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Biomedical subjects

M Shah

Publications and source records attributed to M Shah.

At least 145 records · Page 8Linked to original sources
PubMed1994

Comparison of a low-fat, ad libitum complex-carbohydrate diet with a low-energy diet in moderately obese women.

This study compared the effect of a low-fat, ad libitum, complex-carbohydrate (LFAL) diet with a low-energy (LE) diet on weight loss over 6 mo in moderately obese women. Weight loss was 4.4 kg in the LFAL (n = 47) and 3.8 kg in the LE (n = 42) participants. The difference was not statistically significant. The LFAL participants decreased percent energy from fat by 13%, increased percent energy from carbohydrate by 11.4%, and reduced energy intake by 1654 kJ. The corresponding values in the LE group were 3.8%, 3.5%, and 1991 kJ, respectively. Changes in fat and carbohydrate energy were significantly different by treatment (P < 0.0001). Palatability, satiety, and quality of life (QOL) improved in the LFAL group but diminished in the LE group. Palatability and QOL changes were significantly different by treatment (P < 0.029 and P < 0.048, respectively). It is concluded that an LFAL diet can result in substantial weight loss and is associated with improved palatability and QOL compared with an LE diet.

Adult↗
PubMed1994

Sudden death in recipients of first-generation implantable cardioverter defibrillators: analysis of terminal events. Participating investigators.

Clinical factors and terminal events associated with sudden death in 51 patients were analyzed from among a multicenter experience of 864 recipients of first generation automatic implantable cardioverter defibrillator (AICD) devices (single zone, committed, monophasic pulse with > or = 1 epicardial patch electrode) during the period May 1982-February 1988. For these 51 patients, mean age was 58 years and atherosclerotic heart disease was present in 84%, with a history of ventricular fibrillation (VF) in 61%, and inducible sustained ventricular tachycardia (VT) in 84%; mean left ventricular ejection fraction was 0.26. Nearly 80% experienced one or more appropriate AICD shocks during the median 9 month (range 0-46 months) period prior to death. Of 30 monitored deaths, the first documented terminal rhythm was VF in 12 (40%), VT in 8 (27%), and asystole or electromechanical dissociation in the remaining 10 (33%). Shocks were documented during terminal events in 21 (66%) of 32 witnessed cases of sudden death with activated devices. The proportion of monitored or witnessed sudden deaths that were known or presumed to be tachyarrhythmic (based on terminal VT, VF, or shocks) ranged from 69% (11/16 cases with activated/nondepleted devices and a defibrillation threshold [DFT] < or = 20 J) to 81% (29/36 cases on intention-to-treat basis). Of 27 patients with known or presumed sudden tachyarrhythmic death, the AICD had been deactivated prior to death in 4 (15%); activated, but depleted in 4 (15%); activated/nondepleted, but with DFT of 25 J in 4 (15%); and activated/nondepleted, but without DFT testing in 4 (15%). The remaining 11 (41%) known or presumed sudden tachyarrhythmic deaths occurred in patients with activated/nondepleted devices and DFT < or = 20 J; however, definite or suspected contributory factors (e.g., hematoma under epicardial patch, generator component failure, or drug-induced DFT rise) could be identified in 6 (55%) of 11 cases. Thus, in this first-generation AICD experience: 1) most sudden deaths occurred on the basis of a known or presumed tachyarrhythmia; and 2) an understanding of apparent "failure" of ICD therapy could often be gained through an integrated analysis of associated clinical factors and management practices, as well as device "hardware" function. These observations are likely to remain relevant, even with respect to newer generation ICDs.

Aged↗
PubMed1994

Premedication with oral and transdermal clonidine provides safe and efficacious postoperative sympatholysis.

We studied 61 patients undergoing elective major non-cardiac surgery in a randomized, double-blind, placebo-control clinical trial to test the hypothesis that the addition of clonidine to a standardized general anesthetic could safely provide postoperative sympatholysis for patients with known or suspected coronary artery disease. Patients were allocated randomly to receive either placebo (n = 31) or clonidine (n = 30). The treatment group received premedication with a transdermal clonidine system (0.2 mg/d) the night prior to surgery, which was left in place for 72 h, and 0.3 mg oral clonidine 60-90 min before surgery. Clonidine reduced enflurane requirements, intraoperative tachycardia, and myocardial ischemia (1/28 clonidine patients vs 5/24 placebo, P = 0.05). However, clonidine decreased heart rates only during the first five postoperative hours; the incidence of postoperative myocardial ischemia (6/28 clonidine vs 5/26 placebo) did not differ between the two groups. Patients who experienced postoperative myocardial ischemia tended to have higher heart rates after surgery. Clonidine significantly reduced the plasma levels of epinephrine (P = 0.009) and norepinephrine (P = 0.026) measured on the first postoperative morning. There were no differences in the need for intravenous fluid therapy or antihypertensive therapy after surgery. The number of hours spent in an intensive care setting and the number of days spent in hospital were not different between the two groups. These results suggest that larger doses of clonidine should be investigated for their ability to decrease postoperative tachycardia and myocardial ischemia.

Administration, Cutaneous↗
PubMed1994

Neutralising antibody to TGF-beta 1,2 reduces cutaneous scarring in adult rodents.

Scarring is a major cause of many clinical problems. Scar tissue interferes with growth, impairs function and is aesthetically unpleasant. However, scarring does not appear to be a problem of embryonic life. Embryonic wounds heal with a lower inflammatory and angiogenic response and have a different growth factor profile compared to adult wounds. We have used neutralising antibody to transforming growth factor-beta 1,2 (TGF-beta 1,2) to alter the growth factor profile of cutaneous wounds in adult rodents and studied the effect on scar tissue formation. This paper extends our preliminary report that neutralising antibody to TGF-beta reduces cutaneous scarring in adult rodents. To be effective, the neutralising antibody to TGF-beta needs to be administered at the time of wounding or soon thereafter. The antiscarring effects of this neutralising antibody to TGF-beta were dose dependent. Exogenous addition of neutralising antibody to TGF-beta to incisional wounds reduced the inflammatory and angiogenic responses and reduced the extracellular matrix deposition in the early stages of wound healing without reducing the tensile strength of the wounds. Importantly, the architecture of the neodermis of wounds treated with neutralising antibody to TGF-beta resembled more closely that of normal dermis compared to the unmanipulated control wounds, which healed with an abnormal neodermal architecture resulting in obvious scarring. This study suggests a novel therapeutic approach to reducing scarring in post-natal life.

Animals↗
PubMed1994

Infusional cyclophosphamide, doxorubicin and etoposide in HIV-related non-Hodgkin's lymphoma: a follow-up report of a highly active regimen.

Based on our prior data suggesting a therapeutic advantage for infusional administration of cyclophosphamide (C), doxorubicin (D), and etoposide (E) in patients with relapsed and resistant non-Hodgkin's lymphoma (NHL), we administered C (750 mg/m2), D (50 mg/m2), and E (240 mg/m2) via continuous intravenous infusion over 96 hours as first line therapy for 21 patients with intermediate- or high-grade non-Hodgkin's lymphoma associated with human immunodeficiency virus (HIV) infection. Treatment was repeated every 28 or more days. The median CD4 count of the study group was 87/ul, and the median serum lactate dehydrogenase was 383 IU/L. Extranodal disease, lymphomatous marrow involvement, and lymphomatous meningitis were present at diagnosis in 90%, 33%, and 10% of patients, respectively. Complete response (CR) occurred in 13 patients (62%, 95% confidence intervals 41%, 81%) and partial response occurred in five patients (24%). The estimated median survival of the study group was 18.0 months. Hematologic toxicity required dose reduction for 47% of cycles and for 79% of patients who received at least two cycles. The mean dose intensity for C, D, and E were 73%, 70%, and 73% of the intended dose intensity, respectively. Opportunistic infection included oral/esophageal candidiasis (N = 7), herpes labialis (N = 3), pulmonary Mycobacterium avium-intracellulare (N = 1), candidemia (N = 1), pneumonitis (N = 1), and disseminated aspergillosis than resulted in a single treatment-related death (5%). Treatment resulted in a significant decrease in the CD4+ lymphocytes, as well as total lymphocytes, T lymphocytes, and CD8+ lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

An improved system for exon recognition and gene modeling in human DNA sequences.

A new version of the GRAIL system (Uberbacher and Mural, 1991; Mural et al., 1992; Uberbacher et al., 1993), called GRAIL II, has recently been developed (Xu et al., 1994). GRAIL II is a hybrid AI system that supports a number of DNA sequence analysis tools including protein-coding region recognition, PolyA site and transcription promoter recognition, gene model construction, translation to protein, and DNA/protein database searching capabilities. This paper presents the core of GRAIL II, the coding exon recognition and gene model construction algorithms. The exon recognition algorithm recognizes coding exons by combining coding feature analysis and edge signal (acceptor/donor/translation-start sites) detection. Unlike the original GRAIL system (Uberbacher and Mural, 1991; Mural et al., 1992), this algorithm uses variable-length windows tailored to each potential exon candidate, making its performance almost exon length-independent. In this algorithm, the recognition process is divided into four steps. Initially a large number of possible coding exon candidates are generated. Then a rule-based prescreening algorithm eliminates the majority of the improbable candidates. As the kernel of the recognition algorithm, three neural networks are trained to evaluate the remaining candidates. The outputs of the neural networks are then divided into clusters of candidates, corresponding to presumed exons. The algorithm makes its final prediction by picking the best canadidate from each cluster. The gene construction algorithm (Xu, Mural and Uberbacher, 1994) uses a dynamic programming approach to build gene models by using as input the clusters predicted by the exon recognition algorithm. Extensive testing has been done on these two algorithms.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1994

Recognizing exons in genomic sequence using GRAIL II.

We have described an improved neural network system for recognizing protein coding regions (exons) in human genomic DNA sequences. This coding region recognition system is part of a new version of GRAIL, GRAIL II, and represents a significant improvement over the coding recognition performance of the previous GRAIL system. GRAIL II divides the process of locating exons into four steps. It first generates an exon candidate pool consisting of all possible (translation start-donor), (acceptor-donor), and (acceptor-translation stop) pairs within all open reading frames of the test sequence. The vast majority of these exon candidates are eliminated from consideration by applying a set of heuristic rules. After reducing the size of the candidate pool, GRAIL II uses three trained neural networks to evaluate the coding potential and accuracy of the edges of starting exon, internal exon and terminal exon candidates. These networks output a set of overlapping candidates for each exon which differ by their scores and position of their edges. Multiple candidates for a given exon are grouped into a cluster based on their locations relative to candidates corresponding to other exons, and the highest scoring candidate for each cluster is used as the "best" prediction of the corresponding exon. Unlike the previous GRAIL version, GRAIL II uses variable-length windows to evaluate exon candidates and its performance is nearly independent of exon length. In addition to several strong indicators of coding potential, the system uses several other types of information including scores for splice junctions, GC composition, and the properties of the regions adjacent to an exon candidate, to aid in the discrimination process. On a large set of sequences from Genbank (3), GRAIL II located 93% of all exons regardless of size with a false positive rate of 12%. Among the true positives, 62% match the actual exons exactly (the exons edges are correct to the base), and 93% match at least one edge correctly. These statistics are further improved, especially the false positive rate and accuracy of the edges, through a process of gene model construction by the Gene Assembly Program (GAP III) (4) module of GRAIL II, which uses the scored exon candidates as input and constructs optimal gene models. The gene modeling system will be described elsewhere.

Amino Acid Sequence↗
PubMed1993

F reticulocyte response in sickle cell anemia treated with recombinant human erythropoietin: a double-blind study.

Studies on baboons and preliminary observations in three patients with sickle cell anemia (SS) suggested that high doses of pulse administered recombinant human erythropoietin (rHuEPO) stimulate F-reticulocyte production. We now report on the administration of rHuEPO in a double-blind format to ascertain frequency of response and potential precipitation of side effects. Ten patients were enrolled, but one was discontinued due to the indication of a blood transfusion. Of the other nine, five received rHuEPO in escalating doses (from 400 to 1,500 U per kg twice daily [BID] per week), alternating with a placebo, in blinded fashion. The second group, consisting of four patients, followed an identical protocol (except starting dose was 1,000 U/Kg, BID per week) and were iron supplemented during treatment. The criterion of response was a transient doubling (as a minimum) of the steady-state F-reticulocyte level. We found that none of the five patients in the first group responded to rHuEPO, and two of them became iron deficient, as judged by a significant decrease in ferritin. Of the second group, four patients responded with F-reticulocyte increases. In three patients, open label administration of rHuEPO confirmed the effect. We observed seven painful episodes during this study, two during the EPO administration and five during the placebo arm. Three patients were phlebotomized because the hemoglobin level increased 1.5 g/dL more than steady-state levels. Of the six patients followed-up by percent dense cell determinations, one exhibited increased levels during periods of the treatment, whereas the other five showed no change. No anti-rHuEPO antibodies were detected. We conclude that rHuEPO can stimulate F-reticulocyte response in some patients with sickle cell anemia, without apparent negative clinical side effects. The state of iron stores may be critical. Whether higher doses of rHuEPO and/or a different regimen might induce sustained F cells and fetal hemoglobin increases remains to be determined.

Adolescent↗
PubMed1993

Nitrogen balance in patients treated with extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a commonly used technique in the management of newborn respiratory failure. However, few studies have addressed the optimal nutritional support of these critically ill neonates. Eleven newborns undergoing ECMO for respiratory failure were studied at various levels of intravenous caloric and nitrogen intake, using nitrogen balance techniques, to assess optimal nutritional support necessary to achieve positive nitrogen balance. Nonprotein nitrogen calories > 60 kcal/kg/d, and nitrogen > 240 mg/kg/d were necessary to achieve positive nitrogen balance, while maximum positive balance was seen with nitrogen intake > 400 mg/kg/d. These data suggest that newborns treated with ECMO can achieve positive nitrogen balance with modest amounts of caloric and nitrogen intake.

Energy Intake↗
PubMed1993

Transient cortical blindness due to hypertensive encephalopathy. Magnetic resonance imaging correlation.

Striking reversible signal intense magnetic resonance imaging (MRI) lesions were observed in the occipital cortex of a 16-year-old girl who presented with an attack of transient cortical blindness as the initial manifestation of hypertensive encephalopathy (HTE). The lesions were seen to best advantage on T2-weighted imaging and were not visible on computed tomography (CT). It is proposed that such occipital lobe MRI lesions likely reflect extravasation of fluid and proteins across the blood brain barrier, damaged as a consequence of cerebral autoregulation failure.

Adolescent↗
PubMed1993

Increased ICAM-1 expression in aortic disease.

PURPOSE: In this investigation we evaluated the expression of vascular adhesion molecules: intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1) in normal and diseased aorta. METHODS: Aortic tissue was obtained during operations for abdominal aortic aneurysms (AAA) (inflammatory, n = 3, noninflammatory, n = 6), aortic occlusive disease (AOD) (n = 6), or from fresh cadavers (NL) (n = 5). The tissue was stained with the avidin-biotin complex with the following primary antibodies: anti-ICAM-1-AA6, anti-E-selectin-BB11, and anti-VCAM-1-4B9. The slides were assigned an inflammatory score of 0 to 3, and the percentage of each cell type staining, 0% to 100%. RESULTS: A trend towards a higher inflammatory score was found in the vessel wall in AAA (2.4 +/- 1.8) as compared with AOD (1 +/- 0.37) or NL (0.2 +/- 0.2). There was no statistical difference. A significant elevation in ICAM-1 expression (p < or = 0.06), however, was demonstrated in the adventitial endothelial cells of AAA (85.8% +/- 7.8%), and AOD (80.0% +/- 11.1%), as compared with NL (30.8% +/- 12.2%). Both E-selectin and VCAM-1 were expressed in all groups, but no statistical difference was demonstrated. CONCLUSIONS: Patients with AAA and AOD display a significant upregulation of the expression of ICAM-1, suggesting a role for this protein in the initiation or maintenance of degenerative aortic diseases.

Aged↗
PubMed1992

Control of scarring in adult wounds by neutralising antibody to transforming growth factor beta.

Adult wounds heal with scar-tissue formation, whereas fetal wounds heal without scarring and with a lesser inflammatory and cytokine response. We injected the margins of healing dermal wounds in adult rats with neutralising antibody (NA) to transforming growth factor-beta (TGF-beta). All control wounds (irrelevant antibody, or TGF-beta, or no injection) healed with scarring, whereas the NA-treated wounds healed without scar-tissue formation; NA-treated wounds had fewer macrophages and blood vessels, lower collagen and fibronectin contents, but identical tensile strength and more normal dermal architecture than the other wounds. Early manipulation of the concentrations of selected cytokines may be a new approach to the control of scarring.

Animals↗