Clinical and hormonal effects of chronic gonadotropin-releasing hormone agonist treatment in polycystic ovarian disease

Previously, we reported that short term administration of a highly potent GnRH agonist (GnRHa) for 1 month to patients with polycystic ovarian disease (PCO) resulted in complete suppression of ovarian steroidogenesis without measurable effects on adrenal steroid production. This new study was designed to evaluate the effects of long term GnRHa administration in PCO patients with respect to their hormone secretion patterns and clinical responses. Eight PCO patients and 10 ovulatory women with endometriosis were treated daily with sc injections of [D-His6-(imBzl]),Pro9-NEt]GnRH (GnRHa; 100 micrograms) for 6 months. Their results were compared to hormone values in 8 women who had undergone bilateral oophorectomies. In response to GnRHa, PCO and ovulatory women had rises of serum LH at 1 month, after which it gradually declined to baseline. In both groups FSH secretion was suppressed throughout treatment. Serum estradiol, estrone, progesterone, 17-hydroxyprogesterone, androstenedione, and testosterone levels markedly decreased to values found in oophorectomized women by 1 month and remained low thereafter. In contrast, serum pregnenolone and 17-hydroxypregnenolone were partially suppressed, and dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol levels did not change. Clinically, hyperplastic endometrial histology in three PCO patients reverted to an inactive pattern, and proliferative endometrium in two other PCO patients became inactive in one and did not change in the other. Regression of proliferative endometrial histology occurred in all ovulatory women. Vaginal bleeding occurred in all women studied during the first month of GnRHa administration, after which all but one PCO patient became amenorrheic. Hot flashes were noted by all ovulatory women and by four of eight PCO patients. All PCO patients noted subjective reduction of skin oiliness, and five had decreased hair growth. We conclude that in premenopausal women: 1) chronic GnRHa administration results in apparently complete persistent suppression of ovarian steroid secretion; 2) adrenal steroid secretion is not influenced directly or indirectly; and 3) its use may be helpful in the treatment of endometrial hyperplasia and ovarian androgen excess in women with PCO.     

Comparison of PET, MRI, and CT with pathology in a proven case of Alzheimer's disease

Positron emission tomography (PET) with fluorodeoxyglucose (FDG), magnetic resonance imaging (MRI), and CT were carried out in a patient with Alzheimer's disease 16 months before he died. At autopsy, the gross appearance of the brain correlated with MRI and CT, which showed some regional atrophy. These were much less revealing than PET, which correlated with microscopic findings of neuronal loss and proliferation of glia. In areas of moderately impaired local cerebral metabolic rate of glucose, as revealed by reduced FDG uptake, there was some gliosis, primarily around the numerous senile plaques. In areas of severe metabolic impairment, there was a profound loss of neurons, extensive gliosis, and a diminished appearance of plaques. PET-FDG is a better measure of the severity of Alzheimer's disease than MRI or CT, because it reflects the degree of neuronal pathology.     

Effects of dexamethasone on central and peripheral ACTH systems in the rat

To investigate the simultaneous effects of dexamethasone on peripheral and central adrenocorticotropic hormone (ACTH) systems, rats were treated with dexamethasone or saline for 4 days. Pituitary, plasma, hypothalamus and cerebrospinal fluid (CSF) were then collected and analyzed for ACTH immunoreactivity. Additionally, hypothalamic tissue extracts were analyzed for corticotropin-releasing hormone (CRH) immunoreactivity. Dexamethasone significantly lowered peripheral levels of ACTH as measured in pituitary and plasma. Hypothalamic ACTH content significantly increased while CSF ACTH significantly decreased with dexamethasone treatment. Hypothalamic CRH concentrations showed a small but statistically insignificant decrease. These results suggest that prolonged exposure to dexamethasone affects central as well as peripheral ACTH activity, corroborate our previous findings in rhesus monkeys of decreased CSF ACTH in response to prolonged dexamethasone treatment, suggest that dexamethasone may inhibit the release of ACTH from hypothalamic neurons into the CSF, and provide evidence that the effect of dexamethasone on pituitary ACTH content is of greater magnitude than its effect on hypothalamic CRH.     

Differential diagnosis of poisoning by North American mushrooms, with particular emphasis on Amanita phalloides-like intoxication

It is possible to determine the management and prognosis of mushroom poisoning from the history and initial symptoms with a high degree of confidence. The most important intoxications are those involving Amanita phalloides or other potentially fatal amatoxin-containing mushrooms, which have a latent period of ten to 12 hours before the patient becomes symptomatic. Because aggressive gastroenteric decontamination can reduce the extent of hepatic damage, it is important to attempt to determine during this asymptomatic period whether amatoxin exposure has occurred. Various laboratory methods that might be useful are reviewed.     

Evidence for dual modulation of pepsinogen secretion using isoproterenol, carbachol, CCK-8, forskolin, 8 bromo-cAMP, and A23187 probes

The cellular mechanisms by which pepsinogen (PNG) secretion is controlled are not understood. The aim of this study was to explore whether modulation of PNG secretion is mediated by cAMP or calcium-calmodulin (C-C). PNG secretion in isolated rabbit gastric fundic glands (IGG) was tested, using agents believed to act via cAMP or C-C. IGG were stimulated for 30 minutes with histamine (H) 10(-5) M, isoproterenol (I) 10(-5) M, carbachol (C) 10(-5) M, cholecystokinin-octapeptide (CCK-8) 10(-7) M, forskolin (F) 10(-5) M, 8 bromo-cAMP (8B) 10(-3) M, and A23187 (A) 10(-6) M. PNG levels were determined by spectrophotometric assay of hemoglobin digestion products. PNG amounts secreted were (mean per cent above basal levels of total IGG PNG units +/- SEM): H, -0.02 +/- 0.30%; I, 3.5 +/- 0.9%; C, 5.1 +/- 2.2%; CCK-8, 5.3 +/- 1.5%; F, 10.6 +/- 3.8%; 8B, 13.8 +/- 4.5%; A, 2.1 +/- 1.1%. All secretagogues except H stimulated PNG release significantly above basal levels (p less than 0.05). A primary histaminergic mechanism for pepsinogen secretion is unlikely. Since two other adenylate cyclase activators, isoproterenol and forskolin and the 3':5'-cyclic adenosine monophosphate analog 8-bromo cAMP stimulated pepsinogen secretion, cAMP-dependence is probable. Since carbachol, CCK-8, and A23187, which are believed to act via calcium-calmodulin, also stimulated pepsinogen secretion, this system, too, presumably plays a substantial role. Thus the data support a dual 3':5'-cyclic adenosine monophosphate/calcium-calmodulin modulation of pepsinogen secretion.