Search PubMed⌕ Search

Biomedical subjects

K M Fox

Publications and source records attributed to K M Fox.

At least 91 records · Page 5Linked to original sources
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

Flavoprotein structure and mechanism. 8. Structure-function relations for old yellow enzyme.

The past 5 years have seen tremendous progress in our knowledge of old yellow enzyme (OYE) as a number of OYEs have been cloned and expressed, a high-resolution crystal structure has been determined for one of these, and new substrates have been found that can be turned over by the enzyme. Together these studies do not yet define the physiological role of OYE, but they lead to significant new insights into the enzymatic properties and structure-function relations of OYE.

Amino Acid Sequence↗
PubMed1995

Significant differences between side-mounted and end-mounted intracoronary Doppler flow probes for the measurement of blood flow velocity.

Use of the intracoronary Doppler flow probe is an established method for the assessment of coronary blood flow velocity. The aim of this study was to perform an in vitro comparison of two commonly used Doppler probes, which differ in the location of the piezoelectric crystal (end-mounted vs side-mounted). Blood flow velocity was measured over a wide range of flow rates in a flow simulator using heparinized whole blood. Measurements were made with both Doppler probes assessed in two positions (supported and unsupported) within the tubing. The results were compared with estimated true velocities. Further measurements were made with six side-mounted probes, correcting for the assumed crystal mounting angle and for the angle calculated from magnified images of the individual crystals. Mean velocities for end- and side-mounted probes correlated highly with predicted velocities (all r > or = 0.99), but the side-mounted probes significantly overestimated velocity by > 100%. Estimation of the true crystal mounting angle of the side-mounted probe revealed considerable variability (range 30-42 degrees) and was lower than the recommended angle correction factor of 60 degrees. Velocities corrected for the individual crystal mounting angles agreed more closely with predicted mean velocities. Although both probes are adequate for the assessment of relative changes in flow, the side-mounted probe considerably overestimates mean velocity, which is partly explained by the variable mounting angle of the crystal. The demonstrated limitations of the side-mounted Doppler flow probe in vitro should be considered in undertaking measurement of intracoronary blood flow velocity.

Analysis of Variance↗
PubMed1994

Old yellow enzyme at 2 A resolution: overall structure, ligand binding, and comparison with related flavoproteins.

BACKGROUND: Old yellow enzyme (OYE) was the first flavoenzyme purified, but its function is still unknown. Nevertheless, the NADPH oxidase activity, the flavin mononucleotide environment and the ligand-binding properties of OYE have been extensively studied by biochemical and spectroscopic approaches. Full interpretation of these data requires structural information. RESULTS: The crystal structures of oxidized and reduced OYE at 2 A resolution reveal an alpha/beta-barrel topology clearly related to trimethylamine dehydrogenase. Complexes of OYE with p-hydroxybenzaldehyde, beta-estradiol, and an NADPH analog show all three binding at a common site, stacked on the flavin. The putative NADPH binding mode is novel as it involves primary recognition of the nicotinamide mononucleotide portion. CONCLUSIONS: This work shows that the striking spectral changes seen upon phenol binding are due to close physical association of the flavin and phenolate. It also identifies the structural class of OYE and suggests that if NADPH is its true substrate, then OYE has adopted NADPH dependence during evolution.

Amino Acid Sequence↗
PubMed1994

Chest pain in women: clinical, investigative, and prognostic features.

OBJECTIVE: To characterise clinical, investigative, and prognostic features of women referred with chest pain who subsequently underwent coronary angiography. DESIGN: Analysis of all women with angina referred to one consultant during 1987-91 who subsequently underwent coronary angiography, with follow up to present day. SETTING: Cardiothoracic centre. SUBJECTS: Women with normal coronary arteries; women with coronary artery disease shown on angiography; men with coronary artery disease matched for age; men referred with chest pain during the same period subsequently found to have normal coronary arteries. MAIN OUTCOME MEASURES: Risk factor analysis; results of exercise testing and coronary angiography; intervention; morbidity and mortality. RESULTS: Women comprised 23% (202/886) of patients referred with chest pain who subsequently underwent angiography. 83/202 women had normal coronary angiograms compared with 55/684 men (41% v 8%, P < 0.01). Diabetes mellitus was the only risk factor more frequently encountered in women with coronary artery disease (P = 0.001). The specificity and positive predictive value of exercise testing before angiography were significantly lower in women than men (71% v 93%, P < 0.001 and 76% v 95%, P < 0.001, respectively). Revascularisation procedures were as common in women with coronary artery disease as in men (81 (68%) v 70 (59%)), and there was no difference in event rate during follow up. Many patients with normal coronary arteries, irrespective of sex, had symptoms during follow up (61 (73%) women, 36 (65%) men) and continued to take antianginal drugs (27 (33%) women, 14 (28%) men); 14 (17%) women and six (11%) men required hospital readmission for severe symptoms. CONCLUSIONS: In this series, although women comprised the minority of patients referred with chest pain, a diagnosis of normal coronary arteries was five times more common in women than men. Risk factor analysis and exercise testing were of limited value in predicting coronary artery disease in women. There was no sex bias regarding revascularisation procedures, and outcome was similar. A diagnosis of non-cardiac chest pain in patients with normal coronary arteries was of little benefit to the patient with regard to morbidity.

Angina Pectoris↗
PubMed1994

Effect of acadesine, a new metabolic agent, on exercise-induced myocardial ischemia in chronic stable angina.

Acadesine, the first of a class of adenosine-regulating agents, has been shown to possess antiischemic properties in animal models. The aim of the study was to assess the effect of acadesine on exercise-induced myocardial ischemia in patients with chronic stable angina pectoris. Twelve patients with stable angina entered a five-way, randomized double-blind study comparing the effects of four doses of acadesine with placebo on time to 1 mm ST-segment depression and other parameters of exercise tolerance. At each study period patients underwent baseline exercise testing, followed by drug or placebo infusion after a 60 minute rest period. The exercise test was repeated after 30 minutes infusion, which continued throughout recovery. Time to angina, time to 1 mm ST depression, and total exercise time during the placebo infusion were 301.1 +/- 45.3, 314.8 +/- 50.9, and 399.4 +/- 47.6 seconds. The placebo-adjusted percentage change in time to 1-mm ST segment with acadesine 6, 12, 24, and 48 mg/kg was -0.1 +/- 6.2%, 11.1 +/- 13.8%, 12.9 +/- 8.6%, and -3.2 +/- 6.8%, respectively (p = NS vs. baseline). Time to angina, total exercise time, and recovery time of the ST segment were not consistently altered by acadesine. The lack of effect across all acadesine doses is consistent with animal data from ischemia-reperfusion injury studies, where a clear dose dependency was present with a loss of effect at higher doses. Alternatively, the extent of ischemia induced by treadmill exercise may have been insufficient for the antiischemic activity of acadesine to be evident.

Aged↗
PubMed1994

The interpersonal and psychological functioning of women who experienced childhood physical abuse, incest, and parental alcoholism.

Questionnaires assessing childhood physical abuse (CPA), childhood incest (CI), and parental alcoholism (ACOA) were completed by 253 college women from introductory psychology classes at a large midwestern university. The relationship between these variables and the level of depression, self-esteem and involvement with physically abusive, sexually assaultive, sexually coercive, and chemically dependent partners was assessed. Support was found for an additive model of trauma that predicted a relationship between number of childhood traumas and adult outcomes. Limited support was found for a specificity model of trauma that predicted that specific childhood trauma would be predictive of parallel negative adult outcomes.

Adaptation, Psychological↗
PubMed1994

Correlates of impaired function in older women.

OBJECTIVE: To determine the factors associated with impaired function in older women. DESIGN: Cross-sectional analysis of baseline data collected for a multicenter, prospective study of risk factors for osteoporotic fractures. SETTING: Four clinical centers in Portland, Oregon, Minneapolis, Minnesota, Baltimore, Maryland, and the Monongahela Valley, Pennsylvania. PARTICIPANTS: A total of 9,704 ambulatory, non-black women, aged 65 years and older, recruited from population-based listings. MEASUREMENTS: Independent variables, including demographic and historical information (medical conditions, health habits, and medications) and physiologic measures (anthropometry, blood pressure, mental status, vision, and neuromuscular performance) were obtained from a baseline questionnaire, interview, and examination. Measurement of function was assessed by self-reported ability to perform six physical and instrumental activities of daily living (ADL) and impaired function (dependent variable) was defined as difficulty performing three or more physical and instrumental ADLs. RESULTS: In order of decreasing strength of association, hip fracture, osteoarthritis, parkinsonism, slower walking speed, lower hip abduction force, back pain, greater Quetelet index, osteoporosis, former alcohol use, stroke, never drinking alcohol, lower mental status, use of anxiolytics and/or sleeping medications, inability to hold the tandem position, postural dizziness, cataracts, greater waist to hip ratio, lower physical activity in the past year, greater lifetime cigarette consumption, and lower grip strength were independently associated with impaired function in multivariate analyses. Age, low educational level, diabetes, current heavy alcohol use, postural hypotension, depth perception, and contrast sensitivity were not independent predictors. A combination of neuromuscular performance measures, including decreased muscle strength and impaired balance and gait, appeared to account for the effect of age on disability. CONCLUSION: A combination of many factors, including medical conditions, health habits such as obesity, smoking, alcohol abstinence, and physical inactivity, and direct measures of neuromuscular performance are associated with impaired function in older women.

Activities of Daily Living↗
PubMed1994

Comparison of Doppler derived haemodynamic variables and simultaneous high fidelity pressure measurements in severe pulmonary hypertension.

OBJECTIVE: To assess relations between right ventricular pressure measured with a high fidelity transducer tipped catheter and the characteristics of tricuspid regurgitation recorded with Doppler echocardiography. DESIGN: A prospective non-randomised study of patients with severe pulmonary hypertension referred for consideration of lung transplantation. SETTING: A tertiary referral centre for cardiac and pulmonary disease, with facilities for invasive and non-invasive investigation, and assessment for heart and heart-lung transplantation. PATIENTS: 10 patients with severe pulmonary hypertension being considered for lung transplantation. ENDPOINTS: Peak right ventricular, pulmonary artery, and right atrial pressures; peak positive and negative right ventricular dP/dt; peak Doppler right ventricular-right atrial pressure drop; Doppler derived peak positive and negative right ventricular dP/dt; and time intervals of Q to peak right ventricular pressure and to peak positive and negative right ventricular dP/dt. RESULTS: The mean (SD) pulmonary artery systolic pressure was 109 (29) mm Hg. The peak Doppler right ventricular-right atrial pressure drop underestimated peak right ventricular pressure by 38 (21) mm Hg, and by 21 (18) mm Hg when the Doppler value was added to the measured right atrial pressure (P values < 0.05). This discrepancy was greater for higher pulmonary artery pressures. The timing of peak right ventricular pressure differed, with the Doppler value consistently shorter (mean difference 16 ms, P < 0.05). Values of peak positive and negative right ventricular dP/dt and the time intervals Q-peak positive right ventricular dP/dt and pulmonary closure to the end of the pressure pulse differed between the two techniques in individual patients, but not in a consistent or predictable way. CONCLUSIONS: Doppler echocardiography significantly underestimates the peak right ventricular pressure and the time interval to peak right ventricular pressure in pulmonary hypertension, particularly when severe. These differences may be related to orifice geometry. Digitisation of Doppler records of tricuspid regurgitation provides useful semiquantitative estimates of absolute values and timing of peak positive and negative right ventricular dP/dt. Clinically significant differences may exist, however, and must be considered in individual patients.

Adult↗
PubMed1993

Crystallization of Old Yellow Enzyme illustrates an effective strategy for increasing protein crystal size.

Old Yellow Enzyme (OYE) was the first flavoenzyme discovered, and has been widely used as a model flavoenzyme. Three crystal forms have been grown from natural protease-nicked OYE and one has been grown from intact recombinant OYE. The recombinant OYE crystals are best suited for structure determination and grow from a solution containing polyethylene glycol and MgCl2. They belong to space group P4(3)2(1)2 with unit cell dimensions a = b = 142.88 A, c = 43.01 A and have a single OYE chain per asymmetric unit. In order to optimize the production of large single crystals, we have carried out a systematic study of crystal size versus drop volume. Crystallographic lore holds that the volume of the medium in which the crystals are grown should have a significant effect on the final size of the crystals produced. However, a systematic investigation of the degree to which the volume of the crystallization sample affects the final size of the crystals has not been reported. In order to investigate this phenomenon, drops were set up in both hanging and sandwich geometry at a variety of drop volumes, but otherwise identical crystallization conditions. A 60-fold increase in drop volume produced a 730-fold increase in crystal volume, and a simultaneous increase in the effective diffraction limit of the crystals from near 2.5 A to well beyond 2.0 A resolution. The dramatic crystal volume increase appears to be due both to the increased amount of protein and the slower equilibration rates associated with larger drops. Our results also emphasize that the quality of diffraction data may often be limited by crystal size rather than intrinsic crystal order even in the case of reasonably sized (200 to 400 microns) crystals.

Crystallization↗
PubMed1993

Novel heteronuclear methods of assignment transfer from a diamagnetic to a paramagnetic protein: application to rat cytochrome b5.

15N and 1H resonance assignments for backbone and side-chain resonances of both equilibrium forms of rat ferricytochrome b5 have been obtained, using a combination of novel heteronuclear assignment transfer methods from the known assignments of the diamagnetic protein [Guiles, R. D., Basus, V. J., Kuntz, I. D., & Waskell, L. A. (1992) Biochemistry 31, 11365-11375] and computational methods which depend on an accurate determination of the orientation of the components of the susceptibility tensor. The transfer of amide proton resonance assignments takes advantage of the apparent insensitivity of amide 15N resonances to pseudocontact effects, evident in overlays of 15N-1H heteronuclear correlation spectra. Amide-proton resonance assignments tentatively transferred from the known diamagnetic assignments to the paramagnetic form of the protein were confirmed using conventional assignment strategies employing 600-MHz COSY, HOHAHA, and NOESY spectra of the oxidized protein. As was observed in rat ferrocytochrome b5, more than 40% of all residues exhibited NMR detectable heterogeneity due to the two different orientations of the heme. Complete assignment of both forms enabled accurate determination of the orientation of the susceptibility tensor for both conformations of the heme. The orientation of the z-component of the susceptibility tensors for the two forms are indistinguishable, while the in-plane components appear to differ by about 6 degrees. Differences in the orientation of the in-plane susceptibility components are undoubtedly due dominantly to the relative axial rotation of the heme of between 5 degrees and 10 degrees indicated by the NOESY contacts to the protein observed in the spectra of the ferrocytochrome [Guiles, R. D., Basus, V. J., Kuntz, I. D., & Waskell, L. A. (1992) Biochemistry 31, 11365-11375; Pochapsky, T. C., Sligar, S. G., McLachlan, S. J., & LaMar, G. N. (1990) J. Am. Chem. Soc. 112, 5258-5263].

Amino Acid Sequence↗
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

Reproductive correlates of bone mass in elderly women. Study of Osteoporotic Fractures Research Group.

Results from previous studies of reproductive factors and bone density have been conflicting; some demonstrate a beneficial effect, but others show a detrimental effect on bone density. The present study investigates the association of parity, lactation, and menstruation with radial bone density in 2230 white women, 65 years of age and older. Bone density was assessed by single-photon absorptiometry. Linear multiple regression was utilized to determine if reproductive factors were associated with radial bone density. The number of births, duration of menstrual bleeding, age at menarche, and years menstruating were significant independent predictors of postmenopausal bone density of the radius. A 1.4% increase in distal radius bone density was observed with each additional birth. Women who began menstruation at age 9 had 6.3% higher bone density than women who began at age 16. Women who menstruated for 3 days during each menstrual cycle had 2.8% less distal radius bone density than women who bled for 7 days. Each decade of menstruation was associated with a 2% greater distal radius bone density. No difference in bone density was demonstrated for women who breast-fed and women who did not. Length of the menstrual cycle, amount of menstrual flow, and irregularity of the menstrual cycle were not significantly associated with radial bone mineral density. In conclusion, pregnancy and menstruation are associated with postmenopausal bone density of the radius.

Abortion, Induced↗
PubMed1993

Unstable and stable angina.

Treatment of both stable and unstable angina depends on initially defining the pathophysiological mechanisms. The goal of treatment is to prevent the development of angina pectoris and possibly also to improve the prognosis. beta-blockade is effective in treating effort-related angina, as are calcium antagonists, which are also effective in treating coronary spasm. Combination therapy may be synergistic, but evidence to support this is controversial. In unstable angina the main goal of treatment is the prevention of myocardial infarction and death. While calcium antagonists have not been shown to improve the prognosis, there is more evidence to support the use of beta-blockers, particularly in combination with a calcium antagonist. Aspirin and possibly heparin should be considered as routine treatment.

Adrenergic beta-Antagonists↗
PubMed1993

Lack of rebound during intermittent transdermal treatment with glyceryl trinitrate in patients with stable angina on background beta blocker.

OBJECTIVE: To assess whether intermittent transdermal treatment with glyceryl trinitrate causes clinically significant rebound in patients maintained on beta blockers for stable angina pectoris. DESIGN: Serial treadmill exercise testing in a double blind, randomised, placebo controlled cross over trial. Baseline exercise testing was performed at 0900 and 1100 at visit 1. Transdermal glyceryl trinitrate patches releasing 15 mg/24 h were applied at 2200 the evening before visits 2 and 3, and exercise testing was performed at 0900 the next morning. The patch was removed and replaced with either an identical patch or matching placebo and exercise tests were repeated two hours later. The alternative treatment was given at visit 3. SETTING: Tertiary referral centre. PATIENTS: 14 patients with stable angina pectoris maintained on beta blocker treatment alone. MAIN OUTCOME MEASURES: Time to angina, 1 mm ST segment depression, and total time, together with heart rate, systolic blood pressure, and rate-pressure product. RESULTS: Active treatment improved treadmill performance at 0900 and 1100. Time to angina, time to 1 mm ST segment depression, and total time fell significantly on placebo compared with the 0900 exercise test on active treatment, but were not significantly different to the baseline exercise test either. CONCLUSIONS: Intermittent transdermal treatment with glyceryl trinitrate is not associated with the rebound phenomenon in patients maintained on beta blockers for stable angina pectoris.

Administration, Cutaneous↗
PubMed1993

Clinical trials in silent ischaemia: lessons from TIBET.

The Total Ischaemic Burden European Trial (TIBET) affords the opportunity to investigate the prognostic value of both exercise testing and ambulatory monitoring on and off medical treatment; 682 patients were followed for two years. Patients with < 1 mm ST segment depression on exercise testing have very low risk indeed of an important end point in a two year period, and this effect is partially obscured by the presence of medical treatment. Ambulatory monitoring showed that the presence of silent ischaemia had little prognostic impact in this group of patients.

Aged↗