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Biomedical subjects

M Sharma

Publications and source records attributed to M Sharma.

At least 451 records · Page 25Linked to original sources

Effects of glutathione on alkylation and cross-linking of DNA by mitomycin C. Isolation of a ternary glutathione-mitomycin-DNA adduct.

Mitomycin C (MC), a clinically used antitumor antibiotic, is known to alkylate DNA monofunctionally, and to generate DNA interstrand cross-links by bifunctional alkylation. Both processes are dependent on the reductive activation of MC. Glutathione (GSH) was shown here to cause three types of changes in the pattern of alkylation of DNA by MC: (i) GSH caused a decrease of both the overall covalent binding ratio of MC to Micrococcus luteus DNA and the extent of interstrand cross-linking of 32P-pBR322 DNA, as the concentration of GSH was increased in the reaction media. Approximately 50% inhibition of cross-linking was observed at 20 mM GSH. It is likely that the inhibition is caused by the formation of MC-GSH conjugates competing with DNA alkylation, since both processes are triggered by reductive activation of MC [Sharma, M., and Tomasz, M. (1994) Chem. Res. Toxicol. (preceding paper in this issue)]. (ii) GSH causes a switch from monofunctional to bifunctional activation of MC by the prototype "monofunctional" MC-activating agents H2/PtO2 and NADPH:cytochrome c reductase/NADPH. This was seen by the predominance of bisadducts (i.e., cross-linked adducts) instead of the usual monoadducts in the enzymatic digests of MC-DNA complexes formed in the presence of GSH, as analyzed by HPLC. This finding suggests that GSH participates in the bifunctional activation of MC in vivo. (iii) A ternary MC-GSH-DNA adduct (6) was formed in the presence of GSH both with M. luteus DNA and with a synthetic duplex oligonucleotide; in this adduct the mitosene C1 is linked to N2 of guanine and the mitosene C10 is linked to GSH via sulfur.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkylation↗

Ankle, knee, and hip moments during standing with and without joint contractures: simulation study for functional electrical stimulation.

Joint contractures have been one of the contraindications for use of functional electrical stimulation for standing in paraplegic patients. A simulation study using a three-segment link mechanical model of the human body was performed to calculate the muscle moments at the ankles, knees, and hips during standing with and without having joint contractures. The knee and hip angles were varied in 5 degrees increments, whereas the ankle angles were varied in 1 degree increments. It was assumed that energy efficient posture was obtained with the least sum of the squared moments of the ankles, knees, and hips joints by the muscles. Ankles at 5 degrees of dorsiflexion, knees at 0 degrees, and hips at 15 degrees of extension resulted in the most energy efficient posture without joint contractures. The muscle moments increased with the increase in angle of contractures. The joint contractures at ankle angles > or = 6 degrees of plantar flexion, knee angles > or = 20 degrees of flexion, and/or hip angles > or = 20 degrees of flexion produce a potentially unstable posture. These findings suggest that some degree of joint contractures can be tolerated in paraplegic patients using functional electrical stimulation for standing.

Algorithms↗

Severe tibial growth retardation in total fibular hemimelia after limb lengthening.

Seven patients with total fibular hemimelia who underwent limb-lengthening procedures prior to skeletal maturity were evaluated for tibial and femoral growth after lengthening. The average preoperative follow-up was 6.5 years and all patients were followed to skeletal maturity. Thirteen segments (eight tibiae and five femora) were lengthened by three methods (Wagner, Ilizarov, and modified Ilizarov). The average preoperative limb-length discrepancy was 9.7 cm, and the average projected limb-length discrepancy at skeletal maturity was 12.5 cm. The average tibial lengthening was 6.7 cm (range, 5.3-10) with an average percentage of lengthening of 26% (range, 19-40%). The average postoperative growth rate of the tibia was 80% (range, 70-100%) and of the femur, 83% (range, 70-90%) of the normal side. Five tibiae showed a decrease in the average preoperative growth rate from 82.5% (range, 70-100%) to 39% (range, 26-54%) of the normal side. Two tibiae had no longitudinal growth after lengthening. The average postoperative growth rate of the femur decreased from 83% (range, 70-90%) to 61% (range, 26-125%). In one patient there was an increase in the rate of growth of the femur. These findings suggest that limb lengthening in skeletally immature children with total fibular hemimelia results in severe growth retardation of the tibia after lengthening. The subsequent growth of the tibia after lengthening in patients with total fibular hemimelia is unpredictable.

Bone Lengthening↗

Controlled trial of rice powder and glucose rehydration solutions as oral therapy for acute dehydrating diarrhea in infants.

A controlled, randomized trial was conducted in 50 infants (3 to 18 months old) hospitalized with acute noncholera dehydrating diarrhea to compare the safety, efficacy, and acceptability of the standard World Health Organization (WHO) recommended glucose oral rehydration solution (ORS) (Group A: 25 infants) with that of a rice powder ORS (Group B: 25 infants), containing 30 g/L of rice powder instead of glucose (20 g/L). The electrolyte composition of both solutions was identical. The proportion of successfully treated patients in each group was 92%, and the two rehydrating solutions proved comparable in correcting and maintaining the hydration status and the serum sodium and potassium levels. The mean rehydration time, stool output, stool frequency, ORS intake, weight gain, and urine output were comparable (p greater than 0.05) in both groups. It is concluded that rice powder ORS is safe, effective, and acceptable as the standard WHO glucose ORS for the treatment of acute noncholera dehydrating diarrhea in infants.

Acidosis↗

Purification and characterization of angiotensin converting enzyme-II from bovine seminal plasma.

Angiotensin converting enzyme (EC 3.4.15.1) from bovine seminal plasma was shown to exist in two distinct forms. A lower molecular weight form of the enzyme having higher activity was purified to homogeneity. Final recovery of the enzyme was 18.37%. The apparent molecular weight of the enzyme was estimated to be 1.99 x 10(5) by gel filtration. A value of 1.8 x 10(5) was obtained for the reduced and denatured enzyme by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Stokes' radius, diffusion coefficient and intrinsic viscosity were determined to be 51.89 A degree, 4.2 x 10(-7) cm2/sec and 4.42 cc/g, respectively. Chloride ions were required for the enzyme activity. Studies with EDTA suggest that metal ions which are tightly bound, are required for its activity. Enzyme was inhibited by some heavy metal ions and required disulfide linkages at its active site. Trypsin treatment of the urea denatured enzyme produced a catalytically active Mr 32,000 daltons fragment.

Animals↗

Longitudinal (T1) and transverse (T2) relaxation times of tissue water protons in mouse developing sarcoma 180-A: effect of hyperthermia.

In vitro studies on Swiss mice, inoculated with dead or live sarcoma 180-A ascites cells, were carried out to monitor the changes, if any, in the longitudinal (T1) and transverse (T2) relaxation times of tissue water protons following hyperthermic treatment and subsequent thermotolerance. Both relaxation processes exhibited biexponential relaxation curves. With increasing size of the tumours, the longitudinal relaxation behaviour changed from bi- to mono-exponential. This was not observed for the transverse relaxation phenomenon. Inoculation with either dead or live cells caused an immediate increase in the both relaxation times. In the case of dead cell inoculation, the increase lasted for only 24 h after which the relaxation times became the same as for the uninoculated controls. The transverse relaxation time increased as a result of exposure to hyperthermia. During development of thermotolerance, both the relaxation times decreased.

Animals↗

Assessment of malnutrition in alcoholic and non alcoholic cirrhotics.

OBJECTIVE: To study the nutritional status in patients with chronic liver disease using anthropometric techniques. METHODS: A total of 60 cirrhotic patients (30 Alcoholic (AC), 30 Non-alcoholic (NAC) and 30 control (CO) subjects were studied. Nutritional status was assessed using anthropometric measurements such as stature, body weight, body mass index, (BMI), skinfold thickness measurements and mid upper arm muscle circumference. Serum protein, serum albumin and globulin were measured. RESULTS: The skinfold thicknesses were significantly lower in NAC group of patients. In contrast the AC group of patients showed significantly lower mid upper arm muscle circumference values. Both groups of cirrhotic patients showed significantly lower total serum protein and serum albumin levels. CONCLUSION: Body fat is relatively more affected in NAC group of patients and muscle mass is more affected in AC group of patients.

Adult↗

Prevalence of coronary artery disease in patients with symptomatic peripheral vascular disease.

BACKGROUND: Prevalence of coronary artery disease has been reported to be quite high in patients with peripheral vascular disease in western literature. Therefore, it is important to study the coronary anatomy in patients with symptomatic peripheral vascular disease. METHODS AND RESULTS: Fifty-three patients presenting with symptoms of peripheral vascular disease underwent peripheral angiography in our institute during the last 2 years. The total number of vessels involved in these patients was 117. Fifteen patients had involvement of the upper limb vessels, 46 patients had involvement of the lower limb vessels and 6 patients had involvement of the carotid/vertebral arteries. Coronary arteriography was done in all the patients. Only 8 (15%) patients were found to have coronary artery disease with involvement of 11 arteries. Eighty-four (72%) peripheral vessels out of the 117 vessels involved showed total occlusion, whereas only 2 (18%) coronary arteries out of 11 vessels involved showed total occlusion. CONCLUSIONS: This study shows that the majority of patients with symptomatic peripheral vascular disease have normal coronaries, the extent of their involvement being low despite severe peripheral vascular disease.

Adult↗

Percutaneous transseptal mitral commissurotomy in pregnant women with critical mitral stenosis.

BACKGROUND: Percutaneous transseptal mitral commissurotomy has been successfully performed in selected pregnant patients with severe symptomatic mitral stenosis. Its safety and efficacy needs to be evaluated in a large number of cases. METHODS AND RESULTS: Percutaneous transseptal mitral commissurotomy was performed in 85 severely symptomatic (New York Heart Association functional class III or IV) pregnant women aged 22.7+/-4.1 years (range 18-39 years) with critical mitral stenosis at 24.8+/-4.7 weeks (range 20-34 weeks) of gestation. Percutaneous valvotomy was performed using a flow-guided Inoue balloon in all the patients. The procedure was considered successful in 80 (94%) patients. The hemodynamic mean end-diastolic gradient decreased from 26.7+/-6.8 mm Hg (range 16-35 mmHg) to 4.5+/-3.8 mmHg (range 0-14 mmHg) (p<0.001). The mean diastolic gradient decreased from 29.1+/-9.1 mmHg (range 18-38 mmHg) to 7.2+/-4.1 mmHg (range 4.1-18 mmHg) (p<0.001). The mean mitral valve area assessed by echocardiography increased from 0.75+/-0.5 cm2 (range 0.4-1.0 cm2) to 2.0+/-0.5 (range 1.0-2.7 cm2) (p<0.001). The mean fluoroscopy time was 3.6+/-3.2 minutes. The results of the mitral valvotomy were considered suboptimal in 4 patients. Mitral regurgitation increased by 1 grade in 16 patients and more than 2 grades in 2 patients. One patient developed pericardial tamponade during the procedure and was managed by catheter drainage. Percutaneous mitral valve dilatation was then successfully performed in this patient. No fetal abortion occurred after the procedure. CONCLUSIONS: The results of this study indicate that percutaneous transseptal mitral commissurotomy is a safe and effective procedure for severe symptomatic mitral stenosis in pregnancy.

Adolescent↗

High-risk coronary angioplasty using percutaneous cardiopulmonary bypass support.

BACKGROUND: Balloon angioplasty has a high success rate but results in abrupt closure of the vessel in 2% to 6% of patients. This can lead to haemodynamic collapse and death, particularly if the patient has poor left ventricular function. In the event of abrupt closure of the coronary vessels, such patients may not survive long enough to undergo emergency bypass surgery. The prophylactic use of cardiopulmonary bypass to support patients at high-risk for angioplasty has been reported recently. We describe our initial experience with this technique. METHODS: Eighteen high-risk patients with severe angina were subjected to balloon angioplasty after instituting percutaneous cardiopulmonary bypass support to enhance the safety of high-risk elective coronary angioplasty. All patients had a low ejection fraction, a large amount of viable myocardium perfused by the targeted artery or both (left ventricular ejection fraction < 25% in 13 patients). Triple-vessel disease was present in all of them. Angioplasty of the only remaining vessel was done in 12 patients, 2 vessels in 5 patients and a sequential graft in 1 patient. Bypass flow ranged from 2.8 to 4.5 litres and was discontinued after a mean of 35 minutes. Haemostasis was achieved by external clamp compression in 16 patients. RESULTS: The angioplasty was successfully performed in all the patients and was well tolerated. During the bypass period, the pulmonary artery diastolic pressure ranged from 0 to 8 mmHg. There was no hospital death. Two patients required surgical exploration of the femoral artery puncture site--one because of poor distal perfusion and the other for continued bleeding. During the follow up period of 1 to 10 months, 11 patients were free of angina and 1 had died. CONCLUSION: Our experience confirms that percutaneous bypass support in selected patients undergoing high-risk coronary angioplasty is safe and effective.

Adult↗

Inhibition of human ovarian carcinoma cell- and hexosaminidase- mediated degradation of extracellular matrix by sugar analogs.

Human ovarian carcinoma (HOC) cell beta-N-acetylglucosaminidase (beta-NAG, EC 3.2.1.30) was found to be present in three isoenzymatic forms. All three forms were capable of degrading ECM. Therefore, inhibitors of beta-NAG were sought as potential anti-invasive agents. Two sugar analogs, 2-acetamido-2-deoxy-1,5-gluconolactone (CD80110) and 2-acetamido-1,5-imino-1,2,5-trideoxy-D-glucitol (CD 86022), were evaluated for their ability to inhibit 1) human ovarian carcinoma beta-NAG isoenzyme activities, 2) degradation of radiolabeled ECM mediated by HOC cells and beta-NAG, and 3) cell growth. Both compounds were found to be competitive inhibitors of beta-NAG isoenzyme activities, with Ki values similar for all isoenzymes (2-8 microM). CD 80110 and CD 86022 inhibited HOC cell-mediated degradation of [3H]glucosamine labeled ECM without notable effect on cell growth. Enzyme-mediated degradation of ECM was also inhibited by both sugar analogs. Analysis of degradation products after cell- or enzyme-mediated digestion of ECM revealed a decrease in the amount of both free aminosugars and high molecular material caused by inhibitors. These results support a role for beta-NAG in degradation of extracellular matrix components and suggest the usefulness of hexosaminidase inhibitors as potential antiinvasive agents.

1-Deoxynojirimycin↗

Robotically enhanced coronary artery bypass surgery.

BACKGROUND: Robotically enhanced telemanipulation surgery is a fast developing technique which allows totally endoscopic cardiac surgery with utmost precision and perfection on both beating heart as well as arrested heart. METHODS AND RESULTS: Between December 2002 and February 2004, 125 patients underwent robotically enhanced coronary artery bypass surgery using the da Vinci telemanipulation system (Intuitive Surgical Inc., California). Eleven patients underwent totally endoscopic coronary artery bypass surgery. Of them 9 were done on beating heart while 2 were done on arrested heart. One hundred and fourteen patients had endoscopic takedown of internal mammary artery followed by minimally invasive direct coronary artery bypass in 63 patients and left anterolateral thoracotomy in 51 patients. The internal mammary artery mobilization time was 42 min (35-74 min) while the left internal mammary artery to left anterior descending artery anastomosis time ranged from 20 to 36 min for the totally endoscopic coronary artery bypass patients. In 1 patient, the right internal mammary artery was anastomosed to diagonal artery totally endoscopically. The mean internal mammary artery flow by Doppler measurement done in patients undergoing minimally invasive direct coronary artery bypass was 64 ml/min. Seven patients required conversion to median sternotomy and coronary bypass surgery on beating heart. The mean intensive care unit stay was 1.2 days and the mean hospital stay 4.5 days. There was 1 in-hospital mortality. All 11 patients who underwent totally endoscopic bypass surgery had coronary angiography done at 3 months interval which showed 100% patency in 10 patients while one patient had 50% anastomotic narrowing for which coronary angioplasty was done in the same sitting. CONCLUSIONS: Using telematic technology, a complete endoscopic anastomosis is possible in both single vessel and suitable double vessel disease patients. The use of robotics is now extended to achieve complete myocardial revascularization by harvesting both the internal mammary arteries and making a small thoracotomy for direct anastomosis as well.

Adult↗

Hysterectomy: an analysis of perioperative and post operative complication.

OBJECTIVE: To document peri operative and post operative complication observed after hysterectomy, regardless of route on the operator. MATERIAL AND METHODS: A hospital based prospective study was carried out in department of obstetrics and gynaecology, KMCTH Sinamangal for six months. The study was carried out in patients undergoing hysterectomy who were followed from the time of admission to the time of discharge and two weeks thereafter. And followings were noted--Indication; route of hysterectomy, intraoperative and postoperative morbidities during hospital stay and after two weeks of discharge was noted. RESULT: Total number of hysterectomy carried out was 50. 31 (62%) were Total abdominal hysterectomy, and 19 (38%) were vaginal hysterectomy. Indication for total abdominal hysterectomy were fibroid uterus 12 (24%), DUB 8 (16%), CIN 4 (8%), chronic cervicitis 1 (2%). II U-V prolapse with previous LSCS 1 (2%), endometriosis 1 (2%). Prophylactic for Ca breast 1 (2%), Postmenopausal bleeding 1 (2%). All cases of vaginal hysterectomy were performed for 2nd degree U-V prolapse. Intra operative complication during surgery were two cases of haemorrhage (4%) each in both total abdominal hysterectomy and vaginal hysterectomy. There was one case of bladder injury during abdominal hysterectomy. Postoperative complication noted were febrile morbidity 1 (2%) in abdominal hysterectomy. Urinary tract infection remains the single most common febrile morbidity. There was one case of secondary haemorrhage in both type of hysterectomy. One was managed conservatively and other required laparotomy. There were three (6%) cases of wound infection in abdominal hysterectomy of two which were sanguineous discharge and one was frank pus which required secondary suture.

Adult↗

Screening of patients with acute febrile illness for leptospirosis using clinical criteria and serology.

BACKGROUND: Leptospirosis is one of the common zoonoses but, in most instances, the infection goes unnoticed. Rapid diagnostic modalities are needed to diagnose the disease in the early stages. We assessed the usefulness of clinical criteria and compared these with enzyme-linked immunosorbentassay (ELISA) for the early detection of leptospirosis. METHODS: One hundred patients with a febrile illness for > 7 days were screened by Faine criteria and their sera were subjected to both IgM and IgG ELISA using a commercially available kit (Institut Virion Serion GmbH, Warburg, Germany). RESULTS: Twenty-six patients satisfied the clinical criteria for leptospirosis and 8 of them tested positive for IgM antibodies while 1 patient who was clinically negative tested positive by serology. Thus, Faine criteria had a sensitivity of 88.9%, specificity of 80.2%, positive predictive value of 30.8% and a negative predictive value of 98.6%. Paired serum samples were obtained from 70 patients but the IgG levels of only 2 showed a 4-fold rise. CONCLUSION: Faine criteria has moderate sensitivity and specificity but a high negative predictive value in comparison with IgM ELISA. The high negative predictive value may help to screen patients with acute febrile illness for leptospirosis during the early phase of the disease.

Acute Disease↗