patients will relapse only with low-range proteinuria and will maintain stable long-term kidney function with conservative management alone. In contrast, the relapse rate is as high as 50% in those achieving only a partial remission. Achievement of either a complete or partial remission, however, significantly slows progression and increases renal survival. Membranous nephropathy is a glomerular immune-complex disease. Immune deposits form in the glomerular basement membrane that cause a membrane-like thickening. The constituent immune complexes consist of IgG. Cells called podocytes and their membrane-associated proteins play a pivotal role in the development of the disease by providing antigenic targets for circulating antibodies to form the glomerular immune deposits. Membranous nephropathy is also called membranous glomerulonephritis. The disease can occur before birth due to transmission of antibodies from the mother to the baby. The antibodies are directed against an antigen in podocytes called neutral endopeptidase (NEP). Mutations that truncate (shorten) the metallomembrane endopeptidase (MME) gene, which encodes NEP, have been found to cause the neonatal form of this disease

http://www.medicinenet.com/script/main/art.asp?articlekey=39513

45) The phenomenon where subsequent generations are at risk of earlier and more severe disease is known as a) Anticipation b) ?? A 46) In Langerhans Cell Histiocytosis, the characteristic abnormality seen is a) Birbecks granules A 47) A 45 yr old patient presents with fever, night sweats, weight loss. On X ray a mass in apical lobe of lung is seen. On histopathology found to have caseous necrosis. What is the underlying process a) Enzymatic degeneration b) Hypersensitivity reaction with modified macrophages, lymphocytes and giant cells c) Acute decrease in blood supply ? d) ?? ??? 48) Forward scatter in flow cytometry is used to assess

a) Cell death b) Cell size c) Cell granules d) florecence ANS=B Light scattering occurs when a particle deflects incident laser light. The extent towhich this occurs depends on the physical properties of a particle, namely its size andinternal complexity. Factors that affect light scattering are the cell's membrane,nucleus, and any granular material inside the cell. Cell shape and surface topographyalso contribute to the total light scatter.Forward-scattered light (FSC) is proportional to cell-surface area or size. FSC is ameasurement of mostly diffracted light and is detected just off the axis of the incidentlaser beam in the forward direction by a photodiode (Figure 3-1 on page 14). FSCprovides a suitable method of detecting particles greater than a given size independentof their fluorescence and is therefore often used in immunophenotyping to triggersignal processing Side-scattered light (SSC) is proportional to cell granularity or internal complexity.SSC is a measurement of mostly refracted and reflected light that occurs at anyinterface within the cell where there is a change in refractive index (Figure 3-1). SSC iscollected at approximately 90 degrees to the laser beam by a collection lens and thenredirected by a beam splitter to the appropriate detector

49) Collagen typical of basement membrane a) Type I b) Type V c) Type IV d) Type III C 50) Best hypertensive drug in pulmonary hypertension a) Bosentan b) Amlodipine A 51) Antihypertensive not used in pregnancy a) Enalapril b) Nifidipine A 52) DoC for hypertension in pregnancy

a) Enalpril b) Verapamil c) Alpha Methyldopa C 53) Hyperchromia iridis is caused by a) Latanoprost b) Prednisolone c) Timolol d) Olapatadine A Contributor: Gordon K. Klintworth Heterochromia iridis occurs in several conditions (including Waardenburg syndrome, Fuchs heterochromic iridocyclitis, melanosis oculi, iris melanoma [melanoma - iris] and Horner syndrome). The iris may be excessively pigmented (as in melanosis oculi,, a primary iris melanoma or an iris that has been invaded by a melanoma from the ciliary body [melanoma - ciliary body]. In some of conditions, such as Waardenburg syndrome, the heterochromia can be segmental and only involve part of the iris. In Horner syndrome the iris is ligher than normal on the affected side. Because the iris originally has a normal color Horner syndrome illustrates that an intact sympathetic innervation of the iris is important in the maintaining iris pigmentation. Certain drugs, such as latanoprost [latanoprost complications] can also make the iris darker than normal.

https://eyepathologist.com/disease.asp?IDNUM=327970

54) Adrenergic beta receptor having lipolysis property in fat cells a) Beta 1 b) Alpha 2 c) Beta 3 d) Alpha 1 C

Autonomic Receptors

Autonomic receptors are broadly divided into those for ACh (cholinergic receptors) and those for catecholamines such as NE or EPI (adrenergic receptors or adrenoceptors). As we shall see later, subdivisions of each of these families of receptors are based on sensitivity to various agonist and antagonist drugs.

Cholinergic receptors were originally divided and named on the basis of sensitivity to alkaloids that mimicked some, but not all, of the actions of ACh. These alkaloids are present in the fly agaric mushroom, Amanita muscaria, and in the tobacco plant, Nicotiana tabacum. The alkaloids are muscarine and nicotine, respectively. Thus, cholinergic receptors are broadly classified as muscarinic (mAChR) or nicotinic (nAChR). The 3-dimensional structures of muscarine and nicotine molecules are fairly rigid and differ significantly. By contrast, ACh can assume 3-dimensional structures that are similar to muscarine on the one hand and nicotine on the other hand. Thus, one neurotransmitter molecule can interact with quite different receptor proteins, based on its molecular flexibility.

Nicotinic receptors are located postsynaptically in all autonomic ganglia and at the NMJ. At these junctions nicotinic receptors function as the excitatory receptor for the postsynaptic cell. Release of a sufficient quantity of ACh from the adjoining presynaptic cell causes an excitatory response in autonomic ganglion cells and in somatic muscle fibers.

Muscarinic receptors are located postsynaptically at the parasympathetic neuroeffector junction. At these junctions muscarinic receptors function either to increase or decrease the activity of the effector cells. Muscarinic receptors are also located postsynaptically at the neuroeffector junction of sympathetic fibers in sweat glands. At this junction muscarinic receptors function to increase sweating. Drugs that block muscarinic receptors can thus interfere with sweating. Another important site of muscarinic receptors is on endothelial cells of blood vessels. Although these muscarinic receptors are not innervated by cholinergic nerve fibers, they are sensitive to circulating molecules. In 1948, adrenergic receptors were subdivided into alpha and beta by Ahlquist (a graduate of the University of Washington). The distinction was based on sensitivities of different organs to catecholamines of closely related structure. Regulation of the functions of different organs depends to a greater or lesser extent on alpha or beta receptors. Pharmacological differentiation of alpha and beta receptors, and application of this technology to the treatment of disease, is an outstanding biomedical achievement.

Alpha receptors are located postsynaptically at sympathetic neuroeffector junctions of many organs. In general, alpha receptors mediate excitation or increased activity of the effector cells. Vascular smooth muscle is an important site of alpha receptors. SNS

activity maintains vascular tone, and thus blood pressure, by maintaining a tone of neurotransmitter on vascular alpha receptors. Beta receptors are also located postsynaptically at sympathetic neuroeffector junctions of many organs. In general, beta receptors mediate relaxation or decreased activity of the effector cells. Thus, blood vessels dilate and uterine smooth muscle relaxes in response to activation of beta receptors. Heart muscle is an important exception to this rule. Activation of beta adrenoceptors in heart increases the automaticity and contractility of all parts of the heart.

Cholinergic receptors

Cholinergic, receptors mediate the actions of acetylcholine (ACh). Other choline esters such as methacholine (Mecholyl®) or carbamylcholine (Carbachol®) mimic the actions of ACh at the same receptors. Cholinergic receptors are subdivided into: • muscarinic • nicotinic

Ganglionic and other neural muscarinic receptors (M1) are apparently involved in CNS transmission. They may modulate classical ganglionic transmission process. They have been implicated in promoting the late EPSP of ganglion cells.. These receptors are classified as muscarinic because they are blocked by atropine. Oxotremorine and McNA-343 activate these receptors somewhat selectively. Pirenzepine is a relatively selective antagonist of M1 receptors. Classical muscarinic receptors (M2) (and M3, not shown) subserve effects such as salivation, urination, defecation, pupillary constriction, vasodilation, cardiac slowing, depressed AV nodal conduction, and bronchoconstriction. The classical site of muscarinic receptors is at the postganglionic parasympathetic neuroeffector junction in smooth muscle, heart, and exocrine glands. However, muscarinic receptors also exist on effectors cells, even in the absence of cholinergic innervation. Prototype agonists include muscarine and ACh. The prototype non-selective antagonist is atropine. AF-DX 116 is a selective antagonist of M2 receptors and hexahydrosilafenidol is a selective antagonist of M3 receptors. The main contribution of such selective experimental agents is that they provided evidence for the existence of more than one type of muscarinic receptor, as well as raising the possibility of pharmacologically selective agonism or antagonism. Tiotropium, a selective antagonist of M3 receptors has recently been approved for treatment of chronic obstructive pulonary disease (COPD). One of the advantages tiotropium (over atropine, for example) is that it generally blocks only postsynaptic M3 receptors (that promote bronchoconstriction) but does not block presynaptic M2 receptors (that inhibit the release of ACh). Blockade of presynaptic M2 receptors tends to increase the release of acetylcholine and worsen COPD symptoms). Thus, tiotropium is a prime example of

the therapeutic significance of being able to pharmacologically distinguish between receptor subtypes. Modern molecular biology techniques have identified at least 5 different muscarinic receptors. At present, the pharmacologic and/or therapeutic significance of M4 and M5 is not yet definitive

Nicotinic receptors are cholinergic receptors which, when activated, mediate most of the actions of nicotine and some of those ACh. Examples of nicotinically-mediated effects include the release of catecholamines from the adrenal medulla, ganglionic transmission, and transmission of the somatic neuromuscular junction (NMJ). Autonomic and somatic nicotinic receptors are distinct pharmacologically. Ganglionic nicotinic receptors, (NN) are receptors for which classical agonists include ACh and dimethylphenylpiperazinium (DMPP) and whose antagonists are typified bymecamylamine (Inversine®), trimethaphan (Arfonad®) or hexamethonium. Somatic muscle nicotinic receptors, (NM) are receptors for which prototype agonists include nicotine, and ACh. Phenyltrimethylammonium (PTMA) is a selective agonist. The classical antagonist of the NM receptor is the non-depolarizing neuromuscular junction blocker, d-tubocurarine (Tubarine®). An ingredient of snake venom, alphabungarotoxin, binds almost irreversibly to and blocks the NM receptor. Drugs which act initially as depolarizing neuromuscular junction blockers (NM agonists), and then produce neuromuscular junction blockade even when the motor end plate has repolarized, include decamethonium and succinylcholine (Anectine®). It may be that these agents produce initial block by depolarizing the motor-end plate and then, because they are not rapidly broken down by acetylcholinesterase, promote receptor desensitization.

This diagram summarizes the cholinergic receptor system and some of its agonists and antagonists. The arrows are meant to show the range of selectivity of the various drugs for most practical purposes. Apparent selectivity of agonists or antagonists may be lost at relatively high concentrations. Relative affinities of a given drug for different receptors may be implied, but the affinities of different drugs are not shown in this qualitative guide. For such information, you will need to consult data on the apparent Kd, IC50 or other comparable measurements.

Adrenergic receptors

Adrenergic receptors, also called adrenoceptors, mediate the actions of epinephrine (Adrenalin®) and related compounds. Adrenergic receptors can be acted upon by a variety of agonists and antagonists, most of which are related to beta-phenylethylamine. The classical site of adrenergic receptors is the sympathetic neuroeffector junction. As in the case of cholinergic receptors, however, adrenergic receptors may exist on the cells of effector organs, even in the absence of sympathetic innervation. In other words, not necessarily all adrenergic receptors are innervated. Adrenergic drugs mimic the actions of epinephrine and are also called sympathomimetics. Direct-acting sympathomimetics act by direct stimulation of adrenergic receptors.

Adrenergic receptors may be divided into two major types according to drug (especially antagonist) potency on the receptors. Alpha receptors, when activated, generally produce excitatory responses of smooth muscle in which they are located. Beta receptors, when activated, generally produce inhibitory responses of smooth muscle in which they are located. Alpha receptors may be subdivided into: • Alpha1 receptors are sensitive to blockade by prazosin (Minipress®). Alpha1 receptors are mainly postsynaptic. • Alpha2 receptors are sensitive to blockade by yohimbine. Alpha2 receptors are found mainly presynaptically on sympathetic postganglionic nerve terminals. Activation of the presynaptic alpha2 receptors inhibits the release of NE and the term autoreceptor came into fashion. Some of the pharmacological effects of alphamethyl-norephinephrine (functioning as a false transmitter produced from alphamethyl DOPA) may be due to activation of alpha2 receptors and selective presynaptic inhibition of the release of NE. Recently it has been shown that some alpha2 receptors are present postsynaptically so the distinction between alpha1 and alpha2 receptors should be considered functional, rather than anatomic. Molecular biology has subdivided the alpha1receptors into alpha1A, alpha1B, and alpha1D. The alpha2 receptors subdivide into alpha2A (probably is the presynaptic autoreceptor), alpha2B and alpha2C. The major antihypertensive action of selective alpha agonists such as clonidine (Catapres®), probably occurs as a result of agonism of alpha2A receptors in the CNS.

Beta receptors when activated, generally produce "inhibitory" responses of smooth muscle in which they are located. Bronchodilation and vasodilation in some vascular beds can be produced by activation of beta-receptors. The classical agonist of betareceptors is isoproterenol (Isuprel®). The classical antagonist is propranolol (Inderal®).

Some beta-receptors subserve "excitatory" responses. For example, in heart, betareceptors are excitatory. Sympathetic positive chrono- and inotropism are mediated through excitation of beta-receptors. Therapeutic differentiation of beta-receptors is well established. Thus, we may consider: Beta1 receptors, when activated, produce cardiac positive chrono- and inotropic responses and lipolysis. The beta receptors of the heart are somewhat unique. For example, they produce cardiac excitation and, although NE does not act on betareceptors in vascular smooth muscle, it is equipotent with epinephrine in stimulating the heart. Isoproterenol acts as an agonist of beta1 receptors. Selective antagonists of beta1 receptors include metoprolol(Lopressor®) and CGP 20712A. Beta2 receptors, when activated, produce bronchodilation, vasodilation, and uterine relaxation. Selective beta2 agonists, which are useful in the treatment of asthma, includeterbutaline (Brethine®). Propranolol, which blocks both beta1 and beta2 receptors is generally contraindicated in bronchial asthma. ICI 118551 is a selective antagonist of beta2 receptors. labetalol (Normodyne®) is a clinically useful drug which is a selective alpha1 antagonist, and a non-selective antagonist of both beta1 and beta2 receptors. Beta3 receptors, when activated, produce lipolysis in adipose tissue. The significance and therapeutic application of this knowledge is still in its infancy. BRL 37344 is a relatively selective agonist of beta3 receptors. Antagonists include ICI 118551 and CGP 20712A, each of which is selective for beta1 and beta2 receptors, respectively.

This diagram summarizes the adrenergic receptor system and some of its agonists and antagonists. The arrows are meant to show the range of selectivity of the various drugs for most practical purposes. Apparent selectivity of agonists or antagonists may be lost at relatively high concentrations. Relative affinities of a given drug for different receptors may be implied, but the affinities of different drugs are not shown in this qualitative guide. For such information, you will need to consult data on the apparent Kd, IC50 or other comparable measurements.

https://courses.washington.edu/chat543/cvans/sfp/ansrec.html

55) Methacholine has main agonist action at a) M2 b) M1 c) M4 d) M3 D Airway smooth muscle constriction induced by cholinergic agonists such as methacholine (MCh), which is typically increased in asthmatic patients, is regulated mainly by muscle muscarinic M3 receptors and negatively by vagal muscarinic M2 receptors. http://www.pubfacts.com/detail/23691511/Role-of-m2-muscarinic-receptorin-the-airway-response-to-methacholine-of-mice-selected-for-minimal-o

56) Diuretic which can be given in mild to moderate hypertension

a) Loop diuretic b) Thiazide c) Osmotic diuretic d) Potassium sparing diuretic B 57) All of these drugs can cause Hearing loss except a) Metronidazole b) Vancomycin c) Kanamycin d) Quinine A 58) Which of the following is a protease inhibitor a) Saquinavir b) Nevirapine c) Abacavir d) Enfuvirtide A 59) What is the type of inhibition of Acetylcholinesterase caused by Organophosphates a) Competitive b) Non competitive c) Uncompetitve d) irreversible inhibitor D 60) Which does not act by increasing insulin secretion for its action a) Exenatide b) Sitagliptin c) Rosiglitozone d) Repaglinide C ANS=Rosiglitozone The thiazolidinediones rosiglitazone and pioglitazone are insulin sensitizers. Troglitazone, another thiazolidinedione, was removed from the MARKET in 2000 because of hepatotoxicity. These drugs bind to peroxisome proliferator-activated

receptors (PPARs) in cells, and this drug-PPAR complex (with one or more coactivators) acts on response elements in promoter regions to affect the transcription of as many as 100 genes. They may act to stimulate production of proteins that increase insulin sensitivity, such as adiponectin.14,15 They may also act by blocking transcription of other proteins responsible for insulin resistance or inflammation.14,16 PPARs exist in several different forms: PPARα, PPARδ, and PPARγ. PPARγ is the major target of thiazolidinediones http://clinical.diabetesjournals.org/content/25/4/131.full

61) Nitroglycerine is effective as sublingual medication because a) Non Ionic, highly lipid soluble b) Ionic, lipid soluble c) Ionic, less lipid soluble d) Non ionic, less lip soluble A 62) In a child admitted with H. Influenza meningitis, Cefotaxime was started instead of ampicillin. Which of these is the likely reason for this a) H.influenzae stains known to produce Beta lactamase b) H.influenzae stains known to have altered pencillin binding protein c) More easier to give d) ?? A Antibiotics and supportive care These are the mainstays of treatment. Initially, invasive and serious H influenzae type b (Hib) infections are best treated with an intravenous third-generation cephalosporin until antibiotic sensitivities become available. In Malawi, Africa, intramuscular ceftriaxone was compared with intravenous ceftriaxone and was not found to increase the mortality rate. This may be important in developing countries where the intravenous route may not be possible. [12] The site of infection and the clinical response determine the length of antibiotic treatment. Meningitis Administer parenteral antibiotics (eg, ceftriaxone, ceftazidime, cefotaxime, ampicillin-sulbactam, fluoroquinolones, azithromycin) to patients with uncomplicated meningitis for 7-14 days. Cefotaxime and ceftriaxone are the initial drugs of choice for suspected Hib meningitis. Once the susceptibilities are known, adjust antibiotics accordingly. Do not use ampicillin empirically, since as many as 50% of the isolates are resistant,

usually because of plasmid-mediated beta-lactamase production. 63) Reverse transcriptase is a RNA dependent DNA polymerase. Which of these use it a) Hepatitis A virus b) Hepatitis B virus c) Hepatitis E virus d) Hepatitis C virus B 64) A vesicle on shin… microscopy on Tzank smear showed giant cells. Causative agents is a) Vaccinia virus b) Varicella zoster c) Tuberculous d) Molluscum contagiasum B 65) Vibrio cholerae acts by disrupting which of the following a) Hemidesmosome b) Gap junctions c) Anchoring junctions d) Tight junctions D Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions. Attenuated Vibrio cholerae vaccine strains specifically mutated in genes encoding cholera toxin (CT) are still capable of causing mild to moderate diarrhea. Culture supernatants of V. cholerae strains, both CT-positive and CT-negative, were examined in Ussing chambers, and a toxin was found that increases the permeability of the small intestinal mucosa by affecting the structure of the intercellular tight junction, or zonula occludens. The activity of this toxin is reversible, heat-labile, sensitive to protease digestion, and found in culture supernatant fractions containing molecules between 10 and 30 kDa in size. Production of this factor (named ZOT for zonula occludens toxin) correlates with diarrheagenicity of V. cholerae strains in volunteers and may represent another virulence factor of infectious diarrhea that must be eliminated to achieve a safe and effective live oral vaccine against cholera. http://www.ncbi.nlm.nih.gov/pubmed/2052603

66) Filarial stage of adult worms responsible for diseases in all of the following except: a) Onchocerca volvulus b) Brugia malayi c) Wuchereria bancrofti d) Mansonella ozzardi ANS=D Mansonella ozzardi Mansonella ozzardi nematodes are confined to the westerm hemisphere. These are non-pathogenic filarial nematodes. The parasites cause nodules in the skin of the vertebrate hosts. Morphology The adult worms are located in the mesenteric tissues and their size is comparable to the pathogenic species already discussed (0.6m long). The microfilariae are found in the peripheral blood and range between 173-240µm in length. The nuclei do not extend to the tip of the tail which has a pointed end. The male adult worm is almost unknown. Clinical Disease Infections caused by M. ozzardi are generally symptomless, however lymphadenopathy, arthralgia, fever and eosinophilia have been reported. http://www.phsource.us/PH/PARA/Chapter_10.htm

67) IgE receptor present on a) Mast cell b) NK cell c) B cell d) ?? A 68) Two bodies are found outside the car following an accident. The doctor conducting the autopsy was able to decide who was driver and who was passenger based on all of these features except a) Sparrow foot mark b) Seat belt abrasion over Left shoulder c) Steering wheel imprint d) Whiplash injury?

B ans=b Front seat passenger/ Whiplash injury: It is due to a violent acceleration or deceleration force applied to the passenger, usually front seat occupant. X. He may not get the momentary warning of the impending collision. XI. There may be peculiar facial lacerations due to contact with the shattered windscreen known as “Sparrow Foot marks”. XII. Passenger of the rare seat often escape such injuries, they may be injured against internalFITTINGS ,

like

Doors,

Handles

or

ejected

through

burst-open

doors.

http://www.slideshare.net/neharikasingh9678/road-traffic-injury http://www.slideshare.net/neharikasingh9678/road-traffic-injurY Whether the victim was the driver or the passenger? Some times it is necessary to know who was driving the vehicle for insurance purpose. Following can assist the autopsy surgeon in determining if a particular occupant was the driver. ♣Steering wheel impact abrasions may be seen on the chest. ♣Dicing injuries on the right side of the body. ♣Pattern seat belt abrasions is seen on the right side of the shoulder going diagonally across the chest of the left. ♣Imprint marks of the break and clutch pedals on the sole of shoe is pressed at the time of impact. 45. ′ In different jurisdictions autopsy, surgeons may rule the manner of death in Hit and run pedestrian fatalities as „HomicideA or „accidentA or „undeterminedA depending on the existing protocol. ¬Alcohol, Drugs And Trauma:♣ ♣ Alcohol and substance abuse are major associated factors in all major trauma. About 10% of drivers with blood alcohol level higher then the legal limit account of nearly 1/3rd of non fetal and half of fatal driver deaths.

69) Lower two parts of the sternum fuses with its body by age a) 12 years b) 14 years c) 8 years d) 10 years B In cartilaginous sternum, five double bony centres appear from above downwards during fifth, sixth, seventh, eighth and ninth fetal months. The upper centre forms the manubrium. Remaining four form body of sternum and fuse with one another from below to upwards. Lower two centres fuse at age of 14 years and upper two centres fuse between 14 to 25 years. The centre of xiphoid process appears during the third years or later and fuses with the body at about 40 years

70) Mr.X fired his gun at Mr.Y who moved and escaped with the bullet only grazing his thigh. There was only a little bleeding and no other significant injury. Mr. X is liable for arrest under which section of IPC? a) 302 b) 304 c) 324 d) 326

C Section 324 in The Indian Penal Code 324. Voluntarily causing hurt by dangerous weapons or means.—Whoever, except in the case provided for by section 334, voluntarily causes hurt by means of any instrument for shooting, stabbing or cutting, or any instrument which, used as weapon of offence, is likely to cause death, or by means of fire or any heated substance, or by means of any poison or any corrosive substance, or by means of any explosive substance or by means of any substance which it is deleterious to the human body to inhale, to swallow, or to receive into the blood, or by means of any animal, shall be punished with imprisonment of either description for a term which may extend to three years, or with fine, or with both.

http://indiankanoon.org/doc/724142/

71) High court has the power to stay the execution of a pregnant woman according to section a) 416 Cr. P. C. b) 417 Cr. P. C. c) 418 Cr. P. C. d) 419 Cr. P. C. A 72) A person was advised by his Orthopedician to get regular dressing of his wound done. But the patient did not give much care. The patient visited after some time at which time the Orthopedician again advised regular dressing but dint do the dressing himself as he said he was busy. Finally the wound enlarged and the underlying bone developed osteomyelitis. Which statement is true a) Doctor not guilty under “contributory negligence” b) Doctor guilty under “Last clear chance” doctrine c) d) ANS=B LAST CLEAR CHANCE: HELPLESS PLAINTIFF A plaintiff who has negligently subjected himself to a risk of harm from the defendant's subsequent negligence may recover for harm caused thereby if, immediately preceding the harm, (a) the plaintiff is unable to avoid it by the exercise of reasonable vigilance and care, and (b) the defendant is negligent in failing to utilize with reasonable care and competence his then existing opportunity to avoid the harm, when he (i) knows of the plaintiff's situation and realizes or has reason to realize the peril involved in it or

(ii) would discover the situation and thus have reason to realize the peril, if he were to exercise the vigilance which it is then his duty to the plaintiff to exercise.

https://en.wikipedia.org/wiki/Last_clear_chance Contributory Negligence Sometimes the unexpected results may not be only due to negligence of the doctor but also due to negligence of patients or relatives. This is known as contributory negligence. Examples include: (a) Not coming for follow-up as per the advice of doctor; (b) Failure to follow the instructions given by the treating doctor; (c) Investigations advised by the doctor are not done by the patient; (d) Patient fails to take advice of a specialist (for example, in case of acute abdomen or head injury, the Pediatrician has referred to a surgeon but the patient fails to take such a consultation); and (e) patient leaves the hospital against medical advice. The liability for the damage in such cases is suitably divided between the doctor, patients and relatives. The burden of proof of contributory negligence on the part of patient is on doctors.

http://www.indianpediatrics.net/may2001/may-488-495.htm

73) Rat hole tear is associated with which injury a) Postmortem artifact b) Firearm c) Razor blade d) ?? B 74) Segmented of blood in blood vessel after death is called a) Kevorkian sign b) Rokitansky sign c) Tache noir d) ?? A 75) Acrid (pear like) smell is seen in a) Ether b) Paraldehyde c) Phenol d) ?? B Welcome to the ‘Sniff a Poison’ Challenge! How this works

Below is a list of odo(u)rs. For each different odour try to identify the poison(s) or toxin(s) that can give rise to it – then click on the odour (in blue) to show/hide the answer. If there are multiple answers, the number of answers listed is shown in brackets. Start sniffing! •

Ammonia — ammonia (its good to get off to an easy start…)

•

Bitter almonds — cyanide (40% of people are genetically incapable of smelling this)

•

Burnt rope (2) — marijuana — opium

•

Disinfectant (2) — phenol — creosote

•

Fruity (12!) — nitriles — isopropyl alcohol — ketoacidosis — lacquer — ethanol — isopropanol — chloroform — trichloroethane — paraldehyde — chloral hydrate — methylbromide — nitrites (amyl, butyl)

•

Garlic (7) — phosphorus — tellurium — inorganic arsenicals and arsine gas

— organophosphates — selenium — thallium — dimethyl sulfoxide (DMSO) •

Fish or raw liver (musty) (3) — zinc phosphide — aluminum phosphide — nickel carbonyl

•

Hay — phosgene

•

Mint (2) — methylsalicylate OIL of Wintergreen) — menthol

•

Mothballs (3) — napthalene — camphor — p-dichlorobenzene

•

Pear — chloral hydrate

•

Pepper — o-chlorobenzylidene malonitrile (CS or tear gas)

•

Pine — pineOIL

•

Rotten eggs (5) — Hydrogen sulfide (olfactory fatigue occurs after about 15 minutes at the potentially toxic level of 50 ppm. This happens even faster at higher concentrations – so the victim is at least spared the stench of rotten eggs…) — carbon disulfide — mercaptans — disulfiram — N-acetylcysteine (antidote)

•

Shoe polish — nitrobenzene

•

Tobacco — nicotine!

•

Vinegar (2) — acetic acid — hydrofluoric acid

•

Violets

— turpentine (urinary metabolites) http://lifeinthefastlane.com/toxicology-conundrum-027/

76) A man fell from 35 feet height. Eyewitnesses say that he landed on his feet. Which of the following injuries is possible a) Ring fracture of Foramen magnum + Lumbar spine injury b) Pond fracture skull + Cervical spine injury c) Gutter fracture skull + Cervical spine injury d) Depressed fracture skull + Cervical spine injury A LUMBOSACCRAL SPINE IS MORE PRONE TO FRACTURES AND COMPRESSION INJURIES Fracture around foramen magnum (Ring Fracture) : This is a type of fissured fracture which encircles the base of skull around the foremen magnum running 3 – 5 cm outside foramen magnum at the back and sides of the skull. Such fractures are seen in following cases : (A) Fall from height where a person falls on feet or buttock and impact passes upward through spinal column. (B) Fall from height where head strikes the ground first. (C) Fall of heavy load on head. (D) Violent twisting of head.

77) The “knot” in judicial hanging is placed at a) The back of the neck b) The angle of jaw c) Below the chin d) Choice of hangman B Judicial hanging: The knot is under the angle of jaw in Indian legal death sentence. ------------------------------------------------------------------------------------------------------------------

Hanging is one of the oldest methods for capital punishment in most countries with India being no exception. The procedure of execution has largely remained unchanged over the centuries. Some modifications to its process were introduced in the late 19th century to make it more humane, quick and painless, and without decapitation. But still death in most cases were due to strangulation causing delayed deaths and not the intended fracture of cervical column which would cause instantaneous death. After autopsy examination of many cases of judicial hanging, researchers proposed that for instant death, the position of the knot should be submental and the ‘drop’ length should be based upon the weight of the condemned person. The other concern is the involvement of doctors in the process of execution which is considered against the Hippocratic Oath. Over the years, doctors have helped the state to devise newer methods of execution. They are actively involved in preparing the condemned person, checking on their health with the purpose of supervising their death, prescription of the lethal cocktails, putting in of intravenous lines, pronunciation of death, and some are also involved in removal of their organs. The Medical Council of India should strongly oppose to doctors taking part in execution process. Ethical practice guidelines should be framed in lines similar to American Medical Association. Actions which are at the most acceptable are providing sedative to calm anxiety at the prisoner’s request and certification of death after another person had pronounced it http://www.jaypeedigital.com/Chapter/ChapterDetail/67547…

78) A bomb blast took place in Delhi following which 2 persons died. All of the following are true about their injuries except a) Injuries due to ... burns or air blast b) Force of explosion is directional c) Force of explosion decreases rapidly. d) Bruise, laceration ,fractures are triad of main injuries seen ans=?? A CONTROVERSIAL QUESTION Explosion is a sudden release of previously confined energy characterized by release of large volume of gas with high pressure, heat and noise. Explosion may be from two sources, improvised explosion devices or fuel-air explosion. Four workers were working at a chemical reactor in a pharmaceutical factory. On 5th January, 2013 explosion of chemical reactor took place in pharmaceutical factory at Nakkapalli, two succumbed to blast injuries on spot and two other succumbed to burns in hospital. Explosive forces are directional and decline rapidly.

http://www.jebmh.com/latest-articles.php?at_id=884

Emergency Preparedness 18: Explosion and Blast Injuries Portal In the past, explosive and blast injuries have occurred during times of organized military conflict or have resulted from non-intentional events, such as industrial accidents. More recently, explosive devices have become a preferred weapon of domestic and foreign terrorists since they are inexpensive to produce, capable of causing large numbers of casualties, and effective at instilling fear in large populations.1 Consequently, blast injuries are being observed in non-combat locations during peace time as evidenced in the Alfred P. Murrah Federal Building in Oklahoma City in 1995, the United States Embassy in Lagos, Nigeria, Africa in 1998, and the 9/11 attacks on the WorldTRADE Center and Pentagon in 2001. Whenever medical personnel are called upon to treat patients with explosive or blast injuries, conditions will obviously be difficult or austere. Thus it is important for the health provider team to approach these situations in an organized fashion, cognizant of the team’s resources as well as the potential for injuries unique to blast situations. General Treatment Considerations in Explosion and Blast Injuries In non-war or non-combat situations, for an explosion or blast to occur other than when unanticipated or by surprise is rare. The health care team needs a general plan outlining an approach to these disasters. (Vol III—EMP1 Community-Wide Collaboration)While the organized implementation of this disaster plan is of great value in any large emergency, some considerations are unique to implementing the plan during explosion or blast scenarios. These include: 1. What available resources are at your disposal? o What available resources—including the number of trained medical personnel, support staff, and equipment—can be mobilized in your health care institution? o What community resources can be mobilized to assist with the care of the disaster victims? How will these be obtained? o What resources can be obtained from outside the community? How will these facilities be notified of your needs? o What state or national agencies—such as the State Department of Health, Federal Emergency Management Agency (FEMA), and American Red Cross—need to be contacted? Who will contact these agencies?

2. How will you triage the patients? Large numbers of victims in a disaster situation can overwhelm almost any medical system. The use of an effective triage system helps to assure that limited resources are utilized to do the greatest good for the greatest number of people. One triage method to consider is a modified START Triage System,5 which is based on classifying patients into one of four categories. (See Vol III— EMP9, Triage.) These categories include patients who: o Need immediate care to survive–Priority 1 (P-1). o Need care but can have the care delayed–Priority 2 (P-2). o Do not appear to have any serious injury but need to be held for later evaluation–Priority 3 (P-3). o Will most likely die no matter how you assist them–Priority 0 (P-0). 3. What special problems may be associated with the blast/explosion? These may include additional, non-visible, risks such as: o Biological agent contamination o Exposure to inhalation of toxic agents o Nuclear contamination

o

Repeat terrorist assault

4. What injuries unique to blast situations may your patient have? Explosions can produce unique patterns of injury seldom seen outside of combat. These injuries can involve multiple organ systems, especially the lungs, ears, bowel (gastrointestinal [GI] tract), and central nervous system (CNS). 5. How do you manage the wide range of routine traumatic injuries inflicted on your patients in addition to all of the injuries unique to blasts? 6. How do you manage the post-traumatic stress disorder (PTSD) in the victims of the blast, their friends and relatives, and treating medical staff? Classification of Explosives2 One method of classifying non-nuclear explosives is to divide them as either high-order explosives (HE) or low-order explosives (LE). Examples of HE include TNT, ammonium nitrate fuelOIL , dynamite, and nitroglycerine. Examples of LE include gunpowder, pipe bombs, and pure petroleum-based bombs like Molotov cocktail or aircraft used as guided missiles. HE and LE create different injury patterns, primarily because HE produces a supersonic over-pressurization shock wave that causes unique injuries. The HE shock wave is created at detonation by the rapid chemical decomposition of the explosive material into gas.1 This gas is created under high pressure and temperature and is transmitted as the blast (or shock) wave. This pressure-pulse is only a few millimeters thick and travels outward from the point of detonation at supersonic speeds. The blast (or shock) wave may have focal over-pressure up to eight times atmospheric pressure. This sudden change in environmental pressure (blast-wave) impacting with the body causes the primary blast injuries unique to HE. The blast injuries are especially evident in the gas-filled structures on the body, including the lung, GI tract, and middle ear. As the blast front travels from the explosion, it decreases in pressure until the blast-wave is reduced into an acoustic wave.1This creates a blast-wind, which can propel objects and people considerable distances, resulting in additional damage to life and objects. Basic Categories of Blast Injuries2 1. Primary blast injuries2—result from the impact of the blast-wave with the body. The effects are most evident in gas-filled structures on the body where the over-pressurized blast-wave causes rapid compression and expansion of the gas-filled structures resulting in tissue damage, hemorrhage, or organ rupture. (See below for further information about specific organ damage.) 2. Secondary blast injuries2—are due to objects (including bomb fragments and flying debris) becoming energized by the blast, resulting in their acting as projectiles. These flying objectprojectiles can affect any part of the body with either penetrating or blunt trauma. 3. Tertiary blast injuries2—result from individuals being thrown by the blast-wind or injuries caused by the collapse of structures due to an explosion. Any part of the body can be affected. Common injuries include fractures, amputations, and/or brain injuries. 4. Quaternary (miscellaneous) blast injuries2—This group includes the other explosion-related injuries, illnesses, or diseases not due to one of the three mechanisms just listed. These include burns and the exacerbation or complications of existing conditions such as asthma; chronic obstructive pulmonary disease (COPD); breathing problems from dust, smoke, or toxic fumes; and the patient’s development of angina, hyperglycemia, etc. Specific Blast Injuries 1. Primary Blast Injuries to the Lung (Blast-Lung)2—Blast-lung is a direct consequence of an HE over-pressurized shock wave impacting the body. The signs and symptoms of blast-lung are usually present at the time of initial presentation to the health care facility but may not become

evident for up to 48 hours after the victim is exposed to the explosion. The characteristic clinical triad of severe blast-lung is apnea, bradycardia, and hypotension; but all patients who complain of dyspnea, cough, hemoptysis, or chest pain after an explosion exposure should be evaluated for blast-lung. Lung pathology ranges from simple scattered pulmonary petechiae to confluent lung hemorrhages resulting in severe hypoxia and respiratory failure. Primary blast-lung is the most common cause of death in patients who initially survive an explosion. Management of patients suspected of having blast-lung includes obtaining a routine chest x-ray. The characteristic x-ray finding of significant blast-lung is a butterfly pattern due to pulmonary hemorrhage, but this pattern may not be apparent at the time of initial evaluation. Patients with severe blast-lung may require intubation and respiratory support. Prophylactic chest tubes are recommended for patients suffering from an explosion-generated blast-lung who need general anesthesia or air transport to prevent the patient from developing a post-blast tension pneumothorax during surgery or flight. 2. Ear Injury from Blast2 Ear injuries are a common result of explosion exposure, especially in the ear oriented toward the blast. While a perforated TM is the most common manifestation of a blast-ear injury, not infrequently there are no significant early complaints or physical findings at the time of initial evaluation. Ear signs and/or symptoms such as hearing loss, tinnitus, otalgia, vertigo, bleeding from the ear canal, or otorrhea should raise the provider’s suspicion of ear injury. All patients exposed to a blast should have an otological evaluation and audiogram after the more serious injuries have been treated. 3. Abdominal Injuries from Blast (Blast-Abdomen)2 Gas-containing structures of the GI tract are especially vulnerable to the primary blast effects of a blast-wave. Injuries include: o Immediate or late bowel perforation o Hemorrhage—ranging from small petechiae to large hematomas o Mesenteric shear injuries o Solid-organ lacerations o Testicular rupture Symptoms that may suggest a blast injury to the abdomen in a blast victim include: o Abdominal pain o Nausea and vomiting o Hemetemesis o Rectal pain o Tenesmus o Testicular pain o Unexplained hypovolemia o Evidence for an “acute abdomen” Clinical findings of a blast-abdomen may be delayed from hours to days. 4. Central Nervous System Injuries from a Blast2 Brain injury from a blast can occur without a direct blow to the head. The primary blast (shock) wave can cause varying central nervous system (CNS) damage from a mild concussion (often referred to as mild traumatic brain injury [MTBI]—see below) to severe brain injuries. Blast CNS injuries may include: o Concussion o Closed or open brain injury o Stroke syndrome o Spinal cord injury o Air-embolism induced CNS injury

MTBI3 refers to a syndrome caused by a seemingly mild brain injury or concussion that usually presents with minimal or non-observable symptoms but which may have significant long-term sequelae. Long-term signs and symptoms of patients experiencing MTBI may include3: • Cognitive changes: manifested as attention difficulties, memory problems, difficulty with concentration and orientation. • Physical complaints: headaches, dizziness, insomnia, fatigue, nausea, blurred vision, or ataxia. • Behavior changes: including irritability, depression, anxiety, sleep disturbance, emotional lability, loss of initiative, and relationship problems. A diagnosis of MTBI may be difficult to make since the symptoms are non- specific and are similar to many other medical conditions including PTSD. Consider MTBI in patients with the above symptoms and a history of head trauma or blast exposure, especially if they have amnesia of the event, had loss of consciousness for < 30 minutes, and had a GCS score > 13. 5. Eye Injuries from Blast2 As many as 10% of all blast survivors have a significant eye injury. The most common eye injuries are globe perforations from high-velocity projectiles, foreign bodies on the cornea or in the globe, air emboli, or orbital rim fractures. For a patient to have minimal initial discomfort and not present for care of the eye injury for days, weeks, or even months after the event is not unusual. Symptoms that may suggest eye injury include: • Eye pain • Eye irritation • Foreign body sensation • Altered vision • Findings that suggest an eye injury include: • Periorbital swelling or contusions • Decreased visual acuity • Hyphema • Globe perforation • Subconjunctival hemorrhage • Eye foreign body • Lid laceration 6. Musculoskeletal and Other Soft Tissue Injuries from Blasts1 Musculoskeletal injuries from blasts result from the combination of forces generated by a blast. The abrupt rise in atmospheric pressure created by the passing blast-wave causes many fractures and contributes to limb avulsion. The mechanism of explosive blast amputation is frequently the combination of the coaxial forces of the blast-wave inducing the fracture followed by limb avulsion through the fracture site by the dynamic forces of the blast-wind acting on the whole limb. Blast-induced lower limb amputations are most common at the level of the tibial tuberosity, while the upper limb amputations tend to be more distal in the limb. Other soft tissue injury is also common. The debris and casing fragments energized by the blast are propelled with a tumbling and shimmy effect that increases the amount of tissue damage upon impact with a victim. In addition, the debris is very contaminated with environmental bacteria resulting in extensive wound contamination.

7. Other Special Considerations During Evaluation of Blast Victims1 o o o

Fragments, energized by a blast, do not travel in straight lines after they enter the body. Small entry wounds can be associated with extensive internal injury. Entry wounds in the buttocks, thighs, or perineum can be associated with intra-abdominal injuries.

Health care providers need to maintain a high degree of suspicion that a compartment syndrome may develop in injured extremities. o An entry wound in the groin or the development of a hematoma elsewhere may mean that a major vascular injury has occurred. Special Considerations in the Care of Patients Manifesting Blast Injuries The initial approach to patients who have experienced injuries from an explosion or blast follows the CALS Universal Approach for Critical Patient Care with coordination of the team’s efforts to be as efficient and effective as possible. Some special treatment considerations include: • The potential risk that the victim may have been contaminated with a biological, chemical, or nuclear agent. • The unique syndromes associated with blast exposure including the development of blast-lung or blast-abdomen. • When the number of victims is large compared to the number of providers, how to triage patients to maximize the good performed by the treatment team. • Blast wounds are contaminated with bacteria and debris and are associated with a high risk of infection.1 Meticulous wound care is essential, including the removal of non-metallic foreign material, excision of non-viable tissue, and irrigation of wounds with copious amounts of solution (isotonic if possible) to help remove bacteria and foreign material. • Prophylactic antibiotics should be considered.1 1. Gas gangrene, by anaerobic Clostridium species, is a major threat with blast injuries. Penicillin IV helps reduce the risk. Alternative antibiotics include erythromycin, chloramphenicol, or a cephalosporin. 2. In severely contaminated blast injuries, Pseudomonas aeruginosa may be a problem. Consider giving an aminoglycoside IV or a different drug effective against Pseudomonas. o

3. Open fractures need coverage against gram-positive organisms. A penicillinase-resistant penicillin or a cephalosporin IV is appropriate. 4. Tetanus is a high risk. Give the patient tetanus prophylaxis and consider the need for anti-tetanus immunoglobulin. • Post-Traumatic Stress Disorder4 – The development of PTSD is a risk following any traumatic event associated with a sense of horror or helplessness, the development of serious injury, or the threat of serious injury or death. It may manifest not only in survivors who have directly experienced the traumatic event but also in the relatives and/or close friends of the victims as well as in rescue workers. Frequently, symptoms associated with the PTSD do not become apparent for weeks or months following a traumatic event. The symptoms characteristic of PTSD are similar to those observed with patients suffering with the late sequelae of MTBI and include: 1. Cognitive effects – such as poor concentration, memory loss, shortened attention span, or indecisiveness. 2. Emotional manifestations – including depression, numbness, feeling of being overwhelmed, or volatile emotions. 3. Physical complaints – of nausea, dizziness, rapid heart rate, headache, tremors, or undefined pain. 4. Behavior changes –including irritability, excessive silence, suspicion, argumentum, or withdrawn. The care of patients with injuries as a result of a blast or explosion exemplifies the critical need for the provider team to have a preplanned approach to major disasters. This includes having a well developed disaster plan utilizing all of the available resources as efficiently as possible; a triage system designed to fit your facility; the proper basic equipment to handle critical, life-threatening, emergencies; and a system

built to maximize the cooperation of the health care team. With proper planning, major disasters can be managed to the benefit of the great majority of the victims with a minimum of risk to the provider team. https://calsprogram.org/manual/volume3/Section13/19-EMP18Expl&BlastInjuries13.html

Introduction: An explosion is a process where any substance or device capable of creating a sudden gas expansion, releasing potential energy and thus creating a pressure wave. Compression of the air in front of the pressure wave, which heats and accelerates air molecules, leads to sudden increase in atmospheric pressure and temperature transmitted to the surrounding environment as a radially propagating shock wave, known as the „Blast wave. [1] Injuries directly inflicted by this sudden increase in air pressure after an explosion are referred to as „primary blast injuries, and mainly affect primary gas containing structures (lungs, middle ears and gastrointestinal tract). [1-3] A minimum pressure of about 700 kPa (100 lbs/sq inch) is necessary for severe tissue damage in humans. [4 Secondary blast injuries result from blast-energised bomb fragments and other displaced objects causing penetrating trauma. Tertiary blast injuries occur when the body is accelerated away from the blast wave at first and is then abruptly decelerated on rigid objects resulting in blunt force trauma. [1] Quaternary injuries (Miscellaneous blast related injuries) encompass injuries caused by collisions, falling masonry, buildings, beams, etc. [5] Explosive force is highly directional. The parts of the body directly exposed to the explosive force only are injured. An explosion at ground level mainly injures legs and feet. When a person is in front of a bomb when it blows up, the face, chest, forearms, hands, inner thighs and legs below knees are injured, but the back of the body, the lower legs and face escape. If a person is bending down over the bomb, the face, chest, legs and hands are severely damaged. [4] Orthopaedic trauma resulting from an explosion is manifested as a primary, secondary, tertiary or quaternary (miscellaneous) blast injury in isolation or in combination. Although uncommon in survivors, the direct effects of changes in atmospheric pressure caused by the blast wave (primary blast injury) can fracture bones and it is probably responsible for limb avulsions in victims exposed to stress waves of sufficiently high intensity

http://medind.nic.in/jal/t15/i1/jalt15i1p85.pdf

79) After an incised wound, new collagen fibrils are seen along with growing epithelium. The age of the wound is a) 4-5 days b) About 1 week c) 12-24 hours d) 24 -72 hours A

WOUND HEALING Healing of skin wounds provides a classical example of combination of regeneration and repair described above. This can be accomplished in one of the following two ways: Healing by first intention (primary union): and Healing by second intention (Secondary union) Healing by First Intention (Primary Union) This is defined as healing of a wound which has the following characteristics: i) Clean and uninfected; ii) Surgically incised; iii) Without much loss of cells and tissue; and iv) Edges of wound are approximated by surgical sutures Page 2 Page 3 WOUND HEALING The sequence of events in primary union are described below: 1. Initial haemorrhage: Immediately after injury, the space between the approximated surfaces of incised wound is filled with blood which then clots and seals the wound against dehydration and infection. 2. Acute inflammatory response: This occurs within 24 hours with appearance of polymorphs from the margins of incision. By 3rd day, polymorphs are replaced by macrophages 3. Epithelial changes: The basal cells of epidermis from both the cut margins start proliferating and migrating towards

incisional space in the form of epithelial spurs. A wellapproximated wound is covered by a layer of epithelium in 48 hours. The migrated epidermal cells separate the underlying viable dermis from the overlying necrotic material and clot, forming scab which is cast off. The basal cells from the margins continue to divide. By 5th day, a multilayered new epidermis is formed which is differentiated into superficial and deeper layers. Page 4 WOUND HEALING 4. Organization: By 3rd day, fibroblasts also invade the wound area. By 5th day, new collagen fibrils start forming which dominate till healing is completed. In 4 weeks, the scar tissue with scanty cellular and vascular elements, a few inflammatory cells and epithelialised surface is formed. 5. Suture tracks: Each suture track is a separate wound and incites the same phenomena as in healing of the primary wound i.e. filling the space with haemorrhage, some inflammatory cell reaction, epithelial cell proliferation along the suture track from both margins, fibroblastic proliferation and formation of young collagen. When sutures are removed around 7th day, much of epithelialised suture track is avulsed and the remaining epithelial tissue in the track is absorbed. However, sometimes the suture track gets infected (stitch abscess) or the epithelial cells may persist in the track (implantation or epidermal cysts). Thus, the scar formed in a sutured wound is neat due to close apposition of the margins of wound; the use of adhesive tapes avoids removal of stitches and its complications. http://faculty.ksu.edu.sa/8210/Documents/Inflammation.Lecture9.pdf 80) Sweating is absent in a) Heat stroke b) Heat syncope c) Heat exhaustion d) Miner’s cramps A 81) According to the 2013 amendment the age for sexual consent is a) 16 years

b) 18 years c) 20 years d) 15 years B ans-B 375. A man is said to commit "rape" if he— Rape- (a) penetrates his penis, to any extent, into the vagina, mouth, urethra oranus of a woman or makes her to do so with him or any other person; or (b) inserts, to any extent, any object or a part‘ of the body, not being the penis, into the vagina, the urethra or anus of a woman or makes her to do so withhim or any other person; or (c) manipulates any part of the body of a woman so as to cause penetrationinto the vagina, urethra, anus or any part of body of such woman or makes her todo so with him or any other person; or (d) applies his mouth to the vagina, anus, urethra of a woman or makes her to do so with him or any other person, under the circumstances falling under any of the following seven descriptions:— First. —Against her will. Secondly—Without her consent. ThirdIy—With her consent, when her consent has been obtained byputting her or any person in whom she is interested, in fear of death or of hurt. F ourthly—With her consent, when the man knows that he is not herhusband and that her consent is given because she believes that he is anotherman to whom she is or believes herself to be lawfully married. Fiflhly.—With her consent when, at the time of giving such consent, by reason of unsoundness of mind or intoxication or the administration by him personally or through another of any stupefying or unwholesome substance,she is unable to understand the nature and consequences of that to which shegives consent *****Sixthly—With or without her consent, when she is under eighteen years of age.****** Seventhly.--When she is unable to communicate consent. Explanation I.—For the purposes of this section, "vagina" shall also includelabia majora. Explanation 2.—Consent means an unequivocal voluntary agreement whenthe woman by words, gestures or any form of verbal or non-verbal communication,communicates willingness to participate in the specific sexual act http://indiacode.nic.in/acts-in-pdf/132013.pdf 82) HPV can cause all of these cancers except a) Base of tongue carcinoma b) Tonsillar carcinoma c) Nasopharyngeal carcinoma d) Ca Cervix C What head and neck cancers can be caused by HPV? Ads by RainbowPricesAd Options HPV can cause cancers in the back of the throat, most commonly in the base of the

tongue and tonsils, in an area known as the “oropharynx.” These cancers are called “oropharyngeal cancers.” How does HPV cause cancer? HPV can cause normal cells in infected skin to turn abnormal. Most of the time, you cannot see or feel these cell changes. In most cases, the body fights off the HPV infection naturally and infected cells then go back to normal. But in cases when the body does not fight off this virus, HPV can cause visible changes and certain types of HPV can cause an oropharyngeal cancer. Cancer caused by HPV often takes years to develop after initially getting an HPV infection. It is unclear if having HPV alone is sufficient to cause oropharyngeal cancers, or if other factors (such as smoking or chewing tobacco) interact with HPV to cause these cancers. More research is needed to understand all the factors leading to oropharyngeal cancers. http://www.cancer.med.umich.edu/news/nasopharyngeal-cancer09.shtml What head and neck cancers can be caused by HPV? Ads by RainbowPricesAd Options HPV can cause cancers in the back of the throat, most commonly in the base of the tongue and tonsils, in an area known as the “oropharynx.” These cancers are called “oropharyngeal cancers.” How does HPV cause cancer? HPV can cause normal cells in infected skin to turn abnormal. Most of the time, you cannot see or feel these cell changes. In most cases, the body fights off the HPV infection naturally and infected cells then go back to normal. But in cases when the body does not fight off this virus, HPV can cause visible changes and certain types of HPV can cause an oropharyngeal cancer. Cancer caused by HPV often takes years to develop after initially getting an HPV infection. It is unclear if having HPV alone is sufficient to cause oropharyngeal cancers, or if other factors (such as smoking or chewing tobacco) interact with HPV to cause these cancers. More research is needed to understand all the factors leading to oropharyngeal cancers. http://www.cdc.gov/std/hpv/stdfact-hpvandoralcancer.htm

83) Kashima operation done for a) Vocal cord b) Recurrent Cholesteatoma c) Atrophic rhinitis d) ?? A This video clipping shows coablation technology being used to perform kashima’s operation. This surgery is performed to manage patients with bilateral abductor nerve paralysis of vocal folds.

https://youtu.be/XK_D7oLd28g

84) The main vessel involved in bleeding from JNA a) Internal maxillary A. b) Ascending pharyngeal A. c) ?? A 85) Eustachian tube function is best assessed by a) Politzer test b) VEMP c) Rhinomanometry d) Tympanometry A ans=d>a? politzer’s Test Politzer’s test is performed by compressing one naris into whichthe end of a rubber tube attached to an air bag has been insert-ed while compressing the opposite naris with finger pressure.The subject is asked to repeat the letter K or is asked to swallowto close the velopharyngeal port (Figure 8–13). When the testresult is positive, the overpressure that develops in thenasopharynx is transmitted to the middle ear, thus creating pos-itive middle-ear pressure. Assessment of the middle-ear pressureand the significance of the test results are the same as withValsalva’s test in that a normal result indicates only tubal paten-cy. However, both Valsalva’s and Politzer’s methods can be ofbenefit as a treatment when effusion or high negative pressure ispresent within the middle ear if the patient can successfullyinflate the middle ear. Valsalva’s and Politzer’s maneuvers maybe more beneficial as management options in selected patientsthan they are as methods to assess tubal function, althoughthere is controversy about the efficacy of these procedures fortreatment of middle-ear effusion (see Chapter 9, “Role inManagement of Otitis Media”). ----------------------------------------Tests of Pressure Regulation Function When theTympanic Membrane Is Intact Eustachian tube function in individuals with intact tympanicmembranes may be determined by manometry, tympanometry or sonotubometry. A pressure chamber may or may not be nec-essary for testing. Tympanometry Determination of middle-ear pressure and acoustic immittanceusing electroacoustic impedance equipment were introduced byMetz about 50 years ago.51 These same techniques have beenused to perform tympanometry, which is the measurement ofthe acoustic driving-point immittance as a function of the stat-ic pressure in the canal. If low-frequency tones are used for themeasurement, the static pressure that produces the maximalacoustic immittance is approximately equal to the

gas pressurein the middle ear.Tympanometry in a Pressure Chamber Thomsen adapted theacoustic impedance method for use in a pressure chamber.43 Hevaried the chamber pressure and measured the percentage ofabsorption of a tone presented into the ear canal. He found thatthere was a fall in absorption as the pressure difference betweenthe middle ear and the chamber was increased. The absorptionreached a peak when the two pressures were identical.Unfortunately, Thomsen’s technique failed to account for thechange in middle-ear pressure caused by the measurement pro-cedure. As the pressure in the chamber is varied (in search ofmaximal loudness or absorption), the tympanic membranemoves from its original position to a new position, thus chang-ing the volume of the middle-ear cavity. However, according toBoyle’s law, as the volume of the cavity changes, the pressuremust also change. Thus, by knowing the volume displacementand “measuring” the final pressure, the original pressure can bededuced.Bylander used tympanometry with a pressure chamber toevaluate Eustachian tube function in normal children.23 In thismethod, the resting middle-ear pressure is obtained from theinitial tympanogram. Then the chamber pressure is lowered to100 mm H2O relative to ambient pressure, and a second tym-panogram is obtained, verifying the relative overpressure in themiddle ear. After this deglutition of the subject, a tympanogramis recorded to determine middle-ear pressure. The same proce-dure is repeated with 100 mm H2O relative overpressure in thechamber to assess the subject’s ability to actively equilibrate relative underpressure in the middle ear. With use of this method,the inflation-deflation test was conducted on 50 children, andthe results were compared with the results of tests that measuredtubal function in adults. In this way, the first database for tubalfunction in otologically normal children was established.Shupak and colleagues also used tympanometry inside apressure chamber to assess the ability of naval scuba divers toequilibrate negative middle-ear pressure.5

86) Topical trt for recurrent respiratory papillomatosis includes a) Acyclovir b) Cidofovir c) Ranitidine d) Zinc B Recurrent respiratory papillomatosis (RRP) is a rare but potentially severe disease caused by papillomavirus, most often types 6 and 11. The disease, which occurs in both juvenile and adult forms, is characterized by benign epithelial tumors of the airway that most frequently affect the larynx but can also spread along the entire aerodigestive tract. Recurrent respiratory papillomatosis is the most common benign neoplasm of the larynx in children and the second most frequent cause of childhood hoarseness. Standard treatment, which is palliative only, consists of surgical excision of papillomata to maintain airway patency and improve voice quality. Recurrence despite repeated surgical procedures is the rule. To date, incorporation of adjuvant treatments has not been reliably beneficial in altering the disease course. Several case series have described promising results with cidofovir, a cytosine nucleoside analog with antiviral activity. To evaluate the data available on the safety and

efficacy of cidofovir for the treatment of RRP, we conducted a MEDLINE search for all case reports or series from January 1966-August 2004 describing cidofovir therapy in either adults or children with RRP. The bibliographies of qualifying articles were also searched for relevant references. In both adults and children with mild-to-severe RRP, intralesional administration of cidofovir directly into the site of papillomata was associated with partial-tocomplete regression of papillomata, improvement in voice quality and airway status, and decreased need for surgery. Wide variation in intralesional cidofovir dose (2-57 mg), frequency (every 2-8 wks), and duration (4 mo-4 yrs) was found. Successful outcomes have also been reported with intravenous cidofovir, but data are limited to three case reports. Rash, headache, and precordialgia were the only adverse effects reported with intralesional cidofovir. Nephrotoxicity and neutropenia secondary to either intralesional or intravenous cidofovir were not observed. Long-term risks associated with intralesional administration remain to be seen. Further studies are necessary to determine the most appropriate dose, frequency, and duration of therapy, and to fully characterize the safety profile of cidofovir when given intralesionally. Recurrent respiratory papillomatosis (RRP) is a rare disease caused by human papillomavirus (HPV), most commonly types 6 and 11.[1, 2] Papillomavirus is a small, nonenveloped virus consisting of an icosahedral capsid enclosing a double-stranded, circular DNA genome. At least 70 HPV types have been identified, most of which are associated with epithelial tumors of the skin and mucous membranes, such as plantar warts, condylomata acuminata (anogenital warts), and epidermodysplasia verruciformis.[3, 4] Recurrent respiratory papillomatosis is manifested as exophytic lesions that most frequently affect the larynx but can also spread along the entire aerodigestive tract. The presence of these benign neoplasms can cause symptoms ranging from dysphonia to lifethreatening respiratory distress, and can profoundly affect the quality of life of patients with RRP.[5, 6] Traditionally, RRP has been classified based on patient age at diagnosis, such that two forms of the disease have been described: one with onset in childhood, which is arbitrarily defined as younger than 12 years (juvenile-onset RRP), the other in adulthood (adult-onset RRP). Juvenile-onset RRP is observed more often and is typically more aggressive than its adult counterpart. Peak age for the juvenile form is around 4 years, compared with the third decade of life for the adult form.[7, 8] Among children, RRP is the most common benign neoplasm of the larynx and the second most frequent cause of hoarseness.[9]

http://www.medscape.com/viewarticle/507662

87) The MC mode of spread of retinoblastoma a) Lymphatics b) Optic nerve c) Direct invasion d) Vascular B 88) Evisceration of eye is not done in a) Malignancy b) Panophthalmitis c) Severe globe trauma d) Expulsive Hemorrhage

A 89) Multifocal ERG is very useful because a) Can assess rods b) Can assess macular cones c) Can assess function of ganglion layer d) ?? B Electro Diagnostics 1. Full field Electroretinography (ERG): Test which measures the electrical responses of various cell types in the retina, including the photoreceptors (rods and cones), inner retinal cells (bipolar and amacrine cells). Used to diagnose various retinal degenerations. Retinitis pigmentosa and their variants X-linked juvenile retinoschisis Heredo-macular degenerations Retinal Vascular occlusions Intraocular Foreign Body ***2. Multifocal Electroretinography (mfERG): Multifocal electroretinography (mfERG) is a valuable technique in assessing macular function in retinal disease objectively. It is used to record separate responses for different retinal locations.**** It is also used in the detection of Macular dystrophies Macular hole X-linked retinoschisis Drug toxicity Multifocal choroditis White-dot syndrome 3. Electrooculogram (EOG): This is used to assess the function of the outer retina and Retinal Pigment Epithelium (RPE). EOG is used to confirm Best disease Suspected drug toxicities 4. Pattern Electroretinogram (PERG): This test provides information about central macular and retinal ganglion cell layer. It is also used to differentiate vision loss due to retinal or optic nerve diseases. PERG is used in evaluating Glaucoma and ocular hypertension, Optic neuritis other optic neuropathies, Maculopathies 5. Visually Evoked Responses (VEP): The VEP is a test to detect problems with the optic nerve and lesions in the anterior part of our visual pathway. VEP tests are used to evaluate

Optic neuritis, Compressive Optic neuropathy, Toxic amblyopia Cortical Blindness Demyelenating diseases such as multiple sclerosis. Unexplained visual loss 6. Multifocal Visually Evoked Responses (mfVEP): This test allows for topographical assessment of visual field. In this test multiple individual VEP responses are recorded simultaneously from 60 or so regions of the central 20 to 25° radius of the visual field. This is also known as objective visual field perimetry. Indications are Diagnosing and Following of Optic Neuritis/Multiple Sclerosis Unexplained visual loss Detecting and following of Glaucomatous damage Confirming unreliable or questionable fields http://www.sankaranethralaya.org/patient-care-electra-diagnostics.html 90) When compared to blood, Vitreous humor has high concentration of a) Glucose b) Sodium c) Potassium d) Ascorbate D Vitreous humor contains ascorbic acid at a higher concentration than blood.[1] Different species of animals have different concentrations of ascorbic acid in vitreous humor.[2] During development of the eye. the ascorbic acid content of the vitreous in fetuses was found to increase gradually until the adult level was reached prior to birth.

[3] We report the same to be true in human fetal eye http://www.ijo.in/article.asp?issn=03014738;year=1983;volume=31;issue=2;spage=73;epage=74;aulast=Sen

91) Sensory supply of cornea is by a) Infratrochlear N. b) Infraorbital N. c) Naso lacrimal N d) Supraorbital N. A ans=A Nerve supply of Cornea: Cornea is one of the highly sensitive tissue of human body. Density of the nerve ending in cornea is about 300 times of that of skin. An area of 0.01 mm2 cornea may contain as many as 100 nerve endings. Cornea is primarily innervated through the ophthalmic branch of the trigeminal nerve. The ophthalmic division of the trigeminal nerve

has three parts: the frontal nerve, the lacrimal nerve, and the nasociliary nerve. The nasociliary nerve provides sensory innervation to the cornea. infratrochlear nerve in·fra·troch·le·ar nerve (ĭn'frə-trŏk'lē-ər) n. A branch of the nasociliary nerve, supplying the skin of the eyelids and the root of the nose. The American Heritage® Stedman's Medical Dictionary Copyright © 2002, 2001, 1995 by Houghton Mifflin Company. Published by Houghton Mifflin Company.

http://www.eophtha.com/eophtha/anatomy/anatomyofcornea3.html 92) Universal marker of limbal stem cells A. Elastin B. Keratin C. Collagen D.ABCG2 D Putative positive and negative LESC markers The literature reflects many attempts to prospectively identify LESC using a specific marker. As yet no single, reliable marker has been found. However, the expression of a combination of several features seems to allow for greater specificity. Putative ‘markers’ can either be positive (present) or negative (absent). Limbal basal cells lack differentiation markers such as the 64 kDa cytokeratin 3 (CK3) that is present in all other layers of the corneal epithelium and the suprabasal layers of the limbal epithelium (Schermer et al., 1986). The corneal specific 55 kD protein, cytokeratin 12 (CK12) is also expressed in a similar pattern (Chaloin-Dufau et al., 1990). Furthermore, connexin 43 (Shortt et al., 2007a; Matic et al., 1997) and involucrin (Chen et al., 2004), both markers of cells destined for differentiation, are also absent. The transcription factor p63 is required for formation of epidermis and has been proposed as a putative positive LESC marker (Pellegrini et al., 2001). In vitro,p63 was found to be expressed in limbal epithelial cell derived holoclones with little or no expression in meroclones and paraclones. In vivo, p63 was located in the limbal basal epithelium. However, since these initial observations a number of reports have suggested that p63 is not sufficiently specific to act as an LESC marker as it has also been localised to basal cells of the peripheral and central cornea in humans (Chen et al., 2004; Dua et al., 2003) and in rats (Chee et al., 2006). However, limbal epithelial cells expressing high levels of p63 with a high nuclear to cytoplasmic ratio appear to be more stem like (Arpitha et al., 2005). Further work has since indicated that the ΔNp63α isoform may more specifically label LESC (Di Iorio et al., 2005). Many types of organ-specific stem cells, including LESC have been recently shown to exhibit a side population (SP) phenotype. The SP cells are able to efflux Hoechst 33342 dye through the ATP-binding cassette transporter Bcrp1/ABCG2. ABCG2 has therefore been proposed to be a universal marker for stem cells (Zhou et al., 2001; Watanabe et al., 2004). In putative LESCs, this protein has been immunolocalised to the cell membrane and

cytoplasm of a population of limbal basal cells and a few suprabasal cells (Chen et al., 2004). Furthermore, ABCG2 positive cells produce higher colony forming efficiency values in vitro than their negative counterparts (de Paiva et al., 2005). Our laboratory has localised ABCG2 to the outer edge of holoclones where it is thought that the stem cells reside.

http://www.stembook.org/node/588 93) High molecular wt proteins in cataractous lens seen only in humans A. HM 1&2 B. HM 2&4 C. HM 3&4 D. HM 2&3 ANS=C REF=The Eye Part IB edited by Hugh Davson,p310 Tanak and Benedek measured the protein diffusivity in intact human and bovine lens and could find no evidence of protein longer than alfa-crystallin in normal lens(calf and human aged 43 years),but found large aggregates in human cataracts .Of aggregates found in vitro,only fractions HM3 and HM4 are found exclusively in human cataracts Crystallin is found in epithelial and fiber cells of the ocular lens Crystallin role structural alpha crystallin role molecular chaperones, inhibits crystallin aggregation which form senile cataracts The difference between normal and cataractous lens is the amount of water soluble (same in normal) and insoluble (more in cataractous) HM3 forms cortical cataracts HM4 forms nuclear cataracts tryptophan associated with yellowing of lens due to UV light oxidation Rhodopsin initiates visual transduction, is an intrinsic membrane protein opsin protein portion of rhodopsin nonprotein portion of rhodopsin vitamin A Mucous glycoprotein role biological lubrication, immunological recognition, structural orientation Mucins mucus glycoproteins found in the tear layer, maintain stability of tear layer

mucins secreted by conjuctival goblet cells Which types of collagen are in cornea I (70%), V, VI Vitrosin Type II collagen found in the vitreous humor Type IV collagen found in which structures of the eye bowmen's membrane, lens capsule, blood vessels Descemet's membrance contains which type of collagen VIII, (IV also is associated on nonhelical regions)

94) Right trochlear nerve palsy can lead to all except a) Diplopia on upward gaze and adduction b) Right head tilt c) Exotropia d) Hyperopia AB

A 4th nerve lesion causes atrophy of the superior oblique muscle. When looking down and in (medially) with the bad eye there will be DIPLOPIA. The false image will lie below the true image (vertical diplopia) and will be somewhat oblique (torsional diplopia). The weakness of downward movement of the affected eye, most markedly when the eye is turned inward, results in the patient complaining of difficulty in especially reading or going downstairs. The weakness of the superior oblique in the primary position (looking straight ahead) results in the “bad” eye being slightly extorted and elevated due to the unopposed action of the inferior oblique. This will result in torsional and vertical diplopia. For instance, if the LEFT superior oblique is paralyzed, the LEFT eye is extorted and elevated. In order to get rid of the torsional part of the double vision, the patient will tilt their head to the side OPPOSITE the paralyzed muscle, that is to the RIGHT. This causes reflex (from the otoliths) intorsion of the normal RIGHT eye (on side of head tilt) so that the vertical axis of the two eyes become parallel (the eye associated with the paralyzed superior oblique is already extorted by the unopposed inferior oblique). To alleviate the vertical diplopia, the patient will also FLEX his/her chin when tilted to the RIGHT. In this position the patient will have to elevate the normal RIGHT eye in order to look straight ahead. The “bad” (LEFT) eye is already elevated and when the two eyes are located at the same vertical (up-down) position in the socket, the vertical diplopia is ameliorated. REMEMBER, LESION OF TROCHLEAR NERVE (after it has crossed the midline) = HEAD TILTED AWAY FROM PARALYZED MUSCLE; HEAD ALSO FLEXED

IN THIS POSITION. HOWEVER, IF LESION IS IN THE TROCHLEAR NUCLEUS, HEAD TILT = TOWARDS THE LESION http://www.neuroanatomy.wisc.edu/virtualbrain/BrainStem/19CNIV.html 95) Painful U/L dimness of vision … a) Optic neuritis b) Aortic arch syndrome c) Ischemic … d) ??? A I. Differential Diagnosis: Acute Vision Loss based on pain Minimal or variable pain with Vision Loss Optic Neuritis ASSOCIATED with Multiple Sclerosis) Retinal Detachment Ocular tumor Vitreous Hemorrhage Central Retinal Artery Occlusion (Amaurosis Fugax) Pain present Acute Angle-Closure Glaucoma Iritis Corneal Ulcer Temporal Arteritis (Giant Cell Arteritis) advertisement II. Differential Diagnosis: Acute unilateral Vision Loss Transient Central Retinal Vein Occlusion Retinal Detachment (early) Thromboembolism Uveitis Persistent Acute Angle-Closure Glaucoma Central Retinal Artery Occlusion Central Retinal Vein Occlusion Retinal Detachment (later) Optic Neuritis (Multiple Sclerosis) Ischemic Optic Neuropathy Nonarteritic anterior optic Neuropathy (see Medications with Adverse Ocular Effects) Eye Trauma Tumor Vitreous Hemorrhage Occipital cortex infarction (vertebrobasilar thromboembolic event) Endophthalmitis Keratopathy

Acute Maculopathy Psychogenic visual loss III. Differential Diagnosis: Acute bilateral Vision Loss Transient Migraine Headache aura Congestive Heart Failure Hypertensive Emergency Severe bilateral Carotid Artery Stenosis Transient Ischemic Attack involving visual cortex Persistent Bilateral Occipital Lobe ischemia Temporal Arteritis (Giant Cell Arteritis) Lymphoma Posterior ischemic Neuropathy IV. Risk Factors: Acute Vision Loss predisposing factors Diabetes Mellitus Hypertension Hyperlipidemia Hypercoagulable States Cardiac arrhythmias Carotid Insufficiency Glaucoma Migraine Headaches

http://www.fpnotebook.com/Eye/Sx/ActVsnLs.htm 96) Cherry red spot after trauma is due to a) CRVO b) CRAO c) Berlin’s edema d) ?? C Retina - CHERRY-RED SPOT IN MACULA 1. Cardiac myxomas 2. Cryoglobulinemia 3. Dapsone poisoning 4. Hallervorden-Spatz disease (pigmentary degeneration of globus pallidus) 5. Hollenhorst syndrome (chorioretinal infarction syndrome) 6. Hurler syndrome (MPS I-H) *7. Hypertension (severe) 8. Intralesional chalazion corticosteroid injection 9. Leber congenital amaurosis 10. Macular hemorrhage

* 11. Macular hole with surrounding retinal detachment 12. ML I (lipomucopolysaccharidosis) 13. Myotonic dystrophy syndrome (Curschmann-Steinert syndrome) 14. Multiple sulfatase deficiency *15. Occlusion of central retinal artery (see p. 457) 16. Quinine toxicity 17. Sphingolipidoses A. Cherry-red spot myoclonus B. Farber syndrome (Farber lipogranulomatosis) C. Gangliosidosis GM1-type (juvenile gangliosidosis) D. Gaucher disease (glucocerebroside storage disease) E. Goldberg syndrome F. Infantile metachromatic leukodystrophy (van Bogaert-Nyssen disease) G. Niemann-Pick disease type A H. Niemann-Pick disease type B I. Sandhoff disease (gangliosidosis GM2-type 2) *J. Tay-Sachs disease (gangliosidosis GM-type I) 18. Steroid injection intranasally *19. Temporal arteritis (giant cell arteritis) 20. Traumatic retinal edema (commotio retinae; Berlin edema) 21. Vogt-Spielmeyer cerebral degeneration (Batten-Mayou syndrome)

97) Cherry red spot and Hollenhurst plaque are seen in a) CRAO b) CRVO c) Branch RAO d) Branch RVO A Emboli (clots) can be seen within the retinal arterial system in about 20% of eyes with CRAO. The most common variant is the refractile yellow cholesterol embolus (Hollenhorst plaque), which is thought to most commonly originate from atherosclerotic disease in the carotid arteries in the neck. However, the central retinal artery itself can have atherosclerotic plaque, and it too may produce emboli. These cholesterol emboli are often small and may not totally obstruct retinal arteries. They may even occur asymptomatically. Calcium emboli are less commonly seen, but tend to be larger and cause more severe obstructions. They usually arise from diseased cardiac valves. The vision in eyes with central retinal artery obstruction ranges between counting fingers and light perception in 90% of eyes at the time of initial examination. The presence of an embolus is usually associated with poorer acuity. A few patients are unable to even see light.

Approximately 25% of eyes with a CRAO also have sparing of part of the macular (central) retina. This is due to the presence of a cilioretinal artery. These arteries are usually derived from a different (choroidal) circulation so they are not affected by the retinal artery occlusion. When a cilioretinal artery spares the central retina, the vision may be initially poor, but over a period of weeks improves to 20/50 or better in over 80% of eyes. Although the incidences of rubeosis iridis and neovascular glaucoma following CRAO have previously been thought to range from 1% to 5%, more recent data suggest that the occurrence of iris neovascularization approaches 15% to 20%. The hypothesis has been advocated that acute central retinal artery obstruction causes rapid inner-layer retinal death, thus preventing the elaboration of an angiogenic factor. However, fluorescein angiographic evidence suggests that the more severe, chronic CRAOs are those that predispose to the development of rubeosis iridis. http://www.williamsoneyeinstitute.com/retina-center/retinal-arteryocclusions 98) Drugs causing amorphous whorl like corneal opacity are a/e a) Amiodarone b) Chloroquine c) Indomethacin d) Chlorpromazine ANS=D? Epithelium • Vortex keratopathy, or corneal verticillata, is a common side effect of a number of systemic medications—e.g., amiodarone, aminoquinolones, indomethacin, tamoxifen, atovaquone and tilorone—and results from the intralysosomal accumulation of lipids. This condition presents with golden-brown deposits in a whorl-like pattern normally seen in the inferior corneal epithelium. This configuration is a result of the corneal epithelium’s growth and repair process.2 Patients who present with this finding are typically asymptomatic, though they may report photophobia or halos around lights. Vortex keratopathy as a side effect is indistinguishable from what we see in Fabry’s disease, an inherited lysosomal storage disease. • Amiodarone, an anti-arrhythmic agent, is strongly linked to the development of corneal verticillata. In fact, it is present in 69% to 100% of patients taking 200mg to 2,400mg daily, and is detectable within four to six months. It is concentrated in the tears and appears to be more severe in contact lens wearers.3 Discontinuation of the drug typically allows for resolution of the keratopathy within three to 20 months.4-6 John Dovie, OD, and Andrew Gurwood, OD, reported on a case of amiodarone-induced keratopathy with acute onset of bilateral corneal edema and subepithelial cysts that caused decreased acuity, glare and halos, which persisted for two months after discontinuation of the medication.7 Mesut Erdurmus, MD, and colleagues reported a rare case of amiodarone-associated endothelial deposition, seen with a confocal laser

scanning microscope, in a patient taking 200mg daily for six years.8 Amiodarone has also been linked to lenticular opacities and optic neuropathy.9,10 • Chloroquine (Aralen, Sanofi Aventis) and hydroxychloroquine (Plaquenil, Sanofi Aventis) are antimalarial agents used in the management of rheumatoid arthritis and lupus. Corneal manifestations include vortex keratopathy and decreased corneal sensation. The corneal findings are benign, but the retinal toxicity is concerning, as it is irreversible (even with discontinuation of the drug) and can lead to permanent central and peripheral vision loss.11 While corneal findings had been thought to have no correlation with the development of retinal toxicity, Aljoscha Neubauer, MD, and colleagues conducted a screening of 93 patients with marked corneal deposits who were taking either chloroquine or hydroxychloroquine, and using electro-oculogram and computerized color vision testing, found a 50% sensitivity and 90% specificity for retinopathy.12,13 • Tamoxifen, an estrogen antagonist used in the long-term treatment of breast cancer, creates bilateral, white or multi-colored, whorl-like, central subepithelial opacities that can cause reduced visual acuity.14 Tamoxifen retinopathy is rare, but has been detected at even low levels of treatment. After tamoxifen cessation, almost all of the ocular abnormalities are reversible—except for the retinal opacities, which can include bilateral macular edema, and yellow-white dots in the paramacular and foveal areas. http://www.reviewofcontactlenses.com/con…/d/disease/c/40061/ -------------------------------------------------------------------------------------------Tiny, yellow-white, axially-placedanterior subcapsular lenticular opacitieshave been reported in patients takingamiodarone6. It is unlikely that theseopacities would cause a loss of vision andsimilar deposits have been attributed tochloroquine7.^^^^^ They should be readilydistinguishable from axial pigmentationof the lens - an hourglasslikeconglomeration of tiny pigment depositsseen in many patients in the older agegroups, and the larger stellate opacitiesfrom the use of chlorpromazine^^^^^^^^ http://www.optometry.co.uk/…/5ccb4a0b3629b7e7cc53cfbb916c5f… 99) True statements regarding Direct Opthalmoscopy are a/e a) 2 disc diameter field of vision b) Image is virtual and erect c) Magnification is 5 times d) Self illuminated device C Direct Ophthalmoscopy. Examination of the optic nerve can be performed with a handheld direct ophthalmoscope. Direct ophthalmoscopy provides an upright, magnified (approximately 15x's), monoscopic view of the optic nerve. The structure of the exam is similar to the one described below with the 7 Steps. Depending on the specific patient exam, certain features of the ophthalmoscope should be adjusted. For example, the size of the pupil influences the optimal aperture selected. Ideally, the aperture should approximate the size of the pupil as this will allow sufficient light to enter eye to provide enough illumination of the fundus. The selection of an aperture larger than the pupil introduces more light than can enter the eye and creates secondary problems such as glare and

constriction of the pupil. Additonally, the use of the red-free light can help identify hemorrhages such as optic nerve head (Drance) hemorrhages. Slit-lamp Exam. Slit-lamp examination of the optic nerve is ideal and uses hand-held lenses to magnify and control the view of the exam. This method provides a stereoscopic, inverted view of the optic nerve. Optic Disc Stereophotography. Monitoring progression of optic nerve changes can best be performed with optic disc stereophotography. This method of comparing prior with current optic nerve images allows the examiner to evalute for both gross and fine changes. For example, examination using this method allows for changes seen with optic nerve head hemorrhages that may lead to notching, or monitoring progressiving neuroretinal rim loss by following barring of vessels.

Ancillary Testing[edit source] GDx. The GDx involves scanning laser polarimetry that uses polarized light and bifirengence to monitor retinal nerve fiber layer. OCT. The OCT (Optical Coherence Tomography) can be used to evaluate the optic nerve based on low coherence interferometry. HRT. The HRT (Heidelberg Retina Tomograph) is a confocal scanning laser that uses multiple cross section images to create and analyze three dimensional structures such as the optic nerve.

http://eyewiki.aao.org/Examination_of_the_optic_nerve_at_the_slitlamp_biomicroscope_with_a_handheld_lens

100) In a group of 100 people, the average GFR is 85 ml/min with a standard deviation of 25. What is the range for 90% confidence interval a) 80-90 b) 81-89 c) 75-95 d) 70 -100 B

Confidence Interval Estimates for Smaller Samples

With smaller samples (n< 30) the Central Limit Theorem does not apply, and another distribution called the t distribution must be used. The t distribution is similar to the standard normal distribution but takes a slightly different shape depending on the sample size. In a sense, one could think of the t distribution as a family of distributions for smaller samples. Instead of "Z" values, there are "t" values for confidence intervals which are larger for smaller samples, producing larger margins of error, because small samples are less precise. t values are listed by degrees of freedom (df). Just as with large samples, the t distribution assumes that the outcome of interest is approximately normally distributed.

A table of t values is shown in the frame below. Note that the table can also be accessed from the "Other Resources" on the right side of the page.

Confidence Intervals for One Sample: Continuous Outcome Suppose we wish to estimate the mean systolic blood pressure, body mass index, total cholesterol level or white blood cell count in a single target population. We select a sample and compute descriptive statistics including the sample size (n), the sample mean, and the sample standard deviation (s). The formulas for confidence intervals for the population mean depend on the sample size and are given below. Confidence Intervals for μ For n > 30 For n < 30

Use the Z table for the standard normal distribution.

Use the t table with df=n-1

Example Descriptive statistics on variables measured in a sample of a n=3,539 participants attending the 7th examination of the offspring in the Framingham Heart Study are shown below. Characteristic

n

Sample Mean

Standard Deviation (s)

Systolic Blood Pressure 3,534

127.3

19.0

Diastolic Blood Pressure

3,532

74.0

9.9

Total Serum Cholesterol 3,310

200.3

36.8

Weight

3,506

174.4

38.7

Height

3,326

65.957

3.749

Body Mass Index

3,326

28.15

5.32

Because the sample is large, we can generate a 95% confidence interval for systolic blood pressure using the following formula:

The Z value for 95% confidence is Z=1.96. [Note: Both the table of Z-scores and the table of tscores can also be accessed from the "Other Resources" on the right side of the page.] Substituting the sample statistics and the Z value for 95% confidence, we have

Therefore, the point estimate for the true mean systolic blood pressure in the population is 127.3, and we are 95% confident that the true mean is between 126.7 and 127.9. The margin of error is very small (the confidence interval is narrow), because the sample size is large. The 90% confidence interval for mean systolic blood pressure would be:

.

What is the 90% confidence interval for BMI? (Note that Z=1.645 to reflect the 90% confidence level.)

Answer The table below shows data on a subsample of n=10 participants in the 7th examination of the Framingham offspring Study. Characteristic

n Sample Mean

Standard Deviation (s)

Systolic Blood Pressure

10

121.2

11.1

Diastolic Blood Pressure

10

71.3

7.2

Total Serum Cholesterol

10

202.3

37.7

Weight

10

176.0

33.0

Height

10

67.175

4.205

Body Mass Index

10

27.26

3.10

Suppose we compute a 95% confidence interval for the true systolic blood pressure using data in the subsample. Because the sample size is small, we must now use the confidence interval formula that involves t rather than Z.

The sample size is n=10, the degrees of freedom (df) = n-1 = 9. The t value for 95% confidence with df = 9 is t = 2.262.

Substituting the sample statistics and the t value for 95% confidence, we have

.

Interpretation: Based on this sample of size n=10, our best estimate of the true mean systolic blood pressure in the population is 121.2. Based on this sample, we are 95% confident that the true systolic blood pressure in the population is between 113.3 and 129.1. Note that the margin of error is larger here primarily due to the small sample size.

http://sphweb.bumc.bu.edu/otlt/MPHModules/BS/BS704_Confidence_Intervals/BS704_Confidence_Intervals_print.html 101) “Nikshay” is a newly launched central government software. It is used for tracking a) TB cases b) High risk pregnancies c) High risk new borns d) Cases with malaria A NIKSHAY- A web based solution for monitoring of TB patients To monitor Revised National Tuberculosis Programme (RNTCP) effectively, a web enabled and case based monitoring application called NIKSHAY has been developed by National Informatics Centre (NIC). This is used by health functionaries at various levels across the country in association with Central TB Division (CTD), Ministry of Health & Family Welfare. NI KSHAY covers various aspects of controlling TB using technological innovations. Apart

from web based technology, SMS services have been used effectively for communication with patients and monitoring the programme on day to day basis.

http://nikshay.gov.in/AboutNikshay.htm

Nikshay (Case Based online software) Background: RNTCP since implementation followed international guidelines for recording and reporting for Tuberculosis Control Programme with minor modifications. Epi-info based EPI-CENTRE software was being used for the purpose of electronic data transmission from district level upwards. Initially DOS version was in use and the programme shifted to windows version in 2007. However, the data available at district, state or national level was in aggregated form, with a lead time of >4 months, excluding private sector and neither could help much for TB burden estimation or individual case management or monitoring. To address this Central TB Division (CTD) in collaboration with National Informatics Centre (NIC) undertook the initiative to develop a Case Based Web online (cloud) application named Nikshay. This software was launched in May 2012 and has following functional components. yy Master management yy User details yy TB Patient registration & details of diagnosis, DOT Provider, HIV status, Follow-up, contact tracing, Outcomes yy Details of solid and liquid culture & DST, LPA, CBNAAT details yy DR-TB patient registration with details yy Referral and transfer of patients yy Private health facility registration and TB Notification yy Mobile application for TB notification yy SMS alerts to patients on registration yy SMS alerts to programme officers yy Automated periodic Reports ƒ. Case Finding ƒ. Sputum conversion ƒ. Treatment outcome

Data security / confidentiality Security audit of Nikshay application is done as per guidelines of Department of IT. Password protection is

applicable for each level of user. Password reset facility is available at higher users in hierarchy. Access to relevant information for each user, based on defined functions.

Data quality Since the software do not itself generate information and almost all information is digitized from the source which exists in the programme; the inherent quality of data of the programme is transferred. Transcription errors if any are being evaluated by the programme in implementation research mode. However, Nikshay already has internal validations for most of the variables based on the logic flow and conditionality’s. But a judgement of choice of stricter validations against the availability of complete and accurate information; is also an opportunity to improve processes in the programme. It started with certain mandatory fields which were defined and these now ensure completeness of information regarding those variables e.g. DOT provider details. Unwanted characters avoided at entry. Regular feedback from administrator to check bugs if any, has been established. Most importantly data point formats of Metadata and Data Standards (MDDS) have been followed in the development of this could application. In future, this will be the basis for system integration and interoperability to set an example of EMR/EHR. Till 10th March 2014, status of implementation and is as below: TB Patients Registered under RNTCP 23,69,515 Peripheral Health Institutes (PHI) registered 41,277 Tuberculosis Officials details 2703 District TB Officers details 667 State TB Officers details 35 Contractual Employees details 6901 Non-RNTCP Health Establishments registered 64,073 Non-RNTCP Patients registered 56,087 Culture & Drug Resistant Labs Patients registered 20995 Drug Resistant Tuberculosis Patients registered 1979

Implementation challenges Many of the PHCs in the country do not have adequate ICT infrastructure like computer, internet connectivity

and Data Entry Operator. Also intermittent electricity supply hampers the data entry and use of Nikshay. Also patient treatment cards need to be brought to TU/Block level or even at district level in certain areas for data entry. Slow internet / web connectivity in some places and incomplete treatment cards at many places also slows down the process. However, support from NRHM in terms of ICT infrastructure and data entry operators has significantly contributed to use of Nikshay software across the country.

National e-Governance award NIKSHAY was honored with National e-Governance Award (Gold) 2013-14 during the National Conference on e-Governance held at Kochi on 30-31 January, 2014 under category Sectoral Award – Healthcare. These awards are organized by Ministry of Administrative Reforms, Grievence Redressal and Pensions in collaboration with Department of IT, Ministry of Communication and Information Technology, Government of India. The award was given by Sh Nikhil Kumar, Hon’ble Governor of Kerala, Sh V. Narayanasamy, Hon’ble Minister for State of Personnel, Public Grievances and Pensions. The gold award was received by officials from Central TB Division and NIC.

102) Sensitivity measures a) True positive b) True negative c) False positive d) False negative A 103) In a survey the highest sample of 58 was entered by mistake as 85. This will lead to a) Increased mean, increased median

b) Increased mean, no change in median c) No change in mean, increased median d) Increased mean, decreased median B 104) Immunisation statistical data of the community can be found by a) Sample registration system b) District health mission c) national health survey d) ?? C The National Health Interview Survey (NHIS) provides information on the health status of the U.S. civilian noninstitutionalized population through confidential interviews conducted in households by Census Bureau interviewers. NHIS is the Nation's largest in-person household health survey, providing data on health status, access to and use of health services, health insurance coverage, immunizations, risk factors, and health-related behaviors.

http://www.cdc.gov/nchs/surveys.htm National Family Health Survey (NFHS): The 2005-06, National Family Health Survey (NFHS-3) was the third in a series of national surveys preceded by earlier NFHS surveys carried out in 1992-93 (NFHS-1) and 1998-99 (NFHS-2) with the objective to provide essential data on health and family welfare needed by the Ministry of Health and Family Welfare and other agencies for policy and programme purposes, and to provide information on important emerging health and family welfare issues. Annual Health Survey (AHS): The Ministry of Health & Family Welfare, in collaboration with the Registrar General of India (RGI), had launched an Annual Health Survey (AHS) in the erstwhile Empowered Action Group States (Bihar, Jharkhand, Madhya Pradesh, Chhattishgarh, Uttarakhand, Uttar Pradesh, Orissa and Rajasthan) and Assam. AHS will provide District-wise data on Total Fertility Rate (TFR), Infant Mortality Rate (IMR) and the Maternal Mortality Ratio (MMR) at the regional level. Other RCH indicators like Ante-natal care, Institutional delivery, immunisation, use of contraceptives will also be available. The aim of the survey was to provide feedback on the impact of the schemes under NRHM in reduction of Total Fertility Rate (TFR), Infant Mortality Rate (IMR) at the district level and the Maternal Mortality Ratio (MMR) at the regional level by estimating these rates onanhttp://mohfw.nic.in/

WriteReadData/l892s/3503492088FW%20Statistics%202011%20Revised %2031%2010%2011.pdf annual basis for around 284 districts in these States.

105) Tuberculin test is a cheap and logistically simple test. But it leads to confusion because of

a) High percentage of immunized people b) HIV cases are less? c) Infection is more? d) ?? A 106) Food safety and standards authority of India comes under which ministry a) Rural statistics b) Ministry of Health and Family and welfare c) District level d) Ministry of Agriculture B 107) Haddon matrix is related to a) Injury prevention a Preventing Injuries: the Haddon Matrix 1. Core Knowledge: William Haddon made a useful contribution to thinking about how injuries occur and how to prevent them. The "Haddon Matrix" is a table showing the host, agent and environmental factors involved, set against the time sequence of an incident. The cells of the matrix illustrate the range of risk or protective factors involved; Haddon emphasized the multidisciplinary nature of potential interventions. Nice to Know: Note how the matrix links neatly to the stages of prevention. In this context, primary prevention refers to interventions before the event, to prevent it completely; secondary prevention involves lessening the extent of injury given that an event occurs (e.g., wearing a seatbelt will not prevent the collision but may lessen its effects). Tertiary prevention limits the subsequent difficulties a person encounters given his injuries (rehabilitation, etc.). You couls also add primordial prevention (not shown above), which would refer to underlying social change that would alter the circumstances in which the accident occurred. For example, encouraging public transportation would reduce crowding on the roads, likely preventing some accidents. Haddon also proposed a generic sequence of ten countermeasures to reduce the risk of injuries.

http://www.med.uottawa.ca/sim/data/Injury_Prevention_Haddon_e.htm

108) Increasing number of non communicable disease when compared to previous years is a trend called as a) Cyclical

b) Periodical c) Secular d) Seasonal c Secular trend Implies long-term changes in the frequency of diseases occurring over many years or decades. ... Among the non-communicable diseases, diabetes and coronary heart disease are depicting an upward secular trend REF=Foundations of Community Medicine, 2/e Dhaar - 2008

109) In a study two groups of newborns are checked for their weights based on whether their mothers received food supplements or not. The appropriate test which is can be used for comparing the data is a) Fischer exact test b) Student T test c) Paired T test d) Chi square test ANS=B Student's' t Test (For Paired Samples) Use this test to compare two small sets of quantitative data when data in each sample set are related in a special way. Criteria The number of points in each data set must be the same, and they must be organized in pairs, in which there is a definite relationship between each pair of data points If the data were taken as random samples, you must use the independent test even if the number of data points in each set is the same Even if data are related in pairs, sometimes the paired t is still inappropriate Here's a simple rule to determine if the paired t must not be used - if a given data point in group one could be paired with any data point in group two, you cannot use a paired t test Examples The paired t test is generally used when measurements are taken from the same subject before and after some manipulation such as injection of a drug. For example, you can use a paired t test to determine the significance of a difference in blood pressure before and after administration of an experimental pressor substance. You can also use a paired t test to compare samples that are subjected to different conditions, provided the samples in each pair are identical otherwise. For example, you might test the effectiveness of a water additive in reducing bacterial numbers by sampling water from different sources and comparing bacterial counts in the treated versus untreated water sample. Each different water source would give a different pair of data points.

The value of the paired t test is best demonstrated in an example. Suppose patient 1 responds to a drug with a 5 mm Hg rise in mean blood pressure from 100 to 105. Patient 2 has a 30 mm Hg rise, from 90 to 120. Likewise for several other subjects. The response to the drug varied widely, but all patients had one thing in common - there was always a rise in blood pressure. Some of that experimental error is avoided by the paired t test, which likely will pick up a significant difference. The independent test, which would be improperly applied in this case, would not be able to reject the null hypothesis. Be certain that use of the paired t test is valid before applying it to real data. An applied statistics course or supervision of a qualified mentor may provide the experience you need. Some spreadsheet programs include the paired t test as a built-in option. Even without a built-in option, is is so easy to set up a spreadsheet to do a paired t test that it may not be worth the expense and effort to buy and learn a dedicated statistics software program, unless more complicated statistics are needed.

110) A researcher wants to do a study of ?Plasma lipids among people who jog and those who don’t. But he is now concerned that the joggers might differ from the others in their diet, etc as well. This concern is known as a) Recall bias b) Interviewer bias c) selection bias d) confounding bias? ANS=C? 111) Human Developmental Index is a composite measure which uses a) Life expectancy at age one, standard of living b) Freedom, spice and all things nice icon_wink.gif c) Life expectancy at birth, knowledge, and income d) Life expectancy at age one, knowledge and standard of living C 112) Window period is defined as the time taken from a) Entry of pathogen to appearance of first clinical symptoms b) Exposure to laboratorial detection of disease c) ?? d) ?? C 113) Screening is not useful in which carcinoma a) Ca Prostate

b) Ca Colon c) Ca Breast d) Ca Testis d 114) A 10 yr old boy with dog bite comes to you. Appropriate action is a) Give CCDV b) Withhold vaccine and observe dog for 10 days c) Kill dog and send brain for biopsy d) ?? A 115) Tropical spastic paraparesis is caused by a) HTLV b) Hep B virus c) HIV d) ?? A 116) A person is HBsAg positive, but anti- HBc ab is negative. What should be the next step a) Repeat test after 6 months b) Check HBeAg, if positive start trt c) Check HBV DNA load d) ?? C Initial Assessment of Positive Hepatitis B Surface Antigen Initial laboratory screening to diagnose hepatitis B virus (HBV) infection in an asymptomatic individual generally consists of testing for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (antiHBc)[1,2]. For those patients who have a positive HBsAg, follow-up laboratory testing is indicated to define the stage of their hepatitis B infection. The follow-up laboratory evaluation of a patient with a positive HBsAg should include: Hepatitis B core IgM antibody (IgM anti-HBc) Hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) HBV DNA level Hepatic panel, including measurement of alanine aminotransferase (ALT or SGPT) and aspartate aminotransferase (AST or SGOT), levels, albumin, and prothrombin time The interpretation of the results of these tests (Figure 1) can determine whether the

patient has acute HBV infection, chronic immune tolerant infection, chronic immune active infection with wild-type virus, chronic immune active infection with precore or core promoter mutant virus, or chronic inactive infection (carrier). The phases and classification of chronic HBV infection are discussed in detail in the case Natural History of Chronic Hepatitis B Infection and as noted in the discussion of the natural history, patients with chronic hepatitis B virus infection can have a dynamic transition between the different phases of chronic infection. Acute Infection with HBV In the setting of acute HBV infection, HBsAg typically becomes detectable 4 to 8 weeks after infection. Shortly thereafter, IgM anti-HBc appears in the blood. Thus, the diagnosis of acute hepatitis B is generally made by the simultaneous detection of HBsAg and IgM anti-HBc[3]. The serologic and virologic response to acute HBV infection is discussed in detail in the case Serologic and Virologic Markers of Hepatitis B Virus Infection. Rarely, acute hepatitis B may be diagnosed during the period when HBsAg titers have declined below detectable levels and anti-HBs have not yet appeared. In this scenario, known as the "window period", the diagnosis of acute HBV infection is made based on the presence of positive IgM anti-HBc titers (Figure 2). These patients will thus have isolated anti-HBc as the only marker of acute hepatitis B infection; other scenarios exist that can cause isolated anti-HBc as discussed in detail in the case Interpretation of Isolated Hepatitis B Core Antibody (anti-HBc). The HBV DNA titers are extremely high early in acute infection, often reaching 200 million IU/ mL (1 billion copies/ml)[4]. At this stage, HBeAg is also usually detected, hepatic aminotransferase levels become elevated after HBsAg turns positive, and serum bilirubin may also increase. In severe cases, hepatic production of albumin may significantly decline and other evidence of hepatic dysfunction, such as prolonged prothrombin time, may be present[5]. The differential diagnosis of acute hepatitis B infection includes exacerbation of chronic hepatitis B, superinfection of hepatitis B carriers with hepatitis A, C, or D, and acute hepatotoxicity caused by drugs or other toxins[1,2]. During exacerbations of chronic hepatitis B, anti-HBc IgM may become transiently positive, making differentiation from acute hepatitis B difficult. In such cases, previous test results or a history of recent exposure may assist in the diagnosis of acute hepatitis B. In the other conditions mentioned above, anti-HBc IgM is usually not present[5]. For the patient discussed in this case, the initial laboratory workup should include measurement of anti-HBc IgM. If this test is positive, the diagnosis of acute hepatitis B is likely, although an acute exacerbation of chronic hepatitis B cannot be ruled out without further information. Chronic Immune Tolerant HBV Immune tolerant hepatitis B infection refers to the clinical scenario of persistently normal hepatic aminotransferase levels in the presence of high titers of circulating HBeAg and HBV DNA. These patients with immune-tolerant hepatitis B usually have

become infected early in life through vertical or early horizontal infection. Such infection most often occurs in areas with high rates of endemic infection, low rates of maternal screening, and lack of widely available neonatal prophylaxis with HBV vaccine and hepatitis B immune globulin[6]. Clinically, it is important to determine if patients have evidence of immune tolerance, because such patients generally respond poorly to antiviral therapy, and their management differs from patients with more active hepatic inflammation[7]. Chronic Immune Active HBV Infection (Wild-Type) Patients with chronic hepatitis B infection caused by wild-type virus (defined as a naturally-occurring strain without known mutations) have high titers of circulating HBeAg, almost always coupled with high titers of HBV DNA (defined as greater than 200,000 IU/ml). Indeed, prior to the widespread availability of HBV DNA assays, HBeAg was considered to be the principle marker of HBV replication and high infectivity[3]. The laboratory profile of patients with chronic immune active (wild-type) hepatitis B typically shows the following: HBsAg positive longer than 6 months HBeAg positive, anti-HBe negative Serum HBV DNA greater than 200,000 IU/ml Elevated or normal hepatic aminotransferase levels The natural history for patients with immune active chronic hepatitis B is substantially worse than that of patients in the inactive carrier state. Patients with chronic hepatitis B who become inactive carriers either through spontaneous or treatmentinduced HBeAg seroconversion demonstrate improvement in clinical and biochemical evidence of liver disease[6,8,9]. Furthermore, patients with HBeAg positive chronic hepatitis B have a greater than six-fold increased relative risk of developing hepatocellular carcinoma compared with HBeAg-negative inactive hepatitis B carriers (relative risk, 60.2 versus 9.6)[10]. Patients with chronic immune-active HBV infection usually have intermittently elevated, or persistently elevated liver enzymes. Chronic Immune Active HBV (Precore and Core Promoter Mutants) Some individuals with chronic hepatitis B are infected with a mutant HBV variant that results in HBeAg negative chronic hepatitis. In such patients, viral mutations in the precore or core promoter regions prevent HBeAg production in an otherwise normally replicating HBV. Thus, these patients typically have high serum HBV DNA levels, but negative HBeAg titers. The prevalence of precore or core promoter mutations is highest among persons from Southern Europe and Asia, with prevalence estimates of 60 to 70%[11]. Chronic HBeAg-negative hepatitis B is diagnosed in a patient with the following laboratory profile: HBsAg positive longer than 6 months HBeAg negative, anti-HBe positive Serum HBV DNA greater than 20,000 IU/ml Persistently elevated or intermittently normal hepatic aminotransferase levels Accurate diagnosis of chronic HBeAg-negative hepatitis B is imperative because the

clinical management is markedly different from that of chronic inactive hepatitis B carriers (who are also HBeAg negative but have low serum HBV DNA titers). Chronic Inactive Carrier of HBV Chronic inactive hepatitis B infection is defined as persistent HBV infection of the liver without significant ongoing hepatic inflammation and necrosis[12]. Blood tests on such patients are typically show four characteristic features: HBsAg positive for longer than 6 months HBeAg negative, anti-HBe positive Serum HBV DNA less than 2,000 IU/ml Persistently normal hepatic aminotransferase levels The "chronic inactive carrier" state may persist for decades. Patients who remain in this phase of infection have lower rates of disease progression and hepatocellular carcinoma[13]. Generally, antiviral treatment is not indicated for such patients, unless histologic or clinical signs of cirrhosis are present[12]. Case Summary The patient's blood tests yielded the following results: HBsAg positive, anti-HBs negative Anti-HBc IgM negative, Anti-HBc IgG positive HBeAg positive, anti-HBe negative Serum HBV DNA 200 million IU/ml ALT = 120 U/L, AST = 86 U/L, Albumin = 4.1 g/dL Because the patient is HBeAg positive with a high viral load, he has chronic immune active hepatitis B infection with wild-type virus. Because the ALT and AST are elevated, he is not in the immunotolerant phase of infection, but instead has evidence of hepatic inflammation. http://depts.washington.edu/hepstudy/hepB/mgmt/hbsag/discussion.html

117) In a female who had Steroid Resistant ITP it was decided to perform splenectomy. On day 3 post laparoscopic surgery patient had fever. Which of the following scenarios is likely a) Left lower lobe consolidation b) Port site infection c) Intraabdominal collection d) Urine for pus should be sent ANS=A WHAT ARE THE COMPLICATIONS OF SURGERY TO REMOVE THE SPLEEN? Even though the incisions are small, spleen removal is still a considered a major operation. Whilst laparoscopic surgery is considered a relatively safe and low risk operation, all surgery carries a number of serious complications. It must be stressed, these complications are very rare. Complications are dealt with on a case by case basis. Some of these are:

General Risks:

•

Death: approx. 1/10,000 risk for all patients having this type of operation.

•

Allergic reaction or airway problems related to the anaesthetic.

•

Bleeding: usually occurs either during the operation or in the first 24 hours and may require further surgery. You may require a blood transfusion. •

Blood vessel problems: heart attack, stroke. This is very rare.

•

Infections: Wound, pneumonia, urine, intra-abdominal, IV line related.

•

Clots in the legs that may travel to the lungs. This may be fatal.

•

Wound pain, abnormal (keloid) scarring or hernia of the wound.

•

Bowel obstruction due to hernia or adhesions.

Risks Specific to Laparoscopic Splenectomy:

•

Injury to the tail of the pancreas – resulting in a collection of fluid in the abdomen that may require a further operations or drainage procedures. •

Bleeding from the blood vessels that flow to the spleen requiring a return to the operating

theatre. •

Significant distention of the stomach that may lead to a large vomit. Occasionally some of this vomit may be inhaled into the lungs and cause lifethreatening pneumonia. This is why a tube will be place via your nose into the stomach for the first day after the operation. •

Because the spleen is very close to the left lung, partial collapse of the left lung is quite common after splenectomy. The physiotherapist will work with you to prevent this. It is very common to have a slight fever on the first 1-2 days after the operation because of this lung collapse. •

Injury to any organ in the abdomen: bowel, aorta, liver, stomach. This is rare.

•

Gas Embolism – a bubble of carbon dioxide gets into a blood vessel and causes life threatening heart problems. This is very, very rare. •

Re-operation: if the surgeon has to re-operate for any reason, this may be done with keyhole surgery or an open operation. •

Life-threatening infections related to having no spleen (see below).

http://www.brisliver.com.au/laparoscopicsplenectomy.html 1. Collapse and consolation can occur independently or together 2. Collapse can be partial or complete 3. It is often not clear to what extent the appearance is due to collapse or consolidation or both. The degrees of each are often unclear. 4. If a lobe is only partially collapsed and there is no accompanying consolidation, there may be no increase in opacity 5. In cases of pure collapse, only when the collapse is virtually complete will there be a significant increase in density of the affected lung Left Lower Lobe (LLL) Collapse

The PA view will show a triangular area of increased opacity behind the left heart shadow. • There may be loss of visualisation of the left hemi-diaphragm behind the heart • The lower lobes collapse o downward o medially toward the spine and o posteriorly •

http://www.wikiradiography.net/page/Patterns+of+Collapse

ANS=C? lap splenectomy is followed by fever & tachycardia on 3rd post op day .next best invesigation finding is: a)pus in urine b)LRTI c)intraabdominal collection on USG d)pus in port site

ANS=B>C

Introduction Surgical site infection (SSI) appear to be more frequent in splenectomized patients than might be expected and its incidence can be explained neither by the extent of surgery nor by the risk of bacterial contamination of the operating field. Aim Evaluation the local antibiotic prophylaxis using a gentamicin surgical implant in order to reduce SSI, particularly subphrenic abscesses. Introduction The spleen is one of the most crucial elements of the human immune system, but its function has not been fully recognized [1]. At first, it was believed that its removal did not entail any significant implications. Only later observations of long-term infective complications after splenectomy, such as fulminating sepsis referred to as overwhelming post-splenectomy infection (OPSI) revealed the risk. Because of them, it is currently known that spleen removal causes significant impairment of the immune mechanisms [2, 3].**** Early postoperative, local, infective complications constitute a somewhat less known problem. It has been observed that in patients after splenectomy the surgical site becomes infected (surgical site infections – SSI) much more often than could be expected. Especially, abscesses occur frequently at the site of the removed spleen.****** Its incidence can be explained neither by the range of the procedure nor by the risk of surgical field infection. The considerable risk of

abscess occurrence in the splenic site causes preventive actions. Perioperative systemic antibiotic prophylaxis does not ensure complete protection [4]. Research on local use of antibacterial drugs has been undertaken in order to prevent infections in the splenic site. In the literature concerning the issue no reports of studies of such kind were found.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516976/

118) Which of the following is not an auto immune disorder? a) Ulcerative colitis b) Grave’s disease c) Rheumatoid arthritis d) SLE A 119) Which of the following is false about TRALI a) Develops within 24 hours b) Mostly seen after sepsis and cardiac surgeries c) It’s a cause of non cardiogenic pulmonary edema d) Plasma is more likely to cause it than whole blood A Transfusion-Related Acute Lung Injury (TRALI) clinical TRALI Author: Tanya Petraszko, MD, FRCP(C) Description and Incidence Transfusion-Related Acute Lung Injury (TRALI) is a syndrome characterized by acute respiratory distress following transfusion. All plasma-containing blood products have been implicated including rare reports of IVIG and cryoprecipitate. It is a rare complication of allogeneic blood transfusion but the incidence has not been well established due to difficulty in defining the syndrome and to variable reporting mechanisms worldwide. Various studies have estimated the overall frequency of TRALI to be between 1/1,120 and 1/57,810 units transfused. However, there is wide discrepancy in the literature with the reported frequency is as low as 1/557,000 RBC units and as high as 1/432 platelet units. TRALI is associated with a high morbidity with the majority of patients requiring ventilatory support. However, the lung injury is generally transient with PO2 levels returning to pretransfusion levels within 48 -96 hours and CXR returning to normal within 96 hours. TRALI is associated with a significant mortality rate, often approximated at 5 to 10%. Given the gains in safety made within the blood component

production industry, particularly with respect to transmission of infectious diseases, TRALI is now among the three leading causes of transfusion related fatalities along with ABO incompatibility and bacterial contamination. Clinical Presentation Symptoms of TRALI typically develop during, or within 6 hours of a transfusion. Patients present with the rapid onset of dyspnea and tachypnea. There may be associated fever, cyanosis, and hypotension. Clinical exam reveals respiratory distress and pulmonary crackles may be present with no signs of congestive heart failure or volume overload. CXR shows evidence of bilateral pulmonary edema unassociated with heart failure (non-cardiogenic pulmonary edema), with bilateral patchy infiltrates, which may rapidly progress to complete "white out" indistinguishable from Acute Respiratory Distress Syndrome (ARDS). Treatment and Clinical Course Treatment of TRALI is supportive. Mild forms of TRALI may respond to supplemental oxygen therapy. Severe forms may require mechanical ventilation and ICU support. As with ARDS there is no role for diuretics or corticosteroids. The majority of patients recover within 72 to 96 hours and subsequently recover to their baseline pulmonary function without apparent sequelae. However, some patients are slower to recover and may remain hypoxic with persistent pulmonary infiltrates up to seven days. As stated above, approximately 5 to 10% of cases are fatal in spite of aggressive supportive care. Differential Diagnosis The differential diagnosis of acute lung injury after transfusion includes transfusionassociated circulatory overload (TACO), cardiogenic edema, allergic and anaphylactic transfusion reactions, and bacteremia/sepsis due to transfusion of bacterially contaminated blood products. TRALI may be distinguished from TACO and cardiogenic pulmonary edema by the absence of signs of circulatory overload such as a normal central venous pressure (CVP) and normal pulmonary capillary wedge pressure (PCWP). Clinical response to diuretics also suggests a diagnosis of TACO rather than TRALI. Allergic and anaphylactic transfusion reactions may be manifest as hypotension and respiratory distress but are marked by laryngeal edema or bronchospasm with wheezing and a normal CXR. Transfusion transmitted bacteremia my present with fever, hypotension, and culminate in severe sepsis with associated acute lung injury which may be difficult to distinguish from TRALI. The presence of positive blood cultures is a useful delineating finding.

Pathophysiology The hallmark of acute lung injury (ALI) is that of increased pulmonary microvascular permeability with increased protein in the edema fluid. This is true regardless of the cause of the ALI. It is hypothesized that TRALI may be precipitated by the infusion of donor antibodies directed against recipient leukocytes. The infusion of donor anti-HLA (human leukocyte antigens) or anti-HNA (human neutrophil antigens) antibodies is thought to directly cause complement activation, resulting in the influx of neutrophils into the lung, followed by neutrophil activation and release of cytotoxic agents, with subsequent endothelial damage and capillary leak. Donor derived antibodies to HLA class I antigens and neutrophils have been demonstrated in up to 89% of TRALI cases examined in the literature. An alternate hypothesis argues that TRALI is the result of at least two independent clinical events: the first is related to the clinical condition of the patient (infection, cytokine administration, recent surgery, or massive transfusion) that causes activation of the pulmonary endothelium. This then leads to the sequestration of primed neutrophils to the activated pulmonary endothelium. The second event is the infusion of donor derived anti-HLA or anti-HNA antibodies directed against antigens on the neutrophil surface and/or biological response modifiers (e.g., lipids) in the stored blood component that activate these adherent, functionally hyperactive neutrophils, causing neutrophil-mediated endothelial damage and capillary leak. Many studies in the literature support this hypothesis which may explain how some TRALI reactions occur in the absence of donor HLA/HNA antibodies, or why TRALI reactions do not occur in all recipients of blood components from donors who are known to have these antibodies. Yet a third hypothesis suggests that high levels of donor derived vascular endothelial growth factor (VEGF) or antibodies to class II HLA antigens residing on pulmonary vascular endothelium may directly cause endothelial shape change and fenestration. This theory purports to explain the syndrome in neutropenic patients. Identifying TRALI It is imperative that medical personnel and hospitals identify suspected cases of TRALI and report them to Canadian Blood Services. The reporting of TRALI allows us to better understand the true incidence of this reaction, in addition to its clinical course and associated mortality. Further, by identifying cases of TRALI , CBS can take steps to prevent further cases of TRALI by removing companion components of units that may have caused the reaction and by investigating donors involved in these cases and deferring them from further donations if they are found to be implicated as outlined below.

Definition Canadian Blood Services has adopted the definition put forth by the Canadian Consensus Conference Panel on TRALI as outlined below. This definition is applied consistently to all cases of TRALI reported to CBS and is used to determine whether reported cases will be investigated. Table 1: Canadian Consensus Conference Panel TRALI definitions Term Definition TRALI Acute lung injury (defined below) occurring within 6 hours of completion of transfusion of blood component. No pre-existing acute lung injury. No other temporally associated risk factors for acute lung injury (see below). Possible TRALI Acute lung injury (defined below) occurring within 6 hours of completion of transfusion of blood components. No pre-existing acute lung injury. One of more temporally associate risk factors for acute lung injury. Table 2: Definition of Acute Lung Injury (ALI) Term Definition Acute Lung Injury New onset Hypoxemia SpO2