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Biomedical subjects

A Shah

Publications and source records attributed to A Shah.

At least 127 records · Page 7Linked to original sources
PubMed1999

Disordered N-terminal residues affect the folding thermodynamics and kinetics of maltose binding protein.

Maltose binding protein (MBP) exhibits a slow phase of folding at pH 7.4, 298 K. The kinetics of this phase has been characterized as a function of denaturant concentration and temperature. Denaturant double-jump experiments and the activation energy for folding indicate that the slow phase involves processes other than proline isomerization. Although the first five N-terminal residues are disordered in the MBP crystal structure, mutations in this region slow down folding and destabilize the native structure. This is the first report showing that disordered N-terminal residues can affect folding kinetics and stability.

ATP-Binding Cassette Transporters↗
PubMed1999

Mineralization of glutaraldehyde-fixed porcine aortic valve cusps in the subcutaneous rat model: analysis of variations in implant site and cuspal quadrants.

When evaluating the efficacy of new antimineralization treatments for bioprosthetic heart valves, subcutaneous implantation in a rat model often is used as an initial test. Although this model is widely used, there still are many aspects of its implementation that have not been investigated. To further investigate several parameters that may affect mineralization in the subcutaneous rat model, portions of glutaraldehyde-treated porcine aortic valve cusps were implanted both ventrally and dorsally into 21-day-old male Sprague-Dawley rats. Cusp quadrants were explanted at 1,2, and 3 weeks postimplantation and the calcium levels determined by atomic absorption spectroscopy. The objective of this study was to determine whether or not different implant locations and/or regions of the cusps affect the degree to which tissue mineralizes in the subcutaneous rat model. A total of 270 tissue specimens were examined. While the specific portion of the cusp implanted did not significantly affect the degree of mineralization, dorsal implantation resulted in significantly more mineralization than abdominal implantation (p = 0.007). As expected, longer implantation time was associated with greater calcification (p = 0.0001). The results of this study indicate that inconsistent placement of tissues in the rat subcutaneous implant model can result in significant differences in the degree of mineralization.

Animals↗
PubMed1999

The characteristics of Indian subcontinent origin elders newly referred to a psychogeriatric service.

BACKGROUND: The ethnic elderly population in the United Kingdom is increasing. Clinical, social and demographic characteristics of ethnic elders referred to and utilizing psychogeriatric services are unknown. Thus, this study was designed to compare these characteristics between Indian subcontinent origin ethnic elders and indigenous elders newly referred to a psychogeriatric service. METHOD: All new referrals to a psychogeriatric service over a 2-year period were examined. Clinical, social and demographic characteristics of Indian subcontinent origin ethnic elders were compared with those of indigenous elders. RESULTS: Ethnic elders were younger, had more children, had more people living in their household, were more likely to be married, were less likely to live alone, were more likely to have schizophrenia and less likely to have dementia. There were no differences between the two groups with regard to use of almost all health and social services resources at the time of the referral and after the initial assessment. CONCLUSIONS: These findings do not support the traditional view that ethnic elders do not adequately access psychogeriatric and social services and that they are primarily cared for by extended families.

Aged↗
PubMed1999

The impact of two changes in service delivery on a geriatric psychiatry liaison service.

BACKGROUND: The impact of two changes in service delivery (alteration in the admission policy of the medical unit and the introduction of a formal liaison component to a 'consultation only' liaison geriatric psychiatry service) on the associated liaison geriatric psychiatry service was examined in a naturalistic study. The main null hypothesis was that the referral rate would not be influenced by either change in service delivery. METHOD: The 30-month study period was divided into three phases defined by the two changes in service delivery. The impact of the two changes in service delivery on the (i) referral rate, (ii) reasons for referral, (iii) demographic and clinical characteristics of the referrals and (iv) advice offered after assessment was examined with a retrospective design. RESULTS: There was a significant decline in the number of referrals for each month across the three study phases exclusively accounted for by a decline between phase 2 and phase 3. The number of reasons for referral and management advice offered for social treatments per patient were greater in phase 1 compared to phase 2. The total number of management advice offered for medical treatments per patient was greater in phase 2 compared to phase 3. The cost of a specialist registrar attending a geriatric medicine ward round was more than offset by the associated decline in the number of referrals per month. CONCLUSION: Although this study was not designed as a cost-effectiveness study, the results suggest that the liaison component has the potential to be cost-effective. There is a need for more formal clinical effectiveness and cost-effectiveness studies in liaison geriatric psychiatry.

Aged↗
PubMed1999

Enhancement of cellular immune response in HIV-1 seropositive individuals: A DNA-based trial.

A DNA-based vaccine containing HIV-1 Env and Rev genes was tested for safety and host immune response in 15 HIV-infected asymptomatic patients with CD4-positive lymphocyte counts >/=500/microl of blood and receiving no antiviral therapy. Successive groups of patients received three doses of vaccine at 30, 100, or 300 microg at 10-week intervals in a dose-escalation trial. Some changes were noted in cytotoxic T-lymphocyte activity against gp160-bearing targets. Importantly, enhanced specific lymphocyte proliferative activity against HIV-1 envelope was observed in multiple patients. Three of three patients in the 300-microg dose group also developed increased MIP-1alpha levels which were detectable in their serum. Interestingly patients in the lowest dose group showed no overall changes in the immune parameters measured. The majority of patients who exhibited increases in any immune parameters were contained within the 300 microg, which was the highest dose group. These studies support further investigation of this technology for the production of antigen-specific immune responses in humans.

AIDS Vaccines↗
PubMed1999

Protruding aortic arch atheromas: risk of stroke during heart surgery with and without aortic arch endarterectomy.

BACKGROUND: Stroke occurs in 1% to 7% of heart surgery. Aortic arch atherosclerosis is a risk factor for intraoperative stroke, and endarterectomy has been proposed to prevent stroke during heart surgery in patients with arch atheromas. METHODS AND RESULTS: Intraoperative transesophageal echocardiography was performed in 3404 patients undergoing heart surgery between 1990 and 1996. Use of transesophageal echocardiography was unselected and based on equipment availability. Aortic arch atheromas (>/=5 mm, or mobile) were seen in 268 (8%) patients. They were evaluated for intraoperative stroke (confirmed by a neurologist and cerebral infarction on computed tomography or magnetic resonance imaging). Arch endarterectomy was performed in 43 patients as an adjunct to their cardiac procedure in an attempt to prevent intraoperative stroke. The intraoperative stroke rate in all 268 patients with atheromas was high (15.3%). On univariate analysis, age, previous stroke, and arch endarterectomy were significantly associated with intraoperative stroke. On multivariate analysis, age (odds ratio 3.9, P =.01) and arch endarterectomy (odds ratio 3.6, P =.001) were independently predictive of intraoperative stroke. Mortality rate in all 268 patients was high (14.9%). These patients with atheromas also had a long recovery room, intensive care unit, and total hospital length of stay (48 days). CONCLUSIONS: Patients with protruding aortic arch atheromas are at high risk for intraoperative stroke, significant and multiple morbidity, prolonged hospital stay, and death resulting from heart surgery. Aortic arch endarterectomy is strongly associated with intraoperative stroke; its use should be carefully considered in light of these results.

Aged↗
PubMed1999

Resistance mutations selected in vivo under therapy with anti-HIV drug HBY 097 differ from resistance pattern selected in vitro.

The quinoxaline derivative HBY 097, an orally active nonnucleoside inhibitor of HIV-1 reverse transcriptase (NNRTI), showed an efficient suppression of viral load in a dose-escalating phase I study with mean trough concentrations increasing from 137-1299 ug/l [Rübsamen-Waigmann et al., Lancet 349:1517]. Half-maximal inhibitory concentrations (IC50) for viruses grown from the patients at entry of the study were 0.1-3 nM, except for one patient who had a virus with reduced susceptibility to HBY 097 at entry (IC50: 160 nM). During therapy, only two patients developed a virus with a moderately increased IC50 (2.2 and 15 nM). This reduced susceptibility was associated with the known NNRTI-resistance mutation K ==> N at position 103, in contrast to resistance selection in vitro, which had yielded predominant mutations at positions 179 and 190. The Tyr mutation at position 181, inducing high resistance for other NNRTIs, was never observed. The resistant virus at study entry (IC50 = 160 nM) had a mutation at position 103 as well, combined with an AZT resistance mutation (K ==> R) at position 70, suggesting that nucleoside-resistance mutations may help increasing resistance to HBY 097. This is in line with our in vitro selection studies, where resistance mutations at the 'nucleoside sites' 74 and 75 increased the resistance phenotype of NNRTI mutations. Our findings highlight the crucial importance of IC50 determinations from cultured virus for determination of phenotypic resistance development during therapy and demonstrate that in vivo resistance development cannot be predicted from in vitro selection.

Antiviral Agents↗
PubMed1999

Visualization of enzyme-catalyzed reactions using pH indicators: rapid screening of hydrolase libraries and estimation of the enantioselectivity.

The use of pH indicators to monitor hydrolase-catalyzed reactions is described. The formation of acid following an enzyme-mediated hydrolysis causes a drop in the pH that can be visualized by a change in the color of the indicator-containing solution. The best indicators are those showing a color transition within the operational pH range of the hydrolases, like bromothymol blue and phenol red. The enantioselectivity of lipases and esterases can be estimated using single isomers under the same conditions and comparing the color turnover for each one. The method has been tested to quickly evaluate the enantioselectivity of a lipase towards a set of ester substrates and applied to the hierarchical screening of a library of thermophilic esterases.

Acetonitriles↗
PubMed1999

Hilar adenopathy in allergic bronchopulmonary aspergillosis.

BACKGROUND: A 20-year-old male student developed allergic bronchopulmonary aspergillosis (ABPA). Computed tomography (CT) of the thorax done to detect central bronchiectasis (CB) for confirmation of diagnosis revealed, in addition, right hilar lymphadenopathy. Hilar adenopathy is thought to be rare in ABPA and has been documented only once before. Because of the finding of hilar adenopathy, the earlier reported patient had to undergo an invasive surgical procedure. OBJECTIVE: To report a case of true hilar adenopathy in ABPA. METHODS: This is a single case report. Contrast enhanced CT of the thorax was done. Serum precipitating antibodies against Aspergillus fumigatus were tested using gel diffusion technique, and intradermal testing with antigens of Aspergillus species was performed. Specific IgG antibodies against A. fumigatus and total IgE levels were measured by ELISA. RESULTS: A review of serial chest radiographs over a period of 3 years demonstrated transient pulmonary infiltrates and right hilar prominence. Computed tomography of the thorax revealed right hilar lymphadenopathy along with bilateral central bronchiectasis and patchy infiltrates. Strong bands of precipitins were detected against A. fumigatus. Intradermal testing with antigens of Aspergillus species elicited strong type I (immediate) and type III (Arthus-type) hypersensitivity reactions to A. fumigatus and A. niger. Specific IgG antibodies against A. fumigatus was positive and total IgE level was significantly elevated. Peripheral blood eosinophilia was also detected. CONCLUSIONS: Although extremely rare, ABPA should be considered in the differential diagnosis of hilar adenopathy.

Adult↗
PubMed1999

Some methodological issues in using aggression rating scales in intervention studies among institutionalized elderly.

BACKGROUND: Aggressive behavior among geriatric psychiatry inpatients spontaneously declines during serial measurements over time with rating scales. METHOD: Evidence for decline in aggressive behavior, over a 6-week period, on a continuing-care geriatric psychiatry ward was examined with the Staff Observation Aggression Scale (SOAS) and the Rating Scale for Aggressive Behavior in the Elderly (RAGE). RESULTS: The RAGE and all its subitems did not spontaneously decline. The total number of aggressive incidents on the SOAS, the SOAS total score, and the subitem scores, except for the SOAS results subitem, spontaneously declined after Week 4 and became established by Week 5. CONCLUSION: A "run in" period of at least 4 weeks may be needed in intervention studies using the SOAS to reduce contamination by spontaneous decline.

Aged↗
PubMed1999

Effect of acute hyperglycemia on jejunal compliance and peristaltic reflex in healthy humans.

Acute hyperglycemia has been shown to affect gastric motor function and colonic peristaltic reflex, but little is known about its effects on the small bowel. Our aim was to determine the effect of experimentally induced acute hyperglycemia on small bowel compliance and peristaltic reflex. Ten healthy subjects were studied during euglycemia and induced hyperglycemia. Sequential balloon inflation in the jejunum was used to determine pressure-volume relationships. The frequency of jejunal contractions and motility index proximal and distal to a distending balloon were measured for assessment of the peristaltic reflex. The intestinal pressure-volume relationship was not affected by hyperglycemia (In pressure/volume 0.084+/-0.006 vs 0.096+/-0.006, P = 0.19). During hyperglycemia, there was significantly more distal inhibition of frequency of contractions (51.0+/-26.6% vs 26.7+/-22.3%, P < 0.05) and of motility index (18.8+/-10.8% and 10+/-6.4, P < 0.05) in response to balloon inflation. We conclude that in the small bowel of healthy subjects, experimentally induced acute hyperglycemia has no effect on compliance and little effect on enteric nerve function.

Acute Disease↗
PubMed1999

IgY antiporcine endothelial cell antibodies effectively block human antiporcine xenoantibody binding.

Avian IgY antibodies are structurally different from mammalian IgGs and do not fix mammalian complement components or bind human Fc receptors. As these antibody-mediated interactions are believed to play significant roles in both hyperacute rejection (HAR) and acute vascular xenograft rejection (AVXR), IgY antibodies to xenoantigen target epitopes may inhibit these rejection processes. In this report, we show that chicken IgY antibodies to alpha-Gal antigen epitopes and to other porcine aortic endothelial cell (PAEC) antigens block human xenoreactive natural antibody binding to both porcine and rat cardiac tissues and porcine kidney tissues. Chicken IgY antibodies blocked complement-mediated lysis of PAECs by human serum, and inhibited antibody-dependent cell-mediated lysis of PAECs by heat-inactivated human serum plus peripheral blood leukocytes. Binding of IgY to porcine endothelial cells did not affect cell morphology nor expression of E-selectin. These results suggest that avian IgYs could be of potential use in inhibiting pig-to-human xenograft rejection.

Animals↗
PubMed1999

Allogeneic bone marrow transplantation for advanced Waldenstrom's macroglobulinemia.

Waldenstrom's disease is a lymphoproliferative disorder that is typically treated with plasmapheresis and/or alkylating agents. In young patients, other lymphoproliferative disorders have been treated with allogeneic transplantation. Two patients with aggressive Waldenstrom's disease, who progressed in spite of multi-agent chemotherapy and autologous stem cell transplantation, in one case, underwent allogeneic transplantation from their HLA-identical donors. Both remain alive with event-free survivals of more than 3, and more than 9 years, respectively. Allogeneic transplantation should be considered for young patients with Waldenstrom's disease.

Adult↗
PubMed1999

Gallbladder ascariasis: presentation and management.

BACKGROUND: As many as 1.5 billion people around the world harbour Ascaris lumbricoides in the digestive tract. Gallbladder ascariasis, although less common than bile duct ascariasis, is quite often seen in endemic areas. METHODS: Some 1300 patients with hepatobiliary ascariasis, admitted between October 1992 and June 1998, were analysed prospectively. The clinical features and outcome of 56 cases of gallbladder ascariasis are presented. RESULTS: Forty-seven patients were diagnosed by ultrasonography and nine were diagnosed at laparotomy. Only ten patients diagnosed by ultrasonography expelled the worms spontaneously, with resolution of symptoms and signs. The remaining 37 patients underwent cholecystectomy. CONCLUSION: Gallbladder ascariasis is a significant entity in endemic areas which usually requires cholecystectomy.

Ascariasis↗
PubMed1999

Myocardial bradykinin production during coronary balloon angioplasty in humans.

BACKGROUND: Recent studies have implicated the peptide bradykinin as a potential trigger of ischaemic preconditioning, the phenomenon whereby a brief episode of myocardial ischaemia induces an increased tolerance to subsequent more prolonged ischaemia. Brief myocardial ischaemia occurring during percutaneous transluminal coronary balloon angioplasty in humans is reported to be capable of inducing preconditioning. DESIGN: We studied the intracardiac production of bradykinin in eight patients (seven men, mean age 53.5 years) undergoing elective percutaneous transluminal coronary angioplasty for a single left anterior descending coronary artery stenosis. Paired blood samples were obtained from the coronary sinus and the proximal aorta at baseline, immediately before balloon deflation after a 2-min inflation, and at 1, 3 and 5 min post deflation. Bradykinin levels were measured by radioimmunoassay. RESULTS: There was no significant change either in aortic or coronary sinus bradykinin levels at any time point. CONCLUSIONS: Intracardiac production of bradykinin is unlikely to be a trigger for ischaemic preconditioning after brief myocardial ischaemia in humans.

Adult↗
PubMed1999

Macrophage depletion by albumin microencapsulated clodronate: attenuation of cytokine release in macrophage-dependent glomerulonephritis.

A macrophage plays an important role in mediating the inflammatory response. Cytokines released by activated macrophages contribute to inflammation in glomerulonephritis (GN). Clodronate, a biphosphonate, causes macrophage depletion when administered in an encapsulated form in liposomes. We used albumin as the polymer matrix to microencapsulate clodronate to the microspheres (MS) in the 1-micron size range. The purpose of this study was to (a) determine macrophage depletion by clodronate MS, (b) determine the effect of clodronate MS on endotoxin-induced cytokine release in vitro, and (c) assess the effect of clodronate MS on macrophage infiltration in experimental antiglomerular basement membrane nephritis. Macrophage depletion by clodronate MS was assessed by staining for the EDI marker. The results indicate greater than 95% depletion of macrophages from the spleen, liver, kidney, and blood. In the whole blood model, clodronate MS attenuated endotoxin-induced tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) release, and the attenuation by the microencapsulated form of clodronate was also more effective than the free (solution) form of clodronate. Macrophage infiltration into the glomerulus in experimental GN was also blocked very effectively by pretreatment with clodronate MS. In conclusion, macrophage depletion by clodronate MS may be beneficial in reducing cytokine release and renal damage in GN.

Albumins↗