Reproductive endocrinologists are the gatekeepers for male infertility care in North America: results of a North American survey on the referral patterns and characteristics of men presenting to male infertility specialists for infertility investigations.

OBJECTIVE: To characterize the referral patterns and characteristics of men presenting for infertility evaluation using data obtained from the Andrology Research Consortium. DESIGN: Standardized male infertility questionnaire. SETTING: Male infertility centers. PATIENT(S): Men presenting for fertility evaluation. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Demographic, infertility history, and referral data. RESULT(S): The questionnaires were completed by 4,287 men, with a mean male age of 40 years ± 7.4 years and female partners age of 37 years ± 4.9 years. Most were Caucasian (54%) with other races being less commonly represented (Asian 18.6%, and African American 5.5%). The majority (59.7%) were referred by a reproductive gynecologist, 19.4% were referred by their primary care physician, 4.2% were self-referred, and 621 (14.5%) were referred by "other." Before the male infertility investigation, 12.1% of couples had undergone intrauterine insemination, and 4.9% of couples had undergone in vitro fertilization (up to six cycles). Among the male participants, 0.9% reported using finasteride (5α-reductase inhibitor) at a dose used for androgenic alopecia, and 1.6% reported exogenous testosterone use. CONCLUSION(S): This broad North American patient survey shows that reproductive gynecologists are the de facto gateway for most male infertility referrals, with most men being assessed in the male infertility service being referred by reproductive endocrinologists. Some of the couples with apparent male factor infertility are treated with assisted reproductive technologies before a male factor investigation. The survey also identified potentially reversible causes for the male infertility including lifestyle factors such as testosterone and 5α-reductase inhibitor use.

Is there a role for anterior zone sampling as part of saturation trans-rectal ultrasound guided prostate biopsy?

BACKGROUND: The prostatic anterior zone (AZ) is not targeted routinely by TRUS guided prostate biopsy (TRUS-Pbx). MRI is an accurate diagnostic tool for AZ tumors, but is often unavailable due to cost or system restrictions. We examined the diagnostic yield of office based AZ TRUS-Pbx. METHODS: 127 men at risk for AZ tumors were studied: Patients with elevated PSA and previous extended negative TRUS-Pbx (group 1, n = 78) and actively surveyed low risk prostate cancer patients (group 2, n = 49). None of the participants had a previous AZ biopsy. Biopsy template included suspicious ultrasonic areas, 16 peripheral zone (PZ), 4 transitional zone (TZ) and 6 AZ cores. All biopsies were performed by a single urologist under local peri-prostatic anaesthetic, using the B-K Medical US System, an end-firing probe 4-12 MHZ and 18 ga/25 cm needle. All samples were reviewed by a single specialized uro-pathologist. Multivariate analysis was used to detect predictors for AZ tumors accounting for age, PSA, PSA density, prostate volume, BMI, and number of previous biopsies. RESULTS: Median PSA was 10.4 (group 1) and 7.3 (group 2). Age (63.9, 64.5), number of previous biopsies (1.5) and cores (17.8, 21.3) and prostate volume (56.4 cc, 51 cc) were similar for both groups. The overall diagnostic yield was 34.6% (group 1) and 85.7% (group 2). AZ cancers were detected in 21.8% (group 1) and 34.7% (group 2) but were rarely the only zone involved (1.3% and 4.1% respectively). Gleason ≥ 7 AZ cancers were often accompanied by equal grade PZ tumors. In multivariate analysis only prostate volume predicted for AZ tumors. Patients detected with AZ tumors had significantly smaller prostates (36.9 cc vs. 61.1 cc p < 0.001). Suspicious AZ ultrasonic findings were uncommon (6.3%). CONCLUSIONS: TRUS-Pbx AZ sampling rarely improves the diagnostic yield of extended PZ sampling in patients with elevated PSA and previous negative biopsies. In low risk prostate cancer patients who are followed by active surveillance, AZ sampling changes risk stratification in 6% but larger studies are needed to define the role of AZ sampling in this population and its correlation with prostatectomy final pathological specimens.

Direct induction of CCK and GLP-1 release from murine endocrine cells by intact dietary proteins.

SCOPE: Consumption of high-protein diets cause elevated levels of CCK and GLP-1. Although unknown, this might be due to protein breakdown by various proteases that originate from the gastrointestinal tract. This study investigated which dietary proteins, hydrolysates, or synthetic-peptides are most potent to affect secretion of CCK and GLP-1 in STC-1 cells known for satiety hormone release. METHODS AND RESULTS: Addition of intact proteins to STC-1 cells exerted strong effects on secretion of satiety hormones. Casein, whey, and pea showed strongest effects on CCK release, whereas casein, codfish, egg, and wheat showed most pronounced effects on GLP-1 release. Egg-hydrolysate stimulated release of CCK and GLP-1, whereas all other tested hydrolysates and synthetic-peptides showed no significant effects on hormone release. Addition of a combination of trypsin and casein-hydrolysate, codfish, egg, egg-hydrolysate, sodium-casein, wheat-hydrolysate, or wheat resulted in additional stimulation of CCK release, compared to only the protein. Addition of a combination of DPP-IV and egg-hydrolysate, ovomucoid, or sodium-casein decreased GLP-1 levels. CONCLUSION: This study showed that specific intact, or partially digested proteins, in contrast to protein-hydrolysates and synthetic-peptides, stimulated hormone release. We conclude that intact proteins exert strong effects on satiety hormone release, and may therefore provide potent dietary supplements for prevention or treatment of obesity.

Butyrate modulates oxidative stress in the colonic mucosa of healthy humans.

BACKGROUND & AIMS: Butyrate, a short-chain fatty acid produced by colonic microbial fermentation of undigested carbohydrates, has been implicated in the maintenance of colonic health. This study evaluates whether butyrate plays a role in oxidative stress in the healthy colonic mucosa. METHODS: A randomized, double blind, cross-over study with 16 healthy volunteers was performed. Treatments consisted of daily rectal administration of a 60 ml enema containing 100 mM sodium butyrate or saline for 2 weeks. After each treatment, a blood sample was taken and mucosal biopsies were obtained from the sigmoid colon. In biopsies, the trolox equivalent antioxidant capacity, activity of glutathione-S-transferase, concentration of uric acid, glutathione (GSH), glutathione disulfide and malondialdehyde, and expression of genes involved in GSH and uric acid metabolism was determined. Secondary outcome parameters were CRP, calprotectin and intestinal fatty acid binding protein in plasma and histological inflammatory scores. RESULTS: Butyrate treatment resulted in significantly higher GSH (p<0.05) and lower uric acid (p<0.01) concentrations compared to placebo. Changes in GSH and uric acid were accompanied by increased and decreased expression, respectively, of their rate limiting enzymes determined by RT-PCR. No significant differences were found in other parameters. CONCLUSIONS: This study demonstrated that butyrate is able to beneficially affect oxidative stress in the healthy human colon.

Decreased hepatosplanchnic antioxidant uptake during hepatic ischaemia/reperfusion in patients undergoing liver resection.

Oxidative stress mediates cell injury during ischaemia/reperfusion. On the other hand, experimental findings suggest that ROS (reactive oxygen species) induce processes leading to ischaemic preconditioning. The extent and source of oxidative stress and its effect on antioxidant status in the human liver during intermittent ischaemia and reperfusion remains ill-defined. Therefore the aim of the present study was to investigate the occurrence of oxidative stress in humans undergoing liver resection. Liver biopsies, and arterial and hepatic venous blood samples were taken from ten patients undergoing hepatectomy with an intermittent Pringle manoeuvre. Plasma MDA (malondialdehyde) and hepatic GSSG levels were measured as markers of oxidative stress and plasma uric acid as a marker of xanthine oxidase activity. In addition, changes in hepatosplanchnic consumption of plasma antioxidants and hepatic levels of carotenoids and glutathione (GSH) were measured. After ischaemia, hepatosplanchnic release of MDA and increased hepatic GSSG levels were found. This was accompanied by the release of uric acid, reflecting xanthine oxidase activity. During reperfusion, ongoing oxidative stress was observed by further increases in hepatic GSSG content and hepatosplanchnic MDA release. Uric acid release was minimal during reperfusion. A gradual decrease in plasma antioxidant capacity and net hepatosplanchnic antioxidant uptake was observed upon prolonged cumulative ischaemia. Oxidative stress occurs during hepatic ischaemia in man mainly due to xanthine oxidase activity. Interestingly, the gradual decline in plasma antioxidant capacity and net hepatosplanchnic antioxidant uptake during prolonged cumulative ischaemia, preserved both hydrophilic and lipophilic hepatic antioxidant levels. Decreasing plasma levels and net hepatosplanchnic uptake of plasma antioxidants may warrant antioxidant supplementation, although it should be clarified to what extent limitation of oxidative stress compromises ROS-dependent pathways of ischaemic preconditioning.

Effectiveness of sperm banking in adolescents and young adults with cancer: a regional experience.

BACKGROUND: Improving success in the treatment of cancer has resulted in an increasing number of survivors. An important quality of life issue among younger survivors is the ability to have a family. Current gonadotoxic treatments for cancer pose a challenge to future fertility. Preservation of fertility after gonadotoxic therapy is an important consideration for these patients. In a regional center, the authors evaluated efficacy and utilization of sperm banking for preservation of male fertility in adolescents and young adults (AYA) with cancer. METHODS: A retrospective chart review was conducted to obtain data on clinical features, andrology, and fertility from patients (ages < 30 years) who cryopreserved samples of semen from 1995-2005. RESULTS: Of 821 newly diagnosed male AYA cancer patients, aged 14-30 years, only 146 (17.8%) used sperm cryopreservation technology. Patients who used their cryopreserved semen for attempted conception had a 36.4% success rate with intrauterine insemination (IUI) and a 50.0% clinical pregnancy rate with in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). CONCLUSIONS: Sperm cryopreservation by AYA males with cancer is an efficacious method for preserving future fertility. Awareness and employment of assisted reproductive technologies needs to be implemented by an interdisciplinary team of experts caring for these patients and can result in successful paternity in males after treatment for cancer.

Determination of the antioxidant capacity in blood.

BACKGROUND: A vast amount of scientific research is directed towards the beneficial effects of antioxidants on health. For this reason, several assays have been developed to determine the total antioxidant capacity of blood. METHODS: In this study two procedures based on the use of the green-blue 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical (ABTS(*+)) were compared. In the first (commercially available) procedure, ABTS(*+) was generated in the presence of the blood sample. In the second procedure, referred to as the decolorization assay, antioxidants react with preformed ABTS(*+). RESULTS: It was found that the first procedure leads to greater underestimation of the actual antioxidant capacity and is more prone to artifacts than the second procedure. Therefore, only the latter procedure was evaluated in detail and it appeared that (i) plasma is preferred over serum, (ii) the high background produced by albumin can be circumvented by deproteination, (iii) samples can be stored at -80 degrees C for 12 months, and (iv) the assay has high precision. Due to poor linearity, the procedure has to be standardized to allow sample comparison. CONCLUSIONS: The decolorization assay is a reliable and robust assay that can be applied routinely to predict the antioxidant capacity of blood.

Altered antioxidant status in peripheral skeletal muscle of patients with COPD.

Despite the growing field of interest in the role of pulmonary oxidative stress in chronic obstructive pulmonary disease (COPD), barely any data are available with respect to antioxidant capacity in the peripheral musculature of these patients. The main objective of this study was to assess in detail the antioxidant status in skeletal muscle of patients with COPD. Biopsies from the vastus lateralis of 21 patients with COPD and 12 healthy age-matched controls were analysed. Total antioxidant capacity, vitamin E, glutathione, and uric acid levels were determined and the enzyme activities of superoxide dismutase, glutathione reductase, glutathione peroxidase, and glutathione-S-transferase were measured. Malondialdehyde was measured as an index of lipid peroxidation. The total antioxidant capacity and the uric acid levels were markedly higher in COPD patients than in healthy controls (25%, P = 0.006 and 24%, P = 0.029, respectively). Glutathione-S-transferase activity was also increased (35%; P = 0.044) in patients compared to healthy subjects. Vitamin E level was lower in patients than in controls (P < 0.05). The malondialdehyde level was not different between the two groups. It can be concluded that the muscle total antioxidant capacity is increased in patients with COPD. Together with the reduced vitamin E levels, the increased glutathione-S-transferase activity and normal levels of lipid peroxidation products, these findings suggest that the antioxidant system may be exposed to and subsequently triggered by elevated levels of reactive oxygen species.

Role of superoxide anion on basal and stimulated nitric oxide activity in neonatal piglet pulmonary vessels.

The superoxide anion (O2*-) appears to be an important modulator of nitric oxide bioavailability. Enzymatic scavenging of O2*- is carried out by superoxide dismutase (SOD). The present study was designed to characterize the developmental changes on pulmonary vascular reactivity induced by 1) exogenous Cu/Zn SOD, 2) several putative SOD mimetics, and 3) endogenous SOD inhibition. We also analyzed age-related changes on pulmonary SOD activity and vascular O2*- levels. SOD (1-300 U/mL) produced endothelium-dependent relaxation of U46619-contracted intrapulmonary arteries (fourth branch) and veins from 12- to 24-h-old and 2-wk-old piglets. SOD-induced relaxation was greater in pulmonary arteries and was abolished by the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester. SOD induced a greater pulmonary artery relaxation in the 2-wk-old than in the 12- to 24-h-old piglet. SOD (100 U/mL) did not modify acetylcholine-induced relaxation in pulmonary arteries. In contrast, endogenous SOD inhibition by diethyldithiocarbamate (3 mM) impaired acetylcholine-induced relaxation in pulmonary arteries from newborn but not from 2-wk-old piglets. Total SOD activity in lung tissue did not change with postnatal age. With the use of dihydroethidium, an oxidant-sensitive fluorescent probe, we did not find significant age- or vessel-related differences in O2*- presence. From the putative SOD mimetics tested, only the metal salts MnCl2 and CuSO4 reproduced the vascular effects of SOD. In summary, SOD produces endothelium-dependent pulmonary vascular relaxation by protecting nitric oxide from destruction by O2*-. This effect was less marked in newborns than in 2-wk-old piglets. In contrast, pulmonary arteries from newborn piglets are more sensitive to the inhibition of endogenous SOD.