Search PubMed⌕ Search

Biomedical subjects

R Singh

Publications and source records attributed to R Singh.

At least 307 records · Page 17Linked to original sources
PubMed1998

Prone position ultrasonography in silicone filled eyes.

PURPOSE: To evaluate the efficacy of a new technique of prone position ultrasonography in cases with silicone filled eyes. METHODS: Forty patients with prior pars plana vitrectomy and silicone oil instillation referred to a tertiary eye care centre were the subjects of this study. A prospective clinical trial was undertaken to evaluate the efficacy of prone position ultrasonography in addition to routinely performed supine position ultrasonography in these patients. The technique was undertaken by 2 independent observers and compared with the findings by indirect ophthalmoscopy or surgical results. Interobserver variability was also calculated. RESULTS: Two spikes were observed in supine position corresponding to the intravitreal silicone oil surface and the sclera, whereas a single spike corresponding to the sclera was observed in prone position. Supine position ultrasonography yielded a diagnostic accuracy of 61.8%, which increased to 96.7% when the procedure was supplemented with prone position ultrasonography. Specificity increased from 75 to 100% by the addition of this adjuvant procedure, however, with no significant difference in the interobserver variability ('K'=0.67 Vs 'K'= 0.62). CONCLUSION: Prone position ultrasonography is a useful adjunct to the routinely performed supine position ultrasonography in silicone filled eyes and increases the diagnostic yield.

Diagnostic Techniques, Ophthalmological↗
PubMed1998

Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B.

Febrile seizures affect approximately 3% of all children under six years of age and are by far the most common seizure disorder. A small proportion of children with febrile seizures later develop ongoing epilepsy with afebrile seizures. Segregation analysis suggests the majority of cases have complex inheritance but rare families show apparent autosomal dominant inheritance. Two putative loci have been mapped (FEB1 and FEB2), but specific genes have not yet been identified. We recently described a clinical subset, termed generalized epilepsy with febrile seizures plus (GEFS+), in which many family members have seizures with fever that may persist beyond six years of age or be associated with afebrile generalized seizures. We now report linkage, in another large GEFS+ family, to chromosome region 19q13.1 and identification of a mutation in the voltage-gated sodium (Na+)-channel beta1 subunit gene (SCN1B). The mutation changes a conserved cysteine residue disrupting a putative disulfide bridge which normally maintains an extracellular immunoglobulin-like fold. Co-expression of the mutant beta1 subunit with a brain Na+-channel alpha subunit in Xenopus laevis oocytes demonstrates that the mutation interferes with the ability of the subunit to modulate channel-gating kinetics consistent with a loss-of-function allele. This observation develops the theme that idiopathic epilepsies are a family of channelopathies and raises the possibility of involvement of other Na+-channel subunit genes in febrile seizures and generalized epilepsies with complex inheritance patterns.

Amino Acid Sequence↗
PubMed1998

Autosomal dominant nocturnal frontal-lobe epilepsy: genetic heterogeneity and evidence for a second locus at 15q24.

Autosomal dominant nocturnal frontal-lobe epilepsy (ADNFLE) is a recently identified partial epilepsy in which two different mutations have been described in the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4). An additional seven families are presented in which ADNFLE is unlinked to the CHRNA4 region on chromosome 20q13.2. Seven additional sporadic cases showed no evidence of defective CHRNA4. One of the families showed evidence of linkage to 15q24, close to the CHRNA3/CHRNA5/CHRNB4 cluster (maximum LOD score of 3.01 with D15S152). Recombination between ADNFLE and CHRNA4, linkage to 15q24 in one family, and exclusion from 15q24 and 20q13.2 in others demonstrate genetic heterogeneity with at least three different genes for ADNFLE. The CHRNA4 gene and the two known CHRNA4 mutations are responsible for only a minority of ADNFLE. Although the ADNFLE phenotype is clinically homogeneous, there appear to be a variety of molecular defects responsible for this disorder, which will provide a challenge to the understanding of the basic mechanism of epileptogenesis.

Chromosome Mapping↗
PubMed1998

Determination of malondialdehyde-induced DNA damage in human tissues using an immunoslot blot assay.

Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has been detected in healthy human liver and leukocyte DNA. Analytical methods used so far for the detection of M1-dG have not been applied to a large number of individuals or variety of samples. Often, only a few microg of DNA from human tissues are available for analysis and a very sensitive assay is needed in order to detect background levels of M1-dG in very small amounts of DNA. In this paper, the development of an immunoslot blot (ISB) assay for the measurement of MI-dG in 1 microg of DNA is described. The limit of detection of the assay is 2.5 adducts per 10(8) bases. A series of human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n = 42) of M1-dG per 10(8) normal bases were detected in white blood cell and gastric biopsy DNA, respectively. Results on four human samples were compared with those obtained using an HPLC/32P-post-labelling (HPLC/PPL) method previously developed and indicated a high correlation between M1-dG levels measured by the two assays. The advantages of ISB over other assays including HPLC/PPL, such as the possibility of analysing 1 microg DNA/sample and the fact that it is less time-consuming and laborious, means that it can be more easily used for routine analysis of a large number of samples in biomonitoring studies.

Animals↗
PubMed1998

Post-penetrating keratoplasty glaucoma: risk factors, management and visual outcome.

PURPOSE: To evaluate the incidence, associated risk factors, graft status and treatment modalities in patients with post-penetrating keratoplasty glaucoma. METHODS: A retrospective analysis of 747 consecutive penetrating keratoplasties was undertaken at a tertiary eye care centre. The frequency of post-penetrating keratoplasty glaucoma was determined and correlated with the pre-operative corneal diagnosis, lens status and associated surgeries performed during penetrating keratoplasty. The response to antiglaucoma therapy (i.e. medical, surgical or cyclo-destructive procedures) and graft outcome was also evaluated. RESULTS: The incidence of post-penetrating keratoplasty glaucoma was 10.6% (79/747). Pre-operative corneal diagnosis of adherent leucomas was significantly associated with the development of postoperative glaucoma. Post-penetrating keratoplasty glaucoma was significantly higher in aphakes (odds ratio (OR) 6.6; confidence interval (CI) 3.81-11.69) compared with phakic or pseudophakic eyes. Associated vitrectomy (OR 2.32; CI 1.16-4.73) and anterior segment reconstruction (OR 3.31; CI 1.43-7.72) were other high-risk factors. Most patients responded to medical therapy (41/79; 51.9%), whereas filtering surgery and cyclo-destructive procedures were performed in 29.1 (23/79) and 19% (15/79) of eyes, respectively. Despite clear grafts in 39 eyes (49.4%), visual acuity of 6/18 or better was achieved in 15 eyes (18.9%). CONCLUSIONS: A high incidence of post-penetrating keratoplasty glaucoma occurs in eyes with adherent leucomas. Anterior vitrectomy and associated surgeries further accentuate the risk Anti-glaucoma therapy may not achieve optimum visual outcome, despite a clear graft.

Antihypertensive Agents↗
PubMed1998

Neoadjuvant chemotherapy in locally advanced cervical cancer: two randomised studies.

Between August 1990 and January 1992, 184 patients with squamous cell carcinoma of the cervix, FIGO stage II B IV A were randomised (study 1) to receive either two cycles of bleomycin, ifosfamide-mesna and cisplatin (BIP) chemotherapy (CT) followed by radiotherapy (RT) 'CT-RT Group' n = 94 or RT alone, RT Group n = 90. In the 'CT-RT Group', of evaluable 89 patients, 64 responded: complete response (CR) four (4.5%) and partial response (PR) 60 (67.5%). Of the remaining 25 patients 23 had stable disease and two progressed. Eighty of 89 patients completed RT as planned. Following RT 56 (70%) achieved CR, 19 (23.7%) had residual disease and five (6.3%) had progressed. Patients aged > 45 and those with Hb > 10 gm/dL had significantly better response to CT. Further, CT responders had a better response to RT; 83% (49/59) vs 33.3% (seven/21), p < 0.01. In the 'RT Group' 88 patients were evaluable; 61 (69.3%) patients achieved CR, 25 had residual disease and two progressed. The estimated overall survival at 48 months in the 'CT-RT Group' and the 'RT Group' is 38% +2.01 (SE) and 36% +1.85 (SE), p = 0.59 respectively. In a subsequent randomised study (study 2) 36 patients with stage III B cervical cancer received three cycles of BIP (as above) followed by RT vs 36 patients who received RT alone. In the 'CT-RT Group' 29 patients responded; CR-8 (22.2%), PR-21 (58.3%). Six patients had no response to CT and one patient died of CT toxicity. Following RT-24 of 35 (68-6%) patients achieved CR, eight had residual disease and three patients progressed while on RT. In the 'RT Group'-21 of 36 (58.4%) achieved CR, 12 had residual disease and three progressed. Estimated survival was 71% in the 'CT-RT Group' and 69% in the 'RT Group', p = ns. Nausea/vomiting, alopecia, grade I-II myelosuppression, diarrhoea and mucositis were the major side effects of CT. Three patients died of CT toxicity-two in study 1 and one in study 2. Cystitis, proctitis and local skin reaction after RT occurred equally in the two groups in both the studies. BIP CT prior to RT in patients with locally advanced cervical cancer results in a high response rate. Response to CT predicts response to RT. There is no increase in the toxicity to subsequent RT. Our studies have failed to demonstrate any significant difference in overall and disease-free survival when neoadjuvant CT is added prior to the standard RT regimen.

Adult↗
PubMed1998

Single agent versus combination chemotherapy in recurrent cervical cancer.

OBJECTIVE: Cisplatin and ifosfamide are two most active agents in patients with recurrent and metastatic cervical cancer. Combination of bleomycin, ifosfamide and cisplatinum (BIP) was compared with cisplatinum alone. PATIENTS AND METHODS: One hundred and six patients with recurrent/persistent and metastatic cervical cancer received either a combination of bleomycin, ifosfamide and cisplatinum, (Group A, n = 50) or cisplatinum alone (Group B, n = 56) every 3 weeks for up to 6 courses. Ninety-seven patients were evaluable and were analysed for response and survival. RESULTS: Patients receiving BIP (Group A) had a higher response rate (complete and partial responses), 52.2% vs 29.4%, p < 0.01 with overall median survival, 8 months (1 to 92+ months) vs 6 months (1 to 40+ months), p = 0.18. Chemotherapy responders had a significantly higher survival in both groups compared to the non-responders (Group A: 17 vs 6 months, p < 0.001, Group B: 20.5 months vs 5 months, p < 0.001). Patients in good performance status (ECOG, 0-2) had a significantly higher response rate to chemotherapy (Group A: 70.3% vs 26.3%, p < 0.01, Group B: 38.2% vs 11.7%, p < 0.05). In Group A, patients with extrapelvic disease responded better compared to pelvic disease (83.3% vs 34.5%, p < 0.01). Chemotherapy side effects were mainly nausea/vomiting, alopecia, myelosuppression, reversible encephalopathy (in Group A), and impaired renal functions. Chemotherapy toxicity was higher for patients receiving BIP, 2 patients died of BIP toxicity. Currently, in 'Group A' 8 patients are alive, 7 disease-free and one with disease at a median interval of 51 months after chemotherapy treatment. While in Group B, 3 patients are alive, 2 disease-free and one with disease. CONCLUSIONS: Bleomycin, ifosfamide and cisplatin improved the response rate in recurrent and metastatic cervical cancer compared with cisplatinum alone. However, the toxicity was moderate and survival was not significantly improved. These results need to be confirmed in a phase III, randomized study in larger number of patients.

Adult↗
PubMed1998

Subepithelial fibroblast cell lines from different levels of gut axis display regional characteristics.

The intestine is characterized by morphofunctional differences along the proximodistal axis. The aim of this study was to derive mesenchymal cell lines representative of the gut axis. We isolated and cloned rat intestinal subepithelial myofibroblasts raised from 8-day proximal jejunum, distal ileum, and proximal colon lamina propria. Two clonal cell lines from each level of the gut were characterized. They 1) express the specific markers vimentin, smooth muscle alpha-actin, and smooth muscle myosin heavy chain, revealed by immunofluorescence microscopy and 2) distinctly support endodermal cell growth in a coculture model, depending on their regional origin, and 3) the clones raised from the various proximodistal regions maintain the same pattern of morphogenetic and growth and/or differentiation factor gene expression as in vivo: hepatocyte growth and/or scatter factor and transforming growth factor-beta 1 mRNAs analyzed by RT-PCR were more abundant, in the colon and ileal clones and mucosal connective tissue, respectively. In addition, epimorphin mRNA studied by Northern blot was also the highest in one ileal clone, in which it was selectively upregulated by all-trans retinoic acid (RA) treatment. Epimorphin expression in isolated 8-day intestinal lamina propria was higher in the distal small intestine and proximal colon than in the proximal small intestine. In conclusion, we isolated and characterized homogeneous cell subtypes that can now be used to approach the molecular regulation of the epithelium-mesenchyme-dependent regional specificity along the gut.

Animals↗
PubMed1998

Characterization of rat epimorphin/syntaxin 2 expression suggests a role in crypt-villus morphogenesis.

The rodent intestinal mucosa undergoes a remarkable morphogenesis as the crypt-villus axis is formed. Endoderm-mesenchymal interactions play a critical role in this process. Epimorphin is a mesenchymal protein postulated to play a role in lung and skin morphogenesis. The rat homologue, syntaxin 2, belongs to a family of integral membrane proteins that function in vesicle docking and fusion. To clarify its role in fetal gut morphogenesis, epimorphin expression was examined during ontogeny, in an isograft model of ischemic injury and mucosal repair, and during intestinal adaptation after small bowel resection. Epimorphin/syntaxin 2 mRNA levels were increased in fetal gut during lumen formation and villus morphogenesis. mRNA levels remained elevated in the first 2 wk after birth and then declined at weaning. In situ hybridization showed epimorphin/syntaxin 2 mRNA in gestational day 14 (G14) and G15 intestinal mesenchymal cells and in the mucosal lamina propria during villus formation. Epimorphin/syntaxin 2 mRNA expression increased during villus repair in the isograft. In contrast, in the early stages of intestinal adaptation after small bowel resection, epimorphin/syntaxin 2 mRNA expression was suppressed in the adapting gut. We conclude the cell-specific and temporal patterns of epimorphin expression in the models used in this study suggest a role in the morphogenesis of the crypt-villus axis.

Aging↗
PubMed1998

Estradiol suppresses MCP-1 expression In vivo : implications for atherosclerosis.

The mechanisms by which 17beta-estradiol retards atherogenesis are not known. The adhesion of monocytes to endothelial cells followed by the migration of monocytes into the artery wall are key cellular events that occur throughout the entire atherogenic process and may be responsive to estradiol. Monocyte chemoattractant protein-1 (MCP-1), a chemokine that is expressed in atherosclerotic lesions, is thought to play a major role in stimulating the migration of blood monocytes into developing atherosclerotic lesions. We therefore assessed the effects of estradiol in vivo on MCP-1 protein and mRNA expression in the descending thoracic aorta of rabbits fed a cholesterol-enriched (0.5%) diet for 6 weeks and in animals fed normal chow. MCP-1 protein was quantified by Western blot analysis and monocyte chemotaxis bioassay, and reverse transcription-polymerase chain reaction was used to ascertain the level of MCP-1 mRNA expression. We observed that in both ovary-intact and ovariectomized (OVX) animals, MCP-1 protein and mRNA expression were significantly increased by 6 weeks in animals fed a high-cholesterol diet. The cholesterol-induced increase in MCP-1 protein and mRNA expression was significantly attenuated in OVX rabbits supplemented with estradiol pellets (1.5- and 10.0-mg 60-day-release pellets), which yielded a range of estradiol concentrations encompassing the physiological levels. MCP-1 protein and mRNA expression were increased in normocholesterolemic OVX rabbits compared with normocholesterolemic ovary-intact animals, and this increase was prevented in OVX animals supplemented with estradiol pellets. Our observations indicate that both basal and hypercholesterolemia-induced increases in MCP-1 protein are modulated by physiological concentrations of estradiol.

Animals↗
PubMed1998

Local anaesthetics: an overview of current drugs.

Local anaesthetics are one of the most widely used classes of drugs in clinical practice. When they are given systemically, cardiac, skeletal and smooth muscle may be affected, as well as the peripheral and central nervous systems and the specialized conducting system of the heart. Knowledge of the pharmacology, action, metabolism and side-effects is vital for safe use of these drugs.

Anesthetics, Local↗
PubMed1998

Purification and characterizaton of plastidic pyruvate kinase from developing seeds of Brassica campestris L.

Plastidic pyruvate kinase (ATP: pyruvate phosphotransferase, EC 2.7.1.40) was purified to near homogeneity as judged by native PAGE with about 4% recovery from developing seeds of Brassica campestris using (NH4)2SO4 fractionation, DEAE-cellulose chromatography, gel filtration through Sepharose-CL-6B and affinity chromatography through reactive blue Sepharose-CL-6B. The purified enzyme having molecular mass of about 266 kDa was quite stable and showed a broad pH optimum between pH 6.8-7.8. Typical Michaelis-Menten kinetics was obtained for both the substrates with K(m) values of 0.13 and 0.14 mM for PEP and ADP, respectively. The enzyme could also utilize CDP, GDP or UDP as alternative nucleotide to ADP, but with lower Vmax and higher K(m). The enzyme had an absolute requirement for a divalent and a monovalent cation for activity and was inhibited by oxalate, fumarate, citrate, isocitrate and ATP, and activated by AMP, aspartate, 3-PGA, tryptophan and inorganic phosphate. ATP inhibited the enzyme competitively with respect to PEP and non-competitively with respect to ADP. Similarly, oxalate inhibition was also of competitive type with respect to PEP and non-competitive with respect to ADP. This inhibition by either ATP or oxalate was not due to chelation of Mg2+, as the inhibition was not relieved on increasing Mg2+ concentration even upto 30 mM. Initial velocity and product inhibition studies demonstrated the reaction mechanism to be compulsory ordered type. The enzyme seems to be regulated synergistically by ATP and citrate.

Brassica↗
PubMed1998

Regional effects of ageing on Na+,K(+)-ATPase activity in rat brain and correlation with multiple unit action potentials and lipid peroxidation.

Effects of ageing on Na+,K(+)-ATPase activity in crude synaptosomal fractions from the rat brain parietal cortex, hippocampus, striatum and thalamus has been studied. From 12 months to 24 months, a progressive decline in enzyme activity in the parietal cortex, hippocampus and striatum was found which correlated with increase in lipid peroxidation in the three brain regions. In the thalamus, ageing did not affect the enzyme activity and lipid peroxidation. Age-related decline in multiple unit action potentials was also observed in two brain regions, viz. hippocampus and parietal cortex. Statistical correlations calculated by Pearson's correlation coefficient showed that decline in Na+,K(+)-ATPase activity correlated to decline in multiple unit action potentials. There was rise in lipid peroxidation also and the data indicate that age-related changes in lipid peroxidation and Na+,K(+)-ATPase activity contribute to the deterioration of electrophysiological activity.

Action Potentials↗
PubMed1998

Radiotherapy in locally advanced cancer of the cervix.

Radical radiotherapy is considered as the treatment of choice in locally advanced cancer cervix. In late stages radiotherapy produce optimum palliation and to some extent cure. Three hundred cases of cancer cervix (stage I-IV) comprising stage-I (7), stage-II (144), stage-III (145) and stage IV (4) were evaluated and treated with radiotherapy between April 1990 to July 1994. FIGO stage IB, IIA and IIB (early), were treated with predominant intracavitary radiotherapy (34 Gy X 2 fractions; within one week) followed by external pelvic radiotherapy to a dose of 36 Gy in 18 fractions; treating 200 cGy per fraction, 5 days a week. The late stage (stage-IIB, IIIA and IIIB, IVA) of disease were managed with initial external radiotherapy to a dose of 50 Gy, followed by a single intracavitary dose of 30 Gy to point-A. The median follow up was 33 months (range 12-72 months). The tumor volume less than 100 cc were associated with better survival than volume more than 100 cc (p < 0.05). The five year actuarial survival was 83%, 68% and 58% respectively in FIGO stage I-III disease. There were 0.33% and 2.6% late grade-III bladder and rectal complications. Our experience shows effectiveness of radiotherapy in the management of locally advanced cancer of the cervix.

Adult↗
PubMed1998

Simultaneous radiochemotherapy in the treatment of inoperable, locally advanced head and neck cancers.

The results of radiation therapy alone in locally advanced head and neck cancers are dismal with 5 year locoregional control rates not exceeding 15%. The addition of concomitant chemotherapy with cisplatin and more recently carboplatin has shown promising results. Twenty patients of inoperable stage III and IV oral or oropharyngeal cancers were treated with concomitant chemoradiation with carboplatin 300 mg/m2 i.v. on days 1, 21 and 42 of radiation therapy. Twelve (60%) patients had a complete remission. Thirteen patients were alive at a median follow up of 11 months. The treatment was well tolerated with only 2 patients requiring treatment interruptions for mucositis. Longer follow up would reveal any improvement in overall survival. The relative ease with which carboplatin/RT was administered suggests that other agents might be added as well.

Antineoplastic Agents↗
PubMed1998

Assessment of sperm count in rural population of central India.

Semen samples from 1425 males who visited the Reproductive Biology Unit, M. G. I. M. S., Sewagram during the period from 1984 to 1996 were analysed. The data for sperm count was analysed over the length of period and no change in sperm count was found with passage of time.

Adolescent↗