Long-term discordant xenogeneic (porcine-to-primate) bone marrow engraftment in a monkey treated with porcine-specific growth factors

BACKGROUND: Mixed allogeneic hematopoietic chimerism has previously been reliably achieved and shown to induce tolerance to fully MHC-mismatched allografts in mice and monkeys. However, the establishment of hematopoietic chimerism has been difficult to achieve in the discordant pig-to-primate xenogeneic model. METHODS: To address this issue, two cynomolgus monkeys were conditioned by whole body irradiation (total dose 300 cGy) 6 and 5 days before the infusion of pig bone marrow (BM). Monkey anti-pig natural antibodies were immunoadsorbed by extracorporeal perfusion of monkey blood through a pig liver, immediately before the intravenous infusion of porcine BM (day 0). Cyclosporine was administered for 4 weeks and 15-deoxyspergualin for 2 weeks. One monkey received recombinant pig cytokines (stem cell factor and interleukin 3) for 2 weeks, whereas the other received only saline as a control. RESULTS: Both monkeys recovered from pancytopenia within 4 weeks of whole body irradiation. Anti-pig IgM and IgG antibodies were successfully depleted by the liver perfusion but returned to pretreatment levels within 12-14 days. Methylcellulose colony assays at days 180 and 300 revealed that about 2% of the myeloid progenitors in the BM of the cytokine-treated recipient were of pig origin, whereas no chimerism was detected in the BM of the untreated control monkey at similar times. The chimeric animal was less responsive by mixed lymphocyte reaction to pig-specific stimulators than the control monkey and significantly hyporesponsive when compared with a monkey that had rejected a porcine kidney transplant. CONCLUSION: To our knowledge, this is the first report of long-term survival of discordant xenogeneic BM in a primate recipient.     

精氨酸对烧伤创面愈合的影响

目的 探讨精氨酸对烧伤创面愈合的影响和量效关系。方法 通过大鼠深Ⅱ度烫伤模型,伤后肠道站充不同剂量精氨酸,观察烧伤创面愈合时间,测定烧伤创面愈合面积百分比,创面Ｉ型／Ⅲ型胶原比例,羟脯氨酸（ＯＨＰ）含量和真皮细胞增殖周期,结果 每天补充１００－４００ｍｇ／ｋｇ精氨酸可缩短烧伤创面愈合时间,增加烧伤创面中ＯＨＰ含量,降低烧伤创面Ｉ／Ⅲ型胶原比例,加速真皮细胞ＤＮＡ复制。比较喂不同剂量精氨酸各组,发现     

窥镜下激光治疗前列腺增生症

目的 评价经尿道激光前列腺切除术（ＴＵＬＰ）的疗效及其与前列腺大小的关系。方法 回顾分析了１９８８年至１９９８年１０年,采用ＴＵＬＰ治疗的４６９例前列腺增生症患者对手术技术、手术前后的症关改善情况进行比较,并对２３３例符合条件的患者ＴＵＬＰ手术效果与前列腺大小的相关性进行了研究。结果 ４６９例患者前列腺症状评分（ＩＰＳＳ）平均值由术前的２６．７降到术后的１４．２;最大尿流率平均值由６．２ｍｌ／ｓ上     

Surgical treatment of Ebstein's malformation: report of 108 cases

OBJECTIVE: To review retrospectively the experience of surgical treatment of Ebstein's malformation in 108 patients. METHODS: One hundred and eight patients with Ebsteins malformation underwent surgical correction, including tricuspid valve annuloplasty in 83 patients (73.4%) and tricuspid valve replacement in 30 (5 with redo-operation). Concomitant procedure included division of the abnormal accessory conduction pathway in 8 patients. RESULTS: The overall hospital mortality was 8.8%. The hospital mortality rate was 10.4% before 1990 and 5.5% after that time. There was a significant difference between the two periods (P < 0.05). The main causes of death were low cardiac output, arrhythmias and right heart failure. The mean follow-up time was 6.3 years. The heart function improved to be NYHA class I or II in 92% of the patients. CONCLUSIONS: Early surgical intervention is recommended for patients with Ebstein's malformation, especially for those with symptoms and cardiac enlargement. Tricuspid valve repair should be performed if anterior leaflet of the tricuspid valve well developed. However, tricuspid valve replacement is advocated if anterior leaflet is dysplastic or its origin displaced.     

Immunogenicity of peptides derived from a fibronectin-binding protein of S. aureus expressed on two different plant viruses

The D2 peptide derived from an S. aureus fibronectin-binding protein (FnBP) was expressed on the surface of the icosahedral cowpea mosaic virus (amino acids 1-30 of D2) or on the rod-shaped potato virus X (amino acids 1-38 of D2), termed CPMV-MAST1 and PVX-MAST8, respectively. Mice and rats were immunized subcutaneously with CPMV-MAST1 and mice with PVX-MAST8 in adjuvant and high titres of FnBP-specific antibody were obtained. The mouse IgG was predominantly of the IgG2a and IgG2b isotypes, which strongly bound complement component C1q, suggesting a TH1-bias in the peptide-specific responses. Sera from mice and rats immunized with CPMV-MAST1 and from mice immunized with PVX-MAST8 were shown to completely inhibit the binding of fibronectin to immobilised recombinant FnBP and rat sera against CPMV-MAST1 were able to block adherence of S. aureus to fibronectin. These studies demonstrate that the D2 peptide is highly immunogenic when expressed on 2 different plant viruses and highlight the potential of plant virus-based vaccines to protect against S. aureus infections.     

Estimation of post-lead-time survival under dependence between lead-time and post-lead-time survival

Early detection of cancer by screening advances the date of diagnosis, but may or may not alter time to death. Screening programme need to assess the true benefit of screening, that is, the length of time by which survival has been extended, beyond merely the time by which the diagnosis is advanced (lead-time). One method is to estimate the distribution of the time survived post-lead-time using total survival time data for screen-detected cancer cases, under the assumption of independence of the lead-time and the past-lead-time survival. However, it seems biologically reasonable that the lead-time and the post-lead-time survival are positively correlated. This paper investigates the consequences of departures from independence of lead-time and post-lead-time survival on estimation of post-lead-time survival. We introduce a new model that involves dependence between the lead-time and the post-lead-time survival. We show that the new model can be converted to the model discussed by Xu and Prorok. We consider the non-parametric maximum likelihood estimator of the post-lead-time survival under the new model. We apply the method to data from the HIP (Health Insurance Plan of Greater New York) breast cancer screening trial. We make comparisons with the survival of cancer cases not detected by screening, such as interval cases, cases among individuals who refused screening, and randomized control cases.     

Compromised kidney graft rejection response in Vervet monkeys after withdrawal of immunosuppressants tacrolimus and sirolimus

BACKGROUND: In nonprimates, organ allografts are often not rejected after withdrawal of immunosuppression. In this study, we examined whether such a phenomenon also occurs in primates. METHODS: Vervet monkeys were transplanted with renal allografts and treated for 60 days with tacrolimus, or tacrolimus plus sirolimus. The drugs were totally withdrawn on day 61. The survival of the monkeys was monitored, and their response to donor- or third party-derived alloantigens was examined in vivo and in vitro. RESULTS: The majority (80-100%) of the grafts survived for at least additional 30 days with no signs of acute rejection. The compromised rejection is donor-specific, because recipient monkeys failed to reject a donor-derived skin graft, but a third-party skin graft was rejected. In vitro mixed lymphocyte reaction and interleukin-2 production in the mixed lymphocyte reaction between the recipients and their donors or between the recipients and a third party had no discernable patterns, and thus did not reflect the in vivo status of the immune system. Although the recipients could not reject the graft acutely after drug withdrawal, the kidney grafts and the donor-derived skin grafts had pathological findings of chronic rejection. CONCLUSIONS: The rejection response of the monkeys to an established graft after withdrawal of immunosuppression is compromised. The compromised rejection is specific and is not due to a permanent alteration of the immune system by the initial drug treatment. The allografts are not inert but have low levels of interaction with the recipient immune system.     

The lumbosacral nerves in relation to dorsal S1 screw placement and their locations on plain radiographs

Seven adult cadaver lumbopelvises were harvested to study the anatomic relationship of the L4 and L5 nerves to S1 dorsal screw placement and the location of the L4, L5, and S1 nerves on plain radiographs. The mean lateral angle of S1 screw trajectory toward the L4 nerve was 31+/-8 degrees, and the mean screw trajectory length was 53+/-8 mm. The mean lateral angle of the screw trajectory toward the L5 nerve was 21+/-8 degrees, and the mean screw trajectory length was 38+/-4 mm. On both inlet and outlet radiographs, the lateral angle of the nerves increased from L4 to S1. The L4 nerve coursed over the middle third of the superior ala in the inlet view and the middle third of the lateral mass in the outlet view. The L5 nerve coursed over the inner third of the superior ala and inner third of the lateral mass. On the lateral view, the mean distances from the sacral promontory to the L4, L5, and S1 nerves along the anterior border of the sacrum were 4+/-7 mm, 12+/-5 mm, and 28+/-8 mm, respectively. This study suggests that S1 sacral screws be directed between 30 degrees and 40 degrees lateral to avoid compromising the lumbosacral trunk and sacroiliac joint.     

左主干狭窄的外科治疗

目的 探讨左主干狭窄（ＬＭＳ）≥５０％患者的外科治疗效果。方法 ４２例ＬＭＳ的患者接受了冠状动脉旁路移植术（ＣＡＢＧ）。平均年龄６８．７岁。ＬＭＳ介于５０％￣７５％者１６例,大于７５％者２６例,不稳定型心绞痛２９例。按ＣＣＳＳ标准心绞痛分级,Ⅰ级２例,Ⅱ级５例、Ⅲ级１７例,Ⅳ级１８例。左室射血分数小于５０％者２４例。结果 术前平均住院时间２．３ｄ人均移植血管３．３根,无手术死亡。术后所有患者心绞痛     

Rodent model of chronic central pain after spinal cord contusion injury and effects of gabapentin

Spinal cord injury (SCI) often results in abnormal pain syndromes in patients. We present a recently developed SCI mammalian model of chronic central pain in which the spinal cord is contused at T8 using the NYU impactor device (10-g rod, 2.0-mm diameter, 12.5-mm drop height), an injury which is characterized behaviorally as moderate. Recovery of locomotor function was assessed with an open field test and scored using the open field test scale (BBB scale). Somatosensory tests of paw withdrawal responses accompanied by supraspinal responses to both mechanical punctate (von Frey hairs) and nonpunctate (4 mm diameter blunt probe) as well as thermal (radiant heat) peripheral stimuli were performed. Comparisons at the level of the individual animal between precontusion and postcontusion responses indicated significant increases in reactions to low threshold punctate mechanical stimuli, non-punctate stimuli and thermal stimuli (p < 0.05). To demonstrate the validity of this model as a central pain model, gabapentin, an agent used clinically for central pain, was given i.p. at 10 or 30 mg/kg. Gabapentin treatment significantly and reversibly changed the responses, consistent with the attenuation of the abnormal sensory behavior, and the attenuated responses lasted for the duration of the drug effect (up to 6 h). These results support the use of the spinal contusion model in the study of chronic central pain after SCI.