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Biomedical subjects

K A Fox

Publications and source records attributed to K A Fox.

At least 19 recordsLinked to original sources
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

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

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↗
PubMed1994

Hyperinsulinaemia in ischaemic heart disease: the importance of myocardial infarction and left ventricular function.

Elevated circulating insulin levels have been reported in ischaemic heart disease, and may be of aetiological importance. Previous studies have not considered the potential influence of heart failure or of previous myocardial infarction, as opposed to stable angina. We therefore measured the insulin response to a 75 g oral glucose tolerance test in five groups with normal glucose tolerance, comparing normal male controls to men with chronic stable angina, men with recent myocardial infarction (two groups, 3 weeks and 3 months post infarction), and men with chronic severe heart failure. Only patients with chronic heart failure had fasting hyperinsulinaemia, probably reflecting associated neuroendocrine abnormalities. Stimulated hyperinsulinaemia was present in all patient groups, but was less pronounced and of shorter duration in patients with angina. At 120 min, only patients with heart failure or previous myocardial infarction were hyperinsulinaemic. The degree of stimulated hyperinsulinaemia was not influenced by the presence of heart failure or by the length of time from infarction. Hyperinsulinaemia is associated with impaired peripheral muscle glucose uptake and metabolism, and might contribute to muscular fatigue on exertion in patients with previous myocardial infarction or heart failure.

Administration, Oral↗
PubMed1993

Radiation therapy salvage of Hodgkin's disease following chemotherapy failure.

PURPOSE: This study evaluates the efficacy of comprehensive salvage radiation therapy, with or without chemotherapy, in selected patients with Hodgkin's disease who have failed primary combination chemotherapy. METHODS AND MATERIALS: Between 1972 and 1991, 28 patients with advanced Hodgkin's disease failing intensive combination chemotherapy in previously unirradiated nodal and/or pulmonary sites were treated with salvage radiotherapy with curative intent. Treatment consisted of comprehensive extended field radiotherapy to all known areas of disease. Total radiation doses ranged from 17.0 to 50.0 Gy, with only five patients (18%) receiving < 30.0 Gy to any field. Twelve patients also received chemotherapy as part of their salvage regimen. RESULTS: Twenty-six patients (93%) achieved a complete response and 14 (50%) remain in continuous complete remission at 14 to 133 months. In addition, three patients (11%) who failed salvage radiotherapy are now without evidence of disease following additional therapy. With a median follow-up of 47 months (range 14+ to 198+), actuarial median relapse-free survival and overall survival are 46 and 97 months, respectively. Actuarial 5-year relapse-free survival and overall survival are 40% and 63%, respectively. Patients with an initial complete response to chemotherapy had a significantly longer actuarial relapse-free survival than those with an initial partial response (p = 0.02). Salvage therapy was generally well-tolerated and resulted in no treatment-related deaths. CONCLUSION: Comprehensive salvage radiotherapy is of significant benefit in selected patients and should be considered an option for patients with advanced Hodgkin's disease following chemotherapy failure.

Adolescent↗
PubMed1993

Prospective comparison of unstable angina versus non-Q wave myocardial infarction during antithrombotic therapy. Antithrombotic Therapy in Acute Coronary Syndromes Research Group.

OBJECTIVES: This study was designed to compare the response of unstable angina and non-Q wave myocardial infarction during treatment with antithrombotic therapy. BACKGROUND: Antithrombotic therapy is beneficial in patients with these two coronary syndromes. METHODS: In a multicenter trial of antithrombotic therapy in unstable angina or non-Q wave myocardial infarction, 358 patients admitted within 48 h of chest pain were randomized to antithrombotic therapy with either 1) aspirin alone, or 2) aspirin plus heparin followed by aspirin plus warfarin, and were prospectively followed up for 12 weeks. Admission cardiac enzyme analyses revealed unstable angina in 268 patients and non-Q wave myocardial infarction in 62. Given an event rate of about 25%, this study has a power of 80% to detect a 50% difference between the two groups. RESULTS: Patients with unstable angina and non-Q wave myocardial infarction were similar with regard to age, gender, coronary risk factors and prior antianginal medication. Primary end points at 12 weeks were recurrent ischemia, infarction and death. [table: see text] In the non-Q wave group, all infarctions and death occurred within the 1st week. CONCLUSIONS: Patients with unstable angina or non-Q wave myocardial infarction on antithrombotic therapy have a similar total number of ischemic events by 12 weeks. However, despite maximal medical therapy with antianginal and antithrombotic medication, patients with non-Q wave infarction have a significantly higher rate of reinfarction and death.

Adrenergic beta-Antagonists↗