Molecular epidemiology of multidrug-resistant tuberculosis,New York City, 1995-1997

From January 1, 1995, to December 31, 1997, we reviewed records of all New York City patients who had multidrug-resistant tuberculosis (MDRTB); we performed insertion sequence (IS) 6110-based DNA genotyping on the isolates. Secondary genotyping was performed for low IS6110 copy band strains. Patients with identical DNA pattern strains were considered clustered. From 1995 through 1997, MDRTB was diagnosed in 241 patients; 217 (90%) had no prior treatment history, and 166 (68.9%) were born in the United States or Puerto Rico. Compared with non-MDRTB patients, MDRTB patients were more likely to be born in the United States, have HIV infection, and work in health care. Genotyping results were available for 234 patients; 153 (65.4%) were clustered, 126 (82.3%) of them in eight clusters of >or=4 patients. Epidemiologic links were identified for 30 (12.8%) patients; most had been exposed to patients diagnosed before the study period. These strains were likely transmitted in the early 1990 s when MDRTB outbreaks and tuberculosis transmission were widespread in New York.     

Identification of enzyme inhibitors using combinatorial libraries

Potent enzyme inhibitors have long been recognized as powerful tools for assessing the physiological roles of enzymes and have led to the therapeutic drugs able to modulate their activities in vivo. However, to be valuable tools such inhibitors should be selective so that they do not interfere with other members of the particular enzyme family. Combinatorial chemistry has proven to be a novel approach for the identification of molecules with a desired selectivity profile from the libraries of several million compounds. In recent years it has been extensively used in conjunction with computational methods for the development of potent inhibitors of therapeutically interesting targets. This review describes the various structurally diverse enzyme inhibitors identified by screening combinatorial libraries of peptides and small organic molecules.     

The importance of nicotinic acetylcholine receptors in schizophrenia,bipolar disorder and Tourette's syndrome

As the prevalence of tobacco use has decreased, it has become clear that individuals with mental illness comprise a substantial portion of the remaining smokers. Seventy to eighty percent of patients with schizophrenia smoke and their smoking is established before their first psychotic episodes or the initiation of treatment. Many patients with schizophrenia, and approximately 50% of their first degree relatives have abnormalities in auditory sensory gating and/or smooth pursuit eye movements. These abnormalities are corrected by nicotine, and they appear to be transmitted as autosomal dominant traits. Evidence is accumulating that these abnormalities reflect genetic variations in nicotine receptor number and function, that may increase susceptibility for schizophrenia. Recent studies suggest that bupropion, added to treatment with an atypical antipsychotic, can enhance the likelihood of smoking cessation or reduction in patients with schizophrenia. The prevalence of smoking is also substantially increased among patients with bipolar disorder, perhaps especially so among those with psychotic features. Nicotine delivered by gum or transdermal patch can provide short term relief for exacerbations of Tourette's Syndrome, but its use is limited by frequent toxicity, primarily nausea.     

The Changing Face of Breast Cancer – Meeting the Challenges

We have shown previously in a model of metastatic breast cancer that murine mammary tumor cells express both cyclooxygenase-1 (Cox-1) and Cox-2 isoforms. Growth and metastasis of these tumors in syngeneic hosts are inhibited by either selective Cox-1 (SC560) or selective Cox-2 (celecoxib) inhibitors. To gain insight into the relevant mechanisms involved in the therapeutic response, we determined the effect of Cox inhibitors on tumor cell behavior in vitro. We now report that either selective Cox-1 or Cox-2 drugs inhibited cell replication, but only at concentrations that are no longer selective for either isoform. Growth delay by either nonselective or selective inhibitors was associated with changes in cell morphology including cell rounding; these changes were reversed upon removal of drug. Unlike many other cell types examined, treatment of these mammary tumor cells with Cox inhibitors was not associated with detectable apoptosis. Growth inhibition, induced by either selective or nonselective Cox inhibitors, was accompanied by increased intracellular levels of the sphingolipid ceramide by 1.7–2.6-fold in comparison to vehicle-treated cells. Ceramide changes are associated with cell cycle arrest and we observed that all the Cox inhibitors examined increased significantly the number of cells in G₀/G₁ and reduced the S phase fraction. Likewise, addition of a cell-permeable form of ceramide (C6-ceramide) could mimic the effect of Cox inhibitors on both cell cycle and cell growth inhibition. Thus, mammary tumor cells are growth restricted by Cox inhibitors. These effects are associated with changes in ceramide levels and a block in cell cycle progression.     

Epidemiology of epilepsy--Indian perspective

There are about 20 epidemiological studies on epilepsy from different parts of India. They include both rural and urban studies. The prevalence rate stands at around 5/1000 population (at this rate present estimate of total epileptics in this country is about 5 million) and incidence rate varies from 38 to 49.3 per 100,000 population per year from two community-based studies in India. Case-control studies indicate that febrile seizures, family history of epilepsy and head trauma are significant risk factors. Type of seizure pattern showed maximum number of cases belonged to generalised seizures which is different from Western countries where partial seizure is the commonest variety. Treatment gap, which is a measure of per cent of patient populations not receiving the treatment, estimated to be up to 73.7% to 78% in India. Aetiology is unknown in about two-thirds of cases. Hot water epilepsy is unique in South India and single solitary ring enhancing lesion in brain imaging is a common feature in Indian subcontinent. Evaluation of prevalence study indicates that more case-control studies to find out the aetiology, pharmaco-economic study to find out the affordable drug for general public and mass health education should be undertaken to dispel the social stigma and to bring about change in the attitude about the disease.     

Virilising adrenocortical carcinoma

A 16-year-old, Hindu, female presented with rapidly growing abdominal lump for 6 months, primary amenorrhoea and non-development of secondary sex characters. Her BP was 180/120 mmHg. There was an excessive hirsutism involving face, neck, shoulders, abdomen and thighs. A lump was felt at left lumbar region extending on to left hypochondrium and part of umbilical region. Her serum testosterone level was 224 ng/dl and cortisol level was 15 microg/dl. Ultrasonography revealed a solid mass arising from the upper pole of left kidney. Exploratory laparotomy revealed a huge left adrenal tumour which was removed completely. Histopathology of the resected mass showed sheets of large round to polyhedral cells with hyperchromatic nuclei and eosinophilic granular cytoplasm with numerous giant cells. The case was diagnosed as virilising adrenocortical carcinoma.     

Cerebrospinal fluid rhinorrhoea—Transnasal endoscopic repair

The recent advances in nasal endoscopic surgery in anterior skull base area have made it the procedure of choice for repair of cerebrospinal fluid rhinorrhoea (CSFR). The aim of the present study is to analyze the technique and efficacy of endoscopic repair of CSFR.