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Biomedical subjects

A Pitt

Publications and source records attributed to A Pitt.

At least 37 records · Page 2Linked to original sources

Extent and pharmacokinetic mechanisms of oral atenolol-verapamil interaction in man.

Chronic coadministration of oral verapamil with oral atenolol resulted in a variable increase in atenolol steady-state plasma concentrations in a group of 10 patients on chronic maintenance therapy. Individual subjects showed changes in area under the plasma atenolol concentration-time curve (AUC) of more than 100%, however group comparisons did not achieve statistical significance unless normalized for verapamil dose. Renal clearance of atenolol was shown to be decreased by more than 25% in 2 subjects studied using intravenous dosing of atenolol. This interaction is likely to contribute to the documented clinical intolerance of combinations of atenolol and verapamil.

Administration, Oral↗

Drosophila homolog of the murine Int-1 protooncogene.

We have isolated phage clones from Drosophila melanogaster genomic and cDNA libraries containing a sequence homologous to the murine Int-1 protooncogene. The Drosophila gene is represented by a single locus at position 28A1-2 on chromosome 2. The gene is expressed as a 2.9-kilobase-long polyadenylylated mRNA in embryo, larval, and pupal stages. It is hardly detectable in adult flies. The longest open reading frame of the cDNA clone corresponds to a protein 469 amino acids long. Alignment of the predicted amino acid sequences shows that the Drosophila protein is 86 amino acids longer than its murine counterpart. In spite of the difference in length, the two proteins are highly conserved with an overall sequence homology of 54%. Both Drosophila and murine Int-1 proteins begin with a hydrophobic leader sequence and contain cysteine residues and sites for glycosylation (four in the murine protein and one in the Drosophila protein) in conserved positions, suggesting that they play important functional roles.

Amino Acid Sequence↗

The role of permanent pacing after anterior myocardial infarction complicated by transient complete atrioventricular block.

A randomised study was performed to assess the influence of prophylactic permanent pacing on the incidence of late sudden death in patients surviving transient complete atrioventricular block with acute anterior myocardial infarction. Fourteen patients were studied, of whom ten died within two years, confirming the high overall late mortality in this group. The deaths included eight of the nine paced patients, of whom seven died suddenly. We conclude that prophylactic permanent pacing is not warranted in patients surviving transient complete atrioventricular block with acute anterior myocardial infarction.

Adult↗

Habit training and oxybutynin for incontinence in nursing home patients: a placebo-controlled trial.

In order to determine if a bladder-relaxant drug could enhance the effectiveness of a toileting program for incontinence among functionally impaired nursing home patients, 15 patients with detrusor hyperreflexia were enrolled in a 6-week trial during which they were put on a habit training protocol alone for 2 weeks, habit training (HT) and a placebo for 2 weeks, and then HT and oxybutynin for 2 weeks (2.5 mg three times daily for 1 week, then 5 mg three times daily for 1 week). Bacteriuria, which was present without other symptoms in 11 of the 13 patients who completed the trial, was treated before HT began. Eradication of the bacteriuria resulted in a small, statistically significant increase in cystometric bladder capacity (44 mL; 95% confidence interval 16 to 72 mL), but the detrusor hyperreflexia and frequent episodes of incontinence persisted. HT alone reduced the mean percentage of every-two-hour checks which were wet from 43% to 32% (95% confidence interval of the difference -1% to -21%; P = .04 by a paired t test); addition of placebo and active drug did not result in any further reduction. Cystometric bladder capacity had not changed significantly by the end of the trial (measured while patients were still on active drug), and there was no consistent relationship between changes in bladder capacity and changes in wet checks. Although our sample size is small, the data are consistent with other studies in similar populations. The relatively practical and inexpensive interventions we employed in this study will need to be modified or intensified in order to substantially reduce the frequency of incontinence among functionally disabled nursing home patients.

Aged↗

Treatment of acute serum sickness by plasma ultrafiltration.

The clinical value of a scaled-down prototype of an extracorporeal plasma ultrafiltration system for the treatment of acute serum sickness in rabbits was examined. The system uses two filters: the primary separates red cells from plasma, and the secondary filter excludes high molecular weight proteins from plasma. In vitro and in vivo experiments showed that the secondary filters rejected substantially more IgM (80-90%) than IgG (10-30%) or albumin (10%) and totally rejected immune complexes (IC) prepared in vitro. Two groups of rabbits were submitted to either sham filtration with the primary filter only (n = 5), receiving back the remixed components of their blood, or to the complete ultrafiltration protocol (n = 7), with removal of high molecular weight proteins and IC. Several parameters were studied longitudinally, such as circulating IC, which appeared to rise more slowly in animals whose blood was ultrafiltered, and total proteinuria, which appeared to remain at lower levels in the same animals. Histologic examination of the kidneys, collected after killing, showed evidence of glomerular IC deposition in three of five sham-treated animals (a similar frequency to that observed in a separate group of five rabbits with acute serum sickness), while one of six treated animals had evidence of glomerular deposition of IC. These observations are tentative because of the small number of animals in each group, but are encouraging. Further studies with larger groups of animals are needed to determine whether the observed effects are reproducible and to better characterize the factors directly related to the removal of circulating IC.

Acute Disease↗

Induction of ventricular arrhythmias by programmed ventricular stimulation: a prospective study on the effects of stimulation current on arrhythmia induction.

A protocol for programmed ventricular stimulation is described in which the effect of increasing stimulation current on ventricular refractoriness and arrhythmia induction was specifically examined. The protocol was evaluated prospectively in 70 patients undergoing electrophysiological study for documented or suspected ventricular arrhythmias. Programmed electrical stimulation was performed at the right ventricular apex and outflow tract using single and double extrastimuli and burst pacing. Stimulation currents of 2, 5, 10, and 20 mA were used in ascending order. The initial (lowest) current was never less than twice diastolic threshold and was maintained during each stimulation run until refractoriness was reached. The current was then increased to the next level to facilitate premature capture until refractoriness was encountered at 20 mA or a sustained arrhythmia occurred. Ventricular arrhythmias were induced in 34 patients, 31 of whom had presented with a sustained ventricular arrhythmia. The incidence of induced arrhythmias was low in those patients who had presented with symptoms alone, a non-sustained arrhythmia, or a sustained arrhythmia in association with a predisposing clinical event. Only one patient with a negative result had further ventricular arrhythmias during the mean follow up period of 15 months. Although each increase in stimulation current caused a decrease in measured ventricular refractoriness, this resulted in only four arrhythmias. Only one arrhythmia was induced above 5 mA. These results suggest that this simple protocol using two extrastimuli and a single stimulation current of 5 mA will reliably identify most patients who have symptomatic ventricular arrhythmias.

Adolescent↗

Factors influencing return to work following hospitalization for traumatic injury.

This paper describes the employment experience of 266 individuals one year after traumatic injury severe enough to require hospitalization. Of those working full-time prior to their injury, 56 per cent were employed full-time at one year; an additional 5 per cent were working part-time. Those sustaining a severe head or spinal cord injury were at highest risk of not returning to work (only 43 per cent and 21 per cent, respectively, had returned within the year). Low one-year employment rates (58 per cent) were also noted for individuals whose most severe injury was to one or more extremities. The extent and rate of return to work was examined in relation to selected socioeconomic and personal characteristics. Findings indicate that after controlling for type and severity of injury, personal income, and educational level of the injured person, as well as the identification of a strong social network as defined by the presence of one or more confidants, were important correlates of post-injury employment status.

Adolescent↗

The role of coronary artery disease in complications of abdominal aortic aneurysm surgery.

Coronary artery disease (CAD) is a major cause of morbidity and mortality after elective surgical repair of abdominal aortic aneurysm (AAA). The aim of this study was to determine the relationship between the extent of CAD observed in coronary angiograms (more than 50% stenosis) and the frequency of postoperative myocardial ischemic complications in a consecutive series of 84 patients who underwent elective AAA repair. Ninety-four percent of the patients with clinical evidence of CAD had significant disease as observed in coronary angiograms and eight patients had left main CAD. Seventy-two patients underwent AAA repair with a mortality rate of 1.4%; five patients had preliminary myocardial revascularization, and AAA surgery was not recommended for four patients because of severe cardiac disease. Postoperative myocardial ischemic complications occurred in 13.4% of the patients who had undergone surgery--almost exclusively in patients with clinical evidence of CAD. Both myocardial ischemia and preoperative intervention were more frequent in patients with double- or triple-vessel disease than in patients with less extensive disease. Patients with symptoms and with double- or triple-vessel CAD have a high risk of developing myocardial ischemia after AAA surgery. Preliminary myocardial revascularization may be beneficial in this group of patients.

Aged↗

Assessment of hemodynamic significance of isolated stenoses of the left anterior descending coronary artery using thallium-201 myocardial scintigraphy.

This study tests the hypothesis that the results of stress thallium-201 myocardial perfusion scans (TI-201) are related to the mean transstenotic pressure gradient of coronary stenoses independent of the percent luminal diameter narrowing seen at angiography. The 22 study patients (20 men, 2 women, mean age 47 years, range 30 to 62) had no previous myocardial infarction. Each underwent a symptom-limited, erect bicycle TI-201 test off antianginal therapy, shortly before percutaneous transluminal coronary angioplasty for isolated left anterior descending coronary artery stenosis. The percent narrowing, mean gradient at percutaneous transluminal coronary angioplasty and presence of a visually apparent TI-201 defect were independently evaluated and results compared. All 4 patients with 90% or greater diameter narrowing had positive TI-201 responses, and the mean gradient was 72 +/- 11 mm Hg. Among the 18 patients with less than 90% diameter narrowing, the mean gradient was higher (p less than 0.001) in the 11 with a positive TI-201 (63 +/- 15 mm Hg) than in the 7 with a negative TI-201 (33 +/- 20 mm Hg), but their percent narrowing did not differ significantly (72 +/- 14% vs 66 +/- 19%). Multiple regression analysis showed that the presence of a TI-201 defect was a strong (p = 0.003) and percent narrowing (p = 0.048) a weak independent predictor for gradient. When the mean gradient was normalized for the prestenotic pressure, both percent narrowing (p = 0.003) and TI-201 defects (p = 0.006) were significant independent predictors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Localization of exercise-induced myocardial ischemia with single view and biplanar radionuclide ventriculography: validation in single vessel coronary disease.

The ability of single view and biplanar radionuclide ventriculography (RVG) to determine the location of myocardial ischemia during maximal graded supine bicycle exercise was assessed in 50 patients with chest pain, no prior myocardial infarction, and a single coronary stenosis of greater than or equal to 50% luminal diameter narrowing at coronary angiography. A biplane collimator was used so that both right anterior oblique (RAO) gated first-pass and left anterior oblique (LAO) equilibrium RVG could be performed at rest and exercise. Results were compared with those obtained using 4-view 201Tl myocardial scintigraphy in the same patients. Regional wall motion abnormalities (WMA) and 201Tl perfusion defects were detected and assigned to individual coronary vessels by agreement between at least two of three independent observers, who read all studies blinded along with those from control subjects with chest pain but no angiographically significant coronary artery disease. When scintigraphic abnormalities were detected, both biplanar RVG (36/39 = 92%) and 201Tl (25/25 = 100%) were more frequently correct in predicting the stenosed vessel than single view LAO RVG (24/32 = 75%) (P less than 0.05). At RVG only inferior WMA, in the RAO view, predicted right coronary stenosis. Only posterolateral WMA, in the LAO view, predicted left circumflex stenosis. Thus biplanar, but not single view, LAO exercise RVG is a reasonable alternative to exercise 201Tl for localizing exercise-induced ischemic abnormalities to individual coronary stenoses.

Adult↗

Value of combined assessment of global and segmental ventricular contraction with right anterior oblique ECG-gated first-pass and left anterior oblique equilibrium radionuclide ventriculography.

A semi-automated, variable-region-of-interest method of analysis was used to measure both global and segmental left ventricular (LV) and global right ventricular (RV) contraction with ECG-gated first-pass and equilibrium radionuclide ventriculography. Normal values were defined in 20 healthy volunteers, and in 24 symptomatic patients, the results were compared with right anterior oblique (RAO) contrast left ventriculography. The global LV ejection fraction (LVEF) obtained by equilibrium imaging in the left anterior oblique (LAO) projection correlated closely with the results obtained by the gated first-pass method in the RAO projection (r = 0.95) and those obtained with contrast left ventriculography (r = 0.94); furthermore, the interobserver variability was small (r = 0.985). The normal values for LVEF obtained using radionuclide techniques and contrast ventriculography did not differ, but with the equilibrium radionuclide method, the RV ejection fraction (RVEF) values were underestimated in comparison to those obtained by the RAO gated first-pass technique. In five patients with localised inferior segmental akinesis at contrast angiography, the RAO first-pass cine display demonstrated a corresponding wall-motion abnormality in all cases, but LAO equilibrium cine displays did so in only one out of five patients. For segmental quantitation of LV contraction, a computer programme defined the ventricular edge, divided the RAO LV images into five segments and determined both the segmental area contraction (SAC) and the counts-based segmental ejection fraction (SEF). Radionuclide SAC measurements correlated very strongly with SEF measurements (r = 0.94-0.99). Both radionuclide SAC and radionuclide SEF correlated well with contrast angiographic SAC, except in the inferobasal segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The RNA polymerases of Drosophila melanogaster during early development.

The enzymatic basis for the changing rates of RNA synthesis in early Drosophila development has been examined through a description of the multiple forms, relative proportions, and total and specific activities of the RNA polymerases of the Drosophila embryo. Six chromatographically identifiable forms of RNA polymerase are detectable in embryos (Forms Ia, Ib, IIa, IIb, IIIa, IIIb), one of which (Form IIa) appears to be cytoplasmically localized and is present only in unfertilized eggs and pregastrular embryos, while another (Form IIb) appears only at gastrulation and remains throughout the remainder of development. The total and specific activities of the embryonic RNA polymerases are related to the patterns of embryonic RNA synthesis and to the nuclear and cellular events of holometabolous development.

Animals↗

Control of refractory supraventricular arrhythmias after unsuccessful closed-chest His bundle ablation.

Six patients underwent attempted catheter ablation of the His bundle for control of refractory supraventricular tachyarrhythmias. Permanent complete heart block was achieved in only three patients. All six patients have remained asymptomatic without antiarrhythmic medications over a follow-up period of six to 17 months (mean 10 months). There were no complications of the procedure apart from mild elevation of creatine kinase levels in three patients. In this series, resumption of atrioventricular (AV) conduction following attempted His bundle ablation was not associated with recurrence of symptomatic arrhythmias. Preservation of AV conduction may also obviate the need for permanent ventricular pacing.

Adult↗

Validation of the PEG-IgG screening test for soluble immune complexes by longitudinal studies in experimental acute serum sickness.

A wide variety of tests for the detection of circulating immune complexes (IC) has been proposed by different authors, but there is very little to no information concerning the performance of IC screening assays in samples known to contain in vivo-formed IC. The purpose of our investigation was to compare the behavior of a non-specific assay, the PEG-IgG screening test for IC, with an antigen-specific assay in serum samples sequentially obtained from rabbits to which we induced acute serum sickness. Five animals were used in the study; we were able to detect an increase of IC constituted by the heterologous antigen (human serum albumin) and corresponding antibodies in all, and in 4 animals the results of the PEG-IgG assay closely correlated with the results of the antigen-specific assay (rho values between 0.975 and 1.00). The 4 animals in which IC showed a definite peak by both assays developed proteinuria and IC deposits at the glomerular level, while the animal that failed to develop IC detectable by the PEG-IgG test remained normal throughout the study. These results demonstrate the ability of the PEG-IgG test to detect in vivo-formed IC and suggest that the IC detected by this test have pathogenic potential.

Acute Disease↗

Oral beta-adrenergic blockade with metoprolol in chronic severe dilated cardiomyopathy.

A double-blind crossover trial was performed to assess the effect of metoprolol in 10 patients (mean age 55 years) with severe dilated cardiomyopathy. All patients clinically had idiopathic dilated cardiomyopathy; however, at coronary angiography, four had occult coronary disease. All were in New York Heart Association functional class III with a left ventricular ejection fraction less than 35% as assessed by rest radionuclide ventriculography. Studies were performed before treatment, after 4 weeks of metoprolol therapy and after 4 weeks of placebo administration. Erect bicycle sprint exercise was used to determine maximal work load. Hemodynamic variables and radionuclide left ventricular ejection fraction were recorded at rest and during graded supine bicycle exercise. Cardiac medications were unchanged throughout the trial. The mean (+/- standard error of the mean) dose of metoprolol was 130 +/- 13 mg/day. Metoprolol did not change symptoms, chest X-ray findings or exercise tolerance (baseline 700 +/- 73, placebo 690 +/- 85, metoprolol 710 +/- 81 kilopond-meters [kpm]/min). Metoprolol produced a significant decrease in heart rate at rest and during exercise (p less than 0.001). Mean blood pressure and left ventricular filling pressure did not differ significantly in the baseline, placebo and metoprolol studies. There was a slight, but significant (p less than 0.05) decrease in cardiac index with metoprolol compared with placebo and baseline studies. The small, but significant increase in left ventricular ejection fraction from baseline to the metoprolol and placebo studies (p less than 0.001) was considered a result of spontaneous improvement rather than of therapy. No significant differences were found between the patients with and without coronary disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Acute intravenous and sustained oral treatment with the beta1 agonist prenalterol in patients with chronic severe cardiac failure.

Prenalterol, a beta1 agonist, was given in a single blind acute intravenous study to seven patients with cardiac failure (New York Heart Association class II and III). It was then given in a double blind crossover study of sustained oral prenalterol to six of them. As a result of dose titration studies the oral dose of prenalterol given was 100 mg twice a day in all patients. Erect bicycle sprint tests were performed to exercise tolerance before and after treatment had been started. Cardiac function was assessed at rest and during graded supine bicycle exercise by determining haemodynamic indices using a Swan-Ganz catheter and radionuclide left ventricular ejection fractions. In the intravenous study cardiac function was assessed at rest and during exercise after a control infusion of dextrose and after an infusion of 5 mg prenalterol. In the oral crossover study a placebo or prenalterol were given for two periods of two weeks; at the end of each period exercise tolerance was measured and cardiac function assessed at rest and during exercise. Throughout the study period there was no change in symptoms, medication, or exercise tolerance. Intravenous prenalterol significantly improved cardiac function; left ventricular ejection fraction and cardiac index increased and left ventricular filling pressure fell both at rest and during exercise. Sustained oral treatment with prenalterol, however, did not improve resting left ventricular filling pressure or left ventricular ejection fraction at rest or during exercise but did increase heart rate at rest, and mean blood pressure and peripheral vascular resistance at rest and during exercise; in fact, during exercise left ventricular filling pressure was significantly increased while cardiac index and stroke volume index were decreased by prenalterol. Sustained oral treatment with prenalterol did not have the beneficial effects on cardiac function produced by intravenous treatment and in fact had deleterious effect on the measured indices of cardiac function during exercise.

Administration, Oral↗