Background : Therapeutic drug monitoring for mycophenolic acid (MPA) is increasingly being advocated. Thepresent therapeutic range relates to the 12-hour area under the serum concentration time profile (AUC).However, this is a cumbersome, tedious, cost restricting procedure. Is it possible to reduce this samplingperiod? Aim : To compare the AUC from a reduced sampling strategy with the full 12-hour profile for MPA. Settings and Design : Clinical Pharmacology Unit of a tertiary care hospital in South India. Retrospective, paireddata. Materials and Methods : Thirty-four 12-hour profiles from post-renal transplant patients on Cellcept® wereevaluated. Profiles were grouped according to steroid and immunosuppressant co-medication and the timeafter transplant. MPA was estimated by high performance liquid chromatography with UV detection. From the12-hour profiles the AUC up to only six hours was calculated by the trapezoidal rule and a correction factorapplied. These two AUCs were then compared. Statistical Analysis : Linear regression, intra-class correlations (ICC) and a two-tailed paired t-test were appliedto the data. Results : Comparing the 12-hour AUC with the paired 6-hour extrapolated AUC, the ICC and linear regression(r2) were very good for all three groups. No statistical difference was found by a two-tailed paired t-test. Nobias was seen with a Bland Altman plot or by calculation. Conclusion : For patients on Cellcept® with prednisolone ± cyclosporine the 6-hour corrected is an accuratemeasure of the full 12-hour AUC.

Background : Genotypes of the drug-metabolizing enzyme CYP2D6 influence plasma levels of 25% of commonlyprescribed drugs. This is the first study in India to investigate the genotype-phenotype relationship of CYP2D6. Aim : To study the influence of some CYP2D6 genotypes on the metabolism of its substrate dextromethorphanin healthy South Indian volunteers and to assess the contribution of the CYP2D6*10 and CYP2D6*4 alleles. Materials and Methods : Twenty-six subjects from a previous CYP2D6 genotyping study of healthy volunteerswere included for phenotyping in this study. Selected volunteers belonged to any one of three genotype groups:Group I - two normal activity alleles, Group II - one reduced activity allele and one normal activity allele andGroup III - one loss of function allele along with either a wild type or reduced activity allele. Volunteers werephenotyped for the CYP2D6 enzyme using dextromethorphan as probe drug. Concentrations of the parent drugand metabolite dextrorphan were estimated using high performance liquid chromatography. Metabolic ratioswere calculated as the ratio of parent drug to metabolite in 0-8h urine samples. Statistical Analysis : Metabolic ratios from each genotype group were compared using the Mann-Whitney testat 5% significance, to observe their difference between genotype groups. Results : The mean metabolic ratios±SD in Groups I, II and III were 0.0039±0.0031, 0.0032±0.0017 and0.0391±0.0331 respectively. The mean metabolic ratio of Group III was significantly higher when comparedwith Groups I or II. In heterozygous individuals, the *1 or *2 alleles compensated for the reduced enzymeactivity due to the *10 allele. However, if a heterozygous individual had a *4 allele, the reduced enzyme activitycould not be compensated by the *1 or *2 alleles. Conclusions : The CYP2D6 enzyme activity was found to be decreased in individuals carrying *4 or *5 alleles.The *1 or *2 allele could compensate for the reduced function due to *10 allele, but not for the loss of functiondue to *4 allele.

Background : The technique of transplantation of cultivated limbal epithelium rather than direct limbal tissue isa novel method of "cell therapy" involved in reconstructing the ocular surface in severe limbal stem celldeficiency [LSCD], caused by chemical burns. Aim : To describe a simple feeder-cell free technique of cultivating limbal epithelium on human amniotic membrane[HAM]. Materials and Methods : The limbal tissues (2 mm) were harvested from patients with LSCD. These tissueswere proliferated in vitro on HAM supplemented by human corneal epithelial cell medium and autologousserum. Cultures covering more ?50% area of 2.5x5 cm HAM were considered adequate for clinical use. Thecultured epithelium was characterized by histopathology and immunophenotyping.Results: A total of 542 cultures out of 250 limbal tissues were cultivated in the laboratory from January 2001through July 2005. The culture explants showed that clusters of cells emerging from the edge of the explantsin one-three days formed a complete monolayer within 10-14 days. In 86% of cultures (464 of 542), thegrowth was observed within one-two days. Successful explant cultures were observed in 98.5% (534 of 542cultures) with 91% explant cultures showing an area of ?6.25 cm2 (6.25 - 12.5 cm2 range). The cultivatedepithelium was terminated between 10-14 days for clinical transplantation. The problems encountered wereinadequate growth (2 of 542) and contamination (2 of 542). Conclusions : We demonstrate a simple technique of generating a sheet of corneal epithelium from a limbalbiopsy. This new technique could pave the way for a novel form of cell therapy.

Background : Primary conservative surgery and cisplatin-based chemotherapy have resulted in high cure ratesin malignant ovarian germ cell tumors. A significant proportion of advanced tumors may have post-chemotherapyresidue and it is important to distinguish necrosis or fibrosis without viable tumor from persistent viable tumorand teratoma. Aims : To evaluate the role of laparotomy in assessing the nature of post-chemotherapy residue in ovariangerm cell tumors. Materials and Methods : Eighty-three patients with malignant ovarian germ cell tumors seen at Cancer Institute,Chennai between 1992 and 2002 were studied. Sixty-eight patients completed combination chemotherapywith cisplatin regimes, of whom 35 had radiological residual masses. Twenty-nine out of these 35 patientsunderwent laparotomy to assess the nature of the residue. Results : On laparotomy, three patients had viable tumor, seven immature teratoma, three mature teratomaand 16 only necrosis or fibrosis. None of our patients with dysgerminoma, embryonal carcinoma, absence ofteratoma element in the primary tumor and radiological residue of <5 cm had viable tumor whereas all patientswith tumors containing teratoma component initially had residual tumor. Absence of viable disease was higherin patients who had normalization of serum markers by two cycles of chemotherapy. Conclusion : Our study suggests that patients with absence of teratoma element initially, radiological residue of<5 cm and normalization of serum markers after two cycles of chemotherapy do not require surgery to assessthe nature of post-chemotherapy residue. However, laparotomy should be performed in patients with tumorsthat initially contain teratoma element and in those with sluggish tumor marker response after two cycles ofchemotherapy since they have a high chance of having viable postchemotherapy residue.

Background : Coronary artery disease (CAD) is associated with a higher incidence of allograft failure and mortalityin patients with end-stage renal disease (ESRD) following renal transplant. Aim : To evaluate the efficacy of using carotid intimal medial thickness (CIMT) to predict the presence of CADin patients with ESRD, using coronary angiography (CAG) as the gold standard. Materials and Methods : This prospective study enrolled consecutive patients with ESRD who underwent CAGas a part of pretransplant evaluation to rule out the presence of atherosclerotic CAD. An operator who wasblinded with respect to the results of the CAG, measured carotid IMT in all patients prior to CAG and recordedit on videotape. Two independent observers blinded to the results of CAG measured carotid IMT offline tovalidate its predictive accuracy as a noninvasive test in predicting the presence or absence of CAD. Measurementof carotid IMT was done on USG B mode 7.5 MHZ probe [HP 5500 andover, Massachusetts]. Student's t-testwas used for inter-group comparisons. Pearson correlation coefficient test was used to assess the relationbetween CAD and various risk factors and carotid IMT. Linear regression analysis was applied to identifyindependent factors determining presence of CAD. A P value < 0.05 was considered statistically significant. Results : Mean CIMT was significantly higher in those with CAD as compared to those without [0.80± 0.06 vs.0.70±0.06 mm, P< 0.0001). Patients with CIMT> 0.75 mm were older and had more incidence of diabetes(78% vs. 47%; P=0.001). Only 4/53 (7%) of patients with CIMT< 0.75 mm had CAD, vs. 38/52 (73%) in thosewith CIMT >0.75 mm. The sensitivity and specificity of using CIMT > 0.75 as a predictor of CAD was 90.47%and 73% and its positive and negative predictive values were 0.73 and 0.92. On multivariate analysis, onlyCIMT was a significant predictor of CAD. Conclusion : Carotid IMT can be used to predict CAD in patients with ESRD. In the absence of other risk factors,patients with IMT< 0.75 mm may not need a pretransplant CAG.

Chloroquine (CQ) is the most successful antimalarial drug ever discovered. Unfortunately, parasites resistant to the drug eventually emerged after its large scale use and are now widespread. Although great progress in our understanding of the mechanisms of CQ action and CQ resistance (CQR) has been achieved over the past two decades, including the identification of the molecules responsible for CQR (e.g., Plasmodium falciparum chloroquine resistant transporter, PfCRT) many questions remain unanswered. Here we highlight recent advances in our understanding of the genetics and molecular mechanisms of CQR, with particular emphasis on the role of genes such as pfcrt and pfmdr1 in the resistance to CQ and other drugs. New drug development and applications will undoubtedly benefit from a better understanding of CQR, eventually leading to more effective malaria control measures.

The growing problem of drug resistance has greatly complicated the treatment for falciparum malaria. Whereaschloroquine and sulfadoxine/pyrimethamine could once cure most infections, this is no longer true and requiresexamination of alternative regimens. Not all treatment failures are drug resistant and other issues such asexpired antimalarials and patient compliance need to be considered. Continuation of a failing treatment policyafter drug resistance is established suppresses infections rather than curing them, leading to increasedtransmission of malaria, promotion of epidemics and loss of public confidence in malaria control programs.Antifolate drug resistance (i.e. pyrimethamine) means that new combinations are urgently needed particularlybecause addition of a single drug to an already failing regimen is rarely effective for very long. Atovaquone/proguanil and mefloquine have been used against multiple drug resistant falciparum malaria with resistance toeach having been documented soon after drug introduction. Drug combinations delay further transmission ofresistant parasites by increasing cure rates and inhibiting formation of gametocytes. Most currentlyrecommended drug combinations for falciparum malaria are variants of artemisinin combination therapy wherea rapidly acting artemisinin compound is combined with a longer half-life drug of a different class. Artemisininsused include dihydroartemisinin, artesunate, artemether and companion drugs include mefloquine, amodiaquine,sulfadoxine/pyrimethamine, lumefantrine, piperaquine, pyronaridine, chlorproguanil/dapsone. The standard ofcare must be to cure malaria by killing the last parasite. Combination antimalarial treatment is vital not only tothe successful treatment of individual patients but also for public health control of malaria.

Severe malaria is invariably caused by Plasmodium falciparum. In India, both adults and children are affectedby severe malaria. However, children are more prone for developing anemia and convulsions as manifestationsof severe malaria, while acute renal failure and jaundice are more common among adults. Pregnant women arevulnerable to hypoglycemia, anemia and pulmonary complications. The case-fatality rate due to severe malariais 10-15% in spite of therapy but it increases in the presence of renal failure or respiratory distress (pulmonaryedema or ARDS). Of late, multi-organ failure and high mortality figures are being reported increasingly fromdifferent parts of India. Early diagnosis and prompt treatment will reduce the mortality due to malaria. Cerebral malaria should alwaysbe suspected in a patient with altered sensorium in a malaria-endemic area. However, other causes ofunconsciousness such as encephalitis, meningitis or hepatic coma should also be excluded. Parenteral quinineis the mainstay of therapy. A recent multi-centric study has demonstrated the efficacy of intravenous artesunatein reducing the mortality by 30%. The usefulness of adjunct therapy is still controversial.

The availability of counterfeit and poor quality drugs contribute to resistance and erroneous efficacy study results as well as directly affecting the health of individuals. This report describes the importance of drug quality monitoring as part of a comprehensive disease surveillance program.

′The National health Policy 2002" of India and the "Roll Back Malaria" policy makers have set up an ambitious goal of reducing malaria mortality and morbidity by 25% by 2007, and by 50% by 2010. To achieve these goals, problems should be identified, available evidence analyzed and policy should be changed early. Infection with drug resistant malarial parasites has a tremendous impact on health (prolonged recurrent illness, increased hospital admissions and death), health system (higher cost of treatment) and socioeconomics of the region. In view of the evidence of the economic burden of malaria, it has been suggested that second line treatment could be considered at 10% failure instead of 25%. Effective schizonticidal drugs will not only reduce morbidity and mortality but will also reduce transmission. Studies have shown that prevalence of viable (as tested by exflagellation test) gametocytes is considerably more after the Chloroquine or Chloroquine + Sulphadoxine-Pyrimethamine treatment compared to Quinine. Unfortunately, the only gametocytocidal drug for Plasmodium falciparum, primaquine, is also loosing its efficacy. 45 mg Primaquine reduces gametocyte prevalence by 50% while a new drug, 75 mg bulaquine or 60 mg primaquine reduces it by 90%. Plasmodium vivax forms 60-70% of malaria cases in India. Relapses which occur in 10-20% of cases adds to the burden. Efficacy, as confirmed by Polymerase Chain Reaction-Single Strand Conformational Polymorphism (PCRSSCP) to differentiate relapse and re-infection, of standard dose of primaquine (15 mg/day for 5 days, even 15 mg/day for 14 days) for vivax malaria is reducing. Fourteen day treatment is also impractical as compliance is poor. Newer drugs, newer drug delivery systems are thus needed. Slow release formulations with blood levels maintained for one week may be useful. Rationale of giving primaquine in higher doses and different timing need to be considered. The genome of Plasmodium falciparum and genome of Anopheles gambiae have been unraveled in last past 3 years. This has given us an opportunity to develop new tools. Whatever be the tool, educating health care workers as well as lay public and ensuring appropriate use of available drug are essential to achieve our goals of controlling malaria.

We present a rare case of a patient who presented with atypical cranial nerve palsies, with subsequent isolation of mucormycosis from an upper neck subcutaneous swelling. This is an unusual initial site of isolation of mucormycosis. We believe that this should be considered among the differentials when a diabetic or immunosupressed patient presents with cervical lymphadenopathy and cranial nerve palsies.

There are several reports of Fanconi syndrome (FS) with or without nephrogenic diabetes insipidus (NDI) in patients with human immunodeficiency virus (HIV) infection, treated with various antiretroviral medications like cidofovir, adefovir, didenosine and tenofovir. But neither FS nor NDI has been documented with abacavir therapy. We are reporting the first case of abacavir-induced reversible FS with NDI in a patient with acquired immunodeficiency syndrome, who recovered completely with supportive treatment and discontinuation of abacavir.

Priapism is an uncommon but serious condition with major long-term sequelae. The commoner, ischemicvariety is a medical emergency requiring immediate intervention in order to avoid erectile dysfunction. However,the high flow variety is non-ischemic and the patient may not seek immediate therapy. The options ofmanagement for this rare, painless form of priapism vary from conservative therapy to embolization of theinternal pudendal artery or, in some cases, surgery that may result in subsequent erectile dysfunction. Wepresent a case of a 24-year-old man who presented with priapism of six-day duration, 10 days after perinealinjury. Doppler ultrasonogram of the penis revealed a cavernosal artery pseudoaneurysm. Pudendal arteryangiogram done four days later revealed no leak and the priapism subsided spontaneously with subsequentreturn of normal erections.

Hydatid disease is a parasitic infestation of humans and herbivorous animals, caused by echinococcus granulosus.Dogs and some wild carnivores, like foxes, are definitive hosts, harboring worms in their intestines. Eggs arepassed in feces and eaten by intermediate hosts and larvae encyst in the liver, lungs and other organs. Primarymuscular hydatidosis without involving the thoracic or abdominal organs is extremely rare. A case ofintramuscular gluteal hydatid cyst is being reported with the intent of highlighting this atypical localization ofthe disease. Since the soft tissue tumors may be confused with hydatid cysts, preoperative evaluation ofthese patients is critical for proper handling during surgery to avoid life-threatening complications. We reporta case of a 24-year-old male patient with a cystic gluteal swelling turning out to be hydatid cyst on sonographyand computerized scanning. Surgical excision with postoperative antihelmenthics formed the main modality oftreatment.

Jaundice is a common clinical presentation in severe malaria, seen in approximately 2.5% patients with falciparuminfection but hepatitis is unusual. Although hepatic dysfunction is unusual and hepatic encephalopathy is almostnever seen in malaria, yet, cases of hepatic dysfunction are being increasingly reported in patients with P.falciparum infection, from different parts of world. The extent of hepatocellular dysfunction varies from mildabnormalities in liver function tests to hepatic failure. Patients with hepatocellular dysfunction in malaria aremore prone to develop complications, but have a favorable outcome if hepatic involvement is recognized earlyand managed properly. It is important to meticulously look for hepatic dysfunction in patients with severemalaria, distinguish it from fulminant hepatic failure and manage it aggressively.