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Biomedical subjects

N Kumar

Publications and source records attributed to N Kumar.

At least 109 records · Page 6Linked to original sources

Human herpes virus 8 (Kaposi's sarcoma herpesvirus).

Human herpes virus 8 (HHV-8) is a recently discovered herpesvirus related to Herpesvirus saimiri and Epstein-Barr virus (EBV). It has been assigned to the Rhadinovirus genus (gamma-2 herpesvirus) on the basis of its genomic sequence and structure. HHV-8 is the first member of this genus known to infect humans and it is now evident that it is the likely cause of Kaposi's sarcoma (KS). The virus is present in endothelial and spindle cells of KS, and in HIV disease the presence of HHV-8 in peripheral blood, and/or serum IgG antibodies to HHV-8, predicts the development of AIDS-related KS. HHV-8 can also infect CD19 + B cells and is of aetiological significance in the development of body cavity B cell lymphomas of AIDS. Of note, the translation products of viral open reading frames (ORFs) reveal HHV-8 to be a molecular pirate, capable of producing homologues of several human gene products that may result in alterations in cell cycle arrest, inhibit apoptosis and cell-mediated immune responses, and thus provide the potential for tumour production.

Genitalia, Male↗

Premorbid hair growth over the trunk and severity of alcohol-related liver disease.

It is unclear why only a minority (<15%) of alcoholics develop liver disease. No predisposing host factor other than gender (women are more susceptible than men) has been identified. The present study was carried out to examine the association of another host factor, hair growth over the trunk, and alcoholic liver disease. Forty-four chronic alcohol abusers were categorized into group I (scanty hair growth) and group II (profuse hair growth) based on premorbid hair distribution over the trunk. The results of laboratory tests, liver histology, and incidence of portal hypertension were compared between the two groups. There were 21 patients in group I and 23 in group II. The mean (+/- SD) daily alcohol consumption was greater in group II (230 +/- 146 g) vs group I patients (152 +/- 56 g; P < 0.05), as was the duration of alcohol abuse (17.3 +/- 7.4 vs 11.9 +/- 4.9 years; P < 0.01). Despite lower alcohol consumption, liver tests showed greater derangement in group I compared to group II patients. At histology, severe forms of liver damage were seen more frequently in group I vs group II patients (P < 0.001). Our results indicate a close association between the premorbid truncal hair growth and severity of alcoholic liver disease. These findings provide an easily recognizable clinical sign identifying individuals at increased risk of developing alcohol-related liver damage.

Adult↗

AFB staining in cytodiagnosis of tuberculosis without classical features: a comparison of Ziehl-Neelsen and fluorescent methods.

Fine needle aspirates (FNA) were obtained from lymph node and other sites in 250 suspected cases of tuberculosis. Twenty-four cases proved to be non-tubercular on FNA smears and served as negative controls. Of the smears obtained from the remaining 226 cases, 233 were classified into five groups based on cytomorphological features, i.e. presence of necrosis and granulomas, necrosis alone or acute inflammatory exudate (AIE) with or without granuloma. Cases with AIE alone formed the largest group (n = 123). Staining for AFB was done by Ziehl-Neelsen (ZN) and fluorescent methods in all 250 cases. A correlation of AFB positivity and its semiquantitative scoring (1+ to 3+) with the cytomorphological spectrum was done. Overall AFB positivity by ZN staining was 33.5% and by fluorescent staining 45.4%. When the two methods were combined, AFB positivity was 58.7%. Fluorescent staining was superior to the ZN stain in the presence of a low bacterial load as seen in smears with diagnostic cytomorphological features of tuberculosis. In problem areas like AIE alone or with occasional granulomas, AFB positivity by ZN staining is nearly as good as the fluorescent method, because the bacterial load is high.

Adolescent↗

Characterization of tubular adenoma of breast--diagnostic problem in fine needle aspirates (FNAs).

FNA smears from six histologically documented cases of tubular adenoma of breast were critically analysed and compared with 10 histologically confirmed cases of fibroadenoma (five pericanalicular and five intracanalicular). Initially a cytological diagnosis of tubular adenoma was rendered only in one case. On review, two cases could be characterized as tubular adenoma, while the findings were suggestive in two others. The features helpful in diagnosis of tubular adenoma were the presence of benign ductal cells as three-dimensional cohesive balls and tubular structures in highly cellular smears. Stroma was conspicuously scanty or absent. Myoepithelial cells were present along with sheets of ductal cells as well as bipolar naked nuclei. Confusion with fibroadenoma occurred in two cases due to presence of a stag-horn pattern of ductal cells.

Adenoma↗

Evidence for epitope-specific thymus-independent response against a repeat sequence in a protein antigen.

We have studied the immunogenicity of a recombinant heat-shock protein-related stress protein of 70,000 MW (Pfhsp) of the human malaria parasite Plasmodium falciparum in H-2 congenic and non-congenic strains of inbred and outbred mice. Most mice of different genetic backgrounds produced antibodies to Pfhsp, indicating a lack of any apparent genetic restriction of immune response. A peptide corresponding to the GGMP repeat sequence in the C-terminal region of Pfhsp was recognized by more than 75% of sera from immunized mice. The GGMP repeat epitope-specific antibodies were largely of the IgM isotype, especially in all seven inbred strains of mice tested. The lack of significant boosting of the immune response, a predominantly IgM isotype of antibodies and generation of antibody responses in athymic nude mice suggest a thymus-independent response against the GGMP repeat epitope in the Pfhsp molecule.

Animals↗

Do the diminishing efficacy and increasing toxicity of sodium stibogluconate in the treatment of visceral leishmaniasis in Bihar, India, justify its continued use as a first-line drug? An observational study of 80 cases.

Eighty parasitologically confirmed cases of visceral leishmaniasis (kala-azar) in Bihar, India, were treated daily with 20 mg sodium stibogluconate/kg for 30 days, to assess the current efficacy and toxicity of this 30-day regimen. Clinical and parasitological cure was obtained in 48 (60%) of the patients. However, 26 (33%) patients did not respond to the first course of treatment (primary unresponsiveness), two relapsed after initial clinical and parasitological cure, and two were withdrawn from the study (one on day 6 of treatment because of cardiotoxicity in the form of supraventricular tachycardia and the other on day 24 because of severe loss of appetite). All 30 patients who were not entirely cured with sodium stibogluconate were successfully treated with amphotericin B. Electrocardiographic changes occurred in many of the patients as the result of treatment with sodium stibogluconate. Diminution in the height of the T wave was seen in 32 (40%), inversion of the T wave (Minnesota code 5-1, 5-2) in seven (9%), elevation of the ST segment (Minnesota code 4-1) in three (4%), prolonged QT interval (compared with baseline findings) in six (8%), and diminution in the height of the P, R and T waves in two (3%). Cardiac arrhythmia occurred in five patients (6%), supraventricular arrhythmia (coarse atrial fibrillation) occurred in one patient and ventricular tachycardia, ventricular fibrillation, torsade de pointes and multifocal ventricular ectopics occurred in the four patients (5%) who died of cardiotoxicity. Minor side-effects, such as pain at the site of injection (two cases), mild diminution in appetite (12 cases), metallic taste in mouth (six cases), and joint pain (two cases), were also observed. It was concluded that the efficacy of sodium stibogluconate in the study area has declined over the years and that its toxicity has increased. A more efficacious, safer and cheaper, alternative drug is required as the first line of treatment of kala-azar.

Adolescent↗

Glutaraldehyde-induced esophageal injury. Histologic study of laboratory rats.

RATIONALE AND OBJECTIVES: A patient was encountered with a long esophageal stricture that may have been caused by glutaraldehyde-contaminated endoscopic equipment. An in vivo study of laboratory rats was performed to determine the effect of glutaraldehyde exposure on the esophagus. METHODS: Ten laboratory rats were divided into five groups that received daily gavage of the esophagus with either 3.2% glutaraldehyde solution (treated rats) or 1 mL of normal saline (control rats) for varying durations. After the rats were killed, histologic sections from the esophagus were reviewed in a blind fashion. The degree of inflammatory infiltrate at the gastroesophageal junction was quantified as mild, moderate, or marked. RESULTS: Histologic examination revealed greater neutrophilic infiltration in the submucosa of the gastroesophageal junction in three of four glutaraldehyde-treated rats compared with controls. Treated rats also had evidence of segmental esophageal vasculitis not seen in any of the controls. Both controls and treated rats had areas of myositis and myonecrosis within the esophagus. CONCLUSION: Exposure to glutaraldehyde has a toxic effect on the rat esophagus. Glutaraldehyde-induced esophageal injury should therefore be considered in patients who develop esophagitis or esophageal strictures after upper endoscopy.

Animals↗

Mapping of specific and promiscuous HLA-DR-restricted T-cell epitopes on the Plasmodium falciparum 27-kilodalton sexual stage-specific antigen.

We have characterized HLA-DR-restricted T-cell epitopes on the 27-kDa protein (Pfg27), a sexual stage-specific antigen, of the human malaria parasite Plasmodium falciparum in subjects with a history of malaria. Pfg27, expressed early in the sexual stages, is recognized by monoclonal antibodies capable of reducing the infectivity of gametocytes in mosquitoes. By using 16 Pfg27-specific CD4(+)-T-cell clones derived from three donors, seven different T-cell epitopes were identified. Among them, P11 (amino acids 191 to 210 of the Pfg27 sequence, IDVVDSYIIKPIPALPVTPD) was found to contain a previously described binding motif for multiple HLA-DR allotypes. Indeed, P11 was found to be promiscuous in that it could be recognized by T cells in the context of at least five different HLA-DR molecules. The cytokine profile of the clones was mixed. Seven of nine T-cell clones exhibited a Th0-like cytokine profile, producing high levels of gamma interferon (IFN-gamma) and interleukin-4 (IL-4) upon stimulation with specific peptides and mitogens. The other two clones had a Th1-like cytokine profile with high expression of IFN-gamma and no IL-4. Identification of a promiscuous epitope in Pfg27 could play a significant role in the design of a subunit vaccine for suppressing malaria transmission.

Amino Acid Sequence↗

Echocardiography in systemic lupus erythematosus.

Two dimensional echocardiography with doppler examination was performed in 54 patients with systemic lupus erythematosus (SLE). Nine (17%) had significant cardiac involvement (four left ventricular hypertrophy, one moderate pericardial effusion, one severe aortic regurgitation, and three ventricular systolic dysfunction). We further studied diastolic function in 45 patients who did not have a major abnormality in echo. SLE was graded as active in 16 patients (SLEDAI > 5) and inactive in 29 patients. Twenty age- and sex-matched subjects acted as controls. The data were compared using one way ANOVA test. Patients with active disease had significant diastolic dysfunction compared to inactive patients and controls as indicated by increased peak A (P < 0.01) and decreased E/A ratio (P < 0.01). There was no linear correlation between disease activity and diastolic dysfunction if SLEDAI was considered as a continuous variable (r=0.29 for E/A). Anticardiolipin antibodies (both IgG and IgM) were elevated in five patients (13 studied). One of them had severe mitral regurgitation, one had trace mitral and aortic regurgitation and one had diastolic dysfunction. We conclude that asymptomatic diastolic dysfunction is present in SLE patients.

Analysis of Variance↗

Prostate-sparing effects in primates of the potent androgen 7alpha-methyl-19-nortestosterone: a potential alternative to testosterone for androgen replacement and male contraception.

7alpha-Methyl-19-nortestosterone (MENT) is a potent synthetic androgen that cannot be converted to dihydrotestosterone. In this study we determined the relative androgenic, antigonadotropic, and anabolic potencies of testosterone vs. MENT in the nonhuman primate M. fascicularis. In castrated monkeys, dose-response relationships were generated for the effects of testosterone and MENT on gonadotropin levels, prostate growth, body weight, and lipid metabolism. In a pilot study, four monkeys were castrated, and magnetic resonance imaging (MRI) was used to document a 50% loss of prostate volume within 8 weeks, verifying that MRI is a reliable means to measure prostate size in this species. Two additional groups of six monkeys each were then castrated and serially administered four graded dosages of testosterone or MENT via osmotic minipumps over 20 weeks. Complete suppression of LH was achieved with a minimum of 0.3 mg/day MENT, compared to 3.0 mg/day testosterone. MENT supported body weight 10 times more potently than did testosterone. Baseline prostate volumes were maintained with 0.1-0.2 mg/day MENT vs. 0.3 mg/day testosterone. Thus, in monkeys, MENT is 10 times more potent than testosterone with regard to the clinically desirable end points of gonadotropin suppression and anabolism, but only twice as potent at stimulating prostate growth. These results suggest that MENT may have a wider therapeutic index than testosterone for human androgen replacement and male contraception.

Anabolic Agents↗

Assembly of connexins and MP26 in lens fiber plasma membranes studied by SDS-fracture immunolabeling.

The SDS-fracture immunolabeling technique, unlike conventional freeze-fracture, provides direct evidence for the biochemical nature of membrane constituents. SDS-fracture immunolabeling shows that during differentiation of lens fiber cells the onset of junctional assembly is characterized by the presence of small clusters and linear arrays comprising connexins alpha3 and alpha8. At this initial stage MP26, a major fiber membrane constituent, appears to be colocalized with these two connexins. The application of double-immunogold labeling reveals that when large junctional plaques are assembled MP26 becomes mainly associated with the periphery of the junctional domains. This type of distribution suggests that MP26 may play a role in the clustering and gathering of connexons. In aged nuclear fiber membranes connexins, MP26 and their proteolytic derivatives form an orthogonal lattice of repeating subunits.

Animals↗

A study of current trends in enteric fever.

The results of a study based on 68 cases of blood culture proven enteric fever are presented. Sensitivity to chloramphenicol, ampicillin and cotrimoxazole was found to be 55.88, 54.41, 38.23% respectively. Common clinical features were fever, vomiting, pain abdomen and cough in both the groups. There was no difference in complications in chloramphenicol sensitive against resistant cases. Of the chloramphenicol sensitive cases, 21.05% were resistant to cefotaxime. All cases were sensitive to ciprofloxacin. More than half the cases were sensitive to chloramphenicol and ampicillin.

Anti-Bacterial Agents↗

Effect of Septilin--a herbal preparation on pharmacokinetics of carbamazepine in rabbits.

The study was carried out in rabbits, to see the effects of Septilin, a herbal preparation on the single and multiple dose kinetics of carbamazepine. Single dose treatment of Septilin significantly decreased t 1/2a. t 1/2e. AUCo-alpha of carbamazepine. Steady state Cmax and AUC0-24 of carbamazepine were also reduced significantly in comparison to those of control rabbits after 7 days co-administration of Septilin. We conclude that Septilin decrease/hinder the absorption process of carbamazepine through an unknown mechanism.

Animals↗

A randomized comparison of classical mode of administration of amphotericin B with its newer modes of administration in kala-azar.

UNLABELLED: One hundred thirty parasitologically confirmed cases of kala-azar were randomly divided in two equal treatment groups. Patients in group A were treated by infusion with amphotericin B deoxycholate (ABD), 1 mg/kg day on days 1-20 and the infusion was given in two hours. Patients in group B were treated by an escalating dose of ABD 0.05 mg/kg, 0.1 mg/kg, 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg on days 1-5, respectively and then in the same dosage on alternate days. The infusion was completed in 6 hours. Total dose of 20 mg/kg remaining the same in both the groups, the treatment was completed in 20 days in group A and 43 days in group B. Clinical cure (subsidence of fever, improvement in general well being and regression in the size of the spleen) and parasitological cure (absence of parasites in splenic aspirates at the end of treatment) occurred in all patients in both the groups. Sixty four (99%) patients in each group had not relapsed clinically and parasitologically within 6 months of follow up and were ultimately cured. The two relapsed patients, one in each group were treated with a 20-day course of ABD and were cured. Leukocyte count, haemoglobin, serum albumin increased (P < 0.05) and ESR, spleen and liver size decreased (P < 0.05) at the end of treatment and follow up. Adverse events were similar in both the groups. The minimum cost of treatment estimated was Rs. 14,500 in group B and Rs. 10,000 in Group A. Thus the newer mode of administration was more cost effective. CONCLUSION: It was concluded that newer mode of administration of amphotericin B was as effective and tolerable as the classical mode of administration and was no more toxic. The newer mode of administration of amphotericin B is more cost effective and puts lesser burden on hospital staff and is recommended for use in kala-azar.

Adolescent↗

Nucleolar organiser regions and morphologic subtypes of squamous cell carcinoma of cervix.

Nucleolar organiser regions (NOR) are chromosomal segments coding for ribosomal RNA. The number of nucleolar organiser regions correlates with cellular proliferation and has a diagnostic and prognostic value in neoplastic diseases. The aim of this study was to study the morphologic subtypes of squamous cell carcinoma of the uterine cervix in biopsy and hysterectomy specimens and to determine the AgNOR counts in these morphologic subtypes. One hundred and seventy-nine cases of squamous cell carcinoma of the uterine cervix were classified into three morphological subtypes namely large cell non keratinising squamous cell carcinoma (113), keratinising squamous cell carcinoma (64) and small cell carcinoma (2). A correlation of histologic typing on biopsy and hysterectomy specimens was done in 142 cases with a complete correlation in 90.5%. Fifty-eight of these tumours were stained with silver nitrate to demonstrate Nucleolar organiser regions (AgNORS). The mean AgNOR count was higher (3.66) in keratinising squamous cell carcinoma, which is known to have a worse prognosis as compared to 3.04 in large cell non keratinising carcinoma and (3.45) in the two cases of small cell carcinoma of the uterine cervix.

Adult↗

Splenic abscess caused by Clostridium difficile.

Splenic abscess is a previously unreported complication of Clostridium difficile colitis. A case of Clostridium difficile splenic abscess is reported that developed after the patient had been in intensive care for five weeks. A response was seen to radiologically guided drainage and antibiotic therapy with formal laparotomy, and surgical drainage not being required.

Abscess↗