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Alex Evers

Publications and source records attributed to Alex Evers.

4 recordsLinked to original sources
PubMed2004

Neuroactive steroids have multiple actions to potentiate GABAA receptors.

The effects of neuroactive steroids on the function of GABAA receptors were studied using cell-attached records of single channel activity recorded from HEK293 cells transfected with alpha1 beta2 gamma2L subunits. Activity was elicited with a half-maximal (50 microM) concentration of GABA. Two steroids were studied in detail: ACN ((3alpha,5alpha,17beta)-3-hydroxyandrostane-17-carbonitrile) and B285 ((3alpha,5beta,17beta)-3-hydroxy-18-norandrostane-17-carbonitrile). Four effects on channel activity were seen, two on open time distributions and two on closed times. When clusters of openings were elicited in the absence of steroid, the open time distribution contained three components. ACN produced concentration-dependent alterations in the open time distribution. The prevalence of the longest duration class of open times was increased from about 15% to about 40% (EC50 about 180 nM ACN), while the duration of the longest class increased from 7.4 ms to 27 ms (EC50 about 35 nM ACN). B285 also increased the prevalence of the longest duration open times (EC50 about 18 nM B285) but increased the duration only at concentrations close to 10 microM. The differences in the actions of these two steroids suggest that the effects on proportion and duration of the long duration open time component are produced by independent mechanisms and that there are separate recognition sites for the steroids which are associated with the two functional actions. The closed time distributions also showed three components in the absence of steroid. The rate of occurrence of the two brief duration closed time components decreased with increasing ACN, with an EC50 of about 50 nM ACN. In contrast, B285 did not reduce the rate of occurrence of the brief closings until high concentrations were applied. However, both B285 and ACN reduced the rate of occurrence of the activation-related closed state selectively, with comparable IC50 concentrations (about 40 nM ACN, 20 nM B285). As in the case for action on open times these data suggest that there are two recognition sites and two independent mechanisms, perhaps the sites and mechanisms associated with actions on open times. The presence of 1 microM ACN had no effect on the estimated channel opening rate or on the apparent affinity of the receptor for GABA. Mutation of the carboxy terminus of the gamma2 subunit, but not the alpha1 or beta2 subunits, abolished the ability of ACN to increase the duration of OT3 but had no effect on the reduction of the rate of occurrence of the activation-related closed state. These observations are also consistent with the idea that there is more than one distinguishable steroid recognition site on the GABAA receptor.

Animals↗
PubMed2002

Management of the postpubertal patient with cryptorchidism: an updated analysis.

PURPOSE: Management of the postpubertal cryptorchid testis depends on patient age at presentation. Based on the belief that the risk of death from surgery first exceeds the risk of death from testis cancer at age 32 years patients younger than 32 years are advised to undergo orchiectomy, while those older than 32 years are advised to remain under close observation. However, the data on which this recommendation is based are now a quarter-century old. During this interval significant improvements have been made in perioperative care and germ cell tumor therapy. We revisited the topic using contemporary data to determine whether and how recommendations on management of the postpubertal cryptorchid testis should be changed. MATERIALS AND METHODS: Contemporary data on germ cell mortality in the United States were obtained from the National Center for Health Statistics. From these data the lifetime risk of death from germ cell cancer in the general population was calculated for each 5-year interval between ages 15 and 60 years. Since the lifetime risk of germ cell tumor is believed to be higher in patients with cryptorchidism than in the general population, the lifetime risk of eventual death from germ cell tumor in the cryptorchid population was calculated by multiplying each 5-year lifetime risk by 9.7, which is the generally accepted relative risk of germ cell tumor in a cryptorchid testis. Contemporary literature on perioperative mortality was reviewed and we estimated the current mortality of orchiectomy based on American Society of Anesthesiologists (ASA) class. Mortality rates were plotted to determine the age when operative mortality exceeds the risk of mortality from germ cell malignancy. RESULTS: While perioperative mortality and germ cell neoplasia mortality decreased in the last 25 years, the relative decrease in perioperative mortality was significantly greater. Thus, in ASA class I or II cases mortality from orchiectomy began to exceed mortality from germ cell cancer at age 50 years. CONCLUSIONS: Improvements in therapy for germ cell neoplasia and perioperative care in the last 25 years have dramatically decreased the mortality of each cause. However, the decrease in perioperative mortality has been greater. In contrast to a generation ago, accidental death during routine elective surgery is now extremely rare in healthy patients. Thus, we advocate orchiectomy in all healthy males (ASA I and II) who present with postpubertal cryptorchidism until age 50 years.

Adolescent↗