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.     

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.     

Characterization of opioid peptides in human thyroid medullary carcinoma

A thyroid medullary carcinoma from a man with the multiple endocrine neoplasia syndrome Type IIB was examined for the presence of opioid peptides. The tumor contained peptides derived from all three opioid precursors: pro-opiomelanocortin (POMC), pro-dynorphin, and pro-enkephalin. The tissue concentrations of the various opioid peptides varied considerably. beta-Endorphin, a POMC-derived peptide, was present in concentrations between 9 to 12 pmoles/g tissue; 8 pmoles/g tissue of alpha-neo-endorphin, a pro-dynorphin-derived product, were seen, whereas the pro-enkephalin-associated peptides were present in much lower concentrations (0.6-2.1 pmoles/g tissue). Immunohistochemical studies showed scattered opioid-positive cells in the tumor tissue and in two other thyroid medullary carcinomas. These data demonstrate that malignant neuroendocrine tumors may contain peptides derived from all three families of the endogenous opioids.     

Neutropenic enterocolitis in adults with acute leukemia

Neutropenic enterocolitis has been previously described only by case reports and literature reviews. Of 499 adults with acute leukemia seen over a 23-year period (1962 to 1985), 13 cases (2.6%) of neutropenic enterocolitis have been reported. Eleven of these 13 patients were profoundly neutropenic (mean white blood cell count, 472/cu mm) and developed abdominal symptoms during either initial induction or relapse of acute leukemia. Histologic confirmation was available in ten cases, five cases after surgical resection and five cases at autopsy after nonoperative management. Three patients with isolated ileocecal inflammation without infarction at the time of surgery were successfully managed without resection. Five patients treated with surgery died four to 64 weeks postoperatively (mean survival, 21.6 weeks) of nonsurgical complications of leukemia. Three patients were still alive, one patient 42 months after right hemicolectomy and two patients five months after exploration only. All five patients managed medically died an average of 1.4 days (range, zero to four days) after the onset of abdominal pain. Survival in patients with acute leukemia who develop neutropenic enterocolitis is determined by early recognition and appropriate surgical exploration that can be expected to yield an acceptable operative mortality.     

Action of carnosine and beta-alanine on wound healing

In rats treat-given hydrocortisone to suppress healing, tensile strength of the skin at the site of an incision wound was significantly higher in rats locally treated with carnosine than in untreated animals. Similar effects on the tensile strength of the skin were observed by the administration of beta-alanine and histidine, but not of beta-alanine alone. Exogenous carnosine was degraded in the body by carnosinase and histidine decarboxylase to yield histamine. Since beta-alanine, the other degradation product of carnosine, was found to stimulate the biosynthesis of nucleic acids and collagen, histamine derived from carnosine is considered to have enhanced the process of wound healing by stimulating effusion at the initial stage of inflammation. Thus, the enhancement by carnosine of wound healing may be ascribed to stimulation of early effusion by histamine and of collagen biosynthesis by beta-alanine. The wound-healing effects of carnosine were further demonstrated by the observation that carnosine significantly increased granulation suppressed by cortisone, mitomycin C, 5-fluorouracil, and bleomycin.     

Efficacy of phototherapy in non-haemolytic hyperbilirubinaemia

Clinical experience of phototherapy for non-haemolytic hyperbilirubinaemia in 3999 infants in Kandang Kerbau Hospital, Singapore, is documented. Phototherapy was most effective in extremely preterm infants with very low birth weight (gestation less than or equal to 32 weeks, birth weight less than or equal to 1500 g) and least effective in full term infants with very low birth weight (gestation greater than or equal to 37 weeks, birth weight less than or equal to 1500 g) and large preterm infants (gestation less than 37 weeks, birth weight greater than 2270 g). Overall, phototherapy was effective in almost all the infants, with a failure rate of only 2.00/1000 infants. No characteristic features common to all the failures could be detected. The bilirubin rebound was usually mild; repeat phototherapy was required in only 30 infants (7.50/1000), with the response to the second exposure comparable to that to the first. No infant required a third exposure. All the infants tolerated phototherapy well, none developing any illness that could be attributed to the treatment. This clinical experience shows that phototherapy for the treatment of nonhaemolytic hyperbilirubinaemia is effective and safe.