Term delivery in a woman with severe congenital neutropenia, treated with growth colony stimulating factor

The patient was diagnosed in childhood as having severe congenital neutropenia and had recurrent admissions with severe infections. In 1987, prior to getting married, she was sterilized. She continued to require i.v. antibiotics when she contracted a severe infection. On one occasion, she was treated with growth colony stimulating factor (G- CSF). Her increased neutrophil count was sustained following this treatment. In June 1993, she wished to start a family and underwent in- vitro fertilization (IVF) treatment. G-CSF was given prior to oocyte retrieval. She conceived on her first cycle and an ultrasound scan revealed a singleton pregnancy. Throughout the course of the pregnancy, her white cell count was monitored closely and remained at <1.0x10(9)/l. The pregnancy progressed uneventfully and at 37 weeks gestation she was admitted for G-CSF injections. At 38 weeks she was delivered of a boy weighing 3350 g, by elective Caesarean section. His white cell count was normal. This is the first case of G-CSF being used before conception and during pregnancy in a patient with congenital neutropenia. It shows that advances in cytokine therapy and close interdisciplinary liaison can lead to a successful outcome and help patients, who would otherwise remain childless, to achieve a family.      

Distribution of spermatogenesis in the testicles of azoospermic men: the presence or absence of spermatids in the testes of men with germinal failure [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

The aim of the study was to determine whether a prior diagnostic testicle biopsy can predict success or failure of testicular sperm extraction (TESE) with intracytoplasmic sperm injection (ICSI) in patients with non-obstructive azoospermia caused by testicular failure, and what is the minimum threshold of sperm production in the testis which must be surpassed for spermatozoa to reach the ejaculate. Forty- five patients with non-obstructive azoospermia caused by testicular failure underwent diagnostic testicle biopsy prior to a planned future TESE-ICSI procedure. The diagnostic testicle biopsy was analysed quantitatively, and correlated with the quantitative findings of spermatogenesis in patients with normal spermatogenesis, as well as with the results of subsequent attempts at TESE-ICSI. Men with non- obstructive azoospermia caused by germinal failure had a mean of 0-6 mature spermatids/seminiferous tubule seen on a diagnostic testicle biopsy, compared to 17-35 mature spermatids/tubule in men with normal spermatogenesis and obstructive azoospermia. These findings were the same for all types of testicular failure whether Sertoli cell only, maturation arrest, cryptorchidism, or post-chemotherapy azoospermia. Twenty-two of 26 men with mature spermatids found in the prior testis biopsy had successful retrieval of spermatozoa for ICSI, 12 of their partners became pregnant, and are either ongoing or delivered. The study suggests that 4-6 mature spermatids/tubule must be present in the testis biopsy for any spermatozoa to reach the ejaculate. More than half of azoospermic patients with germinal failure have minute foci of spermatogenesis which are insufficient to produce spermatozoa in the ejaculate. Prior diagnostic testicle biopsy analysed quantitatively (for the presence of mature spermatids) can predict subsequent success or failure with TESE-ICSI. Incomplete testicular failure may involve a sparse multi-focal distribution of spermatogenesis throughout the entire testicle, rather than a regional distribution. Therefore, it is possible that massive testicular sampling from many different regions of the testes may not be necessary for successful TESE-ICSI.      

Adhesion inhibitory activity of β-lactoglobulin isolated from infant formulae

β-Lactoglobulin was isolated from infant formulae that were ultra high temperature (UHT) -treated, sterilized or spray-dried. The effect of the isolated β-lactoglobulin on SfaII-fimbriae-mediated adhesion of Escherichia coli to human ileostomy glycoproteins was studied in vitro. β-Lactoglobulin isolated from sterilized formulae was found to perform significantly less well than preparations from spray-dried formulae (p = 0:05). Great heterogeneity was observed in the adhesion inhibitory capacity of β-lactoglobulin isolated from UHT-treated formulae. Therefore, no significant difference was observed between UHT-treated and sterilized formulae or spray-dried formulae (p < 0:10). It can be hypothesized that β-lactoglobulin from spray-dried and some UHT-treated infant formulae may affect the colonization of mucous membranes by E. coli strains causing neonatal septicaemia and meningitis.     

Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products

Tuberous sclerosis (TSC) is an autosomal dominant disorder caused by a mutation in either the TSC1 or TSC2 tumour suppressor gene. The disease is characterized by a broad phenotypic spectrum that can include seizures, mental retardation, renal dysfunction and dermatological abnormalities. TSC2 encodes tuberin, a putative GTPase activating protein for rap1 and rab5. The TSC1 gene was recently identified and codes for hamartin, a novel protein with no significant homology to tuberin or any other known vertebrate protein. Here, we show that hamartin and tuberin associate physically in vivo and that the interaction is mediated by predicted coiled-coil domains. Our data suggest that hamartin and tuberin function in the same complex rather than in separate pathways.      

Ivermectin for the chemotherapy of bancroftian filariasis: a meta-analysis of the effect of single treatment

Summary The efficacy and safety of ivermectin in the treatment of filariasis due to Wuchereria bancrofti was assessed by a meta-analysis of the results from 15 published clinical trials. Seven hundred and forty-eight microfilaraemic patients were enrolled in 7 dose-finding and 8 comparative studies. Administered as a single dose, ivermectin induced nearly complete clearance of microfilariae from the blood from the first day to 30 days post-treatment, followed by gradual recurrence of microfilaraemia and increase in its intensity. Higher doses of ivermectin showed greater clearance effects and maintained lower microfilaraemia levels for a longer time. The adverse reactions caused by the drug were flu-like, transient, generally mild and well tolerated by patients. The frequency and intensity of adverse reactions were strongly associated with pretreatment microfilaria counts in the blood, but independent of dose. The findings of the meta-analysis suggest that ivermectin given at a single annual dose of 200 μg/kg body weight or higher, whether or not in combination with DEC, has great potential for therapeutic strategies to control bancroftian filariasis.     

多索茶碱及其片剂的高效液相色谱分析

多索茶碱及其片剂的高效液相色谱分析刘春胜，何秀峰，王云萍，谷士杰，周同惠（中国医学科学院、中国协和医科大学药物研究所，北京１０００５０）多索茶碱（ｄｏｘｏｆｙｌｌｉｎｅ）是用于治疗支气管哮喘合并支气管痉挛的慢性阻塞性肺部疾病的新一代黄嘌吟衍生物，其药...