Positive effects of ketamine v. metomidate anesthesia on cardiovascular function, oxygen delivery and survival. Studies with a porcine endotoxin model

Pulmonary and cardiovascular function, oxygen delivery and mortality were compared in endotoxemic pigs spontaneously breathing air and with continuous i.v. infusion of ketamine anesthesia (n = 10) or the equianesthetic dose of metomidate (n = 10). Continuous 6-hour i.v. infusion of endotoxin caused profound pulmonary and cardiovascular derangement in both groups. Cardiac output, mean arterial blood pressure, oxygen delivery and base excess were significantly higher and pulmonary vascular resistance significantly lower from 2-3 hours onwards in the ketamine than in the metomidate group. Six-hour survival was 6/10 and 1/10 in the respective groups. Death was presumably due to insufficient oxygen delivery in relation to tissue demand, reflected in the metomidate group's low base excess values. Control, non-stressed pigs showed no notable physiologic changes with either anesthetic regimen. The study demonstrated the importance of the type of anesthesia in stressful endotoxemic animal models. Although extrapolation of animal data requires great caution, the results may favor use of ketamine over etomidate (the clinical analogue of metomidate) in septic shock states requiring surgical intervention.     

Acute obstruction by enterolith complicating jejunal diverticulosis. Case report

Two cases are presented in which the cause of small-bowel obstruction was enterolith originating in jejunal diverticula.     

Experience with the 'skew flap' below-knee amputation

A review of 353 lower limb amputations over the last 7 years has been performed to assess the results of the skew flap myoplastic below-knee amputation which was introduced in April 1983 because of reported advantages in terms of wound healing and earlier ambulation. Comparing the first 3 1/2 year period with the second, the total number of amputations decreased by 31 per cent. The number of above-knee amputations remained similar in the two periods (82,62), whilst the number of Gritti-Stokes amputations fell from 79 to 21 (0.001 greater than P greater than 0.01). The proportion of below-knee (BK) amputations increased from 50 (23.7 per cent) to 59 (41.5 per cent) (0.01 greater than P greater than 0.025). The groups were comparable in terms of previous vascular surgery and co-existing medical conditions. The time to full stump healing was significantly shorter in the skew flap group compared with the earlier Burgess type BK amputation (P = 0.001), and there was a trend to fewer stump failures in the skew flap group. We therefore feel that the skew flap amputation gives superior results to the Burgess BK amputation in terms of healing and a lower complication rate, allowing a higher proportion of BK amputations to be performed. A prospective randomized trial of the two techniques is in hand to determine the accuracy of this hypothesis.     

The reliability of three methods for evaluating dental sealants

Three evaluation instruments (global, check-list, and criterion referenced) were used by experienced and inexperienced examiners to evaluate dental sealant end products on 40 extracted teeth. Intra- and interexaminer reliabilities were measured. Experienced examiners achieved higher intrarater reliabilities with all three evaluation instruments than did inexperienced examiners. The highest intraexaminer agreement for all examiners occurred with use of the global evaluation. The highest interexaminer reliability was achieved with the second use of the criterion-referenced evaluation by the experienced examiner. Interexaminer reliability was improved for both types of examiners with the criterion-referenced evaluation.     

Metabolic N-oxygenation of 2,4-diamino-6-substituted pyrimidines

Biological oxidation of 2,4-diamino-6-substituted pyrimidines have been studied using hepatic microsomes from various mammalian species. The nature of the enzyme(s) involved in the oxidation has been elucidated using various enzyme inhibitors and inducing agents. The 3-N-oxides were formed with 6-piperidino-, 6-diethylamino-, 6-methyl-, and 6-chloro-substituted 2,4-diaminopyrimidines: no evidence of 1-N-oxide formation was obtained. With the 6-hydroxy-, 6-amino-, and unsubstituted 2,4-diaminopyrimidines and melamine, no N-oxidative metabolite was detected. The differences in N-oxide formation was discussed in terms of the effect of substituents on tautomerism and electron distribution. The N-oxygenation was mediated via a cytochrome P450 dependent system.     

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.