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.     

Antennular projections to the midbrain of the spiny lobster. I. Sensory innervation of the lateral and medial antennular neuropils

The organization of sensory afferents in the antennular nerve (AN) of the spiny lobster and the central arborization of the afferents in the lateral and medial antennular neuropils (LAN, MAN) were analyzed by backfilling the AN with biocytin. The MAN receives primarily thick afferents (diameter ≥ 10 μm) with a consistent pattern of arborization from the medial of the three major divisions of the AN. The LAN, in contrast, receives many thin to medium-sized afferents (diameter ≤ 0.3–5 μm), in addition some with diameters ≥ 5 μm, from the lateral and dorsal divisions of the AN. In contrast to the consistent pattern of arborization in the MAN, afferents projecting to the LAN arborize in widely different patterns. Serially arranged, orthogonal side branches that are suggestive of topographical representation of the serially arranged sensilla on the antennule contribute to the stratification of the LAN. Together with existing electrophysiological data, these morphological findings are consistent with the idea that the MAN receives primarily mechanosensory (largely statocyst) input, as previously thought, but that the LAN receives chemosensory as well as mechanosensory input. The chemosensory input to the LAN would represent a novel pathway for processing chemosensory input from the antennule.     

Effect of amiodarone on signal-averaged and long-term ECG]

This prospective study examined the influence of long-term amiodarone therapy on the parameters of the signal-averaged ECG and their relation to simultaneously derived Holter monitoring data. For this purpose, 23 patients with angiographically confirmed dilated cardiomyopathy or coronary heart disease and high-grade ventricular arrhythmias, in whom an average of four class I antiarrhythmic drugs had proven ineffective, were stabilized on amiodarone. Before the beginning of therapy, as well as after 2 months and, subsequently, every 3 months, a resting ECG, a signal-averaged ECG by Simson's method, and Holter monitoring were performed. Compared to the initial measurement, we found a significant increase in the duration of the total filtered QRS complex from an average of 114 +/- 24 ms to 127 +/- 35 ms, while the change in voltage did not reach the significance level. The incidence of late potentials remained largely constant under amiodarone; 10 patients showed a constant late potential, 12 patients had no late potential, and one patient with coronary heart disease developed a new late potential. In the long-term follow-up, we ascertained a relatively high responder rate under amiodarone between 41% and 81%. No relation could be detected between the results of the signal-averaged ECG and those of 24-h Holter monitoring.     

Reperfusion increases neutrophils and leukotriene B4 receptor binding in rat focal ischemia.

BACKGROUND AND PURPOSE: Neutrophils are critically involved with ischemia and reperfusion injury in many tissues but have not been studied under conditions of reperfusion after focal cerebral ischemia. The present studies were conducted to confirm our previous observations quantifying neutrophils in rat permanent focal stroke using a myeloperoxidase activity assay and to extend them to transient ischemia with reperfusion. In addition, leukotriene B4 receptor binding in ischemic tissue was evaluated as a potential marker for inflammatory cell infiltration. METHODS: Histological, enzymatic, and receptor binding techniques were used to evaluate neutrophil infiltration and receptor binding in infarcted cortical tissue 24 hours after permanent middle cerebral artery occlusion (n = 25) or temporary occlusion for 80 (n = 12) or 160 (n = 22) minutes followed by reperfusion for 24 hours in spontaneously hypertensive rats. RESULTS: Sham surgery (n = 26) produced no changes in any parameter measured. After permanent middle cerebral artery occlusion, neutrophil accumulation was observed histologically, but the infiltration was moderate and typically within and adjacent to blood vessels bordering the infarcted cortex. After temporary middle cerebral artery occlusion with reperfusion, marked neutrophil infiltration was observed throughout the infarcted cortex. Myeloperoxidase activity was increased (p less than 0.05) after permanent occlusion and to a greater extent after temporary occlusion with reperfusion. Myeloperoxidase activity (units per gram wet weight) in ischemic cortex was increased over that in nonischemic (control) cortex 32.2-fold, 54.6-fold, and 92.1-fold for permanent occlusion and 80 and 160 minutes of temporary occlusion with reperfusion, respectively (p less than 0.05). Sham surgery produced no changes in myeloperoxidase activity. Leukotriene B4 receptor binding also was increased (p less than 0.05) after focal ischemia and paralleled the increases in myeloperoxidase activity. Ischemic cortex-specific receptor binding (femtomoles per milligram protein) was 3.87 +/- 0.63 in sham-operated rats and 4.57 +/- 0.98, 8.98 +/- 1.11, and 11.12 +/- 1.63 for rats subjected to permanent occlusion and 80 and 160 minutes of temporary occlusion with reperfusion, respectively (all p less than 0.05 different from sham-operated). Cortical myeloperoxidase activity was significantly correlated with the degree of cortical leukotriene B4 receptor binding (r = 0.66 and r = 0.79 in two different studies, p less than 0.01). CONCLUSION: These data indicate that neutrophils are involved in focal ischemia and that there is a dramatic accumulation of neutrophils in infarcted tissue during reperfusion that can be quantified using the myeloperoxidase activity assay. Leukotriene B4 receptor binding increases in infarcted tissue in a parallel manner, which suggests that the increased leukotriene B4 binding is to receptors located on the accumulating neutrophils.