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Biomedical subjects

K M Fox

Publications and source records attributed to K M Fox.

At least 19 recordsLinked to original sources
PubMed1992

Ambulatory blood pressure monitoring and circadian variation of cardiovascular disease; clinical and research applications.

Ambulatory blood pressure monitoring is an evolving technology. It has an established role in the diagnosis of hypertension, the clinical management of selected patients, and in the evaluation of new medication. From continuous recording much has been learned about the circadian nature of blood pressure and heart rate. Future research holds promise for a greater understanding of the mechanisms and treatment of cardiovascular disease. The purpose of this short review is to describe the development of ambulatory blood pressure monitoring, and outline some of its important contributions to date; and also to explore the research potential and clinical utility of advanced intravascular monitoring techniques, such as the continuous recording of pulmonary artery pressure in ambulant patients.

Adolescent↗
PubMed1992

Purification and characterization of a novel enoyl coenzyme A reductase from Streptomyces collinus.

A novel NADPH-dependent enoyl reductase, catalyzing the conversion of 1-cyclohexenylcarbonyl coenzyme A (1-cyclohexenylcarbonyl-CoA) to cyclohexylcarbonyl-CoA, was purified to homogeneity from Streptomyces collinus. This enzyme, a dimer with subunits of identical M(r) (36,000), exhibits a Km of 1.5 +/- 0.3 microM for NADPH and 25 +/- 3 microM for 1-cyclohexenylcarbonyl-CoA. It has a pH optimum of 7.5, is most active at 30 degrees C, and is inhibited by both divalent cations and thiol reagents. Two internal peptide sequences were obtained. Ansatrienin A (an antibiotic produced by S. collinus) contains a cyclohexanecarboxylic acid moiety, and it is suggested that the 1-cyclohexenylcarbonyl-CoA reductase described herein catalyzes the final reductive step in the conversion of shikimic acid into this moiety.

Amino Acid Sequence↗
PubMed1992

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

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

Adult↗
PubMed1992

A new system for ambulatory pulmonary artery pressure recording.

OBJECTIVE: To develop a complete system for the measurement, recording, and analysis of ambulatory pulmonary artery pressure. DESIGN: The new system consists of a pulmonary artery catheter, an ambulatory recorder, and a desktop computer. Pulmonary artery pressure is measured by a micromanometer tipped catheter with an in vivo calibration system to allow correction for zero drift. This catheter is plugged into a small battery powered recorder. The recorder has two input channels, one for pressure and one for an event marker. The pressure wave is sampled 32 times/s, processed by an in built computer, compressed, and stored in semi-conductor memory. On completion of a recording, data is transferred from the ambulatory recorder through a serial data link to an Acorn Archimedes desktop computer on which further data processing, statistical analysis, graphics, and printouts can be obtained. RESULTS: The system has been used in 18 patients, with technically successful recording in 14, less than 15 minutes of data loss in three, and 12 hours of data loss in one. CONCLUSIONS: A new system for ambulatory pulmonary artery monitoring has been developed and used clinically with success. It may provide new perspectives on the pathophysiology of disease as it applies to everyday life.

Blood Pressure Monitors↗
PubMed1992

Biosynthesis of ansatrienin by Streptomyces collinus: cell-free transformations of cyclohexene- and cyclohexadienecarboxylic acids.

Cell-free extracts of Streptomyces collinus were tested with various cyclohexene- and cyclohexadienecarboxylic acids in order to determine the latter stages of the conversion of shikimic acid to cyclohexanecarboxylic acid. It was demonstrated that the final three steps of this process involve reduction of the alpha,beta-double bond of 1(6),2-cyclohexadienylcarbonyl CoA, an isomerization of the double bond of the resulting 2-cyclohexenylcarbonyl CoA to afford 1-cyclohexenylcarbonyl CoA, and a subsequent reduction of the newly formed alpha,beta-double bond. Both of the reduction steps were shown to require NADPH as a cofactor.

Anti-Bacterial Agents↗
PubMed1991

The influence of right heart catheterisation on pulmonary arterial pressure in chronic heart failure: relationship to neuroendocrinal changes.

Continuous ambulatory measurement of pulmonary arterial pressure was used to investigate changes following right heart catheterisation in patients with chronic heart failure. Ten males, mean age 56 years, with chronic heart failure, underwent 24 hour pressure recording using a micromanometer tipped catheter with in vivo calibration and frequency modulated recording. Eight patients were taking diuretics and 3 vasodilators. Blood was drawn for catecholamines, plasma renin activity and atrial natriuretic peptide 1 hour before catheterisation (-1 h), at the time of catheterisation (0 h) and 1, 2, 3, 4 and 6 hours later and aldosterone, cortisol and growth hormone at -1, 0 and 6 hours. Analysis of variance was used to determine changes in pulmonary arterial pressure, heart rate and hormones from the time of catheterisation in lying, sitting and standing postures. There was no significant change in pulmonary arterial pressure or heart rate over the 12 hours following or 24 hours after catheterisation in any posture. In the majority of patients plasma noradrenaline, plasma renin activity, atrial natriuretic peptide, aldosterone and cortisol were elevated. There was no significant change in hormone levels during the 6 hours following catheterisation. These findings suggest that the effect of invasive haemodynamic monitoring and chronic medical therapy on central haemodynamics is minor, and that a delay between insertion of catheters and measurement of pressure is unnecessary.

Adult↗
PubMed1991

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

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

Aged↗
PubMed1991

Synthesis of 3-carbamoylecgonine methyl ester analogues as inhibitors of cocaine binding and dopamine uptake.

Five (1R-2-exo-3-exo)-3-(N-phenylcarbamoyl)ecgonine methyl ester analogues were synthesized and characterized by 1H and 13C NMR, IR, and thermospray MS. The compounds were synthesized in two or three steps as (-)-stereoisomers from (-)-ecgonine in good yield (56% overall). These cocaine derivatives were assessed for their ability to inhibit [3H]cocaine binding to rat striatal tissue and to inhibit [3H]dopamine uptake into synaptosomes prepared from the same tissue. The most potent of the analogues was (1R-2-exo-3-exo)-2-(carbomethoxy)-8-methyl-8-azabicyclo[3.2.1]octyl 3-N-(3'-nitrophenyl)carbamate. IC50 values for inhibition of cocaine binding and dopamine uptake were 37 and 178 nM, respectively. Amino derivatives were less active than the nitro and (1R-2-exo-3-exo)-2-(carbomethoxy)-8-methyl-8-azabicyclo [3.2.1]octyl 3-N-(4'-aminophenyl)carbamate had the lowest affinity for the receptor with IC50 values of 63 and greater than 100 microM in the aforementioned assays, respectively.

Animals↗
PubMed1991

Therapeutic implications of dynamic coronary stenosis in patients with single vessel coronary artery disease.

Ten patients with proven single-vessel coronary artery disease and a positive exercise test for ischaemia were investigated to establish the importance and therapeutic implications of dynamic coronary stenosis in such patients. All patients interrupted their anti-anginal therapy and under took serial exercise testing in an attempt to identify variability in the ischaemic threshold. Ergonovine testing was performed in nine patients and all underwent 48 h of ambulatory ST segment monitoring while treatment was discontinued. Patients then entered a randomized double-blind study of atenolol and nifedipine; treadmill exercise testing and 48 h of ambulatory ST segment monitoring were performed at the end of each treatment phase. Six (60%) patients showed evidence of variability in coronary vasomotor tone four of whom developed significant ST segment changes during administration of ergonovine; a further two had greater than 30% variability in time to onset of ischaemia during serial treadmill exercise testing. Atenolol significantly increased the time to ischaemia on exercise testing, both in the group as a whole and in the subgroup with evidence of altered vasomotor tone when compared with no therapy, and led to a non-significant reduction in the frequency and duration of ischaemia during the patients' daily lives. Nifedipine, conversely, did not significantly increase time to ischaemia on exercise testing or reduce the frequency or duration of ambulatory ischaemia in either the whole group or the subgroup. With evidence of altered vasomotor tone when compared to no therapy however it was beneficial in terms of reduction in chest pain and requirement for glyceryl trinitrate during daily life.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Avoidance of tolerance and lack of rebound with intermittent dose titrated transdermal glyceryl trinitrate. The Transdermal Nitrate Investigators.

OBJECTIVES: To investigate the efficacy of transdermal glyceryl trinitrate given continuously and with a nocturnal nitrate free period. DESIGN: Double blind placebo controlled study with two parallel limbs. SETTING: Multicentre trial. PATIENTS: 52 patients randomised to receive either continuous treatment (23 patients) or intermittent treatment with an individually titrated dose (29 patients) for 14 days: both treatments were compared with placebo in a cross-over fashion. INTERVENTION: Continuous treatment with 10 mg per 24 hours of transdermal glyceryl trinitrate or intermittent transdermal glyceryl trinitrate titrated to give an arbitrary 10 mm Hg drop in systolic blood pressure (mean dose 18.2 mg) given over approximately 16 hours. MAIN OUTCOME MEASURE: Treadmill exercise stress testing and ambulatory monitoring of the ST segment after 14 days' treatment. RESULTS: After 14 days' intermittent treatment resting supine and standing systolic blood pressure fell by 7.5 mm Hg (95% confidence interval 2.7 to 12.2) and 9.0 mm Hg (95% CI 3.4 to 14.5) respectively (p less than 0.01); resting heart rate was unchanged. Mean heart rate at 1 mm ST segment depression rose by 11.9 beats/min (CI 1.1 to 23.7) (p less than 0.05), mean time to onset of angina increased by 59 seconds (CI 10.8 to 108) (p less than 0.05), and total exercise duration increased by 40 seconds (p less than 0.05). These changes were not seen after continuous treatment. The frequency of ischaemic episodes was not reduced with either regimen nor was the circadian distribution of these episodes altered, in particular nocturnal episodes did not increase during intermittent treatment. CONCLUSION: Tolerance to glyceryl trinitrate was avoided by the use of individually titrated doses administered with a nocturnal nitrate free period. There was no evidence of "rebound" on ambulatory monitoring during this treatment.

Administration, Cutaneous↗
PubMed1991

Circadian rhythms in cardiovascular function.

This short overview discusses circadian rhythms observed in cardiovascular events such as myocardial ischaemia and myocardial infarction, which occur most frequently in the morning. Changes in the frequency of occurrence seem to be related to, and may result from, circadian rhythms in factors such as heart rate, blood pressure, coronary artery tone, platelet adhesiveness and blood fibrinolytic activity, which could be involved in triggering myocardial ischaemia or infarction. Consideration of the circadian rhythm of myocardial ischaemia and serious cardiovascular events may be important when medical therapy is selected.

Circadian Rhythm↗
PubMed1990

Pathophysiology of angina.

The development and pathophysiology of myocardial ischaemia is a dynamic process in which increased myocardial oxygen demand or decreased coronary blood flow are not the sole determinants. Both these factors are inappropriately altered before, during, or after the onset of ischaemia, and a vicious cycle ensues. Drug therapy should be aimed at not only preventing the development of myocardial ischaemia but also at reversing the abnormal hormonal, metabolic, and haemodynamic effects.

Angina Pectoris↗
PubMed1990

Dermatoglyphics in the identification of women either with or at risk for breast cancer.

Fingerprints and palm prints were studied in 78 breast cancer patients, 391 patients at increased risk for developing breast cancer, and 64 control patients for the purpose of finding a pattern that would identify those women with breast cancer or those who are predisposed to its development. A pattern of 6 or more digital whorls was identified more frequently in women with breast cancer than in those without the disease (P less than 0.01). This finding was independent of known risk factors for breast cancer and was present in 28% of the cancer patients. No correlation was noticed between palm prints and breast cancer. The positive predictive value of 6 or more digital whorls was comparable to that of mammography and that of breast biopsy. With increasing age there was an increase in the positive predictive value associated with 6 or more digital whorls. It is concluded that digital dermatoglyphics may have a future role in identifying women either with or at increased risk for breast cancer such that either risk reduction measures or earlier therapy may be instituted.

Adult↗
PubMed1990

Maximal oxygen uptake in severe aortic regurgitation: a different view of left ventricular function.

Respiratory gas exchange was used to assess left ventricular (LV) function in 22 patients with severe aortic regurgitation (19 men and three women, aged 18 and 70 years, mean 49 years). Anaerobic threshold and symptom-limited maximal oxygen consumption (VO2 max) were measured during treadmill exercise, and the results were compared with conventional echocardiographic and radionuclide indices of LV systolic function. The results were considered with respect to the patients' New York Heart Association functional class. Both rest and exercise LV ejection fractions were variable, but the mean results were similar in all classes. The echocardiographic indices of LV cavity dimensions, fractional shortening, radius/thickness ratio, and systolic wall stress also showed a wide range but with similar mean results in each class. In contrast, VO2 max and anaerobic threshold showed a relationship to functional class. VO2 max was 32.4 +/- 3.4 ml/kg/min in age-matched control subjects; in the patients it was 27.9 +/- 4.7 in class I, 24.7 +/- 5.7 in class II, and 14.2 +/- 2 in the combined class III/IV. Results in patients in classes I and II were similar, but both groups were significantly different from control subjects (p less than 0.05) and from patients in class III/IV (p less than 0.01). About half of the patients with moderate LV dysfunction (judged by reduced VO2 max) were asymptomatic, and LV function was impaired in 4 of 10 patients in class I. Thus, unlike conventional indices of LV function, VO2 max appeared capable of distinguishing patients with moderate-to-severe LV dysfunction from those with little or no LV dysfunction. Measurement of respiratory gas exchange appears to be a valid and useful supplementary means of assessing LV function in severe aortic regurgitation. Further long-term evaluation is required.

Adolescent↗
PubMed1990

The haemodynamic response to ST segment changes during coronary arteriography.

Contrast media are known to cause electrocardiographic and haemodynamic changes during coronary arteriography. There is a tendency to proceed with repeated coronary arteriography unless patients develop chest pain, bradycardia or hypotension. We have related the changes in the ST segment to changes in left ventricular end-diastolic pressure, measuring pulmonary arterial diastolic pressure with a transducer tipped catheter. Twenty-five patients were studied, 15 patients with coronary arterial disease, 2 with syndrome X, 3 with coronary arterial spasm (and underlying coronary disease) and 5 normal controls. In control patients, no changes in the ST segment or pulmonary arterial diastolic pressure were recorded. Patients with syndrome X developed ST segment depression in the absence of changes in pulmonary arterial diastolic pressure. Those with coronary arterial spasm and underlying coronary disease developed ST segment depression and a rise in pulmonary arterial diastolic pressure following most injections. In coronary arterial disease, both painful and silent ST segment depression was noted with a rise in pulmonary arterial diastolic pressure. In some instances, a summation effect arose with repeated injections. Major disturbances in the ST segment may occur during coronary arteriography and result in elevation of left ventricular filling pressure.

Angina Pectoris↗
PubMed1990

Characteristics of silent and painful ischaemia during ambulatory monitoring in patients with coronary arterial disease.

We compared the characteristics of silent and painful ischaemia during ambulatory ST segment monitoring in 288 patients with documented coronary arterial disease and stable angina. During 12,436 hours of monitoring, 890 ischaemic episodes were recorded, of which 652 (73%) were silent. Silent and painful ischaemic episodes were similar in terms of heart rate at onset of ischaemia, increase in heart rate prior to ischaemia, duration of ischaemia, and percentage of episodes not preceded by an increase in heart rate. Change in the mean maximal ST segment was greater during painful ischaemic episodes (P less than 0.01). Silent ischaemia is characteristically painful ischaemia without the pain.

Adult↗
PubMed1990

Pulmonary artery pressure changes during exercise and daily activities in chronic heart failure.

Long-term continuous pulmonary artery pressure monitoring was used to investigate pressure changes during different types of exercise and normal daily activities in patients with chronic heart failure. Nine men (mean age 55 years) with treated chronic heart failure underwent continuous pulmonary artery pressure measurement with use of a micromanometer-tipped catheter with in vivo calibration and frequency-modulated recording. The mean (+/- SD) maximal systolic pulmonary artery pressure (in mm Hg) was 59.4 +/- 26.1 on treadmill exercise, 54.9 +/- 30.6 on bicycle exercise, 52.5 +/- 26.1 walking up and down stairs and 43.5 +/- 23.9 walking on a flat surface. The mean maximal diastolic pressure (in mm Hg) was 27.8 +/- 14.6 on treadmill exercise, 25.5 +/- 14.9 on bicycle exercise, 24.9 +/- 14.8 walking up and down stairs and 20.4 +/- 12.5 walking on a flat surface. The increase in pulmonary artery pressure did not correlate with the severity of the limiting symptoms except during walking on a flat surface. All patients had marked postural changes in pressure, with the systolic pressure difference from lying to standing ranging from 8 to 25 mm Hg and the diastolic pressure difference ranging from 3 to 13 mm Hg. Eating meals caused an increase in pressure in three patients, but less than that when lying flat. There was an increase in pressure during urination in four patients equal to that when walking on a flat surface. None of these activities was associated with symptoms. Neither symptoms nor pulmonary artery pressure during maximal exercise is the same as during daily activities. This may restrict the value of maximal exercise tests in assessing patients with chronic heart failure.

Activities of Daily Living↗