Linkage mapping of a mouse gene, iv, that controls left-right asymmetry of the heart and viscera.

Inherited single gene defects have been identified in both humans and mice that lead to loss of developmental control over the left-right asymmetry of the heart and viscera. In mice the recessively inherited mutation iv leads to such apparent loss of control over situs: 50% of iv/iv mice exhibit situs inversus and 50% exhibit normal situs. The affected gene product has not been identified in these animals. To study the normal function of iv, we have taken an approach directed to the gene itself. As a first step, we have mapped iv genetically, by examining its segregation in backcrosses with respect to markers defined by restriction fragment length polymorphisms. The iv locus lies 3 centimorgans (cM) from the immunoglobulin heavy-chain constant-region gene complex (Igh-C) on chromosome 12. A multilocus map of the region suggests the gene order centromere-Aat (alpha 1-antitrypsin gene complex)-(11 cM)-iv-(3 cM)-Igh-C-(1 cM)-Igh-V (immunoglobulin heavy-chain variable-region gene complex).     

Seminal analysis after orchiectomy in stage I teratoma

Seminal analysis was performed within 2 months of orchiectomy on 97 patients with clinical Stage I malignant testicular teratoma managed by surveillance following orchiectomy. Relapse of malignant disease occurred in 28% of 47 patients with a sperm count less than 10 X 10(6)/ml and in 32% of 50 patients with a sperm count greater than or equal to 10 X 10(6)/ml. Of 11 patients with azoospermia, 4 relapsed and 1 developed contralateral testicular germ cell tumour. Of 35 patients with malignant teratoma undifferentiated the relapse rate was 68% in 16 patients with a sperm count less than 10 X 10(6)/ml and 42% in 19 patients with a sperm count greater than or equal to 10 X 10(6)/ml. It was concluded that sperm count analysis is non-contributory in estimating the risk of relapse in clinical Stage I teratoma.     

Surveillance following orchidectomy for stage I testicular seminoma.

An analysis of the primary tumour histopathology was performed on 103 patients managed by orchidectomy and surveillance for stage I seminoma. Patients have been followed for 14-141 months (median 62 months) after orchidectomy. Seventeen patients relapsed, the probability of remaining relapse free at 5 years being 82% (95% confidence intervals, 74%-88%). No patients died of progressive germ cell tumours. The only significant histological factor predicting relapse was the presence of lymphatic and vascular invasion. Four of 42 patients with neither lymphatic or vascular invasion recurred, nine of 53 patients with either lymphatic or vascular invasion recurred and three of eight cases with both lymphatic and vascular invasion recurred (P = 0.05-trend). Though initial recurrence was usually of moderate volume and confined to para-aortic nodes, eight patients were treated with chemotherapy either because of the extent of their initial relapse (four cases), or because of subsequent relapse (four cases). In view of the difficulties of identifying patients at risk and of detecting early relapse, surveillance for stage I seminoma should remain a research protocol.     

Assessment of bioequivalence after subcutaneous and intramuscular administration of urinary gonadotrophins

The objective was to demonstrate bioequivalence between s.c. and i.m. administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio 3:1). In two randomized, single-centre, cross-over studies, 18 healthy volunteers on each formulation were assigned to one of the two administration sequences. Subjects were given single doses of one of the above gonadotrophins after endogenous gonadotrophin production had first been suppressed using high-dose oral contraceptive. Subsequently, rate (Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax and AUC, analysis of variance (ANOVA) was performed on log-transformed data and for tmax ANOVA was performed on ranks. Intramuscular and s.c. injections of Humegon were bioequivalent with respect to the main pharmacokinetic parameters, being AUC and Cmax of FSH absorption. Intramuscular and s.c. injections of Normegon were bioequivalent with respect to the AUC of FSH and not bioequivalent with respect to the Cmax of FSH. For tmax of FSH as well as for most LH variables of both preparations, bioequivalence could not be proven due to the high intra- and interindividual variability and/or concentrations being close to the detection limit. Thus, the main pharmacokinetic FSH variables after i.m. and s.c. administration of Humegon and Normegon were bioequivalent.      

传染性肺结核患者家庭中儿童结核感染发病及预防的研究

目的　分析传染性肺结核患者家庭中的儿童结核感染和发病情况 ,探讨预防儿童发病的有效方案。方法　对与传染性肺结核患者密切接触的儿童进行X线胸透和做结核菌素试验 ;对结核菌素强阳性者给予预防性治疗。结果　与传染性肺结核患者密切接触的儿童感染率为 88 2 %。规则预防治疗组、不规则预防治疗组和不接受预防治疗组的患病率分别为 :8 3%、4 7 6 %、5 8 8%。结论　与传染性肺结核患者密切接触的儿童属于高危人群 ,给予预防性治疗可减少发病。     

Molecular cytogenetic analysis of adult testicular germ cell tumours and identification of regions of consensus copy number change.

A series of adult testicular germ cell tumours consisting of eight seminomas, 14 non-seminomas (including two cell lines) and two combined tumours was analysed by comparative genomic hybridization and, in some cases, by interphase fluorescence in situ hybridization. The gain of 12p was identified in all cases and additional material from chromosomes 7 and 8 was found in over 70% of cases, in keeping with previous analyses. Other consistent regions of gain included 1q24-q31 (50%), 2p16-pter (41%), 2q22-q32 (45%) and Xq11-q21 (50%). The loss of 1p32-p36 (36%), 9q31-qter (36%), 11q14-qter (50%), 16p (36%) and 18p (45%) and the loss of material from chromosomes 4 and 5 (50% and 36% respectively) were also found in all histological subtypes. The loss of 1p material was confirmed in four cases by interphase FISH analysis and shown, with one exception, not to involve the loss of the D1Z2 locus at 1p36.3, which is commonly deleted in paediatric germ cell tumours. An association between gain of 6q21-q24 with cases resistant to chemotherapy (P < 0.01) was observed. In addition, loss of chromosome 19 and 22 material and gain of 5q14-q23, 6q21-q24 and 13q were found at a significantly lower frequency in seminoma than non-seminoma. These regions may contain genes involved in the divergent development of seminoma and non-seminoma.