Evidence that neuropeptide Y (NPY) released into the hypophysial-portal circulation participates in priming gonadotropes to the effects of gonadotropin releasing hormone (GnRH)

NPY exhibits modulatory activity at both the adenohypophysial and the central levels of the rat hypothalamic-pituitary-gonadal axis. In the present studies, the secretion and physiological activity of endogenous irNPY was examined. We have shown that: (i) irNPY is secreted into the hypophysial-portal circulation, (ii) hypophysial-portal concentration profiles of irNPY and irGnRH are parallel throughout the rat estrous cycle, and (iii) removal of endogenous NPY via immunoneutralization inhibits the steroid-induced LH surge in ovariectomized rats. From these observations, we speculate that NPY secreted into the hypophysial-portal circulation participates in priming of gonadotropes to the actions of GnRH on the afternoon of the preovulatory surge.     

Fatal disseminated herpesvirus hominis type 2 infection in an adult with associated thymic dysplasia

Disseminated herpesvirus hominis (HVH) type 2 infection, proved by viral isolation, is described in a previously healthy young woman. The clinical course was characterized by rapidly progressive hepatic failure leading to death 1 week after hospitalization. Postmortem examination showed involvement of many organs by HVH, most severe in the liver. The thymus gland showed dysplasia. It is suggested that this thymic alteration was congenital and was associated with a partial deficiency in cellular immunity, which permitted the patient's relatively long survival but ultimately rendered her susceptible to overwhelming viremia. Six adults with disseminated HVH infection, type unspecified but proved by viral isolation, were found in a review of the literature; predisposing factors (steroids, burns, Hodgkin's disease, malnutrition) existed in five patients. The thymus gland was not described, however, in the autopsy reports on any of the five patients who died.It is concluded that in order to initiate early antiviral therapy, HVH should be a diagnostic consideration in adults with hepatitis, particularly if skin or mucosal lesions are present. Furthermore, the central and peripheral lymphoid system of any patient who dies of a disseminated viral infection should be thoroughly examined.     

Direct effect of dobutamine on action potential duration in ischemic compared with normal areas in the human ventricle.

BACKGROUND AND OBJECTIVES. The arrhythmogenic effect of beta-adrenoceptor stimulation is complex and may differ in ischemic and normal myocardium. In this study we examined the differential effect of beta-adrenergic stimulation on ventricular action potential duration and, hence, dispersion of repolarization in potentially ischemic versus nonischemic human ventricular myocardium. METHODS. Simultaneous biventricular monophasic action potentials were recorded in 14 patients (28 recording sites) during infusion of dobutamine in incremental doses (low dose 5 micrograms/kg per min, high dose 10 to 15 micrograms/kg per min) during atrial pacing. Perfusion at the action potential recording site was assessed by incorporating myocardial perfusion scintigraphy with injection of technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile during the recording at peak doses of dobutamine. Action potential duration during dobutamine infusion was compared with that during atrial pacing to identical rates in the absence of dobutamine. RESULTS. In 21 normal zone recordings, dobutamine produced a variable effect over that produced by atrial pacing to identical heart rates, either lengthening or shortening the action potential duration. The mean (+/- SEM) value for the additional effect of dobutamine was 0.9 +/- 2.5 ms with low doses and -4 +/- 2.6 ms with high doses (p = NS). In seven recordings from potentially ischemic zones, low dose dobutamine had a similar effect (mean change -3.4 +/- 6.5 ms; p = NS vs. normal zone values). However, the high dose dobutamine invariably shortened the action potential duration by a mean of -22.9 +/- 2.9 ms. (p less than 0.05 vs. low dose in ischemic areas, p less than 0.01 vs. normal zone recordings). Pacing alone or the addition of dobutamine had no significant effect on the normal dispersion of action potential duration between two nonischemic recording sites. In recordings in a normal and an abnormally perfused site, high dose dobutamine significantly altered the dispersion of action potential duration. CONCLUSIONS. These results suggest a different effect of beta adrenergic stimulation in potentially ischemic compared with nonischemic human ventricular myocardium. The abnormal dispersion of repolarization thus created may well be important in beta-receptor-mediated arrhythmogenesis during myocardial ischemia.     

Monophasic action potentials at discontinuation of cardiopulmonary bypass: evidence for contraction-excitation feedback in man

Mechanical dysfunction is the strongest predictor of sudden cardiac death due to arrhythmia. Contraction-excitation feedback whereby changes in myocardial length/tension influence the time course of repolarization and excitability would provide a possible mechanism. Such a relationship has been shown in animals but has yet to be demonstrated in man. A useful model for studying this relationship is provided by the process of weaning off cardiopulmonary bypass after routine coronary artery surgery. During this weaning period of approximately 1 min, the heart is converted from being partially empty and flaccid (i.e., a "nonworking" state) to being filled and stretched to support the circulation (i.e., a "working" state). Monophasic action potentials (MAPs) were recorded from the left ventricular epicardium as a measure of repolarization time in 16 patients at discontinuation of cardiopulmonary bypass. Systolic pressure was recorded from the radial artery line. Measurements were made at three stages that related to different dynamic states of the heart: (1) starting to come off bypass ("minimally working"), defined as the time of first appearance of an inflection on the arterial pressure trace indicating the start of left ventricular ejection and valve opening, when arterial pressures represent left ventricular pressure, (2) half off bypass ("partially working"), and (3) off bypass ("wholly working"). During the process of discontinuing bypass MAP duration shortened, while systolic pressure increased. MAP duration at 90% and 60% repolarization (MAP D90, MAP D60) decreased from 288.0 +/- 29.5 msec (mean +/- SEM) and 235.0 +/- 27.9 msec in the minimally working heart to 274.5 +/- 30.2 msec and 224.2 +/- 27.3 msec in the partially working heart (p less than .001), with a subsequent decrease to 261.0 +/- 28.8 and 214.0 +/- 28.7 when the heart was wholly working (p less than .001). Systolic pressure increased from 54.1 +/- 9.3 mm Hg in the minimally working heart to 65.9 +/- 13.8 mm Hg in the partially working heart (p less than .001) and subsequently increased to 75.5 +/- 13.3 mm Hg when the heart was wholly working (p less than .001). Mean heart rates did not change significantly. A strong correlation was obtained between absolute MAP duration and systolic pressure. Regression analysis revealed: MAP D90 vs systolic pressure (p less than .001) and MAP D60 vs systolic pressure (p less than .01).(ABSTRACT TRUNCATED AT 400 WORDS)     

Serological studies in the elderly.

Sera from 108 elderly patients in psychiatric and general hospitals were tested for antibodies to seven viruses. Measles virus antibody levels were significantly higher in patients from the psychiatric hospital, regardless of diagnosis, than in those from other hospitals. Demented patients, regardless of their hospital, had significantly higher levels of antibody to adenovirus than control patients.