Decreased physiological sensitivity mediated by newly synthesized muscarinic acetylcholine receptors in embryonic chicken heart.

Treatment of chicken embryos in ovo for 8 hr with the muscarinic agonist carbachol results in an 85% reduction in the number of muscarinic acetylcholine receptors ( mAcChoR ) present in atrial membrane homogenates. Subsequent treatment of embryos with the muscarinic antagonist atropine results in a gradual increase in mAcChoR number, which returns to control levels after 14 hr. This recovery of receptor number is blocked by administration of the protein synthesis inhibitor cycloheximide, consistent with previous results in cell culture, which suggested that de novo protein synthesis is required for the recovery of mAcChoR after agonist-induced decreases. Measurements of the negative chronotropic response to applied carbachol with isolated atria show that even after recovery of receptor number to control levels the response to agonist is diminished. The IC50 for carbachol is shifted approximately equal to 10-fold from controls at 20 hr after atropine treatment, but less than 3-fold at 28 hr, with no further change in receptor number occurring over this time. This increase in physiological sensitivity is not blocked by cycloheximide. Receptors at 20 hr have binding constants for agonists and antagonists that are indistinguishable from controls. This implies that there is a defect in coupling of mAcChoR binding to the physiological response when mAcChoR reappear following agonist-mediated decreases in receptor number. Recovery of the ability of mAcChoR to inhibit adenylate cyclase parallels recovery of the beating response--that is, the IC50 is shifted approximately equal to 11-fold from controls at 20 hr after atropine treatment, yet only 3-fold at 28 hr. Thus, newly synthesized mAcChoR exhibit decreased physiological and biochemical responses to muscarinic agonists, suggesting that mAcChoR are initially synthesized in a less active form.     

Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

Laparoscopic-assisted colorectal surgery

PURPOSE: To audit the development and outcomes of laparoscopic colorectal surgery at the Royal Brisbane Hospital. METHODS: Since July 1991, laparoscopic-assisted colectomy for benign and malignant colorectal disease has been performed on more than 300 patients at the Royal Brisbane Hospital. This paper summarizes the outcome for the first 240 patients who underwent a laparoscopic colorectal procedure. All laparoscopic data were collected prospectively, and for selected studies, data were compared with open surgical controls. RESULTS: Nineteen patients required open conversion (7.9 percent). There was a significant decrease in wound infection rates in patients having a laparoscopic-assisted colectomy (3.6 percent) compared with historical controls (7.9 percent) (P<0.05; chisquared). There were five anastomotic leaks, five laparotomies for postoperative adhesive obstruction, and four perioperative deaths. A total of 103 patients had a procedure for colorectal cancer. Of the 79 potentially curative procedures, there have been 5 (6.3 percent) recurrences to date. CONCLUSION: The overall morbidity and mortality in this series seem to be acceptable compared with that of open procedures.     

Sex differences in the practice patterns of recently trained obstetrician-gynecologists

Sex differences in practice patterns, as modified by family roles, are investigated in a national survey of 1420 active obstetrician-gynecologists who graduated from medical school between 1974 and 1979. Women are more likely than men to be practicing in multispecialty groups, and men are more likely than women to be practicing in obstetrics-gynecology partnerships. On average, men and women report working over 60 hours per week. In all practice arrangements except academic medicine, women work fewer total hours per week, although the differences are small and translate into significantly fewer patient encounters than men in only two practice arrangements: partnerships and multispecialty groups. When marital status and presence of children under age 18 are controlled, significant sex differences in hours worked remain only for married respondents with children. Family roles have an opposite effect on hours of work reported by men and women, decreasing the number of hours worked by women and increasing the number worked by men.