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Biomedical subjects

K Butler

Publications and source records attributed to K Butler.

At least 19 recordsLinked to original sources
PubMed1995

Correlates between nuclear magnetic resonance spectroscopy, diffusion weighted imaging, and CA1 morphometry following chronic brain ischemia.

Chronic brain ischemia (CBI) was induced in aging (13 month) rats by ligating the left subclavian artery and placing temporary occluders in each common carotid artery [three-vessel occlusion (3-VO)]. Carotid artery occluders were removed after 1, 2, or 3 weeks following brain ischemia or maintained for 9 weeks. Two rats were kept with their occluders in place for 25 weeks. On weeks 3 and 9 after CBI, 31P-/1H-nuclear magnetic resonance (NMR) spectroscopy and high resolution diffusion weighted imaging were performed in vivo, non-invasively for detection of hippocampal high energy phosphates, lactate, intracellular pH, N-acetyl-aspartate, choline, glutamate, creatine, and structural alterations of the brain following CBI. Brains were histologically processed for morphometry of glial fibrillary acidic protein (GFAP) and CA1 damaged neurons 9 weeks after CBI. 31P-/1H-NMR spectroscopy showed that high energy substrates remained normal in ischemic animals when compared to non-ischemic controls except for an elevation of phosphomonesters in the hippocampal region. Rats deoccluded 1 and 2 weeks after initiation of CBI had no NMR spectroscopic or imaging changes. Rats kept ischemic for 9 weeks showed high signal intensities in the parietal cortex detected by diffusion weighted imaging as well as CA1 damage and increased GFAP density but no cortical atrophy or neuronal damage could be detected histologically. Rats kept ischemic for 25 weeks showed extensive cortical atrophy which corresponded to the high signal intensity observed with diffusion weighted imaging in the group kept ischemic for 9 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗
PubMed1995

Characterization of the morphological and functional alterations in rabbit subclavian artery subjected to balloon angioplasty.

BACKGROUND: A number of experimental models for the study of the pathogenesis of the restenotic process have been developed, although many fail to correlate the time courses of both functional and morphological alterations following balloon injury. Our aim was to develop a rabbit model of balloon injury, which studied both of these alterations in detail. METHODS: Male New Zealand White rabbits (12 weeks old) were fed a high-cholesterol diet for 4 weeks, after which they were subjected to balloon injury of the left subclavian artery. After surgery the animals were returned to a normal diet and sacrificed 2, 7, 15 or 30 days after angioplasty. Two further groups of animals were sacrificed either after 4 weeks of high-cholesterol feeding (no angioplasty) or 2 days after a sham angioplasty operation. Angioplasty-induced changes in vasoconstrictor [to 5-hydroxytryptamine (5-HT) and KCl] and endothelium-dependent (ACh and calcimycin) and endothelium-independent (sin-1) vasodilator responses were assessed in isolated vessel rings. Morphological analysis of the size and composition of neointima was also made at each timepoint. RESULTS: Hypercholesterolaemia reduced the responsiveness of the subclavian arteries to the endothelium-dependent vasodilators carbachol and calcimycin; however, this responsiveness was restored after 7 days of a normal diet. The response to carbachol remained depressed in angioplastied arteries until 30 days after angioplasty, whereas recovery of relaxation to calcimycin was unaffected by angioplasty. Responses to 5-HT, KCl and sin-1 were unchanged by either hypercholesterolaemia or angioplasty. Morphological studies demonstrated the development of neointima in all rabbits after 7 days, reaching a maximum size after 15 days. All neointima stained for a smooth muscle actin. Accumulation of macrophages appeared in the media after 7 days and was present in the neointima after 15 days, and subsequently declined. Proliferating smooth-muscle cells were evident in the media 2 days after angioplasty, and in the neointima fro 7 days onwards. CONCLUSION: In the rabbit subclavian artery, we have developed a model that describes fully the temporal development and characteristics of an intimal cellular response and functional changes following balloon injury.

Angioplasty, Balloon↗
PubMed1995

Cuban embargo.

Explore the source record for details and available documents.

Commerce↗
PubMed1994

An updated review of the clinical development of coumarin (1,2-benzopyrone) and 7-hydroxycoumarin.

Several authors have demonstrated that coumarin (1,2-benzopyrone) in combination with cimetidine can produce objective antitumor responses in some patients with advanced renal cell carcinoma. The purpose of this report is to review the clinical development of coumarin, with or without cimetidine, with special reference to renal cell carcinoma (RCC). Previously unpublished data concerning the survival of a population of patients with RCC, who were treated on a phase I trial of coumarin and cimetidine, are presented. The rationale and study design of an active randomized, double-blinded, placebo-controlled trial of coumarin for RCC are discussed. A progress report is given for an ongoing phase I trial of oral 7-hydroxycoumarin, the major human metabolite of coumarin.

Adult↗
PubMed1994

The Cleveland Clinic-Nimbus total artificial heart. Design and in vitro function.

We describe the design and in vitro testing of the Cleveland Clinic-Nimbus electrohydraulic permanent total artificial heart as it nears completion of development. The total artificial heart uses an electric motor and hydraulic actuator to drive two diaphragm-type blood pumps. The interventricular space contains the pump control electronics and is vented to an air-filled compliance chamber. Pericardial tissue valves and biolized blood-contacting surfaces potentially eliminate the need for anticoagulation. In vitro studies on a mock circulatory circuit demonstrated preload-sensitive control of pump output over the operating range of the blood pump: 70 to 160 beats/min and 5 to 9.6 L/min at right and left atrial pressures of 1.0 to 7.0 mm Hg and 5.0 to 12.0 mm Hg, respectively. The pump output was found to be insensitive to afterload over a range of 15 to 40 mm Hg mean pulmonary artery pressure and 60 to 130 mm Hg mean systemic pressure. The left master alternate control mode balanced the ventricular outputs during simulated bronchial artery shunting of up to 20% of cardiac output. A 10% to 15% right-pump, stroke-volume limiter balanced ventricular outputs during maximum output of 9.6 L/min. In response to a sustained increase in systemic venous return, the pump increased output by 2 L/min (29%) in 35 seconds. Thus the Cleveland Clinic-Nimbus total artificial heart meets the National Heart, Lung, and Blood Institute hemodynamic performance goals for devices being developed for permanent heart replacement. The biolized blood-contacting surfaces should decrease the risk of thromboembolism associated with circulatory assist devices.

Cardiac Output↗
PubMed1993

Treatment of transitional cell carcinoma of the bladder with intravesical interleukin-2: a pilot study.

Human recombinant interleukin-2 (rIL-2) administered systemically can mediate the regression of solid tumors in some patients. IL-2 has been detected in the bladder effluent from patients treated with intravesical BCG for transitional cell carcinoma of the bladder (TCC), suggesting that IL-2 may be an effector molecule in the mechanism of action of BCG. The purpose of the pilot study was to determine the response rate, duration of response and toxicity of rIL-2 (Cetus) administered intravesically to previously untreated patients and patients who had failed prior intravesical therapy with other agents. Fourteen patients with biopsy proven transitional cell carcinoma (13 Stage TIS/Ta/T1, 1 Stage T2) were treated with 8 weekly instillations of 12 x 10(6) IU of rIL-2. An index lesion was followed with cystoscopy, biopsy and cytology at three months, with identical follow up every three months thereafter if a response was noted in the index lesion at the first evaluation. There were 3 complete responses (duration of response measured from start of treatment to date of progression) of 9+, 3, 9 months; one patient with TIS, and 2 patients with Ta disease. There were 11 non-responders for an overall response rate of 21%. One patient with extensive CIS had a dramatic partial response and was converted to a complete response with a second 8-week course of rIL-2. All of the complete responders had failed prior intravesical therapy with standard agents. Toxicity from rIL-2 given intravesically was minimal. One patient reported malaise for 24 hours after each treatment and two patients developed asymptomatic lower UTIs.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗
PubMed1992

The no-reflow phenomenon is a post-mortem artifact.

Post-ischemic reperfusion impairment, ("no-reflow phenomenon"), was studied in rats subjected to 8-30 minutes of global brain ischemia. During ischemia, rapid and complete loss of cerebral blood flow, EEG and 31P-high energy phosphates (ATP/PCr) was observed. Brain intravascular perfusion defects were examined by injecting carbon black intravenously in a group of rats with stable cardiopulmonary function and in another group subjected to rapid thoracotomy and intraarterial infusion of the carbon marker. Results indicate that global brain ischemic or non-ischemic control rats given intraarterial carbon black after thoracotomy had varying degrees of vessel filling defects in brain resulting in "pale tissue areas" suggestive of impaired perfusion (no-reflow). All rats given carbon black intravenously whether global brain ischemic or not, showed normal cerebrovascular filling of the carbon black and absence of "pale tissue areas". In addition, post-ischemic cerebral reperfusion following 8-30 minutes global brain ischemia can reverse neuroelectric, energy metabolite and cerebral blood flow loss in rats whose cardiopulmonary function is not compromised. These findings indicate that the "no-reflow phenomenon" is an agonal or post-mortem artifact observed in the presence of cardiopulmonary failure.

Adenosine Triphosphate↗
PubMed1992

The use of tracer gases to determine dust dispersion patterns and ventilation parameters in a mineral processing plant.

A study was conducted in a fluorspar milling plant to assess the effectiveness of tracer gases as a reliable supplement to conventional air-monitoring and ventilation measurements. In the course of this study, a tracer gas was used as a surrogate substance to analyze the direction and the rate of spread of contaminants from various potential dust production points in the plant. Time-weighted average and continuous mineral dust concentrations were measured in several areas of the plant; these results were compared and correlated with steady-state tracer gas concentrations in the mill. Time-weighted average dust concentrations varied between 0.18 and 0.57 mg/m3 for total dust and 0.04 and 0.20 mg/m3 for quartz respirable dust, depending on the location. Correlation of these values with steady-state tracer gas concentrations yielded linear relationships with correlation coefficients (R2) of 0.95 and 0.87, respectively, for total and quartz dust. Results from this study, therefore, indicate that tracer gases may help model the spread of airborne respirable dust from point sources. These tracer gas releases also allowed the simultaneous quantitative determination of air residence times and contaminant clearance times from the building. Hence, tracer gases will help industrial hygienists obtain useful data with respect to building ventilation.

Air Pollutants, Occupational↗
PubMed1991

Return of ATP/PCr and EEG after 75 min of global brain ischemia.

Acute, progressive global brain ischemia was induced in awake or anesthetized rats for 5-75 min. Ischemia was achieved with a subclavian-carotid artery occlusion technique (SCOT). After thoracotomy, both subclavian arteries (proximal to their vertebral branches) were tied-off and carotid artery catheter-snares installed. Results show progressive morphological, physiological and neurochemical damage when CBF was reduced from preischemic levels of 115 ml to 0 blood flow. 31P magnetic resonance spectroscopy of high energy phosphate metabolites in vivo showed loss of PCr and beta-ATP signals after 6 min brain ischemia. Energy metabolite levels, EEG and CBF normalized within hours after reperfusion. Degree of neuropathologic damage to hippocampal region appeared linearly related to the ischemic duration of ischemia. Thus, acute global brain ischemia resulted in loss of high energy phosphate metabolites, EEG and neuronal integrity in the hippocampal subfields. Reperfusion following short (5 min) or long (75 min) periods of global brain ischemia induced return of 31P-spectra, EEG and CBF to normal but was unable to reverse all of the neuronal damage at the end of the 72-h observation period.

Adenosine Triphosphate↗
PubMed1991

Bacterial infections in human immunodeficiency virus type 1-infected children: the impact of central venous catheters and antiretroviral agents.

We conducted a retrospective study to analyze the impact of central venous catheters (CVCs) and antiretroviral therapy on the frequency and the patterns of bacterial infections in children infected with human immunodeficiency virus during a 3-year period. Among 204 bacterial infections other than otitis media reviewed, soft tissue infection (n = 69), bacteremia (n = 57), pneumonia (n = 27) and sinusitis (n = 27) were encountered most frequently. Catheter-related staphylococcal infection was the most common infection in children with CVCs, particularly in those who were less than 6 years old. In children without CVCs, Streptococcus pneumoniae was the most frequent organism. Younger children had more CVC-related infections whereas children with lower CD4 counts had more CVC-related and CVC-unrelated infections. A lower frequency of CVC-unrelated infections was detected in patients who received antiretroviral therapy, especially those receiving a continuous infusion of zidovudine. These data suggest that increased frequency and altered patterns of bacterial infections are associated with the use of CVCs in these patients, but antiretroviral therapy may reduce the frequency of CVC-unrelated infections.

Adolescent↗
PubMed1991

Effect of U74006F on forebrain ischemia in rats.

We examined the effect of a putative lipid peroxidation inhibitor, the 21-aminosteroid U74006F, on transient forebrain ischemia in rats. Acute-treatment rats received either 3 mg/kg U74006F (n = 7) or carrier vehicle (n = 5) intravenously 30 minutes before ischemia, sustained-treatment rats received the same treatment before ischemia followed by 3 mg/kg U74006F (n = 6) or carrier vehicle (n = 5) intraperitoneally every 6 hours for 48 hours, and control rats (n = 7) received no injection. Coronal magnetic resonance images were obtained daily for 3 days, followed by the histological examination of perfusion-fixed brains. Control rats demonstrated magnetic resonance image changes indicative of neuronal damage in the striatum at 24 hours postischemia, followed by changes in the hippocampus and neocortex at 48 hours. No significant effect of U74006F treatment on striatal or hippocampal injury was demonstrated. However, both the acute and sustained U74006F treatments produced a significant reduction in the severity of neuronal damage in the neocortex (p less than 0.05). Our results suggest that U74006F is of benefit in ameliorating ischemic neuronal injury, particularly in the neocortex, and raise the possibility of regional variability in lipid peroxidation following an ischemic insult.

Animals↗
PubMed1991

Phase I evaluation of coumarin (1,2-benzopyrone) and cimetidine in patients with advanced malignancies.

Fifty-four patients with advanced malignancies were treated on this phase I trial of coumarin and cimetidine. The dose of coumarin was escalated, with three patients treated at each dose level, while the cimetidine dose was held constant at 300 mg four times daily. Patients received coumarin alone as a single daily oral dose for 14 days; on day 15, cimetidine was added and both drugs were continued until progression of disease. This trial was initiated with patients receiving coumarin at 400 mg daily and closed at 7 g daily with four of five patients on this dose experiencing nausea and vomiting. Treatment was generally well tolerated over a wide range of coumarin doses. Symptomatic side effects were few, mild, and usually self limited. Side effects included insomnia, nausea, vomiting, diarrhea, and dizziness. Two patients withdrew from therapy because of daily nausea and vomiting. Typically, nausea, vomiting, and dizziness occurred 2.5-3 hours after a dose of coumarin. In most patients, these side effects abated spontaneously with continuation of therapy. There was no significant hematologic or renal toxicity. Hepatotoxicity occurred in only one patient and was manifested by asymptomatic abnormal elevations of serum hepatic transaminases. This toxicity was reversible upon interruption of therapy. Objective tumor regressions were observed in six patients with renal cell carcinoma. Responses occurred at coumarin doses ranging from 600 mg to 5 g daily. Coumarin is a relatively nontoxic, oral, outpatient therapy that warrants further investigations for the treatment of human malignancies. Because of its low toxicity, there is potential for combining coumarin with chemotherapeutic and/or biological agents in an attempt to improve on efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Treatment of hormone-refractory stage D carcinoma of prostate with coumarin (1,2-benzopyrone) and cimetidine: a pilot study.

The combination of coumarin (1,2-benzopyrone) and cimetidine has been reported to render objective tumor regressions among patients with metastatic renal cell carcinoma and malignant melanoma. Subsequently, a pilot trial was conducted to evaluate this regimen for the treatment of stage D hormone-refractory carcinoma of the prostate. Patients received coumarin 100 mg orally as a single daily dose for 14 days; on day 15 cimetidine 300 mg four times daily was added, and both drugs were continued until progression of disease. Fourteen patients with advanced prostate cancer were treated. Nine patients had evaluable disease only, whereas five patients had both measurable and evaluable disease. All patients had bone metastases. Although there was no objective evidence of tumor regression, three patients (with evaluable disease only) experienced significant improvement in bone pain with decreased analgesic use that persisted until disease progression at 3, 5.5+, and 9 months. Although coumarin caused no symptomatic or organ dysfunction toxicity, one elderly patient experienced reversible mental confusion from cimetidine. Coumarin and cimetidine, at the dose and schedule described, are not effective for the treatment of advanced prostate cancer. However, the results of laboratory investigations suggest that further clinical trials of coumarin, at higher doses, may be warranted for the treatment of this disease.

Aged↗
PubMed1990

Low incidence of asymptomatic brain metastases in patients with renal cell carcinoma.

Brain metastases from renal cell carcinoma are uncommon. The present study was undertaken to determine the value of routine computerized tomographic (CT) scanning of the brain in patients with renal cell carcinoma. A review of 106 patients with renal cell carcinoma who had undergone CT scan of the brain revealed brain metastases in only 13.2 percent. Brain metastases were accompanied by central nervous system (CNS) symptoms in 78.6 percent of patients, with headaches constituting the most common presenting symptom (64.3%). Brain metastases were detected in only 3.3 percent of patients who had no CNS symptoms at the time of evaluation. It is concluded that CT scanning of the brain should be performed routinely only for those patients who report CNS symptoms at the time of evaluation.

Adult↗
PubMed1990

Growth and neuroendocrine dysfunction in children with acquired immunodeficiency syndrome.

To assess whether neuroendocrine dysfunction is present in children with acquired immunodeficiency syndrome (AIDS) and growth failure, we evaluated the thyroid, adrenal, and growth hormone-insulin-like growth factor I (IGF-1) axes in nine children with AIDS and failure to thrive. Basal thyroid-stimulating hormone, free thyroxine, and triiodothyronine levels were normal in eight of the nine children and indicated primary hypothyroidism in one child; thyroxine levels were elevated in four and normal in five children. Thyroxine-binding globulin levels were elevated in all children. Serial measurements of thyroid-stimulating hormone, made hourly from 2 to 6 pm and from 10 pm to 2 am, revealed a flat diurnal rhythm of thyroid-stimulating hormone in six children, which may indicate early central hypothyroidism, and a normal nocturnal rise in the remaining three children. Basal plasma corticotropin and aldosterone levels were normal in all children, plasma renin levels were normal in three and elevated in six children, and cortisol levels were normal or elevated in all children. Corticotropin-stimulated cortisol levels exceeded 500 nmol/L (18 micrograms/dl) in all children except one, who was receiving treatment with ketoconazole. Thus adrenocortical function appeared to be grossly intact. The peak growth hormone responses to provocative testing was normal (greater than 7 ng/ml) in eight children and low in one child. The plasma level of insulin-like growth factor I was normal in eight of the nine children and low in one child. We conclude that growth failure in children with AIDS does not usually result from a recognized endocrine cause and that adrenal function is usually normal. However, endocrine deficiency may contribute to morbidity in some children with AIDS.

Acquired Immunodeficiency Syndrome↗