Search PubMed⌕ Search

Biomedical subjects

K M Fox

Publications and source records attributed to K M Fox.

At least 37 records · Page 2Linked to original sources
PubMed2000

A national Survey of Acute Myocardial Infarction and Ischaemia (SAMII) in the U.K.: characteristics, management and in-hospital outcome in women compared to men in patients under 70 years.

AIMS: To assess the clinical characteristics, management and outcome of women compared to men with acute myocardial infarction or ischaemia. DESIGN: A prospective clinical survey was made in a random sample of 94 District General Hospitals in the U.K. 1064 patients, <70 years of age, comprising six consecutive females and six consecutive males from each hospital, diagnosed on admission as acute coronary syndromes (myocardial infarction or myocardial ischaemia) were studied. Outcome measures included: admission and final diagnosis, time to delivery of care, inpatient management, complications and clinical outcome. RESULTS: Five hundred and three women and 561 men were admitted with a diagnosis of acute myocardial infarction or myocardial ischaemia. Women were older, waited longer between seeking and receiving advice, and much less likely to have infarction than men. After adjustment for age, diagnosis and past medical history there were no gender differences in initial and subsequent hospital management, in complications (recurrent ischaemia, arrhythmias, temporary pacing, heart failure), any routine procedure or outcome. Of all patients, 3.4% died in a District General Hospital, 12.2% were transferred to Specialist Cardiac Centres and 84.4% discharged home. Prophylactic medication on discharge was similar for men and women. CONCLUSION: After adjustment for age, diagnosis and past medical history, although women waited longer between seeking and receiving medical advice, in hospital their assessment, management, complications, outcome and follow-up arrangements were the same as for men. In hospital, management and outcomes were mainly influenced by age, diagnosis (infarction or ischaemia), a past history of coronary disease, but not by gender. This large, nationally representative, survey has found no evidence of important gender difference in the hospital management of acute ischaemic syndromes.

Adult↗
PubMed2000

Change in muscle mass and muscle strength after a hip fracture: relationship to mobility recovery.

BACKGROUND: Hip fracture in elderly persons has a serious impact on long-term physical function. This study determines the change in muscle strength and muscle mass after a hip fracture, and the associations between these changes and mobility recovery. METHODS: Ninety community-dwelling women aged 65 years and older who had recently experienced a fracture of the proximal femur were included in the study. At 2 to 10 days after hospital admission, the women's grip strength, ankle dorsiflexion strength, and regional muscle mass (by dual-energy x-ray absorptiometry) were measured, and the prefracture level of independence for five mobility function items was assessed. All measurements were repeated at 12 months. RESULTS: At follow-up, only 17.8% of the women had returned to their prefracture level of mobility function for all five items. Mobility function recovery was not related to change in skeletal muscle mass of the nonfractured leg or the arms. However, women who lost grip strength (mean loss of -28.7%, SD = 16.9%), or who lost ankle strength of the nonfractured leg (mean loss of -21.5%, SD = 14.7%), had a worse mobility recovery compared with those who gained strength (p = .04 and p = .09, respectively). In addition, chronic disease (p = .03), days hospitalized (p = .04), and self-reported hip pain (p = .07) were independent predictors of decline in mobility function. CONCLUSIONS: The results suggest that loss of muscle strength, but not loss of muscle mass, is an independent predictor of poorer mobility recovery 12 months after a hip fracture. When confirmed by other studies, these findings may have implications for rehabilitation strategies after a hip fracture.

Aged↗
PubMed2000

Recovery from hip fracture in eight areas of function.

BACKGROUND: This report describes changes in eight areas of functioning after a hip fracture, identifies the point at which maximal levels of recovery are reached in each area, and evaluates the sequence of recuperation across multiple functional domains. METHODS. Community-residing hip fracture patients (n = 674) admitted to eight hospitals in Baltimore, Maryland, 1990-1991 were followed prospectively for 2 years from the time of hospitalization. Eight areas of function (i.e., upper and lower extremity physical and instrumental activities of daily living; gait and balance; social, cognitive, and affective function) were measured by personal interview and direct observation during hospitalization at 2, 6, 12, 18, and 24 months. Levels of recovery are described in each area, and time to reach maximal recovery was estimated using Generalized Estimating Equations and longitudinal data. RESULTS: Most areas of functioning showed progressive lessening of dependence over the first postfracture year, with different levels of recovery and time to maximum levels observed for each area. New dependency in physical and instrumental tasks for those not requiring equipment or human assistance prefracture ranged from as low as 20.3% for putting on pants to as high as 89.9% for climbing five stairs. Recuperation times were specific to area of function, ranging from approximately 4 months for depressive symptoms (3.9 months), upper extremity function (4.3 months), and cognition (4.4 months) to almost a year for lower extremity function (11.2 months). CONCLUSIONS: Functional disability following hip fracture is significant, patterns of recovery differ by area of function, and there appears to be an orderly sequence by which areas of function reach their maximal levels.

Activities of Daily Living↗
PubMed2000

Inclusion of older women in randomized clinical trials: factors associated with taking study medication in the fracture intervention trial.

OBJECTIVES: The purpose of this study is to describe the early study medication discontinuation (SMD) experience during the first year of follow-up in a randomized clinical trial in older women and to determine the associations between various baseline characteristics and risk of SMD. DESIGH, SETTING, AND PARTICIPANTS: The authors studied 6,459 postmenopausal women aged 55 to 80 from 11 clinical settings during their first year of participation in the Fracture Intervention Trial (FIT). This trial was designed to test the efficacy of alendronate (Fosamax) on fracture prevention among women with low bone mass. RESULTS: Study medication discontinuation was greatest in the first month post-randomization (2.2%) and declined thereafter. Cumulative rates of study medication discontinuation were 4.8% (n = 311) at 3 months and 11.1% (n = 717) at 12 months. SMD was not associated with age, marital status, alcohol consumption, regular exercise, past estrogen replacement therapy use, bone mineral density, or personal or maternal fracture history. After adjusting for covariates and markers of comorbidity, the strongest predictor of SMD was fair-to-poor self-rated health (relative risk (RR) 2.10; 95% confidence interval (CI) 1.47, 2.99). Having four or more depressive symptoms was also a significant predictor and had a risk associated with SMD (RR vs none 1.34; 95% CI 1.05, 1.71) similar to that seen for individuals with good self-rated health (RR 1.49; 95% CI 1.16, 1.91). CONCLUSIONS: Results from this cohort emphasize that clinical trials in older women with multiple concomitant conditions can achieve high levels of adherence. Thought should be given to measuring self-rated health and depressive symptoms before randomization to help identify individuals to be targeted for special assistance programs that focus on encouraging adherence.

Aged↗
PubMed2000

Antianginal and anti-ischaemic efficacy of tedisamil, a potassium channel blocker.

OBJECTIVE: To determine the efficacy and safety of the potassium channel blocker tedisamil versus placebo in the treatment of patients with stable angina. DESIGN: Prospective, double blind, placebo controlled study. 203 patients first completed a seven day placebo run in. They were then randomised to receive 50 mg, 100 mg or 150 mg tedisamil twice daily, or placebo. Treadmill exercise testing was carried out at baseline and after 14 days of double blind treatment. MAIN OUTCOME MEASURES: Primary efficacy parameters were an increase in total exercise duration and a reduction of the sum of ST segment depression using six ECG leads at maximum workload at trough (12 hours after last medication). Secondary aims included increase in exercise time to onset of 0.1 mV ST segment depression, increase in exercise time to onset of any anginal pain, and reduction in ST segment depression in any of the six specified leads at maximum workload. These were all at trough. The same parameters were also assessed at peak concentrations (two hours after administration). Overall attacks of angina and the use of short acting nitrates were assessed from patient diaries. RESULTS: Tedisamil led to a dose dependent prolongation of exercise duration (significant at all concentrations), an effect that was greater at peak than at trough. Treatment also led to a significant dose dependent reduction in the sum of ST segment depression at both trough and peak concentrations. Tedisamil also decreased (in a dose dependent way) the frequency of anginal attacks and the consumption of short acting nitrates, an improvement that became significant for all doses in the second treatment week. Adverse events with tedisamil were few. There was a pronounced rise in the incidence of diarrhoea with the 150 mg twice daily regimen. Bradycardic effects and increases in QT interval were dose dependent, but were no more evident at exercise than at rest. CONCLUSIONS: Tedisamil, at doses of 50-100 mg twice daily, was found to be an effective antianginal and anti-ischaemic agent. At doses above 100 mg twice daily its main side effect, diarrhoea, becomes pronounced; therefore the 50-100 mg twice daily regimen appears to be appropriate.

Aged↗
PubMed2000

Understanding the bariatric surgical patient: a demographic, lifestyle and psychological profile.

BACKGROUND: Although improved recently, the public is generally unaware of current scientific knowledge in bariatrics and the availability of surgery for massive obesity. As bariatric professionals we recognize the need for this education. Understanding the patientís socio-economic, demographic and psychological make-up and lifestyle preferences is a crucial element. METHODS: 1200 obesity surgery patients were sent questionnaires to assess a variety of personal parameters. 395 (33%) were returned and tabulated. A literature review of the obese person's psychological profile was also summarized. RESULTS: An overview of these patients' height, weight, age, ethnicity, marital, educational and employment status, number of children, residential population, and income are presented. Their television and movie viewing, radio listening, social event participation, print media and Internet habits are described. The psychological profile is outlined so that the whole person is understood. CONCLUSION: Understanding the obese person is primary to effectively educating the public. There are many appropriate and much-needed applications of this information to the public, the obese population, other health-care providers, legislators, and insurers.

Adult↗
PubMed1999

The flavin environment in old yellow enzyme. An evaluation of insights from spectroscopic and artificial flavin studies.

Spectroscopic and chemical modification studies of modified flavins bound to old yellow enzyme have led to predictions about the flavin environment of this enzyme. These studies analyzed solvent accessibility and hydrogen bonding patterns of particular flavin atoms, in addition to suggesting amino acid residues that are in close proximity to those atoms. Here, these studies are evaluated in the light of the crystal structure of old yellow enzyme to reveal that the spectroscopic and modified flavin results are generally consistent with the crystal structure. This highlights the fact that these are useful methods for studying flavin binding site structure. Although several of the inferred properties of the flavin environment are not consistent with the crystal structure, these discrepancies occurred in cases where an incorrect choice was made from among multiple plausible explanations for an experimental result. We conclude that modified flavin studies are powerful probes of flavin environment; however, it is risky to specify details of interactions, especially because of uncertainties due to induced charge delocalization in the flavin.

Crystallography, X-Ray↗
PubMed1999

Increased binding of fibrinogen to glycoprotein IIIa-proline33 (HPA-1b, PlA2, Zwb) positive platelets in patients with cardiovascular disease.

AIMS: The GPIIb-IIIa complex on the platelet membrane plays an important part in thrombosis as it is the receptor for fibrinogen. The gene for platelet membrane glyco-protein IIIa has multiple alleles one of which, the GPIIIa-Proline33 (HPA-1b, PlA2, Zwb) allele has been reported in some, but not all studies, to be associated with an increased risk of myocardial infarction. We investigated whether the presence of the Pro33 form of GPIIIa on the platelet membrane is associated with increased fibrinogen binding. METHODS AND RESULTS: Blood samples from 70 patients (54 male) with stable angina of whom 22 (18 male) had a history of previous myocardial infarction, were analysed for the GPIIIa-Leu-Pro33 polymorphism at the genomic level, and for whole blood flow cytometric measurement of platelet fibrinogen binding. The GPIIIa-Pro33 form was present in 20 (28.6%) patients (1 homozygous) representing an allele frequency of 0.85 and 0.15 (GPIIIa-Leu33:Pro33). The incidence of myocardial infarction was higher (40.0%) in patients positive for GPIIIa-Pro33 than in those without (32.0%) but this was not significant (P=0.58). Fibrinogen binding to ADP-stimulated platelets was significantly higher in the GPIIIa-Pro33 positive group at all ADP concentrations (<0.0001; two way ANOVA). There was no association between fibrinogen binding and the level of expression of the GPIIb-IIIa complex, platelet volume or platelet count. Fibrinogen binding in response to thrombin stimulation was not different between the groups (P>0.05). CONCLUSIONS: The increased tendency of platelets from patients with the Pro33 form of GPIIIa may predispose patients with this allele to a higher risk of acute thrombotic events, and argues for selective use of therapeutic agents that inhibit ADP-mediated platelet activation in occlusive vascular disease states.

Aged↗
PubMed1999

Cardioprotection by opening of the K(ATP) channel in unstable angina. Is this a clinical manifestation of myocardial preconditioning? Results of a randomized study with nicorandil. CESAR 2 investigation. Clinical European studies in angina and revascularization.

AIMS: To assess the anti-ischaemic and anti-arrhythmic effects and overall safety of nicorandil, an ATP sensitive potassium (K+) channel opener, with 'cardioprotective' effects, in patients with unstable angina. METHODS: In a multicentre, randomized, double-blind, parallel-group, placebo-controlled study, oral nicorandil 20 mg twice daily or a matching placebo was administered for a minimum of 48 h to patients admitted with unstable angina. Treatment was standardized to include, where tolerated, oral aspirin, a beta-blocker and diltiazem. Continuous Holter ECG monitoring was performed for 48 h to assess the frequency and duration of transient myocardial ischaemia and any tachyarrhythmia, as the predefined end-points of the study. A pain chart recorded the incidence and severity of chest pain throughout the study period. Patients with myocardial infarction identified retrospectively from troponin-T analysis were excluded. RESULTS: Two hundred and forty-five patients were recruited into the study. Forty-three patients were excluded with an index diagnosis of myocardial infarction, two were not randomized and 12 had unsatisfactory tape data. In the remaining 188 patients, six out of 89 patients (6.7%) on nicorandil experienced an arrhythmia, compared with 17 out of 99 patients (17.2%) on placebo (P=0.04). Three nicorandil patients experienced three runs of non-sustained ventricular tachycardia compared to 31 runs in 10 patients on placebo (P=0.087 patients; P<0.0001 runs). Three nicorandil patients had four runs of supraventricular tachycardia, compared to 15 runs in nine patients on placebo (P=0.14 patients; P=0.017 runs). Eleven (12.4%) patients on nicorandil had 37 episodes of transient myocardial ischaemia (mostly silent) compared with 74 episodes in 21 (21.2%) patients on placebo (P=0.12 patients; P=0.0028 episodes). In the overall safety analysis, which included all patients who received at least one dose of study medication, there were no significant differences in the rates of myocardial infarction or death between the nicorandil or placebo-treated groups. CONCLUSIONS: Nicorandil, added to aggressive anti-anginal treatment for unstable angina, reduces transient myocardial ischaemia, non-sustained ventricular, and supraventricular arrhythmia compared to placebo. The anti-arrhythmic activity with nicorandil is probably a secondary effect resulting from its anti-ischaemic action and we suggest that this may be related to its effect on the ATP sensitive potassium channel causing pharmacological preconditioning.

Adenosine Triphosphate↗
PubMed1999

Stent implantation reduces restenosis in patients with suboptimal results following coronary angioplasty.

BACKGROUND: Primary intracoronary stenting reduces the rate of restenosis when compared with balloon angioplasty (PTCA) in selected patients. The strategy of PTCA followed by provisional stent placement for suboptimal PTCA results may be preferable to universal stenting but has not yet been tested in a randomized trial. METHODS: An attempt was made to obtain an optimal result with PTCA alone in 143 patients. Stenting was required in 50 patients (35%) for significant coronary dissection or PTCA failure. In the remaining 93 patients, the angiographic result was assessed immediately using on-line quantitative coronary angiography and classified as either optimal (<15% residual stenosis) or suboptimal (>/=15% residual stenosis). Sixteen patients (11%) had an optimal result from PTCA. The remaining 77 (54%) patients had a suboptimal result and were immediately randomized either to no further treatment or to the placement of a stent. The primary end-point was the rate of restenosis (>50% stenosis), assessed by quantitative coronary angiography, at 6 months. RESULTS: Angiographic follow-up was completed in 132 patients. Restenosis occurred in 53 (36,69)% of patients with a suboptimal result randomized to PTCA alone compared with 24 (12,41)% of patients randomized to stent (P=0.023). There was no significant difference in minimal luminal diameter at follow-up between the randomized groups. The rate of restenosis was 14 (2,43)% in patients with an optimal PTCA result and 14 (5,28)% in those that required stenting. CONCLUSIONS: Optimal angiographic results following conventional PTCA are rare and the restenosis rate following suboptimal results is high. The strategy of stenting suboptimal results is associated with a significant reduction in the rate of stenosis.

Angioplasty, Balloon, Coronary↗
PubMed1999

Intertrochanteric versus femoral neck hip fractures: differential characteristics, treatment, and sequelae.

BACKGROUND: More than 220,000 persons 65 years and older fracture a hip every year in the United States. Although hip fractures have been considered as a single, homogeneous condition, there are two major anatomic types of proximal femoral fractures: intertrochanteric and femoral neck. The present study's objective was to determine if the two types of hip fracture have different patient characteristics and sequelae. METHODS: A prospective study of 923 elderly patients admitted to seven Baltimore hospitals for a hip fracture between 1984 and 1986. RESULTS: Patients with intertrochanteric fractures were slightly older, sicker on hospital admission, had longer hospital stays, and were less likely at 2 months postfracture to have recovered activities of daily living than femoral neck fracture patients. Intertrochanteric fracture patients also had higher mortality rates at 2 and 6 months after fracturing. Long-term recovery (1 year) did not differ between fracture type. CONCLUSIONS: It appears that intertrochanteric fracture patients have intrinsic factors (older age, poor health) impacting upon their risk of fracture and ability to recover. Differences in patient characteristics and sequelae do exist between femoral neck and intertrochanteric hip fracture patients that impact upon recovery.

Activities of Daily Living↗
PubMed1999

Serum concentrations of steroids, parathyroid hormone, and calcitonin in postmenopausal women during the year following hip fracture: effect of location of fracture and age.

BACKGROUND: Hip fracture in the aged is a major health problem, especially considering the increasing proportion of the elderly in the population. This study examines changes in circulating levels of hormones, which are purported to affect bone metabolism, in response to hip fracture in postmenopausal women. METHODS: Patients consisted of women ages 65 and older who had surgery within 2 days of fracture. Serum samples were obtained at 3, 10, 60, 180, and 360 days postfracture. Healthy women without hip fractures from the same age range served as a control group (n = 17). Hormones were determined by radioimmunoassay. Subjects with fractures in the neck region of the femur (n = 78) were compared to subjects with fractures in the trochanteric region (n = 88). RESULTS: Estrone concentration (47.6 +/- 5.7 pg/mL; mean +/- SEM) at 3 days postfracture was elevated (p < .001) compared to control levels of 20.7 +/- 4.6 pg/mL. By 2 months, levels had declined to control levels. Androstenedione and the adrenal hormones, DHEAS and cortisol, displayed similar responses. Parathyroid hormone (PTH) levels were not significantly different from the control concentration at 3 days following fracture, but increased (p < .001) during the year following fracture. Calcitonin concentrations were much higher (p < .001) 3 days postfracture (42.1 +/- 3.7 pg/mL) compared to controls without fracture (9.8 +/- 3 pg/mL). Except for testosterone, no differences could be attributed to fracture location. Only PTH, with concentrations higher in the older age groups (p < .001), showed an age-related response. CONCLUSIONS: Following hip fracture, there are some dramatic responses in hormones that purportedly are mechanistically important in bone metabolism. These changes include transient increases in steroid hormones, chronic elevations in calcitonin, and rising levels of PTH during the year after fracture.

Aged↗
PubMed1999

Simultaneous assessment of myocardial viability and function for the detection of hibernating myocardium using ECG-gated 99Tcm-tetrofosmin emission tomography: a comparison with 201Tl emission tomography combined with cine magnetic resonance imaging.

The aims of this study were to evaluate the simultaneous assessment of myocardial viability and function for the detection of hibernating myocardium using ECG-gated 99Tcm-tetrofosmin single photon emission tomography (SPET), and to compare the technique with 201Tl SPET in combination with cine magnetic resonance imaging (MRI). Fifteen patients aged 41-70 years with impaired left ventricular function (mean LVEF 23.4 +/- 8.1%) and three-vessel coronary artery disease were studied before and after coronary artery bypass grafting (CABG). The following investigations were performed within the 3 months before surgery: stress/redistribution and separate-day rest 201Tl SPET with early and late imaging, stress and ECG-gated rest 99Tcm-tetrofosmin SPET, and resting cine MRI. Between 3 and 6 months post-surgery, stress/redistribution 201Tl SPET and cine MRI were repeated. Tracer uptake in nine segments of the left ventricle was graded visually and by quantitative analysis. Myocardial motion and thickening were graded visually from cine MRI and from gated 99Tcm-tetrofosmin SPET images. Segments were defined as hibernating pre-operatively if tracer uptake was moderately reduced or better but myocardial motion was severely hypokinetic or worse. The accuracy of pre-operative assessment was assessed by comparison with post-operative function assessed by MRI. The sensitivity and specificity for the prediction of functional improvement were 69% and 60% for late rest 201Tl uptake combined with MRI; 58% and 62% for rest 99Tcm-tetrofosmin uptake combined with MRI; and 62% and 45% when gated 99Tcm-tetrofosmin SPET was used to assess both tracer uptake and wall motion. In 21 of 135 segments, contractile function could not be assessed by gated 99Tcm-tetrofosmin SPET because of inadequate tracer uptake; function was improved in 5 (25%) of these segments after CABG. In conclusion, the combined assessment of viability and function using ECG-gated 99Tcm-tetrofosmin SPET is feasible and it allows the assessment of hibernating myocardium with similar accuracy to the combination of ungated 99Tcm-tetrofosmin SPET with MRI. Where tracer uptake is too poor for assessment of function, there is a low incidence of myocardial hibernation. However, ECG-gated 99Tcm-tetrofosmin SPET is not superior to 201Tl SPET combined with cine MRI in the identification of hibernation.

Adult↗
PubMed1999

Crystal structure of thymidylate synthase A from Bacillus subtilis.

Thymidylate synthase (TS) converts dUMP to dTMP by reductive methylation, where 5,10-methylenetetrahydrofolate is the source of both the methylene group and reducing equivalents. The mechanism of this reaction has been extensively studied, mainly using the enzyme from Escherichia coli. Bacillus subtilis contains two genes for TSs, ThyA and ThyB. The ThyB enzyme is very similar to other bacterial TSs, but the ThyA enzyme is quite different, both in sequence and activity. In ThyA TS, the active site histidine is replaced by valine. In addition, the B. subtilis enzyme has a 2.4-fold greater k(cat) than the E. coli enzyme. The structure of B. subtilis thymidylate synthase in a ternary complex with 5-fluoro-dUMP and 5,10-methylenetetrahydrofolate has been determined to 2.5 A resolution. Overall, the structure of B. subtilis TS (ThyA) is similar to that of the E. coli enzyme. However, there are significant differences in the structures of two loops, the dimer interface and the details of the active site. The effects of the replacement of histidine by valine and a serine to glutamine substitution in the active site area, and the addition of a loop over the carboxy terminus may account for the differences in k(cat) found between the two enzymes.

Bacillus subtilis↗
PubMed1998

The management of hypercholesterolaemia in patients with coronary artery disease referred for coronary angiography.

There are clear benefits in treating hypercholesterolaemia in patients with ischaemic heart disease, especially those with previous myocardial infarction. Following publication of trial evidence and treatment guidelines for hypercholesterolaemia, we investigated the current practice of the management of hypercholesterolaemia in patients with coronary artery disease referred for coronary angiography by general physicians. We prospectively reviewed 156 consecutive patients (117 men; mean age 61.5+/-9.6 [S.D.] years) with a history of angina pectoris who attended the day case unit for coronary angiography in a 10 week period. Nearly a tenth of these patients had not been screened for hypercholesterolaemia in this study. Of those patients with a cholesterol level > or =5.5 mmol/l, almost a quarter were not on a statin or any other cholesterol-lowering therapy. Continued effort should be given to the screening and effective management of hypercholesterolaemia in patients with coronary artery disease.

Aged↗