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Biomedical subjects

A Rahman

Publications and source records attributed to A Rahman.

At least 91 records · Page 5Linked to original sources

Constructing a consensus-based prevention outcome measurement instrument.

This article describes Ohio's Prevention Evaluation Project (PEP). The purpose of the project was to develop a process and instrument to assess behavioral and attitudinal outcomes in primary drug abuse prevention programs targeting young people aged twelve to seventeen. One of PEP's principal achievements was the inclusion of community prevention program providers from throughout the state in the evaluation instrument development. The effort produced a self-administered questionnaire to capture data on young peoples' drug use practices, attitudes toward drugs, and problematic behaviors. Most significantly, the product produced was the acceptance and endorsement of community-based programs. The forty-one-item questionnaire has good to excellent reliability for virtually all measures, as assessed by the test-retest method. The instrument is a product of a process that brought together a university-based research team, state alcohol and drug abuse prevention administrators, and representatives of public programs. PEP demonstrates how to productively link service providers, administrators, and evaluators to develop a process for assessing the effectiveness of prevention programs. The process and tools described serve as a model for other communities wanting to evaluate their prevention programming.

Adolescent↗

Differential effects of doxorubicin on atrial natriuretic peptide expression in vivo and in vitro.

Doxorubicin (Dox) is a potent anti-cancer agent with cardiotoxic side-effects but the mechanism of its cardiotoxicity and its effect on expression of the vasoactive atrial natriuretic peptide (ANP), an important marker for cardiac hypertrophy, are little understood. The present study examined Dox-induced changes in vivo in hearts of 6 mongrel dogs and 5 Sprague-Dawley rats and in vitro in cardiac cultures of neonatal rats. Quantitative RT-PCR analysis using gamma 32-p labeled primers for beta-actin, phospholamban (PLB) and ANP showed a selective 5-fold increase of ANP mRNA in Dox-treated dog hearts in comparison to controls. Similarly, northern analysis of GAPD, beta-actin, cardiac alpha-actin and ANP gave a selective 4.5-fold increase in ANP transcripts in Dox-treated rat hearts. On the other hand, there was a selective decrease (approximately 39%) of ANP transcripts in Dox-treated cardiac cultures relative to controls. Immunohistochemistry localized the ANP changes both in tissue sections and in cultures to the cardiomyocytes. The data clearly showed that Dox selectively increases ANP expression in dog and rat hearts in absence of cardiocyte hypertrophy but selectively decreases it in cardiac cultures. This differential effect of Dox on cardiocytes in vivo and in vitro should be a useful parameter for studies of transcriptional control of ANP expression.

Animals↗

Workshop 7 (synthesis): towards a recycling society: systems approach to small-scale reuse of human waste.

Population increase and growing quantities of human excreta create serious problems and high risks for people's health. Alternative solutions are becoming crucial to improve urban living conditions, and to shorten water and nutrient flows into circulation of used water and nutrient in human excreta. The speakers presented a wide range of experiences of "closing the loops" and thereby turning potential waste into productive use. The focus of the workshop deliberations was on simplifying the hygienisation of urine and faeces and the reuse in food production by using urine-diverting toilets, as well as innovative ways to recycle sewage after various stages of treatment.

Conservation of Natural Resources↗

Liposomal-encapsulated chemotherapy: preliminary results of a phase I study of a novel liposomal paclitaxel.

Liposome encapsulation of antineoplastic drugs entered clinical testing in the late 1980s. As carriers for a variety of agents, liposomes can allow successful delivery of agents that may be subject to rapid degradation in the serum and can modify the toxicity profile. In general, liposomes have demonstrated an ability to attenuate toxicities by their different pharmacokinetic profile and pattern of distribution. Differences in the constitution of the liposome can greatly affect the pharmacokinetic profile resulting in different patterns of toxicity. Characteristics such as size, charge, composition, and integrity can affect performance of the liposome. Liposome encapsulation of doxorubicin has been shown to reduce cardiac toxicity. Preliminary data suggest that encapsulation of paclitaxel can greatly modify neurotoxicity without the need for cremephor.

Breast Neoplasms↗

Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia.

PURPOSE: Gemtuzumab ozogamicin (Mylotarg; Wyeth Laboratories, Philadelphia, PA) consists of a semisynthetic derivative of calicheamicin, a cytotoxic antibiotic linked to a recombinant monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML). In this study, we review the preclinical and clinical profiles of this immunoconjugate and the regulatory review that led to marketing approval by the United States Food and Drug Administration. EXPERIMENTAL DESIGN: From the literature and manufacturer's data, we review the activity, tolerability, and pharmacokinetics of gemtuzumab ozogamicin in preclinical and Phase I studies and its activity, efficacy, and side effects in three Phase 2 trials of 142 patients with relapsed AML. RESULTS: In Phase I studies, the major toxicity was myelosuppression, especially neutropenia and thrombocytopenia, resulting from the expression of CD33 on myeloid progenitor cells. The Phase 2 dose was 9 mg/m(2) infused i.v. over 4 h, repeated on day 14. A minority of patients experienced acute infusion-related symptoms, usually transient and occasionally requiring hospitalization. The complete response (CR) rate with full recovery of hematopoiesis was 16%. A subset of patients [CRs with incomplete platelet recovery (CRps)] was identified with blast clearance and neutrophil recovery but incomplete platelet recovery. The duration of responses of CRps appeared to be similar to those of the CRs, although the numbers were small. The question of the equivalence of these response groups was a central issue in the review of this new drug application (NDA). After considerable discussion, the Oncology Drugs Advisory Committee recommended allowing inclusion of CRps resulting in an overall response rate in the Phase 2 studies of 30%. In the subgroup of patients over 60 years of age, the overall response rate was 26%. Response duration was difficult to establish because of the high prevalence of postremission therapies. Tolerability and ease of administration may be improved compared with conventional chemotherapy, except for hepatotoxicity, with 31% of patients exhibiting abnormal liver enzymes. One patient died of liver failure in the Phase 2 trials. CONCLUSIONS: Marketing approval of gemtuzumab ozogamicin was granted on May 17, 2000 by the United States Food and Drug Administration under the Accelerated Approval regulations. Gemtuzumab ozogamicin is indicated for the treatment of patients with CD33 positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy. The approved dose was 9 mg/m(2) i.v. over 4 h and repeated in 14 days. Completion of the ongoing studies of gemtuzumab ozogamicin in relapsed AML and initiation of randomized clinical trials comparing the effects of gemtuzumab ozogamicin in combination with conventional induction chemotherapy to conventional chemotherapy alone on survival are mandated to confirm clinical benefit under the accelerated approval Subpart H regulations. Postmarketing reports of fatal anaphylaxis, adult respiratory distress syndrome (ARDS), and hepatotoxicity, especially venoocclusive disease (VOD) in patients treated with gemtuzumab ozogamicin, with and without associated hematopoietic stem cell transplantation (HSCT), have required labeling revisions and the initiation of a registration surveillance program. Tumor lysis and ARDS have been reported in patients with leukocytes above 30,000/ml treated with gemtuzumab ozogamicin; therefore, the reduction of leukocyte counts to below 30,000/ml is recommended prior to treatment. Patients should be carefully monitored for acute hypersensitivity, hypoxia, and delayed hepatotoxicity following treatment with gemtuzumab ozogamicin.

Adolescent↗

Efficacy of a packaged rice oral rehydration solution among children with cholera and cholera-like illness.

UNLABELLED: In past studies, patients with cholera and cholera-like diarrhoea treated with rice oral rehydration solution (ORS) had lower purging rates and a shorter illness duration. We evaluated a new packet form of rice ORS (CeraLyte-90) in 167 boys aged 5 to 15 y, with acute, dehydrating cholera and cholera-like diarrhoea in Bangladesh. The patients were randomized to receive either CeraLyte-90 (n = 85) or glucose ORS (n = 82) and were given early feeding and early antibiotics. The efficacy of the two solutions was compared for stool output during the first 8 h, the first 24 h, and total output, duration of diarrhoea, hematocrit, serum electrolytes and requirement for unscheduled intravenous fluids. The clinical and laboratory characteristics of the two groups were comparable on admission, and most of the patients had cholera (88% and 84% in the CeraLyte and glucose groups, respectively). The mean (+/- SE) stool output was 20% less in the rice ORS group during the first 8 h of treatment (86.2+/-6.6 ml/Kg vs 108.8+/-7.9 ml/Kg, p < 0.05), but the outputs during the other time periods were similar in the two groups, although children in the rice ORS group had slightly more vomiting on day one (p < 0.05). The mean serum electrolyte concentrations in both groups of children remained within normal range. CONCLUSION: The study documents the safety and efficacy of the new, packaged rice ORS.

Adolescent↗

The efficacy of bismuth subsalicylate in the treatment of acute diarrhoea and the prevention of persistent diarrhoea.

UNLABELLED: A controlled, randomized, double-blind study in Bangladeshi children (ages 4-36 mo) with acute diarrhoea was undertaken to determine whether bismuth subsalicylate (BSS) would prevent the development of persistent diarrhoea (PD) in young children. The children were randomized to two groups: 226 were given liquid oral BSS, (as Pepto-Bismol), 100 mg/kg/d for 5 d; 225 were given placebo of identical appearance. On admission to the study, the two groups were comparable both clinically and microbiologically. Rotavirus was found in 56% of all the children, and enterotoxigenic E. coli in 31% of a subsample studied. Children treated with BSS had less severe and less prolonged illness than those treated with placebo (p = 0.057). There was, however, no difference in the development of PD between the two groups (8% and 11%). Unexpectedly, patients treated with BSS gained significantly more weight (2.3%) than those treated with placebo (0.5%; p < 0.001) during the course of the study. No toxicity of BSS was detected. CONCLUSION: Treatment with BSS had a modest therapeutic effect on acute diarrhoea, as has been previously demonstrated, but with no suggestion of a therapeutic effect on the prevention of persistent diarrhoea in this group of patients.

Acute Disease↗

Continuous quality assessment; development of a simple computer based model for audit.

OBJECTIVE: Accurate assessment of quality of care is a fundamental first step in the process of quality improvement. The vast amount of data generated in a hospital mandates some form of computerization for management of information. We describe a locally developed simple computer based program to access relevant information from a hospital patient management network. The objective was to reduce the amount of manual work involved for busy clinicians attempting to audit quality of care. METHODS: A single surgical procedure, Laparoscopic Cholecystectomy was chosen. Quality indicators were identified by literature review as conversion rate from laparoscopic to open cholecystectomy and length of hospital stay (LOS). A simple query was developed to extract the required information from hospital database. Commercially available spreadsheet software (Microsoft Excel) was used to calculate the rates. Outliers were defined as LOS more than 1 standard deviation from the mean. The second part of the study involved a manual review of case notes to validate the program and determine the causes for deviation from the mean. RESULTS: The program was able to access and process data as planned. In a one-year period from March 1997 to February 1998, two hundred and thirty one laparoscopic cholecystectomies were attempted. Twenty-three were converted to open procedures given a conversion rate of 9.96%. On manual review of case notes no false positives or false negatives were found. The reasons for conversion were similar to those described in the literature. The mean length of stay for laparoscopic cholecystectomy was 3.39 days and 7.17 days for converted cases. The commonest reason for delay in discharge was noted to be non-availability of elective operating time. CONCLUSION: We have successfully developed and used a simple computer based program to access information stored in hospital patient management systems. Quality of care indicators identified from literature were used as standards. Outliers with respect to these were reviewed in detail to identify causes for deviation. The program was validated by manual review.

Computer Simulation↗

Necrosectomy followed by closed cavity lavage for necrotising pancreatitis--report of three cases.

Necrotizing Pancreatitis is a life threatening condition involving pancreas, peripancreatic and retroperitoneal tissues. It's serious regional and systemic involvement causes multiple organ or system failure. Planned and carefully performed necresectomy followed by closed cavity lavage can significantly reduce the mortality and morbidity of this catastrophic condition. Meticulous preoperative resuscitation, preparation and operative necrosectomy followed by continuos irrigation in the postoperative period were done in three consecutive patients. The operative procedure including postoperative management and follow up is reported and analyzed.

Adult↗

Molecular cloning and expression of the Fabs of human autoantibodies in Escherichia coli. Determination of the heavy or light chain contribution to the anti-DNA/-cardiolipin activity of the Fab.

The Fabs of three human autoantibodies (B3/33H11, anti-DNA; UK4, anti-phospholipid) and six related hybrids have been cloned, expressed in Escherichia coli, and purified to homogeneity. SDS-polyacrylamide gel electrophoresis and Western blot analysis of the recombinant Fab demonstrated the purified Fab to be of correct size and in assembled form. Protein expression levels of up to 5-9 mg per liter of culture were achievable. A sensitive and reliable comparative anti-DNA enzyme-linked immunosorbent assay, involving a defined biotinylated 35-mer oligonucleotide in its single- or double-stranded form, is also described. Crithidia assay and anti-DNA or anti-cardiolipin antibody enzyme-linked immunosorbent assay analyses demonstrated convincing binding of the recombinant Fab proteins to DNA/cardiolipin, confirming the expression of functional molecule. The comparative DNA/cardiolipin binding analyses of the nine Fabs revealed that the anti-DNA (light, B3/33H11) or anti-cardiolipin (heavy, UK4) activity lies predominantly on one of the two chains. However, a compatible partner chain is necessary for optimum antigen binding activity of the antibody.

Animals↗

beta(2)-Integrin blockade driven by E-selectin promoter prevents neutrophil sequestration and lung injury in mice.

Interaction of CD11/CD18 beta(2) integrins on polymorphonuclear leukocytes (PMNs) with their counterreceptor, intercellular adhesion molecule-1, on the surface of vascular endothelial cells is a critical event mediating stable PMN adhesion and migration across the pulmonary vascular endothelial barrier. Neutrophil inhibitory factor (NIF), a 41-kDa glycoprotein isolated from the canine hookworm (Ancylostoma caninum), binds to the I domain of CD11a and CD11b and inhibits beta(2) integrin-dependent PMN adhesion. We describe a novel strategy using the endothelial cell-specific E-selectin promoter to induce NIF expression in an inflammation-specific manner in pulmonary vascular endothelial cells. A construct containing NIF cDNA driven by the inducible endothelial cell-specific E-selectin promoter (pESNIF) was transfected into human pulmonary artery endothelial cells (HPAECs). Lipopolysaccharide challenge (known to activate E-selectin) resulted in NIF mRNA and protein expression in transfected HPAECs. NIF expression induced by the E-selectin promoter prevented PMN adhesion to the activated HPAECs, whereas PMNs adhered avidly to activated HPAECs in the absence of NIF expression. To address the utility of this approach in conditionally preventing in vivo PMN sequestration, we injected mice intravenously with cationic liposomes containing the pESNIF construct. Analysis of lung tissue showed that intraperitoneal challenge of Escherichia coli resulted in NIF expression. Inflammation-specific NIF expression induced by the E-selectin promoter prevented lung PMN sequestration and vascular injury induced by E coli challenge. These studies suggest the feasibility of conditionally blocking beta(2) integrin function at sites where the endothelium is activated and thereby of locally preventing PMN activation and migration responses that lead to tissue inflammation.

Animals↗

Evaluation of the efficacy of Lawsonia alba in the alleviation of carbon tetrachloride-induced oxidative stress.

The hepatoprotective activity of the 50% ethanol extract of the bark of Lawsonia alba syn. L. inermis was investigated against the carbon tetrachloride-induced oxidative stress. Pretreatment of rats with doses of 250 and 500 mg/kg of the plant extract significantly (P < 0.001) lowered serum transaminases (GOT and GPT) and LDH levels, respectively, in a dose dependent manner against the significant (P < 0.001) rise of these damage marker enzymes when challenged with CCl4 (1 ml/kg, orally). Parallel to these changes, the plant extract prevented CCl4-induced oxidative stress by significantly maintaining the levels of reduced glutathione (GSH), its metabolizing enzymes and simultaneously inhibiting the production of free radicals. Pretreatment of rats with the extract also inhibited the peroxidation of microsomal lipids in a dose-dependent manner.

Animals↗

Early and long-term results of heart transplantation after previous cardiac surgery.

OBJECTIVES: The aim of this study was to evaluate the preoperative management and long-term survival of patients undergoing heart transplantation as a redo-operation and compare the results with those obtained in patients undergoing transplantation as their first cardiac surgical procedure. METHODS: Between 1990 and 1997, 49 heart transplantation procedures were performed in patients who had undergone previous cardiac surgery (group A). This subgroup of patients was compared to 109 control patients who underwent cardiac transplantation as the primary cardiac procedure (group B). Patient groups were analysed regarding their preoperative, intra-operative, and postoperative variables in addition to survival. RESULTS: Pre-operative events were comparable in both groups but the duration of the operation was longer for group A (311+/-68 min) compared to group B (202+/-34 min); P=0.02. Post-operative exploration for bleeding was 6/49 patients in group A compared to 2/107 patients in group B (P=0.02). Post-operative blood loss and intensive care stay were greater for group A (1302+/-360 ml and 6.1+/-3.1 days, respectively) compared to group B (763+/-126 ml and 4.1+/-1.9 days, respectively); P=0.02. There was no difference in hospital mortality (group A 12.5%, group B 13 % P=0.9) and the 5-year survival rates were 68 and 71% for group A and B, respectively (P=0.9). CONCLUSIONS: Heart transplantation after previous open cardiac surgery is entirely justified in terms of outcome and graft function even in time of profound organ scarcity. Long-term events in these recipients are similar to patients in whom transplantation is the primary procedure.

Adult↗

Does aprotinin reduce lung reperfusion damage after cardiopulmonary bypass?

OBJECTIVE: The role of aprotinin in the prevention of lung reperfusion injury was investigated in the patients undergoing cardio-pulmonary bypass (CPB) for coronary artery bypass grafting (CABG) operations. METHODS: The study was planned randomly and prospectively. Two hundred milliliters of physiological saline solution was added to the prime solution of patients in group I (n=10) whereas, 200 ml aprotinin (Trasylol, Bayer AG) was given to patients in group II (n=10). In order to measure lung tissue malondialdehyde (MDA) levels, glutathion peroxidase (GSH-Px) activity levels and polymorphonuclear leukocytes (PMNs) numbers, lung tissue samples were taken before CPB and 5 min after removing the cross clamp. In addition, alveolo-arterial oxygen difference (AaDO(2)) for tissue oxygenation was calculated by obtaining arterial blood gas samples. RESULTS: MDA levels before CPB increased from 41.72+/-21.00 nmol/g tissue to 66.71+/-13.44 nmol/g tissue in group I and from 43.44+/-5.16 nmol MDA/g tissue to 53.22+/-10.95 nmol MDA/g tissue in group II after cross clamp removal (P=0.001 and P=0.021, respectively). The increase in group II was found to be significantly lower than group I (P=0.048). With the initiation of reperfusion, GSH-Px activity decreased in group I from 3.05+/-0.97 to 2.31+/-0.46 U/mg protein (P=0.015) whereas GSH-Px activity in group II decreased from 3.18+/-1.01 to 2.74+/-0.81 U/mg protein (P=0. 055). This decrease in the group II was less than group I (P=0.049). AaDO(2) significantly increased in the group I and II (P=0.012 and P=0.020, respectively), but elevation in the group I was significant than in the Group II (P=0.049). In histopathological examination, it was observed that neutrophil counts in the lung parenchyma rose significantly following removal of cross clamp in both groups (P=0. 001). The increase in group I was significantly larger than in group II (P=0.050). CONCLUSION: Results represented in our study indicate that addition of aprotinin (2 million units) into the prime solution during CPB can reduce lung reperfusion injury.

Aged↗

Triterpenoid saponins from Bongardia chrysogonum.

Two new triterpenoid saponins, 3-O-[beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->4)-alph a-L-arabinopyranosyl]-hederagenin (1) and 3-O-[beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->4)-alph a-L-arabinopyranosyl]-hederagenin 28-O-[beta-L-glucopyranosyl-(1-->6)-beta-L-glucopyranosyl] ester (2), together with five known saponins, were isolated from an ethanolic extract of the tubers of Bongardia chrysogonum. The structures of 1 and 2 were determined on the basis of spectroscopic studies.

Chromatography, High Pressure Liquid↗