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Biomedical subjects

K Butler

Publications and source records attributed to K Butler.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1990

Dideoxycytidine alone and in an alternating schedule with zidovudine in children with symptomatic human immunodeficiency virus infection.

OBJECTIVE: To determine whether a short course of 2',3'-dideoxycytidine (ddC) could provide safe antiretroviral activity in children with symptomatic human immunodeficiency virus infection and whether it could be used with azidothymidine (AZT, zidovudine). The goal was to maintain uninterrupted antiretroviral therapy while sparing AZT-related myelosuppression and ddC-related neuropathy. METHODS: In a pilot study, we evaluated four dosage levels of ddC--0.015, 0.02, 0.03, and 0.04 mg/kg, given orally every 6 hours--in 15 children between 6 months and 13 years of age with Centers for Disease Control P2 (i.e., symptomatic) human immunodeficiency virus infection. Thirteen patients had not had any prior antiretroviral therapy; two patients had received and benefited from AZT, but dose-limiting neutropenia had developed. At each dosage level, ddC was given for 8 consecutive weeks and then stopped. After a 30-day rest, a schedule of ddC for 1 week was followed by 3 weeks of AZT therapy (180 mg/m2 every 6 hours); this alternating schedule was repeated for as long as tolerated. Age-appropriate psychometric testing was performed before the start of ddC therapy and after 8 weeks. RESULTS: During the 8 weeks of therapy with ddC alone, no neutropenia or anemia was observed; 6 of 9 patients had decreases in p24 antigen levels, and 8 of 15 had an increased CD4 cell count. At the 0.04 mg/kg level, a rash developed in three patients; mild mouth sores developed in 9 of 15 patients. On the alternating ddC/AZT schedule, no neuropathy was observed. CONCLUSIONS: 2',3'-Dideoxycytidine has antiretroviral activity in some children and appears to be safe for short intervals. Longer courses of ddC at lower dosage levels, and schedules integrating ddC into combination regimens, deserve to be explored.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Does magnetic resonance imaging compromise integrity of the blood-brain barrier?

It has been reported that a standard clinical procedure of magnetic resonance imaging (MRI) carried out experimentally in the rat caused temporary opening of the blood-brain barrier. Electron micrography indicated blood-to-brain movement of horseradish peroxidase, a protein tracer that does not normally permeate the barrier. In the present study, permeability-area products (PA), describing the limited permeation of blood-borne [14C]sucrose into brain parenchyma, were measured in anesthetized rats subjected either to 23 min of MRI, to osmotic barrier opening by intracarotid infusion of hypertonic arabinose, or to control conditions. Osmotic opening caused manyfold increases in PA whereas MRI produced no change. The proposal that MRI can compromise integrity of the blood-brain barrier is not supported by these findings.

Animals↗
PubMed1989

Treatment of advanced malignant melanoma with coumarin and cimetidine: a pilot study.

Based on previous results demonstrating that coumarin and cimetidine render objective tumor regressions in renal cell carcinoma, we conducted a pilot study to determine whether these drugs possess activity against malignant melanoma. A total of 22 patients with advanced melanoma received 100 mg coumarin p.o. daily for 14 days; on day 15, cimetidine was added at an oral dose of 300 mg four times daily. Both drugs were continued until progression of disease. In all, 12 patients had previously been treated, but all patients had a favorable performance status. No response was observed in 19 patients. Two patients with a low tumor burden achieved a partial response and a third showed a minor response. There was no toxicity from this regimen. Although coumarin and cimetidine at this dose and schedule did not display significant activity in this study population, further studies are warranted to explore higher doses and focus on patients with relatively low tumor burdens.

Adult↗
PubMed1989

National Pediatric Trauma Registry.

The National Pediatric Trauma Registry (NPTR) is a multi-institutional database designed to compile information concerning all aspects of pediatric trauma care. The registry is designed and operated in a manner that maximizes data accuracy and provides this information to all participating investigators. The growth of the database has allowed the NPTR to provide the first accurate epidemiologic description of pediatric trauma as a national disease, as well as to develop national norms for pediatric trauma care. The registry presently contains 10,177 patients, and is undergoing revisions (phase II) to allow a more focused evaluation of various aspects of the clinical care and rehabilitation of the pediatric trauma patient.

Child↗
PubMed1989

Treatment of renal cell carcinoma with daily low-dose alpha-interferon.

While alpha-interferon has yielded objective tumor regressions in patients with metastatic renal cell carcinoma, such therapy is usually associated with significant toxicity often requiring dose modifications and/or cessation of therapy. In the absence of a clearly defined optimal dose and schedule for alpha-interferon, it appears reasonable to seek a means for improving the therapeutic index for this drug. We report the results of a pilot trial in which patients with renal cell carcinoma were treated with a daily low dose of alpha-interferon. Seventeen patients were treated with alpha-interferon (Roferon-A) at a dose of 1 million U subcutaneously daily. There were no exclusionary criteria for this pilot trial. Sixteen patients were evaluable for response and toxicity. Therapy was well-tolerated with no interruption of therapy for toxicity. No patient experienced the "flu-like" syndrome that is associated with higher doses, and there was no episode of granulocytopenia or thrombocytopenia. Four patients achieved a partial response (PR), with one PR persisting at 20 months. Sites of response included lung (two patients), liver (one patient), and bone (one patient). These results indicate that this regimen is well tolerated and can be expected to render objective responses. Formal Phase II trials are warranted in order to define the response rate for this regimen.

Aged↗
PubMed1988

The E4T electric powered total artificial heart (TAH).

The E4T is a totally implantable total artificial heart (TAH) resulting from many years of research work at the Cleveland Clinic Foundation (CCF) and Nimbus, Inc. It consists of four implanted subsystems: the pumping unit, the variable volume device, the transcutaneous transformer, and the internal battery. The pumping unit consists of two CCF biolized pusher plate pumps, and a Nimbus electrohydraulic energy converter. The control logic is based on a left master, alternating beating scheme. The timing difference between end right eject and end left fill determines the actuator speed adjustment. The pumps free fill, so left-right flow differences are easily accommodated. A prototype system has been built and begun testing to validate and refine the design details.

Electric Power Supplies↗
PubMed1987

Oxidant stress in malaria as probed by stable nitroxide radicals in erythrocytes infected with Plasmodium berghei. The effects of primaquine and chloroquine.

Erythrocytes from normal mice and mice infected with the malarial parasite Plasmodium berghei reduce the water-soluble spin probes 2,2,6,6-tetramethylpiperidine-4-hydroxy-N-oxyl (TEMPOL), 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) and 2,2,6,6-tetramethylpiperidine-4-keto-N-oxyl (TEMPONE) at similar rates under both air and N2 atmospheres. The ESR signal of the lipid-soluble spin probe 5-doxyl-stearate is stable on incorporation into erythrocytes from normal mice. In contrast, parasitized red cells reduce this nitroxide probe, at a rate which increases with the level of parasitemia. Inhibitors of electron transport such as KCN and NaN3, increase the rate of reduction. We propose that nitroxide reduction occurs via the electron transport chain in the parasite. The antimalarial drug primaquine causes reduction of both water-soluble and lipid-soluble spin probes. This action of primaquine is independent of its ability to release H2O2 from oxyhemoglobin, and is ascribed to the ability of primaquine to accelerate flux through the hexose monophosphate shunt. The increased production of NADPH results in increased rates of reduction of the nitroxide radicals. Methylene blue, which also increases flux through the shunt, is even more effective than primaquine at reducing the nitroxides. Chloroquine has no such effect. Parasitized mice treated with chloroquine six hours prior to ESR measurements show less nitroxide reducing capacity than do untreated mice. Chloroquine is known to decrease flux through the hexose monophosphate shunt. The metabolic influences of the two antimalarial drugs are, thus, quite different.

Air↗
PubMed1987

Treatment of metastatic renal cell carcinoma with coumarin (1,2-benzopyrone) and cimetidine: a pilot study.

Forty-five patients with metastatic renal cell carcinoma were treated with coumarin (1,2-benzopyrone) and cimetidine. Patients received coumarin, 100 mg orally daily; cimetidine administration, 300 mg orally four times daily, was initiated on day 15 of therapy, and treatment with both drugs was continued until progression of disease. Three patients are too early to evaluate (on study less than or equal to 2 months with no change in tumor status). Objective responses (greater than or equal to 50% reduction in measurable disease) occurred in 14 of 42 evaluable patients (33.3%) (the 95% confidence interval based on this rate is +/- 14.3%), with three complete responses and 11 partial responses (PR). Complete responses lasted 9.5, 4+, and 9.5+ months. The median duration of response for the PR group was 5 months (range, 4 to 21+ months). Twelve patients experienced stabilization of disease ranging from 4 to 16.5+ months. No response was seen in 16 patients. There was no symptomatic, hematologic, or chemical (organ dysfunction) toxicity among the 45 patients treated. Coumarin and cimetidine appear to be safe and active agents in the treatment of metastatic renal carcinoma. Further studies are required to determine the optimal dose and scheduling of these agents.

Adult↗
PubMed1985

A versatile perfusion technique for metabolic studies by NMR.

A perfusion technique applicable to metabolic studies by NMR is described in detail. The utility and versatility of the approach are demonstrated by following gluconeogenesis from [2-13C]pyruvate in the perfused, isolated mouse liver, and lipogenesis from [2-13C]acetate in perfused Acanthamoeba castellanii cells embedded in agarose filaments.

Acetates↗
PubMed1985

Plasmodium berghei: gluconeogenesis in the infected mouse liver studied by 13C nuclear magnetic resonance.

Using 13C nuclear magnetic resonance, we have compared the gluconeogenic activity of perfused livers isolated from normal starved mice and mice highly parasitized with Plasmodium berghei, using [2-13C]pyruvate as substrate. In both types of livers, 13C labeling of glucose carbons occurred in positions 1, 2, 5, and 6. The equal proportions of [1,6-13C]- and [2,5-13C]glucose in livers from malarial and normal mice suggests that pyruvate enters the gluconeogenic pathway directly and, to an equal extent, via the tricarboxylic acid cycle. The normalized signal heights indicated that at a given time after the addition of [2-13C]pyruvate the degree of 13C labeling in glucose carbons was reduced in livers from malarial animals, when compared to livers from normal animals. During the course of the perfusion experiment, the [2-13C]lactate resonance signal was always more intense from livers of malarial animals than from normal animals. A reduced activity of hepatic gluconeogenesis in malarial animals was further confirmed by a separate set of perfusion experiments which showed a 56% reduction of the measured rate of glucose production in livers from malarial animals, with respect to that of normal animals. A lowered NAD/NADH ratio in livers from malarial animals would explain the increased proportion of lactate observed in the spectra and be related to a decreased gluconeogenic rate. A more reduced oxidoreduction level in the hepatocytes of a malarial animal would result from a defect in the oxidative phosphorylation activity of mitochondria.

Animals↗
PubMed1985

Experimental evaluation of complete electrically powered ventricular assist system.

The LVAS utilizing an intrathoracic blood pump and a parathoracic, electrohydraulic energy converter has a number of promising features. These include: transcutaneous energy transmission and an implanted variable volume device which eliminate the need for percutaneous access; utilization of an intrathoracic blood pump and variable volume device which allow the diaphragm and abdominal cavity to remain intact; parathoracic or subcutaneous location of the transformer secondary, energy converter, internal battery and interconnecting elements allowing replacement with a minor surgical procedure; employment of the "biolized" continuous blood contacting surface which has the potential of long-term use without anticoagulants and utilization of an electrohydraulic energy converter which provides synchronization without requiring transducers and associated electronics and which provides lubrication of mechanical components. The development effort, which began separately in 1977 and has been conducted jointly by Nimbus and the Cleveland Clinic since 1980, has demonstrated that the above features can be incorporated in a reliable LVAS. In particular, the system in vivo test series have demonstrated the soundness of the basic concepts and led to refinements which were demonstrated in the 6-1/2 mo test. All elements of the system have been utilized during the in vivo test program. Component tests of significance include: LVAS and total heart blood pump in vivo experiments of up to 7 mos duration which demonstrate the blood compatibility of the biolized surface without the use of long-term anticoagulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗