Toxicity of 2,3,7,8-tetrabromodibenzo-p-dioxin in rats after single oral administration.

Five male and female rats per dose-group received 2,3,7,8-tetrabromodibenzo-p-dioxin (2,3,7,8-TBDD) once on the first day of the study. Doses of 10, 33, 100, or 300 micrograms 2,3,7,8-TBDD/kg body wt. and the vehicle control were administered by gavage. About 20% of 2,3,7,8-TBDD was excreted via feces. Severe body weight retardation was observed in the 100 and 300 micrograms/kg dose-groups. Most animals in the 300 micrograms/kg dose-group and the females receiving 100 micrograms/kg showed emaciation, rough coat and a poor health (wasting syndrome). Of the animals dosed with 300 micrograms/kg, 3 males and all females died. After 100 micrograms 2,3,7,8-TBDD/kg 3 females died. Measured 4 weeks after dosing, triiodothyronine (T3) was increased and thyroxin (T4) was reduced dose dependently in serum. A dose-dependent decrease in thymus weights was observed at necropsy and histological examinations showed that thymus and spleen were depleted of mature lymphocytes. An increase in liver-to-body weight ratio was observed in all dose-groups. The histological examination revealed hypertrophy of centrilobular hepatocytes in the liver of animals treated with 100 micrograms/kg, which was less severe at the 33 micrograms/kg dose. Hypertrophic hepatocytes were also detected in some animals at the lowest dose. Induction of enzyme activities of the mixed function oxidases ethoxycoumarin O-deethylase (ECOD), ethoxyresorufin O-deethylase (EROD) and aryl hydrocarbon hydroxylase (AHH) in liver tissue differed for each of the three enzymes. Two days after administration, enzyme activities were increased but did not differ substantially between dose-groups. Twenty-eight days after dosing the increase in activity after 10 micrograms/kg was largest and the EROD of the 100 micrograms/kg dose-group in females was close to that of the control. This inverse dose-response relationship may be due to impaired liver cell function at higher doses.     

Magnetic resonance imaging (MRI) of the breast

Zusammenfassung Grundlagen: Der Zweck war es, die Anzahl der im Mammogramm entdeckten duktalen Carcinoma in situ (DCIS) und multizentrische Karzinome aufzudecken. Die verschiedenen Methoden der Biopsie werden diskutiert. Methodik: Rastermammographie (Fokus 0,3 mm) und hochaufl?sende Sonographie (7,5 bis 10 MHz) wurden bei Brustkrebspatientinnen eingesetzt. Ergebnisse: Der Zeitraum der aufgelisteten Patientinnen erstreckt sich über 20 Jahre. Die Zahl der DCIS hat in den letzten Jahren zugenommen und betr?gt nun 18%. Die Mammographie ist hoch sensitiv für Entdeckung von Mikrokalzifikationen. Die Spezifit?t ist gering. Schlu?folgerungen: Die Anzahl der entdeckten DCIS ist in den letzten Jahren besonders angestiegen und wird auch noch weiter bei Verbesserung der mammographischen Techniken ansteigen. Diese Studie wurde vom Ludwig-Boltzmann-Institut für radiologisch-physikalische Tumordiagnostik unterstützt.     

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.