Biomedical subjects

S K Sharma

Publications and source records attributed to S K Sharma.

At least 253 records · Page 14Linked to original sources

PubMed1997

Etiologic factors in Peyronie's disease.

BACKGROUND: The etiology of Peyonie's disease remains a mystery. An attempt is made to resolve this. MATERIALS AND METHODS: A total of 25 patients with Peyronie's disease were examined and investigated for the presence of various implicated etiologic factors. RESULTS: Of the 25 patients examined, two presented with ischemic heart disease, 10 with hypertension, 10 with asymptomatic hyperuricemia, 18 with hypercholesterolemia, two with fibrosing disorders, two with autoimmune disorders, and three with diabetes mellitus. None had any sexually transmitted disease. Seven of the 10 hypertensive patients had received beta-blockers. On comparing the prevalence of these factors between patients and the general population, a significant association was found between hypertension, hypercholesterolemia, hyperuricemia, and Peyronie's disease. CONCLUSIONS: Known factors, such as hypertension and hypercholesterolemia, lead to weakening of the vasculature and its rupture during coitus. This leads to the formation of a hematoma and its subsequent organization in predisposed individuals to fibrous plaques. The identification and treatment of these factors might prevent, secondarily, the development of Peyronie's disease.

Adult↗

PubMed1997

Prevention of hypotension during spinal anesthesia: a comparison of intravascular administration of hetastarch versus lactated Ringer's solution.

This study was designed to compare the efficacy of 6% hetastarch to that of crystalloid administration in reducing the incidence and severity of hypotension during spinal anesthesia. Forty ASA grade I patients scheduled for postpartum tubal ligations under spinal anesthesia were randomly allocated to receive either 500 mL of hetastarch solution or 1000 mL of lactated Ringer's solution prior to spinal anesthesia. Spinal anesthesia was managed identically in both groups by anesthesiologists who were unaware of the type of fluid administered. The incidence of hypotension was 11 of 21 (52%) in the lactated Ringer's solution group and 3 of 19 (16%) in the hetastarch group. The difference in the incidence of hypotension was significant (P < 0.05). The requirement of 5-mg bolus doses of ephedrine to maintain systolic arterial blood pressure > 75% of baseline was significantly greater in the lactated Ringer's group than in the hetastarch group (15 vs 4, P < 0.05). We conclude that an intravenous infusion of 500 mL of 6% hetastarch solution is more effective than 1000 mL lactated Ringer's solution in attenuating spinal anesthesia induced hypotension in women undergoing postpartum tubal ligation.

Adult↗

PubMed1997

The effect of anesthetic techniques on blood coagulability in parturients as measured by thromboelastography.

Anesthetic techniques may affect blood coagulability and the subsequent incidence of thromboembolic events. The purpose of this study was to evaluate the effect of spinal and general anesthesia on blood coagulability in normal pregnant women undergoing cesarean section, using thromboelastography. In the spinal anesthesia group (n = 15), thromboelastography was performed after crystalloid preloading and during the immediate postanesthesia course. In the general anesthesia group (n = 15), thromboelastography was performed before induction and during the immediate postanesthesia course. Values for all thromboelastographic variables (reaction time [r], clot formation time [K], coagulation time [rK], maximum amplitude [MA], elastic shear modulus [G], clot formation rate [alpha angle], and coagulation index [CI]) in the preanesthesia period were similar in both the spinal and general anesthesia groups. However, in the postanesthesia period, r and K significantly decreased (P < 0.05), and alpha angle (P < 0.05) and CI significantly increased (P < 0.01) in the general anesthesia group when compared with the spinal anesthesia group. In the postanesthesia period, MA and G were similar in both groups. In the spinal anesthesia group, thromboelastographic variables did not change significantly in the postanesthesia compared with the preanesthesia period. We conclude that the use of general anesthesia for cesarean section is associated with accelerated coagulability when compared with spinal anesthesia.

Adult↗

PubMed1997

Thromboelastographic changes in healthy parturients and postpartum women.

Thromboelastography (TEG) using disposable plastic cups and pins was performed with native whole blood (native group) in 17 nonpregnant volunteers, 134 healthy term pregnant women (>36 wk gestation), and 69 postpartum women. Thromboelastography was also performed with celite-activated whole blood (celite group) in 15 nonpregnant female volunteers, 38 healthy term pregnant women, and 34 postpartum women. The thromboelastographic parameters r and K were significantly decreased in pregnant and postpartum women compared with nonpregnant women in both groups (P < 0.05). The maximum amplitude MA, elastic shear modulus, and alpha angles were significantly increased in pregnant and postpartum women compared with nonpregnant women in both groups (P < 0.05). The TEG coagulation index was significantly greater in pregnant and postpartum women compared with nonpregnant women in both groups. In this study, TEG showed that pregnancy is a hypercoagulable state and that postpartum women remain hypercoagulable through the first 24 h postdelivery. The use of celite in TEG accelerated the speed of TEG analysis.

Blood Coagulation↗

PubMed1997

Cesarean delivery: a randomized trial of epidural versus patient-controlled meperidine analgesia during labor.

BACKGROUND: Reports indicate that the administration of epidural analgesia for pain relief during labor interferes with labor and increases cesarean deliveries. However, only a few controlled trials have assessed the effect of epidural analgesia on the incidence of cesarean delivery. The authors' primary purpose in this randomized study was to evaluate the effects of epidural analgesia on the rate of cesarean deliveries by providing a suitable alternative: patient-controlled intravenous analgesia. METHODS: Seven hundred fifteen women of mixed parity in spontaneous labor at full term were randomly assigned to receive either epidural analgesia or patient-controlled intravenous meperidine analgesia. Epidural analgesia was maintained with a continuous epidural infusion of 0.125% bupivacaine with 2 microg/ml fentanyl. Patient-controlled analgesia was maintained with 10-15 mg meperidine given every 10 min as needed using a patient-controlled pump. Procedures recorded in a manual that prescribed the intrapartum management were followed for each woman randomized in the study. RESULTS: A total of 358 women were randomized to receive epidural analgesia, and 243 (68%) of these women complied with the epidural analgesia protocol. Similarly, 357 women were randomized to receive patient-controlled intravenous meperidine analgesia, and 259 (73%) of these women complied with the patient-controlled intravenous analgesia protocol. Only five women who were randomized and received patient-controlled intravenous meperidine analgesia according to the protocol crossed over to epidural analgesia due to inadequate pain relief. There was no difference in the rate of cesarean deliveries between the two analgesia groups using intention-to-treat analysis based on the original randomization (epidural analgesia, 4% [95% CI: 1.9-6.2%] compared with patient-controlled intravenous analgesia, 5% [95% CI: 2.6-7.2%]). Similar results were observed for the analysis of the protocol-compliant groups (epidural analgesia, 5% [95% CI: 2.6-8.5%] compared with patient-controlled intravenous analgesia, 6% [95% CI: 3-8.9%]). Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received patient-controlled intravenous analgesia. CONCLUSIONS: Epidural analgesia was not associated with increased numbers of cesarean delivery when compared with a suitable alternative method of analgesia.

Adult↗

PubMed1997

Entomological and rodent surveillance of suspected plague foci in agro-environmental and feral biotopes of a few districts in Maharashtra and Gujarat states of India.

Studies carried out on entomological and rodent surveillance in agroclimatic and feral biotopes of five districts of Maharashtra and two districts of Gujarat revealed that the terrain features of the seven districts surveyed were conducive to wild rodent species, Tatera indica, a natural reservoir of plague and vector flea species, Xenopsylla cheopis. A total of 214 Tatera indica and three Bandicoota bengalensis were collected from burrows by the digging method and 89 rat fleas were retrieved. The flea index calculated ranged from 0.26 to 1.0 in different districts. The examination of blood serum samples, contact tissue impression smears and tissue organs (heart, lung, liver and spleen) of these wild rodents did not reveal any evidence of plague activity. The natural harbourages of Tatera indica were found to be elevated land or raised margins of agricultural fields or barren land with thorny bushes/xerophytic plants and parthenium grass. Agricultural fields having wet soil were found to be the preferred harbourages of Bandicoota bengalensis. Movement of wild rodents toward human settlement was observed to be the common phenomenon during the harvesting season which may lead to the creation of favorable conditions for plague outbreaks.

Animals↗

PubMed1997

Entomological and rodent surveillance in plague-suspected areas during September 1994 and thereafter.

Studies carried out in the states of Maharashtra, Gujarat, Uttar Pradesh and Union Territory of Delhi after the bubonic plague outbreak during 1994 revealed the presence of seven species of rodents, viz. Rattus rattus, R. norvegicus, Mus. musculus, Tatera indica, Suncus murinus, Bandicoota bengalensis and B. indica. The flea species encountered were Xenopsylla cheopis and X. astia. The X. cheopis and X. astia index recorded in different areas of Beed district of Maharashtra; Surat, Vadodra and Baruch districts in Gujarat and Varanasi district in Uttar Pradesh and their implications have been discussed. Insecticide suspectibility tests carried out against DDT, dieldrin, malathion and deltamethrin with X. cheopis collected from Maharashtra, Delhi and Varanasi revealed that this vector species is resistant to DDT and dieldrin but susceptible to malathion and deltamethrin. The prevalence and distribution of rodents species, high cheopis index and prevalence of Tatera indica just at the door steps of houses in village Mamla of Beed district provides highly congenital conditions for the intermingling of wild and domestic rodents and transfer of flea population from wild to domestic rodents and vice-versa. These conditions were found to be highly supportive for bubonic plague transmission in the district. The presence of Yersinia pestis antibodies in Rattus rattus collected from Beed, Surat and Varanasi areas are also indicative of bubonic plague in Beed and Varanasi and pneumonic plague in Surat during 1994.

Animals↗

PubMed1997

Upper urinary tract stones & Ureaplasma urealyticum.

Extensive culture of stones and of pre-operative and renal pelvic urine for isolation of bacteria and Ureaplasma urealyticum were performed in 70 patients of nephrolithiasis. Stones were subjected to biochemical analysis and scanning electron microscopy. Micro-organisms were isolated from 33 (47%) of 70 renal stones. Of the 38 species of micro-organisms isolated, 14 were urea-splitting (U. urealyticum 2; Klebsiella pneumoniae 8; Morganella morganii 1; Acinetobacter spp 3) and 24 were nonurea splitting. U. urealyticum was cultured from the renal stones of two patients. Pelvic urine, unlike voided urine did reflect the bacteriology of the stone. Biochemically, 55 stones (79%) were calcium oxalate phosphate stones, 10 (14%) were calcium oxalate stones and 5 (7%) were uric acid stones. None of the stones were found to be of struvite composition. These data suggest that infection stones are uncommon in this part of the country. Further, infection of renal stones with fastidious organisms like U. urealyticum and multi-drug resistant bacteria necessitate their removal to ensure complete cure.

Adult↗

PubMed1997

Therapeutic value of bovine saliva in wound healing: a histomorphological study.

Biopsies were collected from the control (normal saline solution treated) and saliva treated wounds (back and loin region) of calves on 3rd, 7th, 14th, 21st and 28th days post-wounding. A faster connective tissue and epidermal regeneration was observed in saliva treated group. The inflammatory response was subdued as early as on 3rd day. On the 14th day the test wounds were covered with a dense layer of fibroblast and collagen and epidermal growth started. On 21st day the condensation of collagen and vascularization of the scar tissue was further augmented. By 28th day, the wounds were completely filled and nearly 85% of the wound surface was covered with epidermis.

Animals↗

PubMed1997

Bioenvironmental control of industrial malaria at Bharat Heavy Electricals Ltd., Hardwar, India--results of a nine-year study (1987-95).

A bioenvironmental model to control malaria at Bharat Heavy Electricals Ltd. in Hardwar was developed by using existing resources to reduce mosquito breeding. The civil maintenance department carried out major source reduction work by filling pits, low lying areas, ditches, etc., with fly ash from a coal-fired power station, construction of stand posts and proper drainage, mosquito proofing of overhead tanks, and preventive maintenance of the water supply and the sewage system. The project staff has applied 1) expanded polystyrene beads to underground tanks, leaking sluice valve chambers, and blocked sewage manholes; 2) biolarvicides to water accumulated in factory scraps, blocked drains, and riverbed pools, and 3) larvivorous fish to storm water drains, effluent ponds, and drains for the effective control of mosquito breeding. Improved surveillance and treatment coupled with comprehensive developmental schemes were additional tools to gain community support. As a result of intervention measures, the vector density in the township was significantly lowered compared to that of a control area, and there was a drastic reduction in malaria incidence compared to that of the preintervention year: only 190 cases were recorded in 1995, compared to 3,049 cases in 1985. The study has shown that malaria control in an industrial township through an integrated control approach is practical, sustainable, and economically feasible and reduces insecticide pollution in the environment.

Animals↗

PubMed1996

Macrophages, smooth muscle cells, and tissue factor in unstable angina. Implications for cell-mediated thrombogenicity in acute coronary syndromes.

BACKGROUND: Macrophage expression of tissue factor may be responsible for coronary thrombogenicity in patients with plaque rupture. In patients without plaque rupture, smooth muscle cells may be the thrombogenic substrate. This study was designed to identify the cellular correlations of tissue factor in patients with unstable angina. METHODS AND RESULTS: Tissue from 50 coronary specimens (1560 pieces) from patients with unstable angina and 15 specimens from patients with stable angina were analyzed. Total and segmental areas (in square millimeters) were identified with trichrome staining. Macrophages, smooth muscle cells, and tissue factor were identified by immunostaining. Tissue factor content was larger in unstable angina (42 +/- 3%) than in stable angina (18 +/- 4%) (P = .0001). Macrophage content was also larger in unstable angina (16 +/- 2%) than in stable angina (5 +/- 2%) (P = .002). The percentage of tissue factor located in cellular areas was larger in coronary samples from patients with unstable angina (67 +/- 8%) than in samples from patients with stable angina (40 +/- 5%) (P = .00007). Multiple linear stepwise regression analysis showed that coronary tissue factor content correlated significantly (r = .83, P < .0001) with macrophage and smooth muscle cell areas only in tissue from patients with unstable angina, with a strong relationship between tissue factor content and macrophages in the atheromatous gruel (r = .98, P < .0001). CONCLUSIONS: Tissue factor content is increased in unstable angina and correlates with areas of macrophages and smooth muscle cells, suggesting a cell-mediated thrombogenicity in patients with acute coronary syndromes.

Adult↗

PubMed1996

Identification of active tissue factor in human coronary atheroma.

BACKGROUND: Recent observations suggest that thrombosis in vivo is initiated via the tissue factor (TF) pathway. The TF activity of human coronary atheroma has not been reported. METHODS AND RESULTS: Directional coronary atherectomy (DCA) specimens from 63 lesions were analyzed with the use of a quantitative TF-specific activity assay. The median content of TF was 10 ng/g plaque (95% CI, 6 to 13 ng/g; range, 0 to 47 ng/g). After homogenization of the specimens, TF activity was detected in 28 of 31 lesions (90%). With a polyclonal anti-human TF antibody, the use of immunohistochemistry detected TF antigen in 43 of 50 lesions (86%); TF antigen was expressed in cellular and acellular areas of the plaque. Histologically defined thrombus was present in 19 of the 43 lesions with detectable TF antigen and in none of the 7 lesions without detectable TF antigen (19 of 43 versus 0 of 7; P < .02). TF antigen was undetectable with immunohistochemistry in 4 of 13 restenotic lesions (31%) and in 3 of 37 de novo lesions (8%) (P < .05). CONCLUSIONS: TF contributes to the procoagulant activity of most atherosclerotic lesions treated with DCA. The association of immunohistochemically detectable TF with plaque thrombus suggests that TF plays a role in coronary thrombosis. Diminished TF expression in restenotic lesions may in part account for the lower complication rate that has been associated with DCA of restenotic versus de novo lesions. Inhibition of TF may represent a therapeutic goal for the prevention of thrombotic complications associated with percutaneous coronary interventions.

Antigens↗

PubMed1996

Targeting delavirdine/atevirdine resistant HIV-1: identification of (alkylamino)piperidine-containing bis(heteroaryl)piperazines as broad spectrum HIV-1 reverse transcriptase inhibitors.

A novel class of bis(heteroaryl)piperazine (BHAP) analogs which possesses the ability to inhibit NNRTI (non-nucleoside reverse transcriptase inhibitor) resistant recombinant HIV-1 reverse transcriptase (RT) and NNRTI resistant variants of HIV-1 has been identified via targeted screening. Further investigation of the structure-activity relationships of close congeners of these novel (alkylamino)piperidine BHAPs (AAP-BHAPs) led to the synthesis of several compounds possessing the desired phenotype (e.g., activity against recombinant RTs carrying the Y181C and P236L substitutions). Further structural modifications were required to inhibit metabolism and modulate solubility in order to obtain compounds with the desired biological profile as well as appropriate pharmaceutical properties. The AAP-BHAPs with the most suitable characteristics were compounds 7, 15, and 36.

Animals↗

PubMed1996

A drug resistance mutation in the inhibitor binding pocket of human immunodeficiency virus type 1 reverse transcriptase impairs DNA synthesis and RNA degradation.

Selection of the IIIB strain of human immunodeficiency virus type (HIV-1) resistant to the (alkylamino)piperidine-bis(heteroaryl)piperazine (AAP-BHAP) U-104489 results in substitution of a glycine to glutamate at residue 190 (G190E) of reverse transcriptase (RT). The AAP-BHAP resistant HIV-1 displays reduced in vitro replication capacity [Olmsted, R. A., et. al. (1966) J. Virol. 70, 3698-3705]. We report here that the G190E mutation in recombinant heterodimeric HIV-1 RT, compared to the wild-type RT (G190) or a G190A control mutant, results in a 40% and 80% reduction in the polymerase and RNase H specific enzymatic activities, respectively. A primer-extension assay that allowed determination of DNA elongation by the G190E mutant RT on a heteropolymeric HIV-1 gag-based RNA template showed an overall decrease in DNA polymerization. The size distribution of products generated by G190E RT-associated RNase H digestion of RNA from [35S]poly(rA).poly(dT) was markedly distinct from that of the G190A RT and was consistent with the observed reduction in RT-associated RNase H activity of the G190E RT. When challenged with unlabeled substrates, the G190E RT was relatively nonprocessive with respect to DNA synthesis and RNA degradation. It is concluded that the deleterious effect of the G190E resistance mutation on both of these RT functions is most likely involved in the observed retarded replication capacity of the AAP-BHAP-(U-104489-) resistant HIV-1.

Base Sequence↗

PubMed1996

ZD2767, an improved system for antibody-directed enzyme prodrug therapy that results in tumor regressions in colorectal tumor xenografts.

ZD2767 represents an improved version of antibody-directed enzyme prodrug therapy. It consists of a conjugate of the F(ab')2 A5B7 antibody fragment and carboxypeptidase G2 (CPG2) and a prodrug, 4-[N,N-bis(2-iodoethyl)amino]phenoxycarbonyl L-glutamic acid. The IC50 of the prodrug against LoVo colorectal tumor cells was 47 microM, and cleavage by CPG2 released the potent bis-iodo phenol mustard drug (IC50 = 0.34 microM). The drug killed both proliferating and quiescent LoVo cells. Administration of the ZD2767 conjugate to nude mice bearing LoVo colorectal xenografts resulted in approximately 1% of injected ZD2767 conjugate localizing/g of tumor after 72 h, and blood and normal tissue levels of the conjugate were 10-50-fold lower. A single round of therapy involving the administration of the prodrug 72 h after the conjugate to athymic mice bearing established LoVo xenografts resulted in approximately 50% of the tumors undergoing complete regressions, tumor growth delays greater than 30 days, and little toxicity (as judged by body-weight loss). Similar studies using a control antibody-CPG2 conjugate that does not bind to LoVo tumor cells resulted in a growth delay of less than 5 days, confirming the tumor specificity of this approach. These studies demonstrate the potential of ZD2767 for the treatment of colorectal cancer.

Animals↗

PubMed1996

Characterization of the p68/p58 heterodimer of human immunodeficiency virus type 2 reverse transcriptase.

Recently we demonstrated that the p58 subunit of p68/p58 HIV-2 reverse transcriptase (RT) heterodimer, produced by processing of p68/p68 homodimer with recombinant HIV-2 protease, terminates at Met484 [Fan, N., et al. (1995) J. Biol. Chem. 270, 13573-13579]. Here we describe purification and characterization of the p68/p58 heterodimer of recombinant HIV-2 RT. It exhibited both RT and RNase H activities, obeyed Michaelis-Menten kinetics, and was competitively inhibited by the DNA chain terminator ddTTP (Ki[app] = 305 +/- 20 nM). The HIV-2 RT-associated RNase H exhibited a marked preference for RNA hydrolysis from a HIV-1 gag-based heteropolymeric RNA/DNA hybrid in the presence of either Mg2+ or Mn2+, compared to the [3H]poly(rA).poly(dT) or [3H]poly(rG).poly(dC) homopolymeric substrates. Relative to HIV-1 RT, the RNase H activity of HIV-2 RT was only 5% toward the [3H]poly(rA).poly(dT) in the presence of Mg2+. The size distribution of products generated from [3H]poly(rA).poly(dT) by HIV-2 RT-associated RNase H was markedly distinct from that of HIV-1 RT in the presence of Mg2+ or Mn2+. The p68/p58 HIV-2 RT heterodimer, produced by specific cleavage using HIV-2 protease, should be useful for inhibition and biophysical studies aimed at discovering and designing drugs directed toward HIV-2.

Aspartic Acid Endopeptidases↗

PubMed1996

Synthesis and antitumour activity of new derivatives of flavone-8-acetic acid (FAA). Part 1: 6-Methyl derivatives.

A range of 17 derivatives of flavone-8-acetic acid (FAA) with a 6-methyl substituent have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. While many of the compounds show activity comparable to FAA in vitro, this essentially disappears in vivo, possibly due to degradation before the compounds can reach the tumour site.

Animals↗

PubMed1996

Use of a pneumatic compression system (FemoStop) as a treatment option for femoral artery pseudoaneurysms after percutaneous cardiac procedures.

Pseudoaneurysm (PA) formation is a well-documented complication of femoral arterial puncture in patients undergoing percutaneous cardiac procedures. Besides surgical repair, there has been success in obliterating the PAs by Duplex ultrasound guided compression (mostly those < 4.0 cm). We analyzed the use of prolonged femoral compression using a pneumatic compression system (FemoStop by USCI) in 10 patients who developed femoral PAs following an interventional cardiac procedure. All PAs were diagnosed by ultrasound and had unsuccessful duplex-guided compression. The size of the PA ranged from 2.8-4.0 cm in diameter. All patients had the FemoStop system placed over the PA with continuous pressure for 12-18 hr. PA obliteration was successful in 90% of cases as confirmed by ultrasound. The only complication observed was skin abrasion in two patients. Our results indicate that the FemoStop system is a simple and effective technique for treatment of femoral artery PAs.

Aged↗