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J Sparrow

Publications and source records attributed to J Sparrow.

At least 19 recordsLinked to original sources
PubMed1996

Control of nitric oxide production by endogenous TGF-beta1 and systemic nitric oxide in retinal pigment epithelial cells and peritoneal macrophages.

Both in vivo and in vitro experiments demonstrate that transforming growth factor-beta1 (TGF-beta1) suppresses expression of the inducible form of nitric oxide synthase (iNOS). In this study, we examined the effects of exogenous and endogenous TGF-beta1 on retinal pigment epithelial (RPE) cells and resident peritoneal macrophages ex vivo using cells from TGF-beta1 null (TGF-beta1-/-) mice or age-matched wild-type (TGF-beta1+/+) or heterozygous (TGF-beta1+/-) littermates. RPE cells from both TGF-beta1-/- mice and TGF-beta1+/+ littermates produced NO and were immunocytochemically positive for iNOS protein only following treatment with interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS); however, RPE cells from TGF-beta1-/- mice produced 40% more NO than cells from TGF-beta1+/+ mice. In contrast, resident peritoneal macrophages from both TGF-beta1+/+ and TGF-beta1-/- mice expressed iNOS protein without stimulation and in the absence of detectable production of NO. The expression of iNOS was increased by treatment with IFN-gamma, resulting in detectable levels of NO. Macrophages from TGF-beta1+/+ mice appeared to produce NO in a manner inversely proportional to the serum content of NO2- and NO3- of the mice from which the cells were obtained; no such correlation existed in TGF-beta1+/- or TGF-beta1-/- mice. Treatment of RPE cells or macrophages from both TGF-beta1+/+ and TGF-beta1-/- mice with exogenous TGF-beta1 decreased both iNOS protein and NO production. These findings demonstrate a novel role of endogenous TGF-beta1 in coupling systemic NO production to the production of NO by macrophages, and demonstrate that endogenous and exogenous TGF-beta1 can act differently to suppress NO production.

Animals↗
PubMed1996

Objective assessment of the response to treatment of severe heart failure using a 9-minute walk test on a patient-powered treadmill.

BACKGROUND: No previous studies have demonstrated the changes in exercise capacity that occur during treatment of decompensated severe heart failure. The authors assessed the efficacy and safety of using a patient-powered treadmill to objectively measure exercise capacity and its relationships, if any, to symptom scores and body weight. METHODS AND RESULTS: Changes in time-limited exercise capacity on a patient-powered treadmill were assessed during inpatient treatment of 12 patients with decompensated chronic heart failure (New York Heart Association classes III and IV). Patients performed a 9-minute walk test daily for 7 days and again at the 6-week follow-up examination. They also completed a 24-item symptom score questionnaire. After treatment, there was a rapid, significant increase in total distance walked, with the increase beginning as early as the second day after admission (mean distance walked +/- SEM, 54 +/- 27 m and 174 +/- 54 m on admission and on day 2, respectively, P < .05). Improvement was maintained throughout the period in the hospital and at 6 weeks (P < .001). Patients reported symptomatic improvement, but this did not reach significance until 4 days after admission (P < .05). Weight loss was not significant. Improved exercise capacity correlated with reduced symptoms and weight loss, but preceded these by several days. CONCLUSIONS: In patients with decompensated chronic heart failure, this exercise test provides a safe, practical, inexpensive, and objective assessment of functional capacity, providing certain advantages over other indices of response to therapy, such as symptom scores and weight loss. Improvement of exercise capacity does not occur concurrently with relief of symptoms and weight loss.

Adult↗
PubMed1996

Early continuous ST segment monitoring in unstable angina: prognostic value additional to the clinical characteristics and the admission electrocardiogram.

BACKGROUND AND OBJECTIVE: In unstable angina, clinical characteristics, resting electrocardiography, and early continuous ST segment monitoring have been individually reported to identify subgroups at increased risk of adverse outcome. It is not known, however, whether continuous ST monitoring provides additional prognostic information in such a setting. DESIGN: Observational study of 212 patients with unstable angina without evidence of acute myocardial infarction admitted to district general hospitals, who had participated in a randomised study comparing heparin and aspirin treatment versus aspirin alone. METHODS: Clinical variables and a 12 lead electrocardiogram (ECG) were recorded at admission, and treatment was standardised to include aspirin, atenolol, diltiazem, and intravenous glyceryl trinitrate, in addition to intravenous heparin (randomised treatment). Continuous ST segment monitoring was performed for 48 h and all inhospital adverse events were recorded. RESULTS: The admission ECG was normal in 61 patients (29%), showed ST depression in 59 (28%) (17 > or = 0.1 mV), and T wave changes in a further 69 (33%). The remaining 23 had Q waves (18), right bundle branch block (four), or ST elevation (one). During 8963 h of continuous ST segment monitoring (mean 42.3 h/patient), 132 episodes of transient myocardial ischaemia (104 silent) were recorded in 32 patients (15%). Forty patients (19%) had an adverse event (cardiac deaths (n = 3), non-fatal myocardial infarction (n = 6) and, emergency revascularisation (n = 31)). Both admission ECG ST depression (P = 0.02), and transient ischaemia (P < 0.001) predicted an increased risk of non-fatal myocardial infarction or death, while no patients with a normal ECG died or had a myocardial infarction. Adverse outcome was predicted by admission ECG ST depression (regardless of severity) (odds ratio (OR) 3.41) (P < 0.001), and maintenance beta blocker treatment (OR 2.95) (P < 0.01). A normal ECG predicted a favourable outcome (OR 0.38) (P = 0.04), while T wave or other ECG changes were not predictive of outcome. Transient ischaemia was the strongest predictor of adverse prognosis (OR 4.61) (P < 0.001), retaining independent predictive value in multivariate analysis (OR 2.94) (P = 0.03), as did maintenance beta blocker treatment (OR 2.85) (P = 0.01) and admission ECG ST depression, which showed a trend towards independent predictive value (OR 2.11) (P = 0.076). CONCLUSIONS: Patients with unstable angina and a normal admission ECG have a good prognosis, while ST segment depression predicts an adverse outcome. Transient myocardial ischaemia detected by continuous ST segment monitoring in such patients receiving optimal medical treatment provides prognostic information additional to that gleaned from the clinical characteristics or the admission ECG.

Adrenergic beta-Antagonists↗
PubMed1995

Does the exercise protocol matter when assessing the anti-anginal effects of drug therapy?

Four exercise test protocols (Bruce, Balke, Ellestad and Steep) were compared in 16 patients with proven coronary artery disease in demonstrating the anti-anginal effects of sublingual glyceryl trinitrate in a randomization double-blind trial. Glyceryl trinitrate significantly improved the time, heart rate and rate pressure product to peak exercise, onset of angina and 1 mm ST segment depression in all four protocols (P < 0.05) (except rate pressure product to angina in the Balke protocol). The increase in exercise time was greatest for the Balke protocol at peak exercise (188.1 +/- 187.1) (mean +/- SD in s), at onset of angina (251.9 +/- 247.1) and at 1 mm ST depression (233.6 +/- 243.8), followed by the Steep and Bruce protocols, and was lowest for the Ellestad protocol 41.9 +/- 42.4, 96.5 +/- 65.8, 82.6 +/- 74.0, respectively. Increase in time to peak exercise with glyceryl trinitrate was significantly greater for the Balke protocol in comparison with the other three protocols and for the Bruce and Steep protocols when compared to the Ellestad protocol. Time to 1 mm ST depression with treatment was significantly greater on the Balke and Bruce protocols than the Ellestad protocol, and to onset of angina for the Balke compared to other three protocols. There were no significant differences between the Bruce and Steep protocols for any of the endpoints. The magnitude of treatment effect in the different protocols was accompanied by correspondingly greater inter-patient variability such that no protocol was more, or less, sensitive than another in detecting treatment effect. Changes in heart rate and rate pressure product with treatment were generally similar between the different protocols. In conclusion, a protocol with small and frequent increments (Balke), although able to show greater increase in exercise duration with glyceryl trinitrate than more aggressive protocols, is no more sensitive at detecting treatment effect.

Adult↗
PubMed1995

Actin.

Explore the source record for details and available documents.

Actins↗
PubMed1994

Fluorescence resonance energy transfer within the regulatory light chain of myosin.

Rabbit skeletal muscle myosin regulatory light chain-2 (LC2) contains two reactive cysteine residues, Cys125 and Cys154, and one tryptophan at position 137. Using wild-type rabbit LC2 or its genetically engineered mutant with Cys125-->Arg (C125R), these residues can be selectively modified with fluorescent or chromophoric probes for spectroscopic studies. We have bound suitable donor/acceptor probe pairs to the two cysteine residues and Trp137 in LC2 or C125R, and measured the distance in solution between the probes by fluorescence resonance energy transfer spectroscopy. C125R was made to facilitate specific labelling of the less reactive Cys154, thus allowing the distance between Cys154 and Trp137 to be measured. Our measurements show that these residues are in close proximity to each other, the distance between them ranging from 1.7 nm (between Cys125 and Trp137) to 2.7 nm (Cys125 and Cys154). These results suggest that Cys125, Trp137 and Cys154, spanning up to 29 residues in the sequence of LC2, are spatially close, consistent with these residues residing within a C-terminal globular domain. The distances we obtained are in agreement with previous crosslinking studies [Huber, P. A., Brunner, U.T. & Schaub, M. C. (1989) Biochemistry 28, 9116-9123; Saraswat, L. & Lowey, S. (1991) J. Biol. Chem. 266, 19777-19785] and structure predictions of LC2. LC2 is located at the head-rod junction of the myosin crossbridge, and provides the primary regulatory mechanism in molluscan and smooth muscle. In skeletal muscle, its functional role is unclear, although it has been implicated in modulating actomyosin interaction [Metzger, J. M. & Moss, R. L. (1992) Biophys. J. 63, 460-468]. The incorporation of spectroscopic probes onto the light chains of myosin in solution or in fibres has become a valuable tool for evaluating the dynamic properties of the crossbridge during force generation.

Amino Acid Sequence↗
PubMed1994

Assessment of functional capacity in chronic heart failure: time-limited exercise on a self-powered treadmill.

OBJECTIVES: To assess the efficacy of a 9-minute walking test on a self-powered treadmill in a group of patients with various degrees of heart failure, to investigate the reproducibility of the technique, and to establish the safety of the technique. PATIENTS AND METHODS: 24 controls and 37 patients with various grades of heart failure were studied. Peak oxygen consumption was measured in patients and controls. The distance walked in 9 minutes on a self-powered treadmill was measured in all groups and the test was repeated to assess reproducibility. RESULTS: The distance walked in 9 minutes correlated with peak oxygen consumption in patients, controls, and both groups combined. There was a significant difference in the distance walked by controls and patients and in the distance walked by patients with severe rather than with mild or moderate heart failure. There was no significant difference between the results of successive 9-minute walking tests in any group. No serious adverse reaction was seen in any patient during or after the test. CONCLUSION: The 9-minute walking test on a self-powered treadmill is a sensitive, reproducible, safe, and inexpensive method of assessing functional capacity in patients with all grades of heart failure.

Adult↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗