Plasma lipids in kidney transplanted children and adolescents: influence of pubertal development, dietary intake and steroid therapy

Abstract. Plasma triglycerides and/or cholesterol were significantly increased in twenty-four of thirty kidney transplanted children and adolescents with stable renal function, at least one year after the last rejection crisis who received low dose prednisone therapy. The cholesterol increment was related to both low density and high density lipoproteins. However, similar to findings in adult allograft recipients, these increases were very variable: six subjects had normal levels, eight had increased triglycerides, five increased triglycerides and cholesterol, and eleven increased cholesterol. No influence of renal function was found in this series of patients all of whom had plasma creatinine below 160 μmol/1. Subjects who had achieved sexual development had lower cholesterol values. An insignificant difference was observed between patients receiving daily and alternate-day steroid therapy, but a significant negative correlation was found between plasma triglycerides and fractional urinary excretion of 17 OH corticosteroids in the first 6 h after an oral dose of prednisone. Finally, no correlation was found between energy intake and triglycerides; but a significant correlation was observed between protein intake and plasma cholesterol.
In conclusion, some patients show a high level of triglycerides and/or cholesterol after renal transplantation, possibly due to a different individual response to steroid therapy.     

Do men undergoing sterilizing cancer treatments have a fertile future?

This study was designed to assess the effect of cancer treatments on the natural and assisted reproductive potential of men. A cohort of men with cancer, in whom radiotherapy and/or chemotherapy was planned, were invited to participate. Twenty-two pre- and post-treatment semen samples were analysed. The reproductive potential of participants was assessed with respect to the current range of fertility treatment options available. Abnormal sperm concentrations were found in 27% of patients pre-treatment compared to 68% post-treatment following a mean latency of 20 months from treatment. Fifty-nine percent of patients experienced a clinically significant decrease in sperm, concentration following radiotherapy and/or chemotherapy; 23% developed azoospermia following treatment. Eighty-two percent of patients with testicular malignancy had oligo- or azoospermia post-treatment. Only one patient had a clinically significant reduction in the percentage of motile spermatozoa post-treatment. Cryopreservation of semen prior to treatment improved the fertility prospects of 55% of patients. Intracytoplasmic sperm injection (ICSI) enhanced the fertility prospects of a further 14%. In the absence of, or after depletion of, cryopreserved semen, ICSI could enhance the fertility prospects of 45% of patients. Fertilization has been achieved by ICSI using spermatozoa retrieved by testicular biopsy from an azoospermic testicular cancer survivor 8 years after chemotherapy. It was concluded that chemotherapy and/or radiotherapy may depress semen concentration to the extent of rendering a man infertile. The severity of the reduction in sperm concentration following treatment is unpredictable but likely to be most severe in those with testicular malignancy and those treated with radiotherapy or alkylating chemotherapy agents. Not all men are keen to undergo an appraisal of their post-treatment fertility potential, for reasons which are unclear. Improving awareness and education of patients concerning the effects of both cancer and cancer treatments on reproductive potential is essential. With the advent of ICSI, it is possible to offer a very reasonable chance of conception in all men with cancer who present for cryopreservation of semen prior to treatment in whom spermatozoa (even in very low concentrations) are present in the ejaculate.      

Cloning and characterization of the guinea pig C5a anaphylatoxin receptor: interspecies diversity among the C5a receptors

The anaphylatoxin C5a receptor (C5aR, CD88 in man) plays a prominent role in mediating inflammatory and host defense processes. Direct evidence of C5aR involvement in host defense mechanisms was demonstrated recently using C5aR knockout mice. Mice deficient in C5aR were unable to clear intrapulmonary-instilled bacteria. The guinea pig system is perhaps unique for exhibiting cross-reactivity with human complement components and its high sensitivity to anaphylatoxins. Therefore, we cloned the guinea pig C5aR from a megakaryocyte cDNA library. The deduced amino acid sequence of guinea pig C5aR is 67% identical to human, 61.6% to dog, 60.2% to mouse and 63.6% to rat C5aR. Transient expression of guinea pig C5aR in COS-7 cells and stable expression on L cell fibroblasts were confirmed by FACS analysis. Competitive binding studies using [125I]C5a and stimulation of calcium mobilization by C5a proved that functional C5aR was expressed on these stably transfected L cells. The N-terminal extracellular region of guinea pig C5aR was five to seven residues shorter than the same region in C5aR from other species and sequence homology was limited to 11%. Other outer membrane loops were also poorly conserved (8-33%) when compared across five species. Transmembrane segments were highly conserved between these various species (46-86%). Guinea pig C5aR binds human C5a, therefore residues critical for C5a binding have been conserved between these species. Sequence comparison of C5aR from multiple species permits conserved elements of the ligand binding sites to be elucidated.      

IL－2对NOD鼠糖尿病的影响

ＮＯＤ鼠是人类胰岛素依赖型糖尿病的动物模型，其发病与自身免疫有关。环磷酰胺（ＣＰ）可以加速这一过程，使ＮＯＤ鼠糖尿病的发病率提高或提前。一些研究表明：ＮＯＤ鼠的淋巴细胞在淋巴细胞混合反应中（ＭＬＲ），在有或无刺激物的存在下，白细胞介素２（ＩＬ－２）的产量均明显低于正常鼠的淋巴细胞。该实验对注射了一次大剂量的ＣＰ（３００ｍｇ／ｋｇ体重）后的ＮＯＤ鼠试用了ＩＬ－２治疗。结果显示：对于年幼的ＮＯＤ鼠ＩＬ－２治疗１４无可以明显减轻注射ＣＰ后的胰岛破坏加速。病理检查显示三组胰岛炎严重程度积分分别为２９；８１；８８。ＩＬ－２处理组明显低于ＣｏｎＡ处理组与对照组。这个研究还显示，对于１２周龄的ＮＯＤ鼠，经１４天的ＩＬ－２治疗，可以完全预防ＣＰ诱导的糖尿病的发生。糖尿病发病率在ＩＬ－２组为０／１２；对照组为７／１２。但对已发病的ＮＯＤ鼠自发性糖尿病ＩＬ－２不能使其缓解。     

The circulating platelet count is not dictated by the liver,but may be determined in part by the bone marrow: analyses from human liver and stem cell transplantations

Summary. Background: The platelet count varies considerably between individuals, but within an individual the platelet count is remarkably stable over time. Mechanisms controlling the platelet count are not yet established. Objective: In the present study, we tested the hypothesis that the liver is important in controlling the circulating platelet count, as the liver is the main producer of thrombopoietin. Methods: We compared the platelet count prior to and after liver transplantation in > 250 patients transplanted for familial amyloidotic polyneuropathy (FAP). In contrast to most patients undergoing liver transplantation, patients with FAP have normal liver function before transplantation. Furthermore, we compared platelet counts in 89 living liver donors with the platelet count in the recipients of these grafts. Finally we compared platelet counts in donor‐recipient pairs of hematopoietic stem cells. Results and conclusions: The platelet count prior to transplantation correlated with the platelet count at 3 or 12 months after transplantation in patients with FAP (r = 0.48, P < 0.0001 at 3 months, r = 0.39, P < 0.0001 at 12 months), whereas the platelet count in a living liver donor did not correlate with the platelet count in the recipient at 3 or 12 months after transplantation (r = 0.16, P = 0.26 at 3 months, r = 0.11, P = 0.30 at 12 months). The platelet count of related donors of hematopoietic stem cells correlated with the platelet count in the recipient after transplantation (r = 0.25, P = 0.011). Conclusions: These results suggest that the liver, in spite of being the prime producer of thrombopoietin, does not dictate the circulating platelet count, whereas the bone marrow does appear to play a role.     

保存前去白细胞血液制品可诱发低血压性输血反应

低血压是少见的输血并发症,可以单独发生,也可以为输血相关急性肺损伤、细菌感染及输血过敏的反应综合征的一部分。缓激肽(BK)和血管性激肽(des-Arg-BK)为血管性激肽,半寿期短(大约30sec至8min),在低血压的发生中起着重要作用。在血管紧张素转化酶(ACE)抑制物存在的条件下,激肽的蓄积更加容易,ACE是BK的主要代谢酶。已证实,在ACE抑制物引起的先天性血管水肿的病人降解激肽的能力先天性缺     

The effect of casein phosphopeptide-amorphous calcium phosphate on erosive dentine wear

Background:  Erosive tooth wear is a growing concern in clinical dentistry. Our aims were to assess the effect of Tooth Mousse (TM) in managing erosive dentine wear in vitro .
Methods:  Opposing enamel and dentine specimens from 36 third molar teeth were worn under a load of 100 N for 75 000 cycles in electromechanical tooth wear machines. In experiment 1, TM was applied continuously at the wear interface and the mean dentine wear rate was compared with those of specimens subjected to continuous application of hydrochloric acid (HCl, pH 3.0) and deionized water (DW, pH 6.1) as lubricants. In experiment 2, specimens were subjected to TM application every 1600 cycles at both pH 3.0 and 6.1, and the mean dentine wear rates were compared with those of specimens worn with continuous application of HCl and DW lubricants.
Results:  Dentine wear was reduced significantly with continuous application of TM compared with HCl and DW lubricants. Specimens prepared with continuous TM application displayed smooth wear facets, whereas more pronounced microwear details were observed with HCl and DW lubricants.
Conclusions:  Both remineralization and lubrication seem to contribute to reduction in dentine wear associated with TM application, although lubrication appears to have a more pronounced effect.     

Double-blind placebo-controlled trial of lithium in episodic cluster headache

Lithium is widely used in the prophylaxis of episodic cluster headache without formal evidence of efficacy. Placebo-controlled clinical trials are not easy in conditions characterized by frequent severe pain. In this study, it was assumed that lithium would work quickly if at all, and placebo response would be zero. Strict diagnostic criteria excluded uncertain or atypical cases. Patients were male in so-far untreated episodes expected to last for at least 3 weeks more. In a double-blind, placebo-controlled comparison of matched parallel groups, treatment was either slow-release lithium carbonate, 800 mg/day, or placebo. After 7 days, compliance was estimated by tablet count, blood was taken for lithium assay, efficacy was assessed (attacks stopped or substantially improved) and adverse reactions were recorded. The study was stopped after planned sequential analysis of the 27th patient (13 on lithium, 14 on placebo). Estimated compliance was usually but not always good. Plasma lithium levels were mostly in the range 0.5–0.6 mmol/1 on lithium, zero on placebo. Cessation of attacks within 1 week occurred in two patients in each group, substantial improvement in 6/14 (43%) on placebo, 8/13 (62%; NS) on lithium. Only minor adverse events were reported. Lithium treatment was therefore associated with a useful subjective improvement rate but the assumptions made at outset had proved wrong. The trial was stopped because superiority over placebo could not be demonstrated. There were lessons for future trials.