Perfluoroalkyl and polyfluoroalkyl substances and measures of human fertility: a systematic review

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are found widespread in the environment and humans. The relation of PFASs to fertility has now been examined in a relatively large number of epidemiologic studies and a synthesis is in order. The aim of this study was to assess the current human epidemiologic evidence on the association between exposure to PFASs and measures of human fertility, with particular emphasis on perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Systematic literature searches were initially conducted in MEDLINE and EMBASE and subsequently in references and citations of included papers. Studies were included if they assessed exposure to PFASs in biological samples in relation to reproductive hormones, semen characteristics, or time to pregnancy (TTP). Study characteristics and results were abstracted to predefined forms, and the studies were assessed for the risk of bias and confounding. Sixteen studies investigated the association between PFAS exposure in men and semen parameters, reproductive hormone levels, or TTP. There was a lack of consistent results among the numerous investigated exposure-outcome combinations. However, subtle associations between higher PFOS and lower testosterone or abnormal semen morphology cannot be excluded. Eleven studies assessed the association between PFAS exposure in women and TTP or reproductive hormones levels. Four of eight studies found prolonged TTP with higher PFOS or PFOA, but only one study found an association when restricting to nulliparous women. In men, there is little evidence of an association between PFAS exposure and semen quality or levels of reproductive hormones. For PFOS and PFOA, the literature indicates an association with female fecundability in parous women, which is most likely not causal.     

Preoperative octreotide treatment in newly diagnosed acromegalic patients with macroadenomas increases cure short-term postoperative rates: a prospective, randomized trial

CONTEXT: Surgery is the primary treatment of acromegaly. However, it often fails to cure the patient. New strategies that improve surgical outcome are needed. OBJECTIVE: Our objective was to investigate whether 6-month preoperative treatment with octreotide improves the surgical outcome in newly diagnosed acromegalic patients. PATIENTS: During a 5-yr period (1999-2004), all newly diagnosed acromegalic patients between 18 and 80 yr of age in Norway were screened and invited to participate in the study. A total of 62 patients was included in the Preoperative Octreotide Treatment of Acromegaly study. RESEARCH DESIGN AND METHODS: After a baseline evaluation, patients were randomized directly to transsphenoidal surgery (n = 30) or pretreatment with octreotide (n = 32) 20 mg im every 28th day for 6 months before transsphenoidal surgery. Cure was evaluated 3 months postoperatively primarily by IGF-I levels. RESULTS: According to the IGF-I criteria, 14 of 31 (45%) pretreated patients vs. seven of 30 (23%) patients with direct surgery were cured by surgery (P = 0.11). In patients with microadenomas (< or = 10 mm), one of five (20%) pretreated vs. three of five (60%) with direct surgery were cured (P = 0.52). In patients with macroadenomas, 13 of 26 (50%) pretreated vs. four of 25 (16%) with direct surgery were cured (P = 0.017). CONCLUSIONS: Six-month preoperative octreotide treatment might improve surgical cure rate in newly diagnosed acromegalic patients with macroadenomas. These results have to be confirmed in future studies.     

A randomised trial of a pre-synaptic stimulator of DA2-dopaminergic and alpha2-adrenergic receptors on morbidity and mortality in patients with heart failure

BACKGROUND: By pre-synaptic stimulation of DA(2)-dopaminergic and alpha(2)-adrenergic receptors, nolomirole inhibits norepinephrine secretion from sympathetic nerve endings. We performed a clinical study with nolomirole in patients with heart failure (HF). METHODS: The study was designed as a multicentre, double blind, parallel group trial of 5 mg b.i.d. of nolomirole (n=501) versus placebo (n=499) in patients with severe left ventricular systolic dysfunction, recently in New York Heart Association (NYHA) class III/IV. The primary endpoint was time to all cause death or hospitalisation for HF, whichever came first. The study was event driven and required 420 primary events. The study was completed as scheduled. RESULTS: Mean age of patients was 70 years, and 73% were male. Heart rate and blood pressure were not different in the two treatment groups. There were no changes in blood pressure. There were 233 primary events in the nolomirole group versus 208 in the placebo group (p=0.1). There were 142/145 deaths and 369/374 all cause hospitalisations in the nolomirole/placebo groups. There were no differences in walking distance, quality of life or NYHA class. CONCLUSION: A dose of 5 mg b.i.d. of nolomirole was not beneficial (or harmful) in patients with heart failure.     

大鼠骨髓基质干细胞定向分化为成骨细胞及体外增殖过程中地塞米松的抑制性干预

目的:地塞米松在体外诱导骨髓基质干细胞向成骨细胞分化过程中起着关键性作用。验证骨髓基质干细胞向成骨细胞分化的能力,观察成骨细胞分化早期地塞米松对骨髓基质干细胞体外增殖的抑制效果。方法:实验于2006-09/12在南方医科大学组织工程研究中心完成。①实验方法:取5周龄雄性SD大鼠10只,经颈椎脱位法处死后取股骨,去除双侧干骺端,用DMEM高糖完全培养基冲洗骨髓腔,收集骨髓细胞,离心后按(1～2)×107L-1密度接种,加入条件培养液(DMEM高糖完全培养基,体积分数为0.1的标准胎牛血清,50mg/L维生素C,10mmol/L的B-甘油磷酸钠,100U/mL青霉素、100U/mL链霉素)进行体外培养。分别于细胞传代培养后第0,2,4天向培养基中加入1μmol/L地塞米松1mL,并设立仅加入等量培养基的空白对照组。②实验评估:以2d为间隔,倒置显微镜下观察细胞生长情况。采用CellTiter96试剂盒各组细胞增殖情况。结果:①骨髓基质干细胞向成骨细胞的分化:原代培养中贴壁细胞多呈长梭形,少数呈小圆形或三角形。原代培养六七天后进行传代,多数细胞在加入地塞米松后逐渐呈均一的长梭形,随着时间延长呈叠形多层排列,细胞外基质明显增多,并逐渐形成多个小结样结构。空白对照组细胞形态欠均一,少数细胞呈多边形或三角形,细胞外基质明显少于地寒米松组,罕见小结样结构。传代后10～12d可达80%～90%致密层,细胞生长速度较原代细胞明显增快,至第10代细胞仍未出现衰老现象。②骨髓基质干细胞的增殖检测:与空白对照组比较,细胞传代培养后第0,2,4天加入地塞米松,干预处理8,10,12d时的细胞数量均明显下降(t=5.0445～11.3795,P均<0.01)。结论:①传代的骨髓基质干细胞经地塞米松处理后,细胞形态趋于成熟,生长速度加快,可定向分化为成骨细胞。②在向成骨细胞分化早期,地塞米松能够抑制骨髓基质干细胞的体外增殖。     

Multiparametric analysis of colorectal cancer immune responses

Colorectal cancer(CRC) is a heterogeneous disease, with a diverse and plastic immune cell infiltrate. These immune cells play an important role in regulating tumour growth-progression or elimination. Some populations of cells have a strong correlation with disease-free survival, making them useful prognostic markers. In particular, the infiltrate of CD3~+ and CD8~+ T cells into CRC tumours has been validated worldwide as a valuable indicator of patient prognosis. However, the heterogeneity of the immune response, both between patients with tumours of different molecular subtypes, and within the tumour itself, necessitates the use of multiparametric analysis in the investigation of tumour-specific immune responses. This review will outline the multiparametric analysis techniques that have been developed and applied to studying the role of immune cells in the tumour, with a focus on colorectal cancer. Because much of the data in this disease relates to T cell subsets and heterogeneity, we have used T cell populations as examples throughout. Flow and mass cytometry give a detailed representation of the cells within the tumour in a single-cell suspension on a per-cell basis. Imaging technologies, such as imaging mass cytometry, are used to investigate increasing numbers of markers whilst retaining the spatial and structural information of the tumour section and the infiltrating immune cells. Together, the analyses of multiple immune parameters can provide valuable information to guide clinical decision-making in CRC.     

The sensitivity of fecal calprotectin in predicting deep remission in ulcerative colitis

Background: Mucosal healing is proposed as treat-to-target in ulcerative colitis (UC), even though the definition of mucosal healing remains contested as it has been suggested to be assessed by either endoscopy, histology or both. However, all definitions require an endoscopic evaluation of the mucosa. As endoscopies are invasive and uncomfortable to the patient we aimed to calibrate noninvasive predictors of mucosal inflammatory status defined by both endoscopy and histology.

Methods: UC patients (n?=?106) undergoing a sigmoid-/colonoscopy were prospectively included. Feces (fecal calprotectin, FC), blood samples (hemoglobin, C-reactive protein, orosomucoid, erythrocyte sedimentation rate, albumin) and symptom scores (Simple Clinical Colitis Activity Index, SSCAI) were collected and analyzed. The colonic mucosa was assessed by the Mayo endoscopic sub score and biopsies were obtained for a histologic grading by Geboes score. Predictive cutoff values were analyzed by receiver operating characteristics (ROC). A combined endoscopic and histologic assessment defined deep remission (Mayo =0 and Geboes ≤1) and activity (Mayo ≥2 and Geboes >3).

Results: Only FC showed a significant ROC curve (p?230. The complete ROC data is presented, enabling extraction of an FC cutoff value’s sensitivity and specificity.

Conclusions: FC predicts endoscopic and histologic assessed deep remission and inflammatory activity of colon mucosa. Neither the markers in blood nor the SCCAI performed significant ROC results.     

Sub‐threshold transcranial magnetic stimulation applied after the go‐signal facilitates reaction time under control but not startle conditions

The presentation of a startling acoustic stimulus (SAS) in a simple reaction time (RT) task significantly reduces RT due to the involuntary early initiation of a prepared movement; however, the underlying neural mechanism remains unclear. It has been proposed that a SAS triggers a cortically stored motor program by involuntarily increasing initiation‐related activation. Sub‐threshold transcranial magnetic stimulation (TMS) can be used to investigate cortical processes, as it increases cortical excitability for 6–30 ms and significantly reduces RT. The purpose of the present experiments was to determine whether the application of sub‐threshold TMS over motor cortex in close temporal proximity to a SAS would facilitate startle RT in the same manner as control RT, providing evidence for cortical involvement in startle‐related RTs. Participants completed a simple RT task requiring targeted wrist extension in response to an auditory go‐signal, which was randomly replaced by a SAS on 25% of trials. On a subset of trials, sub‐threshold TMS was applied 30 ms following the go‐signal in control trials or at ?15, 0, +15 or +30 ms with respect to the SAS in startle trials. In all three experiments, sham and real TMS significantly reduced RT in control trials, with real TMS having a larger effect, but there was no effect of either real or sham TMS on startle‐related RT. These results suggest that there may be limited cortical involvement in the initiation of movements in response to a SAS. As an alternative, startle may produce the fastest possible RTs, with little room for additional facilitation.     

Treatment of exercise-induced asthma, respiratory and allergic disorders in sports and the relationship to doping: Part II of the report from the Joint Task Force of European Respiratory Society (ERS) and European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA(2)LEN

Aim: The aims of part II is to review the current recommended treatment of exercise‐induced asthma (EIA), respiratory and allergic disorders in sports, to review the evidence on possible improvement of performance in sports by asthma drugs and to make recommendations for their treatment. Methods: The literature cited with respect to the treatment of exercise induced asthma in athletes (and in asthma patients) is mainly based upon the systematic review given by Larsson et al. (Larsson K, Carlsen KH, Bonini S. Anti‐asthmatic drugs: treatment of athletes and exercise‐induced bronchoconstriction. In: Carlsen KH, Delgado L, Del Giacco S, editors. Diagnosis, prevention and treatment of exercise‐related asthma, respiratory and allergic disorders in sports. Sheffield, UK: European Respiratory Journals Ltd, 2005:73–88) during the work of the Task Force. To assess the evidence of the literature regarding use of β₂‐agonists related to athletic performance, the Task Force searched Medline for relevant papers up to November 2006 using the present search words: asthma, bronchial responsiveness, exercise‐induced bronchoconstriction, athletes, sports, performance and β₂‐agonists. Evidence level and grades of recommendation were assessed according to Sign criteria. Results: Treatment recommendations for EIA and bronchial hyper‐responsiveness in athletes are set forth with special reference to controller and reliever medications. Evidence for lack of improvement of exercise performance by inhaled β₂‐agonists in healthy athletes serves as a basis for permitting their use. There is a lack of evidence of treatment effects of asthma drugs on EIA and bronchial hyper‐responsiveness in athletes whereas extensive documentation exists in treatment of EIA in patients with asthma. The documentation on lack of improvement on performance by common asthma drugs as inhaled β₂‐agonists with relationship to sports in healthy individuals is of high evidence, level (1+). Conclusions: Exercise induced asthma should be treated in athletes along same principles as in ordinary asthma patients with relevance to controller and reliever treatment after careful diagnosis. There is very high level of evidence for the lack of improvement in athletic performance by inhaled β2‐agonists.     

Exercise-induced hypersensitivity syndromes in recreational and competitive athletes: a PRACTALL consensus report (what the general practitioner should know about sports and allergy)

Exercise-induced (EI) hypersensitivity disorders are significant problems for both recreational and competitive athletes. These include EI-asthma, EI-bronchoconstriction, EI-rhinitis, EI-anaphylaxis and EI–urticaria. A group of experts from the European Academy of Allergology and Clinical Immunology and the American Academy of Allergy Asthma and Immunology met to discuss the pathogenesis of these disorders and how to diagnose and treat them, and then to develop a consensus report. Key words (exercise with asthma, bronchoconstriction, rhinitis, urticaria or anaphylaxis) were used to search Medline, the Cochrane database and related websites through February 2008 to obtain pertinent information which, along with personal reference databases and institutional experience with these disorders, were used to develop this report. The goal is to provide physicians with guidance in the diagnosis, understanding and management of EI-hypersensitivity disorders to enable their patients to safely return to exercise-related activities.