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H Patel

Publications and source records attributed to H Patel.

At least 109 records · Page 6Linked to original sources
PubMed1999

Calcium regulation in the human myocardium affected by dilated cardiomyopathy: a structural basis for impaired Ca2+-sensitivity.

Calcium regulation in the human heart is impaired during idiopathic dilated cardiomyopathy (IDC). Here, we analyze the structural basis for impairment in the regulatory mechanism. Regulation of contractility was monitored by MgATPase and Ca2+-binding assays as a function of calcium. Myofibrillar proteolysis and expression of troponin T isoforms were established by gel electrophoresis and by Western blots. Myofibrillar ATPase assays in low salt however, revealed a drastic lowering of calcium sensitivity in IDC myofibrils as indicated by reductions in both activation by high calcium and in EGTA-mediated inhibition of MgATPase. Structural changes in myofilament proteins were found in most IDC hearts, specifically proteolysis of myosin light chain 2 (LC2), troponin T and I (TnT and TnI), and sometimes a large isoform shift in TnT. IDC did not induce mutations in LC2 and troponin C (TnC), as established by cDNA sequence data from IDC cases, thus, calcium binding to IDC myofibrils was unaffected. Reassociation of IDC myofibrils with native LC2 raised MgATPase activation at high Ca2+ to control levels, while repletion with intact, canine TnI/TnT restored inhibition at low Ca2+. A model, identifying possible steps in the steric blocking mechanism of regulation, is proposed to explain IDC-induced changes in Ca2+-regulation. Moreover, shifts in TnT isoforms may imply either a genetic or a compensatory factor in the development and pathogenesis of some forms of IDC.

Adenosine Triphosphatases↗
PubMed1999

Pharmacological characterization of the muscarinic receptor antagonist, glycopyrrolate, in human and guinea-pig airways.

1. In this study we have evaluated the pharmacological profile of the muscarinic antagonist glycopyrrolate in guinea-pig and human airways in comparison with the commonly used antagonist ipratropium bromide. 2. Glycopyrrolate and ipratropium bromide inhibited EFS-induced contraction of guinea-pig trachea and human airways in a concentration-dependent manner. Glycopyrrolate was more potent than ipratropium bromide. 3. The onset of action (time to attainment of 50% of maximum response) of glycopyrrolate was similar to that obtained with ipratropium bromide in both preparations. In guinea-pig trachea, the offset of action (time taken for response to return to 50% recovery after wash out of the test antagonist) for glycopyrrolate (t1/2 [offset]=26.4+/-0.5 min) was less than that obtained with ipratropium bromide (81.2+/-3.7 min). In human airways, however, the duration of action of glycopyrrolate (t1/2 [offset]>96 min) was significantly more prolonged compared to ipratropium bromide (t1/2 [offset]= 59.2+/-17.8 min). 4. In competition studies, glycopyrrolate and ipratropium bromide bind human peripheral lung and human airway smooth muscle (HASM) muscarinic receptors with affinities in the nanomolar range (K1 values 0.5-3.6 nM). Similar to ipratropium bromide, glycopyrrolate showed no selectivity in its binding to the M1-M3 receptors. Kinetics studies, however, showed that glycopyrrolate dissociates slowly from HASM muscarinic receptors (60% protection against [3H]-NMS binding at 30 nM) compared to ipratropium bromide. 5. These results suggest that glycopyrrolate bind human and guinea-pig airway muscarinic receptors with high affinity. Furthermore, we suggest that the slow dissociation profile of glycopyrrolate might be the underlying mechanism by which this drug accomplishes its long duration of action.

Animals↗
PubMed1999

Anti-spasmogenic activity of isoenzyme-selective phosphodiesterase inhibitors in guinea-pig trachealis.

1 The anti-spasmogenic potential of SK&F 94120 (PDE3-selective), rolipram (PDE4-selective), zaprinast (PDE5-selective), zardaverine (dual PDE3/4 inhibitor) and theophylline (non-selective) was evaluated in guinea-pig trachealis. 2 SK&F 94120 or rolipram (10 and 100 microM) antagonized histamine-induced tension generation in a concentration-dependent and non-competitive manner whereas ACh-induced contractions were unaffected. Similarly, SK&F 94120 and rolipram in combination were anti-spasmogenic with respect to both contractile agonists to an extent that was greater than the effect of either drug alone. Identical results were obtained with zardaverine (1, 10 and 100 microM) and theophylline (100 microM and 1 mM). 3 Zaprinast protected guinea-pig trachealis against histamine-, but not ACh-induced contractile responses in a manner that was indistinguishable from the results obtained with SK&F 94120. However, in contrast to the interaction between SK&F 94120 and rolipram, no further antagonism was seen when zaprinast and rolipram were used in combination. 4 Pre-treatment of tissues with SNP (10 and 100 microM) antagonized histamine-induced tension generation in a concentration-dependent and non-competitive manner. However, no further antagonism was produced when SNP and rolipram were used concurrently. Likewise, the protection afforded by a combination SNP and SK&F 94120 was no greater than that produced by SNP alone. 5 These results demonstrate that an inhibitor of PDE3 enhances the anti-spasmogenic activity of rolipram but not drugs that elevate cyclic GMP mass. Moreover, the ability of SNP and zaprinast to protect guinea-pig trachealis against histamine-induced contractions apparently is not due to the inhibition of PDE3.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

Arrhythmias and women.

The incidence and risk factors for a variety of arrhythmias differ among men and women. Although symptomatic atrial reentrant tachycardias have a female predominance, the reverse is true for atrial fibrillation. Women have a lower incidence of sudden death. On the other hand, drug-induced torsades de pointes and symptomatic long QT syndrome have a female predominance. The incidence of arrhythmias seem to be increased during pregnancy. The mechanisms of these gender differences are unclear but may be related to hormonal effects and the shorter QT interval in men. Pharmacologic and nonpharmacologic therapy are equally efficacious in men and women.

Anti-Arrhythmia Agents↗
PubMed1999

Utilization analysis of an observation unit for children with asthma.

BACKGROUND: Short-stay observation unit (OU) care for children with asthma has the potential to reduce hospitalization rates for this common pediatric condition. In the effort to increase the efficiency of such a unit, knowledge of predictive factors for successful discharge is important. OBJECTIVES: 1) To define clinical predictive factors determined at the time of initial presentation in the emergency department (ED) that would identify which children with asthma are most likely to be successfully discharged from an OU. 2) To compare the management provided in the initial 3 hours upon arrival at the ED between the children who are eventually successfully discharged from an OU to those who require an inpatient admission. 3) To compare the length of stay in the OU between the patients who eventually go home to those who require an inpatient admission. DESIGN: Case control study. SETTING: Urban, tertiary-care pediatric ED. PARTICIPANTS: From a collected database of all patients with asthma 1 to 18 years of age, presenting to the ED from July 1, 1993 to June 30, 1994 (n = 2248), a random sample of 350 patients was identified. All children meeting the definition of "case" or "control" from this sample were included. Cases were defined as children with asthma who were successfully discharged after a stay in the OU. Controls were defined as children with asthma who were not successfully discharged; that is, children who required subsequent inpatient admission. RESULTS: Of the 350 children with asthma in the randomly selected subset sample, 47 cases and 21 controls were identified. In both cases and controls, patients had similar characteristics regarding mean age, sex, mean weight, previous history of asthma, and mean length of illness. The use of medications in the 24 hours prior to presentation to the ED was similar between both groups. No differences were found in the mean respiratory rate upon presentation between the cases and the controls (40/min vs. 44/min; P = 0.2), mean oxygen saturation (95 vs. 94%; P = 0.4). However, there was a significant difference in the requirement of supplemental oxygen between cases and controls (15 vs. 43%; P = 0.01; OR = 0.23:0.07 to 0.76). No further differences were found in the first 3 hours of ED management. The number of albuterol and ipratropium nebulizations was similar. The use, dosage, and timing of systemic steroids were also similar between the groups. The cases remained in the OU for a shorter period of time (8.7 hours vs 9.2 hours; 95% C.I.: -2.8 to 1.8) than the controls. CONCLUSION: No clinical predictive factors determined at the time of arrival to the ED were identified for children with asthma who were successfully discharged from the OU except for a lesser need of oxygen supplementation. The patients observed in the OU had similar management in the initial 3 hours of arrival and similar length of stay in the OU, regardless of their disposition outcome. Maximal OU efficiency remains limited by the lack of clear predictive factors for successful discharge. Further study in this area is indicated.

Acute Disease↗
PubMed1999

Surgical training for the next millennium.

The Calman reforms in training have meant that surgical training now consists of a 2-year basic training period followed by a 6-year period of higher surgical training. This article addresses the problems faced by the new Calman surgical trainees and proposes some new measures which could be introduced for surgical training in the next millennium.

Education, Medical, Graduate↗
PubMed1999

An assessment of the efficacy of atorvastatin in achieving LDL cholesterol target levels in patients with coronary heart disease: a general practice study.

Adherence to evidence-based guidelines for the secondary prevention of coronary heart disease (CHD) has been shown to be poor in a number of surveys. In this open-label, non-comparative 17-week trial, 399 patients with existing CHD and LDL cholesterol concentration > 3.4 mmol/l (130 mg/dl) were treated with atorvastatin 10 mg daily. After 5 weeks, the dose of atorvastatin was adjusted according to a patient's LDL cholesterol level. Of the 379 patients remaining in the study after five weeks of treatment, dose titration was not required for 355 patients (94%) who had reached the target LDL cholesterol of < or = 3.4 mmol/l. Of the 23 patients titrated to higher doses, 11 achieved the target LDL cholesterol after treatment for 17 weeks. Atorvastatin was well tolerated during the course of the study. Achieving LDL cholesterol targets without the need for dose titration simplifies clinical management and should encourage better adherence to evidence-based recommendations for secondary prevention of CHD.

Anticholesteremic Agents↗
PubMed1998

Inadequate control of lipid levels in patients with a previous myocardial infarction.

AIM: To access the current lipid management of late survivors of acute myocardial infarction. METHODS: A systematic follow-up of all survivors who had previously been screened for enrolment into one of three randomised clinical trials in Auckland was undertaken from December 1995 to January 1997. All contacted survivors were asked to answer a questionnaire regarding their current therapy and were invited to undergo venepuncture for a lipid assay. RESULTS: Of the 1036 patients with acute myocardial infarction screened for enrolment in the three trials there were 984 (95%) who survived 30 days. At a median of 5.5 years (interquartile range 3.2-8.5) follow-up, 641 (86%) survivors agreed to have a fasting lipid test. The mean total cholesterol level was 5.7 +/- 1.1 mmol/L high density lipoprotein cholesterol 1.1 +/- 0.3 mmol/L, low density lipoprotein cholesterol 3.8 +/- 0.9 mmol/L and triglyceride level 1.9 +/- 1.1 mmol/L. Two hundred and seven (32%) patients were treated with a lipid-modifying agent. Four hundred and forty-five (69%) patients had a cholesterol level > or = 5.2 mmol/L 381 (59%) patients had a level > or = 5.5 mmol/L and 72 (11%) patients had a level > or = 7.0 mmol/L of whom 62 patients were not being treated with a lipid-modifying agent. For the 107 patients with coronary artery bypass grafts, the mean cholesterol level was 5.4 mmol/L and the mean low density lipoprotein cholesterol level was 3.7 +/- 0.9 mmol/L, with 57 (53%) patients not being treated with a "statin" or "fibrate". CONCLUSION: Lipid management is suboptimal in this high risk population of patients post-infarction and greater efforts need to be made to achieve better control. Diet is frequently inadequate in these patients at high risk and statin therapy is indicated.

Aged↗
PubMed1998

A conventional myosin motor drives neurite outgrowth.

Neuritic outgrowth is a striking example of directed motility, powered through the actions of molecular motors. Members of the myosin superfamily of actin-associated motors have been implicated in this complex process. Although conventional myosin II is known to be present in neurons, where it is localized at the leading edge of growth cones and in the cell cortex close to the plasma membrane, its functional involvement in growth cone motility has remained unproven. Here, we show that antisense oligodeoxyribonucleotides, complementary to a specific isoform of conventional myosin (myosin IIB), attenuate filopodial extension whereas sense and scrambled control oligodeoxyribonucleotides have no effect. Attenuation is shown to be reversible, neurite outgrowth being restored after cessation of the antisense regimen. Myosin IIB mRNA was present during active neurite extension, but levels were minimal in phenotypically rounded cells before neurite outgrowth and message levels decreased during antisense treatment. By contrast, the myosin IIA isoform is shown to be expressed constitutively both before and during neurite outgrowth and throughout exposure to myosin IIB antisense oligodeoxyribonucleotides. These results provide direct evidence that a conventional two-headed myosin is required for growth cone motility and is responsible, at least in part, for driving neuritic process outgrowth.

Animals↗
PubMed1998

Transcatheter retrograde radio-frequency perforation of the pulmonic valve in pulmonary atresia with intact ventricular septum, using a 2 French catheter.

A neonate with pulmonary atresia with intact ventricular septum (PA/IVS) underwent successful retrograde transcatheter perforation of the pulmonary valve, using a 2 Fr radio-frequency catheter with subsequent anterograde balloon dilation of the valve. Due to persistent hypoxemia, the neonate underwent placement of a 4-mm modified Blalock-Taussig shunt. Transcatheter retrograde transductal perforation of the pulmonic valve in PA/IVS is feasible and may be a potential alternative to anterograde perforation.

Cardiac Catheterization↗
PubMed1998

Catheter therapy for fontan baffle obstruction and leak, using an endovascular covered stent.

A 6 1/2-year-old (weight 20 kg) patient was found to have significant cavo-atrial obstruction and significant right-to-left shunt via multiple large fenestrations in the baffle, with oxygen saturation of 81% 3 1/2 yr after a fenestrated Fontan operation. In one session, this patient had undergone placement of a Palmaz stent at the cavo-atrial narrowing in order to increase anterograde venous return into the pulmonary artery. This was unsuccessful in improving the oxygen saturation because of the large leak in the baffle. Therefore, at a second catheterization session, two telescoping dacron-covered experimental vascular self-expanding stents were placed from the right atrial origin (distal to the hepatic veins) into the pulmonary artery connection delineated by the Palmaz stent, with complete reconstruction of the baffle and improvement in oxygen saturation to 95%.

Cardiac Catheterization↗
PubMed1998

Effect of chlorhexidine on multi-species biofilms.

With human saliva as an inoculum, microcosm dental plaques were grown on dental amalgam in a constant-depth film fermentor (CDFF) in the presence (suc +ve) and absence (suc -ve) of sucrose. The biofilms were then exposed to 0.2% chlorhexidine gluconate (CHG) for 1, 5, or 60 min and the survivors enumerated. Suc +ve biofilms had higher proportions of streptococci but lower proportions of veillonellae than suc -ve biofilms. Exposure to CHG for 1 min reduced the viable count of suc -ve and suc +ve biofilms by 53% and 89% respectively. In both cases, reductions were mainly attributable to killing of streptococci and actinomyces. After 60 min of exposure, 4% of the bacteria in the suc -ve and 2% in the suc +ve biofilms remained viable. This study has shown that large numbers of bacteria in microcosm dental plaques can survive a 1-min exposure to 0.2% CHG and that even after a 60-min exposure, substantial numbers of bacteria remain viable.

Bacteria↗
PubMed1998

Successful pregnancy outcome after complicated varicella pneumonia.

BACKGROUND: Maternal and fetal morbidity and mortality associated with varicella pneumonia in the peripartum period are increased further with multiple complications. CASE: The patient had varicella pneumonitis acquired at 32 weeks' gestation and complicated by bacterial superinfection, adult respiratory distress syndrome, endotoxin shock, and bronchiolitis obliterans organizing pneumonia. CONCLUSION: Aggressive, timely management of respiratory failure, control of infection, correction of endotoxin shock, treatment of biopsy-proven bronchiolitis obliterans organizing pneumonia, and obstetric intervention for fetal compromise produced a good outcome for mother and infant.

Adult↗
PubMed1998

Reasons for non-compliance with screening for infection with Helicobacter pylori, in a multi-ethnic community in Leicester, UK.

In this study, we aimed to identify reasons for non-compliance with a screening programme for Helicobacter pylori (H pylori), in a multi-ethnic community and to assess the effectiveness of Asian language materials towards increasing compliance. A serological screening test for infection with H pylori was offered to 200 Asians and 200 non-Asians (mainly Europeans), aged 21-55 y, registered at a single general practice. Reasons for non-attendance for screening were identified by reply slip or interview. A second group of 200 Asians who were offered screening were sent information in Gujarati as well as English. When information was mailed in English only, 30% Asians and 22% non-Asians attended (P = 0.09, ns). Stated reasons for non-attendance in the Asian group were not generally language related; reasons were similar in the Asian and non-Asian groups and were most frequently related to other commitments. The use of materials in Gujarati did not improve compliance. Language problems should not be assumed to dominate reasons for non-compliance with screening in ethnic minority groups. In common with those of UK origin, subjects from ethnic minority groups may more generally have insufficient interest in preventive medicine for them to prioritise health screening above other commitments.

Adult↗