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Biomedical subjects

J Goodfellow

Publications and source records attributed to J Goodfellow.

At least 37 records · Page 2Linked to original sources
PubMed1999

Endothelial dysfunction in hypopituitary adults with growth hormone deficiency.

OBJECTIVES: Adult hypopituitarism with growth hormone deficiency (GHD) results in reduced exercise capacity, detrimental changes in body composition and lipid profiles and may be associated with an excess cardiovascular mortality. Endothelial dysfunction is an early event in the pathogenesis of atherosclerosis and predisposes to the deposition of unstable atherosclerotic plaques. We have used a noninvasive method to assess endothelial function in the brachial arteries of a group of treated hypopituitary adults with GHD, and a group of healthy age- and sex-matched controls. PATIENTS: Seventeen hypopituitary adults with GHD (13 male, 4 female) aged 26-54 years were studied. Each patient was receiving standard replacement therapy for all other hormonal deficiencies such that all target hormones were maintained in the normal reference range. All observations obtained were compared with those made in age- and sex-matched control subjects. All study subjects had no identifiable risk factors for endothelial dysfunction. MEASUREMENTS: Using an ultrasound vessel wall tracking system, the diameter of the left brachial artery was measured at rest, in response to reactive hyperaemia (endothelium-dependent dilation) and following sublingual glyceryl trinitrate (GTN) (endothelium-independent vasodilatation). We also measured fasting lipids, insulin, plasma glucose, glycated haemoglobin (HbA1c) and IGF-1, and studied the relationship of these parameters to endothelial function. RESULTS: Flow mediated endothelium-dependent dilatation (FMD), expressed as a percentage change from resting base-line diameter, was significantly impaired in the GHD group (3.70 +/- 2.36% vs. 7.30 +/- 2.42%, P < 0.001). In contrast, GTN-mediated dilatation was similar in both groups. There were no differences in total cholesterol, HDL cholesterol, LDL cholesterol or plasma triglyceride between the groups. Both fasting insulin (27.1 +/- 18.1 vs. 15.89 +/- 6.65 mU/l, P < 0.05) and glycated haemoglobin (HbA1c) levels (5.29 +/- 0.43 vs. 4.91 +/- 0.43%, P < 0.05) were significantly higher in the GHD group. FMD in both groups showed an inverse relationship with total cholesterol (r = -0.58, P < 0.05, GHD and r = -0.55, P < 0.05 controls). However, in the GHD subjects, there was a strong inverse relationship between FMD and LDL-cholesterol (r = -0.81, P < 0.0001). No other relationships were noted between FMD and any other metabolic parameters, or characteristics of GHD. CONCLUSIONS: Endothelial dysfunction is present in GH deficient adults prior to the onset of overt atherosclerotic disease. The similar glucose yet elevated fasting insulin levels imply a state of relative insulin insensitivity. The strong inverse correlation between endothelial dysfunction and LDL-cholesterol suggests a possible aetiological role for LDL-cholesterol in the pathogenesis of any excess cardiovascular risk associated with adult hypopituitarism.

Adult↗
PubMed1999

Technician run open access exercise electrocardiography.

OBJECTIVE: To evaluate the safety, efficacy, and feasibility of the technician run open access exercise electrocardiography service at Freeman Hospital. DESIGN: Questionnaire analysis of the responses of the general practitioners of randomly selected patients who used the service. SETTING: A tertiary care cardiac centre, providing an open access service to general practitioners in the community. PATIENTS: 269 patients randomly selected from 552 who underwent open access exercise electrocardiography over a 2.5 year period. OUTCOME MEASURES: Utilisation of service: the reasons for referral, whether the service was optimally used by the general practitioners, and its effect on their management practice; effect on number of cardiology referrals; benefit to the patients; safety, efficacy, and feasibility of a technician run service; general practitioners' assessment of the service. RESULTS: 147 of 178 general practitioners (82.6%) responded to the questionnaire, on 247 of 269 patients (91. 8%). General practitioners used the service for diagnosing ischaemic heart disease in 72.5% of cases, for prognostic purposes in 17.8%, or both in 5.3%. In 197 cases (79.8%), the general practitioners felt that the service had changed the way they managed their patients. The exercise test was positive in 90 patients (36.5%) and identified 38 as at high risk. The service was effective in optimising the cardiology service by reducing referrals by 47%. CONCLUSIONS: The service was used by general practitioners primarily for diagnosing ischaemic heart disease and not so often for prognosis. The utilisation of the service was optimal as assessed by the high positivity rate. The service meets its primary objective of assisting general practitioners in the management of patients with suspected ischaemic heart disease, and may have helped to optimise resources by reducing the number of referrals to cardiologists. It has helped prioritize patient management and may have benefited high risk patients by facilitating rapid identification and referral. It can be run safely and effectively by trained technicians.

Adult↗
PubMed1998

Syndrome X and endothelial dysfunction.

OBJECTIVE: Syndrome X (angina, normal coronary arteriogram and positive exercise test) remains an enigma with unexplained features and apparent conflicts of evidence. The present study addressed whether (i) the Syndrome is characterised by generalised flow-related endothelial dysfunction, (ii) myocardial thallium201 defects reflect myocardial or microvascular dysfunction, (iii) endothelial dysfunction and its consequences can be improved by oral L-arginine. METHODS: Flow-mediated brachial artery dilatation was measured by ultrasonic 'wall-tracking' in 7 Syndrome X patients, further characterised as having thallium201 defects and no known cause of endothelial dysfunction, and a normal control group. Syndrome X patients entered a 4-week randomised double-blind placebo-controlled cross-over trial of oral L-arginine (7 g twice daily), with brachial artery studies, exercise tests and technetium99 tetrafosmin scans. RESULTS: Flow-mediated dilatation was absent in Syndrome X vs. normal. Stress technetium99 tetrafosmin and thallium201 scans showed similar defects. Flow-mediated dilatation, symptom-limited exercise duration and peak oxygen consumption (VO2max) were increased but rate-pressure-product (RPP) and radionuclide defects were unchanged after L-arginine vs. placebo. CONCLUSIONS: The study supports coronary microvascular rather than myocardial dysfunction and shows loss of flow-mediated dilatation in systemic arteries. Oral L-arginine improved flow-mediated dilatation, exercise capacity and VO2max (by ca. 17%) despite unchanged RPP. The findings support generalised endothelial dysfunction. The arginine effects imply NO-mediated improvement of skeletal muscle perfusion suggesting improved homogeneity of microvascular distribution.

Administration, Oral↗
PubMed1998

Endothelial function is impaired in fit young adults of low birth weight.

OBJECTIVE: Non-insulin-dependent diabetes, hypertension and ischaemic heart disease, with insulin resistance, are associated with low birth weight (the 'Small Baby Syndrome'). Common to these adult clinical conditions is endothelial dysfunction. We tested the hypothesis that endothelial dysfunction could precede their development in those of low birth weight. METHODS: Endothelial function was measured by ultrasonic 'wall-tracking' of flow-related brachial artery dilatation in fit 19-20 year old subjects randomly selected (blind to the investigators throughout the study) from low (< 2.5 kg) and normal (3.0-3.8 kg) birth weight subjects in the 1975-7 cohort of the Cardiff Births Survey and with no known cause for endothelial dysfunction. RESULTS: Flow-related dilatation was impaired in low birth weight relative to normal birth weight subjects (median 0.04 mm [1.5%] [n = 22] cf. 0.11 mm [4.1%] [n = 17], p < 0.05; 0.04 mm [1.5%] [n = 15] cf. 0.12 mm [4.4%] [n = 12], p < 0.05 after exclusion of inadvertently included ever-smokers). CONCLUSION: The findings suggest that endothelial dysfunction is a consequence of foetal malnutrition, consistent with contributing to the clinical features of the 'Small Baby Syndrome' in later adult life.

Adult↗
PubMed1998

Clinical evaluation of recombinant factor IX.

The pharmacokinetics, safety, and efficacy of recombinant factor IX (rFIX) have been evaluated in previously treated and untreated patients with hemophilia B. In a study of 56 previously treated patients, there was a total of 1,070 hemorrhages, which required 1,514 infusions of rFIX. Of the 1,070 episodes, 80% resolved after a single rFIX infusion. The majority of the remaining episodes requiring more than 1 infusion were either major or complicated hemorrhages. Eighty-seven percent of the 1,514 infusions were rated by the physicians or patients as providing an excellent or good response. These results are consistent with the efficacy data from other hemophilia product clinical trials. rFIX has also been administered as bolus doses or by continuous infusion in conjunction with 13 surgical procedures. Estimated blood loss during and after surgery was as expected when compared with blood loss for similar procedures in patients without hemophilia, and 97% of the clinical responses during and after surgery were rated by physicians or patients as excellent or good. Pharmacokinetic comparison of rFIX with one plasma-derived product showed a statistically significant lower recovery (28% less) of rFIX. The half-lives between the two products were comparable. Common adverse events associated with rFIX treatment have been comparable to other factor IX products. As expected, there has been no evidence of viral transmission by rFIX.

Drug Evaluation↗
PubMed1997

Antimicrobial susceptibilities of blood culture isolates obtained before and after the introduction of ciprofloxacin.

The in-vitro susceptibilities of 1658 blood culture isolates to ciprofloxacin and 13 other antimicrobial agents were determined, and compared with the results for isolates obtained before and after the availability of ciprofloxacin in 1989. Only six (0.6%) of 995 Enterobacteriaceae were resistant to the fluoroquinolones tested; all of the ciprofloxacin-resistant strains were isolated after 1989 (P = 0.04). No significant increase in ciprofloxacin resistance was found in Pseudomonas aeruginosa or Acinetobacter spp. No resistance to ciprofloxacin was found in 124 Staphylococcus aureus isolates prior to 1989, but five (2.4%) of 208 S. aureus strains recovered after 1989 were ciprofloxacin-resistant (P = 0.16). Rates of resistance to ciprofloxacin and other antimicrobial agents commonly used to treat bacteraemic infections have remained relatively low in this Canadian teaching hospital over the past 16 years.

Acinetobacter↗
PubMed1997

Dynamic obstruction of the external iliac artery in endurance athletes and its relationship to endothelial function: the case of a long distance runner.

There have been recent reports of exercise induced claudication in endurance trained athletes attributed to narrowing of the external iliac artery. Most patients have been competitive cyclists, and intimal hyperplasia has been cited as the cause. The case is reported here of a long distance runner who presented with similar symptoms.

Adult↗
PubMed1996

Cardiovascular syndromes X, endothelial dysfunction and insulin resistance.

Cardiac Syndrome X (microvascular angina) and the more recently described metabolic Syndrome X (an epidemiological association between insulin resistance and atheroma, dyslipidaemia, and hypertension) may have more in common than the chance of their common sobriquet, in view of evidence that microvascular angina too is characterised by insulin resistance and endothelial dysfunction. The implications are discussed.

Endothelium, Vascular↗
PubMed1995

Endothelial control of arterial distensibility is impaired in chronic heart failure.

BACKGROUND: Vascular tone is a determinant of conduit artery distensibility. The aim of this study was to establish whether endothelium-derived relaxing factor (EDRF) influences the distensibility of conduit arteries and whether endothelium-mediated increases in distensibility are impaired in chronic heart failure (CHF). METHODS AND RESULTS: Conduit artery distensibility was measured by two methods in healthy subjects and in nine patients with CHF caused by dilated cardiomyopathy. In the first method, pulse-wave velocity (PWV) was measured in the right common iliac artery at rest and during local infusions of acetylcholine (10(-7) to 10(-5) mol/L) or adenosine (2 x 10(-7) to 2 x 10(-5) mol/L), with correction for systemic effects. Acetylcholine induced concentration-dependent local reductions of PWV in healthy subjects (-5%, -15%, and -26%) but not in CHF patients (3%, 1%, -4%, P < .01), whereas adenosine induced similar reductions of PWV in healthy subjects and CHF patients. In the second method, brachial artery diameter, blood flow, and blood pressure were measured noninvasively by high-resolution ultrasound, continuous-wave Doppler, and photoplethysmography during reactive hyperemia in the hand and after sublingual glyceryl trinitrate (GTN, 400 micrograms). Hyperemic flow, similar in healthy subjects and CHF patients, was associated with increases in diameter and distensibility in healthy subjects (8.8% and 18.4%, respectively) but not in CHF patients (0.3% and -4.5%), whereas GTN induced similar effects in healthy subjects and CHF patients. CONCLUSIONS: These data indicate that conduit artery distensibility is increased by acetylcholine and increased blood flow in healthy subjects but not in CHF patients, whereas the effects of adenosine and GTN on distensibility are preserved in CHF patients. This implies that EDRF-mediated increases in distensibility are impaired in CHF patients, thus adding to cardiac work.

Acetylcholine↗
PubMed1995

Reversal of atropine-resistant atrioventricular block with intravenous aminophylline in the early phase of inferior wall acute myocardial infarction following treatment with streptokinase.

We report three patients with acute inferior myocardial infarction treated with aspirin (150 mg) and streptokinase (1.5 MU over 60 min), who developed atropine-resistant bradyarrhythmias during or immediately following streptokinase. The bradyarrhythmias responded to aminophylline, thus avoiding the need for temporary pacing.

Aged↗
PubMed1995

Comparison of E test and agar dilution for antimicrobial susceptibility testing of Stenotrophomonas (Xanthomonas) maltophilia.

Currently recommended dilution test methods for the determination of antimicrobial susceptibility of Stenotrophomonas (Xanthomonas) maltophilia are labor-intensive and often impractical in many clinical laboratories. We compared the E test with the agar dilution method for susceptibility testing of 176 clinical isolates of S. maltophilia against 16 antimicrobial agents. The MICs obtained by E test correlated well with those determined by the agar dilution method, with an overall agreement of 94%. Very major and major errors occurred infrequently (0.6 to 2.9%) when testing beta-lactam agents, tobramycin, trimethoprim-sulfamethoxazole, and fluoroquinolones. The E test was found to be accurate and easy to perform. For most antimicrobial agents tested against S. maltophilia, the E test is an acceptable alternative susceptibility test method.

Agar↗
PubMed1995

Comparison of short term outcomes of open and laparoscopic cholecystectomy.

OBJECTIVE: To compare the three month outcome of open and laparoscopic cholecystectomy. DESIGN: Prospective assessment of outcome for a series of patients encompassing the introduction of the laparoscopic technique. SETTING: One teaching hospital. PATIENTS: 269 patients admitted for open cholecystectomy between January 1989 and March 1992 and 122 admitted for laparoscopic cholecystectomy between January 1991 and March 1992. MAIN MEASURES: Patients' reported symptoms and self assessed scores with the Nottingham health profile before operation and at three month follow up. Incidence of complications and adverse events after discharge. RESULTS: Similar improvements in symptom rates and health scores were seen regardless of surgical technique. A lower rate of postoperative complications was seen in the patients given laparoscopic surgery (6/95(6%) v 45/235(19%)), and their mean length of stay was lower (4.5 v 9.8 days). Similar results were obtained when the analysis was restricted to a subset of fairly uncomplicated cases (patients aged 60 or less without other illnesses on admission who were not undergoing emergency or urgent surgery), which constituted a larger proportion of the group given laparoscopy (35/95(37%) v 40/235(17%)). Between these two groups no significant difference was seen in the frequency of relevant readmissions to hospital or visits to general practitioners or accident and emergency departments. CONCLUSION: Ideally, a new surgical technique would be evaluated in a randomised trial. In the absence of such a trial, this observational study provides some evidence that the switch from open to laparoscopic cholecystectomy has brought benefits, particularly in terms of reduced length of stay in hospital. A range of clinical and patient derived indicators suggests that these gains have not been associated with a reduction in the quality of the outcome at three months.

Cholecystectomy↗
PubMed1994

Aortic valve disease in patients with Wegener's granulomatosis.

Wegener's granulomatosis usually affects the upper and lower respiratory tract as well as the kidney. Cardiac involvement is rare, although electrocardiographic abnormalities, coronary artery vasculitis, cardiac arrhythmias, and myocardial infarction have been described. We report two cases of aortic valve disease associated with Wegener's granulomatosis that were progressive despite clinical remission of Wegener's disease in both patients. One patient has undergone successful valve replacement and the other is currently awaiting surgery. Aortic valve histopathology showed myxoid degeneration that was most likely due to previously active vasculitis affecting the vessels of the aortic wall and valvular necrosis with subsequent progressive degeneration of the cusps.

Adult↗