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Biomedical subjects

S Sharma

Publications and source records attributed to S Sharma.

At least 271 records · Page 15Linked to original sources
PubMed2001

Topical tacrolimus (FK506) leads to profound phenotypic and functional alterations of epidermal antigen-presenting dendritic cells in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease in which antigen-presenting epidermal dendritic cells (DCs), ie, Langerhans cells and the so-called inflammatory dendritic epidermal cells (IDECs) expressing the high-affinity receptor for IgE (FcepsilonRI) may play a significant pathophysiologic role. Therapeutic efficacy of the immunosuppressive macrolide tacrolimus (FK506) in AD has been demonstrated in clinical trials, but little is known of its mode of action. OBJECTIVE: The present study focused on the effects of topical tacrolimus treatment on epidermal CD1a+/FcepsilonRI+ DC populations in lesional AD. METHODS: Immunohistological analysis, epidermal DC phenotyping, and functional studies were performed on skin biopsy specimens from treated and untreated lesional skin of 10 patients with AD participating in a clinical trial with tacrolimus. RESULTS: Untreated lesional skin was characterized by a high proportion of CD1a+ cells, which was largely due to a high proportion of IDECs strongly expressing FcepsilonRI. Epidermal DCs isolated from untreated lesional skin exhibited high stimulatory activity toward autologous T cells, which was strongly reduced while clinical improvement was seen during application of tacrolimus. Concomitantly, a decreased FcepsilonRI expression was observed in both Langerhans cells and IDECs. Finally, topical tacrolimus led to a progressive decrease in the IDEC population within the pool of CD1a+ epidermal DCs and also to a decrease in their CD36 expression, which is indicative of lower local inflammation. CONCLUSION: Epidermal CD1a+ DCs may represent a target for topical tacrolimus in the treatment of AD.

Administration, Topical↗
PubMed2001

Economic assessment of rheolytic thrombectomy versus intracoronary urokinase for treatment of extensive intracoronary thrombus: Results from a randomized clinical trial.

BACKGROUND: Despite advances in mechanical and pharmacologic therapy, thrombus-containing lesions are at high risk for adverse events and remain a challenging subset for percutaneous coronary revascularization. Recently, rheolytic thrombectomy with the AngioJet device has been shown to safely remove intracoronary thrombus, but the overall cost-effectiveness of this technique is unknown. METHODS: We determined in-hospital and 1-year follow-up costs for 349 patients with overt intracoronary thrombus who were randomly assigned to treatment with intracoronary urokinase (6- to 30-hour infusion followed by definitive revascularization; n = 169) or immediate thrombectomy with the AngioJet device (n = 180) as part of the Vein Graft AngioJet Study (VeGAS) 2 trial. Catheterization laboratory costs were based on measured resource utilization and 1998 unit costs, whereas all other costs were estimated from hospital charges and cost center-specific cost-to-charge ratios. RESULTS: Compared with urokinase, rheolytic thrombectomy reduced the incidence of periprocedural myocardial infarction (12.8% vs 30.3%, P <.001) and major hemorrhagic complications (2.8% vs 11.2%, P <.001) and shortened length of stay by nearly 1 day (4.2 vs 4.9 days; P =.02). As a result, AngioJet treatment reduced procedural costs, hospital room/nursing costs, and ancillary costs with resulting hospital cost savings of approximately $3500 per patient during the initial hospitalization ($15,311 vs $18,841, P <.001). These cost savings were maintained at 1 year of follow-up ($24,389 vs $29,109, P <.001). CONCLUSIONS: Compared with standard treatment with intracoronary urokinase, rheolytic thrombectomy both improves clinical outcomes and reduces overall medical care costs for patients with extensive intracoronary thrombus.

Angioplasty, Balloon, Coronary↗
PubMed2001

Habitual diet in four populations of African origin: a descriptive paper on nutrient intakes in rural and urban Cameroon, Jamaica and Caribbean migrants in Britain.

BACKGROUND: The prevalence of chronic diseases is increasing in West Africa, the Caribbean and its migrants to Britain. This trend may be due to the transition in the habitual diet, with increasing (saturated) fat and decreasing fruit and vegetable intakes, both within and between countries. OBJECTIVE: We have tested this hypothesis by comparing habitual diet in four African-origin populations with a similar genetic background at different stages in this transition. DESIGN: The study populations included subjects from rural Cameroon urban Cameroon Jamaica and African-Caribbeans in Manchester, UK all aged 25-74 years. Habitual diet was assessed by a food-frequency questionnaire, specifically developed for each country separately. RESULTS: Total energy intake was greatest in rural Cameroon and lowest in Manchester for all age/sex groups. A tendency towards the same pattern was seen for carbohydrates, protein and total fat intake. Saturated and polyunsaturated fat intake and alcohol intake were highest in rural Cameroon, and lowest in Jamaica, with the intakes in the UK lower than those in urban Cameroon. The percentage of energy from total fat was higher in rural and urban Cameroon than in Jamaica and the UK for all age/sex groups. The opposite was seen for percentage of energy from carbohydrate intake, the intake being highest in Jamaica and lowest in rural Cameroon. The percentage of energy from protein increased gradually from rural Cameroon to the UK. CONCLUSIONS: These results do not support our hypothesis that carbohydrate intake increased, while (saturated) fat intake decreased, from rural Cameroon to the UK.

Adult↗
PubMed2001

Sera from lupus patients inhibit growth of P. falciparum in culture.

A large number of malaria immune persons from Eastern India were found to possess antibodies to the ribosomal phosphoprotein P0 (PfP0) of the human malarial parasite Plasmodium falciparum. The characterization of PfP0 has been reported recently, and it has been shown that antibodies against PfP0 inhibit P. falciparum in vitro. About 10-15% of the patients suffering from the autoimmune disorder Systemic Lupus Erythematosus (SLE) possess autoantibodies to the human ribosomal P proteins. In order to test the cross-reactivity of the human and Plasmodium falciparum P0 proteins and to compare the SLE patients' and malaria immune persons' response, sera from 41 Indian SLE patients were tested against the P. falciparum PfP0 by Western blot analysis. Four of these samples (9.75%) were found to be cross-reactive to the carboxy-terminal domain of PfP0, but not to the amino-terminal domain of PfP0. The PfP0 reactive SLE sera inhibited the growth of Plasmodiumfalciparum in vitro. IgG purified from one such cross-reactive serum sample inhibited the growth of P. falciparum. Depletion of anti-P0 antibodies from this IgG preparation resulted in the removal of growth inhibition. Sera samples were collected from one of the PfP0 positive SLE patient from Mumbai, India, at different stages of the disease progression, and screened for the presence of anti-PfP0 antibodies. This patient's serum inhibited the parasite growth in vitro only during the phase in which anti-PfP0 antibodies were detected.

Amino Acid Sequence↗
PubMed2001

p38-mediated regulation of an Fas-associated death domain protein-independent pathway leading to caspase-8 activation during TGFbeta-induced apoptosis in human Burkitt lymphoma B cells BL41.

On binding to its receptor, transforming growth factor beta (TGFbeta) induces apoptosis in a variety of cells, including human B lymphocytes. We have previously reported that TGFbeta-mediated apoptosis is caspase-dependent and associated with activation of caspase-3. We show here that caspase-8 inhibitors strongly decrease TGFbeta-mediated apoptosis in BL41 Burkitt's lymphoma cells. These inhibitors act upstream of the mitochondria because they inhibited the loss of mitochondrial membrane potential observed in TGFbeta-treated cells. TGFbeta induced caspase-8 activation in these cells as shown by the cleavage of specific substrates, including Bid, and the appearance of cleaved fragments of caspase-8. Our data show that TGFbeta induces an apoptotic pathway involving sequential caspase-8 activation, loss of mitochondrial membrane potential, and caspase-9 and -3 activation. Caspase-8 activation was Fas-associated death domain protein (FADD)-independent because cells expressing a dominant negative mutant of FADD were still sensitive to TGFbeta-induced caspase-8 activation and apoptosis. This FADD-independent pathway of caspase-8 activation is regulated by p38. Indeed, TGFbeta-induced activation of p38 and two different inhibitors specific for this mitogen-activated protein kinase pathway (SB203580 and PD169316) prevented TGFbeta-mediated caspase-8 activation as well as the loss of mitochondrial membrane potential and apoptosis. Overall, our data show that p38 activation by TGFbeta induced an apoptotic pathway via FADD-independent activation of caspase-8.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Enhancement of enzyme activity through three-phase partitioning: crystal structure of a modified serine proteinase at 1.5 A resolution.

Three-phase partitioning is fast developing as a novel bioseparation strategy with a wide range of applications including enzyme stability and enhancement of its catalytic activity. Despite all this, the enzyme behaviour in this process still remains unknown. A serine proteinase, proteinase K, was subjected to three-phase partitioning (TPP). A 3 ml volume of proteinase K solution (3 mg/ml in 0.05 M acetate buffer, pH 6.0) was brought to 30% (w/v) ammonium sulphate saturation by addition of saturated ammonium sulphate. tert-Butanol (6 ml) was added to this solution and the mixture was incubated at 25 degrees C for 1 h. The precipitated protein in the mid-layer was dissolved in 3 ml of 0.05 M acetate buffer, pH 6.0. The specific activity of the processed enzyme was estimated and was found to be 210% of the original enzyme activity. In order to understand the basis of this remarkable enhancement of the enzyme activity, the structure of the TPP-treated enzyme was determined by X-ray diffraction at 1.5 A resolution. The overall structure of the TPP-treated enzyme is similar to the original structure in an aqueous environment. The hydrogen bonding system of the catalytic triad is intact. However, the water structure in the substrate binding site has undergone a rearrangement as some of the water molecules are either displaced or completely absent. Two acetate ions were identified in the structure. One is located in the active site and seems to mimic the role of water in the enzyme activity and stability. The other is located at the surface of the molecule and is involved in stabilizing the local structure of the enzyme. The most striking observation in respect of the present structure pertains to a relatively higher overall temperature factor (B = 19.7 A(2)) than the value of 9.3 A(2) in the original enzyme. As a result of a higher B-factor, a number of residues, particularly their side chains, were found to adopt more than one conformation. It appears that the protein exists in an excited state which might be helping the enzyme to function more rapidly than the original enzyme in aqueous media. Summarily, the basis of increased enzymatic activity could be attributed to (i) the presence of an acetate ion at the active site and (ii) its excited state as reflected by an overall higher B-factor.

Crystallography, X-Ray↗
PubMed2001

Tc-99m tetrofosmin uptake in male breast cancer.

Breast carcinoma occurs rarely in men. Its imaging by mammography is difficult because male breast tissue is normally small in volume and adequate compression is not possible, which is a prerequisite for performing mammography. The authors describe a 65-year-old man with a right breast mass in whom the result of fine-needle aspiration cytology was inconclusive. A mammogram was also noncontributory because adequate compression was not possible as the mass was tender. Tc-99m tetrofosmin scintimammography showed intense focal uptake in the right breast. Excision biopsy confirmed the diagnosis of breast carcinoma.

Aged↗
PubMed2001

Ectopic goiter masquerading as submandibular gland swelling: a case report and review of the literature.

Ectopic thyroid glands generally occur in the midline as a result of abnormal median migration, and their presence lateral to the midline is rare. A 12-year-old boy had a swelling in the left submandibular region that imaging techniques showed to be an ectopic thyroid gland, although no thyroid tissue was seen in the normal location. Only eight cases of lateral aberrant thyroid tissue have been reported. The importance of being aware of the possibility of ectopic thyroid tissue as a submandibular region swelling has an important bearing on disease management. A pertinent review of the literature and its management is included.

Child↗
PubMed2001

Treatment and outcome of nocardia keratitis.

OBJECTIVE: To report our experience in treatment and outcome ofNocardia keratitis. METHODS: Medical and microbiology records of seven cases of culture-provenNocardia keratitis seen between January 1997 and March 1999 were reviewed retrospectively. In all patients, corneal scrapings were obtained for direct microscopic evaluation and culture. Drug sensitivity was determined by the Kirby-Bauer disk-diffusion method. The minimum inhibitory concentration of ciprofloxacin and amikacin for these isolates was determined by agar dilution method. Response to medical therapy and the end result were analyzed. RESULTS: By the in vitro Kirby-Bauer disk-diffusion techniques, all isolates were sensitive to amikacin; six of these isolates were sensitive to gentamicin and four were sensitive to ciprofloxacin. The minimum inhibitory concentration (MIC) of amikacin for all isolates by the agar-dilution technique was well below the MIC breakpoint forNocardia resistance, whereas the MIC of ciprofloxacin was above the MIC breakpoint forNocardia resistance. All patients responded to medical therapy. The corneal infection resolved in three patients after treatment with ciprofloxacin, in one patient after fortified gentamicin, and in three patients after fortified amikacin. Outcome details were available for six patients. There was good visual recovery in four patients, with visual acuity of 20/25 or better in three. The cornea of two patients developed nonvascularized scars, and in four patients in whom the infiltrates were peripheral, vascularization was seen. CONCLUSIONS: Although patients ofNocardia keratitis may respond to other antibiotics, amikacin appears to be a drug of choice. In this small series, when appropriate therapy was initiated,Nocardia keratitis resolved promptly with good visual recovery.

Amikacin↗
PubMed2001

Detection of coronary artery disease by stress thallium scintigraphy in diabetic patients.

We investigated the efficacy of exercise stress thallium in the diagnosis of coronary artery disease in patients with diabetes mellitus. Forty-three patients with known diabetes and suspected of having coronary artery disease were included in the study. All the patients underwent coronary angiography, 24 had significant coronary artery stenosis and 19 had normal coronaries. Out of the 24 patients with a positive angiographic finding, thallium scintigraphy was positive in 21 patients (sensitivity, 87.5%); and false negative in only three of the 24 patients. Out of the 19 patients with normal angiography findings, 16 patients had a normal thallium scan (specificity, 84.2%) and the remaining three had a positive thallium scan. This gives thallium scintigraphy a positive predictive value of 87.5% and negative predictive value of 84.2% when compared with coronary angiography. The findings of this study suggest that stress thallium scintigraphy is a useful modality in screening of coronary artery disease in diabetic patients.

Aged↗
PubMed2001

Postoperative morphine requirements of free TRAM and DIEP flaps.

In a review of the charts of 158 patients who had undergone breast reconstruction with free transverse rectus abdominis musculocutaneous (TRAM) or deep inferior epigastric perforator (DIEP) flaps and who were treated for postoperative pain with morphine administered by a patient-controlled analgesia pump, the total dose of morphine administered during hospitalization for the flap transfer was measured. Patients whose treatment was supplemented by other intravenous narcotics were excluded from the study. The mean amount of morphine per kilogram required by patients who had reconstruction with DIEP flaps (0.74 mg/kg, n = 26) was found to be significantly less than the amount required by patients who had reconstruction with TRAM flaps (1.65 mg/kg; n = 132; p < 0.001). DIEP flap patients also remained in the hospital less time (mean, 4.73 days) than did free TRAM flap patients (mean, 5.21 days; p = 0.026), but the difference was less than one full hospital day. It was concluded that the use of the DIEP flap does reduce the patient requirement for postoperative pain medication and therefore presumably reduces postoperative pain. It may also slightly shorten hospital stay.

Analgesia, Patient-Controlled↗
PubMed2001

Incidence of hematoma associated with ketorolac after TRAM flap breast reconstruction.

Ketorolac is frequently used as an adjunct for postoperative pain relief, especially by anesthesiologists during the immediate postoperative period. It can be used alone as an analgesic but is more often used to potentiate the actions of narcotics such as morphine or meperidine in an attempt to reduce the total dose and side effects of those drugs. The manufacturer of ketorolac cautions against its use in patients who have a high risk of postoperative bleeding, for fear of increasing the risk of hematoma, but the risk in transverse rectus abdominis musculocutaneous (TRAM) flap patients has never been reported. In a study of 215 patients who had undergone TRAM flap breast reconstruction, it was determined that patients who received intravenous ketorolac (n = 65) as an adjunct to their treatment with morphine administered by use of a patient-controlled analgesia device required less morphine (mean cumulative dose, 1.39 mg/kg) than did patients who did not receive ketorolac (n = 150; mean cumulative dose, 1.75 mg/kg; p = 0.02). There was no increase in the incidence of hematoma in patients who were treated with ketorolac. The data presented in this study suggest that the use of intravenous ketorolac does reduce the need for narcotics administration in patients undergoing TRAM flap breast reconstruction, without significantly increasing the risk of hematoma.

Adult↗
PubMed2001

The cost-effectiveness of early vitrectomy for the treatment of vitreous hemorrhage in diabetic retinopathy.

Diabetic vitrectomy has been found to be efficacious for the treatment of vitreous hemorrhage secondary to diabetic retinopathy. The purpose of this study is to determine the cost-effectiveness of early vitrectomy for the management of vitreous hemorrhage secondary to diabetic retinopathy. The analysis was performed from the perspective of a third-party insurer. A cost-utility Markov model was used to determine the cost per quality-adjusted life year (QALY) gained from early versus deferral of vitrectomy. The model used 2-, 3-, and 4-year results from the Diabetic Retinopathy Vitrectomy Study, patient-based utilities, life expectancy data, and incremental medical costs. Early vitrectomy was the dominant strategy and was associated with a gain of 0.41 QALYs over the 57-year expected life span for a hypothetical patient. The cost per additional QALY gained from early vitrectomy treatment was $1910 (US$ discounted at 3%). When sensitivity analyses were performed by varying efficacy probabilities and utilities across their 95% confidence intervals, early treatment was always the dominant strategy. Additionally, even at the extreme sensitivity values, the cost per QALY of early vitrectomy treatment remained under $10,000. Overall, early vitrectomy for the treatment of vitreous hemorrhage secondary to diabetic retinopathy is highly cost-effective.

Adult↗
PubMed2001

Structural studies on the cobra venom factor: isolation, purification, crystallization and preliminary crystallographic analysis.

Cobra venom factor (CVF) is the complement-activating protein in cobra venom. It is a three-chain glycoprotein with a molecular weight of 149,000 Da. In serum, CVF forms a bimolecular enzyme with the Bb subunit of factor B. The enzyme cleaves C3 and C5, causing complement consumption in human and mammalian serum. CVF is frequently used to decomplement serum to investigate the biological functions of complement and serves as a tool to investigate the multifunctionality of C3. Furthermore, CVF bears the potential for clinical application to deplete complement in situations where complement activation is involved in the pathogenesis of disease. CVF was isolated from Indian cobra (Naja naja naja) venom. The protein was crystallized at room temperature using the sitting-drop vapour-diffusion technique. The crystals diffract to 2.7 A resolution and belong to the tetragonal space group P4(1), with unit-cell parameters a = b = 62.7, c = 368.1 A.

Animals↗
PubMed2001

Importance of accurate geometry in the study of the total cavopulmonary connection: computational simulations and in vitro experiments.

Previous in vitro studies have shown that total cavopulmonary connection (TCPC) models incorporating offset between the vena cavae are energetically more efficient than those without offsets. In this study, the impact of reducing simplifying assumptions, thereby producing more physiologic models, was investigated by computational fluid dynamics (CFD) and particle flow visualization experiments. Two models were constructed based on angiography measurements. The first model retained planar arrangement of all vessels involved in the TCPC but incorporated physiologic vessel diameters. The second model consisted of constant-diameter vessels with non-planar vascular features. CFD and in vitro experiments were used to study flow patterns and energy losses within each model. Energy losses were determined using three methods: theoretical control volume, simplified control volume, and velocity gradient based dissipation. Results were compared to a simplified model control. Energy loss in the model with physiologically more accurate vessel diameters was 150% greater than the simplified model. The model with nonplanar features produced an asymmetric flow field with energy losses approximately 10% higher than simplified model losses. With the velocity gradient based dissipation technique, the map of energy dissipation was plotted revealing that most of the energy was dissipated near the pulmonary artery walls.

Algorithms↗
PubMed2001

Therapeutic potential of human neutrophil peptide 1 against experimental tuberculosis.

The therapeutic efficacy of human neutrophil peptide 1 (HNP-1) against experimental tuberculosis in mice on the basis of numbers of CFU has been examined. Mice infected with 1.5 x 10(4) CFU of Mycobacterium tuberculosis H(37)Rv and treated with different doses of HNP-1 injected subcutaneously exhibited significant clearance of bacilli from lungs, livers, and spleens. There were time- and dose-dependent decreases in the bacillary load in lungs, livers, and spleens of the HNP-1-treated animals compared to that in controls (untreated animals). These observations strongly suggest the therapeutic activity of HNP-1 against tuberculosis.

Animals↗