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Onno E Janssen

Publications and source records attributed to Onno E Janssen.

At least 19 recordsLinked to original sources

Calpain-10 variants and haplotypes are associated with polycystic ovary syndrome in Caucasians.

PCOS is known to be associated with an increased risk of T2DM and has been proposed to share a common genetic background with T2DM. Recent studies suggest that the Calpain-10 gene (CAPN10) is an interesting candidate gene for PCOS susceptibility. However, contradictory results were reported concerning the contribution of certain CAPN10 variants, especially of UCSNP-44, to genetic predisposition to T2DM, hirsutism, and PCOS. By means of MALDI-TOF MS technique, we genotyped an expanded single nucleotide polymorphism panel, including the CAPN10 UCSNP-44, -43, -56, ins/del-19, -110, -58, -63, and -22 in a sample of 146 German PCOS women and 606 population-based controls. Statistical analysis revealed an association between UCSNP-56 and susceptibility to PCOS with an odds ratio (OR) of 2.91 (95% CI=1.51-5.61) for women carrying an AA genotype compared with GG. As expected, the 22-genotype of the ins/del-19 variant, which is in high linkage disequilibrium (r2=0.98) with UCSNP-56, was also significantly associated (OR=2.98, 95% CI=1.55-5.73). None of the additionally tested variants alone showed any significant association with PCOS. A meta-analysis including our study (altogether 623 PCOS cases and 1,224 controls) also showed significant association only with ins/del-19. The most common haplotype TGG3AGCA was significantly associated with a lower risk for PCOS (OR=0.487, P=0.0057). In contrast, the TGA2AGCA haplotype was associated with an increased risk for PCOS (OR=3.557, P=0.0011). By investigating a broad panel of CAPN10 variants, our results pointed to an allele dose-dependent association of UCSNP-56 and ins/del-19 with PCOS.

Adult↗

Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline.

OBJECTIVE: The Androgen Excess Society (AES) charged a task force to review all available data and recommend an evidence-based definition for polycystic ovary syndrome (PCOS), whether already in use or not, to guide clinical diagnosis and future research. PARTICIPANTS: Participants included expert investigators in the field. EVIDENCE: Based on a systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, we tried to identify studies evaluating the epidemiology or phenotypic aspects of PCOS. CONSENSUS PROCESS: The task force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the AES Board of Directors. No section was finalized until all members were satisfied with the contents and minority opinions noted. Statements that were not supported by peer-reviewed evidence were not included. CONCLUSIONS: Based on the available data, it is the view of the AES Task Force on the Phenotype of PCOS that there should be acceptance of the original 1990 National Institutes of Health criteria with some modifications, taking into consideration the concerns expressed in the proceedings of the 2003 Rotterdam conference. A principal conclusion was that PCOS should be first considered a disorder of androgen excess or hyperandrogenism, although a minority considered the possibility that there may be forms of PCOS without overt evidence of hyperandrogenism but recognized that more data are required before validating this supposition. Finally, the task force recognized, and fully expects, that the definition of this syndrome will evolve over time to incorporate new research findings.

Androgens↗

C-terminal amino acid alteration rather than late termination causes complete deficiency of thyroxine-binding globulin CD-NeuIsenburg.

CONTEXT: T(4)-binding globulin (TBG) is the main transport protein for T(4) in blood and a member of the superfamily of serine proteinase inhibitors. So far, 14 mutations leading to familial complete TBG deficiency have been reported. Eleven of these are caused by mutations leading to truncation of the molecule, and three are caused by single amino acid substitutions. OBJECTIVE: We report and study the complete deficiency TBG variant found in a patient from NeuIsenburg, Germany (TBG-CDNI). METHODS: Direct DNA sequencing was used to identify the TBG-CDNI mutation in the propositus, which was confirmed by allele-specific amplification. Site-directed mutagenesis and expression in Xenopus oocytes was used to study the secretion defect of TBG-CDNI and several variants by Western blot and T(4)-binding assay. RESULTS: The deletion of two nucleotides in codon 384 (1211_1212delTC) causes a frameshift altering the last 11 residues, introduces a new glycosylation site, and elongates the molecule by seven new amino acids. In contrast to normal TBG, TBG-CDNI was not secreted by Xenopus oocytes. Elongation of normal TBG by seven alanines did not affect its secretion or binding properties. On the other hand, neither disruption of its new glycosylation site nor termination of TBG-CDNI at the normal length repaired its secretion defect. CONCLUSIONS: In this first late termination variant of complete TBG deficiency, alteration of beta-strand 5B, located in the core of the molecule, rather than elongation of the molecule or introduction of a new glycosylation site, suffices to disrupt secretion of TBG-CDNI.

Adult↗

Metformin treatment of polycystic ovary syndrome improves health-related quality-of-life, emotional distress and sexuality.

BACKGROUND: In polycystic ovary syndrome (PCOS), changes in physical appearance, menstrual disturbances and infertility result in psychological distress and reduced quality-of-life. Metformin improves biochemical, clinical and reproductive parameters in PCOS women. In a prospective, observational study, we analysed the effects of metformin treatment on health-related quality-of-life (HRQL), emotional well-being and sexuality in PCOS. No placebo-treated control group was included. METHODS: Before, during and after 6 months of treatment, changes in clinical and endocrine parameters, quality-of-life, psychological disturbances and sexuality were assessed in 64 PCOS patients using validated questionnaires (SF-36, SCL-90-R) and visual analogue scales. Patients were also compared with published normative data for the validated questionnaires. RESULTS: During treatment, HRQL, particularly the psychosocial aspects (indicated by significant increases in SF-36 scales Vitality, Social Function, Emotional Role Function, Mental Health, Psychological Sum scale) and emotional well-being (reflected by significant lowering of SCL-90-R scales) improved. These improvements in HRQL were significantly correlated with a reduction in body weight and significantly more pronounced in patients with normalized menstrual cycles. In addition, PCOS women were significantly more satisfied with their sex life and reported higher frequencies of sexual intercourse following treatment. CONCLUSION: Treatment can improve the psychosocial, emotional and psychosexual situation of PCOS patients. Although at least some of these effects may be related to the reduction of individual clinical symptoms (i.e. weight loss, normalization of menstrual disturbances, improvement of acne), this observational study does not allow us to clearly discern the role of symptom constellation and does not preclude non-specific and/or placebo effects. Nevertheless, emotional distress and reduced quality-of-life are clearly not an inevitable consequence of PCOS and should be considered as adjunct treatment goals in future studies.

Adult↗

Determinants of emotional distress in women with polycystic ovary syndrome.

BACKGROUND: The goals were to analyse the incidence of mental distress in women with untreated polycystic ovary syndrome (PCOS) using self-report measures, to characterize PCOS patients at risk for psychiatric disease with regard to sociodemographic and clinical characteristics, and to assess the impact of emotional distress on quality of life. METHODS AND RESULTS: Complete metabolic, hormonal, clinical and self-report psychological data [emotional distress, Symptom Check List 90 (SCL-90-R); quality of life, Short-Form Health Survey 36 (SF-36); sexual satisfaction, visual analogue scales; sociodemographic data] were obtained from n = 143 untreated women with PCOS. Prior psychiatric diagnoses were exclusionary. Twenty-two patients (15.4%) had a possible psychological disorder, based on SCL-90-R global severity index (GSI) scores > or =63 (SCL cases). SCL cases had significantly elevated body mass index (BMI), but did not differ from SCL non-cases in other clinical, endocrine, metabolic or sociodemographic variables. Stepwise multiple regression analyses identified GSI as a significant predictor of SF-36 Psychological Sum score, along with age and current wish to conceive (R2 = 0.47); the SF-36 Physical Sum score was predicted by BMI and education (R2 = 0.27), but not GSI. CONCLUSIONS: Psychiatric illness may go undetected in a proportion of PCOS patients. Although the majority of patients exhibit subclinical levels of psychological disturbances, emotional distress together with obesity lead to large decrements in quality of life in PCOS.

Adult↗

Posterior retroperitoneoscopic adrenalectomy--results of 560 procedures in 520 patients.

BACKGROUND: The posterior retroperitoneoscopic adrenalectomy is less popular than the laparoscopic transabdominal method. Due to the direct approach to the adrenal glands, however, the posterior retroperitoneal access is easy to use and may offer advantages not available with other endoscopic procedures for adrenalectomy. METHODS: Between July 1994 and March 2006, we performed 560 adrenalectomies (right side: n = 258; left side: n = 302) by the posterior retroperitoneoscopic approach in 520 patients (200 male, 320 female; age, 10 to 83 years). Of the 520 patients, 21 suffered from Cushing's disease, 499 patients had adrenal tumors (157 Conn's adenomas, 120 pheochromocytomas [13 bilateral], 110 Cushing's adenomas [6 bilateral], and 112 other tumors). Tumor size ranged from 0.5 to 10 cm (mean, 2.9 +/- 1.7 cm). The procedures were performed with the patients in the prone position usually with 3 trocars. RESULTS: Mortality was zero. Conversions to open or laparoscopic lateral surgery were necessary in 9 patients (1.7%). Major complications occurred in 1.3% of patients, minor complications in 14.4%. Mean operating time was 67 +/- 40 min and declined significantly (P < .001) from the early procedures (106 +/- 46 min) to the later operations (40 +/- 15 min). CONCLUSIONS: The posterior retroperitoneoscopic adrenalectomy is a safe and fast procedure. In experienced hands, this method represents the ideal approach in adrenal surgery.

Adolescent↗

Decreased soluble leptin receptor levels in women with polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and a high incidence of obesity. Leptin, the product of the ob gene, is involved in the regulation of energy balance and obesity and circulates in both free and bound forms. The soluble leptin receptor (sOB-R) is the most important leptin-binding protein, thus influencing the biologically active free leptin level. DESIGN: We assessed the correlation of metabolic and endocrine parameters with leptin and sOB-R levels in 122 PCOS women (aged 27 +/- 5.7 years) and 81 healthy controls (aged 25 +/- 4.0 years). METHODS: Leptin and sOB-R levels were measured using ELISA kits. In addition, anthropometric variables, body fat and endocrine parameters were evaluated and a glucose tolerance test performed to assess indices of insulin resistance and glucose metabolism. RESULTS: In PCOS patients, no correlation was found between leptin or sOB-R and parameters of hyper-androgenism. However, as expected, body mass index (BMI), body fat, waist circumference and indices of insulin resistance were significantly correlated with leptin in PCOS subjects and controls. In a subgroup analysis of lean, overweight and obese PCOS patients, significant differences were found in leptin (29.7 +/- 20.7 vs 45.4 +/- 25.0 vs 67.7 +/- 28.8 ng/ml, P < 0.0001) and sOB-R (8.0 +/- 3.4 vs 6.4 +/- 2.5 vs 5.7 +/- 2.3 ng/ml, P < 0.05). Compared with BMI-matched controls, lean PCOS patients had lower sOB-R levels (8.0 +/- 3.4 vs 12.7 +/- 4.7 ng/ml, P < 0.0001) and higher free leptin indices (4.5 +/- 3.9 vs 2.8 +/- 2.2, P = 0.0285). CONCLUSION: Taking into account that low sOB-R levels supposedly compensate diminished leptin action, PCOS per se might cause leptin resistance.

Adult↗

The CC genotype of the GNAS T393C polymorphism is associated with obesity and insulin resistance in women with polycystic ovary syndrome.

OBJECTIVE: Variants in the Gs protein alpha subunit gene (GNAS1) are known to be involved in the pathogenesis of several endocrine and metabolic disorders. To understand genetic determinants of androgen excess, insulin resistance, and obesity in polycystic ovary syndrome (PCOS), we investigated the effect of the common GNAS1 T393C polymorphism on the phenotype of German PCOS women. DESIGN: Two hundred and seventy-eight PCOS women and 820 Caucasian controls were genotyped for the common T393C polymorphism in GNAS1. To this end, genomic DNA was amplified by PCR with specific oligonucleotides and genotypes were determined using the restriction enzyme FokI. In addition, we evaluated whether the T393C polymorphism had an influence on the response to 6 months metformin treatment in a subgroup of 105 PCOS women. METHODS: Anthropometric variables, metabolic parameters including indices of insulin resistance measured by oral glucose tolerance testing, and endocrine biochemical as well as clinical parameters were measured in all PCOS subjects. RESULTS: GNAS1 genotype distributions were not significantly different between PCOS women and controls. In PCOS women, no significant differences in endocrine clinical and biochemical variables were found between the genotypes. However, the C-allele carrier group had significantly higher mean body weight, body mass index, leptin levels, and higher indices of insulin resistance compared with women with GNAS1 TT-genotype. Metformin treatment significantly improved hyperandrogenism, menstrual cyclicity, body weight, and insulin resistance independent of GNAS1 genotype. The major determinant of weight loss was body weight before treatment. CONCLUSION: The T393C polymorphism is not associated with PCOS in Caucasian women, but may represent a genetic marker for increased susceptibility for obesity in this cohort.

Androgens↗

Free androgen index is superior to total testosterone for short-term assessment of the gonadal axis after renal transplantation.

OBJECTIVE: Recent studies have assessed gonadal function in association with different immunosuppressive drugs in transplanted patients mainly relying on the measurement of total testosterone. It is the aim of this study to assess the short-term changes of the hypothalamic-pituitary-gonadal axis following renal transplantation using the free androgen index (FAI). PATIENTS AND METHODS: The sequential changes in total testosterone, sex hormone-binding globulin (SHBG), gonadotropin and prolactin concentrations were measured in 22 male patients before and after 1-3 days, and 1, 2 and 3 weeks following renal transplantation. RESULTS: Total testosterone and SHBG concentrations dropped significantly after transplantation (total testosterone: baseline: 15.2 +/- 1.6 nmol/l vs. 1 week: 7.9 +/- 0.8 nmol/l vs. 2 weeks: 9.8 +/- 0.9 nmol/l, SHBG: baseline: 29.9 +/- 3.2 nmol/l vs. 1 week: 19.9 +/- 2.1 nmol/l, 2 weeks: 18.9 +/- 2.4 nmol/l, p < 0.01). FAI decreased significantly after day 1-3 returning to values near baseline thereafter (baseline: 60 +/- 9% vs. day 1-3: 38 +/- 6%, 2 weeks: 61 +/- 7%; p < 0.01). There was a significant positive correlation between FAI and renal function. CONCLUSION: Measurement of the free androgen index is superior to total testosterone for assessment of the pituitary-gonadal axis in the first weeks after renal transplantation.

Adult↗

Effects of interferon-beta 1a on the hypothalamic-pituitary-adrenal axis, leukocyte distribution and mood states in multiple sclerosis patients: results of a 1-year follow-up study.

Acute interferon-beta (IFN-beta) administration transiently activates the hypothalamic-pituitary-adrenal (HPA) axis, increases granulocytes, and reduces lymphocytes in peripheral blood. To test whether these effects are still present after long-term treatment, 13 patients with relapsing-remitting multiple sclerosis were analyzed at baseline, and 1, 2, 4, and 8 h after IFN-beta 1a injection at two occasions: at the initial administration and after 1 year of continuous treatment. Long-term treatment reduced the responsiveness of the HPA axis to the injection, and abolished the distributional changes in leukocyte numbers. One-year treatment with IFN-beta 1a did not induce mood alterations as assessed by the Profile of Mood States. These results suggest that long-term IFN-beta therapy has a profound impact on leukocyte distribution and the neuroendocrine response to the drug.

Adjuvants, Immunologic↗

Behavioral conditioning with interferon beta-1a in humans.

Behavioral conditioning is one of the most impressive demonstrations of brain-immune system interaction. Numerous animal studies have demonstrated behavioral conditioned effects on immune functions, however, human studies are rare. We investigated whether it is possible to behaviorally condition the acute response to interferon (IFN)beta-1a. In a double-blind placebo-controlled study, 30 healthy subjects received a single injection of IFN(beta)-1a (6MIU of REBIF, Serono International) (unconditioned stimulus, UCS) together with a novel drink (conditioned stimulus, CS). Blood was drawn at baseline, 4, 8, and 24 h after drug administration. Within the first 8 h peripheral granulocytes significantly increased, while monocytes, lymphocytes, T-, B- and natural killer (NK) cell numbers were significantly reduced. In parallel, body temperature, heart rate, norepinephrine and interleukin (IL)-6 plasma levels were heightened within 8 h after injection. 8 days later, all previously IFN(beta)-treated subjects received a subcutaneous placebo (NaCl) injection, but only 15 subjects were re-exposed to the CS (experimental group), while a control group (N=15) drank water and an additional group of subjects (n=8) remained untreated (untreated group). Blood sampling was performed at baseline and at 4, 8, and 24 h. Re-exposition to the CS did not elicit conditioned responses in the experimental group. Moreover, no differences were observed between groups. These data provide negative findings regarding behavioral conditioning of cytokine effects in humans employing a one-trial learning paradigm.

Adult↗

Sensitive thyrotropin and thyrotropin-receptor antibody determinations one month after discontinuation of antithyroid drug treatment as predictors of relapse in Graves' disease.

OBJECTIVE: After primary successful antithyroid drug treatment (ATDT), Graves' disease has a relapse rate of 30% to 50%. Previous studies have evaluated age, gender, goiter volume, smoking habits, and the presence of thyrotropin-receptor antibodies (TRAb) as predictive markers to facilitate an individualized patient management. Despite higher sensitivity and specificity of the new second generation human TSH-receptor assay, the predictive value of TRAb for relapse of hyperthyroidism is still controversial. In a recent prospective multicenter study we have previously shown that suppressed or low TSH values predict both early (persistence) and late relapse of Graves' disease. We now present a more detailed analysis of the predictive value of TSH and TRAb for recurrent hyperthyroidism. METHODS: Four weeks after withdrawal of ATDT, 96 patients were available for thyroid function tests, including a sensitive third-generation TSH assay and a second-generation recombinant TSH receptor assay. Relapse of Graves' disease was evaluated for a total follow-up of 2 years. RESULTS: Within 2 years, 47 of 96 patients (49%) developed relapse of hyperthyroidism. Nine patients relapsed within the first 4 weeks after withdrawal of ATDT and were thus considered to have persistent Graves' disease. Ten of 15 other patients with TSH levels below 0.3 mU/L without overt hyperthyroidism relapsed within 2 years. Twenty-five of 65 patients with normal TSH (0.3-3.0 mU/L) and 3 of 4 patients with TSH values above 3 mU/L also had recurrent hyperthyroidism. After ATDT cessation, TSH had a positive predictive value of 70% and a negative predictive value of 62% (specificity 85%) for relapse of Graves 'disease. Mean TRAb levels in the group of patients with relapse were significantly higher (11.1 IU/L +/- 0.17) than TRAb values in the remission group (4.5 IU/L +/- 0.6), p < 0.001. Using a cutoff value of 1.5 IU/L, TRAb had low positive and negative predictive values of 49% and 54%, respectively (specificity, 14%), but with a cutoff level of 10 IU/L, predictive values improved to 83% and 62%, respectively (specificity, 92%). Combination of TSH and TRAb determinations did not further improve prediction of relapse. Other factors such as gender, age, goiter volume, smoking habits, presence of thyroid-associated ophthalmopathy, and urinary iodine excretion did not show a significant influence on relapse rate. CONCLUSION: Low TSH values 4 weeks after ATDT withdrawal predict relapse of Graves' disease, both early (persistence) and, to a lesser extend, within 2 years of follow-up. Also, TRAb above 10 IU/L found in a small subset of patients, correlated with a higher relapse rate.

Adult↗

The peroxisome proliferator activated receptor gamma Pro12Ala polymorphism is associated with a lower hirsutism score and increased insulin sensitivity in women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and chronic anovulation. The genetic background of the insulin resistance frequently associated with PCOS is unclear. OBJECTIVES: To examine the influe nce of the Pro12Ala polymorphism of the peroxisome proliferator activated receptor gamma (PPARgamma), which is thought to play a role in the regulation of insulin sensitivity, on endocrine and metabolic parameters in PCOS patients. METHODS: PPARgamma alleles were analysed in 102 PCOS patients (age 27 +/- 5.3 years) and 104 age matched control women. PCOS was defined by the NIH-criteria as the presence of chronic oligo- or anovulation and hyperandrogenism. Family history and clinical parameters were evaluated by personal interview and physical examination, parameters of insulin resistance [homeostasis model assessment (HOMA) and Matsuda-index] were evaluated with a glucose tolerance test. RESULTS: Seventy-nine (77.5%) PCOS patients were carriers of the wild-type PPARgamma allele (Pro/Pro), while 23 (22.5%) had at least one Ala allele (X/Ala), with an equal distribution in controls. X/Ala PCOS women were more insulin-sensitive, evidenced by lower fasting insulin, HOMA index and insulin secretion. Differences in insulin resistance did not depend on body mass index. The genotype had no influence on lipid status, leptin, adiponectin, ghrelin, or family history of type 2 diabetes. A significantly lower proportion of Pro/Ala patients had hirsutism and they had on average lower hirsutism scores than Pro/Pro patients. No relationship was found between the Pro/Ala polymorphism and other signs of hyperandrogenism. CONCLUSION: The Pro12Ala polymorphism of the PPARgamma gene is associated with increased insulin sensitivity and lower hirsutism scores in PCOS women.

Adult↗

Effects of mind-body therapy on quality of life and neuroendocrine and cellular immune functions in patients with ulcerative colitis.

BACKGROUND: The aim of this study was to investigate the effects of mind-body therapy on neuroendocrine and cellular immune measures, health-related quality of life and disease activity in patients with ulcerative colitis (UC) in remission. METHODS: Thirty UC patients in remission or with low disease activity were randomly assigned to an intervention group (n = 15) or a usual-care waiting control group (n = 15). Intervention consisted of a structured 60-hour training program over 10 weeks which included stress management training, moderate exercise, Mediterranean diet, behavioral techniques and self-care strategies. Quality of life, perceived stress and disease activity were assessed with standardized questionnaires (IBDQ, SF-36, PSS, CAI). In addition, the distribution of circulating lymphocytes and lymphocyte subsets as well as the beta-adrenergic modulation of TNF-alpha production in vitro were analyzed. Urine catecholamines and plasma cortisol, prolactin and growth hormone were measured pre- and postinterventionally, and were compared with a healthy control group (n = 10). RESULTS: In response to therapy, patients in the intervention group showed significantly greater improvement in the SF-36 scale Mental Health and the Psychological Health Sum score compared with changes observed in the usual-care waiting control group. Patients in the intervention group showed significantly greater improvement on the IBDQ scale Bowel Symptoms compared with the control group. However, no significant group differences in circulating lymphocyte subsets or endocrine parameters were observed in response to therapy. In addition, no significant effects of intervention on either the basal levels of TNF-alpha or the suppressive action of the beta-adrenergic agonist isoproterenol on TNF-alpha production were observed. CONCLUSION: Mind-body therapy may improve quality of life in patients with UC in remission, while no effects of therapy on clinical or physiological parameters were found, which may at least in part be related to selective patient recruitment.

Adult↗

Clinical and psychological correlates of quality-of-life in polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) has been shown to cause a reduction in quality of life. This study examines the extent of different PCOS symptoms on quality-of-life, psychosocial well-being and sexual satisfaction. METHODS: Complete metabolic, hormonal, clinical and psychosocial data were obtained from a total of 120 women with PCOS. Patients were compared with 50 healthy women to establish reductions in quality-of-life and emotional well-being. In addition, the correlation between psychosocial variables and the major clinical PCOS features obesity (body mass index (BMI)), excessive body hair (hirsutism score), acne, hyperandrogenism (serum testosterone levels), disturbed insulin regulation (area under the insulin response curve and homeostasis model assessment of insulin resistance), menstrual cycle disturbances and infertility were analyzed. RESULTS: PCOS patients showed significant reductions in quality-of-life, increased psychological disturbances, and decreased sexual satisfaction when compared with healthy controls. BMI and hirsutism scores, but not the presence of acne, were associated with physical aspects of quality-of-life and sexual satisfaction. No clear effect of androgens or insulin resistance on psychosocial variables was detected. Similarly, the type of menstrual cycle disturbances or infertility had no impact on psychological well-being. CONCLUSION: In PCOS, changes in appearance, particularly obesity and hirsutism, reduce physical dimensions of quality-of-life and decrease sexual satisfaction. The role of biochemical, endocrine and metabolic parameters as well as menstrual irregularities and infertility appeared to be less important. Clinicians should pay attention to the psychosocial dimensions of PCOS on an individual basis, regardless of symptom severity or treatment response.

Acne Vulgaris↗

Repeated acupuncture treatment affects leukocyte circulation in healthy young male subjects: a randomized single-blind two-period crossover study.

Acupuncture is the most popular component of traditional Chinese medicine in western countries, which has been widely used in the treatment of numerous medical conditions, e.g., pain, emesis or asthma. However, the effects of acupuncture on neuroendocrine and immune functions in humans remain unclear. Therefore, the present study was performed to analyse whether acupuncture treatment affects leukocyte circulation as well as plasma levels of cortisol and norepinephrine in humans. Ten healthy young male subjects were enrolled in a randomized single-blind two-period crossover study. Each period contained three sessions of either acupuncture or sham acupuncture (placebo) treatment. After randomisation, the group 1 (n=5) received acupuncture treatment at acu-points ST36, LI11, SP10, and GV14, while sham acupuncture was performed for group 2 (n=5). Two weeks later, each group received the alternative treatment. Blood samples were taken before needling, 10 min after, and 30 min after removing the needles in the first and the third session. In addition, blood pressure and heart rate were determined simultaneously. Although acupuncture treatment did not affect leukocyte circulation in peripheral blood after the first session, we observed a significant decrease in leukocyte and lymphocyte values after the third session. In contrast, cortisol and norepinephrine plasma levels remained unchanged by acupuncture. These data indicate that repeated acupuncture treatment can affect leukocyte circulation in healthy humans by still unknown mechanisms.

Acupuncture Therapy↗

Partial versus total adrenalectomy by the posterior retroperitoneoscopic approach: early and long-term results of 325 consecutive procedures in primary adrenal neoplasias.

The retroperitoneoscopic approach is a standardized operative procedure for primary adrenal gland tumors. It allows direct access with a detailed view of the adrenal gland. Thereby, a clear differentiation between normal and neoplastic adrenal tissue is often possible, which permits a planned partial resection of the gland in selected cases. Between July 1994 and November 2003 325 posterior retroperitoneoscopic adrenalectomies were performed for primary benign adrenal gland tumors (106 Conn's adenomas, 83 pheochromocytomas, 76 Cushing's adenomas, 60 nonfunctioning tumors; size: 2.8 +/- 1.5 cm; site: 160 right, 165 left) in 318 patients (122 M, 196 F, age: 49.0 +/- 14.3 years). In 96 patients 100 tumors were removed by partial adrenalectomy (30 Conn's adenomas, 33 pheochromocytomas, 20 Cushing's adenomas, 17 nonfunctioning tumors; site: 61 right, 59 left) maintaining tumor-free parts of the adrenal gland. Of this group, 15 patients suffered from bilateral adrenal neoplastic diseases. During the same period, 225 total adrenalectomies (76 Conn's adenomas, 50 pheochromocytomas, 56 Cushing's adenomas, 34 nonfunctioning tumors; site: 109 right, 116 left) were performed in 224 patients. There was no mortality. Major complications were seen in 1.8%, minor complications in 14.5%. Three conversions were necessary to an open or a laparoscopic approach (2 patients and 1 patient, respectively). There are no differences between the two groups (total versus partial adrenalectomy) with regard to tumor size (2.8 +/- 1.6 cm versus 2.8 +/- 1.5 cm), operating time (80 +/- 44 minutes versus 79 +/- 42 minutes), and blood loss (33 +/- 71 ml versus 29 +/- 31 ml). In all patients with partial adrenalectomy, biochemical healing was proven. Fourteen of 15 patients with bilateral diseases had preservation of adrenocortical function. After a mean follow up of 51 months (range: 7-120 months) local recurrence or relapse of the initial diseases was noticed in 6 patients after total adrenalectomy: in 4 patients with Conn's syndrome and bilateral hyperplasia, and in 2 patients with malignant pheochromocytoma and adrenocortical carcinoma, respectively. Our data demonstrate that partial adrenalectomy is a safe procedure not only perioperatively but also in the long-term follow-up.

Adrenal Cortex Neoplasms↗

[Cardiovascular effects of oral hypoglycemie drugs].

In the recent years there has been increasing interest in the effects of oral hypoglycemic drugs on the cardiovascular system. This has arisen because of recognitions that thiazolidine-diones, peroxisome proliferators-activated receptor gamma (PPAR-gamma), may have antiatherogenic actions and that sulphonylureas are capable of closing the ATP-dependent potassium channel. PPAR-gamma agonists exert antiatherogenic action by inhibition the production of monocyte inflammatory cytokines, inhibition of expression of adhesion molecules in endothelial cells, inhibition of the proliferation of vascular smooth muscle cells and have antioxidative effects. The United Kingdom Prospective Diabetes Study (UKPDS), published in 1998, found that the use of sulphonylureas had no increase in cardiovascular mortality and that metformin therapy in obese individuals with type 2 diabetes mellitus was associated with reduced cardiovascular death. Recently, the STOP-NIDDM trial has been shown that patients with impaired glucose tolerance treated with the alpha-glucosidase inhibitor acarbose had a significant reduction in the risk of cardiovascular disease. Currently, the results of the UKPDS trial are the only available clinical data on which to base the choice of treatment for type 2 diabetic patients. When a glucose-lowering oral drug is considered necessary and is not contraindicated, the firstline choice is a sulphonylurea or a glinide (repaglinide or nateglinide) for diabetics who are not overweight and metformin for those who are.

Administration, Oral↗