A sudden increase in factor VIII inhibitor development in multitransfused hemophilia A patients in The Netherlands. Dutch Hemophilia Study Group

The development of antibodies to factor VIII (inhibitors) in response to clotting-factor concentrates administration in hemophilia is common during the first few years of treatment but rare in multitransfused patients. We have investigated the possible association of a recently introduced factor VIII concentrate (Factor VIII CPS-P) in The Netherlands with the occurrence of inhibitors. To this effect, we conducted two studies. First, we performed a national multicenter study in which clinical information and inhibitor test results were obtained for 447 hemophilia A patients over the period 1988 through 1991. Secondly, for a baseline comparison we estimated the frequency of inhibitor development in a closely followed cohort of 144 patients, from 1984 through 1989. Before the introduction of Factor VIII CPS-P, the incidence of new inhibitors was 4.4/1,000 patient-years in the national study from March 1988 through May 1990, and 3.9/1,000 patient- years in the cohort followed from 1984 through 1989. These figures are similar to the incidence of new inhibitors that was found in a large cohort of patients in the United States followed in the 1970s. In the period that the new concentrate Factor VIII CPS-P was on the market, from June 1990 through November 1991, 11 clinically relevant inhibitors were detected, which yielded an incidence over this interval of 20.1/1,000 patient-years, a 4.5-fold increase compared with the previous interval (C195: 1.4 to 14.3). Nine of these 11 patients had in their lifetime received over 250 infusions with factor VIII preparations. whereas all of the inhibitors detected in the previous time interval, and all of the 24 inhibitor patients described in the US study, had received less than 250 infusions in their lifetime. All patients who developed inhibitors after June 1990 had been exposed to Factor VIII CPS-P, whereas only 75% of the patients who did not develop an inhibitor had been exposed to this product. In a prospective extension of the study, with a second inhibitor measurement after 3 months, we found that one additional inhibitor had developed during 52.5 patient-years of Factor VIII CPS-P use. In conclusion, there has been a sudden increase in the frequency of inhibitor patients, for a large part among multitransfused patients. It seems more than likely that this increase is associated with the introduction of a new factor VIII concentrate in The Netherlands.(ABSTRACT TRUNCATED AT 400 WORDS)     

抗真菌药物的研究Ⅱ．C－端含氧代赖氨酸二肽的合成及抗白念珠菌活性

引用违法传递概念设计合成了１１个Ｃ－末端含氧代赖氨酸二肽，进行抗深部致病菌－白念珠菌活性试验，体外实验结果显示极强的抑菌活性，ＭＩＣ在１２．５～０．８μｇ／ｄｉｓｋ之间，较母体氧化赖氨酸大５０～１３５倍（克分子比）。     

核苷甲基化对酵母tRNAPhe反密码环结构与功能影响的研究

通过用甲基选择性地取代核苷的氢原子，研究修饰的全面贡献。实验表明某些情况下核苷甲基化仅能略微地改变局部残基构象，而在另一些情况下却能显著地改变构象。     

Pustular acral erythema in a patient with acute graft-versus-host disease

Acral erythema is a well-known side-effect of chemotherapy treatment but it is not common in patients undergoing bone marrow transplant. We report a post-transplant patient with clinical and histological acute graft-versus-host disease (GVHD) who concurrently developed acral erythema presenting as painful, well-defined and self-limiting palmar erythema with pustules. A skin biopsy from the palm showed abnormal keratinocyte maturation and eccrine squamous syringometaplasia. This case illustrates the difficulties in establishing the differential diagnosis of cutaneous eruptions in patients undergoing bone marrow transplant.