Association of HLA types A1-B8-DR3 and B27 with rapid and slow progression of HIV disease

We examined how HLA types A1-B8-DR3 and B27 were related to progression of clinical disease and rate of loss of CD4 lymphocytes in the Edinburgh City Hospital cohort of HIV-positive patients, mainly injection drug users. Patients (n = 692) were prospectively followed from 1985 through March 1994. Accurately estimated seroconversion times were determined retrospectively for a subgroup of 313 (45%). Of 262 patients (39%) who were fully or partially HLA typed, 155 (50%) had known seroconversions. Of 34 patients typed positive for A1-B8-DR3, 29 progressed to CDC stage IV, 22 to AIDS and 20 died. Twelve patients were typed positive for B27; six of these progressed to CDC stage IV, one to AIDS and none died. In a proportional hazards analysis of the 313 patients with known seroconversions, A1-B8-DR3 was significantly associated with covariate-adjusted relative risks of 3.7 (95% CI 1.9- 7.2), 3.1 (1.6-6.0) and 1.9 (1.1-3.2) for progression from seroconversion to death, AIDS and CDC stage IV, respectively. Events for B27 were too rare to include B27 in analyses to death and AIDS, but B27 was significantly associated with slower progression to CDC stage IV (0.3, CI 0.1-0.9). Random effects growth curve models were used to estimate individual rates of loss of square root CD4 count and loss of CD4 percentage, for 603 and 617 patients, respectively. A1-B8-DR3 was associated with rapid loss of both markers (p = 0.02 and p = 0.01, respectively); B27 was associated with slow loss of both markers (p = 0.04 and p < 0.005).      

The glycosyl phosphatidylinositol-linked FcγRIII(PMN) mediates transmembrane signaling events distinct from FcγRII

To investigate the ability of FcγRIII(PMN), the GPI-anchored isoform of FcγRIII (CD16) in polymorphonuclear leukocytes (PMN), to mediate transmembrane signaling events, we measured changes in membrane potential with DiOC(5) and in intracellular calcium with indo-1. FcγR were ligated by anti-FcγRIII mAb 3G8 (IgG and Fab), anti-FcγRII mAb IV.3 (IgG and Fab), and human IgG aggregates. Cell bound mAbs were also crosslinked by goat F(ab’)(2) anti-mouse IgG. 3G8 IgG elicited a rapid change in [Ca(2+)](i), which was unaffected by EGTA, Vibrio cholerae toxin (CT), or Bordetella pertussis toxin (PT), and was abolished by BAPTA . Univalent receptor binding with 3G8 Fab gave no response but crosslinking with F(aV)2 GAM gave a rapid [Ca2,](i) response. Neither IV.3 Fab, IV.3 IgG, nor crosslinking of IV.3 Fab elicited a calcium signal. PI-PLC-treated PMN with the density of FcγRIII(PMN) reduced to that of FcγRII showed an unattenuated change in [Ca(2+)](i), with a 3G8 stimulus. The effects of IgG aggregates paralleled those of 3G8 mAb. These data indicate that multivalent ligation of FcγRIII(PMN) initiates an increase in [Ca(2+)];, derived from intracellular stores, that is distinct from both the FMLP- and FcγRII-induced responses. Ligand-dependent interaction with FcγRII is not required. Since FcγRIII(PMN) can internalize the FcγRIII-specific probe Con A-opsonized E and lyse anti-FcγRIII heteroantibody-opsonized chick E, this GPI-anchored molecule mediates both signal transduction and integrated cell responses.     

Inhibition of an anti-Pr1d cold agglutinin by citrate present in commercial red cell preservative solutions

A patient with known cold autoimmune hemolyticanemia was admitted for surgery. Routine cold agglutinin evaluations, using commercial red cells (RBCs) in modified Alsever's preservative solution, revealed a cold agglutinin titer of 4 to 16. However, using RBCs washed four times with saline, a high-titer (greater than 2000 at 4 degrees C) cold autoagglutinin was demonstrated. The cold agglutinin was shown to be an IgM kappa paraprotein with anti-Pr1d specificity. The addition of Alsever's solution to washed RBCs inhibited the cold agglutinin. Each major component of Alsever's solution (neomycin, chloramphenicol, inosine, dextrose, and citrate) was tested individually; only citrate inhibited the patient's cold agglutinin. Various compounds structurally related to citrate were tested and found to cause various degrees of inhibition. The strongest inhibition correlated with the presence of either three carboxyl groups on molecules devoid of double-bonded carbon atoms or two carboxyl groups in cis configuration. A panel of 54 cold agglutinins, including 7 with anti-Pr specificity, was analyzed. None was significantly inhibited by Alsever's solution, although one with anti-Pr2 specificity was weakly inhibited. In summary, these studies describe an anti-Pr1d cold autoagglutinin that was inhibited by citrate in RBC preservative solutions. The failure to detect such a cold agglutinin can result from not washing RBCs free of citrate before testing.     

Endovascular repair of a spontaneous carotid artery dissection with carotid stent and coils

Dissection of the internal carotid artery is an under-recognized cause of transient ischemic attack and cerebral vascular accident. Spontaneous dissections, in which no precipitating cause can be identified, occur infrequently. Endovascular intervention is an evolving treatment option in patients in whom anticoagulation therapy alone is not adequate, who are not suitable candidates for major surgery, or who have extremely distal dissections that are difficult to access. We report a case of successful endovascular stenting and coil application in a patient with spontaneous dissection of the distal cervical internal carotid artery with extension to its petrous portion and an accompanying pseudoaneurysm at the level of the skull base.     

超声心动图诊断手术前后心下型完全性及部分性肺静脉异位引流

目的 利用多普勒超声心动图术前诊断心下型完全性及部分性肺静脉异位引流,判断术后肺动脉压力及是否存在吻合口狭窄。方法 回顾分析25例心下型完全性肺静脉异位引流及30例心下型部分性肺静脉异位引流患儿超声心动图诊断资料。结果 超声心动图对心下型肺静脉异位引流诊断率可达100%。手术后近期未发生吻合口狭窄者,肺动脉压峰值及右心室/左心室舒张末内径比值与术前差异有统计学意义(P＜0.05);发生吻合口狭窄者,肺动脉压峰值及右心室/左心室舒张末内径比值与术前差异无统计学意义。结论 超声心动图可准确诊断心下型肺静脉异位引流,有利于确定手术方案。     

Educational objectives and requirements of an undergraduate clerkship in general practice. The outcome of a consensus procedure

OBJECTIVES: The main aim of this study was to reach consensus between students, faculty and general practice teachers on the educational objectives and requirements of the clerkship in general practice. METHOD: The consensus procedure consisted of four steps and all active general practice teachers (n = 116) were asked to participate in the study. RESULTS: We identified 189 educational objectives: 127 complaints (problems, symptoms, syndromes), 29 clinical skills and 37 objectives concerning the theoretical dimensions of general practice. Educational requirements crystallized to 16 essential preconditions of a teaching practice and 35 didactic activities to be performed by the general practice teachers. CONCLUSIONS: These consensus results will be used to structure the medical curriculum and as guidelines for the educational process during the clerkship.      

Nitric oxide inhibits development of embryos and implantation in mice

The objectives of this study were to evaluate the effects of a nitric oxide (NO) donor on embryo development in vitro and on implantation of embryos in vivo in mice. Mouse embryos (2-cell) were incubated in media containing different concentrations of diethylenetriamine/NO (DETA/NO), a nitric oxide donor, and development was monitored daily for 4 days. Specificity of NO effects was assessed by using DETA without NO or 48 h preincubated DETA/NO. In in-vivo studies, mated mice were continuously infused, subcutaneously, with various concentrations of DETA/NO or DETA through mini-osmotic pumps (from day 1 of pregnancy), and implantations in the uterus were assessed on day 6. None of the embryos progressed beyond 4-cell stage when exposed to 0.1 or 1.0 mM DETA/NO compared with 94.5% of control embryos that developed beyond the morula stage by day 4. Embryo development was unaffected by lower (0.001 and 0.01 mM) concentrations of DETA/NO, 48 h preincubated DETA/NO, or DETA only. Infusion of DETA/NO to mice caused inhibition of embryo implantation in a dose-dependent manner. No implantation sites were observed in mice infused with a daily dose of 20 micromol DETA/NO rate, compared with an implantation rate of 81.8% in control or DETA-treated mice. This study demonstrates for the first time that higher concentrations of NO inhibit both embryo development in vitro and implantation in vivo in mice.