Conformationally constrained anesthetic steroids that modulate GABA(A) receptors

Various cyclic ether and other 3 alpha-hydroxyandrostane derivatives bearing a conformationally constrained hydrogen-bonding moiety were prepared. Their anesthetic potency and their binding affinity for GABA(A) receptors, measured by intravenous administration to mice and inhibition of [(35)S]TBPS binding to rat whole brain membranes, were compared with that of known anesthetic 3 alpha-hydroxypregnan-20-ones. Synthetic steroids with similar in vitro and in vivo activities to the endogenous 3 alpha-hydroxypregnan-20-ones all had an ether oxygen on the beta-face of the steroid D-ring. These results suggest that for optimal GABA(A) receptor modulation, the hydrogen bond-accepting substituent should be near perpendicular to the plane of the D-ring on the beta-face of the steroid.     

Electrolytic lesions in the depressor area of the ventrolateral medulla of the rat abolish depressor responses to the aortic nerve stimulation

The pressor (VLPA) and the depressor (VLDA) areas in the ventrolateral medulla were identified with the microinjections of L-glutamate (1.77 nmol/site) in artificially ventilated, pentobarbital-anesthetized male Wistar rats. Electrical stimulation of the left or right aortic nerve (1-6 V, 10-40 pulses/s, 3 ms) produced usual depressor responses. Electrolytic lesions (2.5 mA for 30 s) were placed bilaterally in the VLDA. Lack of responses to subsequent microinjections of glutamate into the VLDA indicated that the lesions were complete. The function of the VLPA was not compromised because it continued to respond to microinjections of glutamate. Subsequent stimulation of the aortic nerves failed to elicit the usual depressor responses. These results confirm our earlier reports indicating that the VLDA is important in mediating the depressor component of the aortic baroreflex.     

Case report 688

The double spinous process sign at multiple levels is a reliable indication of fractures of multiple spinous processes. When multiple thoracic vertebrate are involved, as in the patient reported here, the AP radiograph may offer the sole clue to the extent of injury on the plain films.     

Psychometric testing of SPIDER: data capture tool for systematic literature reviews.

OBJECTIVE: Systematic literature reviews contribute to evidence-based occupational therapy, yet no data capture tool currently exists to validly and reliably appraise the characteristics and quality of primary studies. METHOD: We determined the psychometrics of Systematic Process for Investigating and Describing Evidence-Based Research (SPIDER) and piloted it with 201 studies included in a systematic literature review. RESULTS: Content validity showed item relevance with 73% agreement between two experts. For the quality construct, seven of nine quality indicators were positively (p < .05) correlated with the overall quality score. The quality scores were positively correlated (p < .05) with two objective measures, inferring criterion validity. Intrarater reliability was moderate to perfect (kappa = 0.4-1.0). Cross-tab analyses showed less variation in experienced reviewers' interrater reliability. CONCLUSION: SPIDER provides plausible opportunities for occupational therapy researchers and graduate students to appraise the characteristics and quality of primary studies but requires testing across other settings.     

Cauda equina syndrome without mechanical cauda compression: a report of 2 cases

Study design Case report. Objective To highlight the concept of Cauda Equina Syndrome without cauda compression. Summary of background data Cauda equina syndrome (CES) is a rare disorder. CES occurs usually due to direct physical compression of the cauda nerve roots, most often from the extruded nucleus pulposus; other rare causes reported in the literature include compression by tumour, infection, fracture, penetrating trauma, chiropractic manipulation, free epidural fat graft, postoperative haematoma, ankylosing spondylitis, metastatic invasion, schwnnoma, Paget’s disease and laminar hook compression. All these causes of CES physically compress the cauda. Chemical irritation of the root can cause radicular pain but this has not been noted to cause CES before. We present two cases of Cauda Equina Syndrome was brought on by non-physical compression of the cauda. Annular tears can induce CES by chemical irritation of the cauda by inflammatory mediators. Conclusion The idea of presenting this paper is to highlight that cauda equina syndrome can be caused by non-mechanical cauda compression; in our cases it was due to chemical irritation and caudal epidural steroid injection has produced satisfactory outcome. Awareness of non-physical cauda equina syndrome is essential to identify and to initiate appropriate treatment, and the outcome seems to be satisfactory.     

Reversal of testicular function after prolonged suppression with an LHRH agonist in rhesus monkeys

Using subcutaneously implanted osmotic pumps, four male rhesus monkeys were continuously infused for 18 months with 100 micrograms/day of [(imBzl)-D-His6-Pro9-NEt]-LHRH (LHRH-A), a potent agonist of LHRH. After an initial increase, serum testosterone levels declined to 10% of pretreatment levels in three monkeys and the response to electroejaculation was lost. There was a decrease in testicular volume. Androgen replacement in the form of subcutaneous SILASTIC implants releasing 7 alpha-methyl-19-nor-testosterone acetate led to a restoration of ejaculatory response and the electroejaculates were devoid of spermatozoa. Under this treatment regimen (100 micrograms LHRH-A + 100 micrograms androgen daily), azoospermia was essentially maintained in the three monkeys for about 8 months. Withdrawal of LHRH-A and androgen treatment led to a complete restoration of testicular function. Serum testosterone returned to control levels and spermatozoa reappeared in the ejaculates with sperm counts reaching the normal range. Testicular volumes showed a gradual increase. These results indicate that continuous administration of an LHRH agonist together with an androgen can induce an extended period of azoospermia in rhesus monkeys. These results also show that after prolonged suppression (more than one year) of testicular function complete recovery occurs after cessation of treatment.