The hippocampal formation: morphological changes induced by thyroid, gonadal and adrenal hormones

The hippocampal formation is of considerable interest due to its proposed role in a number of important functions, including learning and memory processes. Manipulations of thyroid, gonadal and adrenal hormones have been shown to influence hippocampal physiology as well as learning and memory. The cellular events which underlie these hormone-induced functional changes are largely unexplored. However, studies suggest that hormonal manipulations during development and in adulthood result in dramatic morphological changes within the hippocampal formation. Because neuronal physiology has been suggested to depend upon neuronal morphology, we have been determining the morphologic sensitivity of hippocampal neurons to thyroid and steroid hormones in an effort to elucidate possible structural mechanisms to account for differences in hippocampal function. In this review, hormone-induced structural changes in the developing and adult hippocampal formation are discussed, with particular emphasis on their functional relevance. Sex differences, as well as the developmental effects of thyroid hormone and glucocorticoids, are described. Moreover, the effects of ovarian steroids, thyroid hormone and glucocorticoids on neuronal morphology in the hippocampal formation of the adult rat are reviewed. These hormone-induced structural changes may account, at least in part, for previously reported hormone-induced changes in hippocampal function.     

Adrenal steroids regulate postnatal development of the rat dentate gyrus: I. Effects of glucocorticoids on cell death.

The rat dentate gyrus undergoes a period of naturally occurring cell death during the first postnatal week. In the adult rat, removal of circulating adrenal steroids by adrenalectomy is followed by massive death in the granule cell layer, thus raising the possibility that developmental cell death results from low levels of these hormones. Interestingly, the first two postnatal weeks of life in the rat, termed the stress hyporesponsive period, are characterized by very low levels of adrenal steroids. In order to determine whether low levels of adrenal steroids enable developmental cell death to occur in the dentate gyrus, we examined the density of pyknotic and healthy cells in the dentate gyrus of rat pups which received one of the following treatments: (1) injections of the endogenous rat glucocorticoid corticosterone during the first postnatal week, or (2) adrenalectomy at the time when glucocorticoid levels normally rise. Quantitative analysis of the density of pyknotic cells in the granule cell layers revealed significant decreases with corticosterone treatment by the end of the first postnatal week. In these same brains, treatment with corticosterone resulted in a substantial increase in the density of pyknotic cells in the hilus. Adrenalectomy resulted in a significant increase in the density of pyknotic cells in the granule cell layer as well as in the hilus. Despite the dramatic alterations in the density of pyknotic cells with both increases and decreases in glucocorticoid levels, the density of healthy cells remained the same. These observations suggest that glucocorticoids regulate several processes, possibly including neurogenesis and migration, in addition to cell death.     

Ro 5-4864, like picrotoxin, enhances EPSP-spike coupling in the freely behaving rat

To help determine its mechanism of action, the convulsant benzodiazepine Ro 5-4864 was administered (15-20 mg/kg) intraperitoneally (IP) and electrophysiological and behavioral effects were compared; parallel studies were conducted with picrotoxin (PTX; 1 mg/kg). Both PTX and Ro 5-4864 produced myoclonic seizures, primarily between 15-40 min after administration; myoclonus was followed by more severe seizures after PTX. Both Ro 5-4864 and PTX produced a maximal increase in amplitude and decrease in threshold of the population spike (PS) evoked in the dentate gyrus (DG) by stimulation of the dorsal perforant path prior to peak seizure activity; start latency of the PS and initial slope and amplitude of the population slow wave (SW) were not changed. Amplitude of the PS was already increased by 5 min after administration of Ro 5-4864 and was maximally increased 1.8- to 3-fold, depending on stimulus intensity, usually by 10 min. Similarly, by 20 min after administration, PTX had also increased PS amplitude in the absence of an effect on PS latency or the SW. The increase in PS amplitude without concomitant changes in the SW suggests that Ro 5-4864 enhanced coupling between the excitatory postsynaptic potential (EPSP) and firing of the postsynaptic neurons, i.e., it enhanced E-S coupling, as has also been suggested for PTX. The similarity in the effects of Ro 5-4864 and PTX suggests that antiGABAergic effects, perhaps along feedforward inhibitory pathways, are involved in both the seizures and enhanced E-S coupling.     

Treatment of esophageal varices by sclerotherapy in children

Bleeding from esophageal varices may be a serious or lethal complication of portal hypertension in children. The standard therapy over the past 30 years has been to create a portosystemic shunt. In children physiologic complications leading to high rates of perioperative morbidity and early and late thrombosis with recurrence and encephalopathy have been common. Over a 42 month period, we treated six patients aged 5 to 18 years, with endoscopic injection of 3 percent sodium tetradecyl sulfate into the varix. Five patients required only injection, whereas one underwent direct oversewing of gastric varices followed by endoscopic sclerosis of the esophageal varices which remained. A total of 38 endoscopic procedures were performed. There has been complete cessation of bleeding in two patients, minimal subsequent bleeding in two others, and anemia requiring transfusion in the last two treated. These last two patients, although still requiring occasional transfusions, have been free from hypotensive or exsanguinating hemorrhage since beginning sclerotherapy. No deaths or serious complications were encountered in this series. Follow-up has ranged from 18 to 42 months (mean 26 months). The results of this trial suggest that repeated endoscopic sclerotherapy of varices, combined with operative oversewing of gastric varices when necessary, offered a viable alternative therapy for patients with esophageal varices.     

Hepatic angiosarcoma: Detection with computed tomography

Hepatic angiosarcoma is a rare vascular neoplasm which occurs typically in men aged between 50 and 70 years. The cause is unknown but previous studies have linked several carcinogens to its pathogenesis. A case of advanced multifocal hepatic angiosarcoma with splenic metastasis is presented with brief discussion of the clinical and histological features. Typical CT features and contrast enhancement characteristics are also reviewed.     

The effect of selective electrical stimulation of non-myelinated vagal fibres on heart rate in the rabbit

The bradycardia evoked by electrical stimulation of the peripheral cut end of the rabbit vagus nerve is mediated by both myelinated and non-myelinated fibres. The purpose of this study was to assess the effects of non-myelinated fibres on heart rate in the rabbit using selective electrical stimulation techniques. In 8 rabbits selective activation of non-myelinated fibres using reversed polarity triangular shaped pulses (10 Hz, 20 s), resulted in a slowly developing fall in heart rate of 24.1 +/- 1.1 beats/min which outlasted the period of stimulation by 58.4 +/- 4.2 s. In 4 rabbits stimulation of myelinated fibres at 10 Hz for 20 s resulted in a fall in heart rate of 24.5 +/- 2.6 beats/min. On stimulation of both myelinated and non-myelinated fibres heart rate fell by 39.9 +/- 3.2 beats/min. Heart rate returned rapidly to control value following stimulation of myelinated fibres (5.6 +/- 0.5 s) but only slowly after stimulation of both myelinated and non-myelinated fibres (56.7 +/- 4.9 s). Atropine (5 mg/kg, i.v.) abolished all effects of vagal stimulation on heart rate. Hexamethonium (15 mg/kg, i.v.) abolished the effect of myelinated fibres on heart rate but did not affect the fall in heart rate produced by non-myelinated fibres. We suggest that the prolonged effects on stimulation of non-myelinated fibres may reflect the persistent action of a non-cholinergic excitatory transmitter at the cardiac parasympathetic ganglia.     

Evidence-Based Review of the Use of Cryosurgery in Treatment of Basal Cell Carcinoma

BACKGROUND: Cryosurgery has been used to treat basal cell carcinoma (BCC), and it has many technical advantages over other methods. It is therefore important to establish its efficacy as a treatment for BCC. OBJECTIVE: To review systematically the body of literature reporting on the efficacy of cryosurgery of BCC in terms of recurrence rates and cosmetic results. METHODS: A review is given of MEDLINE, EMBASE, CancerLit, and the Cochrane Database of Systematic Reviews for studies that examined cyosurgery in treatment of BCC patients. RESULTS: We found 13 noncontrolled prospective studies and 4 randomized clinical trials comparing cryosurgery to other methods of treatment for BCC. Because of the inability to double blind or placebo control treatment of BCC, none of the studies met criteria for A and B grade evidence, as defined by Sackett. Therefore, all studies were assigned grade C. CONCLUSIONS: According to the best evidence, recurrence rates of BCC treated with cryosurgery are low (less than 10%). Except in one study, recurrence rates are calculated based on clinical, rather than histologic diagnosis, which may cause the rates to appear somewhat lower than they actually are, especially with a short follow-up period. Cosmetic results of cryosurgery treatment reported in literature are described as good by most investigators. Overall, there are sufficient data to consider cryosurgery as a reasonable treatment for BCC. There are no good studies, however, comparing cryosurgery with other modalities, particularly with Mohs surgery, excision, or electrodessication and curretage so that no conclusion can be made whether cryosurgery is as efficacious as other methods. Also, there is no evidence on whether curetting the lesions before cryosurgery affects the efficacy of treatment.     

Endozepine stupor in children

Recurring episodes of stupor in adults have been shown to be related to increased levels of endozepines, which are endogenous ligands for the GABAA receptors. We report here two children presenting with recurrent episodes of stupor associated with fast EEG activity who had increased levels of endozepine-4 in plasma. Mass spectroscopy did not reveal commercially available benzodiazepines. Interictal endozepine-4 levels were normal. In one of the patients, administration of flumazenil (0.25 mg i.v.), a benzodiazepine inverse agonist, induced improvement of consciousness and attenuation of EEG fast activity. In conclusion, children presenting with recurrent episodes of stupor and EEG fast activity should be evaluated for endozepine levels and can be effectively treated with i.v. flumazenil.