Beyond the benzodiazepines: The search for new anxiolytics. A summary of pre-clinical approaches

The clinical efficacy of the benzodiazepines in reducing anxiety is widely accepted. However, the search for novel anxiolytics continues, motivated by the hope of finding a non-sedative anxiolytic. This article reviews the pre-clinical evidence for new compounds as it relates both to their anxiolytic actions in animal tests and to their sedative potential. Drugs acting at sites on the GABA-benzodiazepine receptor complex are discussed, as well as the potential importance of aminergic and peptidergic pathways.     

The metabolism of dopamine in the median eminence reflects the activity of tuberoinfundibular neurons

The purpose of the present study was to characterize the metabolism of dopamine (DA) in tuberoinfundibular (TI) neurons terminating in the median eminence and to examine the effects of procedures that alter the synthesis and turnover of DA in these neurons on the concentrations of dihydroxyphenylacetic acid (DOPAC) in the median eminence. The DA uptake inhibitor nomifensine (25 mg/kg, i.p.; 30 min) failed to alter median eminence DOPAC concentrations indicating that very little released DA is recaptured and metabolized by TIDA neurons. Within 5 min following the administration of the monoamine oxidase inhibitor pargyline (50 mg/kg, i.v.) median eminence DOPAC concentrations declined to 15% of control demonstrating that this metabolite has a high turnover rate and is rapidly removed from the median eminence. Median eminence DOPAC concentrations in diestrous female rats, whose TIDA neuronal activity is higher than in the male, were two-fold greater than in male rats. Prolactin (10 micrograms/rat, i.c.v.; 12 h), which increases TIDA neuronal activity, produced a corresponding increase in median eminence DOPAC concentrations in male rats. Restraint stress (30 min), which decreases TIDA neuronal activity, produced a corresponding decrease in median eminence DOPAC concentrations in diestrous female rats. The results from the present study suggest that DOPAC concentrations in the median eminence can be used as an index of TIDA neuronal activity.     

Improved estimates of discordance ratios in twin studies

In the study of monozygotic twins relative to disease and risk factors, particular interest focuses on the subset who are discordant for some suspected risk factor (for example, smoking), since such twins constitute a natural case-control pair. In such studies, questionnaires designed to identify the status of all twin pairs are sometimes error prone and can yield misleading estimates of the concordance-discordance ratios. Greater efforts to verify the characteristics of apparently discordant pairs than to verify those of apparently concordant pairs can result in the 'unequal ascertainment' fallacy. Using the results of a questionnaire with known error rates and the 'apparent' frequencies yielded, we present unbiased, maximum likelihood estimates of the 'true' proportions of concordant and discordant pairs. concordant and discordant pairs. We also present approximate covariances among these estimates.     

Aspiration drainage of splenic abscesses

The successful use of guided percutaneous needle aspiration in the management of four patients with solitary splenic abscess is described. Two patients had needle aspiration alone and two patients, with large splenic abscesses, had drainage tubes inserted. The procedures were well tolerated and allowed rapid microbiological diagnosis with selection of appropriate antibiotic therapy. The techniques were useful in patients felt to be poor anaesthetic risks, and the complications of splenectomy were avoided.     

Breast reconstruction by tissue expansion for congenital and burn deformities

We have used tissue expanders to treat 10 patients with breast deformities, 2 the result of burns and 8 congenital in origin. The expanders are placed in the subglandular plane and expanded incrementally until the desired amount of growth is obtained. In patients with congenital deformities, the desired size of the reconstructed breast (implant size) is determined during the expansion phase. Reconstructions of the nipple-areola complex are done either at the time of the exchange or as separate procedures. Patients with burn deformities present a variety of problems not seen with the congenital deformities. The expander is placed in the subglandular plane and filled to the desired volume. We have noted a marked permanent softening of the scar and grafts encasing the breast, which persists after the expander is removed and the breast reconstructed. The interval between expansion and definitive reconstruction is delayed for several months to allow scar softening to take place. If the parenchyma is not burned and pedicle tissue is not required, the expander can be deflated and the skin coverage observed to determine if it will remain soft. If it does, the expander can be removed and the breast reconstructed. In patients who require pedicle coverage in the reconstruction and who have unburned scar surrounding the breast, massive overexpansion is carried out. The pedicle skin is used to resurface the breast after removal of the appropriate areas of scar and skin grafts. In all burned patients, the inframammary fold must be reconstructed if the breast is to be protuberant. The nipple-areola complex also requires reconstruction. To date there has been great acceptance by patients with both congenital and burn deformities; however, we believe that tissue expansion techniques offer possibilities that have not as yet been fully explored.     

227. Der gestielte Peronaeus-Insellappen als Alternative zum freien Gewebetransfer am distalen Unterschenkel und Fuß

Zusammenfassung Der distal gestielte Peronaeus-Insellappen, erstmals 1984 von Yoshimura publiziert, ist ein fasciocutaner Lappen, der über einen Hautast der A. peronea ernährt wird. Die A. peronea weist distal, ca 5 cm oberhalb des Sprunggelenkes, einen Ramus perforans zur A. tibialis anterior auf und über einen Ramus communicans besteht eine Verbindung zur A. tibialis posterior. Unterbindet man die A. peronea proximal der Abgangsstele der Hautarterie, so kommt es über die distalen Anastomosen zur retrograden Durchblutung. Der distal gestielte Peronaeuslappen besitzt einen großen Schwenkbereich bis hin zum Fußrücken. Die Durchgängigkeit der drei Unterschenkelarterien ist die Voraussetzung für die Durchführbarkeit. Die Indikation ergibt sich bei oberflächlichen Knochen- und Hautdefekten im distalen Unterschenkeldrittel, der Malleolengabel, der Ferse und des Fußrückens.     

Cardiac involvement in Lyme disease: manifestations and management

Cardiac involvement in Lyme disease may manifest as atrioventricular block, myopericarditis, and left ventricular dysfunction. Diagnosis depends on recognition of the systemic nature of Lyme disease, including cardiac involvement, and its natural history. Serologic tests that are both sensitive and specific may aid in diagnosis. Although current recommendations for the treatment of Lyme disease with carditis include antibiotics and salicylates or corticosteroids, these types of therapy have not been unequivocally demonstrated to alter the natural history of cardiac involvement. Supportive therapy may necessitate temporary transvenous cardiac pacing in symptomatic patients.