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Biomedical subjects

K A Fox

Publications and source records attributed to K A Fox.

At least 91 records · Page 5Linked to original sources
PubMed1996

Measurement of platelet volume using a variety of different anticoagulant and antiplatelet mixtures.

Mean platelet volume (MPV), a measure of platelet size, has previously been noted to change in a time dependent manner in ethylene-diaminetetraacetic acid (EDTA) and citrate anticoagulants. We measured MPV in healthy volunteers using several different anticoagulants and at different temperatures. In ten volunteers MPV was measured (Sysmex NE 8000 autoanalyser) serially over a 29 h period in 15 different anticoagulant/antiplatelet combinations kept at room temperature and on ice-water mixture. We evaluated the following mixtures: K3EDTA, K3EDTA/prostaglandin E1 (PGE1), K3EDTA/PGE1/theophylline, Na2EDTA, Na2EDTA/PGE1, citrate 1:9, citrate 1:4, citrate 1:9/PGE1/theophylline, citrate 1:4/PGE1/theophylline, citrate 1:9/PGE1, citrate 1:9/dextrose, citrate 1:4/dextrose, acid-citrate-dextrose (ACD) 15%, ACD 11.9%, ACD 11.9%/Na2EDTA. In a second experiment we evaluated MPV, at room temperature only, in a further 20 volunteers in K3EDTA, citrate 1:9, ACD 11.9%/Na2EDTA, ACD 11.9% (total = 30) and citrate-phosphate-dextrose-adenine (CPDA; total = 20). Over the 29 h period there was a significant positive trend of increasing MPV in K3EDTA, CPDA and ACD 11.9%/Na2EDTA and a negative trend in citrate 1:9. ACD 11.9% showed no significant change in MPV with time at room temperature. This methodology should enable the wider application of MPV measurement for routine clinical and research studies.

Adult↗
PubMed1996

Latissimus dorsi muscle: assessment of stimulation after cardiomyoplasty with Doppler US tissue imaging.

PURPOSE: To evaluate Doppler ultrasound (US) tissue imaging for assessment of stimulated skeletal muscle contraction. MATERIALS AND METHODS: Seven patients were studied after left latissimus dorsi cardiomyoplasty. Myograft contraction programmed on alternate cardiac cycles was assessed with Doppler US tissue imaging. Beat-to-beat variation in inferior wall motion was assessed by examining peak myograft velocities during 10 muscle-assisted and 10 nonassisted cardiac cycles. The temporal relationship between electrostimulation and myograft contraction, changes in cardiac geometry, and the effect of alterations in stimulation voltage and muscle synchronization were assessed. RESULTS: Significant beat-to-beat variation in velocity profile could be detected in the proximal myograft in six patients (P < .05). Potentiation of infero-posterior wall motion was measurable in five patients (mean peak systolic wall velocity: nonassisted, 2.5 cm.sec-1 +/- 0.5 [standard deviation]; assisted, 7.8 cm.sec-1 +/- 6.3). The response between stimulation voltage and inferoposterior wall velocity was sigmoid. CONCLUSION: Doppler US tissue imaging depicted the effects of myostimulator programming on muscle contraction and ventricular wall motion.

Cardiomyoplasty↗
PubMed1996

Autosomal dominant polycystic kidney disease and hypertension in the aviator.

Autosomal dominant polycystic kidney disease is a relatively common familial disorder which frequently affects multiple organ systems. The condition is associated with hypertension, cardiac valvular abnormalities, cerebral berry aneurysms, and chronic renal failure. We describe an aviator with a long history of hypertension that was found to be due to autosomal dominant polycystic kidney disease. Following an extensive evaluation, he was found capable of continuation of flying duties. The epidemiology, pathogenesis, diagnosis, evaluation, and aeromedical implications of autosomal dominant polycystic kidney disease in an aviator are discussed.

Adult↗
PubMed1995

Left ventricular function after extended hypothermic preservation of the heart is dependent on functional coronary capillarity.

BACKGROUND: A growing body of knowledge has led to the hypothesis that injury to the microcirculation during hypothermic myocardial preservation may result in decreased contractility of hearts upon reperfusion. METHODS AND RESULTS: To test this hypothesis, we examined the relationship between no-reflow and left ventricular function after hypothermic cardiac preservation after reperfusion with solutions containing dilute whole blood (DWB) or washed red blood cells (K2RBC). Rat hearts were arrested with high-potassium cardioplegia, then flushed and stored for 6 hours in low-potassium cardioplegia at 4 degrees C. Hearts were reperfused at a constant flow rate (4 mL/min) with K2RBC for 60 minutes (group 1, n = 5) or DWB for 7 minutes followed by 53 minutes of K2RBC (group 2, n = 5). Left ventricular developed pressure (LVDP) was measured with an intraventricular balloon. Immediately after functional assessment, hearts were perfused with an india ink solution to mark flow, then glutaraldehyde. Morphometric techniques were used to determine the degree of capillary compression [delta d(c)], perfused capillary number per fiber area [QA(0)P], and perfused capillary surface area per fiber volume [Sv(c,f)P]. Capillaries were moderately compressed in both groups after reperfusion (group 1, 19 +/- 1%; group 2, 20 +/- 1%). QA(0)P and Sv(c,f)P were highly correlated with delta d(c) in hearts reperfused with K2RBC (r = .92 and r = .92; P < .01). Although statistically significant, the correlation was not as strong in DWB-reperfused hearts (r = .66 and r = .67; P < .05). LVDP was correlated to QA(0)P and Sv(c,f)P (r = .86 and r = .87, respectively) for groups 1 and 2. CONCLUSIONS: The weaker correlation between capillary perfusion and capillary compression in DWB-reperfused hearts suggests that factors other than compression contribute to no-reflow after hypothermic preservation. Regardless of the composition of the reperfusate, recovery of left ventricular function after hypothermic ischemia is directly related to coronary capillary perfusion upon reperfusion.

Animals↗
PubMed1995

A comparison of hirudin with heparin in the prevention of restenosis after coronary angioplasty. Helvetica Investigators.

BACKGROUND: The likelihood of restenosis is a major limitation of coronary angioplasty. We studied whether hirudin, a highly selective inhibitor of thrombin with irreversible effects, would prevent restenosis after angioplasty. We compared two regimens of recombinant hirudin with heparin. METHODS: We randomly assigned 1141 patients with unstable angina who were scheduled for angioplasty to receive one of three treatments: (1) a bolus dose of 10,000 IU of heparin followed by an intravenous infusion of heparin for 24 hours and subcutaneous placebo twice daily for three days (382 patients), (2) a bolus dose of 40 mg of hirudin followed by an intravenous infusion of hirudin for 24 hours and subcutaneous placebo twice daily for three days (381 patients), or (3) the same hirudin regimen except that 40 mg of hirudin was given subcutaneously instead of placebo twice daily for three days (378 patients). The primary end point was event-free survival at seven months. Other end points were early cardiac events (within 96 hours), bleeding and other complications of the study treatment, and angiographic measurements of coronary diameter at six months of follow-up. RESULTS: At seven months, event-free survival was 67.3 percent in the group receiving heparin, 63.5 percent in the group receiving intravenous hirudin, and 68.0 percent in the group receiving both intravenous and subcutaneous hirudin (P = 0.61). However, the administration of hirudin was associated with a significant reduction in early cardiac events, which occurred in 11.0, 7.9, and 5.6 percent of patients in the respective groups (combined relative risk with hirudin, 0.61; 95 percent confidence interval, 0.41 to 0.90; P = 0.023). The mean minimal luminal diameters in the respective groups on follow-up angiography at six months were 1.54, 1.47, and 1.56 mm (P = 0.08). CONCLUSIONS: Although significantly fewer early cardiac events occurred with hirudin than with heparin, hirudin had no apparent benefit with longer-term follow-up.

Angina, Unstable↗
PubMed1995

In-hospital mortality after out-of-hospital cardiac arrest.

In-hospital management of out-of-hospital cardiac arrest is complicated by uncertainty about prognosis and the need to identify markers of adverse outcome in individuals surviving initial resuscitation. We sought to identify factors that predict in-hospital death among patients who initially survive out-of-hospital cardiac arrest. We investigated 346 consecutive cases of out-of-hospital cardiac arrest received by a single centre in Edinburgh, UK (270 cases examined retrospectively, 76 prospectively). Of the retrospective cohort, 246 cases were thought to be of cardiac origin. There were associations between in-hospital mortality and pre-arrest variables, resuscitation variables, and factors measured during admission. Crew-witnessed arrests were associated with low mortality; arrest rhythm (p < 0.001), resuscitation by a health professional (p < 0.05), conscious level on admission (p < 0.001), and requirement for ventilation (p < 0.05) independently predicted in-hospital mortality. A weighted prognostic scoring system based on three of these variables accurately predicted the likelihood of in-hospital death in the prospective test group. Further assessment of conscious level during admission with the Glasgow coma score predicted mortality rates in the study population, but coma did not predict a hopeless prognosis in individual cases unless it persisted for 72 h or more. Accurate prognostic assessment of out-of-hospital cardiac arrest survivors can be made from information available on admission. Of factors that independently predicted outcome, the skill of the resuscitator is most readily modified. This suggests that public training in resuscitation may reduce mortality rates.

Adult↗
PubMed1995

Aspiration pneumonia following surgically placed feeding tubes.

BACKGROUND: The enteral route is preferred in surgical patients requiring nutritional support; however, controversy surrounds the choice of location of feeding tube placement. Although jejunostomy has been commonly accepted as superior to gastrostomy for long-term nutritional support because of an assumed lower risk of aspiration pneumonia, recent studies suggest that reevaluation of common practices of surgical tube placement is warranted. PATIENTS AND METHODS: We conducted a retrospective chart review of gastrostomy and jejunostomy procedures from 1986 to 1993. Demographic information and complications related to the procedure were reviewed. Aspiration pneumonia was defined as respiratory symptoms, leukocytosis, and infiltrate on chest radiograph. RESULTS: Sixty-nine gastrostomies and 86 jejunostomies were performed during the study period. Six patients were diagnosed with aspiration pneumonia; 2 cases of which occurred with jejunostomy and 4 cases occurred with gastrostomy (P = not significant). CONCLUSIONS: There was no difference in rates of pulmonary aspiration or other complications between gastrostomy and jejunostomy. We suggest that when a surgically placed feeding tube is required, the determination of appropriate procedure be based on clinical factors such as the technical difficulty of the operation or long-term feeding goals.

Enteral Nutrition↗
PubMed1995

Optimizing muscle synchronization after dynamic cardiomyoplasty. Two educational cases.

Muscle stimulator programming is fundamental in ensuring optimal latissimus dorsi graft function after cardiomyoplasty. The ventricle-muscle synchronization delay has a significant effect on graft function, but can be difficult to optimize. The established method for ensuring appropriate synchronization involves the use of M-mode echocardiography. We present two educational cases in which M-mode and Doppler echocardiography have been instrumental in illustrating electrophysiologic and haemodynamic factors which need to be considered in evaluating an appropriate synchronization delay.

Atrial Fibrillation↗
PubMed1995

r-hirudin in unstable angina pectoris. Rationale and preliminary data from the APT pilot study.

Therapeutic strategies for patients with unstable angina have been hampered by the difficulty in defining a homogenous cohort of patients, and identifying their risk for subsequent cardiovascular events. Despite the similarities in pathophysiological mechanisms between unstable angina and acute myocardial infarction, an analysis of recent trials of thrombolytic therapy in unstable angina has failed to reveal evidence of improved clinical outcome. However, both aspirin and heparin have shown evidence of benefit and in order to test more specific and potent thrombin inhibitors (for example hirudin) it is necessary to identify a cohort of patients with a high risk of subsequent cardiac events. This small scale pilot study set out to identify patients with unstable angina or non-Q wave infarction with a high risk of subsequent cardiac events, and to undertake a feasibility study of two dose regimens of recombinant hirudin (HPW023). The impact on haemostatic parameters and the need for dose adjustment in order to achieve the target therapeutic range of activated partial thromboplastin time (aPTT) was also assessed. Firstly, the study revealed that it was possible to identify a high risk patient population (6/43, 14% had sustained infarction; 10/43, 23% required emergency or urgent revascularization and 11/43, 26% elective revascularization). Secondly, it was possible to achieve stable antithrombin regimens with the two selected doses of hirudin (at least 78% of patients were within the target range at any of the time points). Haemostatic parameters were compared, but larger scale studies are required to establish safety, with a reliable estimate of the impact of hirudin on clinical events.

Angina, Unstable↗
PubMed1995

Skeletal muscle contraction in healthy volunteers: assessment with Doppler tissue imaging.

PURPOSE: To evaluate Doppler tissue imaging (DTI) in the measurement and characterization of skeletal muscle movement and contraction. MATERIALS AND METHODS: Five healthy male subjects were examined with a commercially available ultrasound imaging unit modified for DTI. Velocities of the rectus femoris and gastrocnemius-soleus muscle motion were measured during the patellar and ankle reflexes, respectively. Velocity profiles were analyzed after digitization of the DTI images. Time to peak velocity, velocity range, and relaxation time were examined in each case over three contractions. For reflex contractions, reproducibility was examined by determining the latency period, area under the velocity curve, and duration of contraction for each of five consecutive reflexes. RESULTS: Isotonic muscle contraction could be distinguished from passive movement by a higher tissue velocity range, by a more rapid initial acceleration slope, and by the velocity differential across the muscle. The intensity and duration of the contraction and plateau and relaxation phases of isotonic contraction could be measured in all muscle groups. CONCLUSION: DTI provides detailed information about the dynamics of skeletal muscle contraction.

Adult↗
PubMed1994

Tissue-type plasminogen activator and plasminogen activator inhibitor activities as predictors of adverse events in unstable angina.

Among patients with recent-onset unstable angina and evidence of ischemia or coronary artery disease, the incidence of subsequent cardiovascular events is high. The aim of this study was to investigate, in this high-risk population, whether unstable angina was associated with abnormalities of tissue-type plasminogen activator (t-PA) or plasminogen activator inhibitor (PAI) activities and whether, in a prospective study, any of these parameters would identify patients with an adverse cardiovascular prognosis. A group of 22 high-risk patients with unstable angina (64% event rate at 3 months) was studied prospectively for 12 weeks, and the fibrinolytic parameters measured at presentation were related to subsequent cardiovascular progress. A group of 20 age- and sex-matched healthy subjects acted as control subjects. Patients who had subsequent cardiovascular events (acute myocardial infarction or severe recurrent angina +/- intervention) had significantly elevated PAI activity at presentation compared with both those who remained event-free (p < 0.05) or with control subjects (p < 0.02). In addition, basal activation of fibrinolysis was demonstrated in unstable angina at presentation; this persisted at 9 weeks in patients with a favorable outcome (p < 0.02 vs control subjects), whereas it was no longer evident in those who developed cardiac events. These findings suggest that measurements of t-PA/PAI activity may reflect the underlying pathophysiologic state and relate to subsequent cardiovascular events in unstable angina.

Aged↗
PubMed1994

Effects of captopril therapy on endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction.

OBJECTIVES: This study investigated the effects of captopril therapy on endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction. BACKGROUND: Angiotensin-converting enzyme inhibitors reduce the incidence of acute coronary syndromes in patients with mild left ventricular dysfunction after myocardial infarction. Abnormal endogenous fibrinolysis, reflected in increased levels of endogenous tissue-type plasminogen activator (t-PA) antigen and plasminogen activator inhibitor type 1 activity, is associated with an increased risk of myocardial infarction in patients with ischemic heart disease. METHODS: In a randomized, double-blind crossover study beginning 8 weeks after uncomplicated myocardial infarction, patients received 4 weeks of placebo and 4 weeks of captopril (75 mg daily) therapy. At the end of each treatment period, we measured t-PA antigen and plasminogen activator inhibitor type 1 antigen and activity. RESULTS: Median values in the 15 patients after placebo and in 12 normal men matched for age and body mass index were, respectively, t-PA antigen 16.0 versus 9.5 ng/ml (p = 0.001), plasminogen activator inhibitor type 1 antigen 17.3 versus 8.6 ng/ml (p = 0.29) and plasminogen activator inhibitor type 1 activity 13.2 versus 6.3 AU/ml (p = 0.04). After 4 weeks of treatment with captopril in the 15 patients, the estimated (95% confidence interval) median reduction in t-PA antigen was 7.3 ng/ml (-4.6 to -10.3 ng/ml, p = 0.001), in plasminogen activator inhibitor type 1 antigen 3.1 ng/ml (+1.5 to -8.4 ng/ml, p = 0.17) and in plasminogen activator inhibitor type 1 activity -2.2 AU/ml (-1.0 to -4.3 AU/ml, p = 0.02). CONCLUSIONS: Treatment with captopril after uncomplicated myocardial infarction is associated with a significant decrease in elevated levels of t-PA antigen and plasminogen activator inhibitor type 1 activity. This may help to explain the reduction in risk of coronary thrombosis associated with the use of angiotensin-converting enzyme inhibitors.

Captopril↗
PubMed1994

Stereotactic fine-needle aspiration cytology of nonpalpable breast lesions: an analysis of 258 consecutive aspirates.

BACKGROUND: The role of stereotactic fine-needle aspiration cytology (SFNAC) in the diagnosis of nonpalpable breast lesions is poorly defined. PATIENTS AND METHODS: Data were prospectively collected from 225 consecutive patients with nonpalpable breast lesions who had aspiration cytology followed by immediate surgical excision. RESULTS: Between 1988 and 1993, 258 such procedures were performed. The results of 84 (33%) were interpreted as benign, 84 (33%) as atypical, 28 (11%) as suspicious for malignancy, and 49 (19%) as malignant. In all, 88 (34%) surgical specimens were malignant. SFNAC had an 80% sensitivity, a 96% specificity, a 91% positive predictive value, and an 89% negative predictive value. There were 18 false-negative and 7 false-positive aspirates. CONCLUSIONS: SFNAC for diagnosing nonpalpable breast lesions is moderately sensitive and highly specific, and has a high positive and negative predictive value. In conjunction with mammography and clinical assessment, the procedure is useful for determining which patients with nonpalpable breast lesions may require surgical biopsy.

Adult↗
PubMed1994

Prospective evaluation of a prostacyclin-sparing aspirin formulation and heparin/warfarin in aspirin users with unstable angina or non-Q wave myocardial infarction at rest. The Antithrombotic Therapy in Acute Coronary Syndromes Research Group.

The aim of this trial was to compare the efficacy of combination antithrombotic therapy with a prostacyclin-sparing aspirin plus anticoagulation versus conventional aspirin plus anticoagulation, when added to antianginal therapy, in patients with unstable angina or non-Q wave myocardial infarction already being treated with aspirin. In a double-blind (for the aspirin) study, 144 prior aspirin users were randomized; 72 patients received controlled-release, prostacyclin-sparing aspirin 75 mg daily plus anticoagulation (intravenous heparin followed by warfarin to maintain the international normalized ratio at 2-3), and 72 patients received conventional aspirin 75 mg daily plus the same anticoagulation. Controlled-release aspirin was formulated to preserve endothelial cell prostacyclin synthesis. Trial therapy was begun by 13.2 +/- 12.3 h of qualifying pain, and continued for 12 weeks. The frequency of recurrent angina with electrocardiographic changes, myocardial infarction, or death, was analysed by intention to treat. At 12 weeks, events were: [table: see text] Twenty-six of the 42 (62%) recurrent ischaemic events occurred within 7 days of presentation. Four of the 144 patients (3%) experienced a major bleeding complication. It is concluded that in spite of maximal antithrombotic therapy, there is a significant failure rate of medical therapy in aspirin users presenting with unstable angina or non-Q wave myocardial infarction while at rest. Prostacyclin-sparing aspirin offers no clinical benefit over conventional aspirin.

Adult↗
PubMed1994

Raised plasma endothelin in unstable angina and non-Q wave myocardial infarction: relation to cardiovascular outcome.

BACKGROUND: Among patients with independent evidence of coronary disease and recent onset unstable angina or non-Q wave myocardial infarction the incidence of subsequent cardiovascular events is high. Markers predictive of adverse cardiac outcome in unstable angina and non-Q wave myocardial infarction need to be defined more accurately. Endothelin-1 is a potent endothelium derived vasoconstrictor peptide that may play a part in the pathophysiology of acute myocardial ischaemia. AIM AND STUDY DESIGN: In a study that specifically identified high risk patients a group of 16 consecutive patients with either unstable angina at rest or non-Q wave myocardial infarction were prospectively investigated to establish whether these conditions are associated with high plasma immunoreactive endothelin and whether endothelin concentration at presentation is related to cardiovascular events within the next 12 weeks. Controls consisted of a group of 40 healthy subjects. RESULTS: Patients had significantly higher mean (SD) plasma endothelin at presentation than did healthy controls (7.4 (1.1) v 5.0 (1.2) pg/ml, P < 0.0001). At nine weeks plasma endothelin was still significantly higher in those patients who had subsequent cardiovascular events, (n = 9, acute myocardial infarction or refractory angina with electrocardiographic changes and revascularisation procedures, 8.5 (2.6) pg/ml, P < 0.005 v controls) whereas its concentration returned to normal in those patients who had a favourable outcome (n = 7, 5.9 (0.7) pg/ml). Compared with those patients who had an uneventful course, patients with subsequent events had significantly higher plasma endothelin, both at presentation and at nine weeks (P < 0.05 on both occasions). IMPLICATIONS: Endothelin may contribute to the pathophysiology of acute coronary syndromes and may relate to subsequent cardiovascular outcome.

Adolescent↗
PubMed1994

Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group.

BACKGROUND: The purpose of this study was to compare combination antithrombotic therapy with aspirin plus anticoagulation versus aspirin alone, when added to conventional antianginal therapy in patients with unstable rest angina or non-Q-wave myocardial infarction who were nonprior aspirin users. METHODS AND RESULTS: Two hundred fourteen patients were randomized; 109 were randomized to receive aspirin alone (162.5 mg daily) and 105 to receive a combination of aspirin plus anticoagulation, ie, aspirin 162.5 mg daily plus heparin (activated partial thromboplastin time, two times control) followed by aspirin 162.5 mg daily plus warfarin (international normalized ratio, 2 to 3). Trial therapy was begun by 9.5 +/- 8.8 hours of qualifying pain and was continued for 12 weeks. Primary end points were recurrent angina with ECG changes, myocardial infarction, and/or death. Analysis by intention to treat of primary events at 12 weeks was performed. At 14 days, there was a significant reduction in total ischemic events in the combination group versus aspirin alone (10.5% versus 27%, P = .004). An efficacy analysis of primary events at 12 weeks also revealed a large reduction in total ischemic events in the combination group versus aspirin alone (13% versus 25%, P = .06). Bleeding complications were slightly more common with combination therapy. CONCLUSIONS: In nonprior aspirin users, combination antithrombotic therapy with aspirin plus anticoagulation significantly reduces recurrent ischemic events in the early phase of unstable angina.

Angina, Unstable↗
PubMed1994

Cardiac effects of sodium stibogluconate: myocardial, electrophysiological and biochemical studies.

The pentavalent antimonial sodium stibogluconate is the mainstay of anti-leishmanial therapy. Sodium stibogluconate is less cardiotoxic than antimony and the trivalent derivatives, but has been associated with dose-related electrocardiographic changes. The effect of the currently-used regimen of sodium stibogluconate (20 mg/kg/day for 20 days) on cardiac function is uncertain. We studied 12 soldiers, mean age 24 years, with proven cutaneous leishmaniasis treated with this regimen. There were no significant changes in echocardiographic indices of left ventricular systolic or diastolic function during treatment. Indices of myocardial electrical stability (heart-rate variability and episodes of overt supraventricular and ventricular arrhythmias) were unchanged, but there was a reversible decrease in T-wave amplitude during treatment. Systolic and diastolic blood pressure fell and the heart rate increased during treatment. This regimen of sodium stibogluconate does not measurably impair left ventricular systolic or diastolic function. Minor T-wave changes occur during treatment, but there is no increase in arrhythmia frequency or change in heart-rate variability. In most young fit patients, this regimen has no cardiac side-effects. However, idiosyncratic reactions cannot be excluded, and patients with malnutrition, impaired renal function or pre-existing heart disease may be more sensitive to any cardiotoxic properties of sodium stibogluconate.

Adult↗