method for thin-layer chromatography, Appendix 4. 6, using silica gel GF254 as the coating substance and a mixture of 60 volumes of chloroform

Carry out the method for thin-layer chromatography, Appendix 4. 6, using silica gel GF254 as the coating substance and a mixture of 60 volumes of chloroform, 10 volumes of ether and 10 volumes of glacial acetic acid as the mobile phase Apply separately to the plate 10 µl of each of the following solutions For solution (1) dissolve 0.2 g of the substance being examined in sufficient glacial acetic acid to produce 10 ml. For solution (2) dilute 1 ml of solution (1) to', 4 ml with glacial acetic acid For solution (3) dilute 1 ml of solution (1) to 200 ml with glacial acetic acid. For solution (4) dissolve 25 mg of albendazole RS in sufficient glacial acetic acid to produce 5 ml. After removal of the plate, allow it to dry in air and examine under ultra-violet light (254 nm). Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the principal spot. in the chromatogram obtained with solution (3) Heavy metals: Not more than 10 ppm, determined on 2.0 g by Method B, Appendix 3.12. .Sulphated ash: Not more than 0 2%, Appendix 3. 22. Loss on drying: Not more than 0.5%, determined on 1 g by drying in an oven at 105o for 4 hours, Appendix 8. 6. Assay. Weigh accurately about 0.5 g, dissolve in 80 ml of anhydrous glacial acetic acid and carry out Method B for non-aqueous titration, Appendix 3.45, using crystal violet solution as indicator. Perform a blank determination and make any necessary correction. Each ml of 0.1 M perchloric acid is equivalent to 0 02653 g of C12H15N3O2 SALBENDAZOLE swallowing. STANDARDSAIbendazole Tablets contain not less than 92.5 per cent and not more than 107 5 per cent of the stated amount of albendazole, C12H15N3O2Sldentification A Carry out the method for thin-layer chromatography, Appendix 4. 6, using silica gel GF254 as the coating substance and a mixture of 60 volumes of chloroform, 10 volumes of ether and 10 volumes of glacial acetic acid as the mobile phase apply separately to the plate 1 0 p.I of each of the following solutions. Prepare solution (1) in the following manner Add a quantity of the powdered tablets equivalent to 200 mg of Albendazole to 20 ml of a mixture of 1 S volumes of chloroform and 1 volume of formic acid, warm the suspension on a water-bath for 15 minutes, cool and filter. Dilute 10 ml of the filtrate with an equal volume of glacial acetic acid For solution (2) dissolve 25 mg of albendazole RS in sufficient glacial acetic acid to produce S ml. After removal of the plate, allow it tc -try in air and examine under ultra-violet light (254 nm). The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2). B: Extract a quantity of the powdered tablets equivalent to 100 mg of Albendazole with 100 nil of 0.1 M methanohc hydrochloric acid, filter and dilute 1 ml of the filtrate to 100 ml with 0.1M sodium hydroxide. Absorbance of the resulting solution at the maximum at about 309 rim, about 0.74, Appendix 5.5. Other requirements: Comply with the requirements of tests stated under Tablets Assay: Weigh and powder 20 tablets Weigh accurately,a quantity of the powder equivalent to about 0 1 g of Albendazole, add about 150 nil 0.1 M methanohc hydrochloric acid, shake for 15 minutes and dilute to 250 0 ml with O. IM methanohc hydrochloric acid. Mix, filter and dilute 5.0 ml of the filtrate to 250.0 ml with O 1 M sodium hydroxide. Measure the absorbance of the resulting solution at the maximum at about 309 nm, Appendix 5.5. Calculate the content of C12H15N3O2S taking 742 as the value of A(1%, 1 cm) at the maximum at about 309 nm HUMAN ALBUMINHuman Normal Albumin; Human Albumin Solution Human Albumin is a sterile non-pyrogenic solution of the albumin component obtained from pooled human blood or from normal placentae frozen immediately after collection. It is obtained by fractionating source material such as blood, plasma, serum or placentae from healthy human donors and tested individually for the absence of hepatitis B surface antigen and HIV antibodies and complies with other tests and requirements prescribed by the appropriate national control authority Source material obtained from donors who do not meet all the requirements stated may be used provided that it has been demonstrated to the national control authority that the process of fractionation will remove any known agent capable of adversely affecting the health of subjects treated with the preparation. It may be prepared from pooled source materials by precipitation with organic solvents under controlled conditions of pH, ionic strength and temperature or by chromatography or by any other method which does not affect the integrity of the product and has been shown to yield consistently a product containing not less than 95% w/v of thetotal protein as albumin which is safe for intravenous injection. Residual organic solvent, if present, is removed by freeze-drying or other suitable treatment

sleep disturbances, including nightmares, reduction in efficiency, feeling fatigued and tired are also present.

something dreadful is going to happen are the commonest. Difficulty in concentration and forgetfulness, sleep disturbances, including nightmares, reduction in efficiency, feeling fatigued and tired are also present. TYPES: 1. Acute - also known as Panic Disorder. Autonomic disturbances are marked. Patients are restless and agitated, and have a fear of impending doom. Recurrence is common. 2. Chronic - Also known as Generalised Anxiety Disorder. Physical and psychological symptoms are marked, mild to moderate in severity and tend to run a chronic course, sometimes leading to a state of physical and mental tiredness or exhaustion (neurasthenia). Prognosis - Determined by: 1. Duration of illness - shorter duration carries better prognosis. 2. Personality - Well adjusted personalities recover more easily than the neurotic, maladjusted personalities. 3. Precipitating factors - Possibility of environmental manipulations to make the environment less stressful for the person ensures quicker and long lasting remission of symptoms. Management: 1. Hospitalization - in severe cases of panic disorder. 2. Drugs -Benzodiazepines are drugs of choice for rapid alleviation of symptoms. Diazepam 5-10 mg), alpra-zolam (0.5-1 mg), chlordiazepoxide (10-20 mg), lorazepam (1-2 mg), oxazepam (15-30 mg), clonazepam (0.5-2 mg), or clolazam (10-20 mg), by mouth, or diazepam 10 mg iv bring quick relief. Maintenance is best with tricyclic antidepressants e.g. imipramine (75-300 mg/day) or clomipramine (10-75 mg/day) or with selective serotonin re-uptake inhibitors like fluoxetine (20-60 mg/day) sertraline (50-200 mg/day) all orally. (b) Generalised Anxiety Disorder 3. Psychotherapy and case work - Supportive psychotherapy gives relief from troublesome symptoms in healthy and well adjusted personalities. Deep analytical psychotherapy may be needed for chronic maladjusted personalities since the modification of basic psychic structure is important to get any lasting benefit. 4. Behavioural therapy Deep muscle relaxation, yoga and other forms of meditation. 5. Biofeedback techniques - have been used with some success. I.I Phobic Disorder Definition: A disorder characterised by intense fears of an object or situation which the patient consciously recognises as posing no danger to him Etiology: 1. Age - The disorder usually begins in childhood, adolescence or early adulthood. 2. Sex - Equal incidence in both sexe. 3. Personality factors - Persons with anxious, obsessive and passive dependent personality traits are more likely to suffer from phobic neurosis. 4. Psychoanalytic theories - Failure of repression to prevent intrapsychic conflicts from seeking conscious representation leads to anxiety which alerts the ego to use additional defence mechanisms of displacement. In this way, anxiety is displaced or transferred from the original stimulus to a seemingly unimportant object or situation which symbolically represents the original stimulus, and which now has the property of evoking the same anxiety. 5 Learning theory - Anxiety that has been aroused by an intensely frightening stimulus occurs in contiguity with a second inherently neutral stimulus. As a result of the contiguity, the original neutral stimulus takes on the capacity of arousing anxiety by itself - it becomes a conditioned stimulus for anxiety. Clinical manifestations There are three main types of phobic disorders. 1. Simple phobias - are fears of specific objects (e. g. animals) or situations (heights, closed spaces). 2. Agoraphobia - marked fear of being alone or in public places (e. g. crowds, tunnels, public transports) .3. Social phobias -Situations provoking anxiety are social gatherings or meetings in which the person feels that he might be looked at critically. Management: 1. Drugs - Anxiolytics, as in the treatment of anxiety states. 2. Behaviour therapy - to eliminate the conditioned avoidance behaviour. This is done by a process of systematic desensitization, which involves a gradual exposure, either in imagination or reality, to the feared object or situation. III. Obsessive compulsive disorder Definition A disorder in which there is persistent intrusion of unwanted thoughts, urges or actions that the patient is unable to stop. Etiology 1 Heredity - Higher incidence in families of patients. This could be due to the upbringing rather than genetic factors per se. 2. Age - Majority under age of 40 years. 3. Sex - No significant sex differences .4. Intelligence - Incidence is higher in those with high intelligence levels. 5. Organic factors - Although obsessions and compulsions are known to occur in patients with temporal lobe lesions, encephalitis and head injury, there is no evidence yet of possible organic basis for this disorder. G. Psychoanalytical theories - Obsessions and compulsions are disguised selfreproaches in connection with incidents which have occurred during the early years. Conflicts between feelings of love and hate towards parental figures who are seen as interfering with the pursuit of pleasurable activities leads to states of doubt. There is a displacement of affect from these repressed conflicts onto the symptoms which thus act as substitutes. 7. Learning theory - According to this theory, the compulsive rituals are viewed as the equivalent of avoidance responses .8. Personality factors - Persons with obsessive traits are more likely to suffer from this disorde. Clinical

Defective surfactant aggravated by high oxygen concentration, poor airway drainage, asphyxia, hypoxia, hypovolemia leading

surfactant in alveolar lining. Defective surfactant aggravated by high oxygen concentration, poor airway drainage, asphyxia, hypoxia, hypovolemia leading to pulmonary ischemia and cold stress.(2). Small alveoli which inflate with difficulty and tend to collapse on expiration. (3). Weak and compliant chest wall. PATHOPHYSIOLOGY: Surfactant (dipalmityl phosphatidyl choline) deficiency leads to collapse owing to increased surface tension, so there is a failure to maintain functional residual capacity Surfactant synthesis by Type II alveolar cells increases with foetal maturity. Diameters of airways upto bronchioles are smaller in prematures, requiring greater force for inflation and larger trans-pulmonary pressure to keep them from deflating. Also highly compliant chest wall at this time compounds tendency to atelectasis, offering poor resistance. These factors produce near-atelectasis, dyspnoea and tachypnoea, increased airway resistance and work of breathing, and eventually hypoxia, hypercapnia and acidosis. These events cause pulmonary vasoconstriction, maintenance of ductal blood flow and foramen ovale flow in an attempt to perfuse the lungs Decreased lung flow causes ischemic necrosis of surfactant cells and the vasculature causing effusion of protein-like material into alveolar spaces, producing the hyaline membrane. Lungs appear liver-like. Microscopically there is extensive atelectasis, engorgement of vessels and lining of alveoli by acidophilic homogenous membrane, membranes are seen only 6-8 hours after birth. Clinical features: Signs appear minutes after birth; may require resuscitation. Late tachypnoea is very unusual. (1) Rapid shallow respirations increasing to 60 or more per minute. (2) Audible grunting (ominous sign). (3) Intercostal and subcostal retractions. (4) Nasal flare. (5) Duskiness with increasing cyanosis poorly responsive to oxygen. (6) Breath sounds normal or diminished with harsh, tubular quality, fine crepitations on deep inspiration at lung bases. Worsening is characterised by increased dyspnoea, air hunger, progressive cyanosis, decrease and then absence of grunting, absent breath sounds despite chest movement, hypothermia, hypotension, irregular breathing, acidosis and apnoea, progresses to death in a few hours Death is rare after 3 days if an infant survives severity of newborn respiratory distress judged by Anderson Silvermans score (see p 619). Complications: A Of the disease - (1) Hypoxia, hypercapnia, acidosis, respiratory failure. (2) Persistence of ductus arteriosus - delayed closure due to hypoxia, acidosis, increased pulmonary pressure, immaturity of the infant and local release of ductal dilators such as prostaglandin E1 and E2 causes persistent apnoea, systolic or continuous murmur, increases oxygen dependancy, aggravates hypercapnia, cardiomegaly and cardiac failure (3) Intraventricular and pulmonary haemorrhage. B. Of intensive care - (1) Tracheal intubation - Obstruction of tube, cardiac arrest during suction, bleeding and ulceration of nose and throat from trauma, vocal cord avulsion, subglottic stenosis, laryngeal oedema and stridor (2) Umbilical catheterization - Vascular embolism, thrombosis, perforation, ischemic necrosis of viscera, gangrene of legs, haemorrhage after removal of heparinised catheter. (3) Oxygen toxicity - Retrolental fibroplasia, broncho-pulmonary dysplasia. (4) Pneumothorax and pneumoperitoneum (with intubation, respirator). (5) Secondary infection. (6) Anemia due to frequent blood collections. Diagnosis: (1) Low pO2 <> 50 mm Hg and acidosis signal respiratory failure. (2) X-ray chest -Fine reticular granularity of lung fields with air bronchogram seen within 6-12 hours characteristic but not pathognomonic other causes of neonatal respiratory distress (a) Respiratory causes - i. Prenatal, natal meconium aspiration. 2 Intrauterine or postnatal pneumonia, esp group B streptococcal pneumonia. 3 Pneumothorax, pneumomediastinum. 4. Pulmonary haemorrhage 5 Transient tachypnoea of the full-term newborn (persistence of lung fluid, recovers fully). 8. Wilson-Mikity syndrome (late onset dyspnoea. X-ray shows 'bubbly1 lungs, cause unknown). 7. Congenital malformations - Choanal atresia, Pierre Robin syndrome (small chin, cleft palate, tendency for tongue to fall back), laryngeal webs, stenosis, atresia, vascular rings, ectopic goitre, T-O fistula, congenital lobar emphysema, pulmonary agenesis, diaphragmatic hernia, congenital tumours, e g cysts, teratomas. (b) Cardiovascular - CCF from any cause, congenital heart disease, severe anemia, polycythemia, diabetic offspring (c) Neurological - Birth asphyxia or injury, intracranial haemorrhage, plexus injuries in breech deliveries (d) Metabolic -Acidosis, uremia, inborn errors of metabolism (hyperammonemia). Treatment: Course can be altered by intensive care and supportive therapy 1 Treatment of inadequate gas exchange - Warm humidified oxygen to keep arterial blood levels between 50 to 70 mm Hg with stable vital signs, while minimising risks of toxicity. Inspired concentration safely kept at 40-70% If > 50 mm Hg O2 cannot be achieved, use of continuous positive airway pressure (CPAP) by nasal prongs or head box is used Persistent apnoea, blood pH<72,>60 mm Hg, pO2<50>

biopsy Ultrasound is the preferred imaging technique to mark the position of the kidney It is particularly preferred

Microscopic and macroscopic hematuria with or without proteinuria - Patients with distorted red cells in urine (which suggests a glomerular lesion) often have IgA nephropathy. or thin membrane nephropathy. Other glomerular lesions e. g. lupus glomerulonephritis may be present Biopsy should be witheld if GFR is normal. 4. Impaired renal function, proteinuria and hematuria - Biopsy is mandatory. 5. Systemic disorders associated with hematuria, proteinuria or impaired renal function - Biopsy important for determining diagnosis and prognosis Severity of renal lesion may influence nature of therapy e. g. in SLE, serial biopsies may be useful in judging response to treatment. 6. Acute renal failure - if obstruction, hypovolemia, low cardiac output and septicemia have been excluded as primary causative factors. Early biopsy may reveal treatable form of rapidly progressive glomerulonephritis, such as polyarteritis or antiglomerular basement disease. 7. Chronic and end-stage renal failure - provided kidneys are not small and shrunken, biopsy is useful in determining the cause and prognosis Certain forms of nephritis (e g focal glomerulosclerosis and mesangiocapillary glomerulonephritis) recur in transplants, and it is helpful to know this for future management. 8. Special situations - (a) Uncontrolled hypertension may lead to renal impairment, hematuria and proteinuria, and this may occasionally result in nephrotic syndrome. Once hypertension is controlled, renal biopsy may be the sole criterion for determining whether the problem is due to pure hypertension or underlying nephritis. (b) In 10-20% of patients with diabetes mellitus, proteinuria and impaired renal function may be due to causes other than diabetic nephrosclerosis, particularly in those with no other evidence of microvascular disease e g diabetic retinopathy. 9. Renal allograft dysfunction - (a) It provides only reliable method of distinguishing rejection from cyclosporin nephrotoxicity (b) It helps in deciding the scale of antirejection therapy and differentiating allograft nephropathy form recurrent or de novo nephritis Contraindications - 1. Single kidney or severe malfunction of one kidney 2 Uncontrollable bleeding diathesis. 3. Small, shrunken kidneys (difficult to locate and information obtained usually nonspecific) 4 Presence of cystic disease, nephrolithiasis, reflux nephropathy or obstruction or hemangioma Technique - Localization of the kidney- Lateral border of lower pole of kidney is the safest part to biopsy Ultrasound is the preferred imaging technique to mark the position of the kidney It is particularly preferred in patients with impaired function as it avoids use of contrast media (as in IVU). Attachments are available for ultrasound probes which can precisely direct the needle to the kidney. Biopsy needle -.(a) Franklin-modified Vim Silverman needle. (b) Tru-Cut needles are disposable needles and not composed of different parts (c) Biopsy gun is a spring-loaded device which shoots' a variant of tru-cut needle into the organ (d) Biopsy needles with tips which are easily seen by ultrasound They are smaller but adequate tissue can usually be obtained Biopsy of the native kidney - (a) Pre-medication to allay anxiety and pain. (b) 'Fixing1 the kidney - so that it does not move significantly with patient's respirations Patient's upper abdomen and lower chest should be supported by pillows so adjusted that patient's diaphragm is well splinted. (c) Sedation - with IV diazepam to produce deep sleep. (d) Position of lower pole of the kidney as determined by ultrasound is marked on the skin and depth of the kidney measured. (e) Biopsy is then performed Enough tissue must be taken for light microscopy, electron microscopy, immuno-fluorescence or immunoperoxidase techniques and, if appropriate for culture Biopsy of transplanted kidney - The allograft may be easily palpable in the iliac fossa but it should be localised by ultrasound aiming for the lateral border of upper pole Since transplanted kidney often becomes encased in fibrous tissue, this must be penetrated before biopsy is taken If it is not, cutting prongs of a modified Vim Silverman needle or cutting tip of a Tru-Cut disposable needle may 'bounce' off the kidney and lacerate it, causing hemorrhage Fine-needle aspiration biopsy (FNAB) - is used in diagnosis of renal transplant dysfunction It is less traumatic and analgesia and sedation are normally unnecessary. FNAB can diagnose acute cellular reaction, but not early vascular rejection. Also it is not possible to judge severity of allograft damage in order to determine the nature and dose of anti-rejection therapy. Complications - COMMON - (a) Bleeding is most common complication. (b) Arterio-venous fistula within the kidney. It can cause bleeding Treatment - Bleeding can be controlled with bed rest and transfusion. If necessary identification and control of bleeding point of A-V fistula by transdermal percutaneous arteriography followed by embolization UNCOMMON - (a) Pneumothorax. (b) Ileus. (c) Laceration of liver, spleen, mesenteric artery and bowel.2. HEMATURIA Causes - .1. In the urinary tract - Kidney - 1. Congenital anomalies Polycystic disease, angioma .2. Calculus .3. Mobile kidney 4 Infections - Pyelonephritis, tuberculosis, glomerulonephritis 5. Neoplasms -Renal carcinoma, Wilm's tumour .6. Drugs - Sulphonamides, anticoagulants. 7. Trauma - Ruptured kidney. 8. Oxaluria. 9. Post-

Gangrene of tips of fingers and toes, cancrum oris, septicemia, candidosis, reactivation of pulmonary tuberculosis,

Other uncommon complications - Gangrene of tips of fingers and toes, cancrum oris, septicemia, candidosis, reactivation of pulmonary tuberculosis, possibly abortion or prematurity if infection occurs during pregnancy. Diagnosis - can be confirmed retrospectively with paired serology, salivary antibody detection is a non-invasive method of confirming the diagnosis Differential Diagnosis - PRE EXANTHEMATOUS STAGE - Common cold, influenza, catarrhal stage of whooping cough EXANTHEMATOUS STAGE - 1. Rubella - No Koplik's spots, small shotty enlargement of suboccipital, posterior cervical and post-auricular lymphnodes, catarrhal symptoms and systemic disturbances slight In measles mucous membrane is injected and dirty, in rubella it is pale and clean. 2. Drug eruption - especially that caused by ampicillin Tends to persist longer and may have an urticarial element Absence of catarrh and failure of rash to evolve from above downwards. 3. Serum rashes - Rash dense at site of injection, typical wheals. 4. Infectious mononucleosis - Fever, adenopathy, and sore throat Maculopapular rash, splenomegaly Atypical lymphocytes in blood smear. 5. Erythema infectiosum - Rash but usually no constitutional symptoms. Rash appears in three phases. It begins with livid erythema of the cheeks (slapped cheeks), followed by maculopapular rash on extremities and trunk, and as the rash fades it has a lacy reticular appearance. 6. Roseola infantum (Exanthema subitum) - Acute viral disease of young children. 3 to 4 days of high fever As fever falls by crisis, pink maculopapules appear on chest and trunk and fade in 1 -3 days. 7. Erythema multiforme - Circular or irregular erythematous blotches usually occurring on backs of hands and forearms. Constitutional symptoms may be present. 8. Other exanthemas - (a) .Coxsackie virus A. Hand-foot and mouth disease is the most specific syndrome. After a short prodroma of malaise, anorexia and fever, a vesicular exanthem develops involving buccal mucosa. A vesicular exanthem also appears on hands and feet in many patients. (b) Other viral infections -Adenovirus, parainfluenza virus, respiratory syncitial virus may occasionally be associated with macular or maculopapular rashes. 9. Paratyphoid - Sometimes profuse pinkish brown maculopapules. Longer prodromal illness, characteristic temperature chart, agglutination test positive .10. Typhus - Early prostration, mental symptoms, rash bright red, subcuticular mottling, no well defined edges, not marked on face. 11. Scarlet fever - Short prodromal period, sore throat, anterior cervical adenitis, scarlet rash, circumoral pallor and punctuate hemorrhages. Skin folds in groin, neck, axillae and knees become dark red (Pastia's lines) Circumoral pallor is common and skin often has a fine sandpaper texture. Strawberry tongue Management - Bed rest in quiet shaded room during febrile period Frequent fluid intake Paracetamol for fever Irrigation of eyes with boric lotion. Cough linctus to suppress the dry cough Antibiotics such as ampicillin if complications such as otitis media or pneumonia. Should be given prophylactic ally to 'poor-risk1 children. Vitamin A 200,000 units IU orally for 2 days, will prevent ocular complications and reduce respiratory infections and measles-related mortality Prevention - (a) ACTIVE IMMUNIZATION - Single dose of attenuated live-virus vaccine for all children at the beginning of second year of life. Contraindications - Personal history of convulsions, intercurrent illness or recent exposure to other infectious disease, those receiving corticosteroids, or other immunosuppressive agents, leukemia, tuberculosis, and in any stage of pregnancy. Untoward effects- Febrile reaction after one week, sometimes rash Rarely convulsions and very rarely encephalitis. Acyclovir may be used to treat secondary herpetic infection. Oral and intestinal candidosis require antifungal treatment. (b). PASSIVE IMMUNIZATION - with immunioglobulin is useful in debilitated patients in contact of measles patients followed in 3 months by vaccine. Dose 0 25 ml/kg IM It should be given within 5 days of exposure RUBELLA (German Measles) Etiology - Causative agent - Rubella is an exanthema caused by an RNA virus of the togavirus family Transmission - Droplet inhalation from an infected person Neonates with congenital infection are prominent shedders of the virus, which may be found, often as long as G months Incubation period -14-21 days Period of infectivity-from 7 days before to 4 days after appearance of rash. Clinical features - Exanthem - Rash occurs more often in older children and adults on first or second day of illness, first on face and behind the ears, and then spreads downwards to trunk and limbs. The predominant lesion is a pink macule, although maculopapular and hemorrhagic elements may be found. The rash seldom persists for more than 4 days and is not followed by staining or desquamation. Rubella without rash is common in young children. In a dark-skinned patient all that may be seen is prominence of hair follicles giving a goose-pimpled appearance. Lymphadenopathy -Slight enlargement of lymphnodes, particularly of suboccipital and posterior auricular groups Buccal mucous membranes - are inflamed, with blotchy erythema and prominent follicles on soft palate, accompanied by mild conjunctivitis and coryza

to degenerative changes in the tubular epithelium. Cellular casts - are hyaline or granular casts with t

or immunoglobulin incorporated in their matrix. They are found in same conditions as excess hyaline casts. (ii) Densely granular -are found in all forms of glomerulonephritis, diabetic nephropathy, and in large numbers in amyloid disease, and malignant phase of essential hypertension. Waxy - Advanced stages of glomerulonephritis and renal amyloid disease. Fatty - Fat droplets embedded in hyaline casts in nephrotic syndrome Granular, epithelial, fatty and lipoidal casts all point to degenerative changes in the tubular epithelium. Cellular casts - are hyaline or granular casts with tubular epithelial cells on their surface. Those with only an occasional cell are common in many forms of renal disease; casts thickly covered with tubular cells are characteristic of acute tubular necrosis and the rapidly progressive and acute types of glomerulonephritis. White cell casts in acute pyelonephritis 'Renal failure casts' - Broad and large casts probably originating in distal tubules. Renal tubular epithelial cells - A sharp rise in these cells may be produced by certain drugs. Their number is greatly increased in acute tubular necrosis Malignant cells - may be visible as syncitia with prominent nuclei in stained filter preparations. "Telescoped urinary sediment" - Presence of more than 2 types of casts in a single urinary specimen together with leucocytes and erythrocytes usually implies lupus nephritis IV BACTERIOLOGICAL EXAMINATION - Bacteria - most commonly found are E. Coli, Pseudomonas pyocyaneus, Staphylococcus aureus, Proteus vulgaris, Klebsiella pneumoniae and Streptococcus faecalis. A clear relationship has been demonstrated between in vitro sensitivity of the organism and the outcome of treatment, and laboratory control of chemotherapy improves the chances of successful treatment. Spirochetes - Leptospira icterohemorrhagica Ova and parasites - Trichomonas vaginalis and ova of oxyuris vermicularis and of schistosoma hematobium Larvae of filaria Scolices and booklets of hydatid cysts Spermatozoa - sometimes found following nocturnal emissions, convulsions or prostatic massage. V. SPECIAL TESTS -Pregnancy test - Concentration of human chorionic gonadotrophin (HCG) increased (1-5 IU/ml) within one week after the first missed period Urinary free cortisol, catecholamines, etc - See Chapter 5. Assessment of Renal Function Indications -1. Renal disease - (a) Detection (b) Evaluating its severity. (c) Following its progress. 2. Evaluation of safety and effectiveness of drugs excreted by the kidneys TESTS AND INTERPRETATION OF RESULTS - I. Urine examination and usually a quantitative measurement of proteinuria II Glomerular filtration rate (GFR) is the most widely used test of renal function CALCULATION OF CLEARANCE GRF is assessed by estimating the clearance of a substance excreted by glomerular filtration The most commonly performed tests are - 1 Measurement of plasma concentrations of creatinine and urea which indirectly reflect GFR 2 Creatinine clearance estimations, which are much less convenient. and performed at infrequent intervals to follow the long-term course of diseases potentially causing renal failure Formula: The rate at which a substance is filtered will be the same as the rate of appearance in urine, that is, UV mmol/minute, where U is the concentration in urine (mmol/ml) and V is urine flow rate (ml/minute) The clearance (volume/time) can then be calculated by determining the volume of plasma which contains UV/mmoI/minute of the sustance, that is where P(mmol/1) is the plasma concentration To summarize formula for clearance Clearance = GFR if the substance is freely filtered Since the rate of glomerular filtration depends broadly on the number of glomeruli (hence nephrons) present, the amount of renal damage and therefore the severity of renal failure can be assessed by measuring GFR Factors influencing GFK: Increase - (a) Pre-renal factors - dehydration, hypotension, severe cardiac failure (b) Renal damage. (c) Urinary tract obstruction. (d) Low-protein diet. (e) Drugs-ACE inhibitors, NSAIDS Increase. - (a) High protein diet/meal. (b) Early diabetes. (c) Pregnancy (d) Growth hormone. (e) Acromegaly. (f) Diurnal variation (increased in afternoon) Plasma creatinine and creatinine clearance Creatinine is the most useful endogenous metabolism for assessing glomerular function, and is virtually all excreted by the kidneys, mainly by process of glomerular filtration To measure creatinine clearance, patient's urine output is collected for 24 hrs Plasma creatinine concentration (Per mmol/1) and urine creatinine concentration (Ucr mmol/ 1) are measured and the duration of urine collection and volume collected are recorded Normal creatine clearance is about 120 ml/minute (varies with body size). Creatinine Clearance (ml/min) - Plasma creatinine concentration - Normal Per is 0 04-0 11 mmol/1. Factors influencing plasma creatintine concentration - Increase- (a) Reduced GFR. (b) Increased creatinine load (increased muscle mass). (c) Reduced tubular creatinine secretion due to drugs (e g trimethoprim, triamterene, amiloride, spironolactone, probenecid). (d) Hemoconcentration (e.g. diabetes insipidus). Decrease - (a) Increased GFR. (b) Reduced creatinine load. (reduced muscle mass, liver failure). (c) Hemodilution (eg antidiuretic hormone excess) Plasma urea concentration: Normal equal to or <>

. Treatment of associated bacterial infection – e. g. pneumonia (aspiration or spontaneous), gram negative bacteremia

Ventilation. 12. Treatment of associated bacterial infection – e. g. pneumonia (aspiration or spontaneous), gram negative bacteremia, urinary tract infection, etc Combined treatment with benzyl penicillin and gentamicin, or cefoperazone is useful in patients who deteriorate clinically without identifiable source of infection (b) Diamidines - (i) Pentamidine isethionate - 4 mg. /kg. body weight on alternate day V or IM for 7-10 days (ii) Hydroxystilbamidine - 5 mg/kg body weight IV daily for 10- days, the course is repeated after 10 days Less potent than antimonials but may be adequate for the less resistant forms, or useful for alternating with antimonials when repeated courses are required Danger of primary trigeminal neuropathy Severe side-effects including hypoglycemia, hypotension, arrhythmia and pancreatitis (c) Amphotericin B - For refractory cases found effective in some advanced infections. 1 0 mg/kg body weight IV in 5% glucose solution on alternat e days over 4-6 hours for 45-700 days Toxic but useful in patients resistant -to antimonials and diamidines (d) Aminosidine 15 mg/kg/day for 20 days (e) a-interferon - combined with antimony compounds Dose - 100-400/mg/m2/day i.m. for 10-40 days Side effects -Fever and pain at site of injection (f) Allopurinol - 16-24 mg/day in 3 divided doses for 10 weeks The drug prevents growth and division of amastigotes (g) Ketoconazole 600 mg/day p o x 28 days. 2. Supportive treatment - (a) Antibiotics for secondary bacterial infection (b) Iron and folate for anemia (c) Relapse and resistance -Further SB therapy once or twice a day for prolonged period or alternative drugs. 3. Splenectomy - only if spleen is much enlarged and several courses of treatment have been unsuccessful. 4. Post-kala-azar dermal Leishmaniasis (PKDL) - is a cutaneous manifestation of L. donovani disease that occurs after re-treatment and recovery from kala-azar. Macules, papules and nodules all over the body particularly on face which do not ulcerate. Nodules can occur on tongue and mucous membranes. Hypopigmented or hyper pigmented skin areas may also be seen. Parasites can be isolated from the papular or nodular lesions of the skin. PKDL has also been described in acute visceral Leishmaniasis and in patients who have been symptom less previously or who have not been treated for kala-azar. Tr - Antimony gluconate 15-20 mg/kg i.m. for 4 months to one year Nodules and macules disappear quickly but depigmented macules are the last to disappear. Cutaneous Leishmaniasis Cutaneous leishmaniasis is classified according to the geographical area to which Leishmania spp. are restricted Old world cutaneous leishmaniasis - is caused by L major (desert areas), L tropica (urban areas) and L. aethiopica. It occurs in middle East, East Africa and some Mediterranean areas: It is transmitted by Phlebotomus spp and main reservoirs are rodents (L major) and hyrax (L aethiopica). Cl. Fs. - The lesion begins as small erythematous papules where the sandfly has fed. After inbubation period of 1-8 weeks, the lesion gradually enlarges, forming a nodule which later ulcerates. Multiple lesions can coexist in different areas of the skin. Lesions heal spontaneously leaving a hypopigmented area but may persist for months or years. DIFFUSE CUTANEOUS LEISHMANIASIS caused by L. aethiopica is characterised by an initial papular lesion that does not ulcerate Satellite lesions develop and eventually multiple cutaneous nodules appear on face and