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Biomedical subjects

R Heller

Publications and source records attributed to R Heller.

At least 145 records · Page 8Linked to original sources

The intergroup Hodgkin's disease in children. A study of stages I and II.

A total of 228 previously untreated and eligible children with pathologic Stage I or II Hodgkin's disease were registered in the Intergroup Study of Hodgkin's Disease in Children between February 1977 and April 1981. Patients were randomized in the Southwest Oncology Group (later the Pediatric Oncology Group [POG] to involved-field (IF) radiotherapy alone or IF radiotherapy followed by six courses of mechlorethamine, vincristine, prednisone, and procarbazine (MOPP) chemotherapy; patients in the Children's Cancer Study Group (CCSG) and Cancer and Leukemia Group B (CALGB) were randomized to receive extended-field (EF) radiotherapy or IF radiotherapy followed by six courses of MOPP. An estimated 97% of patients receiving IF + MOPP were relapse-free and surviving (RFS) at 5 years, which was significantly better than 41% for patients receiving IF alone; however there was essentially no overall difference in survival experience between groups. Patients in CCSG and CALGB receiving IF + MOPP had significantly superior RFS at 5 years than patients receiving EF. Survival rate was not different between these two groups, an estimated 93% of patients surviving 5 years or longer. Although patients were not randomized between IF or EF radiotherapy, they were similar with respect to patient characteristics. There was some statistical evidence that RFS was superior at 5 years for patients receiving EF than for IF; however, there was no evidence of a difference in survival experience. The percentages of patients with late effects of therapy were not significantly different by treatment. The most common types of late effects were endocrine dysfunction and impaired resistance to infection. Overall, the response rate to therapy for relapse patients was good, being 83% among all patients who relapsed. Patient characteristics related to poor prognosis were the presence of constitutional (B) symptoms (fever, night sweats, and weight loss) and poor performance status.

Adolescent↗

Platelet membrane defects in fawn hooded bleeder rats.

An inbred strain of fawn hooded rats with a congenital platelet defect shows a marked bleeding tendency with prolonged bleeding time. This haemorrhagic disorder has been exclusively related to a deficiency of nucleotides in platelet dense granules. When tested in cell electrophoresis platelets from fawn hooded bleeder rats showed a significantly lower electrophoretic mobility than normal rat platelets. Subsequent studies on the platelet membrane protein pattern by high resolution two-dimensional gel electrophoresis revealed the deficiency of a membrane glycoprotein (apparent molecular mass 90.000, isoelectric point 5.6), which is detectable in normal rat platelets after surface labeling by periodate-tritiated sodium borohydride. It seems likely, that this glycoprotein defect contributes at least partially to the disorder of platelet function in fawn hooded bleeder rats.

Animals↗

The Dubbo study: an Australian prospective community study of the health of elderly.

The proportion of Australian population over 60 years has risen progressively over the last 40 years and this growth is projected to continue. Major health problems of the elderly include coronary heart disease, cerebro-vascular disease, osteoporosis and fracture. The risk factors for coronary heart disease and stroke in middle-aged subjects have been extensively documented in prospective studies in Australia and elsewhere, and include lipid disorders, hypertension, cigarette smoking, diabetes and family history. Few prospective studies have been targeted exclusively on the elderly and information available with respect to vascular risk factors is fragmentary and contradictory. This is the background to a new prospective study of the health of elderly Australians now under way in Dubbo, NSW. The goals of the Dubbo Study are to identify predictors of mortality, hospitalisation and placement in long-term care, while specific aims are the study of risk factors for chronic diseases and disability. This report describes the study rationale, reasons for selecting Dubbo as the study site, methods and measures, participation rates and demography. The target population included all non-institutionalised subjects 60 years and over, domiciled in Dubbo, and is comprised of 1693 males and 2167 females. The attendance rate for an extensive medical and sociological baseline assessment over a 13 months' period was 73% for both sexes. The prospective study is now in place and within three to five years will be generating definitive information in the elderly.

Aged↗

[Four-week training of patients with large anterior wall infarct: comparison with a randomized untrained control group].

Thirty-nine male patients (average age 50.8 years +/- 8.4 years) with a large anterior myocardial infarction (average 45.6 days +/- 10.5 days ago) and with moderate to severe left-ventricular dysfunction (RNVA EF less than 50%) participated in the study. The patients were randomly assigned to either a training group or to a control group. They were also subdivided into training/control groups (EF less than 30% and EF = 30-50%). The training program consisted of three to four sessions per day, 5 days a week, at an intensity of up to 1 W/kg body wt. (approximately 4-5 METS). The following evaluations were recorded prior to and following the 4-week training program: relative heart volume (x-ray), echocardiographic data (enddiastolic diameter, ES-distance, and shortening fraction), and exercise stress test (work capacity, heart rate). Filling pressures, cardiac outpout, and stroke volume index were calculated from right-heart catheterization (Swan-Ganz) at rest and during exercise. Results indicate that there were no significant changes in relative heart volume, end-diastolic volume, ES-distance, resting heart rate, PCP at rest, and ejection fraction during exercise as a result of the training program. Shortening fraction showed a tendency to improve (not significant). Work capacity increased by 15 W (p less than 0.05) in the training group and by 28 W (1.5 METS, p less than 0.05) in the EF less than 30% training-group as compared with the control group. Cardiac output at rest decreased by 10% (p less than 0.05). Stroke-volume index increased in the EF greater than 30% training-group, while heart rate was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗

Cost-benefit analysis of early return to work after uncomplicated acute myocardial infarction.

The economic consequences of an Occupational Work Evaluation designed to identify low risk patients recovering from uncomplicated acute myocardial infarction (AMI) and hasten their return to work was evaluated in a randomized trial. Two hundred one employed, clinically low risk men recovering from AMI were randomized to undergo an intervention (intervention group, 99 patients) consisting of an Occupational Work Evaluation or to receive usual care (usual care group, 102 patients). The time to return to work was reduced from 75 days in usual care patients to 51 days in intervention patients (p less than 0.002). Significant differences were found between groups for medical costs and occupational income during follow-up. Total medical costs per patient were lower in the intervention patients than in the usual care patients in the 6 months after AMI ($2,970 vs $3,472). Occupational income per patient was higher in intervention patients than in the usual care group in the 6 months after AMI ($9,655 vs $7,553). The per capita benefit accounting for medical costs and occupational income was $6,685 for intervention patients and $4,081 for usual care patients. Projected to the greater than 300,000 low risk, employed survivors of AMI annually in this country, the savings generated by the Occupational Work Evaluation could yield an annual economic benefit greater than 800 million dollars.

Algorithms↗

Electrofusion of individual animal cells directly to intact corneal epithelial tissue.

An electromechanical process was developed to electrofuse human and nonhuman cultured cells directly to rabbit corneal epithelial tissue in vitro and in situ. This new process was utilized successfully to incorporate functional gonococcal membrane attachment receptors from human lymphoma cells into superficial rabbit corneal epithelium. Thus, cell-tissue electrofusion biotechnology may be employed to establish unique and novel animal models for investigating receptor-mediated processes in vivo.

Animals↗

Role of Na+/H+ exchange in thrombin-induced platelet-activating factor production by human endothelial cells.

Thrombin-stimulated endothelial cells produce platelet-activating factor (PAF) in a dose-dependent manner: the activation of a Ca2+-dependent lyso-PAF acetyltransferase is the rate-limiting step in this process. The present study shows that acetyltransferase activation and consequent PAF production induced by thrombin in human endothelial cells are markedly inhibited in Na+-free media or after addition of the amiloride analog 5-(N-ethyl-N-isopropyl)amiloride, suggesting that a Na+/H+ antiport system is present in endothelial cells and plays a prominent role in thrombin-induced PAF synthesis. Accordingly, thrombin elicits a sustained alkalinization in 6-carboxyfluorescein-loaded endothelial cells, that is abolished in either Na+-free or 5-(N-ethyl-N-isopropyl)amiloride-containing medium. Extracellular Ca2+ influx induced by thrombin (as measured by quin2 and 45Ca methods) is completely blocked in the same experimental conditions, and monensin, a Na+/H+ ionophore mimicking the effects of the antiporter activation, evokes a dose-dependent PAF synthesis and a marked Ca2+ influx, which are abolished in Ca2+-free medium. An amiloride-inhibitable Na+/H+ exchanger is present in the membrane of human endothelial cells, its apparent Km for extracellular Na+ is 25 mM, and its activity is greatly enhanced when the cytoplasm is acidified. These results suggest that Na+/H+ exchange activation by thrombin and the resulting intracellular alkalinization play a direct role in the induction of Ca2+ influx and PAF synthesis in human endothelial cells.

Acetyltransferases↗

Methylene blue inhibits the arachidonic acid metabolism in human blood platelets.

When human blood platelets are incubated with methylene blue (MB) that oxidizes cellular NADPH, a marked inhibition of platelet aggregation and of the metabolism of arachidonic acid (AA) in both the cyclooxygenase and lipoxygenase pathway is found. The inhibition of aggregation and AA metabolism is prevented, at least partially, by the thiol-oxidizing agent diamide. The results indicate an involvement of the reduced coenzymes NADPH and glutathione (GSH) in the regulation of cyclooxygenase and lipoxygenase activity in platelets.

Arachidonic Acids↗

Regulation of carbamoyl phosphate synthetase-aspartate transcarbamoylase-dihydroorotase gene expression in growing and arrested cells.

We have studied expression of the carbamoyl-P synthetase-aspartate transcarbamoylase-dihydroorotase (CAD) gene in growing or confluent Syrian hamster cells, and also in cells arrested by depriving them of serum or restimulated by adding fresh serum. In contrast to other biosynthetic enzymes such as dihydrofolate reductase, the amount of the CAD enzyme decreased very little when growth was arrested, as judged by the small change in aspartate transcarbamoylase activity. However, the level of CAD mRNA was about 10-fold lower in arrested cells than in growing cells. The rate of transcription of CAD, measured by the nuclear run-off technique, decreased roughly in parallel with the decrease in the steady-state level of the mRNA, suggesting that control of transcription is probably an important element in the overall regulation of CAD gene expression. Expression of a different gene which lies near the 5' end of CAD changed in parallel with that of CAD, but expression of two other genes in the same region was insensitive to the growth state of the cells. Therefore, control of gene expression as a function of growth was specific rather than a reflection of more general changes in chromatin structure in the vicinity of CAD.

Amidohydrolases↗

Forestomach motility in the camel (Camelus dromedarius).

There is a cyclical pattern of motility in compartments 1 and 2 of the forestomach of the camel which can be categorized into A- and B-contractions. An average motility cycle is composed of 7 A- and 5 B-contractions and lasts 5 min, including a pause of 2.3 min. The glandular sacs within the caudal sac of compartment 1 contract 1.7 sec earlier than the caudal sac. The proximal part of the canal between compartment 2 and 3 contracts 1.2 sec prior to the distal part. Forestomach motility is stimulated by distention of the cranial sac of compartment 1 and inhibited by distention of the tubiform portion of compartment 3.

Animals↗