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Minimally invasive approaches to proctocolectomy with ileal pouch anal anastomosis have become the standard of care with one benefit being the reduced risk of adhesion-related complications. However, a lack of pouch adherence to the pelvis can lead to increased mobility as well as volvulization, placing pouch viability at risk. We aimed to describe our institutional experience with pouch volvulus.Patients who presented with pouch volvulus from 1983 to 2020 were identified through a search of our pelvic pouch registry and enterprise-wide electronic medical record. Pouch volvulus was defined as a reducible rotation of the J-pouch on its mesenteric axis with evidence of a properly oriented ileo-anal anastomosis. Patients with 'twisted pouches' were excluded.In total, 5760 patients underwent ileal pouch anal anastomosis from 1983 to 2020. Six patients (five women) were identified with a diagnosis of 'pouch volvulus' consistent with our definition. The six pouches were constructed utilizing laparoscopic techniques and the mean time from construction to volvulus was 2.36 years. All patients underwent urgent surgery, with a paucity of adhesions noted in five. Reduction and pouch pexy was performed in three and pouch excision in three, with immediate pouch reconstruction in two and end ileostomy creation in one. At a median follow-up of 9 months, pouch survival was 50%.Pelvic pouches constructed using minimally invasive techniques may be at risk of volvulus due to reduced adhesion development. A high index of suspicion is warranted in pouch patients with obstructive symptomatology. CT imaging may be diagnostic, and prompt surgical intervention may facilitate pouch salvage.

Objective:There is an ongoing debate on the potential negative effect of contact sport participation on long-term neurocognitive performance due to inherent exposure to concussive and subconcussive head impacts. The aim of the present study was to investigate whether cognitive ageing is exacerbated in elite soccer players compared to the general population.Method:Neurocognitive performance in 6 domains was compared between 240 elite soccer players and a normative sample from the general population (n = 585) using the computerised test battery CNS Vital Signs. We used two-way factorial ANOVA to analyse the interaction between age groups (15–19, 20–29, 30–39, 40–49 years) and study population (female soccer players vs. norm sample) in their effects on neurocognitive performance.Results:We found no significant interaction effect of age group and study population in five of six test domains. For processing speed, the effect of age was more pronounced in female soccer players (F= 16.89,p= .002). Further, there was a clear main effect of study population on neurocognitive performance with generally better scores in soccer players.Conclusions:Elite female soccer players generally performed better than the norm sample on tests of cognitive function, and further, cognitive ageing effects were similar in elite soccer players and controls in all but one domain. A lifespan approach may facilitate insightful future research regarding questions related to long-term neurocognitive health in contact sport athletes.

Background and Objectives Darolutamide is a novel androgen receptor (AR) antagonist approved for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC). Accordingly, the drug–drug interaction (DDI) potential of darolutamide was investigated in both nonclinical and clinical studies. Methods In vitro studies were performed to determine the potential for darolutamide to be a substrate, inducer or inhibitor for cytochrome P450 (CYP) isoforms, other metabolizing enzymes and drug transporters. A phase I drug-interaction study in healthy volunteers evaluated the impact of co-administering rifampicin [CYP3A4 and P-glycoprotein (P-gp) inducer] and itraconazole [CYP3A4, P-gp and breast cancer resistance protein (BCRP) inhibitor] on the pharmacokinetics of darolutamide. Two further phase I studies assessed the impact of co-administering oral darolutamide on the pharmacokinetics of midazolam (sensitive CYP3A4 substrate) and dabigatran etexilate (P-gp substrate) and the impact on the pharmacokinetics of co-administered rosuvastatin [a substrate for BCRP, organic anion-transporting polypeptide (OATP)1B1, OATP1B3 and organic anion transporter (OAT)3]. Results In vitro, darolutamide was predominantly metabolized via oxidative biotransformation catalyzed by CYP3A4 and was identified as a substrate for P-gp and BCRP. The enzymatic activity of nine CYP isoforms was not inhibited or slightly inhibited in vitro with darolutamide, and a rank order and mechanistic static assessment indicated that risk of clinically relevant DDIs via CYP inhibition is very low. In vitro, darolutamide exhibited no relevant induction of CYP1A2 or CYP2B6 activity. Inhibition of BCRP-, P-gp-, OAT3-, MATE1-, MATE2-K-, OATP1B1- and OATP1B3-mediated transport was observed in vitro. Phase I data showed that darolutamide exposure increased 1.75-fold with co-administered itraconazole and decreased by 72% with rifampicin. Co-administration of darolutamide with CYP3A4/P-gp substrates showed no effect or only minor effects. Rosuvastatin exposure increased 5.2-fold with darolutamide because of BCRP and probably also OATPB1/OATPB3 inhibition. Conclusions Darolutamide has a low potential for clinically relevant DDIs with drugs that are substrates for CYP or P-gp; increased exposure of BCRP and probably OATP substrates was the main interaction of note. Electronic supplementary material The online version of this article (10.1007/s13318-019-00577-5) contains supplementary material, which is available to authorized users.

Dysregulation of lipid metabolism is common in cancer. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been implicated with various cancer types. Here we analyzed by immunohistochemistry its expression in 2,197 breast cancers. LPCAT1 staining was found in 97.8% of 1,774 interpretable tumors, including 48.1% with weak, 28.7% with moderate, and 14.4% with strong expression. The frequency of LPCAT1 positivity depended on the histological tumor type. Moderate or strong LPCAT1 positivity was more common in cancers of no special type (NST) (46.2%) than in lobular carcinomas (25.9%; p

The growth of uterine fibroids is sex hormone-dependent and commonly associated with highly incapacitating symptoms. Most treatment options consist of the control of these hormonal effects, ultimately blocking proliferative estrogen signaling (i.e., oral contraceptives/antagonization of human gonadotropin-releasing hormone receptor [hGnRH-R] activity). Full hGnRH-R blockade, however, results in menopausal symptoms and affects bone mineralization, thus limiting treatment duration or demanding estrogen add-back approaches. To overcome such issues, we aimed to identify novel, small-molecule hGnRH-R antagonists. This led to the discovery of compound BAY 1214784, an orally available, potent, and selective hGnRH-R antagonist. Altering the geminal dimethylindoline core of the initial hit compound to a spiroindoline system significantly improved GnRH-R antagonist potencies across several species, mandatory for a successful compound optimization in vivo. In a first-in-human study in postmenopausal women, once daily treatment with BAY 1214784 effectively lowered plasma luteinizing hormone levels by up to 49%, at the same time being associated with low pharmacokinetic variability and good tolerability.

BackgroundAdverse long-term effects of playing football due to repetitive head impact exposure on neurocognition and mental health are controversial. To date, no studies have evaluated such effects in women.AimsTo (1) compare neurocognitive performance, cognitive symptoms and mental health in retired elite female football players (FB) with retired elite female non-contact sport athletes (CON), and to (2) assess whether findings are related to history of concussion and/or heading exposure in FB.MethodsNeurocognitive performance, mental health and cognitive symptoms were assessed using computerised tests (CNS-vital signs), paper pen tests (Category fluency, Trail-Making Test, Digit Span, Paced Auditory Serial Addition Test), questionnaires (Hospital Anxiety and Depression Scale, SF-36v2 Health Survey) and a symptom checklist. Heading exposure and concussion history were self-reported in an online survey and in a clinical interview, respectively. Linear regression was used to analyse the effect of football, concussion and heading exposure on outcomes adjusted for confounders.ResultsFB (n=66) performed similar to CON (n=45) on neurocognitive tests, except for significantly lower scores on verbal memory (mean difference (MD)=−7.038, 95% CI −12.98 to –0.08, p=0.038) and verbal fluency tests (MD=−7.534, 95% CI –13.75 to –0.46, p=0.016). Among FB weaker verbal fluency performance was significantly associated with ≥2 concussions (MD=−10.36, 95% CI –18.48 to –2.83, p=0.017), and weaker verbal memory performance with frequent heading (MD=−9.166, 95% CI –17.59 to –0.123, p=0.041). The depression score differed significantly between study populations, and was significantly associated with frequent heading but not with history of concussion in FB.ConclusionFurther studies should investigate the clinical relevance of our findings and whether the observed associations point to a causal link between repetitive head impacts and verbal memory/fluency or mental health.

Background Continuous epidural infusion (CEI) is the standard application setting for epidural infusion. A new mode, the programmed intermittent epidural bolus (PIEB) technique, showed reduced local anesthetic (LA) consumption and improved analgesia in obstetric analgesia. Goal of this trial was to evaluate the effects of PIEB versus CEI [combined with patient-controlled bolus (PCEA)] on LA consumption and pain scorings in major abdominal cancer surgery. Methods Following ethical approval, patients scheduled for major abdominal cancer surgery under general anesthesia in combination with epidural analgesia were randomized to receive either a PIEB mode of 6 mL/h or a CEI mode set at 6 mL/h of ropivacaine 0.2%, both combined with a PCEA mode set at a 4 mL bolus. LA consumptions and pain scorings were documented until the second postoperative evening. Results Eighty-four datasets were analyzed (CEI: n = 40, PIEB: n = 44). Regarding the primary endpoint, cumulative LA PCEA bolus volumes until day 2 differed significantly between the groups [PIEB 10 mL (2–28 mL) versus CEI, 28 mL (12–64 mL), median (25th–75th percentiles), p = 0.002]. Overall, LA consumption volumes were significantly lower in the PIEB group versus in the CEI group [PIEB: 329 mL (291–341 mL) vs. CEI: 350 mL (327–381 mL), p = 0.003]. Pain scores were comparable at each time point. Conclusions This trial demonstrates reduced needs for PCEA bolus in the PIEB group. There were no clinically relevant benefits regarding morphine consumption, pain scorings, or other secondary outcome parameters. Trial registration This study has been registered retrospectively in the ClinicalTrials.gov registry (NCT03378804), date of registration: December, 20th 2017. Electronic supplementary material The online version of this article (10.1186/s12871-018-0613-6) contains supplementary material, which is available to authorized users.

Objective Concussion diagnosis and management in sports largely relies on neurocognitive testing. In the absence of baseline assessment, only norm values of the general population are available for comparison with scores of concussed athletes. To evaluate whether (elite) sport specific norm values are needed, cognitive performance was compared between top-level football players and the general population. Methods Cognitive performance of 425 top-level football players was evaluated using the computerized test battery CNS Vital Signs. Players were split into two age groups (15-19 and 20-29 years) and test results were compared with a norm sample (n = 268) by means of age-standardized scores using Cohen's d effect size statistics. Results The younger age group outperformed the norm sample in all domains, with small to moderate effects on tests of processing speed (d = 0.58, 95% CI = 0.31,0.85), cognitive flexibility (d = 0.27, 95% CI = 0.01,0.53) and psychomotor speed (d = 0.97, 95% CI = 0.69,1.24). In the older age group, no differences were found on four out of six domains; a moderate positive effect was found for psychomotor speed (d = 0.74, 95% CI = 0.54,0.93), a small negative effect for reaction time (d = -0.47, 95% CI = -0.66,-0.28). Relative to the norm, older football players scored lower than younger football players on all test domains. Conclusion Cognitive performance of elite football players may be different from the general population. It is recommended to use football-specific norm scores for comparison with test results of concussed players, and to choose an adequate control group when investigating effects of contact sport on cognition. Studies with older/retired football players are needed to further analyze potential sport-specific age effects.

Background Preclinical and clinical studies suggest amantadine immediate-release (IR) may reduce dyskinesia in Parkinson’s disease (PD), although higher doses are associated with increased CNS adverse events (AEs). ADS-5102 is an extended release amantadine capsule formulation, designed for once-daily dosing at bedtime (qhs) to provide high concentrations upon waking and throughout the day, with lower concentrations in the evening. The pharmacokinetics (PK) of ADS-5102 were assessed in two phase I studies in healthy subjects, and a blinded, randomized phase II/III dose-finding study in PD patients. Methods The first phase I study assessed single ADS-5102 doses (68.5, 137, and 274 mg) in a crossover design, whereas the second phase I study evaluated ADS-5102 137 mg for 7 days followed by amantadine IR 81 mg twice daily (or reverse order). In the phase II/III double-blind study, PD patients with dyskinesia were randomized to ADS-5102 (210, 274, or 338 mg) or placebo for 8 weeks. Results Single ADS-5102 doses resulted in a slow initial rise in amantadine plasma concentration, with delayed time to maximum concentration (12–16 h). Amantadine plasma concentrations were higher in PD patients versus healthy volunteers. The steady-state profile of once-daily ADS-5102 was significantly different from that of twice-daily amantadine IR, such that the two formulations are not bioequivalent. PK modeling suggested the recommended daily ADS-5102 dosage (274 mg qhs) resulted in 1.4- to 2.0-fold higher amantadine plasma concentrations during the day versus amantadine IR. Conclusions ADS-5102 can be administered once-daily qhs to achieve high amantadine plasma concentrations in the morning and throughout the day, when symptoms of dyskinesia occur. Electronic supplementary material The online version of this article (10.1007/s40262-018-0663-4) contains supplementary material, which is available to authorized users.

Background and objectives In-vitro data suggest that clearance of vilaprisan is mediated by cytochrome P450 3A4 (oxidation) and aldoketoreductases (reduction). To fully understand the elimination and biotransformation pathways of vilaprisan, a selective progesterone receptor modulator, and to quantify the impact of cytochrome P450 3A4 inhibition on the pharmacokinetics of vilaprisan, two clinical studies in healthy postmenopausal women were conducted. Methods In study 1, pharmacokinetics, mass balance, and metabolite patterns were determined after single oral administration of 5 mg of [14C]-labeled vilaprisan in six subjects. In study 2, pharmacokinetics were determined after single oral administration of 4 mg of vilaprisan without and with concomitant administration of the strong cytochrome P450 3A4 inhibitor itraconazole (200 mg/day) in 14 subjects. In addition, a microtracer dose of vilaprisan was given intravenously to determine absolute bioavailability, clearance, and volume of distribution. Results The dominant single compound in plasma was vilaprisan. No plasma metabolites exceeding 10% of total drug-related area under the concentration–time curve were detected. The absolute oral bioavailability of vilaprisan was ~ 60%. The mean clearance was ~ 7 L/h and the volume of distribution at steady state was ~ 360 L. Excretion occurred primarily via feces (73.5 ± 3.70% of dose; urine: 13.1 ± 1.71%; total recovery: 86.6 ± 2.81%), mostly in a metabolized form. Only small amounts of the parent drug were found in excreta. When vilaprisan was administered together with itraconazole, exposure to vilaprisan was increased 6.2-fold (90% confidence interval 5.4–7.2). Conclusions Vilaprisan is predominantly metabolized in the liver to a complex variety of metabolites, which are mainly excreted with feces. The pivotal role of cytochrome P450 3A4 in the metabolism of vilaprisan was confirmed. Clinical Trial Registration EudraCT numbers 2013-000707-16 (mass balance study) and 2014-004929-41 (drug–drug interaction/microtracer study); NCT02456129 (drug–drug interaction/microtracer study). Electronic supplementary material The online version of this article (10.1007/s40262-017-0607-4) contains supplementary material, which is available to authorized users.

Embryo cryopreservation offers many benefits by allowing genetic preservation, genetic screening, cost reduction, global embryo transport and single embryo transfer. However, freezing of embryos decreases embryo viability, as intracellular ice crystal formation often damages embryos. Success rates of frozen embryo transfer are expected to be 15-20% less than fresh embryo transfer. We have developed a noninvasive embryo assessment technique (NEAT) which enables us to predict embryo viability based on buoyancy. The purpose of this research was twofold. First was to determine if a NEAT, through a specific gravity device can detect embryo survival of cryopreservation. Second, it was to relate embryo buoyancy to embryo viability for establishing pregnancies in sheep. Blastocysts descent times were measured on one-hundred sixty-nine mice blastocysts before cryopreservation, according to standard protocol and post-thawing blastocysts descent times were measured again. There was a significant difference in blastocyst post-thaw descent times with NEAT in those blastocysts which demonstrated viability from those that did not (P 0.05). This suggests NEAT is successful in determining blastocysts viability in cryopreserved mice blastocysts. At a commercial ovine facility, NEAT was performed on fourteen frozen and thawed ovine blastocysts. Blastocysts of similar descent times were paired and transferred into recipient ewes as twins. Pregnancy was later confirmed by blood test and multiple gestation outcomes were determined at lambing. Six of seven recipient ewes were pregnant and all pregnant ewes delivered lambs without complication. Four ewes delivered twin lambs and two ewes delivered singletons, which totals ten of the fourteen (71%) blastocysts surviving to term. This pregnancy rate is comparable to expected to pregnancy rates in a commercial setting. The blastocysts which did not establish pregnancy demonstrated less buoyancy versus those blastocysts which established pregnancies which survived to term (P 0.05). These results suggest NEAT can identify which blastocysts survive cryopreservation, thus significantly reduce the transfer of non-viable embryos. Further studies on a larger scale commercial setting will evaluate the efficacy of NEAT.

Background: Although injuries to the head represent a small proportion of all sport injuries, they are of great concern due to their potential long-term consequences, which are even suspected in mild traumatic brain injuries. Objective: The aim of this review was to compare the incidence of concussions and other head injuries in elite level football, rugby, ice hockey and American Football. Methods: Four electronic databases (CINAHL, PsycINFO, Web of Science, PubMed) were searched. Prospective cohort studies on the incidence of concussion in elite athletes aged 17 years or older that were published in an English-language peer-reviewed journal since 2000 were included. Two authors independently evaluated study eligibility and quality. The extracted data on concussions were pooled in a meta-analysis using an inverse-variance fixed-effects model. The extracted data on head injuries were reported in a narrative and tabular summary. Results: The search yielded 7673 results of which 70 articles were included in the qualitative and 47 in the quantitative analysis. In our meta-analysis, we found the highest concussion incidences in rugby match play (3.89 and 3.00 concussions per 1000 h and athletic exposures (AEs), respectively), and the lowest in men’s football training (0.01 and 0.08 per 1000 h and AEs, respectively). Overall, concussions and all head injuries were rare in training when compared to match play. Female players had an increased concussion risk in football and ice hockey when compared to male players. Conclusion: Future research should focus on concussion in women’s contact sports, as there is little evidence available in this area. Methodological deficits are frequent in the current literature, especially regarding sample size and study power, and should be avoided.

Introduction: The primary aim of this study was to compare the objective and subjective outcomes and short-term complication rates of an adjustable single-incision mini-sling (SIMS) vs. standard mid-urethral slings (SMUS). The secondary aim was to report pain perception and complications at the one-year follow up. Material and methods: The study was designed as a multicenter prospective randomized trial where women were included from eight centers in Denmark, Norway and Sweden. The trial was registered at ClinicalTrials.gov: NCT01754558. A total of 305 women less than 60 years old with verified stress urinary incontinence were included. All women were randomized to SIMS (Ajust ®; n = 155) or SMUS (TVT, TVT-O or TOT; n = 150) and were evaluated by stress test and bladder diary before and after surgery and symptoms related to incontinence using ICIQ-SF, PISQ-12 and PGI-S and PGI-I. Objective cure was defined as no leakage during a stress test and subjective cure defined as no leakage stated in the bladder diary or no indication of urinary leakage in the ICIQ-SF. Furthermore, mesh exposure and dyspareunia were recorded. Results: In total, 280 women [141 (91%) in the SIMS and 139 (94%) in the SMUS groups] participated in the one-year follow up. No difference between the groups was observed regarding objective and subjective outcomes. VAS score disclosed a lower postoperative pain perception in the SIMS group than in the SMUS group. Conclusions: Ajust ® appears to be as efficient as SMUS regarding objective and subjective outcomes and was associated with less pain perception during the postoperative period.

Background The variability of published acupuncture protocols for patients undergoing In-Vitro Fertilization (IVF) complicates the interpretation of data and hinders our understanding of acupuncture’s impact. In 2012, an acupuncture treatment protocol developed by a Delphi consensus process was published to describe the parameters of best practice acupuncture for Assisted Reproductive Technology and future research. However, there has been no clinical trial utilizing this protocol to assess the effects of acupuncture. This study aims to a sse ss the implementation of Dephi consensus acupuncture protocol and to examine the impact of acupuncture on stress and uterine and ovarian blood flow among women between ages 21-42 years seeking IVF. Methods/Design This study is a one site prospective, two-arm randomized controlled non-blind clinical trial conducted in a medical school-affiliated fertility center . Participants will be randomized 1:1 into either the acupuncture group or the standard of care (no acupuncture) group using computer generated tables. Both groups will have 3 regular clinical visits as their standard IVF care during an approximately 2 to 3 weeks window. Women who are randomized into the acupuncture group would receive three sessions based on the Delphi consensus acupuncture protocol in addition to the standard care. The first treatment will be administered between days 6 to 8 of the stimulated IVF cycle. The second session will be performed on the day of embryo transfer at least 1 h prior to the transfer. The third session will be performed within 48 h post-embryo transfer. Participants will be followed for their pregnancy test and pregnancy outcome when applicable. The outcomes stress and blood flow will be measured by a validated perceived stress scale and vasoactive molecules, respectively. Discussion Although recruitment and scheduling could be challenging at times, the Delphi consensus acupuncture protocol was implemented as planned and well-accepted by the patients. Because of the time-specified sessions around patients’ IVF cycle, it is highly recommended to have on-site study acupuncturist(s) to accommodate the schedule. Trial Registration ClinicalTrials NCT02591186 registered on October 7, 2015. Electronic supplementary material The online version of this article (doi:10.1186/s12906-017-1693-4) contains supplementary material, which is available to authorized users.

The aim of this study was to assess the prevalence of health problems and associated risk factors in former elite female football players. A cross-sectional research design was employed, using an online questionnaire on personal characteristics and health complaints during/after the career. One hundred fifty-two (response rate: 62.0%) former first German league players answered the survey. Around 70% described their current health as good or very good. Over half (57.9%) reported knee problems during the last 4 weeks while exercising and a third (33.6%) during normal daily activities. The second most common location for complaints was the head (53.3%). Almost one quarter (23.7%) of players suffered from osteoarthritis (OA). Regression analysis showed that OA in knee/ankle and physical complaints (PC) in knee/ankle/head were significantly predicted by number and severity of previous injuries (P

We compared cure rates of tension-free vaginal tape (TVT) with intravaginal slingplasty (IVS) and evaluated changes in cure rates over time.One hundred three underwent TVT and 213 underwent IVS. Follow-ups were done at 3 months, 1 year, and 5 years.The following results were found: objective cure for TVT 98-95-94% vs. IVS 86-86-80% (p0.03); subjective cure for TVT 82-79-74% vs. IVS 79-81-71% (NS). In IVS, a significant decline in subjective cure took place. Vaginal erosions were found in 11.8% of women in the IVS group and none in the TVT group.TVT is an effective and stable treatment, whereas IVS has a significant inferior objective cure rate, and a significant decline in subjective cure rate occurred over time. A high rate of vaginal erosions was found in the IVS group. We cannot recommend the use of multifilament polypropylene tape (IVS) for surgical treatment of stress urinary incontinence.

Background Epidemiological information on injury/illness is required to develop effective injury prevention strategies. Aim To assess the frequency and characteristics of injuries/illnesses (1) in the 4 weeks prior to and (2) during the Federation Internationale de Natation (FINA) World Championships 2015 compared with 2013 and 2009. Method (1) Athletes answered a retrospective questionnaire, and (2) the medical staff reported injuries/illnesses prospectively during the championships. Results (1) A quarter of responding athletes reported symptoms in the 4 weeks prior to the championships. More than half of all affected athletes presented with substantial severity, 80% took medication, 70% had overuse injuries and 30% did not modify their training regime despite symptoms. At the start of the championships, 70% of affected participants were still symptomatic. (2) During the championships, injury and illness incidence was 12.9 per 100 athletes. The most common injuries were shoulder sprains (5.7%) and muscle cramps of the lower back (5.7%). The most common illnesses were infections of the respiratory (33.9%) and gastrointestinal tract (23.5%). Risk factors included discipline and age, but not gender. Incidence was highest in athletes competing in high diving (HD), water polo (WP) and diving (DIV) for injuries, and WP and swimming (SW) for illnesses. The significantly higher incidence of injuries and illnesses at the FINA World Championships 2015 compared with 2013 and 2009 was most probably due to a similarly improved response rate of the medical staff. Conclusions In aquatic sports, surveillance and health promotion should focus on prevention of out-of-competition overuse injuries and athlete education.

Condoms have proven effective when used correctly; however, few studies have examined the relationship between a student's previous sex education and his or her general condom knowledge and ability to use a condom correctly. Educational systems in Texas provide a myriad of types of sexual education to their student populations. The objective of the present study was to compare the type of previous sex education with the condom knowledge and condom use skills among students attending college. Participants were recruited at health fairs conducted at a major Texas university during October 2010 and March 2011. Students were first asked to complete a computerized questionnaire and then participated in a condom demonstration. Of 180 students who completed both the questionnaire and the condom demonstration, 67% failed to apply the condom correctly. Further, the results were equally poor regardless of previous sex education format. The results of this study suggest that none of the current training mechanisms provide adequate information to ensure the proper use of condoms by college students and that alternatives need to be considered to protect the health and well-being of this important segment of the state's population.

Objective— The molecular mechanisms underlying sex differences in dyslipidemia are poorly understood. We aimed to distinguish genetic and hormonal regulators of sex differences in plasma lipid levels. Approach and Results— We assessed the role of gonadal hormones and sex chromosome complement on lipid levels using the four core genotypes mouse model (XX females, XX males, XY females, and XY males). In gonadally intact mice fed a chow diet, lipid levels were influenced by both male–female gonadal sex and XX–XY chromosome complement. Gonadectomy of adult mice revealed that the male–female differences are dependent on acute effects of gonadal hormones. In both intact and gonadectomized animals, XX mice had higher HDL cholesterol (HDL-C) levels than XY mice, regardless of male–female sex. Feeding a cholesterol-enriched diet produced distinct patterns of sex differences in lipid levels compared with a chow diet, revealing the interaction of gonadal and chromosomal sex with diet. Notably, under all dietary and gonadal conditions, HDL-C levels were higher in mice with 2 X chromosomes compared with mice with an X and Y chromosome. By generating mice with XX, XY, and XXY chromosome complements, we determined that the presence of 2 X chromosomes, and not the absence of the Y chromosome, influences HDL-C concentration. Conclusions— We demonstrate that having 2 X chromosomes versus an X and Y chromosome complement drives sex differences in HDL-C. It is conceivable that increased expression of genes escaping X-inactivation in XX mice regulates downstream processes to establish sexual dimorphism in plasma lipid levels.

The molecular mechanisms underlying sex differences in dyslipidemia are poorly understood. We aimed to distinguish genetic and hormonal regulators of sex differences in plasma lipid levels.We assessed the role of gonadal hormones and sex chromosome complement on lipid levels using the four core genotypes mouse model (XX females, XX males, XY females, and XY males). In gonadally intact mice fed a chow diet, lipid levels were influenced by both male-female gonadal sex and XX-XY chromosome complement. Gonadectomy of adult mice revealed that the male-female differences are dependent on acute effects of gonadal hormones. In both intact and gonadectomized animals, XX mice had higher HDL cholesterol (HDL-C) levels than XY mice, regardless of male-female sex. Feeding a cholesterol-enriched diet produced distinct patterns of sex differences in lipid levels compared with a chow diet, revealing the interaction of gonadal and chromosomal sex with diet. Notably, under all dietary and gonadal conditions, HDL-C levels were higher in mice with 2 X chromosomes compared with mice with an X and Y chromosome. By generating mice with XX, XY, and XXY chromosome complements, we determined that the presence of 2 X chromosomes, and not the absence of the Y chromosome, influences HDL-C concentration.We demonstrate that having 2 X chromosomes versus an X and Y chromosome complement drives sex differences in HDL-C. It is conceivable that increased expression of genes escaping X-inactivation in XX mice regulates downstream processes to establish sexual dimorphism in plasma lipid levels.

It was the aim of this study to record common diseases in dairy cows in Schleswig-Holstein, Germany, and to describe associations between lactation number (LN: 1, 2,2), first test-day milk yield (TD1:30 kg, ≥ 30 kg) and herd milk yield (HM: ≤ 7500 kg,7500 kg), the latter parameter serving as a proxy for herd management (extensive vs. intensive). Data of 98 dairy herds (6439 lactations) were processed on cow level using mixed logistic regression models with LNTD1, HM and calving season as fixed effects and herd as random effect. Lactational incidences were as follows: hypocalcaemia (5.0%), dystocia (13.2%), retained placental membranes (7.2%), clinical metritis/endometritis (4.9%), clinical mastitis (15.3%), subclinical mastitis (61.9%), ketosis (1.6%), displaced abomasum (0.4%), lameness (15.4%). Number of lactation (2,2 vs. 1) was a risk factor for hypocalcaemia (OR 3.715, 23.047), retained placental membranes (OR 1.764, 2.479), clinical mastitis (2 vs. 1 OR 2.118), subclinical mastitis (OR 1.668,4.397), ketosis (2 vs. 1 OR 3.936) and lameness (OR 1.275, 2.070). Older cows had a lower risk for dystocia (OR 0.373, 0.357). TD1 (≥ 30 kg) was not a risk factor of disease except for subclinical mastitis in first parity animals (OR 1.319). Herd milk yield (7500 kg) was a risk factor for clinical metritis/endometritis (OR 1.971), displaced abomasum (OR 7.764), lameness (OR 1.618) and hypocalcaemia (cows with high TD1 [OR 2.273]). In conclusion, not individual milk yield, but herd milk yield as an indicator of differences in intensity of herd management as well as number of lactation seemed to influence the frequency of common diseases in dairy cows.

Previous research has suggested a correlation between the subtle rise in progesterone induced by the administration of human chorionic gonadotropin (hCG) and cycle outcome in patients undergoing in vitro fertilization with embryo transfer (IVF-ET). The data suggest that patients who have2-fold increase in progesterone levels will not conceive as a result of that IVF-ET attempt (poor responders). Further, if the luteinizing-granulosa cells of poor responders are placed in culture, their steroid hormone production will be significantly less than that of the luteinizing-granulosa cells of patients with a normal response to hCG (3-fold; normal responders). Recent studies have demonstrated that steroidogenic acute regulatory protein (StAR) regulates the rate-limiting step in steroid hormone biosynthesis. The objective of the present study was to determine whether StAR expression differed in normal responders and poor responders undergoing IVF-ET.The luteinizing-granulosa cells of 6 patients were isolated after follicular aspiration and assayed for StAR expression. Three sets of cells were from patients exhibiting a normal response to hCG administration and 3 sets were from patients exhibiting a poor response.Data suggest a 17% drop in StAR protein in patients with a poor response to hCG administration when compared with those with a normal response.Although StAR protein was expressed in all 6 cellular extracts, expression appeared greatest in cells recovered from normal responders. Further, although two thirds of the patients with a normal response reported term pregnancies, no pregnancies were reported in the poor responders. Low levels of progesterone and absence of pregnancy may be due to a defect in the mechanism that converts granulosa and theca-lutein cells to luteal cells after the luteinizing hormone surge (or hCG administration). Data from the current study would suggest that the StAR protein may be involved.

To examine the changes in stone composition from 1990 to 2010. A retrospective review was performed of all renal and ureteral stones submitted from the state of Massachusetts to a single laboratory (Laboratory for Stone Research, Newton, MA) for the years 1990 and 2010. Stone composition was determined by infrared spectroscopy and/or polarizing microscopy. A total of 11,099 stones were evaluated (56.7% from 1990, 43.3% from 2010). From 1990 to 2010, the percentage of stones from females (i.e., female/male ratio) increased significantly (29.8% in 1990 to 39.1% in 2010, p0.001). Among women, from 1990 to 2010, there was a significant increase in stones which were50% uric acid (7.6-10.2%, p0.005) and a significant decrease in struvite stones (7.8-3.0%, p0.001). Among women with calcium stones, the % apatite per stone decreased significantly (20.0 vs. 11.7%, p0.001). Among men, there were no changes in stones which were majority uric acid (11.7-10.8%, p = 0.2). Among men with calcium stones, the % apatite per stone increased significantly (9.8 vs. 12.5%, p0.001). Males also demonstrated a significant increase in both cystine (0.1-0.6%, p0.001) and struvite stones (2.8-3.7%, p = 0.02). The epidemiology of stone disease continues to evolve and appears to vary according to gender. While some of these findings may be related to population changes in body mass index and obesity, the etiology of others remains unclear.

In supervisory selection and development it is important to assess individuals' supervisory competencies. In a field study, the Test of Supervisory Skills was validated against a surrogate criterion of supervisory performance, based upon position classification and supervisory experience. Subjects ( N = 2,406), workers and applicants of both sexes, were recruited from multiple sources, tested, and the data analyzed to evaluate the usefulness of the test in human resource management applications. Both the current and prior results show significant relationships between scores on this test and various criteria of supervisory performance.

Chronically instrumented awake healthy sheep (n = 6) received the synthetic catecholamine, dopexamine, during or without a background infusion of the nitric oxide synthase inhibitor. L-nitro-arginine-methylester (L-NAME). Three days later, hypotensive-hyperdynamic circulation was induced and maintained by continuous infusion of Salmonella typhosa endotoxin (10 ng/kg per min). After 24 h of continuous endotoxin infusion, the dopexamine L-NAME protocol was repeated. In healthy and endotoxaemic animals with and without nitric oxide synthase inhibition dopexamine caused the same haemodynamic changes: heart rate and cardiac output increased, mean arterial pressure and systemic vascular resistance decreased. L-NAME infusion induced normalisation of the hypotonic-hyperdynamic circulation in endotoxaemic animals. Dopexamine reduced some adverse effects of L-NAME treatment, like increased pulmonary vascular resistance and decreased oxygen delivery. In conclusion the haemodynamic effects of dopexamine are independent of the amount of nitric oxide production. Dopexamine may attenuate some of the adverse effects of nitric oxide synthase inhibition.

Health days are an established forum for prevention and health promotion for different groups in the general population. Through the use of modular questionnaires "Global Risk Assessment" (GloRiA) on computers (handheld and desktop), the recording of patient data and presentation of the results can be optimized. Possible applications include identification of risk factors, early detection of patients at risk, epidemiology and health services research, promotion of patient adherence by visualizations (e.g. risk scores). Up to 12 different question modules are available (e.g. risk for the occurrence of cardiovascularevents by Framingham score, forfuture riskof diabetes mellitus using FindRisk score, smoking, COPD, pain, comorbidities).During 57 health days in 2010 and 2011, data were collected from 3451 persons (53% women, mean age 59.6 +/- 15.4 years) using GloRiA. The percentage of former smokers was 32.7%, while that of current smokers was 14.7%. The average 10-year risk based on the Framingham score (calculated with 1739 persons) in 53.7% of respondents was at10%, in 37.0% at 10-20%, and in 9.3% at20%. In men risk was higher than in women. Smoking cessation would theoretically reduce the mean 10-year risk from 10.9 +/- 9.2% to 7.4 +/- 6.6%. In 50.5% of participants blood pressure measurement revealed elevated values, and in 10% or 2%, respectively, a moderately high or high 10-year riskof incident diabetes mellitus according to FindRisk.The use of GloRiA for the consolidation of health data under the framework of health days provides new and sustained possibilities in early detection of cardiovascular disease. The calculation and visualization of risks and the impact of treatment decisions, e.g. reduction of cardiovascular risk by smoking cessation, were communicated directly to the participants. The individual health report facilitates the diagnostic procedures bya physician.

To investigate the hypothesis that nitric oxide synthase (NOS) inhibition restores the vasopressor response to norepinephrine (NE) in ovine hyperdynamic sepsis, eight sheep were chronically instrumented. In the non-septic portion of the study, NE was titrated to achieve an increase in mean arterial pressure (MAP) by 15 mm Hg ("small dose"). Small-dose NE was repeated 1 h after administration of the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME; bolus 5 mg/kg, followed by 1 mg.kg-1.h-1). After 3 days of recovery, sepsis was induced by a continuous endotoxin infusion (Salmonella typhosa, 10 ng.kg-1.h-1). Three animals died during this period (data excluded). After 24 h, small-dose NE was given. If MAP increased less than 15 mm Hg, the NE dose was increased to achieve the targeted MAP change ("large dose"). Finally, both doses of NE were given after L-NAME administration. To increase MAP by 15 mm Hg in nonseptic animals, the rate of NE infusion was 0.18 +/- 0.03 microgram.kg-1.min-1 (small dose). During L-NAME infusion, this NE dose increased MAP by 32 +/- 8 mm Hg. In septic animals, small-dose NE increased MAP by only 9 +/- 2 mm Hg (P < 0.05 versus nonseptic state). To increase MAP by 15 mm Hg, the NE dose had to be increased to 0.34 +/- 0.06 microgram.kg-1.min-1 (large dose). During L-NAME infusion, NE administration increased MAP by 16 +/- 2 mm Hg and 28 +/- 4 mm Hg (small and large dose, respectively). Thus, L-NAME restored the vasopressor response to NE in sepsis, and increased the vasopressor response to NE in a similar fashion in healthy and septic sheep.

Objective To evaluate coagulation parameters during IVF cycles with elevated E2. Design Prospective clinical study. Setting Human volunteers in an IVF clinic. Patients Infertile women undergoing IVF procedures. Interventions Coagulation factors were measured in blood along with E2 and P after singular hMG or leuprolide acetate (LA) plus hMG up to 14 days after hCG. Main outcome measures Plasma coagulation factors. Results Some coagulation factors were statistically but not clinically elevated after LA-hMG-induced hyperestrogenism. For the most part, this was not correlated with E2. Conclusion This study suggests that endogenous E2 increases due to fertility drugs cause a molecular activation of some coagulation factors, which do not result in an increased thrombosis.

We have developed a one-hour standardised, accelerated diagnostic investigation programme to evaluate women with urinary incontinence (UI). The purpose of the study was to record how many patients followed the programme and had a diagnosis and a treatment plan after a one-hour visit and to describe the causes of deviation from the programme. A second purpose was to monitor patient satisfaction.In this retrospective cohort study, 276 women with the diagnosis UI participated. All patients completed a standardised investigation programme that included their medical history and an evaluation of the fluid/urination schedule. Before patients left the clinic, they were given a diagnosis and a treatment plan.A total of 91% of the patients underwent examination and had a treatment plan after one consultation; 9% made multiple visits. The median patient age was 59 years (range 17-99 years); body mass index was 27 kg/m² (range 18-50 kg/m²); and the number of childbirths was 2.4; no significant difference were observed between the two groups. In the multiple-visits group, the number of previous gynaecological surgical procedures was significantly larger (67% versus 32%). These patients had significantly more chronic diseases (88% versus 58%). A total of 81 patients completed a post-examination questionnaire and (99%) were satisfied with the accelerated programme.A total of 91% of the patients underwent an examination and received a treatment plan after one consultation; 9% paid several visits due to chronic diseases and previous gynaecological surgery. The patients expressed great satisfaction with the accelerated investigation programme.not relevant.not relevant.

To determine: 1) if 18 mg iron daily is sufficient to cover the iron need during normal pregnancy, and 2) if women, who will not need iron supplementation during pregnancy, can be identified by early screening.In a prospective study the women were randomized to receive either 18 or 100 mg iron daily from the 16th week until delivery. Investigations were performed in the 16th, 30th, and 38th week.Healthy nulliparae (n = 43) experiencing a normal singleton pregnancy. Only women with a normal hemoglobin concentration and intact iron stores (S-Ferritin15 micrograms/1) in the 16th week were included.These measurements were done consecutively: 1) the total hemoglobin mass (with carbon monoxide). 2) S-Ferritin, 3) S-Transferrin, 4) S-Iron, 5) red cell indices (hemoglobin concentration, hematocrit, MCV, MCHC).Changes in red cell indices and S-Transferrin were equal in the two groups. There was no significant difference in S-Ferritin in the 16th week. In the 30th week 3 women (14%) in the 100 mg group and 11 (52%) in the 18 mg group had empty iron stores (p0.05). The numbers were 1 (5%) and 15 (72%) in the 38th week (p0.0001). The increment in total hemoglobin mass was equal in the two groups from the 16th to the 30th week (13% in the 100 mg group and 12% in the 18 mg group). From the 30th to the 38th week the increment in total hemoglobin mass was largest in the 100 mg group (8.1% versus 2.7%, p0.05).Despite a normal hemoglobin concentration and intact iron stores in the 16th week, an iron supplementation of 18 mg daily is not sufficient to cover the iron need in many pregnant women in the 3rd trimester.

The degree of pulmonary perfusion may have an important role in the pathogenesis of inhalation injury. We studied this in sheep that had only one lung exposed to smoke. The right lung and upper airway of 12 chronically instrumented sheep were insufflated with cotton smoke. In six animals, the left pulmonary artery was occluded between 4 and 10 h after smoke insufflation. All animals were studied for 24 h and then killed, and lung tissue was harvested. The smoked as well as the air-insufflated lung of all animals showed an increase in wet-to-dry weight ratio and tissue conjugated dienes (products of lipid peroxidation). Neither the intermittent blood flow increase to the smoked lung nor the simultaneous blood flow reduction with a concomitant polymorphonuclear neutrophil entrapment in the air-insufflated lung significantly affected the histopathological outcome of the respective lung. We conclude that tissue damage after inhalation injury cannot be diminished by increasing the flow to smoked areas. Ischemia-reperfusion injury does not have a major role in the lung damage seen with inhalation injury.

To determine safety and efficacy of induction with prostaglandin E2 gel, we compared the outcome of 25 patients (study group) with an unfavorable cervix, a medical indication for delivery, and one prior low cervical transverse cesarean section to 56 patients (comparison group) with one prior low cervical transverse cesarean section and spontaneous labor. We placed 1 mg of prostaglandin E2 in gel intracervically in the 25 study patients. Common indications for delivery were: diabetes, post dates, and preeclampsia. Although most labor and delivery variables were similar, the study group had a longer mean latent phase (14.2 +/- 13.8 versus 7.3 +/- 3.7 hours: p less than 0.002), but had a shorter mean length of active phase (4.0 +/- 3.5 versus 5.7 +/- 3.0 hours; p less than 0.02). None of the patients in either group had a dehiscence of the uterine scar, nor rupture of the uterus. Both groups had a similar cesarean section rate. Since from the few reported, nonrandomized studies it appears that prostaglandin E2 gel use in patients with a prior low cervical transverse cesarean section may be useful and relatively safe, it may be time to attempt randomized trials of prostaglandin E2 gel versus oxytocin for induction of patients with a prior low cervical transverse cesarean section, unfavorable cervix, and a medical indication for delivery.

The effects of intraoperative changes in plasma colloid osmotic pressure (COP) on the formation of intestinal edema were studied in patients during modified Whipple's operation (hemipancreato-duodenectomy). Eighteen patients (ASA physical status I or II) were randomly assigned to one of three groups. They received either lactated Ringer's (RL group, n = 6), 10% hydroxyethyl starch (HES group, n = 6), or 20% human albumin (HA group, n = 6) as a volume replacement solution, which was given to maintain central venous pressure (CVP) at the preoperative level. Jejunal specimens were obtained after the first transsection of the jejunum and prior to the jejuno-jejunostomy. Their water fraction (g H2O/g tissue dry weight) was measured gravimetrically. COP was determined prior to induction of anesthesia and upon removal of the second jejunal sample. In the RL group, 3,850 +/- 584 ml (data are means +/- SEM) of volume replacement solution were infused from induction of anesthesia to removal of the second jejunal sample. In the HES group, 1,358 +/- 45 ml were infused, and in the HA group, 463 +/- 49 ml were infused. During this time, COP decreased from 20.3 +/- 0.5 mmHg to 14.1 +/- 0.6 mmHg in the RL group, remained at 22.0 +/- 0.9 mmHg in the HES group, and increased from 20.7 +/- 0.9 mmHg to 28.1 +/- 0.9 mmHg in the HA group.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was a retrospective single-institutional study approved by the Committee on Human Research and was HIPAA compliant. A waiver for informed consent was granted. The purpose of the study was to evaluate the effect of four peak voltage settings on the in vitro conspicuity of gallstones in an anthropomorphic phantom at computed tomography (CT). An anthropomorphic phantom was scanned with (n = 86) or without (n = 85) gallstones at CT by using 80, 100, 120, and 140 kVp. The sensitivity for gallstone detection was significantly higher at 140 kVp (86% [74 of 86] for reader 1 and 81% [70 of 86] for reader 2) than at lower voltage settings (up to 67% [58 of 86] for reader 1 and 63% [54 of 86] for reader 2, P < .05 for each reader), regardless of gallstone size (

We identified 40 patients (25 men and 15 women) who developed calculi composed totally or partially of sulfonamides (acetylsulfamethoxazole, sulfadiazine, and acetylsulfisoxazole) between 1980 and 1987. The incidence of sulfonamide stones is less than 1% of stones. Patient characteristics were determined from questionnaires sent to the patients and attending physicians. The majority of patients developed symptoms 1 to 4 weeks after beginning sulfonamide therapy. The bladder was the most common stone location. Obstruction of the urinary system by the acetyl derivatives of the drug is the most serious consequence of sulfonamide therapy. Early recognition of drug-related stones is essential to protect patients from recurrences, reduce the risk of renal complications, and avoid continuing ineffective therapeutic regimens.

To estimate the efficacy of lidocaine ointment in relieving pain after a vaginal delivery with an episiotomy or perineal laceration.In a randomized, double-blind, placebo-controlled trial, 200 women received lidocaine ointment (n = 108) or a placebo (n = 92). Pain relief was assessed by the amount of ointment used (weight of jar before use - weight of jar after use), total number of pain pills used, and a pain questionnaire. The sample size was calculated using a beta of.2 and an alpha of.05 with an expected reduction of other pain medications from an average use of six pills to four pills for the population.There was no significant difference in the amount of lidocaine versus placebo used for postpartum day 1 (5.1 g versus 4.0 g, respectively [P =.13]) or day 2 (3.7 g versus 2.6 g, respectively [P =.18]). Patients receiving lidocaine instead of the placebo showed no significant difference in the total amount of postpartum pain medications (6.3 versus 6.8 tablets, respectively [P =.53]), subjective pain parameters (P =.36), or satisfaction from ointment (P =.99). Patients with an episiotomy used more pain medications than those with a laceration (7.9 versus 5.6 tablets, respectively [P =.003]). Those with minor versus major lacerations required fewer pain pills (6.1 versus 10.8 tablets, respectively [P.001]) and used less ointment (4.3 g versus 7.9 g, respectively [P =.02]) on the first postpartum day.Topical application of 5% lidocaine ointment was not effective in relieving episiotomy or perineal laceration pain.

Therapy with hydroxyethyl starch (HES) is associated with a high incidence of persistent pruritus due to HES storage in cutaneous nerves. Up to now it has been unknown if HES also accumulates in the extracutaneous peripheral or central nervous system. To study this, five rats including one pregnant one were infused with a single dose (34–150 mg) of HES (70/200/450 kDa molecular weight) conjugated with fluorescein isothiocyanate (FITC). In addition, four sheep were infused with a cumulative dosage of 30 g, 120 g, and 420 g HES (200 kDa), respectively. After 7–13 days, biopsies from the adult rats, four fetal rats and sheep were taken from various organs. The specimens were analyzed by light, electron, and confocal laser scanning microscopy. Typical HES storage vacuoles were found in macrophages of the skin, liver, spleen, lung, and kidney. HES storage in healthy animals was not associated with signs of either inflammation or apoptosis contrary to a previously described animal hemorrhagic shock model. Beyond that, fetus biopsies did not show any storage phenomenon, confirming that HES does not cross the placental barrier. Deposits of HES could be detected in Schwann cells of cutaneous nerve fibers as well as in perineural and endoneural cells of sciatic nerve in one rat (HES 450 kDa) and three of four sheep. No HES storage was found in the central nervous system. Our findings clearly demonstrate that storage of HES is detectable only in small peripheral nerves, suggesting a cutaneous origin of the HES-induced pruritus.

The aim of this study was to evaluate symptoms and bother in patients with pelvic organ prolapse (POP) and to compare symptoms with POP-Q grading and measurements. One hundred and ten women with POP filled in a symptom-bother questionnaire concerning frequency of mechanical, bladder, bowel and sexual problems, and a 4-point bother score. The POP was grouped grade 0-1 versus gradeor=2 in each compartment. Symptoms more than once per week were associated with a higher bother score. Mechanical symptoms, reported in 70%, were the most troublesome. Various bladder, bowel and sexual symptoms were reported in 5%-52%, 5%-39%, and 35%-57%, respectively. We concluded that symptoms from all domains were frequent and reported generally and with little relation to prolapse in a specific compartment or POP-Q value.

Compound A generation and accumulation in sevoflurane anaesthesia is dependent on fresh gas flow. We investigated the extent of generation of compound A.After Institutional Review Board approval and informed consent, patients with normal renal function were randomized to receive either sevoflurane (n = 33) or isoflurane (n = 43) minimal flow anaesthesia (0.5 L min-1) for at least 2 h under standardized conditions. Compound A concentrations were quantified and blood and urine samples were taken to assess renal involvement. Both groups were comparable.No significant differences concerning blood chemistry and urine measurements were found. The maximum mean compound A concentration was observed 90 min after flow reduction being 40 +/- 9 p.p.m. at a corresponding mean sevoflurane concentration of 2.1 +/- 0.5 vol%. Mean inspiratory compound A exposure was 102 +/- 33 p.p.m h-1.Compound A concentrations using 0.5 L min-1 fresh gas flow and a heated absorber were higher than previously published values using an inflow of 1 L min-1. Compound A exposure was similar to other clinical studies which did not show changes in renal and hepatic function.

To determine if the dose of hCG affects the initial rise in progesterone seen in patients undergoing IVF-ET and therefore affects it usefulness as a predictor of cycle outcome.Comparison of the rise in progesterone with cycle outcomes for IVF patients receiving 5,000 or 10,000 mIU hCG to stimulate oocyte maturation.University-based infertility program. Patients-One hundred six patients undergoing IVF-ET on a long protocol of down-regulation with GnRH, hMG stimulation, and hCG to stimulate oocyte maturation. Stimulation protocol varied only in dose of hCG [5,000 mIU (N = 72) vs. 10,000 mIU (N = 34)].Rise in progesterone from 12 hours before to 12 hours after hCG administration and its relationship with cycle outcome.All 106 women exhibited a rise in progesterone following the administration of hCG. As seen in earlier studies, there appeared to be a relationship between minimal progesterone increases (3-fold) and cycle failure in patients receiving 5,000 mIU (P.02). However, using the criteria of the previous study, there appears to be no relationship between progesterone and cycle outcome in patients receiving 10,000 mIU (P = .30). Further, the higher dose of hCG appeared to induce greater increases in progesterone over the 24-hour period examined (P.02). After readjustment of the critical value to 3.5-fold, there was an increased tendency toward cycle failure in women exhibiting a minimal progesterone increase. Unlike the relationship associated with 5,000 mIU hCG, though, the relationship between 10,000 mIU hCG and progesterone levels was not statistically different (P = .10).Increasing the dose of hCG used to stimulate oocyte maturity shifts the previously described relationship between progesterone and IVF-ET-cycle outcome. However, while it remains unclear if progesterone can be used as a predictor of outcome at the higher hCG dose, it appears clear that a relationship exists between minimal progesterone response to hCG and cycle failure.

Recently, it was suggested that peripherally-mediated analgesia can be accomplished by the intra-articular delivery of the mu-opioid morphine or of the a2-agonist clonidine. This clinical study assesses the potential peripheral analgesic effect of the combination of morphine and clonidine after intra-articular administration. Sixty patients (American Society of Anesthesiologists status I or II) undergoing arthroscopic repair of the knee during general anaesthesia were randomized to receive after operation, in a double-blind manner, either 1 mg morphine intra-articularly (group 1); 150 microg clonidine intra-articularly (group 2); or 1 mg morphine + 150 microg clonidine intra-articularly (group 3); or normal saline intra-articularly (group 4) in a volume of 30 mL, respectively. Visual analogue pain scores (VAS), duration of analgesia as defined by first demand for supplemental analgesics, subsequent 24 h consumption of postoperative supplementary analgesics, and patient satisfaction were evaluated. Co-administration of morphine + clonidine (group 3) resulted in a significant VAS reduction at 2 h after injection compared with the other groups. There was a tendency towards a lower need for supplementary rescue analgesia and towards a more prolonged analgesia in group 3 (211 min +/- 224 min SD) compared with group 1 (173 min +/- 197 min SD) and group 4 (91 min +/- 21 min SD). More patients were very satisfied with the postoperative analgesic regimen receiving the combination of morphine and clonidine (group 3) at 24 h postoperatively. Thus we conclude, that the peripheral co-delivery of an opioid and an a2-agonist will result in improved postoperative pain relief, when compared with each single agent given alone.

This study was undertaken to search for differences between fetal weights estimated both ultrasonographically and clinically before and after amniotomy in laboring gravid women.Estimates of fetal weight (ultrasonographic and clinical) were obtained for laboring gravid women before and after amniotomy. These estimates were compared with actual birth weights determined post partum.One hundred sixty-two patients completed the study protocol. Comparisons made with unpaired Student t test analyses demonstrated a difference (P.001) between ultrasonographically estimated fetal weights before and after amniotomy. Simple regression analysis showed a correlation between both ultrasonographic and clinical estimates of fetal weight and actual birth weights before and after amniotomy, with postamniotomy clinical estimates having the strongest correlation (ultrasonographic preamniotomy estimate, R = 0.717; ultrasonographic postamniotomy estimate, R = 0.630; clinical preamniotomy estimate, R = 0.742; and clinical postamniotomy estimate, R = 0.788). Of all ultrasonographic parameters measured, preamniotomy abdominal circumference correlated best with actual birth weight (R = 0.730).Clinical estimates of fetal weight after amniotomy correlated well with actual birth weights. Preamniotomy abdominal circumference was the ultrasonographic parameter best for prediction of actual birth weight. Maternal weight affected clinical but not ultrasonographic estimates of fetal weight in this study. However, clinical estimates of fetal weight were actually superior to ultrasonographic estimates of fetal weight in this study.

To evaluate levels of various fibrinolytic factor antigens in women during ovulation induction using controlled ovarian hyperstimulation.Plasma tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and the plasminogen activator inhibitors (PAI-1 and PAI-2) were evaluated and compared with plasma 17 beta-estradiol levels, ranging from 20 pg/mL to5,000 pg/mL during the course of treatment. Sixteen patients undergoing IVF were compared prior to (Controls) and following treatment with leuprolide acetate down-regulation followed by menopausal gonadotropin-CG ovulation induction for 14 days.A significant positive correlation was found between tPA and PAI-1 during treatment, while tPA and PAI-1 were negatively correlated with estradiol levels. Mean levels of tPA and PAI-1 significantly decreased as estradiol levels increased.As the plasminogen activator decreased with increasing estradiol levels, this suggests a potential for thrombosis. However, the major plasminogen activator inhibitor (PAI-1) also decreased; thus, the net clinical effect in terms of increased potential for thrombosis should be minimal. Furthermore, the levels of both tPA and uPA were still within normal ranges. The overall data from this study suggest that ovarian hyperstimulation with fertility-enhancing drugs does not enhance the potential for thrombosis even though there are elevated 17 beta-estradiol levels.

The biotransformation of dimethindene (CAS 5636-83-9, dimethindene maleate, CAS 3614-69-5) after oral administration was determined in urine using an HPLC gradient method. Besides the phase I metabolites the conjugates of the hydroxylated metabolites with glucuronic and/or sulfuric acid were quantitatively determined after enzymatic deconjugation. The cumulative excretion of 6-hydroxydimethindene and 6-hydroxy-N-demethyldimethindene in human urine after hydrolysis of the conjugates ranged from 18 to 23% of the administered dose, independent of the amount of the dose applied. The results indicate that conjugated 6-hydroxydimethindene is the main metabolite of dimethindene. Increasing doses of 5 to 20 mg dimethindene maleate did not affect the relative amount of the excreted metabolites but changed the ratio of 6-hydroxydimethindene to 6-hydroxy-N-demethyldimethindene from 3:1 to 1:1. In rats about 4 to 8% of the administered dose of dimethindene was excreted as dimethindene-N-oxide which is the main metabolite in rat urine. After administration of R-(-)-dimethindene the elimination of all metabolites was 2 to 3 fold higher compared to the administration of the S-(+)-enantiomer. By chiral HPLC, in 10 human volunteers a stereoselective elimination of N-demethyl-dimethindene after oral administration of racemic dimethindene with the predominant excretion of the R-(-)-enantiomer was observed.

Subarachnoid haemorrhage is commonly associated with natriuresis and hyponatraemia. One possible explanation for these features is a defect in the central regulation of renal sodium reabsorption with increased secretion of a natriuretic factor. We investigated whether excess sodium secretion in patients with subarachnoid haemorrhage is related to increased secretion of natriuretic peptides or to the presence of digoxin-like immunoreactive substances.We measured the plasma concentrations of digoxin-like immunoreactive substances (by a fluorescence polarisation immunoassay) and natriuretic peptides, aldosterone, renin, and antidiuretic hormone (by radioimmunoassay) in ten patients with aneurysmal subarachnoid haemorrhage, ten patients undergoing elective craniotomy for cerebral tumours, and 40 healthy controls of similar age and sex distribution. Samples were collected before surgery, 1 h, 4 h, and 12 h after surgery, then daily until 7 days postoperatively in the two groups of patients.All patients with subarachnoid haemorrhage, but none of the tumour patients, showed increased urine output and urinary excretion of sodium (p = 0.018 for comparison of means of curves to 7 days). The patients with subarachnoid haemorrhage had much higher plasma concentrations of brain natriuretic peptide (BNP) than controls, on admission (mean 15.1 [SE 3.8] vs 1.6 [1.0] pmol/L, p0.001) and throughout the study period, accompanied by lower than normal aldosterone concentrations and normal plasma concentrations of atrial and C-type natriuretic peptides (ANP, CNP). The patients with tumours had similar plasma concentrations of ANP, BNP, and CNP to the controls. We did not detect digoxin-like immunoreactive substances in either group of patients.Salt-wasting of central origin may induce hyponatraemia in patients with aneurysmal subarachnoid haemorrhage, possibly as a result of increased secretion of BNP with subsequent suppression of aldosterone synthesis.

Benzodiazepines are the most commonly used anxiolytic agents. Among the benzodiazepines, midazolam has the advantage of a short elimination half-life, which is especially useful in outpatient surgery. However, in contrast to other commonly prescribed benzodiazepines, such as chlorazepate dipotassium, oral premedication with midazolam has not been thoroughly investigated. Therefore, the present study was performed to compare anxiolysis, sedation and stress reduction with midazolam and clorazepate dipotassium in adults. METHODS. After IRB approval and informed consent had been obtained, 85 patients scheduled for breast biopsy were studied. The patients were chosen at random to receive either 7.5 mg midazolam (n = 29), 20 mg clorazepate dipotassium (n = 28) or placebo (n = 28) preoperatively. Before premedication, immediately prior to surgery and postoperatively in the recovery room, the following parameters were determined with visual analogue scales (VAS): "asthenia," "depression," oral salivation, muscle tension, motoric restlessness and sweating of the palms. In addition, anxiety (STAI-G-X-1, Spielberger), heart rate and arterial blood pressure were measured. Before patients underwent surgery, the degree of sedation was evaluated by the anaesthesiologist. RESULTS. Clorazepate dipotassium and midazolam both caused a reduction in anxiety as compared with the placebo (P0.05). Only clorazepate dipotassium reduced anxiety postoperatively (P0.05). Neither midazolam nor clorazepate dipotassium caused a reduction in "asthenia" and "depression." Midazolam was more effective in preventing increased blood pressure than clorazepate dipotassium and the placebo (P0.05). Furthermore, after premedication with midazolam, salivation, muscle tension, motoric restlessness and sweating of the palms remained stable, in contrast to the results after premedication using clorazepate dipotassium or placebo (P0.05). CONCLUSIONS. The anxiolytic effects of 7.5 mg midazolam and 20 mg clorazepate dipotassium were similar after oral application. However, the anxiolytic effect of midazolam is shorter-lived than that of clorazepate dipotassium. In contrast to clorazepate dipotassium, midazolam produced no increase in arterial blood pressure and stabilized oral salivation, production in the palms, muscle tension and motoric restlessness.

The conversion of an "attempt to treat" to "prolongation of dying" represents an important problem in modern intensive care. If the actual or presumed will of the patient is unknown, the physician has to decide about the extent of treatment in a paternalistic manner. In these difficult decisions the physician has to consider prognosis, and certainty of prognosis and has to carefully balance between the right to live and the right to die. This decision about the extent of therapy is a very personal medical activity and can be taken off the physician's shoulders by nobody. Consultation with other physicians involved, relatives, nurses and clergy, however, is mandatory, as a joint decision should be sought. If the situation is hopeless and further medical interventions are futile, then allowing the patient to die by therapy reductions is not only a possibility but a mandatory act of humanity. In that case it does not matter whether new treatment modalities are abandoned or whether already instituted medical measures are withdrawn. In clinical practice, however, the "fine tuning" of therapy reduction has to be tailored to the individual case and largely depends on prognostic certainty.

The intubation conditions and time-course of action of a 0.3 mg kg-1 bolus of rocuronium were studied under alfentanil/propofol and fentanyl/thiopentone/enflurane anaesthesia. Forty healthy patients were randomly allocated to induction of anaesthesia with either alfentanil 20 micrograms kg-1 and propofol 2.0-2.5 mg kg-1, or fentanyl 3 micrograms kg-1 and thiopentone 4-6 mg kg-1. Approximately 5 min later, after calibration of mechanomyography, an i.v. bolus of 0.3 mg kg-1 rocuronium was administered. Laryngoscopy and tracheal intubation were attempted when maximum block occurred. Intubation was completed successfully in 39 patients. The passage of the tube was rated good or excellent in 18/20 (alfentanil/propofol group) and 18/19 patients in the other group. The times of onset were 65 s and 69 s, respectively. It is concluded that a 1 x ED90 dose of rocuronium will rapidly provide good or excellent intubation conditions in the majority of cases.