Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11

In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia were analysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involving several DNA loci, while an additional patient had an inherited deletion. They were mapped to three different subregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second and third subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletions observed were not overlapping but the extension of the deleted Y DNA in each subregion was similar in each patient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phase when the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletion occurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesis loci in Yq11 and that each locus is active during a different phase of male germ cell development. As the most severe phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc. Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed.      

The expression of type III hyperlipoproteinemia: involvement of lipolysis genes

Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In addition, 188 normolipidemic Dutch control panels (NDCP) and 141 hypertriglyceridemic (HTG) patients were genotyped as well. No associations were found for four HL gene polymorphisms and two LPL gene polymorphisms and type III HLP. The frequency of the rare allele of APOC3 3238 G>C and APOA5 −1131 T>C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (P<0.05). Furthermore, the frequencies of the APOA5 c.56 G>C polymorphism and LPL c.27 G>A mutation were higher in type III HLP patients, though not significant. Some 58% of the type III HLP patients carried either the APOA5 −1131 T>C, c.56 G>C and/or LPL c.27 G>A mutation as compared to 27% of the normolipidemic APOE2/2 subjects (odds ratio 3.7, 95% confidence interval=1.8–7.5, P<0.0001). The HTG patients showed similar allele frequencies of the APOA5, APOC3 and LPL polymorphisms, whereas the NDCP showed similar allele frequencies as the normolipidemic APOE2/2. Patients with the APOC3 3238 G>C/APOA5 −1131 T>C polymorphism showed a more severe hyperlipidemia than patients without this polymorphism. Polymorphisms in lipolysis genes associate with the expression and severity of type III HLP in APOE2/2.     

Development of an instrument for the identification of frail older people as a target population for integrated care

Background

Primary care is increasingly interested in the identification of frailty, as it selects the target population for integrated care. However, instruments for the identification of frailty specifically validated for use in primary care are scarce. This study developed the Easycare Two-step Older persons Screening (Easycare-TOS), which provides a valid, efficient, and pragmatic screening procedure to identify frail older people.

Aim

This paper aims to describe the development of the Easycare-TOS and the data from the pilot studies.

Design and setting

Observational pilot study in seven academic GP practices in and around Nijmegen, The Netherlands.

Method

The Easycare-TOS was developed in a cyclic process with the input of stakeholders. In every cycle, the requirements were first defined, then translated into a prototype that was tested in a pilot study. The Easycare-TOS makes optimal use of prior knowledge of the GP, and the professionals’ appraisal is decisive in the frailty decision, instead of a cut-off score. Further, it considers aspects of frailty, as well as aspects of the care context of the patient.

Results

The pilot data have shown that after step 1, two-thirds of the patients do not need further assessment, because they are judged as not frail, based on prior knowledge of the GP. The overall prevalence of frailty in this pilot study is 24%. Most professionals who participated in the pilot studies considered the time investment acceptable and the method to be of added value.

Conclusion

The Easycare-TOS instrument meets the predefined efficiency, flexibility, and acceptability requirements for use as an identification instrument for frailty in primary care.     

Semen parameters and testicular pathology in men with testicular cancer and contralateral carcinoma in situ or bilateral testicular malignancies

We evaluated 14 patients with bilateral testicular tumour, one-sided tumour and contralateral carcinoma in situ (CIS) of the testis or testis tumour in single testis with respect to their fertility. We analysed semen parameters, serum hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone], testicular sonography, testicular volumes and testicular histology prior to further anti-cancer treatment. Ten out of 14 patients showed normal or reduced sperm concentrations, while 4/14 patients were azoospermic. Serum FSH levels showed a significant negative correlation with sperm concentrations in patients with testicular malignancies (r = -0.64, P = 0.025). Testicular volumes revealed a significant positive correlation with semen parameters in patients with testes that were affected by CIS (r = 0.733, P = 0.038). We conclude that even bilateral testicular cancer and/or CIS do not preclude fertility and, therefore, patients should be offered andrological investigation and therapy, including possibly surveillance strategy or the chance for cryopreservation of the semen prior to further treatment in order to preserve their chances for paternity.      

Uptake of newer vaccines in Chandigarh

Objective To ascertain the uptake of newer vaccines in Chandigarh. Methods Uptake of newer vaccines was ascertained in underfive children through house to house survey during Jan 2004–Sep 2005 in sector 44 of chandigarh. Results Of 1031 children of the total urban population, More than 40% got immunised with newer vaccines. Maximum coverage was seen for Hepatitis B 461 (44.7%) for 3 doses followed by immunisation against Hib 287 (27.8%). MMR vaccine coverage was 285 (27.6%). For typhoid and varicella coverage was less. More than 50% children got immunisation from private sector. Conclusion The newer vaccines are available in the market and being used by the people especially being catered by the private sector.     

治疗性单克隆抗体药动学相互作用的风险评估策略

生物制剂可用于治疗各种疾病,包括肿瘤、风湿、胃肠道疾病、皮肤科疾病、呼吸道疾病、激素缺乏症和感染。尽管近来批准了很多生物制品,但有关其药物间相互作用临床研究还不多。单克隆抗体是最主要的一类治疗性生物制品,本文介绍评价其药物间相互作用的风险评估策略,指出了评估中的关键因素,并建议将相互作用风险评估作为治疗性生物制品综合药物开发的一部分。     

The recognition of mental health disorders and its association with psychiatric scepticism,knowledge of psychiatry,and the Big Five personality factors: an investigation using the overclaiming technique

The present study examined the general public’s ability to recognise mental health disorders and this ability’s association with psychiatric scepticism, knowledge of psychiatry, and the Big Five personality factors. A total of 477 members of the British general public completed an overclaiming scale, in which they were asked to rate the degree to which they believed 20 mental health disorders (of which five were foils designed to resemble real disorders) were real or fake. Participants also completed a novel scale measuring psychiatric scepticism, a single-item measure of knowledge of psychiatry, and a measure of the Big Five personality factors. Results showed that participants were significantly more likely to rate foils as fake disorders than real disorders. In addition, the difference between real and foil ratings was significantly predicted by knowledge of psychiatry, psychiatric scepticism, and the Big Five personality factors of agreeableness and openness to experience. These results are discussed in relation to the overclaiming technique as a novel method to study mental health literacy.     

109Use of EPR Spectroscopy to Measure Tissue Oxygen in an Ischemic Flap Model

Methods to reliably measure tissue oxygenation in situ are currently lacking. We have developed a vertically oriented, dorsal, bipedicle flap model that is easy to perform, reliably reproduces tissue ischemia, eliminates craniocaudal variation, and is amenable to studying therapeutic modalities. The effect of narrowing this flap on tissue oxygenation measured with Licox electrodes has previously been presented. In this study we utilize in situ EPR spectroscopy to demonstrate the oxygen gradient in the flap as a function of flap width and placement of a silicone sheet directly under the flap. The effect of wound healing over a 2 week period is demonstrated. Twenty four, 300 gm male Sprague‐Dawley rats underwent creation of the bipedicle flap according to the following groups: 2.5 cm flap with silicone, 2.0 cm flap without silicone, 2.0 cm flap with silicone. Each group of 6 animals was injected with EMS char at 2 cm intervals along the flap and one injection in the control, non‐ischemic tissue. A 4^th group underwent 2.0 cm flaps with silicone and use of lithium phthalocyanin as the paramagnetic material. Wound measurements and EPR spectroscopy were performed on days 3, 7, 10 and 14. On day 14, after EPR measurements, the animals were sacrificed and their wounds excised. One flap and one control wound were preserved for histologic analysis, the other flap and control wounds were prepared for lactate measurements. EPR spectroscopy demonstrated a gradient of oxygen that was lowest in the center of the flap and greatest at either end. Changes in the oxygen gradient correlated with narrowing and placement of the intervening silicone sheet. This new technology has never been utilized in an animal model of impaired wound healing. Comparison of recently developed paramagnetic materials for optimal tissue oxygen and free radical measurements will be presented.