Development and validation of a high-performance liquid chromatographic method for bioanalytical application with rimonabant

A simple and feasible high-performance liquid chromatographic method with UV detection was developed and validated for the quantification of rimonabant in human plasma. The chromatographic separation was carried out in a Hypersil BDS, C₁₈ column (250 mm × 4.6 mm; 5 μm). The mobile phase was a mixture of 10 mM phosphate buffer and acetonitrile (30:70, v/v) at a flow rate of 1.0 ml/min. The UV detection was set at 220 nm. The extraction recovery of rimonabant in plasma at three quality control (QC) samples was ranged from 84.17% to 92.64%. The calibration curve was linear for the concentration range of 20–400 ng/ml with the correlation coefficient (r²) above 0.9921. The method was specific and sensitive with the limit of quantification of 20 ng/ml. The accuracy and precision values obtained from six different sets of QC samples analyzed in separate occasions ranged from 88.13% to 106.48% and 0.13% to 3.61%, respectively. In stability tests, rimonabant in human plasma was stable during storage and assay procedure. The method is very simple, sensitive and economical and the assay was applied to human plasma samples in a clinical (pharmacokinetic) study of rimonabant.     

Presentation and outcome of emphysematous renal tract disease in patients with diabetes mellitus

BACKGROUND: Emphysematous renal tract disease (ERTD) is a rare necrotizing infection of the renal parenchyma and urinary tract caused by gas-producing organisms. ERTD deserves special attention because of its life-threatening potential. OBJECTIVES: To study the clinical features, radiological classification and prognostic factors of ERTD; and to compare the modalities of management and the outcome among the various radiological classes of ERTD. PATIENTS AND METHODS: Twenty consecutive patients with diabetes and ERTD, seen over last 3 years in a tertiary care institute of north India, were included in the study. All patients were subjected to computerized tomography (CT) after initial diagnosis by ultrasonography. They were classified into 5 classes as previously described. All patients included in the study were conservatively managed with appropriate antibiotics and/or percutaneous drainage or surgery if required. RESULT: Mean age (+/- SD) of these subjects was 54.4 +/- 20.6 years; duration of diabetes mellitus 8.6 +/- 5.8 years, and duration of symptoms related with ERTD ranged from 3 days to 3 months. Two patients had isolated emphysematous cystitis, 13 patients had emphysematous pyelonephritis (EPN), 3 had both EPN and cystitis, and 1 patient had EPN with cholecystitis, and 1 patient had EPN with pyomyositis. Only 7 (35%) patients had a history of pneumaturia. Escherichia coli was the commonest microorganism. The radiological distribution in 18 (2 had isolated cystitis) patients with EPN was: 2 patients had class 1; 1 had class 2; 2 had class 3A; 11 had class 3B, and 2 had class 4. Of 20 patients 11 (55%) survived. However, those patients who died had severe EPN based on radiological class (6 had class 3B and 1 had class 4). There was no significant difference between the survivor and non-survivor groups with respect to age, gender, duration of diabetes mellitus, duration of symptoms, serum creatinine level, total leukocyte count, hemoglobin, platelet count and culture positivity. CONCLUSION: Computerized tomographic class 3B or 4 is the most reliable predictor of outcome in patients with ERTD.     

Predictors of outcome in myxoedema coma: a study from a tertiary care centre

Background  

With the easy availability of thyroid hormone assays, thyroid disorders are now recognised even in a subclinical state. However, patients are still seen with advanced manifestations of the disease, particularly in developing countries. This observational study analysed the predictors of outcome in patients with myxoedema coma and tested the validity of different modules to define morbidity and mortality in these patients.     

Automated Computational Detection of Interstitial Fibrosis,Tubular Atrophy,and Glomerulosclerosis

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Impact of patient characteristics and infection type on clinical outcomes of patients who received linezolid or vancomycin for complicated skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus: a pooled data analysis

Phase III randomized, clinical trials are primarily designed to evaluate overall treatment-outcome comparisons. Although valuable data are gained from such comparisons, it is difficult to draw meaningful inferences about potential outcomes differences in specific patient groups and infection types. It is well established that clinical outcomes are dependent on host, treatment- and pathogen-related factors and understanding which groups benefit from one treatment relative to another is of great importance. This study sought to determine if clinical success in the treatment of complicated skin and skin structure infections (cSSSI) caused by methicillin resistant Staphylocccus aureus (MRSA) with linezolid or vancomycin varied across subpopulations and infection type. Data from 3 prospective, randomized trials evaluating linezolid and vancomycin for the treatment of MRSA cSSSI were pooled. Treatment related differences in outcomes were found, on both the absolute and relative scales, for most subpopulations and infection types. Identifying treatment differences in outcome by patient subpopulation can enhance clinical decision making.     

Foreign body in the nasopharynx of a child

Introduction of foreign body into the nasal cavity of the children by themselves is very common, but lodgment of foreign body in the nasopharyux following introduction through mouth is unusual. Here a case is presented from the Otorhinolaryngology department of S.S.K.M. Hospital, Kolkata, where a child was brought by their parents with history of introduction of a metallic foreign body in the mouth of the child by himself and this foreign body was found to be lodged in the nasopharynx of the child. The foreign body was removed orally in the out patient department. The patient returned home without any complication.     

ACUTE PSYCHOSIS ASSOCIATED WITH ABRUPT WITHDRAWAL OF CARBAMAZEPINE FOLLOWING INTOXICATION

SUMMARY Carbamazepine is regularly used in the treatment of trigeminal neuralgia. Although exacerbation of psychosis has been described following abrupt discontinuation of carbamazepine in chronic schizophrenics, a withdrawal syndrome has not been reported previously in patients treated for trigeminal neuralgia. The case presented here suggests that abrupt withdrawal of toxic concentrations of carbamazepine may precipitate a withdrawal reaction, which is manifest some days after discontinuation of the drug. Therefore it may be advisable to withdraw therapy slowly in these situations.     

Pharmacogenetics of antiarrhythmic therapy

Individuals vary widely in their responses to therapy with most drugs. Indeed, responses to antiarrhythmic drugs are so highly variable that study of the underlying mechanisms has elucidated important lessons for understanding variable responses to drug therapy in general. Variability in drug response may reflect variability in the relationship between a drug dose and the concentrations of the drug and metabolite(s) at relevant target sites; this is termed pharmacokinetic variability. Another mechanism is that individuals vary in their response to identical exposures to a drug (pharmacodynamic variability). In this case, there may be variability in the target molecule(s) with which a drug interacts or, more generally, in the broad biological context in which the drug-target interaction occurs. Variants (polymorphisms and mutations) in the genes that encode proteins that are important for pharmacokinetics or for pharmacodynamics have now been described as important contributors to variable drug actions, including proarrhythmia, and these are described in this review. However, the translation of pharmacogenetics into clinical practice has been slow. To this end, the creation of large, well-characterised DNA databases and appropriate control groups, as well as large prospective trials to evaluate the impact of genetic variation on drug therapy, may hasten the impact of pharmacogenetics and pharmacogenomics in terms of delivering personalised drug therapy and to avoid therapeutic failure and serious side effects.     

Instant 99mTc-ciprofloxacin scintigraphy for the diagnosis of osteomyelitis in the diabetic foot

BACKGROUND: The diagnosis of osteomyelitis of the foot in patients with diabetes mellitus remains a challenge. This study was conducted to evaluate bone infections using scintigraphy with instantly prepared single-vial kit, radio-labeled ciprofloxacin (Diagnobact TM) in comparison to a bacterial culture taken from the involved site. METHODS: Twenty-five patients with type 2 diabetes mellitus having foot ulcers, including six with superficial ulcers and positive 99mTc-methylene diphosphonate (MDP) bone scan as a control, were subjected to 99mTc-ciprofloxacin scan and subsequent bacteriological culture. RESULTS: 99mTc-ciprofloxacin scan was positive in 13 patients and negative in 12 patients, including the six with superficial ulcers. Bacterial culture was positive in 18 patients and negative in seven, including one with osteomyelitis on bone biopsy only. 99mTc-ciprofloxacin scan showed "true positive" results in 12, "true negative" in six, "false positive" in one, and "false negative" in six. The specificity and sensitivity of the test were 66.7% and 85.7%, respectively. The positive and negative predictive values and an accuracy of 92.8%, 50% and 72%, respectively. Staphylococcus aureus and Escherichia coli were the most frequently isolated organisms. CONCLUSION: 99mTc-ciprofloxacin is a sensitive and specific marker to diagnose bone infection in patients with diabetes mellitus, but care must be taken in case of fastidious organisms and ciprofloxacin-resistant bacterial flora in which false results may be obtained.     

A young woman with endometriosis of kidney

Endometriosis of kidney is a rare manifestation of a relatively common disease. We report a case in which ovarian and renal endometriosis were diagnosed concurrently. The disease was probably silent for a long time due to coexistent thyrotoxicosis modifying estrogen metabolism. Fine needle aspiration cytology clinched the diagnosis of endometriosis and avoided unnecessary nephrectomy.