Aprotinin or tranexamic acid in cardiac surgery: a propensity analysis

Canadian Journal of Anesthesia/Journal canadien d'anesthésie -     

Platelet storage pool deficiency in pigs

We report a new bleeding disease--storage pool deficiency (SPD) of platelets--in pigs from the Mayo swine colony of homozygous von Willebrand's disease (vWD) and of heterozygous carriers of vWD. Levels of factor VIII, von Willebrand factor antigen (vWF:Ag), and ristocetin cofactor (RCof) were similar in the vWD carriers and SPD pigs. The latter pigs, however, had bleeding times of 15 minutes or more and were severe bleeders, in contrast to clinically normal vWD carriers. Platelet aggregation in response to collagen was reduced in most SPD pigs. Total platelet content of ADP, ATP, and serotonin was less than that of normal pigs. While the initial uptake of 14C-labeled serotonin into platelets was similar in SPD and normal pigs, retention of serotonin was reduced in platelets of SPD pigs. Transmission electron microscopy showed a large decrease of dense bodies in the platelets of SPD pigs. These findings support a diagnosis of SPD. Genetic analyses suggest an autosomal recessive mode of inheritance. A breeding program is under way to produce pigs affected only at the SPD gene, thus allowing further characterization of SPD and SPD-carrier pigs.     

肿瘤坏死因子对牛肺动脉内皮细胞的损伤及蛋白激酶C抑制剂的抑制作用

研究表明:肿瘤坏死因子(TNF)可剂量依赖地引起牛肺动脉内皮细胞乳酸脱氢酶释放率(LDH%)升高,促进中性粒细胞向内皮细胞粘附,并可抑制内皮细胞增殖和DNA合成。蛋白激酶C(PKC)抑制剂1-(5-异喹啉磺酰基)-2-甲基哌嗪(H-7)和槲皮素一方面可剂量依赖地抑制TNF对内皮细胞的直接损伤,另方面又可通过抑制TNF诱导的中性粒细胞对内皮细胞粘附增加,减轻TNF对内皮细胞的间接损伤作用,同时还可抑制TNF对内皮细胞增殖和DNA合成的影响,从而间接加强内皮细胞对损伤的自我修复。     

Deletion of the distal COOH-terminus of the A2B adenosine receptor switches internalization to an arrestin- and clathrin-independent pathway and inhibits recycling

Background and purpose:

We have investigated the effect of deletions of a postsynaptic density, disc large and zo-1 protein (PDZ) motif at the end of the COOH-terminus of the rat A_2B adenosine receptor on intracellular trafficking following long-term exposure to the agonist 5′-(N-ethylcarboxamido)-adenosine.

Experimental approach:

The trafficking of the wild type A_2B adenosine receptor and deletion mutants expressed in Chinese hamster ovary cells was studied using an enzyme-linked immunosorbent assay in combination with immunofluorescence microscopy.

Key results:

The wild type A_2B adenosine receptor and deletion mutants were all extensively internalized following prolonged treatment with NECA. The intracellular compartment through which the Gln³²⁵-stop receptor mutant, which lacks the Type II PDZ motif found in the wild type receptor initially trafficked was not the same as the wild type receptor. Expression of dominant negative mutants of arrestin-2, dynamin or Eps-15 inhibited internalization of wild type and Leu³³⁰-stop receptors, whereas only dominant negative mutant dynamin inhibited agonist-induced internalization of Gln³²⁵-stop, Ser³²⁶-stop and Phe³²⁸-stop receptors. Following internalization, the wild type A_2B adenosine receptor recycled rapidly to the cell surface, whereas the Gln³²⁵-stop receptor did not recycle.

Conclusions and implications:

Deletion of the COOH-terminus of the A_2B adenosine receptor beyond Leu³³⁰ switches internalization from an arrestin- and clathrin-dependent pathway to one that is dynamin dependent but arrestin and clathrin independent. The presence of a Type II PDZ motif appears to be essential for arrestin- and clathrin-dependent internalization, as well as recycling of the A_2B adenosine receptor following prolonged agonist addition.     

一阶导数差示脉冲极谱法的建立及在药物分析中的应用

本文研究了一阶导数差示脉冲极谱法,并将其运用于扑尔敏、氟哌啶醇、维生素B₆及其制剂的定量分析中。方法简便、快速、灵敏、结果准确。     

A Third world international health elective for U.S. medical students. The 16-year experience of the State University of New York,Health Science Center at Brooklyn

The Department of Preventive Medicine and Community Health at the State University of New York, Health Science Center at Brooklyn (SUNY, HSCB) instituted an eight-week third world international health elective for fourth year medical students in 1980. Since that time, ninety students have participated. The purposes of this elective are to provide fourth year medical students with an opportunity to observe and study the structure and functions of a health care delivery system in a third world country, to provide medical service, and to have a crosscultural experience. The emphasis in this elective is on public health, preventive medicine, and primary care. There is a high level of student competition for this elective, with 46.9% of applicants having been accepted over a fifteen-year period. Although women comprise 40% of the average medical school class, they represent 50% of participants in this elective program. The percentage of African-American and Hispanic students has been 20%. These two minority groups represented from 8% to 10% of the student body during the period under study. Careful screening, including an examination of academic records and personal interviews, has resulted in the selection of highly motivated, adaptable, and dedicated students who have performed well at overseas sites. Student satisfaction levels with this elective are extremely high, with most rating it the best experience of their medical school years. Students undergo extensive preparation prior to going overseas. This covers issues related to individual health and safety, travel and lodging, and the nature of the host country culture, health care system, and assignment site. Our students are especially experienced at cross-cultural understanding because of the unusual diversity of the patients they treat in Brooklyn, and the ethnic diversity of local hospital staffs and the medical school class. This Brooklyn experience in cross-cultural understanding has been cited by many participants as having been the best preparation for functioning in a foreign culture. The Alumni Fund of the College of Medicine has strongly and consistently supported this elective both with philosophical commitment and financial grants to help defray travel costs. This type of support is unusual among medical schools in New York City. Overseas preceptors have willingly given of their time and institutional resources to make these experiences available and meaningful for students.     

Prevention of recurrence and prolonged survival in primary central nervous system lymphoma (PCNSL) patients treated with adjuvant high-dose methylprednisolone

Five patients at risk for primary central nervous system lymphoma (PCNSL) recurrence were treated with high-dose methylprednisolone (HDMP) to prevent 'trafficking' of malignant lymphocytes into the central nervous system (CNS). HDMP was chosen because of its ability to stabilize the 'blood brain barrier (BBB)'. Three men with newly diagnosed PCNSL, ages 62, 76 and 78y, whose survival was projected to be 6.6 months, began treatment after achieving complete response (CR) to initial radiation therapy alone and survived 27, 37 and 59 months after treatment. In none was death from recurrent disease in CNS but one patient did die of systemic non-Hodgkin's lymphoma (NHL) five years after PCNSL diagnosis. A 20 y old man was treated with HDMP after successful combined modality therapy and is alive 75+ months after initial diagnosis without evidence of disease recurrence. A 34 y old man relapsed after combined modality initial treatment and failed to respond to HDMP when treatment was begun after unsuccessful salvage therapy; he died of disease 12 months after initial diagnosis. There were no treatment complications. The promising results in this pilot study from the basis for a North Central Cancer Treatment Group (NCCTG) 96-73-51, a Phase 2 clinical trial of brain radiotherapy and HDMP for PCNSL patients 70y of age and older, a group of patients at high risk for toxicity from intensive combined modality therapy.     

A randomized prospective comparison of oral versus intraperitoneal ofloxacin as the primary treatment of CAPD peritonitis

Summary: Oral ofloxacin has been successfully used in our centres for the primary treatment of peritonitis complicating continous ambulatory peritoneal dialysis (CAPD). In view of the progressive rise in the resistance rate to ofloxacin among peritoneal bacterial isolates, a study was conducted to determine if oral ofloxacin remains a viable first line treatment for CAPD peritonitis in our centres and if the result can be improved by changing from an oral to an intraperitoneal (i.p.) route. In patients on three 2 L daily CAPD exchanges, ofloxacin given at the i.p. dosage of 200 mg loading followed by 25 mg/L of peritoneal dialysate achieved overnight trough peritoneal levels which are at least four times the minimal 90% inhibitory concentration (MIC90) of most bacterial pathogens without significant accumulation in the systemic circulation. This i.p. dosage was therefore chosen for the clinical study and the result was compared to that using ofloxacin given in the oral dosage of 400 mg loading followed by 300 mg once daily as maintenance. of all the recruited episodes, 35 were eligible for analysis. the overall primary cure rate including primary failures and relapses was 55.6% (10/18) in the oral treatment group and 70.6% (12/17) in the i.p. treatment group. the corresponding figures for gram positive bacterial (g +) infections were 36.4% and 50%, for gram negative bacterial (g -) infections were 66.7 and 80% and for culture negative infections were 75 and 80%. In culture positive cases, all treatment failures were due to resistant infections which were observed in 42.3% of all bacterial isolates, 47.1% of g + isolates and 33.3% of g - isolates. Due to the high background level of bacterial resistance among our CAPD population, ofloxacin monotherapy given either by the oral or the i.p. route can no longer be recommended for the primary treatment of CAPD peritonitis.