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Multivariate analysis to predict letrozole efficacy in improving sperm count of non-obstructive azoospermic and cryptozoospermic patients： a pilot study

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Asian Journal of Andrology 2013年第6期15卷 806-811,I0009-I0010页

作者： Giorgio Cavallini Giulio Biagiotti Elisa Bolzon Andros-ltalia Outpatient Clinic of Ferrara Ferrara 44121 Italy Androsqtalia Outpatient Clinic of Perugia PeruRia 06128 Italy

We tested the hypothesis that letrozole increases sperm count in non-obstructive azoospermic or cryptozoospermic patients with a testosterone （T）/17-beta-2-oestradiol （E2） ratio 〈 10. Forty-six patients with no chromosomal aberrations were randomized into two groups： 22 received letrozole 2.5 mg per day for 6 months （Group 1：6 azoospermic＋ 16 cryptozoospermic patients）, while 24 received a placebo （Group 2：5 azoospermic＋19 cryptozoospermic patients）. The following data were collected： two semen analyses, clinical history, scrotal Duplex scans, body mass index （BMI）, Y microdeletion, karyotype and cystic fibrosis screens and follicle-stimulating hormone （FSH）, luteinizing hormone （LH）, E2, T and prolactin levels. Both before and after letrozole or placebo administration, the patients underwent two semen analyses and hormonal assessments. The differences were evaluated using the Mann-Whitney Utest. The relationships between sperm concentration after letrozole administration with respect to FSH, TIE2 ratio, bilateral testicle volume and BMI before letrozole administration were assessed using multivariate analysis. The side effects were assessed using the chi-square test. Group 1 had sperm concentration （medians： 400-1.290× 10^6 ml^-1; P〈0.01） and motility （medians： class A from 2% to 15%; P〈0.01）, FSH, LH and T significantly increased, while Group 2 did not. E2 levels diminished significantly in Group 1, but not in Group 2. Eight patients in Group 1 demonstrated side effects, whereas no patient side effects were observed in Group 2. The sperm concentration after letrozole administration is inversely related to TIE2, FSH and BMI; a direct relationship emerged between sperm concentration and testicular volume.

关键词： cryptozoospermia letrozole male infertility non-obstructive azoospermia

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Real-life outcome of anti-tumor necrosis factor α in the ambulatory treatment of ulcerative colitis

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World Journal of Gastroenterology 2015年第11期21卷 3282-3290页

作者： Enayatullah Baki Philipp Zwickel Anna Zawierucha Robert Ehehalt Daniel Gotthardt Wolfgang Stremmel Annika Gauss Division of Gastroenterology University of Heidelberg outpatient clinic of Gastroenterology

AIM:To evaluate the outcome of anti-tumor necrosis factor alpha(anti-TNFα) therapy in outpatients with ulcerative colitis at a tertiary referral ***:All patients with a confirmed diagnosis of ulcerative colitis undergoing therapy with infliximab and/or adalimumab at the outpatient clinic for inflammatory bowel diseases at the University Hospital Heidelberg between January 2011 and February 2014 were retrospectively *** with a followup period of less than 6 mo from start of anti-TNFα therapy were *** records of all eligible individuals were carefully ***-free clinical remission of a duration of at least 3 mo,colectomy rate,duration of anti-TNFα therapy,need for anti-TNFα dose escalation,and the occurrence of adverse events were evaluated as the main outcome ***:Seventy-two patients were included(35 treated with infliximab,17 with adalimumab,20 with both consecutively).Median follow-up was 27 mo(range:6-87 mo).Steroid-free clinical remission was achieved by 22.2% of the patients(median duration:21 mo until end of follow-up; range:3-66 mo).Patients attaining steroid-free clinical remission displayed lower hemoglobin and albumin blood levels at the start of treatment than those who did not achieve *** overall colectomy rate was 20.8%.Nearly 50% of the patients underwent anti-TNFα dose escalation during the follow-up *** both the infliximab and the adalimumab treated patients,non-response to anti-TNFα therapy was the major reason for treatment discontinuation.18.2% of the infliximab-treated patients and 13.5% of the adalimumab-treated patients had to discontinue their therapy due to adverse ***:Real-life remission rates of ulcerative colitis under anti-TNFα are overall low,but some patients have a clear long-term benefit.

关键词： Inflammatory bowel disease Tumor necrosis factor α

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Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients

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World Journal of Gastroenterology 2009年第4期15卷 449-456页

作者： Markus Moehler Martin F Sprinzl Murad Abdelfattah Carl C Schimanski Bernd Adami Werner Godderz Klaus Majer Dimitri Flieger Andreas Teufel Juergen Siebler Thomas Hoehler Peter R Galle Stephan Kanzler 1st Medical Department Johannes Gutenberg-University outpatient clinic outpatient clinic of City Hospital outpatient clinic of 1st Medical Department outpatient clinic of 2nd Medical Department Leopoldina Krankenhaus

AIM:To investigate the efficacy and safety of capecitabine plus irinotecan±bevacizumab in advanced or metastatic colorectal cancer patients. METHODS:Forty six patients with previously untreated,locally-advanced or metastatic colorectal cancer(mCRC) were recruited between 2001-2006 in a prospective open-label phaseⅡtrial,in German community-based outpatient *** received a standard capecitabine plus irinotecan(CAPIRI) or CAPIRI plus bevacizumab(CAPIRI-BEV) regimen every 3 wk. Dose reductions were mandatory from the first cycle in cases of>grade 2 *** treatment choice of bevacizumab was at the discretion of the *** endpoints were response and toxicity and secondary endpoints included progression-free survival and overall survival. RESULTS:In the CAPIRI group vs the CAPRI-Bev group there were more female than male patients(47% vs 24%) ,and more patients had colon as the primary tumor site(58.8%vs 48.2%) with fewer patients having sigmoid colon as primary tumor site(5.9%vs 20.7%) .Grade 3/4 toxicity was higher with CAPIRI than CAPIRI-Bev:82%vs 58.6%.Partial response rates were 29.4%and 34.5%,and tumor control rates were 70.6%and 75.9%,*** complete responses were *** median progression-free survival was 11.4 mo and 12.8 mo for CAPIRI and CAPIRI-Bev,*** median overall survival for CAPIRI was 15 mo(458 d) and for CAPIRI-Bev 24 mo(733 d) .These differences were not statistically *** the CAPIRI-Bev,group,two patients underwent a full secondary tumor resection after treatment,whereas in the CAPIRI group no cases underwent this procedure. CONCLUSION:Both regimens were well tolerated and offered effective tumor growth control in this outpatient *** gastrointestinal toxicities and thromboembolic events were rare and if observed were never fatal.

关键词： First-line therapy Metastatic colorectalcancer Bevacizumab Capecitabine Irinotecan Tumorresponse

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Sperm DNA damage and its clinical relevance in assessingreproductive outcome

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Asian Journal of Andrology 2004年第2期6卷 139-148页

作者： R. K. Sharma T. Said A. Agarwal Centerfor Advanced Research in Human Reproduction infertility and Sexual Function Glickman Urological Institute The Cleveland Clinic Foundation Cleveland Ohio 44195 USA

The routine examination of semen, which assesses sperm concentration, percentage motility and morphology, does not identify subtle defects in sperm chromatin architecture. The focus on the genomic integrity of the male gamete has intensified recently due to the growing concern that genetic diseases may be transmitted via assisted reproductive techniques (ART). Accordingly, the intent of this review is to describe the details of the information pertaining to mitochondrial/nuclear sperm DNA damage with an emphasis on its clinical significance and its relation ship with male infertility. Assessment of sperm DNA damage appears to be a potential tool for evaluating semen samples prior to their use in ART. Testing DNA integrity may help select spermatozoa with intact DNA or with the least amount of DNA damage for use in assisted conception. In turn, this may alleviate the financial, social and emotional problems associated with failed ART attempts.

关键词： DNA damage human male infertility sperm

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Neuromuscular trunk activation patterns in back pain patients during one-handed lifting

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World Journal of Orthopedics 2017年第2期8卷 142-148页

作者： Juliane Mueller Tilman Engel Stephan Kopinski Frank Mayer Steffen Mueller University outpatient clinic Sports Medicine and Sports OrthopaedicsUniversity of Potsdam

AIM To analyze neuromuscular activity patterns of the trunk in healthy controls(H) and back pain patients(BPP) during one-handed lifting of light to heavy loads. METHODS After assessment of back pain(graded chronic pain scale according to von Korff) all subjects(n = 43) performed a warm-up(treadmill walking). Next, subjects were instructed to lift 3 × a 20 kg weight placed in front of them(with both hand) onto a table(height: 0.75 m). Subsequently, all subjects lifted with one hand(left-side, 3 repetitions) a weight of 1 kg(light), 10 kg(middle) and 20 kg(heavy) in random order from the ground up onto the table left of them. Trunk muscle activity was assessed with a 12-lead EMG(6 ventral/6 dorsal muscles; 4000 Hz). EMG-RMS(%) was averaged over the 3 repetitions and analyzed for the whole one-handed lifting cycle, then normalized to RMS of the two-handed lifting. Additionally, the mean(normalized) EMG-RMS of four trunk areas [right/left ventral area(VR/VL); right/left dorsal area(DR/DL)] was calculated. Data were analyzed descriptively(mean ± SD) followed by student's t-test comparing H and BPP(α = 0.05). With respect to the unequal distribution of subjects in H and BPP, a matched-group analysis was conducted. Seven healthy controls were gender- and age-matched(group H_(matched)) to the 7 BPP. In addition, task failure was calculated and compared between H/H_(matched) vs BPP using χ~2. RESULTS Seven subjects(3m/4f; 32 ± 7 years; 171 ± 7 cm; 65 ± 11 kg) were assigned to BPP(pain grade ≥ 2) and 36(13m/23f; 28 ± 8 years; 174 ± 10 cm; 71 ± 12 kg) to H(pain grade ≤ 1). H and BPP did not differ significantly in anthropometrics(P > 0.05). All subjects were able to lift the light and middle loads, but 57% of BPP and 22% of H were not able to lift the heavy load(all women). χ~2 analysis revealed statistically significant differences in task failure between H vs BPP(P = 0.03). EMG-RMS ranged from 33% ± 10%/30% ± 9%(DL, 1 kg) to 356% ± 148%/283% ± 80%(VR, 20 kg) in H/BPP with n

关键词： Lifting Core Trunk EMG MISPEX

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The contribution of Asian scientists to global research in andrology

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Asian Journal of Andrology 1999年第1期1卷 7-12页

作者： Geoffrey MH WAITES clinic for infertility and Gynaecological Endocrinology University Hospital of Geneva SWITZERLAND and Department of Medicine Unnversity of Sydney Sydney NSW 2006 AUSTRALIA

Aim: To present a personal account of the involvement of the World Health Organization (WHO) in the collaborativedevelopment in Asia of those areas of andrology concerned with male contraception and reproductive ***: The andrology training through workshops and institution support undertaken by the WHO HumanReproduction Programme (HRP) and how they contributed to the strengthening of andrology research in Asia aresummarised. Results: The author's experience and the Asian scientific contributions to the global research in thefollowing areas are reviewed: the safety of vasectomy and the development of new methods of vas occlusion; gossypoland its failure to become a safe, reversible male antifertility drag; Tripterygium and whether its pure extracts will passthrough the appropriate toxicology and phased clinical studies to become acceptable contraceptive drugs; hormonalmethods of contraception for men. Conclusion: The WHO policy of research capacity building through training andinstitution strengthening, together with the collaboration of Asian andrologists, has created strong National institutionsnow able to direct their own programmes of research in clinical and scientific andrology.

关键词： andrology Asia contraception vas occlusion gossypol Tripterygium hormonal methods World Health Organization

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Beneficial effects of switching from β-blockers to nebivolol on the erectile function of hypertensive patients

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Asian Journal of Andrology 2006年第2期8卷 177-182页

作者： MichaelDoumas AlexandrosTsakiris StellaDouma Alkiviadis Grigorakis AngelosPapadopoulos AthinaHounta SotiriosTsiodras Dimitrios Dirnitriou Helen Giamarellou Hypertension outpatient clinic Fourth Department of Internal Medicine Urologic outpatient clinic Second Department of UrologyUniversityof AthensAttikon HospitalAthens 12461Greece

Aim： To investigate the effect of substituting β-blockers with nebivolol on the erectile function of patients suffering from essential hypertension. Methods： Forty-four young and middle-aged men （31-65 years） with essential hypertension visited our outpatient clinic and took β-blocker treatment （atenolol, metoprolol or bisoprolol） for more than 6 months. All the patients completed a questionnaire regarding erectile function （International Index for Erectile Function）. Patients were then switched to an equipotent dose of nebivolol for 3 months and, at the end of this time period, filled out the same questionnaire. Results： Twenty-nine out of the 44 （65.9%） patients who took p-blockers （atenolol, metoprolol or bisoprolol） had exhibited erectile dysfunction （ED）. Their systolic and diastolic blood pressure did not change significantly with the treatment switch. In 20 out of these 29 （69%） patients, a significant improvement in the erectile function score was exhibited after 3 months of nebivolol administration, and in 11 of these 20 patients, erectile function was normalized. Conclusion： Nebivolol seems to have a beneficial effect on ED （possibly due to increased nitric oxide availability）; however, further prospective, randomized, placebo-controlled studies are needed to confirm the beneficial effects of nebivolol. （Asian J Androl 2006 Mar; 8： 177-182）

关键词： erectile dysfunction essential hypertension β-blockers nebivolol

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Y microdeletions in the Istria county,Croatia

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Asian Journal of Andrology 2005年第2期7卷 213-216,页

作者： I.Medica N.Gligorievska M.Prenc B.Peterlin Division of Medical Genetics Department of Obstetrics and GynecologyUniversity Medical CentreLjubljana 1000Slovenia Outpatient Pediatric ClinicPula 52100Croatia Division of Medical Genetics Department of Obstetrics and GynecologyUniversity Medical CentreLjubljana 1000Slovenia outpatient infertility clinic Department of GynecologyGeneral Hospital PulaPula 52100Croatia

Aim:To establish the frequency of Y chromosome microdeletions in an unselected group of infertile Croatian men. Methods:An unselected group of 105 patients (male partners of infertile couples),both with idiopathic and non- idiopathic infertility,consecutively referred to the outpatient infertility clinic,gynecology department,General Hospital Pula,Istria County,Croatia,was examined for the presence or absence of Y chromosome microdeletions by poly- merase chain reaction ***:One of the 105 men (0.95 %,95 % CI=0.17-5.2 %) was found to have a ***:A low frequency of Y chromosome microdeletions was found in the group of unselected infertile Croatian men.

关键词： male infertility Y chromosome AZF region microdeletion

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International Journal of clinical Medicine 2012年第7期3卷 598-602页

作者： Gerhard Lonnemann Eike Wrenger outpatient clinic of Nephrology Hemodialysis Center Eickenhof Langenhagen Germany outpatient clinic of Nephrology Hemodialysis Center Eickenhof Langenhagen Germany.

Aim: This observational clinical study tested the effect of injection frequency of the biosimilar epoetin zeta on the weekly dose needed to maintain stable hemoglobin levels in chronic kidney diseases (CKD) patients on intermittent high-flux hemodialysis (HD). Patients and Methods: CKD patients (n = 33) on regular HD therapy 3 times a week were treated for 18 months with epoetin zeta i.v. The hemoglobin levels, the weekly dose as well as the injection frequency of epoetin zeta were monitored at least every two weeks. Patients were followed in three time periods: 1) extended follow-up (months 1 - 18);2) intervention phase (months 19 - 21);and 3) post intervention observation phase (months 28 - 30). During extended follow-up the majority of patients (n = 21) received only one injection of epoetin zeta per week. During the intervention phase, injection frequency was increased to 3 injections per week in all patients accompanied by a reduction in weekly doses of approximately 20% - 30%. Following a 9 month period of dose adjustment all parameters were monitored again in the post-intervention phase. Results: During the first 18 months of epoetin zeta therapy the mean hemoglobin level was stable between 11 and 12 g/dl. The mean weekly dose of epoetin zeta was 7939 IU/week in month 6 and 7909 IU/week in month 18 (p = not significant). The mean frequency (injections/week) was 1.27 in month 6 and 1.29 in month 18 (not significant). Compared to month 18, at the end of the observation at month 30, hemoglobin levels were stable, mean injection frequency increased to 2.25 (p < 0.001) and the mean weekly dose decreased to 5469 IU/week (-31.7%, p < 0.001). Conclusions: Increasing the injection frequency of the short acting biosimilar epoetin zeta to two to three injections per week reduces the weekly dose and thereby the costs of ESA therapy of renal anemia significantly.

关键词： Epoetin Zeta Renal Anemia Drug Efficiency Injection Frequency Chronic Hemodialysis

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Relationship between acrosin activity of human spermatozoa and oxidative stress

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Asian Journal of Andrology 2004年第4期6卷 313-318页

作者： Adel A.Zalata Ashraf H.Ahmed Shyam S.R.Allamaneni Frank H.Comhaire Ashok Agarwal Department of Medical Biochemistry Department DermatologyCenter for Advanced Research in Human ReproductionUniversity Hospital GhentCenter for Advanced Research in Human Reproduction Faculty of Medicine Mansoura University Egypt Venereology & Andrology Faculty of Medicine Mansoura University Egypt Infertility and Sexual Function Glickman Urological Institute and Department of Obstetrics-Gynecology Cleveland Clinic Foundation Ohio USA Department of Internal Medicine Section of Endocrinology Ghent Belgium Infertility and Sexual Function Glickman Urological Institute and Department of Obstetrics-Gynecology Cleveland Clinic Foundation Ohio USA

Aim: To study the association between seminal oxidative stress and human sperm acrosin activity. Methods: It is a prospective study consisting of 30 infertile men and 12 fertile normozoospermic volunteers. A full history, clinical examination and scrotal ultrasound were done to exclude other related factors such as smoking and varicocele. Presence of white blood cells (WBCs) in semen samples was evaluated by peroxidase staining. Lipid peroxidation in spermatozoa was induced after incubating with ferrous sulphate (4 mmol/L) and sodium ascorbate (20 mmol/L). Induced peroxidation of spermatozoa was assessed by determining the production of thiobarbituric acid reactive substances (TBARS). Acrosin activity was measured using the gelatinolysis technique. The halo diameters around the sperm heads and the percentages of spermatozoa showing halo formation were evaluated. An acrosin activity index was calculated by multiplying the halo diameter by the halo formation rate. Results: A significant difference was observed in acrosin activity parameters and TBARS levels between samples with WBCs (>1×106/mL of ejaculate) and those without. This difference was also noted between the normozoospermic and the oligoasthenoteratozoospermic semen samples. The TBARS production by spermatozoa had a significant negative correlation with the acrosin activity index (r = -0.89, P <0.001). Conclusion: The presence of oxidative stress in an individual with leukocytospermia and/or abnormal semen parameters is associated with impaired sperm function as measured by its acrosin activity.

关键词： acrosin gelatinolysis reactive oxygen species lipid peroxidation leukocytospermia spermatozoa oligo-astheno-teratozoospermia infertility

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