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Biomedical subjects

Y Shah

Publications and source records attributed to Y Shah.

At least 19 recordsLinked to original sources
PubMed2006

Peroxisome proliferator activated receptor gamma in colonic epithelial cells protects against experimental inflammatory bowel disease.

INTRODUCTION: Peroxisome proliferator activated receptor gamma (PPARgamma) is expressed in epithelial cells, macrophage, and T and B lymphocytes. Ligand induced activation of PPARgamma was reported to attenuate colitis activity but it is not clear whether this protection is mediated by epithelial or leucocyte PPARgamma. METHODS: Mice with targeted disruption of the PPARgamma gene in intestinal epithelial cells, generated using a villin-Cre transgene and floxed PPARgamma allele and designated PPARgamma(DeltaIEpC), were compared with littermate mice having only the PPARgamma floxed allele with no Cre transgene that expressed PPARgamma in the gut, designated PPARgamma(F/F). Colitis was induced by administering dextran sodium sulphate (DSS) and the two mouse lines compared for typical symptoms of disease and expression of inflammatory cytokines. RESULTS: PPARgamma(DeltaIEpC) mice displayed reduced expression of the PPARgamma target genes ADRP and FABP in the gut but were otherwise normal. Increased susceptibility to DSS induced colitis, as defined by body weight loss, colon length, diarrhoea, bleeding score, and altered histology, was found in PPARgamma(DeltaIEpC) mice in comparison with PPARgamma(F/F) mice. Interleukin (IL)-6, IL-1beta, and tumour necrosis factor alpha mRNA levels in colons of PPARgamma(DeltaIEpC) mice treated with DSS were higher than in similarly treated PPARgamma(F/F) mice. The PPARgamma ligand rosiglitazone decreased the severity of DSS induced colitis and suppressed cytokine production in both PPARgamma(F/F) and PPARgamma(DeltaIEpC) mice. CONCLUSIONS: These studies reveal that PPARgamma expressed in the colonic epithelium has an endogenous role in protection against DSS induced colitis and that rosiglitazone may act through a PPARgamma independent pathway to suppress inflammation.

Animals↗
PubMed2000

Mild cognitive impairment. When is it a precursor to Alzheimer's disease?

There is good evidence suggesting that onset of Alzheimer's disease is commonly preceded by an interim phase known as mild cognitive impairment (MCI). Persons who experience this condition are at increased risk for the development of Alzheimer's disease. Diagnosing MCI involves excluding other morbidities and determining whether the patient meets predefined assessment criteria. There is no treatment for the prevention of MCI, but an understanding of the condition can improve patient management. Several clinical trials are underway to investigate potential potential MCI agents.

Aged↗
PubMed1993

The role of the human placenta in embryonic nutrition. Impact of environmental and social factors.

The human placenta has been implicated in the poor growth and development of the embryo/fetus due to alterations in blood flow and reductions in the transfer of nutrients such as amino acids and carbohydrates. Deficiencies of such nutrients have been the principal of many research investigations. The role of micronutrients, however, may also be major factors in appropriate growth and development, and there may be a general reduction in the availability of such nutrients, for example, the role of folate supplementation during early pregnancy and the reduction in the incidence of neural tube defects. Vitamins are not all transported via a common mechanism. Therefore, the modulation of human placental transport can be different for different vitamins, for example, A and B12. It is apparent that the human placenta can oxidatively metabolize retinoids (isotretinoin and tretinoin) to more toxic or less toxic metabolites. These metabolites can then be transferred to the fetal circulation. Such metabolism/transfer is in contrast to how vitamin B12 is bound to transcobalamin proteins, which are produced by the placenta and directionally released into the maternal and fetal circulations.

Embryonic and Fetal Development↗
PubMed1992

Lymphocyte adenosine deaminase activity (L-ADA) in leprosy, during and after treatment of reactions.

Twenty-five patients with type 1 (lepra) and type 2 (E.N.L.) leprosy reactions were studied for lymphocyte adenosine deaminase activity (L-ADA), during and after treatment of the reactions, using a standard technique, in order to establish its pattern and if possible, its value in assessing the course of reactions. The results were compared with those from 30 control subjects, comprising 10 normal healthy adults, 10 patients with borderline tuberculoid (BT) leprosy, four patients with borderline lepromatous (BL) leprosy and six patients with lepromatous (LL) leprosy. The level of L-ADA in the leprosy controls was higher than that of normal healthy subjects. The L-ADA values in patients with different types of reactions were about 10-fold higher than those obtained from leprosy controls, emphasizing a possible role in assessing reactions in leprosy. However, there was no significant variation in L-ADA levels, either between the various leprosy controls or reaction groups, before and after treatment.

Adenosine Deaminase↗
PubMed1992

Reaction in leprosy: acute phase reactant response during and after remission.

Sera from 25 patients with type 1 (Lepra), upgrading and downgrading, and type 2 (erythema nodosum leprosum [ENL]) reactions were assayed, during the reaction and after its clinical remission, for changes in levels of alpha-1-antitrypsin (A1A) and C-reactive protein (CRP). The results were compared with those from normal healthy adults and patients of leprosy without history and/or clinical evidence of reaction. The A1A levels correlated better with changes in status of type 1 reaction; whereas CRP levels correlated well with alterations in type 2 reactions and were definitely superior to A1A in this situation for monitoring the course of these episodes.

Adolescent↗
PubMed1991

Soluble interleukin-2 receptors: levels in leprosy, and during and after type 1 (lepra) and type 2 (ENL) reactions.

Twenty-five patients with Type 1 (lepra) and Type 2 (ENL) reactions, were assayed for SIL-2R in serum--before and after treatment for their acute condition--and the results were compared with 10 normal healthy adults and 20 patients of leprosy per se. Classification of each subject into different leprosy groups, and into various types and subtypes of reactions, was done according to standard criteria, prior to inclusion into the study. Detailed statistical evaluation of the data revealed significantly higher levels of SIL-2R in all leprosy patients, as compared to normal controls, with higher levels in the multibacillary groups as compared to the paucibacillary group. SIL-2Rs appeared higher in Type 1 upgrading reaction than in other forms of reaction, though this was not statistically significant. There was no significant change in levels following treatment and clinical remission.

Adolescent↗
PubMed1990

The neuropharmacology of emesis: the role of receptors in neuromodulation of nausea and vomiting.

The basic pharmacological mechanisms involved in mediating nausea and vomiting are still poorly understood. Several classes of drugs have been identified that alleviate the symptoms of nausea and vomiting, either prophylactically or acutely. None of these is completely effective in all cases. They include antihistamines, dopamine antagonists, steroids, cannabinoids, benzodiazepines, serotonin antagonists, and anticholinergics. This paper examines the evidence that links each of these classes of drugs with the distribution of specific neurotransmitter receptor sites on which they may be acting. Studies on the central nervous system distribution of binding sites for one of these classes of drugs, the anticholinergics, are described. Binding sites for the muscarinic cholinergic radioligand [3H]quinuclidinylbenzilate occur in different concentrations throughout the dorsal vagal complex of the rabbit medulla oblongata. The distribution of such sites in this nonvomiting experimental animal is markedly different from that in the cat, an animal that has been used for many physiological and pharmacological studies of emesis. A previous study has suggested that muscarinic binding sites may occur presynaptically on vagal afferent terminals that synapse in the dorsal vagal complex of the cat; this appears not to be the case in the rabbit. Possible implications of these findings for the identification of the site of action of anticholinergic, antiemetic drugs are discussed.

Animals↗
PubMed1989

Impaired coronary vasodilator reserve in the immediate postcoronary angioplasty period: analysis of coronary artery flow velocity indexes and regional cardiac venous efflux.

The ratio of peak hyperemic/basal mean coronary flow velocity, an index of coronary vasodilator reserve, immediately after coronary angioplasty normalizes in less than 50% of patients. To evaluate other indexes of coronary vasodilator capacity, both intracoronary arterial velocity and cardiac venous efflux were measured at rest and during vasodilator-induced coronary hyperemia (intracoronary nitroglycerin and papaverine) before and after angioplasty in 27 patients; 17 patients had measurements of intracoronary velocity alone and 10 had thermodilution measurements of great cardiac vein flow. Coronary flow velocity responses were also measured in 6 angiographically normal segments in patients undergoing angioplasty and in 10 normal left coronary artery segments in patients with normal coronary arteries or isolated right coronary artery disease. Despite significant angiographic (72 +/- 12 to 23 +/- 11% diameter narrowing) and hemodynamic (49 +/- 12 to 19 +/- 12 mm Hg aortocoronary gradient) improvement, coronary vasodilator reserve ratios for both arterial velocity and venous flow after angioplasty were only minimally affected. Angioplasty did not significantly increase rest coronary vein flow or artery flow velocities, but did result in significantly higher papaverine responses after angioplasty. Mean and phasic coronary velocity, diastolic coronary flow velocity integral and measured great cardiac vein flow ratios were significantly lower when compared with those in 16 angiographically normal coronary artery segments. These data indicate that maximal hyperemic coronary flow velocity is increased after angioplasty, but the reserve ratios, calculated by any of several flow velocity indexes, remain minimally improved. Angiographic correlations (percent coronary diameter, absolute diameter or cross-sectional area) with variables of coronary blood flow or velocity suggest that no single variable is useful in assessing angioplasty results. However, postangioplasty arterial mean velocity and diastolic flow velocity integral are nearly normalized in most patients, whereas relative changes remain attenuated. These findings are important in studies assessing coronary vasomotor responses in patients with atherosclerotic coronary disease, especially after angioplasty.

Adult↗
PubMed1989

Prognostic value of early exercise stress testing after successful coronary angioplasty: importance of the degree of revascularization.

The prognostic value of early exercise testing after successful coronary angioplasty was determined in 196 and 225 consecutive patients with single-vessel and multivessel coronary disease, respectively, who underwent a symptom-limited exercise test within 30 days of the procedure. The incidence of exercise-induced ST segment depression greater than or equal to 1 mm was significantly greater in patients with multivessel versus single-vessel disease (27% versus 14%; p less than 0.005) and in patients with multivessel coronary disease who had incomplete versus complete revascularization (36% versus 10%; p less than 0.001). An abnormal exercise ECG result was associated with a significantly increased risk of cardiac events in patients with multivessel disease but not in patients with single-vessel disease. Exercise-induced angina occurred in a small and similar proportion of patients with single and multivessel coronary disease (8% versus 12%). The presence of exercise-induced angina was associated with a higher incidence of follow-up cardiac events in patients with multivessel disease and incomplete revascularization (52% versus 33%; p less than 0.05). Exercise duration was significantly less in patients with multivessel disease who had a subsequent cardiac event compared with that in patients who did not have such an event (458 +/- 168 versus 519 +/- 156 seconds; p = 0.01). Thus an abnormal exercise ECG finding within 1 month of successful coronary angioplasty is predictive of subsequent cardiac events in patients who have multivessel disease. The prognostic content of the test might be further improved if the test were performed several months after the procedure when the risk of restenosis is greatest.

Angina Pectoris↗
PubMed1988

Safety and diagnostic accuracy of dipyridamole-thallium imaging in the elderly.

The noninvasive diagnosis of coronary artery disease in the elderly can occasionally be difficult. Intravenous dipyridamole-thallium imaging is a potentially useful diagnostic test to determine presence and severity of coronary disease; however, the safety of the procedure has not been determined in an older population. The side effect profile and frequency of severe ischemic responses after 0.56 mg/kg of intravenous dipyridamole were compared in 101 patients greater than or equal to 70 years old and 236 patients less than 70 years old. There were no side effects in 64% and 62% of patients greater than or equal to 70 and less than 70 years old, respectively (p = NS). Among the 337 patients tested, there were no complications of myocardial infarction or death. The most common cardiac side effect was chest pain, which occurred in 21 (21%) of the 101 patients aged greater than or equal to 70 years and in 64 (27%) of the 236 patients less than 70 years (p = NS). Aminophylline was required to reverse cardiac or noncardiac side effects in 15 (15%) and 36 (15%) of the patients greater than or equal to 70 and less than 70 years old, respectively (p = NS). A severe ischemic response occurred in 2% and 2.5% of patients greater than or equal to 70 and less than 70 years old, respectively (p = NS). The sensitivity of intravenous dipyridamole-thallium imaging for obstructive coronary artery disease was 86% (25 of 29) and 83% (68 of 82) in older and younger patients, respectively (p = NS); the specificity was 75% (6 of 8) and 70% (16 of 23), respectively (p = NS). Thus, intravenous dipyridamole-thallium imaging is a safe noninvasive method for assessment of older patients with obstructive coronary disease; its side effect profile and diagnostic accuracy are similar to those seen in younger patients. The technique is associated with severe ischemic responses in only a small minority of patients.

Adult↗
PubMed1986

An infra-red fibre optic device for cardiac cycle timing and photoplethysmography.

In this work a simple fibre optic device using infra-red radiation is used to obtain information on the timing of the cardiac cycle and blood volume changes in the flow of blood in the body. The device is small, non-invasive and free from interference by surrounding electromagnetic fields enabling it to be used in the environment of such devices as NMR scanners.

Cardiography, Impedance↗
PubMed1985

Optical fibre plethysmograph.

We describe a method for obtaining blood volume information from the external jugular vein or carotid artery by means of an optical fibre transducer. The device may be used to obtain accurate predictions of the state of the cardiac cycle, thereby enabling a range of physiological measurements to be made. The transducer is entirely non-invasive and non-magnetic; it is extremely robust and is unaffected by the electrically and magnetically hostile environment created by an NMR scanner.

Biomedical Engineering↗
PubMed1985

A prospective randomized study of the clinical efficacy and safety of transvenous cardioversion for termination of ventricular tachycardia.

The clinical efficacy and safety of transvenous cardioversion for termination of sustained ventricular tachycardia (VT) were examined by a prospective randomized study design in 22 patients (19 men, three women; mean age 64 +/- 9 years) with organic heart disease and sustained VT. Patients were randomly assigned to undergo an incremental low-energy protocol from 0.03 to 2.2 J (group A, 11 patients) or an incremental high-energy protocol from 0.5 to 10.0 J (group B, 11 patients). Transvenous cardioversion was performed during electrophysiologic studies in the control (drug-free) state and during serial antiarrhythmic drug testing in all patients. Both groups were comparable for demographic, disease and functional status, and electrophysiologic parameters. A total of 77 episodes of VT (group A, 45; group B, 32) were analyzed. The overall efficacy of transvenous cardioversion for termination of VT was 62% (group A 56% vs group B 72%; p less than .01). Antiarrhythmic drug therapy did not significantly enhance efficacy of transvenous cardioversion (control 59% vs drug 65%; p greater than .2). Stepwise discriminant analysis correlated successful transvenous cardioversion with longer VT cycle length (p less than .0005), higher energy (p less than .025), lower energy waveform tilt (p less than .025), shorter time to initial cardioversion attempt (p less than .025), and shorter QRS duration in sinus rhythm (p less than .05). Acceleration of VT was frequent (8% incidence per delivered shock). Thirty-one percent of all incremental shock protocols were terminated because of this complication. After cardioversion, transient arrhythmias were common (bradyarrhythmias 23%, supraventricular tachyarrhythmias 12%). Displacement of electrode catheters after transvenous cardioversion was uncommon (3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1985

Comparative efficacy of transvenous cardioversion and pacing in patients with sustained ventricular tachycardia: a prospective, randomized, crossover study.

We performed a prospective, randomized crossover study to evaluate the comparative efficacy of transvenous cardioversion and rapid ventricular pacing for termination of induced ventricular tachycardia in patients with spontaneous ventricular tachycardia and organic heart disease. Sixty-two episodes of ventricular tachycardia were induced in 15 patients, mean age 60 +/- 10 years, during electrophysiologic studies. All patients underwent a preselected electrical therapy protocol in a randomized crossover sequence. Transvenous cardioversion was performed by an incremental protocol of three sequential shocks (0.5, 1.1, and 2.7 J). Six asynchronous sequential bursts of rapid ventricular pacing (10 and 15 paced stimuli at 90%, 75%, and 65% of ventricular tachycardia cycle length) were used. Mean cycle length of ventricular tachycardia for the study population was 391 +/- 85 msec. The morphology of the tachycardia was left bundle branch block in 27, right bundle branch block in 32, and indeterminate in three. Characteristics of ventricular tachycardia terminated by the two techniques were comparable. Rate of success for termination of tachycardia with the two methods was also comparable (transvenous cardioversion 83%, rapid ventricular pacing 80%; p greater than .1) and these responses were concordant in 78%. The modes of termination of ventricular tachycardia were similar. The incidence of acceleration of ventricular tachycardia per episode with these preselected protocols was also comparable (transvenous cardioversion 11%, rapid ventricular pacing 6%; p greater than .2). Transient supraventricular tachyarrhythmias were more frequent after transvenous cardioversion (23%) than after rapid ventricular pacing (3%). Significant patient discomfort occurred only after transvenous cardioversion (incidence of 57%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Clinical efficacy and electropharmacology of continuous intravenous amiodarone infusion and chronic oral amiodarone in refractory ventricular tachycardia.

The clinical efficacy and electropharmacologic effects of continuous intravenous (i.v.) amiodarone infusion (10 to 20 mg/kg/day for 4 to 7 days) followed by chronic oral amiodarone therapy (400 to 800 mg/day for 24 to 53 days) were evaluated in 17 patients with refractory sustained ventricular tachycardia (VT) or ventricular fibrillation. Intravenous amiodarone infusion prolonged the RR interval (from 754 +/- 85 to 860 +/- 157 ms, p less than 0.05), PR interval (from 192 +/- 53 to 212 +/- 54 ms, p less than 0.01) QRS duration (from 103 +/- 21 to 117 +/- 25 ms, p less than 0.001) and QTc interval (from 423 +/- 22 to 466 +/- 31 ms, p less than 0.001). Chronic oral amiodarone treatment had similar but more pronounced effects on electrocardiographic intervals. The ventricular effective refractory period tended to prolong after i.v. amiodarone infusion (p less than 0.1 to greater than 0.05) but prolonged significantly after chronic oral amiodarone (p = 0.025). Mean serum amiodarone concentration was 1.7 +/- 1.0 mg/liter with infusion and 1.5 +/- 0.6 mg/liter with oral therapy. Intravenous amiodarone infusion suppressed spontaneous VT in 5 of 9 patients with frequent VT recurrences, but had no effect on cycle length of spontaneous VT. Chronic amiodarone therapy either suppressed spontaneous VT recurrences or prolonged cycle length during VT recurrences. VT induction after i.v. amiodarone was not predictive of VT induction or spontaneous VT recurrences after chronic oral amiodarone treatment. Thus, i.v. amiodarone has limited value in acute control of VT and clinical or electrophysiologic response to it is not predictive of long term therapeutic results with amiodarone.

Administration, Oral↗