Return of autologous blood donors as homologous blood donors

Autologous blood donors (ABDs) have been reported to have favorable attitudes toward returning as homologous blood donors (HBDs), but the frequency of return has not been well documented. ABDs eligible by history to be HBDs were followed at one blood center: 255 donating for elective surgery and 234 donating during pregnancy were followed for an average of 18 months and 20 months, respectively, from time of eligibility after surgery or postpartum. Male ABDs had a higher rate of return as HBDs, as 34 percent (21/62) returned to donate an average of 3 units, whereas 13 percent (56/427) of female ABDs returned as HBDs to donate an average of 2 units. Although a history of donation was associated with a higher rate of return (30%, 34/113), 11 percent (43/376) of ABDs with no history as HBDs returned to donate homologous units, despite having been recruited less frequently than prior HBDs. Overall, all male ABDs and female ABDs with an HBD history returned most frequently. The extra effort required for an autologous donor program may result in the recruitment of new donors into the HBD pool.     

Tissue and lineage-specific variation in inactive X chromosome expression of the murine Smcx gene

To understand how gene expression patterns are established on the inactive X chromosome during development, we have studied the murine gene Smcx, which is expressed from both the active and inactive mouse X chromosomes. In all tissues assayed, Smcx only partially escapes X inactivation, with expression levels from the inactive X allele approximately 30-65% that of the active X allele. Additionally, inactive X expression levels differed between extraembryonic and embryonic tissues and among different tissues from newborn and adult mice. Imprinted extraembryonic tissue had the lowest levels of inactive X Smcx expression, whereas the highest levels were in heart. These data suggest that the chromosomal basis of X inactivation differs among tissues, perhaps reflecting differences in the timing or regulation of inactivation in these cell lineages.      

Recurrent urinary tract infection in girls. Group with lower tract findings and a benign course

A group of girls is described with recurrent urinary tract infections characterized by predominantly lower tract symptoms. Clinical, laboratory, and radiography findings during the period of follow-up are presented. Infection persisted in most patients over several years. Response to medical and surgical treatment was unsatisfactory. The mean interval between the initial and most recent radiological study was 6 1/2 years. No case of renal parenchymal scarring was seen.     

A model of corrective gene transfer in X-linked ichthyosis

Single gene recessive genetic skin disorders offer attractive prototypes for the development of therapeutic cutaneous gene delivery. We have utilized X-linked ichthyosis (XLI), characterized by loss of function of the steroid sulfatase arylsulfatase C (STS), to develop a model of corrective gene delivery to human skin in vivo. A new retroviral expression vector was produced and utilized to effect STS gene transfer to primary keratinocytes from XLI patients. Transduction was associated with restoration of full-length STS protein expression as well as steroid sulfatase enzymatic activity in proportion to the number of proviral integrations in XLI cells. Transduced and uncorrected XLI keratinocytes, along with normal controls, were then grafted onto immunodeficient mice to regenerate full thickness human epidermis. Unmodified XLI keratinocytes regenerated a hyperkeratotic epidermis lacking STS expression with defective skin barrier function, effectively recapitulating the human disease in vivo. Transduced XLI keratinocytes from the same patients, however, regenerated epidermis histologically indistinguishable from that formed by keratinocytes from patients with normal skin. Transduced XLI epidermis demonstrated STS expression in vivo by immunostaining as well as a normalization of histologic appearance at 5 weeks post-grafting. In addition, transduced XLI epidermis demonstrated a return of barrier function parameters to normal. These findings demonstrate corrective gene delivery in human XLI patient skin tissue at both molecular and functional levels and provide a model of human cutaneous gene therapy.      

Blood loss and replacement in total hip arthroplasty: a multicenter study. The Preoperative Autologous Blood Donation Study Group

To determine blood loss, the number of transfusions, and the hemoglobin levels achieved in patients via transfusion in the course of total hip arthroplasty, 324 patient records from 1987 through 1989 were reviewed at three university and three community hospitals. Calculated blood loss was 3.2 +/- 1.3 units in primary procedures and 4.0 +/- 2.1 units in revision procedures (mean +/- SD). Of 777 red cell units transfused, 455 (59%) were autologous units. Transfused patients received 2.0 +/- 1.8 units for primary procedures and 2.9 +/- 2.3 units for revision procedures (mean +/- SD). The maximum number of units given to 95 percent of the transfused patients was 4 for primary procedures and 6 for revision procedures. The mean postoperative hemoglobin level after all transfusions was 103 to 110 g per L, regardless of patient age group of physical status, autologous donor status, or hospital. No difference in length of hospital stay was observed for patients less than 65 years old with hemoglobin concentrations of 80 to 139 g per L at discharge.     

急性冠状动脉综合征置入支架患者使用替罗非班和阿司匹林时泮托拉唑对消化道保护作用的评价

目的:急性冠状动脉综合征(ACS)置入支架患者使用盐酸替罗非班、阿司匹林、氯吡格雷、低分子肝素(四联)时,评价泮托拉唑对消化道的保护作用.方法:选择ACS置入支架治疗的患者266例,随机分入观察组134例,对照组132例,所有患者均服用阿司匹林、氯吡格雷、低分子肝素和盐酸替罗非班.观察组患者静脉注射泮托拉唑40 mg/d 4～5天,之后改为泮托拉唑片剂40 mg/次,2次/天,服用30天.观察两组间30天全因死亡、再次心肌梗死、再次经皮冠状动脉介入治疗(PCI)、再次住院、颅内出血和消化道出血状况.结果:观察组134例患者30天内全因死亡5例、再次心肌梗死4例、再次PCI4例和再次住院8例;对照组132例患者分别为8例、6例、5例和13例,两组相比差异均无统计学意义(P>0.05);两组均无颅内出血发生.观察组消化道大出血0和总消化道出血事件3例,对照组分别为5例和15例,两组比较观察组消化道大出血和总消化道出血事件少于对照组(P<0.05),差异均有统计学意义.结论:ACS置入支架治疗的患者,盐酸替罗非班治疗是安全有效的,未见颅内出血发生.静脉注射和口服泮托拉唑并不增加30天全因死亡、再次心肌梗死、再次PCI和再次住院发生,同时可以减少30天内消化道出血发生率特别是消化道大出血事件的发生,具有良好的消化道保护作用和安全性.     

Complete brain-type creatine kinase deficiency in mice blocks seizure activity and affects intracellular calcium kinetics

Purpose:   Brain-type creatine kinase (CK-B) and ubiquitous mitochondrial creatine kinase (UbCKmit) act as components of local phosphocreatine ATP shuttles that help in the compartmentalization and maintenance of pools of high-energy phosphate molecules in both neurons and glial cells. We investigated the role of these brain-type creatine kinases during extreme energy-demanding conditions in vivo (generalized tonic–clonic seizures) and in vitro.
Methods:   The physiologic response of wild-types and mice lacking both CK-B and UbCKmit (CK--/--mice) to pentylenetetrazole (PTZ)–induced seizures was measured using electroencephalography (EEG) recordings and behavioral monitoring. In vitro intracellular Ca²⁺ kinetics in hippocampal granule neurons were monitored upon single and repetitive depolarizations.
Results:   PTZ induced in only a few CK--/-- mice PTZ seizure-like behavior, but in all wild-types a full-blown seizure. EEG analysis showed that preseizure jerking was associated with high-amplitude discharges. Wild-type EEG recordings showed continuous runs of rhythmic 4–6 Hz activity, whereas no rhythmic EEG activities were observed in the few CK--/-- mice that developed a behavioral seizure. All other CK--/-- mice displayed a sudden postictal depression without any development of a generalized seizure. Hippocampal granule neurons of CK--/-- mice displayed a higher Ca²⁺ removal speed following repetitive KCl-induced depolarizations.
Discussion:   Deficiency for creatine kinase is affecting brain energy metabolism and will likely contribute to the disturbance of seizure development. Because CK--/-- hippocampal neurons exhibited an increase in Ca²⁺ removal rate of elevated intracellular levels, we conclude that altered Ca²⁺ clearance in CK--/-- neurons could play a role in the abnormal EEG and seizure activity.