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Biomedical subjects

B Osborne

Publications and source records attributed to B Osborne.

At least 37 records · Page 2Linked to original sources

Biochemical effects of losartan, a nonpeptide angiotensin II receptor antagonist, on the renin-angiotensin-aldosterone system in hypertensive patients.

We investigated the effects of angiotensin II (Ang II) type 1 receptor blockade with losartan on the renin-angiotensin-aldosterone system in hypertensive patients (supine diastolic blood pressure, 95 to 110 mm Hg). Qualifying patients (n = 51) were allocated to placebo, 25 or 100 mg losartan, or 20 mg enalapril. Blood pressure, plasma drug concentrations, and renin-angiotensin-aldosterone system mediators were measured on 4 inpatient days: end of placebo run-in, after first dose, and 2 and 6 weeks of treatment. Plasma drug concentrations were similar after the first and last doses of losartan. At 6 weeks, 100 mg losartan and 20 mg enalapril showed comparable antihypertensive activity. Four hours after dosing, compared with the run-in day, 100 mg losartan increased plasma renin activity 1.7-fold and Ang II 2.5-fold, whereas enalapril increased plasma renin activity 2.8-fold and decreased Ang II 77%. Both drugs decreased plasma aldosterone concentration. For losartan, plasma renin activity and Ang II increases were greater at 2 than at 6 weeks. Effects of losartan were dose related. After the last dose of losartan, plasma renin activity and Ang II changes were similar to placebo changes by 36 hours. These results indicate that long-term blockade of the feedback Ang II receptor in hypertensive patients produces modest increases of plasma renin activity and Ang II that do not appear to affect the antihypertensive response to the antagonist.

Adult↗

A pilot study of etoposide, vinblastine, and doxorubicin plus involved field irradiation in advanced, previously untreated Hodgkin's disease.

BACKGROUND: Advanced stage Hodgkin's disease (HD) usually is treated with combination chemotherapy with or without supplemental irradiation. The risk of significant acute and long term toxicity when the chemotherapy regimen contains alkylating agents has provided the impetus for the development of systemic combinations that do not include alkylating agents. This trial was designed to assess the toxicity and efficacy of a regimen of etoposide, vinblastine, and doxorubicin (EVA) as part of a combined modality approach in patients with moderate to high risk HD. METHODS: This was a prospective pilot study that included 26 previously untreated patients. They received 6 cycles of EVA, and complete responders received low dose (1500-2500 cGy) involved field radiation. RESULTS: Four patients were hospitalized for sepsis during chemotherapy. Complete response was achieved in 54% of patients, and 46% patients experienced induction failures. Two year failure-free survival is 44%, while 2 year overall survival is 86%. Median follow-up is 27 months. CONCLUSIONS: The EVA regimen is no more efficacious than other programs already in use and may be less so. It also is potentially leukemogenic because of the presence of etoposide. New combinations that do not contain etoposide should be explored in therapy programs for advanced HD in the hopes of discovering an efficacious treatment program that has minimal long term side effects.

Adolescent↗

Emergence of leprosy in a patient with mycosis fungoides.

A patient with mycosis fungoides that had progressed to tumor stage responded to chemotherapy and electron beam treatment, but 6 years later a peripheral neuropathy, extensive plaques, erythroderma, and enlarged pinnae containing acid-fast organisms developed while he was being treated with photopheresis. The skin lesions cleared with administration of rifampin and dapsone, but a reversal reaction biopsy specimen showed features of both mycosis fungoides and leprosy. This case raises the question of whether there may be an association between mycosis fungoides and leprosy.

Antineoplastic Combined Chemotherapy Protocols↗

An outbreak of respiratory syncytial virus in a bone marrow transplant center.

An outbreak of respiratory syncytial virus (RSV) infection occurred among 31 patients in a marrow transplant center over a 13-week period beginning in January 1990. RSV infection was also documented in 35 family members and employees. Of 18 patients with pneumonia, 14 (78%) died. None of 13 with upper respiratory infection died. Preengraftment patients tended to develop pneumonia more frequently than did engrafted patients. Early administration of ribavirin may have had a beneficial effect in patients with pneumonia. Antigenic and genomic analysis of 14 available isolates suggested that at least four different viral strains were responsible for the outbreak. One group of patients and 1 employee in spatial proximity were infected with the same strain and likely acquired their infections nosocomially. RSV infection in marrow transplant patients is a serious and life-threatening infection with a high mortality rate once pneumonia develops.

Adolescent↗

A subchronic toxicity study of two inhaled aerosolized atropine sulfate formulations in rats and dogs.

The potential subchronic (21 days) toxicity of inhaled metered aerosol formulations (solution and suspension) of atropine sulfate was investigated in rats and dogs. The doses administered to rats were 0.78 and 2.5 mg/kg/day (solution) or 1.4 and 3.2 mg/kg/day (suspension). In the dog, the daily doses achieved were 0.5 and 1.3 mg/kg/day, regardless of formulation. In both species, sham control animals inhaled air only and vehicle control animals inhaled either placebo solution or placebo suspension. There was no mortality or other evidence of a toxic effect of atropine sulfate. The expected mydriatic effect of atropine sulfate was seen in both species and, similarly, the pupillary light reflex was impaired in rats and dogs receiving either formulation of atropine sulfate at both dose levels. Reduced salivation was also noted and ophthalmologic examinations in both species were unremarkable. In dogs, atropine sulfate (high-dose) caused tachycardia but there was no evidence of an adverse effect on the electrocardiogram or on systolic blood pressure. In both species, atropine sulfate did not alter body weight, food consumption or clinical pathology parameters. Necropsy observations and histopathological findings revealed no effect of atropine sulfate in either species although, in the rat, adrenal gland hypertrophy in both sexes followed inhalation of the suspension at both dose levels. With this possible exception, nothing but the expected pharmacological effects of atropine sulfate were seen in either rats or dogs.

Administration, Inhalation↗

Twenty-five years of renal trauma at a teaching hospital.

In a study of 535 patients with renal trauma admitted to the Medical College of Virginia Hospitals from 1962 to 1988, the authors found indications of a decrease in the rate of total nephrectomy in patients with blunt trauma, due in part to advances in diagnostic technology. In the cases of gunshot wounds, however, a persistently high rate of nephrectomy prevailed, reflecting, the authors believe, the proliferation of increasingly lethal weaponry.

Humans↗

Response variation in instrumental extinction in rats with fornix transections.

The present experiment examined spatial and response variation interpretations of the large difference in magnitude between operant and instrumental extinction deficits seen in hipocampally damaged animals. Latency measures and detailed behaviors of rats with fornix transections were compared to those of control rats during acquisition and extinction in an enriched spatial runway. Control rats, in comparison to rats with fornix transections, exhibited larger increases in start box, runway, and goal box latencies, but no spatial gradients were found. Control rats also exhibited less goal persistence and more response variation following the transition to extinction. The results suggest no fundamental difference between operant and instrumental deficits following hippocampal damage, but an interaction between strategies employed and traditional response measures.

Animals↗

Effects of fornix transection and pituitary-adrenal modulation on extinction behavior.

We examined whether the absence of a dynamic pituitary-adrenal response contributes to the behavioral deficit seen in hippocampally damaged rats following the transition to extinction of a learned behavior. In the first experiment, total lever presses and detailed behaviors of rats with fornix transection and replacement ACTH4-10 or ACTH were compared with the behavior of fornix-transected and sham-transection groups during acquisition and extinction of lever pressing. Fornix-transected rats showed increased resistance to extinction and an altered pattern or mode of extinction responding. ACTH4-10 or ACTH acted similarly in reducing extinction lever presses in fornix-transected rats without altering the mode of extinction responding. In the second experiment the extinction behaviors of rats with fornix transection were compared with those of normal, sham-transection adrenalectomized, or dexamethasone-treated rats. Fornix-transected rats again showed increased resistance to extinction and a different mode of responding during extinction. Adrenalectomized rats showed an extinction deficit but differed from fornix-transected rats. The behavior of dexamethasone-treated rats was similar to that of controls. The results are interpreted to mean that ACTH and corticosterone both affect extinction behavior (in opposite ways) but do not account for the extinction deficit seen in hippocampally damaged rats.

Adrenocorticotropic Hormone↗

Behavioral and adrenal responses and meal expectancy in rats with fornix transection.

The behavioral and corticosterone responses of control rats and rats with fornix transections were examined during eating sessions and when consummatory behavior was blocked but cues controlling the behavior were maintained. Rats with fornix transection exhibited increased frequencies of eating, trips away from the food cup, and exploration, but decreased durations of these behaviors, and differential organization of behavior during eating and blocked eating sessions. Control rats exhibited increased corticosterone levels to blocked eating; fornix transected rats did not. The groups did not differ on basal corticosterone levels or hormonal responses to deprivation, and neither group exhibited conditioned hormonal responses to repeated sampling. The results indicate that control rats, but not rats with fornix transection, respond to the violation of an expectation with increased corticosterone levels.

Animals↗

Meal patterns following changes in procurement cost for rats with fornix transection.

The purpose of the present study was to explore the effects of a varied procurement cost on the foraging behavior of rats with fornix transection. An operant analog of foraging requirements was used to examine the feeding patterns of the animals under free feeding, low procurement cost (FR5), and high procurement cost (FR80) situations, in an environment with minimal sensory distraction. It was found that animals with fornix transection did not differ from control rats in general consumption. Both groups were also able to adapt their feeding behavior to the varied procurement cost. As the procurement cost increased, the number of meals consumed decreased while the meal duration increased. The meal patterns themselves were different for the fornix transected animals and the control group. Animals with fornix transections ate more meals over the course of a day than did control animals; their meals were of a longer duration, and their intermeal intervals were shorter than those of control animals. During the course of a meal, the rats with fornix transections took a larger number of breaks, during which they drank, explored, or engaged in activities other than eating. These differences in the feeding patterns were seen across all procurement cost levels. The data support the possibility of hippocampal involvement in behavioral organization or sequencing.

Animals↗

Disrupted patterns of consummatory behavior in rats with fornix transections.

The feeding and drinking behavior was examined in male rats with fornix transections and sham-operated control rats. Total food and water consumption was recorded but supplemented by a pattern analysis of feeding and drinking behavior. The behavior of the rats was continuously monitored during four hour morning and afternoon sessions under ad lib access and during a two hour session following adaptation to a restricted access feeding schedule. Rats with fornix transections were more active and exhibited increased frequencies of rearing, eating and drinking. The increased meal frequency in rats with fornix transections was accompanied by decreased meal durations and a reduction in the length of intermeal intervals. Total food and water consumption was unaffected by fornix transection as were the duration of sleep bouts and the frequencies of grooming, sleeping and carrying shavings. Fornix transections also reduced food carrying and food hoarding but only under conditions of restricted food access. The results suggest that fornix transection does not alter major homeostatic regulatory mechanisms nor does it alter the components of feeding and drinking behavior. Fornix transection alters, instead, the organization of microregulatory feeding and drinking patterns.

Animals↗

Primary lymphomas of the nasal cavity and paranasal sinuses.

Extranodal lymphomas which present in the nasal cavity and/or the paranasal sinuses are rare. Thirty-eight patients with disease that was clinically limited to the head and neck (Ann Arbor Stages IE-IIE) were admitted between 1947 and 1983. Twenty-eight patients were treated with radiotherapy alone and 10 received combination chemotherapy in addition. The overall 5-year survival figure was 56%. The corresponding result for Stage IE was 67%. No patient with Stage IIE disease survived 5 years. Extent of the extranodal disease also influenced results for Stage IE patients who were treated with radiotherapy only. When the extranodal disease was staged using the American Joint Committee TNM system, the 5-year disease-free survival for T1 and T2 patients was 78% as compared with 19% for patients with T3 and T4 disease. The addition of combination chemotherapy improved results for patients with T3 and T4 lesions.

Adult↗

Heterogeneity of non-Hodgkin's lymphoma probed by nucleic acid cytometry.

Flow cytometric analyses of cellular DNA, RNA, and double-stranded RNA content were performed on lymph nodes and extranodal tissue from 177 patients with non-Hodgkin's lymphoma. With increasing histologic grade, a higher incidence of aneuploidy, higher proliferative activity, and higher total and double-stranded RNA content were found. Despite considerable cytometric heterogeneity within histologic grades and morphologic subdivisions, conformity between cytometric and morphologic classifications was observed in 85% of cases. Among intermediate-grade and high-grade lymphomas, increased proliferative activity and diploidy were associated with more frequent responses to treatment. Thus, nucleic acid-derived parameters relate to morphologic subtypes and permit an objective approach to lymphoma classification based on ploidy, proliferation, and RNA characteristics that also had prognostic implications.

Aneuploidy↗

Characterization of a porcine genomic clone encoding a major histocompatibility antigen: expression in mouse L cells.

A porcine genomic clone encoding a major histocompatibility, (MHC) antigen was isolated by direct screening of a swine genomic library with a heterologous human MHC cDNA probe. Mouse L cells transformed with DNA from the clone stably express swine MHC antigen. Pig alloantisera specifically lyse transformant but not control cell lines in a complement-mediated cytotoxicity assay. Direct immunoprecipitation of radiolabeled cellular protein from transformed lines by pig alloantiserum results in the coprecipitation of swine MHC heavy chain and mouse beta 2-microglobulin, demonstrating the association of heterologous subunits of MHC antigens.

Animals↗

Lymph node involvement by histiocytosis X.

Lymph node involvement by histiocytosis X is usually secondary to nearby bone or skin lesions. A patient with histiocytosis X confined to lymph nodes is rarely seen; however, we studied two such persons. In each, a lymph node biopsy was performed because the clinical aspects caused us to suspect neoplastic disease.

Adult↗

The role of visual and haptic cues in children's discrimination learning.

Three experiments using kindergarten boys and girls (Ns = 126, 84, and 72, respectively) tested the hypothesis that adding haptic to visual information facilitates discrimination of three-dimensional objects on more difficult (three-choice) problems, but not on easier (two-choice) problems. Kindergartners were given a two-or three-choice discrimination problem under one of four conditions of cue availability: visual cues, haptic cues, and visual plus haptic cues with stimuli touched or not touched before choosing. Addition of haptic cues did not improve performance either on two-choice problems (two or three experiments), as predicted, or on three-choice problems (all three experiments), contrary to predictions.

Child, Preschool↗

Bacterial infection stimulating granulocytic sarcoma of the small bowel.

A 57-year-old white man who had abdominal pain and distension, died after a short hospitalization for increasing ascites, anorexia, and deteriorating mental status. At autopsy, the principal gross finding was a dilated, hyperemic, thickened proximal jejunum that by light microscopy consisted of a transmural infiltrate of large mononuclear cells. Intense naphthol AS-D chloroacetate esterase (NASD) positivity was observed within most of the cells, suggesting granulocytic sarcoma. However, bacterial strains and electron-microscopic examination revealed that the massive jejunal infiltrate was composed of macrophages containing numerous phagocytosed bacteria. Although occasional cells had primary and secondary granules characteristic of myeloid precursors present within their cytoplasm, most cells lacked specific granules. Attempts to reproduce this markedly enhanced NASD result experimentally in peritoneal macrophages of mice were unsuccessful. This case shows that intense NASD cytoplasmic staining may occasionally occur macrophages that have phagocytosed large numbers of bacteria.

Animals↗