Extracellular signal-regulated kinase (ERK) activation by the pre-T cell receptor in developing thymocytes in vivo

The first checkpoint in T cell development occurs between the CD4(-)CD8(-) and CD4(+)CD8(+) stages and is associated with formation of the pre-T cell receptor (TCR). The signaling mechanisms that drive this progression remain largely unknown. Here, we show that extracellular signal-regulated kinases (ERKs)-1/2 are activated upon engagement of the pre-TCR. Using a novel experimental system, we demonstrate that expression of the pre-TCR by developing thymocytes induces ERK-1/2 activation within the thymus. In addition, the activation of this pre-TCR signaling cascade is mediated through Lck. These findings directly link pre-TCR complex formation with specific downstream signaling components in vivo.     

Brain Death and Organ Donation in Germany: Analysis of Procurement in a Neurosurgical Unit and Review of Press Reports

Summary  Objective. A prospective study was undertaken to determine the number of potential organ donors in a neurosurgical intensive care unit and to record the actual number of organ donations. The reasons for refusal of organ donations were analysed with respect to the controversial public discussion of the brain death concept and the transplantation law in Germany.  Methods. From 1994 to 1997, the number of cases of brain death, and the number of cases in which relatives consented or refused to organ donation as well as the number of actual organ explantations was recorded. Over the same period, press reports of 5 German language newspapers were analysed with regard to the authors' position on brain death and transplantation law, their qualification, intention, and mode of presentation.  Results. Annually, about 70 deaths occurred on the department's intensive care unit of which almost 30% of the patients were determined to have suffered brain death without any obvious contraindications against organ donation. The refusal rate of relatives rose from 56% up to 78%, and the rate of organ donors thus decreased from 5% in 1994 to 4% presently in the department. About 100 reports were published each year in the analysed newspapers, of which about 90% voiced approval of organ transplantation. During the review period, the depiction became more objective (57% in 1994 to 82% in 1997) and the suspicious attitude toward the technique of brain death diagnosis declined. Whereas 50% of the articles rejected the brain death concept in 1994, this figure decreased to 39% in 1997 and conversely the concept of consent rose from 33% in 1994 to 56% in 1997.  Conclusion. In Germany, the relatives refusal rate in organ donation is continuously high, presumable due to a depressing 39% of press reports rejecting the brain death concept, and resulting in a very low number of organ donations. There is hope that the transplantation law which has finally passed German parliament in 1997, confirming the brain death concept as well as the legal principle of prior consent by the donor or consent by the relatives will eventually result in an increase of organ donation especially when supported by an educational campaign which is embodied in the transplantation law.     

Pain and health related quality of life after heart, kidney, and liver transplantation

No study has focused particularly on the sensory and affective experience of bodily pain among transplanted patients. The aim of this study was to explore pain and other factors that influence health related quality of life (HRQOL) in heart, kidney, and liver transplant recipients during the first 2 yr after transplantation, and to define similarities and/or differences in the three groups. A total of 76 patients, 18-60 yr old, undergoing heart, kidney, or liver transplantation between 1995 and 1997 with a follow-up of 6-24 months were included. HRQOL and pain were investigated by using the Short-Form-36 items (SF-36), the Hospital Anxiety and Depression Scale (HAD), and the Pain-O-Meter (POM). Overall, the patients show satisfactory HRQOL. There were no differences in experienced HRQOL 6 24 months after transplantation between kidney, liver, and heart transplant recipients except in the area of Role-Physical (RP). Fifty-three percent of all patients reported bodily pain. The most common locations were the hands, feet, and back, and sensory experiences were burning, stabbing, or dull pain. There was a correlation between number of rejections and total score for POM-VAS (p < 0.05) (rho = 0.47). There was also a correlation between the number of rejection episodes and the total pain intensity score for POM-WDS (p < 0.05) (rho = 0.48). Patients with pain scored higher in the area of depression (p < 0.05). Bodily pain is an important problem after organ transplantation, affecting daily living even in patients with good allograft function and it limits physical function. vitality, and general health.     

An active liver transplant programme for hepatocellular carcinoma in cirrhotic patients: is it justified?

Even at an early stage, hepatocellular carcinoma (HCC) in patients with cirrhosis is often deemed unresectable because of limited liver reserve. In these circumstances, liver transplantation (LTx) offers some hope for palliation or cure. The results of LTx for selected cirrhotic patients with HCC were analysed. The outcomes were compared with those of patients who underwent LTx for other forms of hepatic malignancy and those who underwent LTx for non-malignant conditions. Four hundred and eighty LTx were performed in 441 patients between January 1986 and December 1998. Twenty-eight LTx recipients (25 males, 3 females) of mean age 51 (14 63) yr had cirrhosis and HCC. Twenty-seven patients had underlying predisposing conditions (11 had hepatitis B, 10 had hepatitis C, 2 had hepatitis B and C, 1 had haemochromatosis, 1 had autoimmune hepatitis, 1 had alcoholic cirrhosis and 1 had alpha-1 antitrypsin deficiency). In 22 patients, HCC was diagnosed pre-LTx, and in 6 patients, the cancers were discovered incidentally. The average tumour size and number were 2.8 (0.4-11.5) cm and 1.3 (1-4), respectively. Two patients with known HCC died during and shortly after the LTx operation. Of the other patients, 3 died; 1 died of HCC recurrence 18 months post-LTx, 1 died of graft failure from recurrent hepatitis C and 1 died of fungal sepsis. Twenty-three (82%) patients survived to 22.5 (0.5-96) months post-LTx without HCC recurrence and with 1- and 3-yr actuarial patient survival rates of 87 and 76%, respectively. Equivalent survival rates of patients who underwent LTx for other malignancies (n = 11) were 82 and 46% (p = NS), and for those who underwent LTx for benign causes (n = 402), they were 77 and 73% (p = NS). All 15 patients with known HCC, who met the selection criteria now in use, survived. LTx can result in prolonged. cancer-free survival in a good proportion of patients with cirrhosis and HCC, particularly when the cancers are incidental, or when diagnosed pre-LTx, conforming to established selection criteria. An active LTx programme for this group of patients is justified.     

Prospective study of microchimerism in transplant recipients

BACKGROUND: We evaluated peripheral blood microchimerism in 48 consecutive organ transplant recipients (35 kidneys, ten livers, one kidney-liver, one kidney-pancreatic islet, one kidney pancreas) up to 12 months post-transplantation. Patients were categorized according to the presence or absence of rejection episodes, and the patterns of microchimerism in the two groups were then compared. METHODS: DNA was extracted from donor, pre-transplant, and post-transplant peripheral blood samples. Several polymerase chain reaction (PCR)-based assays were developed for the detection of microchimerism. Assay sensitivities ranged from 0.0001 to 3%. RESULTS: Microchimerism was detected only in sex-mismatched cases (male donors and female recipients) using nested PCR for a Y-chromosome marker. There were ten such cases (six kidneys, two livers, and two combined organ transplants). In patients without rejection (n = 7), there was a peak of donor-DNA at 1-3 wk post-transplantation followed by a second peak between 3 wk and 4 months. In patients with biopsy-proven rejection (n = 3), the peaks were absent and the levels of microchimerism were extremely low (< 0.001%). Microchimerism levels declined in all 10 patients and were barely detectable 1 yr post-transplantation. Microchimerism was not detected in the remaining 38 patients despite using a battery of sensitive PCR-based assays. CONCLUSIONS: In our study, microchimerism was detected using the Y-chromosome PCR assay only and the level of donor-DNA in a given patient varied over time. This study highlights the difficulties in establishing a correlation between microchimerism and transplant tolerance.     

Impact of a preceding striatal excitotoxic lesion and treatment with ciliary neurotrophic factor on striatal graft survival

The survival of grafted embryonic striatal tissue, dissected from the lateral ganglionic eminence, depends on the status of the host striatum. We found significantly larger volumes of surviving graft tissue and of striatal-like tissue (P-zone) within the graft, when the host striatum had been subjected to an excitotoxic lesion prior to transplantation surgery. Concomitantly the numbers of surviving grafted cells, assessed in both cresyl violet-stained sections and in sections stained with an immunohistochemical marker for striatal neurons, increased as compared to when graft tissue was placed in an intact unlesioned striatum. Finally, we examined the impact of treatment of the donor tissue with ciliary neurotrophic factor (CNTF) on graft survival. CNTF has previously been shown to protect striatal neurons against excitotoxic insults both in vitro and in vivo, but it did not improve striatal graft survival when added to the cell suspension prior to implantation.     

多脏器微栓塞病细胞综合征动物实验模型──定义、判断标准、发生机制及其与临床的关系

利用健康杂交犬制作了多脏器微栓塞病细胞综合征（ＰＯＭＳ）模型,观察在不同时限、不同组织器官造成的病理生理改变。从中发现,钳夹腹主动脉阻断血流后,其供血器官都发生了ＲＯＭＳ,且不同器官的功能与结构损害有发生时间和程度的不同,但均有不同程度的微栓塞形成趋势,这有助对“多脏器衰竭”概念认识的深化。     

Interobserver variation in the assessment of pelvic organ prolapse

The aim of this study was to determine the interobserver agreement of two grading systems for pelvic organ prolapse: the vaginal profile and the International Continence Society (ICS) draft proposal. Forty-nine consecutive women referred for evaluation of urinary incontinence and/or pelvic organ prolapse were studied. Patients were first examined by a physician and a nurse clinician using the vaginal profile, followed by an examination according to the technique described in the ICS draft proposal for standardization of terminology (1994). statistic and Pearson's correlation coefficient were used to determine interobserver variability for the ICS system by overall stage, by stage-specific comparison, and by specific anatomic location. The vaginal profile was evaluated by obtaining a for overall degree of prolapse, stage-specific comparison and by anatomic area. The for the ICS stage was 0.79 (P<0.001), and the for the vaginal profile by area of greatest prolapse was 0.68 (P<0.001), indicating substantial interobserver agreement for both systems. The ICS system was noted to have substantial interobserver agreement by a stage-specific comparison. All anatomic locations of the ICS staging system were found to correlate significantly, and a high degree of interobserver precision was found. The vaginal profile also showed significant interobserver agreement by overall degree of prolapse, by specific degree of prolapse, and by anatomic area. It was concluded that both the proposed ICS staging system and the traditional vaginal profile show significant interobserver agreement both by overall stage, stage-specific analysis and specific location. The registered nurse examination correlated well with the physican examination, indicating that the most important factor in obtaining reproducible results may be definition and close attention to examination technique.EDITORIAL COMMENT: There has recently been a great deal of interest in the anatomy and physiology of the pelvic floor and the various investigative techniques to define its function. The lack of a standardized and reproducible system to describe pelvic organ prolapse through the hiatus of the pelvic floor has hampered research into its pathophysiology and treatment. The authors applied a validated statistic and Pearson's correlation coefficient to convincingly measure interobserver reliability for the ICS system and indicated an index of trend between points on the ICS scale as well.     

Delayed transient neurologic toxicity due to tacrolimus: CT and MRI

We report a case of transient neurologic toxicity secondary to tacrolimus. The clinical and imaging findings are reported and their subsequent regression after interruption of therapy in the patient following a bone-marrow transplant is also described. The etiology of the neurotoxicity and its analogy with other immunosuppressant agents are discussed. Received: 18 June 1999/Accepted: 14 December 1999