Plasma Norharman (β-Carboline) Levels are Elevated in Chronic Alcoholics

Based on the hypothesis that condensation products of neurotransmitters with aldehydes are involved in the pathogenesis of alcoholism, aromatic beta-carbolines (norharman and harman) were measured in the blood plasma of alcoholics and nonalcoholics. The identity of the extracted compounds was confirmed by various elution conditions of the high performance liquid chromatography (HPLC), newly developed radioreceptor assays, and the mass spectrum of norharman. The levels of norharman and harman in nonalcoholics were unchanged after a load with ethanol (1 g/kg body weight). The norharman levels of the alcoholics were significantly higher than that of the nonalcoholic controls (99.5 +/- 26.6 pg/ml vs. 26.9 +/- 10.7 pg/ml; p less than 0.001) and did not change significantly during a 3-week detoxication period. In the subgroup of alcoholics with delirium or hallucinosis, a slight increase of norharman during detoxication could be detected while in alcoholics with vegetative withdrawal symptoms norharman levels dropped slightly over time (p = 0.07). No difference was found with respect to harman between nonalcoholics and alcoholics. These results suggest disturbed regulatory processes in the formation and/or metabolism of norharman in alcoholics. Further investigations are needed to reveal a possible marker function of norharman in alcoholic patients.     

Measurement of quality of life in bone marrow transplantation survivors

This study was designed to assess the reliability and validity of a Quality of Life (QOL) instrument on a sample of 179 allogeneic Bone Marrow Transplant (BMT) survivors. The QOL-BMT tool was developed specifically for this population and was based on the investigators' prior research and a conceptual model of Quality of Life. Patients who were at least 100 days post BMT completed the 30 item visual analogue questionnaire. The instrument measured physical symptoms (e.g., weight loss, frequent colds, skin changes, cataracts, sexual problems), psychological to illness, social concerns (e.g., relationship adjustment, return to work), and spiritual well-being (e.g., sense of control, future goals). Psychometric analysis of the instrument included measures of reliability and validity. The study findings demonstrate the unique aspects of QOL dimensions in BMT survivors and the value of QOL assessment in clinical practice and research.This study was supported by the City of Hope National Medical Center, NCI Cancer Center Core Grant, R30 CA 33572 and the City of Hope BRSG Grant Support.     

Effects of castration, exogenous testosterone and estrogen on endotoxin response in male rats

Using an experimental model of continuous endotoxin infusion, the effects of castration, testosterone and estrogen substitution on disseminated intravascular coagulation in male rats were investigated. Male rats which are not pretreated react in the same way to an endotoxin infusion as female animals, with an increase in free plasma hemoglobin, decrease of fibrinogen level, decrease of hematocrit and platelets and glomerular fibrin depositions. Different experimental groups of testectomized rats were pretreated with (i) 0.3 micrograms (pregnancy-conserving dose) or (ii) 30 micrograms ethinylestradiol (ovulation-suppression dose) or (iii) 250 mg testosterone. They were then compared to groups of animals treated with sesame oil as well as untreated group of rats. The pretreatment with testosterone and estrogens in the small-dose group had only an insignificant effect on the shock sequence. Only those animals which were treated with a high dose of estrogens showed a dramatic enhancement of their endotoxin sensitivity. It was also shown that in male animals an increased estrogen level might mediate a state of 'preparation', but testosterone does not 'prepare' castrated rats for the generalized Schwartzman reaction. The possible significance of enhancement of endotoxin toxicity by estrogens in explaining some pathophysiological characteristics of disseminated intravascular coagulation in pregnancy is discussed.     

Possibilities for frequency adjusted heart stimulation

In the sick sinus syndrome, in sinu-atrial conduction defects or in atrial flutter or fibrillation a stress-adapted, frequency-adapted stimulation cannot be obtained by the processing of the atrial potential. Here one depends on partly extracardiac parameters which contain informations about the metabolic and stress situation, respectively. A survey of the parameters for a frequency-adapted stimulation discussed at present is given and a critical valuation of them is carried out. It is shown that all parameters up to now experimentally and clinically, respectively, tested are more or less problematic and that the way out of the difficulty most consist in deriving the controlled variable for a stress adapted stimulation rate from several parameters.     

Perioperative morbidity and quality of life in long-term survivors following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Improved prognosis can be achieved in selected patients with peritoneal carcinomatosis (PC) by major surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). METHOD: Sixty seven patients with PC were operated with the aim of complete macroscopical cytoreduction followed by HIPEC (using cisplatin, mitomycin or mitoxantrone). Quality of life was assessed with the EORTC QLQ-C30 questionnaire. RESULTS: The patients had a variety of primary tumours, including appendix carcinomas (22/67). Mean operating time was 7 hours and complete cytoreduction was achieved in 58% of the patients. Overall morbidity was 34%. Post-operative mortality was 4.5%. The mean score for global health status of long-term survivors (20 questionnaires/25 patients) was 62.6 (73.3 for the control population, p=0.07). Functional status, particularly the role (56.4) and the social functioning (53.9) were impaired. CONCLUSION: Cytoreductive surgery combined with HIPEC is associated with an increased morbidity and mortality. Complications are predominantly related to major surgery. Following this aggressive treatment, survivors may achieve a satisfactory quality of life.     

Primary pulmonary hypertension in childhood--clinical course and morphologic correlations with particular reference to the endocrine heart

This is a case report of a 13-year-old girl who developed clinical symptoms of primary pulmonary hypertension (PPH). The prognosis is determined by progressive overloading of the right heart. Tissue from both the right and the left atria was examined using immunohistochemical methods. Cardiodilatin/alpha-ANP (atrial natriuretic peptide)-producing myoendocrine cells were analysed. As recent investigations have shown, the atrium and especially the atrial appendages of the heart function as an endocrine organ which is stimulated by pressure and volume overload, and which produces a natriuretic and vasodilatory peptide hormone from myoendocrine cells. In our case we found a general hyperplasia of the myoendocrine cells of the right atrium which is interpreted as a secondary reaction towards an increasing overload. This also means a temporary compensation of the progressive obstruction of the small pulmonary arteries, initiated by vasodilatory heart peptides. These investigations are in agreement with those of other groups who found an increased production of cardiac hormones in atrial overload. In the perinuclear area, electron microscopy shows zones of autophagolysis and the typical specific atrial granules which account for a dysfunction of atrial myoendocrine cells, as seen in other cardiac diseases. Our results may contribute to a better understanding of the pathogenesis of PPH and may help in diagnosis and therapy.     

Glucose consumption in cultured corneal cells

The rate of glucose consumption in cultured epithelium, endothelium, and keratocytes was measured; and the effect of reduced glucose availability on the consumption rate of these three cell lines was delineated. All three cell types exhibited an asymptotic decrease of glucose over time while being incubated in Krebs-Ringers solutions of varying glucose concentrations. At a concentration resembling that of the aqueous, epithelium (EPI), endothelium (ENDO), and keratocytes (K) consumed 6.7, 7.4, and 9.0 micrograms/cm2/hr respectively. Each cell type consumed glucose at a rate that was related to the amount of available glucose. As glucose concentration was reduced from 90 to 30 mg%, which was a 66% reduction in available glucose, the consumption of EPI, ENDO, and K dropped 74%, 61%, and 44% respectively.     

A longitudinal study of the effect of different social rearing conditions on cerebrospinal fluid norepinephrine and biogenic amine metabolites in rhesus monkeys

The purpose of this study was to determine whether disruption of early social attachment alters the activity of brain biogenic amine systems in rhesus monkeys (Macaca mulatta). Male rhesus monkey infants were deprived of maternal interaction, peer interaction, or both, during the first 22 months of life. Cerebrospinal fluid (CSF) was collected under rigorously controlled conditions approximately every month and assayed for levels of norepinephrine (NE), its major metabolite, and the metabolites of dopamine and serotonin. Mother-Deprived infants had lower levels of CSF NE than Mother-Reared infants. Mother-Deprived infants also failed to develop the same pattern of intercorrelations between compounds and month-to-month stability in levels of neurotransmitter and metabolites in CSF as the Mother-Reared infants. Finally, there were changes in CSF NE levels associated with social separation and social group formation. The brain NE system appears to be sensitive to changes in the social environment. Its level of activity, as reflected in levels of NE in CSF, appears to depend on both the prevailing social environment and the prior rearing environment.     

Evaluation of a peer assessment approach for enhancing the organizational capacity of state injury prevention programs.

To conduct a formative and pilot impact evaluation of the State Technical Assessment Team (STAT) program, a visitation-based (visitatie) peer assessment program designed to enhance the organizational capacity of state health department injury prevention programs. The formative evaluation was based on observational, record review, and key informant interview data collected during the implementation of the first 7 STAT visits. Pilot impact data were derived from semi-structured interviews with state injury prevention personnel one year after the visit. Formative evaluation identified 6 significant implementation problems in the first visits that were addressed by the program planners, resulting in improvements to the STAT assessment protocol. Impact evaluation revealed that after one year, the 7 state injury prevention programs had acted on 81% of the recommendations received during their STAT visits. All programs reported gains in visibility and credibility within the state health department and increased collaboration and cooperation with other units and agencies. Other significant program advancements were also reported. Specific program standards and review procedures are important to the success of peer assessment programs such as STAT. Early impact evaluation suggests that peer assessment protocols using the visitatie model can lead to gains in organizational capacity.