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Biomedical subjects

M Sharma

Publications and source records attributed to M Sharma.

At least 145 records · Page 8Linked to original sources

Cardiac status in typhoid fever.

Fifty adult patients with culture-proved typhoid fever were subjected to daily clinical, electrocardiographic (ECG), and electrolyte assessment to evaluate and correlate their cardiac status. Transaminases and creatine kinase (CCK-MB) were estimated on alternate days and echocardiographic assessment was done once during hospitalization. The patients were distributed into groups: I (21) who did not have any ECG or enzymes changes, IIa (17) who had both ECG as well as enzymes changes, IIb (5) who had ECG changes only, and IIc (7) who had elevated enzymes only. Various types of ECG abnormalities were observed in 22 patients. Transaminases were significantly raised (P < 0.001) in group IIa and IIc patients (24). However, CK-MB was significantly raised (P < 0.001) only in the 5 patients of group IIa. There was no relationship among the elevated enzyme levels, severity of disease, and ECG changes. Further, ECG changes were observed during the convalescence stage also, but transaminases were found to be elevated only during the acute stage. It is concluded that definite injury to the heart occurs during typhoid fever. However, it is difficult to ascertain the exact time and extent of the injury. Further, CK-MB was not found to be superior to transaminases for assessment.

Adult↗

Reversible parotid enlargement and pseudo-Sjögren's syndrome secondary to hypertriglyceridemia.

We describe 2 patients with a Sjögren-like syndrome apparently secondary to hypertriglyceridemia. Both had bilateral parotitis in addition to musculoskeletal and sicca symptoms. Parotid gland histology revealed fatty infiltration with no inflammation. Therapy with dietary modification and triglyceride lowering drugs resulted in resolution of symptoms and parotid swelling in one patient. In the 2nd patient, hypertriglyceridemia was resistant to triglyceride lowering drugs, and parotid symptoms and swelling continued unabated. Our findings suggest aggressive treatment of hyperlipidemia in pseudo-Sjögren's syndrome may result in amelioration of musculoskeletal and parotid symptoms.

Adult↗

The effect of hematocrit on the efficiency of hemodialysis in cases of chronic renal failure.

Twenty patients of chronic renal failure were evaluated to study the effect of increase in hematocrit (Hct) on the efficiency of hemodialysis. All the patients were subjected to two hemodialysis of identical duration with an interdialytic interval of 48 hours. All were anemic with a mean hemoglobin of 6.73 gm% and a hematocrit of 22.2%. Hematocrit was raised to a mean of 32.02% following transfusion of 2 units (600-700 ml) of whole blood (p < 0.001) in the interdialytic interval. Blood clearances (Kb). Dialysate clearance (Kd), fractional decrement and Kt/V ratio of solutes (urea, creatinine and phosphates) were calculated during both the dialysis and compared with each other. Kt/V of urea decreased from 1.0589 +/- 0.24 to 0.89 +/- 0.15 (p < 0.001), and that of creatinine 1.003 +/- 0.19 to 0.832 +/- 0.009 (p < 0.001) and phosphates 0.992 +/- 0.16 to 0.826 +/- 0.006 (p < 0.001) and it showed a negative correlation with rise in hematocrit. It was significant for creatinine and phosphates and insignificant for urea, suggesting thereby that the efficiency of dialysis decreased with increase in hematocrit. This is important in view of under dialysis in patients of normal or near normal hematocrit and suggests the need for modification of dialysis prescription in such situations.

Adult↗

Escalating paclitaxel doses combined with carboplatin/etoposide and thoracic radiotherapy as preoperative or definitive treatment for stage III non-small cell lung cancer.

We have evaluated escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with carboplatin, cisplatin, etoposide, and concurrent thoracic radiotherapy in patients with stage III non-small cell lung cancer. Dose-limiting toxicity was observed at paclitaxel 90 mg/m2. Subsequent modifications resulted in a new regimen, which consists of a 3-hour paclitaxel infusion on day 1 (three dose levels: 80, 100, and 120 mg/m2), etoposide 40 mg/m2 intravenously over 1 hour daily on days 2 to 5, and carboplatin given at an area under the concentration-time curve of 4 mg/mL x min on day 1 after paclitaxel. Treatment courses were repeated every 28 days. Eleven patients considered eligible for surgery received two courses. Nonsurgical patients (five) received three courses. No episodes of grade > or = 3 nausea and vomiting, dermatitis, anorexia, esophagitis, or thrombocytopenia were observed. The dose-limiting toxicity (grade 4 granulocytopenia) occurred in three of five patients at 120 mg/m2 paclitaxel (level 3). Grade 3 radiation pneumonitis was observed in three patients. Nine patients have undergone pulmonary resection: four pneumonectomies, four lobectomies, and one segmental resection. No operative deaths, respiratory insufficiency, or cardiovascular complications were observed. Clinical partial remissions have been observed in 11 of 16 patients overall, and two histologic complete remissions were achieved in nine surgical patients. Our preliminary results show that pulmonary resection is feasible following treatment with radiation and concurrent paclitaxel-containing chemotherapy. Although the maximum tolerated paclitaxel dose in the present study was relatively low, favorable initial responses warrant further study of paclitaxel-containing combination chemotherapy and concurrent radiation. We next plan to delete etoposide from our chemoradiotherapy regimen and escalate the paclitaxel dose.

Agranulocytosis↗

Comparison of sodium nitroprusside added peritoneal dialysis and standard haemodialysis.

Thirty patients of acute or acute on chronic renal failure (ACRF) were randomly divided into two group of 15 cases each. Group A patients received 36 cycles of intermittent peritoneal dialysis (PD) with an exchange volume of one litre and duration of one hour per cycle. The 36 cycles of PD were divided into 12 clearance periods of 3 cycles each. Sodium Nitroprusside (SNP) was added in a dose of 4 mg/litre of dialysate in alternate clearance periods. Group B patients were given 4 hours of haemodialysis (HD) to compare the efficacy of two modes of dialysis. Symptomatic relief was observed in various uraemic signs and symptoms like vomiting, level of consciousness, fluid overload, hiccough and asterexis in most of the patients in both the groups. The percentage fall in blood urea and serum creatinine was 57.02 Vs 58.04 mg% and 46.9 Vs 47.8 mg% in group A and B respectively (P 70.5 each). Total dialysate urea removal following PD and HD was 118.8 +/- 57.3 gm and 98.5 +/- 37.0 gm respectively and also there was no significant difference in total creatinine removal. No untoward effects were observed with PD. However, following HD, 5 patients developed hypotension, supraventricular tachycardia was observed in one and disequilibrium syndrome in 8 of them. Therefore, it can be concluded that SNP added PD is comparable to 4 hours of haemodialysis both clinically as well as biochemically and in situations where facilities for HD do not exist or it is contraindicated, PD may be preferred mode of therapy.

Adult↗

Versatile intermediates in the selective modification of the amino function of 2-amino-2-deoxy-D-mannopyranose and the 3-position of 2-acetamido-2-deoxy-D-mannose: potential membrane modifiers in neoplastic control.

A general method has been developed to selectively modify the amino group of 2-amino-2-deoxy-D-mannopyranose (D-mannosamine), a precursor of the terminal membrane sugar, sialic acid. 1,3,4,6-Tetra-O-acetyl-2-amino-2-deoxy-alpha-D-mannopyranose oxalate was prepared via two routes that allowed introduction of various acyl groups onto the amino function. These compounds were evaluated for their antineoplastic properties. The most significant preclinical therapeutic finding was the antileukemic activity found in mice for tetra-O-acetyl-2-epi-streptozotocin (the acetylated alpha-mannosamine epimer of streptozotocin). Administration of 50 mg/kg/day x 5 to leukemia L1210-bearing DBA/2Ha mice resulted in 5/5 35-day survivors. Neutralization of 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-alpha-D-mannopyranose oxalate under aqueous conditions led to 2-acetamido-1,4,6-tri-O-acetyl-2-deoxy-alpha-D-mannopyranose, the oxidation of which gave 2-acetamido-4,6-di-O-acetyl-1,5-anhydro-2-deoxy-D-erythro-hex-1-en-3- ulose. This agent demonstrated an IC50(2) of 25 microM with a murine L1210 cell culture. Administration of 100 mg/kg/day x 5 resulted in 42% ILS3 in DBA/2 mice with ip L1210 leukemia. Several other nonacetylated derivatives were also prepared by direct N-acylation, producing, for example, fluorescently tagged N-dansylmannosamine.

Animals↗

Capillary electrophoretic separation and laser-induced fluorescence detection of the major DNA adducts of cisplatin and carboplatin.

Micellar electrokinetic capillary chromatographic separation of a dansylated mixture of normal nucleotides and platinated cross-link adducts of d(pGpG) and d(pApG) was optimized with baseline resolution. The introduction of a laser-induced fluorescence (LIF) detector overcame the lack of sensitivity characteristic of capillary electrophoresis (CE) due to the small injection volume and the short optical path length. CE/LIF was able to detect 1 adduct/10(4) normal nucleotides/micrograms DNA by fluorescence postlabeling assay. The enrichment of the adduct, prior to dansylation, enhanced the detection limit to 1 adduct/10(7) normal nucleotides/micrograms DNA. Calf thymus DNA was reacted in vitro with cisplatin and carboplatin with total input drug/nucleotide ratios of 0.05 and 0.5, respectively. A2780 human ovarian carcinoma cells were exposed in culture to 25 microM cisplatin for 2 h. The cells were incubated with drug-free medium for 3 h before harvesting. The identification of the cross-link adducts in modified DNA was confirmed by cochromatography with authentic markers. The same 1,2-intrastrand cross-link adducts were induced by both cisplatin and its second-generation drug carboplatin. This report has demonstrated, for the first time, the utility of CE/LIF as an analytical tool for assaying DNA damage [corrected].

Animals↗

Role of ligaments and facets in lumbar spinal stability.

STUDY DESIGN: The issue of segmental stability using finite element analysis was studied. Effect of ligament and facet (total and partial) removal and their geometry on segment response were studied from the viewpoint of stability. OBJECTIVES: To predict factors that may be linked to the cause of rotational instabilities, spondylolisthesis, retrospondylolisthesis, and stenosis. SUMMARY OF BACKGROUND DATA: The study provides a comprehensive study on the role of facets and ligaments and their geometry in preserving segmental stability. No previous biomechanical study has explored these issues in detail. METHODS: Three-dimensional nonlinear finite element analysis was performed on L3-L4 motion segments, with and without posterior elements (ligaments and facets), subjected to sagittal moments. Effects of ligament and facet (partial and total) removal and their orientations on segment response are examined from the viewpoint of stability. RESULTS: Ligaments play an important role in resisting flexion rotation and posterior shear whereas facets are mainly responsible for preventing large extension rotation and anterior displacement. Facet loads and stresses are high under large extension and anterior shear loading. Unlike total facetectomy, selective removal of facets does not compromise segmental stability. Facet loads are dependent on spatial orientation. CONCLUSIONS: Rotational instability in flexion or posterior displacement (retrospondylolisthesis) is unlikely without prior damage of ligaments, whereas instability in extension rotation or forward displacement (spondylolisthesis) is unlikely before facet degeneration or removal. The facet stress and displacement distribution predicts that facet osteoarthritis or hypertrophy leading to spinal stenosis is most likely under flexion-anterior shear loading. Selective facetectomy may restore spinal canal size without compromising the stability of the segment. A facet that is more sagittally oriented may be linked to the cause of spondylolisthesis, whereas a less transversely oriented facet joint may be linked to rotational instabilities in extension.

Biomechanical Phenomena↗

Effect of dietary fibre from cereal brans and legume seedcoats on serum lipids in rats.

The present investigation was carried out to study the hypolipidemic effect of dietary fibre from cornbran and blackgram seedcoat in rats. Isoproteinous diet having one percent cholesterol and ten percent dietary fibre from cornbran and blackgram seedcoat was fed to four groups of albino rats for six weeks. With consumption of both the grain husks, total lipids, cholesterol and tryglycerides were lowered while HDL-cholesterol was found to be significantly increased. However, serum phospholipids were not affected significantly by grain husks. Cornbran was observed to be more hypolipidemic than blackgram seedcoat.

Animals↗

Localization and measurement of occupied androgen receptors in thaw-mounted rat and human prostate tissue sections by in vitro autoradiography.

In this paper we present an in vitro exchange binding assay procedure for measurement of androgen receptors in slide-mounted tissue sections. This method allows quantitative autoradiographic determinations with an anatomical resolution approaching the cellular level. Tissue sections are incubated with the synthetic androgen [3H]R1881 in the presence of triamcinolone acetonide to suppress possible binding of the radioligand to the progestin receptor. Adjacent tissue sections are incubated with [3H]R1881 in the presence of excess unlabeled 5 alpha- dihydrotestosterone or R1881 to assess nonspecific binding. Following incubation, the tissue sections are washed to remove unbound radioligand and either scraped for immediate determination of androgen receptor binding or placed against emulsion-coated film for the production of an autoradiographic image. In validation experiments with rat prostate sections from castrated, gonad-intact, and androgen-supplemented animals, maximum levels of androgen binding were observed with incubation at 4 degrees C or 72 h. Markedly less binding was detected with shorter incubations or with incubations at even slightly elevated temperatures. Very little androgen receptor binding was detected in castrated animals whereas receptor levels in intact and androgen-supplemented animals were 79.3 fmol/mg and 143.6 fmol/mg protein, respectively, suggesting that the method is selective for occupied receptors. Saturation binding analysis revealed binding to a single class binding site with high affinity (kd = 1.475 +/- 0.12 nM). Autoradiographic images of androgen binding in the prostate reflected the findings with the scraped sections: essentially no specific binding was present in sections from castrated animals whereas much heavier labeling was present in sections from intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vitro labeling of gonadal steroid hormone receptors in brain tissue sections.

Autoradiographic methods have been developed for measurement of gonadal steroid receptors in situ in brain tissue sections. Based on principles established previously for estrogen receptors in the rat brain using a 125I-labeled ligand, procedures have been developed for in vitro labeling of estrogen, androgen, and progestin receptors with commercially available tritiated ligands. Addition of protamine sulfate to the incubation buffer precipitates the receptors in situ in the tissue sections, allowing them to be detected autoradiographically after incubation with labeled steroid and subsequent washing to remove unbound and nonspecifically bound ligand. Occupied and unoccupied estrogen receptors can be measured selectively using appropriately modified incubation conditions. In the case of androgen and progestin receptors, unoccupied receptors are readily detected by in vitro labeling of tissue sections, but occupied receptors do not appear to label efficiently. Preliminary data suggest that these methods should be equally applicable to a variety of laboratory animals, including the rat, mouse, guinea pig, and monkey.

Animals↗

The pharmacokinetics and neuromuscular effects of rocuronium bromide in patients with liver disease.

To determine the effect of liver disease on the pharmacokinetics of rocuronium, the authors administered 0.6 mg/kg (twice the ED95) to 10 patients with liver disease and compared these results to values in 10 healthy surgical patients. Anesthesia was induced with thiopental and maintained with isoflurane (0.9%-1.1% end-tidal concentration) and nitrous oxide (60%). Venous blood samples were obtained for 6 h after rocuronium injection and plasma concentrations were measured using gas chromatography. Pharmacokinetic differences between groups were determined using a population-based pharmacokinetic analysis (NONMEM). Hepatic impairment did not alter the plasma clearance of rocuronium (217 +/- 21.8 mL/min, mean +/- SE, for both groups), but did increase the volume of the central compartment (5.96 +/- 1.01 L for controls, 7.87 +/- 1.33 L for patients with liver disease) and volume of distribution at steady state (16.4 L for controls, 23.4 L for patients with liver disease). In turn, elimination half-life was longer in patients with liver disease (111 min) compared to controls (75.4 min). The authors conclude that liver disease alters the pharmacokinetics of rocuronium by increasing its volume of distribution. The longer elimination half-life might result in a longer duration of action of rocuronium in patients with liver disease, particularly after prolonged administration.

Adult↗

Methionine-induced alterations in the life span, antioxidant enzymes, and peroxide levels in aging Zaprionus paravittiger (Diptera).

The median and maximum life spans of both sexes of Zaprionus paravittiger increased with methionine (100 mM) feeding. It was accompanied by higher catalase and peroxidase enzyme activities. The lipid peroxide level as measured by malondialdehyde content and the inorganic peroxides showed an increase with age and a decrease in methionine-fed insects. The reduction was, however, more pronounced in females than in males. The findings indicate that a life-prolonging effect of methionine on Z. paravittiger may be by virtue of its free radical scavenging effect.

Animals↗