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Biomedical subjects

C Higgins

Publications and source records attributed to C Higgins.

At least 55 records · Page 3Linked to original sources

Lymphoblastic lymphoma in adults.

Fifty-one patients with lymphoblastic lymphoma (LBL) treated with one of five successive intensive chemotherapy protocols for acute lymphoblastic leukemia (ALL) since 1971 were reviewed. The patients were divided into leukemic and nonleukemic groups, and their clinical and laboratory parameters compared. The projected 5-year survival rate for all patients treated with the L10/17 protocols was 45% for both leukemic and nonleukemic LBL. The response to treatment was compared with that of 111 patients with ALL and was nearly identical. Poor prognostic factors were age beyond 30, WBC greater than 50,000/microL, failure to achieve a complete response (CR), and a late CR during induction. Leukemia at presentation, T cell surface markers, and the presence of a mediastinal mass did not adversely affect survival. The use of intensive chemotherapy protocols has proven to be a significant advance in the treatment of LBL.

Adolescent

Inhibition of testicular LDH-X from laboratory animals and man by gossypol and its isomers.

The inhibitory effect of (+)-, (-)-, (+/-)-gossypol and (+/-)-gossypol acetic acid upon testicular cytosolic LDH-X was measured in vitro. Gossypol acetic acid (0-100 mumol/l) inhibited LDH-X prepared from the testes of the mouse greater than rabbit greater than human greater than rat greater than hamster. There was no relationship between inhibition and in-vivo antifertility activity. LDH activity measured in vitro in serum of men and hamsters was unaffected by gossypol. Gossypol and its isomers were non-competitive inhibitors of human and hamster LDH-X with respect to the coenzyme NADH, competitive inhibitors of human LDH-X and noncompetitive-competitive inhibitors of hamster LDH-X with respect to the substrate alpha-ketobutyrate. Co-incubation with human serum albumin or poly-L-lysine but not lysine protected human and hamster LDH-X from gossypol.

Animals

Terminology and anatomy of angulated coronary arteriography.

Angulated views in coronary arteriography have been increasingly utilized because of their superiority in demonstrating lesions not well seen in standard right and left oblique projections. The importance of these angulated views has been repeatedly demonstrated. It is the purpose of this article to review some basic coronary anatomy angulation terminology, and then to describe the particular advantages of the angulated views in coronary arteriography. Illustrations of these particular views of both coronary systems will be provided.

Angiography

Primary therapy of acute promyelocytic leukemia: results of amsacrine- and daunorubicin-based therapy.

Remission rates for patients with acute promyelocytic leukemia (APL) have improved with the use of anthracyclines and proper management of disseminated intravascular coagulopathy. In a prospective randomized trial of chemotherapy in patients with acute nonlymphoblastic leukemia, there were 16 patients with APL. All 7 of the patients receiving the amsacrine-containing regimen and 5 of 9 receiving the daunorubicin-containing regimen achieved a remission. All patients, except 2 of the 3 who underwent bone marrow transplantation, remain alive and in remission from 1+ to 25+ mo. Amsacrine is an effective replacement for daunorubicin in the treatment of APL, and its use does not compromise the favorable remission duration characteristic of APL.

Adult

Arthrographic studies in painful hemiplegic shoulders.

The rehabilitation of hemiplegic patients is often prolonged by the problem of painful shoulder. The specific etiology of this problem is controversial and treatment does not always produce the desired results. Thirty hemiplegic patients with painful, stiff ipsilateral shoulder joints were studied. The mean interval from the onset of stroke to the onset of painful shoulder was 3 months. On shoulder arthrography, 23 patients had capsular constriction typical of frozen shoulder (adhesive capsulitis). Seven patients had normal arthrograms. None showed rotator cuff or capsular tears. Electromyography revealed electrical silence in the shoulder musculature at rest. These findings indicate that the painful, stiff shoulder developing after hemiplegia is not caused by rotator cuff tear or by spasticity, but probably has a pathogenesis similar to that of idiopathic frozen shoulder.

Adult

Pulmonary blood volume: analysis during exercise in patients with left ventricular dysfunction.

Recent reports have demonstrated substantial increases in pulmonary activity during radionuclide stress exercise studies in patients with coronary heart disease. These studies have shown that the degree of the increase reflected the severity of the underlying disease. We studied the effects of supine exercise on systolic function and pulmonary activity in ten normal control subjects and 20 patients with congestive cardiomyopathy (12 ischemic and 8 idiopathic). Ejection fraction rose in the normals (P less than 0.001), end-diastolic volume increased slightly but significantly (P less than 0.05), and pulmonary activity rose by less than 16%, (mean 10%) while cardiac output increased by 162%. On the other hand, the myopathy patients demonstrated a small increase in cardiac output, (+49%) with a more substantial increase in pulmonary activity (+25%, P less than 0.05 vs normals). In these patients, ejection fraction did not change during exercise, while end-diastolic and end-systolic volumes rose. In the myopathy patients, the cause for an increase in cardiac output was a rise in heart rate, with little change in stroke volume. We conclude that pulmonary activity rises in myopathy patients to a greater extent than in normal controls. This probably reflects the greater elevation in filling pressures these patients need to maintain forward cardiac output.

Adult

Mechanism of increase in left ventricular end-diastolic pressure after contrast ventriculography in patients with coronary artery disease.

Elevation in left ventricular (LV) end-diastolic pressure (EDP) after contrast ventriculography (CV) has been proposed as a form of stress intervention in patients with coronary artery disease (CAD). The mechanism of this change has not been delineated. Accordingly, we performed two studies in CAD patients. In study 1 (n = 10), CV was repeated 3 minutes after an initial study. LVEDP rose from 14.9 +/- 6.6 mm Hg prior to the first ventriculogram to 26.9 +/- 10.8 mm Hg 3 minutes after the first ventriculogram (p less than 0.05) and immediately prior to the repeat CV (performed to evaluate the changes in volume produced by the first ventriculogram). In four patients with LV micromanometer pressures, the entire diastolic pressure-volume relation was shifted upward. LV ejection fraction (EF) and end-diastolic volume (EDV), peak LV pressure, and peripheral vascular resistance were unchanged at the time of repeat CV, and there was no correlation between the change in EDP and any of these variables. In study 2 (n = 6), gated radionuclide angiography was performed prior to and at minutes 2 to 7 after CV as were measurements of LV and right ventricular (RV) pressures. While both LV and RV EDP rose following contrast ventriculography, LV and RV EDV and EF were unchanged. We conclude that alterations in LVEDP after CV are unrelated to changes in LV or RV EDV and are most likely mediated by a decrease in myocardial compliance.

Adult

The mechanism of action of the antiinflammatory agents dexamethasone and Auranofin in human polymorphonuclear leukocytes.

Human polymorphonuclear neutrophils (PMN) were treated with the antiinflammatory agents dexamethasone or Auranofin. PMN treated with dexamethasone in a dose range of 0.25-1 microM or Auranofin, 5-15 mM, were stimulated with 10(-7)M N-formyl-methionyl-leucyl-phenylalanine (FMLP). These agents were shown to inhibit the functional responses of degranulation and superoxide production in a dose-dependent manner. Similarly, the change in electrophoretic mobility, reflecting cell surface charge, was blocked. While both agents inhibited change in the fluorescence of the calcium chelate probe chlorotetracycline (CTC), the pattern of inhibition was significantly different. Dexamethasone appeared to inhibit the CTC response during its latter phases, while Auranofin inhibited all aspects of the CTC response. Auranofin was additionally shown to significantly decrease specific binding of FMLP, as well as the number of FMLP receptors. The two agents thus appear to act by different mechanisms. Dexamethasone is shown to have an effect on membrane-bound calcium release as measured by CTC, while Auranofin interferes with receptor binding.

Auranofin

Synergistic effect of heparin and chemotactic factor on polymorphonuclear leukocyte aggregation and degranulation.

The in vitro effects of therapeutic amounts of polyanionic heparin on human polymorphonuclear leukocytes (PMN) aggregation and on the release of cationic lactoferrin from PMN-specific granules were investigated. Incubation of 1 X 10(7) human PMNs with 0.3 unit/ml of heparin followed by stimulation with the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) 2 X 10(-7) M significantly increased PMN aggregation, compared with controls. Cytochalasin B potentiated aggregation, which was further increased by incubation of the PMNs with heparin. Similarly, heparin also increased PMN degranulation and lactoferrin release following stimulation with FMLP with or without cytochalasin B, compared with controls. In addition, human lactoferrin complexed with heparin on a sucrose density gradient and caused a significant shift in the migration of 3H-heparin. Finally, rabbits pretreated with intravenous heparin resulting in prolongation of their activated partial thromboplastin time (APTT) to 1.5 to 2.5 times baseline had more profound reduction in PMN counts following a challenge with the secretagogue phorbol myristate acetate (PMA). These studies demonstrate that heparin can interact synergistically with chemotactic stimuli known to evoke lactoferrin release, which in turn leads to enhancement of PMN aggregation. Our data further suggest that heparin may be contraindicated in the treatment of syndromes with increased PMN aggregation such as endotoxin-induced Schwartzman-type reactions.

Animals

Mother-child separation: a study in a remote health care setting.

The literature indicates that the birth of a sibling and the consequent temporary separation from the mother is usually a stressful experience for a child. It was hypothesized that this stress would result in an increased number of visits by the child to health care facilities because of new health problems. In a controlled study of 89 matched pairs of Indian families in a remote region of northwestern Ontario this hypothesis was not supported. During the intervals studied - the anticipatory period before delivery, the separation itself and the period immediately following the mother's return home - the number of diagnoses of new medical problems was significantly less for the children who were separated from their mothers for the birth of a sibling. As well, the number of diagnoses of new medical problems in the children separated form their mothers decreased over the three intervals. The fathers' reluctance to seek health care probably played a major role in this decrease.

Age Factors

Changes in energy metabolism, structure and function in alveolar macrophages under anaerobic conditions.

To determine whether the change in energy metabolism of guinea-pig alveolar macrophages (AM) would alter their function to resemble peritoneal macrophages (PM), AM were exposed to strict anaerobic environments for 96 h. Exposure of cultivated AM to hypoxic conditions resulted in a decreased activity of cytochrome oxidase, a key enzyme in oxidative phosphorylation, whereas pyruvate kinase activity, a key enzyme in glycolysis, increased to levels observed in PM. Under hypoxic conditions the total mitochondrial structure available for respiratory activity also decreased in the glycolytic energy-dependent AM. Accompanying the shift in energy metabolism, adaptive changes in the functional responses of lectin-receptor activity occurred in the AM exposed to hypoxic conditions. Culture of AM in an anaerobic environment led to a loss in their ability to mobilize their lectin receptors in response to cytochalasin B, whereas AM maintained in an aerobic environment could mobilize their receptors in response to either cytochalasin B and D. Alterations in O2 tension affect AM metabolism, morphology and function and indicate that the AM is able to change its energy metabolism according to environmental circumstances.

Anaerobiosis

Accumulation of circulating macrophages in lungs of guinea pigs exposed to hyperoxia.

Superoxide dismutase (SOD) and glutathione peroxidase (GPx) key enzymes in alveolar macrophages regulating levels of superoxide anion and hydrogen peroxide, respectively, were observed to fluctuate in response to FIO2 of 50 and 85% for 18 to 90 hr. At the lower oxygen tension, SOD rose two-fold and GPx decreased significantly by 18 hr and throughout the exposure periods compared to a delayed increase in SOD activity which was not sustained beyond 66 hr of exposure and a sustained rise in GPx to an FIO2 of 85%. Peritoneal macrophages containing lower SOD activity and greater GPx activity than resident alveolar macrophages upon injection into the circulation resulted in 10-fold accumulation in the lungs during exposure of animals to FIO2 of 85% but not at 50%. This study indicates that brief exposure to FIO2 of 85% but not 50% resulted in alterations of the vascular integrity of the lungs resulting in the accumulation of circulating macrophages to the alveolar macrophage pool. The delayed rise in SOD activity and the sustained increase in GPx activity in alveolar macrophages from animals exposed to FIO2 of 85% could in part be related to this influx of circulating macrophages with enzymatic characteristics observed for peritoneal macrophages.

Animals

The use of slow-scan video for CME in a remote area.

Since August 1977 a slow-scan video system has been operating in a remote area of northwestern Ontario, Canada. This system, using regular dial-up telephone lines, interconnects the local hospital, five remote communities, and two teaching hospitals in Toronto, 1,000 miles distant. Since August 1978 the system has been used on a regular basis for continuing medical education programs, graduate medical education including X-ray rounds, medical rounds, nursing rounds, in-service education, and patient education. These CME programs for physicians have been accepted for study credits by the College of Family Physicians of Canada.

Education, Medical, Continuing