therapy has the advantage of other medcallons being give simullaneously (In PE co-msdcarions are ramovad Jointly with

0.4g/kg/day for 5 days. Effeciive In reding the disabillty in the disease 11 Combination therapy - In conkast to PE. IV Igtherapy has the advantage of other medcallons being give simullaneously (In PE co-msdcarions are ramovad Jointly with the exchange ) Hence [V]g therapy has been combined with high dose IV methylprednisolone (500 mg daily for 5 days) 12 Llquorpheresis (CSF miration] - is a technique to purity CSF from pathological laciare (probably responsible for manifestations of GBS) it has been postulated that pathological cellular or humoral lactars are concentrated in the CSF and these block sodium channels and hence liquorpherasis is altempled as a direct therapeutic intervantion Miller-F is her syndrome - & charaiieriaad by aphthalmplegia. ataxia and areflexia without weakness It s considered to be a varianl of GB ayntfome -i: nodes id ganglloslde GQ1 b are seen in 90% of 1patients Chronic Inflammatory demyelinatlng pofyneuropathy [CIDP) - is asubacute or ohm me progressive damy linallng neuropathy Progression over 2 months distinguishes it from G-B syndrome "the disorder is associated with increased frequency of HLA DR.3, Indicating that the disease may result from an aberrant immune response leading id a chronic form of G-B syndrome (III) Vasculatic neuropathies - In systemic disorders such as RA and PAN which produce a number -f different lesions within the nerve and are hence terrred multitocal Because of the multifocal onset, the comblnatioan of indivisual peripheral n involvement is called 'mononeuritis mulliplex'. Diagnosis -High ESR or positive antinuclear facter or aniinuclear cytoplasmlc antibody Nerve biopsy reveals patchy multifocal process IV Mutifocal motor nauropathy -resembles CIDP, but does not respond -well to steroite. It has considerable similarities to LMN form of MNO. aspecially becauae of marked fasciculations Disorder is suspected in patients that present with asymmetrical upper limb wasting in absence d sensory disturtance Diagnose - Evidence of conduction block often between supraclavicular fossa and axilla. (c) Elecirodiagnostic studies Evidence of nerve conduction slowing or block C Features making the dagnnsls doubtful 1 Warded paiabtent asymmetry of weakness . 2. Marked bladder or

of patients may develop one or two types of antibody - (I) cold agglutination which agglulinates human group O erylhrocytes

50-75% of patients may develop one or two types of antibody - (I) cold agglutination which agglulinates human group O erylhrocytes at 40-45"F, (ii) an antibody which agglutinates a certain strain of non-hernotytic streptococcus designated MG These antibodes arise coring the 2nd or 3rd week of illness Antiviral agents ACYCLOVIR - is effective and without significant side-effects The specificity is because the phosphorylation required for Its activation occurs only in cells infected with herpes viruses. In case of HSV and VZV, the viral thyrldine kinase enzyme phosphorylates acyclovir Acyclovir monophosphate Is further phosphorylated to the triphosphate by cellular enzymes, the triphosphals becomes incorporated into the growing DNA chain and acrs as an obligate chain Terminator so Inhibiting the DNA polymerase of all herpes viruses. It also inhibits the enzyme directly GANCICLOVIR AND PENCICLQVIR - are activated in a similar manner but have adverse effects Ganckclovir can cause significant bone marrow depression and Is only adwised for life or sight threatening CMF infections Penciclovir Is well tolerated clinically PRODRUGS The bioavailability of the above compounds can be improved by use of prooVugs Farrclclovlr Is the prodrug of penciclovir and valaciclovlr of acyclovir FOSCARNET - Is used Iv for cytomegalovirus relinitis and induction therapy for mucocutaneous HSV unresponsive to acyclovir Side-effects are renal impairment and anemia PURINE ANALOGUES - Rlbavlrln inhibits DNA and RNA viruses, and is active against influenza, respiratory syncytial. herpes simplex. It can Inhibit hepatitis B replication In chronic hepatitis B carriers Aerosol form is indicated for RSV bronchiolilis or pneumonia, severe influenza and among immunocornpromised far parainfluenza and measles IV formulation has been used in lassa fever, and hemorrhagic lever with renal synctoma due to Hanlaan virus. TPICYCLIC AMINES - Rimantadine and Amantadne inhibit Influenza A virus They are not recommended for children below 10 years They can also be used for herpes zostar IMMUNQPQTENTIATORS - (a) Inosine pranobex - has been used In HSV 1 and 2 akin or mucous membrane lesions, subacule sclerosing encephalitis and as atjunctive treatment for genital warts It is not recommended in cnidren (b) Interferons - are a group of highly homologous species specific proteins that act by augmenting cellular resistance to virus and exert a nonspecific antiviral effect Indfcations are chronic active hepatitis with HBV DNA and chronic hepatitis C with raised serum transminases Adverse reactions include influenza-like syndrome, neuro-psychlairlc changes, bone marrow suppression, thyroid dysfunction. VIRUS AND DRUGS DISEASE Herpes sinplex Ocular herpes 3% acyclovir olntment Herpes labialis 5% acyclovir cream or 3% foscarnel cream. Genital Primary Acyclovir 1000 mg/day po. or 5 mg/kg i.d.s l.v Aliernate FCV Recurrent Asyclovir 1000 mg/day p.o. Alternate FCV Prophylaxis Acyclovir 400-1000 mg/day p.o. Encephalitis Aoyclovir . Forschhelmer,s spots - Soil palate lesions In rubella Gram-staining - Common organisms - I Gram-positive cocci - Staph spp. Strap spp. 2 Gram-negative cocci - Gonococcus, menlngococcus. 3 Gram-positive bacilli - Clostrldum spp.. Bacillus spp, C. diphtheriae. Actinomyes israeli Gardenereila vaglnalls, Llsieria monocytogenes 4. Gram-negative bacilli - Enierobacterlaceae (E.

Tryposomal chancre Periods of febrile illness (hemolympriatic stage) lasting for one week or more and accompanied

trypanosomiasis - Tryposomal chancre Periods of febrile illness (hemolympriatic stage) lasting for one week or more and accompanied by severe headache, general malaise, myalgia and joint pains, and progressive lymphadenopathy (especially In T brucei gambiensee infection) Transitory erythematous rash (circinate erythema) Other organ lesions may develop - myocarditis, splenomegaly, hepatomegaly Meningoencephalitis may develop during the course of infection. Diagnosis - Trypanosomes in blood or tiesuelluid Immunodlagnostic tests - Indrect fluorescence antibody test (IFAT) and ELISA. CSF In case of meningo-encephalitis. 20 Melioidose with acute sepsticemia Clinical features of Gram-negative septicemia with melaslalic abscesses particularly in lungs, liver and spleen Diagnose - Demonstration of bipolar Gram-negative rods in films of pus or secretions Culture - Isolation of Pseudomonas pseudomallei 21. Opportunistic infections of AIDS - See AIDS Management I. Specific - (a) Chloramphenicol - 500 mg 6-hourly till temperurature comes 10 normal, then 500 mg 8-hourly until next day. When oral admisteiraiion is not possible, it can be given in doses of 1 gm. IM every 12 hours For chidren about half the adult dose, as syrup of stearate or palmitate containing In each 4 ml. ( one teaspoonful ) 125 mg of Chloramphenicol No longer drug of choice because of increasing resistance Also danger of bone marrow suppression (b) Quinolones - First drug of choice. Drugs and dosage schedules: Olloxacin 200 mg b d for 7-14 days Clprofloxacln 750 mg b.d till afebrile. Then 500 mg b.d for 7-14 days Pefloxacln 400 mgb.d for 7-14 days Nortloxacln 800 mg b.d. till alebrlle. then 400 mg b d for 7-14 days, (c) Third generation cephalosporlns -Indications (i) Clprofloxaciri resistance (II) Typhoid meningitis (iii) Enreric lever In pregnancy and those <17>

released into bloodstream, as also endogenous pyrogens and other toxins from necrotlc cells

supervenes, (i) CSF -Clear or ground glass Pressure increased. Protein-normal at first, rises to 100-200 mg. per 100 ml during second week Sugar normal. Cells 60-100. mostly polymorphs at first, later lymphocytes Rarely normal fluid. Signs - (a) Pulse fast and out of proportion to rise of Temperature, (b) Excessive perspiration, (c) Patient is alert 3 Paralytic stage - usually develops between 2nd and 5lh days after onset of signs of Involvement of nervous system May set in without initial symptoms Characteristics are - (\) Usually appears while there Is still fever (ii) Maximum al onset (ill) Distribution often asymmetrical (iv) Usually begins within 1 to 5 days after onsal of illness, progresses for 1 to 3 days, remains stationary for about a week and then shows rapid improvement for some weeks and then slower ev) Absence of sensory loss DISTRIBUTION OF PARALYSIS - usually patchy, may produce monoplegia, paraplegia and quadriplegla. (a) Lower limbs - more frequently affected Usually quadriceps. tibialis anterior and peroneal group (b) Upper limbs - most commonly deltoid, (c) Trunk - abdominal muscles, muscles of back, intercostals or diaphragm (d) Respiratory disturbances - due to paratysis of daphragm and intercostal muscles, or affection of respiratory centre in bulbar type - anxiety. Increasing weakness of voice, cough, sucking In of epigastric or intercostal spaces with increasing use of accessory muscles of respiration, cfmlnulion in the numbers a palient can count after one inspiration, andcyanosis 4. Convalescence -India! paralysis usually diminlshes to some extant after two or more weeks, and improvement may continue for several monihs The allected muscles become flaccid white contraction will tend to produce severe deformities unless these are prevented When chronic stage is reached six months to a year atler inilial Infection, no further spontaneous improvement can bs expected. Clinical types - Infection of a susceptible Indvrdual may result In one of clinical manifestations -1 Inapparent infection - in majority of cases Does not progress beyond involvement at regional lymphnodes However replication of virus in lymphoid tissue stlmufales the Immune system 2 Abortive illness-occurs In4-8%cases. Infection reaches virerric phase and foreign protein from virus is released into bloodstream, as also endogenous pyrogens and other toxins from necrotlc cells. This is results in (a) Abortive poliomyelitis - Presumptive diagnosis during epidemic. Brief Influenza-like illness with one or more of the following symptoms - malaise, anorexia, nausea, vomiting, headache, sore throat, constipation and localised abdominal pain Fever seldom more than 103°F Coryza and cough uncommon, (b) Non-paralytic poliomyelitis - Subjective symptoms as In abortive type but headache, nausea, vomiting more intense, and soreness and stiffness of posterior muscles o( neck, trunk and limbs Fleeting paralysis of bladder not uncommon 3. Paralytic poliomyelitis - (a) Spinal form - Paralysis of flrccid Type usually asymmetrical and scattered in distribution, Though more severe in one extremity Legs most frequently Involved. Respiratory paralysis may result from involvement of daphragrn and intercostal muscles Transient bladder involvement in some (b) Bulbar form - Muscles supplied by bulbar nuclei Involved alone or with spinal musculature Facial, palatal and sometimes pharyngeal paralysis causes change in voice, difficulty in swallowing, nasal regurgiiation and choking

association with hydrocephalus. Conjunctivitis and cornea! ulcers (d) Rash - Erythematous macules when soon become

adults, more often during winter epidemics Transmission - by way of nasopharynx Carriers are the principal source of transmission Acquisition is followed by meningitis and seplticemia. Incubation period - 1 to 5 days Clinical features - 1 STAGE OF INVASION - Abrupt onset with severe headache, vomiting of cerebral type, fever, pains in neck and back, rigors or in children convulsions, restlessness, insomnia, delirium 2 MENINGEAL STAGE - (a) More severe headache, intense lumbar pain (b) Muscular rigidity - Neck rigidity, head retraction Kemig's and Brudzinski's signs, sometimes muscular twitchings and tremors (c) Ocular symptoms - Include optic neuritis, uveitis or purulent choroiditis usually unilateral Optic atrophy may result particularly in association with hydrocephalus. Conjunctivitis and cornea! ulcers (d) Rash - Erythematous macules when soon become petechial (spotted fever) Petechiae in the conjunctivae. (e) Temperature variable, usually more than 30°C [f] Exaggeration of deep jerks (g) Retention of urine and constipation (h) Herpes febrilis (i) Pulse - slow in relation lo temperature, may be irregular [j) Rapid emaciation DIAGNOSIS - (a] Leucocytosis - 20.000-30.000 per c mm. (b) CSF • Turbid or purulent, under pressure, large number of pus cells mainly polymorphs . and presence of meningococci on smear or culture (c) Polymerase chain reaction-(PCR)-based identification of bacterial pathagens in cellular CSF increases menigococcal diagnostic rates Complications and sequelae - 1. Septicerria - Meningitis is associated with meningococcal septicemla and the organism may setlle in lungs, bones, joints or eyes causing local infection 2 Arthritis - either purulent occurring early in the illness, or arthritis ol later onset, possibty due to immune reaction 3. Neurological - (a) Cerebral oedema of severe degree causing fluctuating neurological signs (b) Focal neurological damage - e.g.. deafness (c) Psychiatric problems and mental retardation (d) Hydrocephalus - rare 4 Cardivascular Myocarditis 5 Waterhouse-Friderichsen syndrome - from haemorrhage necrosis of both adrenals Circulatory failure, cyanosis and widespread petechiae or purpura. Circulating steroid levels are usually high 6 DIC - often present Treatment - BenzyIpenicillin 20-30 mg/kg 4-hour!y for 5-7 days if pentaiilln allergy Cephalosporin(e.g cefotaxlme 1 -2g i.v. 12 hrly) PROPHYLAXIS - Penicillin does not eradicate the organism from nasopharynx Patient, and any close contacts should be given rilarrplcin 10 mg/kg b.d. for 2 days Clprofloxacin 500 mg in a single dose. If rlfampicin la canlralndtcated Menigococcal vaccine (A and C and W 135) can be given 2 Pneumtcoccal meningitis - asaocialed with lobar pneumonia, rarely with chronic at it is media, sinusitis or head injury Muscular spasms common More severe loxemla CSF ihtek greenish lluid. Gram positive diplococci in CSF and blood, or detection o) pneumococcal antigen In CSF Tr - PenicllHn or cefotaxirne/ceflriaxone for atleast 7 days and continued till patient is apyrexial for 48 hrs VACCINATION -Vaccine is effective and should be given to all patients in high-risk groups, other than neonates, in whom it is of limited efficacy Patients undergoing splenectomy snould be immunized before surgery 3. Hemophilus Influenzae meningitis -common in children under 5. Preceding or accompanying infection of respiratory or ear infection The illness often develops insidiously with drowsiness and irritability Subdural effusion is a common complication and may cause convulsions or become infected. CSF purulent with a high protein and polymorph count and low sugar.

Anaemia appears after several days of oliguria Anaemia at onset is due to haemorrhage or haemolysis

) Neuromuscular - Drowsiness, confusion and agitation occur in advanced uremia and may Indicate water or drug intoxication Convulsions, coma or focal neurological signs may also be observed Muscular twitching or cramps are uncommon in absence of plasma electrolyte disorders. (f) Infection
- Secondary sepsis is a major risk in patients with ARF. BIOCHEMICAL DISTURNABCES - 1. Nitrogen retention - Blood urea rises rapidty during the first few days but the increase is not closely related with the clinical severity of uremia 2 Sodium - Hyponatremia is common usually with hypochloremia. 3. Potassium -Hyperkalemia. Rarely hypokalemia due to loss of potassium by Gl tract, alkalosis or dextrose-rich hyperalimentation. 4 Bicarbonate - Metabolic acidosis results from reduced secretion of hydrogen ions and accumulation of acid from Increased protein break down 5. Calcium - Moderate hypocalcemia is conrnon but tetany is uncommon because of concomitant hypomagneserria and acidosis which increase fonised calcium 6 Hematological disorders - Anaemia appears after several days of oliguria Anaemia at onset is due to haemorrhage or haemolysis Bleeding tendency and platelet function abnormalities appear in patients with uncontrolled uremia DIURETIC STAGE -This phase of the disease is ushered in by increase in urinary output to about out 1000 ml. in 24 hours.s this may progress to polyuria Febrile reaction is common and uremic symptoms may be aggravated and lead to coma. With profound duresis dehydration may set In Differential Diagnosis: 1. Acute exacerbation of CRF - Features which suggest underlying CRF - (I) Severe normochrorric normocytic anemia. (II) Pigmentation (iii) LV hypertrophy (iv) Radiologcal evidence of renal osteodystrophy (v) Evidence of bilateral small kidneys (<>

Increased soluie delivery to the macula densa, stlmulating anglotensin release from Juxtaglomerular cells

In Increased soluie delivery to the macula densa, stlmulating anglotensin release from Juxtaglomerular cells (c) More severe tubular damage causes reduction in tubular flow thus predsposing to intraluminal tubular obstruction. Sparing of some tubules may be the explanation for non-oliguric acute tubular necrosis (d) In ATM- apart from tubular damage, some toxins may impair glomerular permeability damaging endothelial or rnasangial cells, or indirectly by affecting glomerular blood flow. Clinical features - Stages -1 EARLY OR PPE-OLIGURIC STAGE - This is overshadowed by symptorrs of the primary cause Symptoms like lethargy , nausea, headache, are incfcative overhydration and should arouse suspicion of impending renal Insufficiency Characteristics are lack of structural damage, retention of the ability to concentrate urine and rapid reversibility if circulatory Insufficiency is corrected promptly and completely. 2. OLIQURIC STAGE -1 2. (a) oligurla - less than 400 ml urine In 24 hours in adults) sets In majority within 24-48 hours The duration varies, average being 4-10 days. Complete anuria is rare and indicates either a severe renal catastrophe or obstructive etiology (b) Gastrointestinal -Anorexia, nausea, vomiting, at times diarrhoea, mouth ulceration. Adynarric ileus or pseudo-paritonitis if these are related to uncontrolled uremia, they dsappear after dialysis (c) Circulatory -Hypertension is common in acute glomerulonephritis, renal infarct and cortical necrosis and when ARF results from intoxication by organic solvents Severe hypertension Is usual in malignant nephrosclerosis or thrombotic rrilcroanglopathy Pericardtis is uncommon, (d) Respiratory Dyspnoea is related to metabolic acidosis, to pulmonary infection or oedema