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Biomedical subjects

J Sparrow

Publications and source records attributed to J Sparrow.

At least 37 records · Page 2Linked to original sources

Social reinforcement of operant behavior in rats: a methodological note.

An apparatus was developed to study social reinforcement in the rat. Four Long-Evans female rats were trained to press a lever via shaping, with the reinforcer being access to a castrated male rat. Responding under a fixed-ratio schedule and in extinction was also observed. Social access was found to be an effective reinforcer. When social reinforcement was compared with food reinforcement under similar conditions of deprivation and reinforcer duration, no significant differences were observed.

Animals↗

Atenolol or nicardipine alone is as efficacious in stable angina as their combination: a double blind randomised trial.

BACKGROUND: Beta blockers and calcium antagonists are widely used in the management of angina pectoris in the belief that the combination is more efficacious than either drug alone. METHODS: This double blind randomised crossover placebo controlled study compares the effects of nicardipine, atenolol and their combination in 30 patients with chronic stable angina. Each treatment period lasted 6 weeks with dose titration after 3 weeks. Symptom limited treadmill exercise testing and radionuclide ventriculography at rest was carried out at the end of each treatment period. RESULTS: Total exercise duration and time to 1-mm ST-segment depression was significantly prolonged by nicardipine and atenolol when compared to placebo, the combination offered no additional benefit. Time to onset of angina was significantly prolonged by nicardipine and the combination but not by atenolol. Indices of left ventricular function were not significantly affected by any treatment other than an increase in left ventricular end diastolic volume on atenolol and the combination. CONCLUSIONS: Nicardipine and atenolol are equally effective in prolonging exercise duration and time to onset of ischemia in patients with chronic stable angina while the combination appeared to offer no additional benefit. Nicardipine prolonged the time to onset of angina significantly; again there was no further improvement with the combination. Neither drug appears to have an important effect on the parameters of diastolic function studied in patients with chronic stable angina.

Adult↗

Long term follow up of severely ill patients who underwent urgent cardiac transplantation.

OBJECTIVE: To assess long term survival (> 5 years) and quality of life in severely ill patients referred for urgent cardiac transplantation. SETTING: Tertiary referral centres: before transplantation at the National Heart Hospital (late 1984 to end 1986); after transplantation at Harefield Hospital. SUBJECTS: Eighteen patients (15 men; three women) who had required intensive support in hospital before cardiac transplantation and were alive at short term follow up. INTERVENTIONS: Intravenous infusions of cardiac drugs (mean 2.2 infusions), intravenous diuretics (17 patients), and many other drugs before transplantation. Intra-aortic balloon counterpulsation (four patients), temporary pacing (two), and resuscitation from cardiac arrest (three). Patients had specialised nursing care on a medical intensive care unit in almost every case. MAIN OUTCOME MEASURES: Long term survival in patients after urgent cardiac transplantation and perceived quality of life. RESULTS: Of 18 patients who were alive at short term follow up (mean (range) 19.4 (10-33) months), 14 were still alive in 1992 (69 (61-83) months). Ten still worked full time, and 11 reported no restrictions in their daily activities. Three of four patients who died in the intervening period survived > 5 years after transplantation. Overall, 17 of 18 patients survived at least 5 years. CONCLUSIONS: In severely ill patients who undergo urgent cardiac transplantation and survive in the short term, long term (5-7 year) survival and quality of life seem good.

Cardiomyopathy, Dilated↗

The lens in diabetes.

This paper reviews the changes which occur in the human lens in diabetes. They include refractive changes and cataract and age-related increases in thickness, curvatures, light scattering, autofluorescence and yellowing. The incidence of cataract is greatly increased over the age of 50 years, slightly more so in women, compared with non-diabetics. Experimental models of sugar cataract provide some evidence for the mechanism of the uncommon, but morphologically distinct, juvenile form of human diabetic cataract, where an osmotic mechanism due to sugar alcohol accumulation has been thoroughly studied in diabetic or galactose-fed rats. The discrepancy between the ready accumulation of sugar alcohol in the lens in model systems and the very slow kinetics of aldose reductase (AR) has not been satisfactorily explained and suggests that the mechanism of polyol formation is not yet fully understood in mammalian systems. The activity of AR in the human lens lies mainly in the epithelium and there appears to be a marginal expectation that sufficient sorbitol accumulates in cortical lens fibres to explain the lens swelling and cataract on an osmotic basis. This is even more so in the cataracts of adult diabetics, which resemble those of age-related non-diabetic cataracts in appearance. The very low levels of sorbitol in adult diabetic lenses make an osmotic mechanism for the increased risk of cataract even less likely. Other mechanisms, including glycation and oxidative stress, are discussed. The occurrence of cataract is a predictor for increased mortality in the diabetic.

Adolescent↗

Prognostic significance of transient ST segment changes after coronary artery bypass surgery: a long-term (4-10 year) follow up study.

OBJECTIVE: To assess the long-term (four to 10 years) prognostic significance of transient ST segment changes on ambulatory ST segment monitoring after coronary artery bypass grafting (CABG). PATIENTS AND METHODS: 76 patients (67 men, nine women) underwent CABG between 1982 and 1984 (n = 31) and between 1987 and 1988 (n = 45) and at a mean age of 57. All underwent 48 hours of ambulatory ST segment monitoring at a mean of 19 weeks after surgery. The results were available for assessment. All general practitioners were contacted and patients' notes reviewed. Patients were contacted by telephone. Details were recorded of intervening events (acute myocardial infarction, unstable angina, need for further revascularisation, and deaths). Event free survival curves were produced for those with and without transient ST segment changes during routine postoperative ambulatory ST segment monitoring. RESULTS: During 3213 hours of monitoring after CABG, 21 (27.6%) of 76 patients had transient ST segment changes, of which 70% were silent. Over a mean 70 month follow up period, patients with such ischaemic changes were no more likely to have either an objective (myocardial infarction or cardiac death) or subjective (unstable angina or another revascularisation) event than those patients without ischaemic changes. This finding was the same in patients operated on between 1987 and 1988 and between 1982 and 1984. CONCLUSIONS: Although ambulatory ST segment monitoring is becoming increasingly popular in some countries as a routine investigation for ischaemia in various coronary subgroups, the findings of such an investigation, when performed after CABG, do not help to identify a subgroup more likely to have an adverse outcome during up to 10 years of follow up. There seems to be no reason to perform this investigation after surgery, and particularly to refer patients for reinvestigation because of the detection of predominantly silent ST segment changes of uncertain relevance.

Adult↗

Effects of dual-chamber pacing with short atrioventricular delay in dilated cardiomyopathy.

Mitral or tricuspid regurgitation of long duration may so shorten the ventricular filling time in dilated cardiomyopathy that stroke volume is limited. We assessed the effects of changing the atrioventricular interval during temporary or permanent dual-chamber DDD pacing in twelve dilated cardiomyopathy patients with short ventricular filling times due to regurgitation. We measured ventricular filling time and cardiac output with doppler echocardiography and exercise capacity on a treadmill, at baseline and with the best atrioventricular delay during pacing. The durations of both mitral and tricuspid regurgitation were significantly shorter at the shorter atrioventricular interval (mean reductions 85 [95% CI 60-110] ms and 110 [75-150] ms, respectively; p < 0.001 for both). There were consequent increases in left-ventricular and right-ventricular filling times (65 [35-95] ms and 90 [60-120] ms, p < 0.001). For each 50 ms reduction in atrioventricular delay, left-ventricular filling time increased by 35 ms in six subjects with presystolic mitral regurgitation and right-ventricular filling time by 30 ms in nine subjects with presystolic tricuspid regurgitation. At the short atrioventricular interval, cardiac output was greater than baseline (by 1.1 [0.8-1.4] l/min, p < 0.01) and there were rises in exercise duration (104 [45-165] s, p < 0.05) and maximum oxygen consumption (2.1 [1.5-2.7] ml kg-1 min-1, p < 0.05). There was a decrease in the Likert visual analogue score of breathlessness at peak exercise (8.6 [SD 2.1] vs 4.9 [3.1], p < 0.01). Although from a small sample, these findings suggest that DDD pacing with a short atrioventricular delay may have therapeutic potential in patients with dilated cardiomyopathy, even in the absence of conventional indications for pacemaker implantation.

Aged↗

Effects of coronary artery bypass surgery and angioplasty on the total ischemic burden: a study of exercise testing and ambulatory ST segment monitoring.

To assess the effects of standard therapeutic interventions on the total ischemic burden, 86 patients with stable angina underwent 48 hours of ambulatory ST segment monitoring and treadmill exercise testing before and at a mean of 10 weeks after coronary artery bypass surgery (CABG) (group 1, N = 46) or percutaneous transluminal coronary angioplasty (PTCA) (group 2, N = 40). There were 72 male and 14 female patients with a mean age of 56.4 years. All patients had documented coronary artery disease (24, single-vessel; 28, two-vessel; 34, three-vessel disease). Both groups were characteristically similar apart from more severe coronary artery disease (p less than 0.001) and more previous myocardial infarctions (p less than 0.05) in group 1. Groups with CABG and PTCA had significant prolongation of exercise time after intervention (group 1: 7.6 to 9.8 minutes, p less than 0.0001; group 2: 8.1 to 10.0 minutes, p less than 0.001), and both interventions led to a significant reduction in ischemic responses (group 1: 33 to 4, p less than 0.001; group 2: 20 to 13, p less than 0.05) to exercise. During a total of 7643 hours of ST segment monitoring, 253 episodes of ischemia were recorded in 3768 hours before and 44 ischemic episodes in 3875 hours after intervention (group 1, 113 episodes in 24 patients and 21 episodes in 10 patients; group 2, 140 episodes in 13 patients and 23 episodes in six patients). Both interventions reduced the mean frequency of ischemia per 24 hours (group 1: 1.24 to 0.22 episodes per 24 hours; p less than 0.01; group 2: 1.9 to 0.3 episodes per 24 hours; p less than 0.05). Almost 28% (N = 24) of resting electrocardiographic findings were altered as a result of intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

Predictors of prognosis in severe chronic heart failure.

A total of 127 patients with chronic heart failure referred to our exercise laboratory were studied retrospectively to identify parameters predictive of prognosis. Patients were followed for a mean of 14.6 months. The group as a whole had severe ventricular dysfunction with a median ejection fraction of 17% and a median peak rate of oxygen consumption of 13.7 ml/kg/min. During the follow-up period 23 patients (18%) died and 18 (14%) underwent cardiac transplantation. The effect of the following variables on outcome (death or transplantation) were examined: age, cause of heart failure, cardiothoracic ratio on chest radiography, left ventricular end-systolic dimension on echocardiography, left ventricular ejection fraction on radionuclide ventriculography, mean dose of diuretic, plasma sodium and urea concentrations, and peak oxygen consumption during exercise. Although all variables except cause of heart failure affected outcome on univariate analysis, multivariate analysis identified three variables that were statistically significant and independent predictors of outcome. In order of importance these were plasma sodium level, left ventricular ejection fraction and peak oxygen consumption. Even in this group of patients with severe heart failure, these variables were predictive of outcome.

Exercise Test↗

Iris neovascularization in proliferative vitreoretinopathy.

PURPOSE: The purpose of this study is to report on the prevalence, incidence, and associated risk factors of iris neovascularization in nondiabetic patients undergoing vitrectomy for retinal detachment complicated by proliferative vitreoretinopathy (PVR). METHODS: The authors conducted a retrospective review of 141 consecutive non-diabetic patients undergoing vitrectomy for recurrent retinal detachment resulting from PVR. Univariate and multivariate analyses were performed on all patients to determine which preoperative, intraoperative, and postoperative factors were associated with the development of postoperative iris neovascularization. RESULTS: Twenty-seven of the 141 (19%) patients were noted with preoperative and/or postoperative iris neovascularization. Four of eight patients presenting with preoperative iris neovascularization had complete regression after successful reattachment of the retina. Results of analysis of the remaining 133 patients without iris neovascularization preoperatively showed residual retinal detachment as the most significant risk factor for postoperative iris neovascularization. In the absence of panretinal photocoagulation, none of the 27 patients developed neovascular glaucoma. CONCLUSIONS: The development of iris neovascularization preoperatively or post-operatively is not necessarily a predictor of a poor anatomic and/or visual result. Iris neovascularization in PVR rarely if ever progresses to neovascular glaucoma. Panretinal photocoagulation is not indicated in these patients. Retinal reattachment is the most important factor in the prevention and/or resolution of postoperative iris neovascularization. The development of iris neovascularization in PVR appears to be a multifactorial process requiring multiple variables acting in concert.

Adolescent↗

Contrast sensitivity and glare in cataract using the Pelli-Robson chart.

There is a need for a convenient, clinically applicable test of glare disability which can be used in the preoperative evaluation of patients with cataract. In this study, contrast sensitivity (using the Pelli-Robson letter chart), near vision, and visual acuity were compared, with and without the introduction of a glare source in 70 patients with cataract, 15 with intraocular lenses, and 19 controls. A disposable pen torch was shone at the pupillary margin to induce glare. Contrast sensitivity demonstrated the most marked reduction during glare testing. Cortical cataracts were most affected followed by posterior subcapsular opacities. The glare disability was significantly less in pseudophakic patients and was absent from patients with non-cataractous phakic eyes. Glare testing with a disposable pen torch and a Pelli-Robson contrast sensitivity letter chart provides a rapid test of glare disability which can be easily incorporated into the clinical appraisal of patients with cataract.

Aged↗

Value of ambulatory ST segment monitoring in patients with chronic stable angina: does measurement of the "total ischaemic burden" assist with management?

OBJECTIVE: To assess the prognostic significance of transient ischaemic episodes during daily activities in patients with stable angina. PATIENTS AND METHODS: 172 patients with stable angina attending the cardiac outpatients departments of Hillingdon Hospital (n = 155) and the National Heart Hospital (n = 17) were prospectively studied by exercise testing and 48 hours of ambulatory ST segment monitoring, and followed for prognostic purposes for up to 39 months (mean 24.5 months). Patient inclusion depended on a clinical diagnosis of stable coronary artery disease which necessitated outpatient review (and antianginal treatment in 94% of patients). It was not dependent on objective evidence of reversible ischaemia. Events recorded during the follow up period included death, non-fatal myocardial infarction, unstable angina, and the requirement for revascularisation. RESULTS: 72 patients (42%) had transient ischaemic episodes during daily activities, and 104 patients (60.5%) had an ischaemic response to exercise. 63 patients (36%) had evidence of ischaemia on both investigations; with 59 (34%) having no documented ischaemia on either investigation. There were 27 patient events (15.7%) recorded over a mean 24.5 month follow up, including five deaths (2.9%) (three cardiac related (1.7%)), six non-fatal myocardial infarctions (3.5%), six admissions with unstable angina (3.5%), and 10 revascularisation procedures (5.8%). Of the nine "hard" or objective end points (cardiac death and non-fatal myocardial infarction), only two had evidence of transient ischaemia on ambulatory ST segment monitoring at initial investigation, with 10 of the 25 patients (38.5%) with any cardiac event having such episodes. CONCLUSIONS: The outcome in patients with chronic stable angina receiving standard medical treatment was good over a mean two year follow up period. For the purpose of assessing prognosis over this time scale, there was no advantage to performing ambulatory ST segment monitoring in such patients.

Adult↗

Evaluation of two infrared autorefractors in pseudophakia.

We investigated the viability of using an objective infrared autorefractor to identify high corneal astigmatism (> 3.00 D) in a pseudophakic population. The eyes of 91 patients, who had recently undergone cataract extraction and intraocular lens implanation, were refracted manually and using two infrared autorefractors, a Canon RK-1 and a Nikon NR-2000. Autorefractor measurements were repeated to provide estimates of reliability for each instrument. LogMAR visual acuities were also recorded with both the manual and autorefractor corrections. Approximately 75% of repeat autorefractor measurements were within 0.50 D of the initial readings, and about 75% of measurements were within 1.00 D of the manual refractions. Visual acuities with manual corrections were, on average, one line better than with autorefractor corrections. By validating the autorefractors against manual refraction, the efficiency of the autorefractors for detecting astigmatism > 3.00 D was calculated. Setting the cut-off criterion to ensure high sensitivity (95%), so that almost all patients with > 3.00 D were detected, resulted in both instruments having a poor specificity of about 40%.

Adult↗

Functional and ultrastructural effects of a missense mutation in the indirect flight muscle-specific actin gene of Drosophila melanogaster.

A single-site mutation of the flight-muscle-specific actin gene of Drosophila melanogaster causes a substitution of glutamic acid 93 by lysine in all the actin encoded in the indirect flight muscle (IFM). In these Act88FE93K mutants, myofibrillar bundles of thick and thin filaments are present but lack Z-discs and all sarcomeric repeats. Dense filament bundles, which are probably aberrant Z-discs, are seen in myofibrils of pupal flies, but early in adult life these move to the periphery of the fibrils and are not seen in skinned adult fibres. Consistent with this observation, alpha-actinin and other high molecular weight proteins, possibly associated with Z-discs, are not detected on SDS/polyacrylamide gels or Western blots of skinned adult IFM. The mutation lies at the beginning of a loop in the small domain of actin, near the myosin binding region. However, that the mutant actin binds myosin heads is shown by (1) rigor crossbridges in electron micrographs, (2) the appropriate rise in stiffness when ATP is withdrawn in mechanical experiments, and (3) equal protection against tryptic digestion provided by rigor binding between actin and myosin in both wild-type and mutant fibres. Reversal of rigor chevron angle along some thin filaments reflects reversal of thin-filament polarity due to lattice disorder. The absence of Z-discs, alpha-actinin and two high molecular weight proteins, and binding studies by others, suggest that the substitution at residue 93 affects the binding of the mutant actin to a protein, possibly alpha-actinin, which is necessary for Z-disc assembly or maintenance.

Actins↗

Double-blind randomised placebo-controlled dose-efficacy study of sustained release verapamil in chronic stable angina.

The efficacy and tolerability of sustained release verapamil (Securon SR) was investigated in twenty-four patients with chronic stable angina. Patients entered four randomised, double-blind treatment periods, each lasting one week of verapamil-SR 240 mg once daily, 360 mg once daily, 240 mg twice daily, and matching placebo. Four patients were withdrawn, but in one instance this was attributable to side effects from verapamil. Among the remaining twenty patients, mean frequency of angina fell from 4.25 episodes during the last five days of placebo to 2.35, 2.6 and 1.3 episodes during respective active treatments (all P less than 0.001). Compared with placebo the median percentage increase in time to 1 mV ST depression during treadmill exercise (12 hours post dose) was significant only with the regimen of verapamil-SR 240 mg given twice daily at +11% (P = 0.04). Total duration of exercise was also significantly longer and maximum ST depression significantly less only with the twice daily treatment (704 + 186 sec vs 648 + 203 sec; P = 0.03, and 1.75 + 0.73 mm vs 2.15 +/- 0.62 mm; P = 0.02). Side effects, predominantly constipation, breathlessness, and swollen ankles, occurred most frequently with verapamil-SR 360 mg. Thus, sustained release verapamil is well tolerated and effective in the treatment of angina. A regimen of 240 mg given twice daily emerges as superior to once daily treatments for 24-hour prophylaxis of angina.

Aged↗

Protein engineering and the study of muscle contraction in Drosophila flight muscles.

We describe an experimental approach to the use of genetics to study muscle contraction in Drosophila melanogaster. Mutations induced by in vitro mutagenesis are inserted into the genome of flies using P-element mediated transformation, permitting the effects of the mutant genes to be studied in vivo in the indirect flight muscles (IFMs). Details of how mechanical experiments can be performed on skinned IFMs, despite their small size, are provided. The effects of two in vitro actin mutations, G368E and E316K, are described. The problems of performing biochemical and biophysical experiments on the IFMs and their myofibrillar proteins are described, together with indications as to how these may be overcome.

Actins↗

Lens opacity and mortality in diabetes.

A population-based cohort of 294 diabetic patients were examined for the presence of lens opacities and followed up for a median of 6 years. Only two patients were lost to follow-up but there were 73 deaths, 49 in the 108 patients with opacities and 24 in the 184 patients without (odds ratio 2.4, 95% Cl 1.5-3.9). Lens opacities were a powerful predictor of death and the effect was independent of other prognostic factors. The presence of cataract identifies a high risk sub-group of elderly diabetic patients.

Age Factors↗