Biochemical markers surrogating on vascular effects of sex steroid hormones.

The main mechanism of possible cardioprotection by estrogens appears to be a direct effect on the vasculature, resulting in an improvement of endothelial function and inhibition of atherogenesis. Numerous observational and experimental studies have demonstrated a positive correlation between estrogens and various biochemical markers surrogating direct vascular effects. In general, most markers are influenced in a similar way by oral and transdermal hormone therapy, although oral therapy may have a faster and more pronounced effect. The main difference between oral and transdermal administration may be confined to markers that are mainly or exclusively produced in the liver. Clinical studies demonstrate that progestogen addition can have an impact on the beneficial estrogen-induced changes of biochemical markers. Concerning the effects of tibolone, inconsistent data have been found. Overall, tibolone-induced beneficial changes on the various biochemical markers appear to be less marked compared with those of hormone therapy. The few data available on the direct effects of androgens on the vascular wall indicate a less favorable action of androgens on biochemical markers than of estrogens. The practical relevance of marker measurements is currently under discussion. Although evidence strongly supports some of these markers as predictors of acute events, it remains to be established whether modifying circulating levels of these markers will influence outcomes.     

Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer

Rhenium-186 hydroxyethylidene diphosphonate (¹⁸⁶Re-HEDP) has been used for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using ¹⁸⁶Re-HEDP Twenty-four patients with hormone-resistant prostate cancer entered the study. Each patient had at least four bone metastases and adequate haematological function. Groups of at least three consecutive patients were treated with doses starting at 1295 MBq and increasing to 3515 MBq (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose-limiting toxicity, while leucopenia played a minor role. Early death occurred in one patient (10 days after administration) without clear relationship to the ¹⁸⁶Re-HEDP therapy. Transient neurological dysfunction was seen in two cases. Two patients who received 3515 MBq ¹⁸⁶Re-HEDP showed grade 3 toxicity (thrombocytes 25–50 × 10⁹/1), defined as unacceptable toxicity. After treatment alkaline phosphatase levels showed a transient decrease in all patients (mean: 26% ± 10% IUA; range: 11%–44%). Prostate-specific antigen values showed a decline in eight patients, preceded by a temporary increase in three patients. From this study we conclude that the maximally tolerated dose of ¹⁸⁶Re-HEDP is 2960 MBq. A placebo-controlled comparative study on the efficacy of ¹⁸⁶Re-HEDP has been initiated.     

Optimization of the quinoline and substituted benzyl moieties of a series of phenyltetrazole leukotriene D4 receptor antagonists.

This report describes the development of a series of highly potent quinoline-based leukotriene D4 (LTD4) receptor antagonists containing an N-benzyl-substituted phenyltetrazole moiety. They were designed to provide both the correct positioning of the acidic function and secondary lipophilic domain required for strong receptor binding. Members of this series possess high activity in blocking LTD4-induced contractions of isolated guinea pig ileum. Compound 32, LY287192 (2-[[5-[3-[2-(7-chloroquinolin-2- yl)ethenyl]phenyl]-2H-tetrazol-2-yl]methyl]-5-fluorobenzoic acid sodium salt), blocked contraction with a pKB value of 9.1 +/- 0.3. Qualitative structure-activity studies have demonstrated specific requirements for the best activity. In particular, ortho substitution of the benzyl group with an acidic function was crucial for maximum potency. In cases similar to 32, where the benzyl group possesses an ortho carboxylate, the N-2-substituted tetrazole isomer showed 100-fold greater activity relative to the corresponding N-1 isomer. This pattern was reversed when the acid was substituted at the para position. The quinoline unit may be replaced by other nitrogen-containing heterocycles.     

Early Teenage Substance Use as a Predictor of Educational-Vocational Failure

The authors report on the relationship of early adolescent substance use (up to the time of the 16th birthday) to educational-vocational performance in the early adulthood of 612 African-American urban subjects. Voluminous prospective data were available on the behavior, test performance, and families of 612 urban African-American subjects, from birth up to 7 years of age. Scarcer prospective data were available for school performance during later years of school. Control variables were derived from these data to determine the amount of variance in each dependent educational-vocational outcome variable that was accounted for, independently of the amount of variance accounted for by early substance use. (American Journal on Addictions 1994; 3:325–336)     

Über die Behandlung der Tibiakopffrakturen

Ohne Zusammenfassung Mit 2 Textabbildungen.     

Vitamin K administered to the mother during labor as a prophylaxis against hemorrhage in the newborn infant

This investigation has been conducted as two separate studies. Part I consisted of the determination of the prothrombin activity in normal newborn infants together with observations on the alterations in this activity which result from the administration of vitamin K to the mother. Part II was concerned with the practical application of the knowledge gained from the first study. It aimed to show the value of intra-partum vitamin K administration in reducing the incidence of hemorrhage in newborn infants.     

Liver resection without hilus preparation and with selective intrahepatic hilus stapling for benign tumors and liver metastasis

Background Nowadays, liver resection is a routine operative procedure in surgical centers, and strategies must be aimed at avoiding additional risk factors. Extrahepatic isolation of portal vein, hepatic artery and hepatic duct, as well as lymphadenectomy of the liver hilum are generally accepted steps of liver resection, even for metastatic and benign indications. Our primary aim was to analyze the feasibility, blood loss, blood transfusion requirements, incidence of complications, and outcome using the approach for intrahepatic devascularization leaving the extrahepatic hilus untouched. Materials and methods Thirty-eight consecutive patients with resection for metastases and benign liver tumors were selected. After hilar examination, the extrahepatic structures remain intact, and during parenchyma dissection, the whole right or left or the appropriate bi-segmental pedicle is isolated intrahepatically and then transected using a stapler device. Results The used technique was feasible in all cases, and no intra- or postoperative surgical complications were observed. To date, no tumor recurrence was found in the hilum during the follow-up period. Conclusion The intrahepatic pedicle stapling technique appears to be feasible and safe in liver resection. Hilar dissection can, thus, be avoided in liver metastasis and benign liver tumors.