Sildenafil citrate in the treatment of pain in primary dysmenorrhea: a randomized controlled trial.

STUDY QUESTION: Is a vaginal preparation of sildenafil citrate capable of alleviating acute menstrual pain in patients with primary dysmenorrhea (PD)? SUMMARY ANSWER: A vaginal preparation of sildenafil citrate is capable of alleviating acute menstrual pain in patients with PD with no observed adverse effects. WHAT IS KNOWN ALREADY: Oral preparations of nitric oxide (NO) donor drugs augment relaxant effects of NO on myometrial cells, reverse the vasoconstriction caused by prostaglandins and successfully alleviate pain, but the incidence of side effects is too high for routine clinical use. Sildenafil citrate inhibits type 5-specific phosphodiesterase (PDE5), thus preventing the degradation of cyclic guanosine monophosphate (cGMP) in the muscle and augmenting the vasodilatory effects of NO. Therefore, by inhibiting PDE5, the tissue remains relaxed and more blood can circulate through. It has been used previously in a vaginal form with no observed side effects, and it enhances endometrial blood flow. STUDY DESIGN, SIZE, DURATION: A double-blind, randomized, controlled trial comparing vaginal preparation of sildenafil citrate (100 mg single dose) to a placebo in 62 PD patients at the time of painful menstruation was conducted. The primary outcome was total pain relief over 4 consecutive hours (TOPAR4) comparing sildenafil citrate to placebo, where higher TOPAR4 scores represent better pain relief. Secondary outcomes were pain relief as measured by the visual analog scale (VAS) and uterine artery pulsatility index (PI). Subjects were recruited from December 2007 to January 2011. The trial was stopped due to closeout of the funding for the study. PARTICIPANTS, SETTINGS, METHODS: Participants were women in good health, were aged 18-35 years and suffered from moderate to severe PD. They were randomized to either vaginal placebo or 100 mg vaginal sildenafil citrate in a 1:1 ratio using random permuted blocks having a block size of 4. At baseline and 1, 2, 3, and 4 h post-treatment, patients were asked to provide assessment of their degree of pain using two scales: (i) pain on the 5-level ordinal scale used for TOPAR4 calculation and (ii) pain level on the VAS. The study ended 4 h after treatment initiation. MAIN RESULTS AND THE ROLE OF CHANCE: Twenty-five subjects completed the study. Using the TOPAR4 score, the sildenafil citrate group had significantly better pain relief compared with the placebo group [mean (SD): 11.9 (3.2) versus 6.4 (2.1), respectively; difference in means = 5.3; 95% CI: (2.9,7.6); P < 0.001)]. On the VAS, sildenafil citrate provided better pain relief than placebo at each time point. At the 2-h time point, the PI was significantly lower in the sildenafil citrate group compared with the placebo group [mean (SD): 1.6 (0.6) versus 2.3 (0.5), respectively; difference in means = -0.7; 95% CI: (-1.2, -0.1); P = 0.01)]. LIMITATIONS, REASONS FOR CAUTION: Since we did not meet our sample size due to the loss of funding and could not confirm our primary hypothesis, larger studies of longer duration, likely multi-center, are needed to confirm the findings from this study. WIDER IMPLICATIONS OF THE FINDINGS: A number of medications have been investigated to improve the treatment options for PD, but most have proven unsuccessful or to have an unfavorable risk/benefit ratio. Since PD is a condition that most women suffer from and seek treatment for at some point in their lives, our study offers hope that vaginal sildenafil citrate is a safe and effective option for patients who do not desire or are unresponsive to treatments now available on the market. STUDY FUNDING/COMPETING INTERESTS: Funding for this study was provided by National Institutes of Health (NIH) grants RO3 TW007438 and K24 HD01476. The authors report no relevant conflicts of interest. TRIAL REGISTRATION NUMBER: NCT00123162 (Clinical trials.gov).

Handling ability of gaseous microemboli of two pediatric arterial filters in a simulated CPB model.

OBJECTIVE: The purpose of this experiment was to compare the Sorin KIDS D131 and the Terumo Capiox AF02 pediatric arterial filters in a simulated CPB procedure to determine which filter is the better for clinical use. METHODS: The experimental circuit was primed with an 800 ml combination of lactated Ringer's solution and human blood (hematocrit (Hct) 30%). The two filters were tested under flow rates of 500, 1000, and 1500 ml/min at room temperature and their purge lines opened and closed as 5cc of air was injected into the circuit. RESULTS: As the flow rates increased, the number of gaseous microemboli (GME) being returned to the pseudo patient increased for both of the pediatric arterial filters. Having an open purge line increased the number of GME removed from the CPB circuit, caused less of a pressure drop than when closed and increased the total hemodynamic energy loss than when closed. Both of the filters performed and reacted similarly in decreasing GME, hemodynamic energy loss and pressure drop. The only minor difference was that the Capiox AF02 had slightly less stolen blood flow (109.5 ± 1.7 ml/min at 500 ml/min, 114.7 ± 1.1 ml/min at 1000 ml/min and 105.8 ± 4.2 ml/min at 1500ml/min) from the open purge line than the KIDS D131 (119.5 ± 2.5 ml/min at 500 ml/min, 128.3 ± 1.0 ml/min at 1000 ml/min and 126.3 ± 3.1 ml/min at 1500 ml/min). CONCLUSION: Our study confirmed that both the Sorin KIDS D131 and the Terumo Capiox AF02 were equivalent in their ability to remove significant numbers of GME, the amount of pressure drop and the total hemodynamic energy loss across the arterial filters at the various flow rates. An arterial filter is not an option, but a necessity for removing microemboli delivered to the patient.

Hemodynamic evaluation of arterial and venous cannulae performance in a simulated neonatal extracorporeal life support circuit.

OBJECTIVE: To construct an ideal extracorporeal life support (ECLS) circuit in terms of hemodynamic performance, each component of the circuit should be evaluated. Most cannulae manufacturers evaluate their products using water as the priming solution. We conducted this study to evaluate the different sizes of arterial and venous cannulae in a simulated neonatal ECLS circuit primed with human blood. METHODS: The simulated neonatal ECLS circuit was composed of a Capiox Baby RX05 oxygenator, a Rotaflow centrifugal pump and a heater & cooler unit. Three Medtronic Bio-Medicus arterial cannulae (8Fr, 10Fr, 12Fr) and three venous cannulae (10Fr, 12Fr, 14Fr) were tested in seven combinations (8A-10V, 8A-12V, 10A-10V, 10A-12V, 10A-14V, 12A-12V, 12A-14V). All the experiments were conducted using human blood at a hematocrit of 40% and at a constant temperature of 37°C. The "tip to tip" priming volume of the entire circuit was 135ml. The blood volume of the pseudo patient was 500ml. RESULTS: Flow rates increased linearly with increasing size in both venous and arterial cannulae at the same pump speeds. The increase in flow rate was greater when changing the arterial cannulae (next size larger) compared to changing the venous cannulae (next size larger). The pressure drops of the arterial cannula were correlated with the flow rates, regardless of the pseudo patient pressure and the venous cannula used simultaneously. CONCLUSIONS: The results show the difference in flow ranges and pressure drops of seven combinations of arterial and venous cannulae. It also suggests that the arterial cannula, not the venous cannula, has greater impact on the flow rate when a centrifugal pump is used in a neonatal ECLS circuit. The results of this study have been translated to further advancing the clinical practice in our institution.

Effects of dynamic exercise on mean blood velocity and muscle interstitial metabolite responses in humans.

We examined the effects of dynamic one-legged knee extension exercise on mean blood velocity (MBV) and muscle interstitial metabolite concentrations in healthy young subjects (n = 7). Femoral MBV (Doppler), mean arterial pressure (MAP) and muscle interstitial metabolite (adenosine, lactate, phosphate, K(+), pH, and H(+); by microdialysis) concentrations were measured during 5 min of exercise at 30 and 60% of maximal work capacity (W(max)). MAP increased (P < 0.05) to a similar extent during the two exercise bouts, whereas the increase in MBV was greater (P < 0.05) during exercise at 60% (77.00 +/- 6.77 cm/s) compared with 30% W(max) (43.71 +/- 3.71 cm/s). The increase in interstitial adenosine from rest to exercise was greater (P < 0.05) during the 60% (0.80 +/- 0.10 microM) compared with the 30% W(max) bout (0.57 +/- 0.10 microM). During exercise at 60% W(max), interstitial K(+) rose at a greater rate than during exercise at 30% W(max) (P < 0.05). However, pH increased (H(+) decreased) at similar rates for the two exercise intensities. During exercise, interstitial lactate and phosphate increased (P < 0.05) with no difference observed between the two intensities. After 5 min of recovery, MBV decreased to baseline levels after exercise at 30% W(max) (4.12 +/- 1.10 cm/s), whereas MBV remained above baseline levels after exercise at 60% W(max) (Delta19.46 +/- 2.61 cm/s; P < 0.05). MAP and interstitial adenosine, K(+), pH, and H(+) returned toward baseline levels. However, interstitial lactate and phosphate continued to increase during the recovery period. Thus an increase in exercise intensity resulted in concomitant changes in MBV and muscle interstitial adenosine and K(+), whereas similar changes were not observed for MAP or muscle interstitial pH, lactate, or phosphate. These data suggest that K(+) and/or adenosine may play an active role in the regulation of skeletal muscle blood flow during exercise.

Radioprotection to the eye during CT scanning.

BACKGROUND AND PURPOSE: The lens of the eye is sensitive to radiation. Children undergoing CT of the head and patients undergoing repeated CT scanning of the head are vulnerable to this complication. The purpose of this study was to test the ability of a heavy metal, bismuth, in reducing radiation to the lens of the eye during routine cranial CT. METHODS: Both phantom and human studies were done. Using a standard head-attenuating phantom, scanning was performed with detectors placed over the eye, first without the protectors, and then with shielding by one (1T), two (2T), or three thickness (3T) of bismuth-coated latex. The patient study included 30 patients randomized into one of three groups with eye protection provided by 1T, 2T, or 3T of the bismuth-coated latex. Control measurements were done using thermoluminescent dosimeters over the forehead above each eye. Image artifact from the bismuth shields was assessed. RESULTS: The phantom study demonstrated that the use of bismuth-coated shielding over the eyes decreased radiation dosage by 48.5%, 59.8%, and 65.4% using 1T, 2T, and 3T, respectively. The effect of eye shielding in decreasing radiation dosage to the eye was highly significant for all three thicknesses (P = 2.9 x 10(-81) to 1.9 x 10(-89)). In the patient study, the use of 1T, 2T, and 3T of bismuth-coated latex saved an average radiation dose of 39.6%, 43.5%, and 52.8%, respectively. While the use of shielding was statistically significant in saving radiation for all thicknesses (P = 2.2 x 10(-10) to 1.4 x 10(-21)), there was no statistical difference between 1T, 2T, and 3T of bismuth-coated latex shielding found in patients. However, the trend was for increased radiation savings to the eye with increased thickness of shielding used. A review of all 30 studies showed no significant artifact caused by the eye shielding, regardless of thickness. CONCLUSION: Bismuth-coated latex shielding of the eye during cranial CT is simple to apply, inexpensive, and causes up to a 50% reduction in radiation to the lens of the eye.

Measurement of the resonant d(mu)t molecular formation rate in solid HD.

Measurements of muon-catalyzed dt fusion ( d(mu)t-->4He + n + mu(-)) in solid HD have been performed. The theory describing the energy dependent resonant molecular formation rate for the reaction (mu)t + HD-->[(d(mu)t)pee](*) is compared to experimental results in a pure solid HD target. Constraints on the rates are inferred through the use of a Monte Carlo model developed specifically for the experiment. From the time-of-flight analysis of fusion events in 16 and 37 microg x cm(-2) targets, an average formation rate consistent with 0.897+/-(0.046)(stat)+/-(0.166)(syst) times the theoretical prediction was obtained.

Role of androgens in the growth of endometrial carcinoma: an in vivo animal model.

OBJECTIVE: We sought to create an animal model for the development of endometrial cancer in women with androgen excess. We examined the effects of estradiol and androgen, both alone and as precursors to estrogen biosynthesis on human endometrial cancers transplanted into a nude mouse model. STUDY DESIGN: We transplanted an estrogen-responsive, well-differentiated, established human endometrial carcinoma, EnCa-101, subcutaneously into athymic male nude mice. We established, first, that aromatase was expressed in this cell line, inducible by estrogen. We measured the growth of the tumor in the various groups weekly with Vernier calipers. We examined the effects of estradiol and androgens, both aromatizable and nonaromatizable, on tumor growth. RESULTS: Estrogen-supplemented tumors showed the greatest rate of growth and were significantly greater than the growth rate in castrate mice. Androgen-supplemented tumors showed a growth rate similar to that of tumors without significant hormonal exposure (castrate mice). Dihydrotestosterone had no effect on tumor growth in comparison with an agonadal state. CONCLUSIONS: Aromatizable and nonaromatizable androgens have little growth-promoting effect on a well-differentiated endometrial carcinoma. Estradiol is the most potent growth stimulus in our model.

Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome.

PURPOSE: Women with polycystic ovary syndrome are hyperandrogenemic and insulin resistant, which are associated with alterations in circulating lipid and lipoprotein levels. We sought to determine the prevalence of, and risk factors for, lipid abnormalities in these women. SUBJECTS AND METHODS: Non-Hispanic white women with polycystic ovary syndrome (n = 195) and ethnically matched control women (n = 62) had fasting blood obtained for hormone and lipid levels. Subjects were categorized by body mass index (nonobese <27 kg/m(2), obese > or =27 kg/m(2)), and analyses were adjusted for age. RESULTS: Total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels increased significantly in obese women with polycystic ovary syndrome (n = 153) compared with obese control women (n = 35; mean difference in total cholesterol level = 29 mg/dL; 95% confidence interval [CI]: 14 to 45 mg/dL; P <0.001; mean difference in LDL-C level = 16 mg/dL; 95% CI: 4 to 30 mg/dL; P = 0.006). Similarly, total cholesterol and LDL-C levels increased significantly in nonobese women with polycystic ovary syndrome (n = 42) compared with nonobese control women (n = 27; mean difference in total cholesterol = 32 mg/dL; 95% CI: 13 to 52 mg/dL; P <0.001; mean difference in LDL-C level = 32 mg/dL; 95% CI: 15 to 52 mg/dL; P <0.001). In obese women, high-density lipoprotein cholesterol (HDL-C) and triglyceride levels increased significantly in women with polycystic ovary syndrome compared with control women (mean difference in HDL-C level = 6 mg/dL; 95% CI: 2 to 12 mg/dL; P = 0.002; mean difference in triglyceride level = 34 mg/dL; 95% CI: 1 to 77 mg/dL; P = 0.04). Differences in LDL-C and HDL-C levels, but not triglyceride levels, remained significant after adjusting for alcohol intake, smoking, and exercise. Although age, body mass index, and polycystic ovary syndrome status were significant predictors of lipid levels, these factors accounted for no more than 25% of the variance. CONCLUSIONS: In this large study of non-Hispanic white women, elevations in LDL-C levels were the predominant lipid abnormality in women with polycystic ovary syndrome, independent of obesity. The characteristic dyslipidemia of insulin resistance was absent. Indeed, obese women with polycystic ovary syndrome had relatively elevated HDL-C levels, which may confer some protection against cardiovascular disease.

The use of clinical CT for baseline bone density assessment.

PURPOSE: Many patients having an abnormal initial bone densitometry study have had a previous abdominal/pelvic computed tomography (CT) for other clinical reasons. This study evaluates if a nondedicated quantitative CT (QCT) abdominal/pelvic CT scan could be used as reliable baseline data for subsequent dedicated bone density studies. SUBJECTS AND METHODS: Twenty-six patients (13 men, 13 women) undergoing clinically-indicated non-i.v. and i.v. contrast abdominal/pelvic CT had dedicated QCT performed immediately following scans of the L1, L2, and L3 vertebral bodies. QCT was then performed on all three scans. A repeated measures analysis of variance model was used to analyze the data in order to compare noncontrast clinical CT with QCT and noncontrast clinical with contrast clinical CT. RESULTS: The mean bone mineral density for the noncontrast clinical study was 98.51 (mg/cc) versus 90.56 (mg/cc) for QCT (p = 0.0003; 95% confidence interval: 3.90 to 13.71). There was no significant difference (p = 0.085) between QCT performed from non-i.v. and i.v. contrast clinical CT scans. CONCLUSION: Bone densitometry can be performed from either non-i.v. or i.v. contrast clinical CT scans if a conversion factor is applied. This can be determined by utilizing a formula Daverage = -7.83 + (0.99 x NCaverage), where Daverage and NCaverage are the abbreviations of "dedicated" and "noncontrast clinical" BMD averaged over vertebral bodies L1-L3, respectively.

Effects of forearm bier block with bretylium on the hemodynamic and metabolic responses to handgrip.

We tested the hypothesis that a reduction in sympathetic tone to exercising forearm muscle would increase blood flow, reduce muscle acidosis, and attenuate reflex responses. Subjects performed a progressive, four-stage rhythmic handgrip protocol before and after forearm bier block with bretylium as forearm blood flow (Doppler) and metabolic (venous effluent metabolite concentration and (31)P-NMR indexes) and autonomic reflex responses (heart rate, blood pressure, and sympathetic nerve traffic) were measured. Bretylium inhibits the release of norepinephrine at the neurovascular junction. Bier block increased blood flow as well as oxygen consumption in the exercising forearm (P < 0.03 and P < 0.02, respectively). However, despite this increase in flow, venous K(+) release and H(+) release were both increased during exercise (P < 0.002 for both indexes). Additionally, minimal muscle pH measured during the first minute of recovery with NMR was lower after bier block (6.41 +/- 0.08 vs. 6.20 +/- 0.06; P < 0.036, simple effects). Meanwhile, reflex effects were unaffected by the bretylium bier block. The results support the conclusion that sympathetic stimulation to muscle during exercise not only limits muscle blood flow but also appears to limit anaerobiosis and H(+) release, presumably through a preferential recruitment of oxidative fibers.

Underestimation of case severity by emergency department patients: implications for managed care.

The objective was to examine differences in symptom severity assessment by emergency department (ED) patients and by emergency physicians (EPs) and to relate these assessments with case management and disposition. The design was prospective convenience sample of ED patients. The setting was a U.S. university hospital ED with an annual ED patient census 28,000. The participants were all ED patients registered when first author was in ED; excluded were patients treated by the major trauma response team and those with a psychiatric chief complaint. All patients were interviewed by the first author and asked to classify their symptoms as emergent, urgent, or nonurgent; the EP attending classed patients' symptoms at presentation and after work-up was complete. Three hundred-one cases were entered in the study from May to August 1996. Although 28% of ED patients self-rated their symptoms as nonurgent, 5% of this group required hospital admission. Of this group 35% were assessed by the EP attending as having required emergent or urgent ED care. Of this group 5% also rated by the EP initially as nonurgent had their case severity upgraded after work-up. Reliance on either patient symptom self-assessment or physician screening assessment by telephone to determine appropriateness of an ED visit is not reliably safe for at least 5% of presenting patients. Even prospective ED visit severity assessment does not reliably identify "unnecessary" ED visits.

The mentor effect in student evaluation.

OBJECTIVE: To determine if faculty mentors rate their mentored students higher than do nonmentors, and to ascertain if gender is a factor. METHODS: All third-year students (n = 101) from academic years 1996-1998, who performed their obstetrics and gynecology clerkship at the Milton S. Hershey Medical Center in the Penn State Geisinger Health System and were evaluated by full-time faculty (n = 18), were included in the study (total observations = 545). Students were rated by faculty on an ordinal scale in five categories. Generalized estimating equation methodology was used to fit proportional odds models for ordinal data to assess whether there were statistically significant mentor or faculty/student gender effects. RESULTS: Student evaluations from mentors were more likely to have better scores than student evaluations from nonmentoring-faculty for all five categories (all P <.01). The odds ratios (OR) for the mentor effect ranged from 2.1 (95% confidence interval [CI] 1.4, 3.2) for fund of knowledge to 3.2 (95% CI [2.1, 4. 8]) for attitude. For problem-solving and technical skills, male faculty were more likely than female faculty to give male students better scores (problem-solving skills: odds ratio [OR] = 1.7, 95% CI [1.0, 2.7]; technical skills: OR = 2.2, 95% CI [1.1, 4.6]). Mentoring-faculty evaluations were not strongly correlated with the students' objective examination scores. CONCLUSION: Overall, mentors score their mentored students statistically higher than do nonmentors. Gender differences in evaluation, while present, are less consistent and smaller than the mentor effect.

Detection of Björk-Shiley convexo-concave heart valve outlet strut single leg separations: consensus image acquisition and interpretation using two different cineradiographic imaging technologies.

BACKGROUND: Conventional cineradiology has been used clinically to detect partially broken outlet struts (single leg separations, SLSs) in normally functioning Björk-Shiley convexo-concave (C/C) heart valves. The value of radiographic screening has, however, been debated in the medical literature. This study uses the same radiographic technique in sheep implanted with known-status C/C valves in combination with a newly developed geometric image magnification radiography system. This study was designed to test whether sensitivity and specificity of radiographic screening of C/C valves in detecting SLSs could be improved through the combination of readers and imaging modalities. METHODS: Twenty-one sheep with mitral C/C valves were studied on both systems. Five were used for extensive scanning training. When operators were expert on both systems, 16 blinded study valves (4 intact and 12 with outlet strut SLSs) were scanned twice on both systems, first on a modified conventional and then a prototype geometric image magnification (Feinfocus(TM)) cineradiographic system by two expert physicians working together. RESULTS: Among the 32 scanned valves, the two combined expert physicians were required to evaluate 40 intact legs and 24 with an SLS. For all SLS valves, the conventional and Feinfocus systems separately detected 50 (12/24) and 54% (13/24), respectively. When the two systems were combined, the final consensus score was correct in 67% (16/24) of all SLS valves. CONCLUSIONS: Combined modality, paired expert physicians detected 67% of all SLSs. The Feinfocus system might be best reserved for those patients in whom the Siemens screening study demonstrates in minimally suspicious (grade 2) or suspicious (grade 3) appearance of a C/C valve outlet strut leg.

A comparison of mixed effects logistic regression models for binary response data with two nested levels of clustering.

We compare mixed effects logistic regression models for binary response data with two nested levels of clustering. The comparison of these models occurs in the context of developmental toxicity data sets, for which multiple types of outcomes (first level) are measured on each rat pup (second level) nested within a litter (third level). Because the nested nature of such data is occasionally accommodated by ignoring one level of clustering, we consider three models: (i) a three-level model adjusting for clustering due to both pup and litter (M1); (ii) a two-level model adjusting for just pup (M2); and (iii) another two-level model adjusting for just litter (M3). The three types of effects of interest are: (i) differences among malformation types (first-level effects); (ii) differences among groups of pups (for example, sex of pup, second-level effects); and (iii) differences among groups of litters (for example, dose, third-level effects). Simulations and data analyses suggest that the M3 model leads to more bias than the M1 or M2 models for all three types of effects. In terms of coverage of confidence intervals for fixed effects log odds ratio parameters, the M1 model achieves nominal coverage, whereas the M2 model reduces coverage for the third-level effects and the M3 model obtains poor coverage for both first- and second-level effects. These reductions in coverage for certain model-parameter combinations worsen as baseline risk increases. The data analyses support these simulation-based conclusions to some extent.

Characteristics of the muscle mechanoreflex during quadriceps contractions in humans.

We examined muscle sympathetic nerve activity (MSNA) in the nonexercising lower limb during repetitive static quadriceps contraction paradigm at 25% maximal voluntary contraction in eight men. Subjects performed 20-s contractions with 5-s rest periods for up to 12 contractions. Although the workload was constant, we found that MSNA amplitude rose as a function of contraction number [0.6 ln (amplitude/min)/contraction]; this suggests chemical sensitization of the muscle reflex response. We employed signal-averaging techniques and then integrated the data to examine the onset latency of the MSNA response as a function of the 25-s contraction-rest period. We observed an onset latency of approximately 4-6 s. Moreover, although the onset latency did not appear to vary as a function of contraction number, the rate of MSNA increase took approximately four contractions to reach a steady-state rate of rise; this suggests contraction-induced sensitization. The onset latency reported here is similar to findings in recent animal studies, but it is at odds with latencies determined in prior human handgrip contraction studies. We believe our data suggest that 1) mechanically sensitive afferents contribute importantly to the MSNA response to the paradigm employed and 2) these afferents may be sensitized by the chemical products of muscle contraction.

Oocyte donors as gynecologic teaching associates.

OBJECTIVE: To fulfill the need for gynecologic teaching associates for an expanded pelvic examination module for third-year medical students, we sought women who were able to provide feedback to medical students. Oocyte donors were hypothesized as a useful potential pool of gynecologic teaching associates. METHODS: Gynecologic teaching associates were recruited from a pool of women who were involved in our oocyte donor program. Students were evaluated on a scale of 1 (best) to 5 (worst) on their performance on the pelvic examination by themselves (n = 91), by the gynecologic teaching associate (n = 10), and by the supervising faculty (n = 6). Students were shown their evaluations, and these were reviewed at the end of the session to provide students with immediate feedback. RESULTS: Students consistently ranked their skills lower than either the gynecologic teaching associate or supervising faculty member for all four categories evaluated (communication skills, technical skills, professional demeanor, and overall performance) (P < .001). Students gave their communications skills the highest mean rankings, whereas gynecologic teaching associates gave them the lowest. The highest correlation and agreement between pairs of evaluators were between the gynecologic teaching associate and the supervising faculty member. Gynecologic teaching associates and faculty members also were more likely to praise the students' performance in written comments (chi2 58.2, P < .001), whereas no student found anything praiseworthy in his or her performance. CONCLUSION: Oocyte donors represent a useful pool of potential gynecologic teaching associates. They provide important feedback to students. Their evaluation of the proficiency of the student correlates well with that of the supervising faculty member.

Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women.

Women with polycystic ovary syndrome (PCOS) are insulin resistant, have insulin secretory defects, and are at high risk for glucose intolerance. We performed this study to determine the prevalence of glucose intolerance and parameters associated with risk for this in PCOS women. Two-hundred and fifty-four PCOS women, aged 14-44 yr, were prospectively evaluated at 2 centers, 1 urban and ethnically diverse (n = 110) and 1 rural and ethnically homogeneous (n = 144). The rural PCOS women were compared to 80 control women of similar weight, ethnicity, and age. A 75-g oral glucose challenge was administered after a 3-day 300-g carbohydrate diet and an overnight fast with 0 and 2 h blood samples for glucose levels. Diabetes was categorized according to WHO criteria. The prevalence of glucose intolerance was 31.1% impaired glucose intolerance (IGT) and 7.5% diabetes. In nonobese PCOS women (body mass index, <27 kg/m2), 10.3% IGT and 1.5% diabetes were found. The prevalence of glucose intolerance was significantly higher in PCOS vs. control women (chi2 = 7.0; P = 0.01; odds ratio = 2.76; 95% confidence interval = 1.23-6.57). Variables most associated with postchallenge glucose levels were fasting glucose levels (P < 0.0001), PCOS status (P = 0.002), waist/hip ratio (P = 0.01), and body mass index (P = 0.021). The American Diabetes Association criteria applied to fasting glucose significantly underdiagnosed diabetes compared to the WHO criteria (3.2% vs. 7.5%; chi2 = 4.7; P = 0.046; odds ratio = 2.48; 95% confidence interval = 1.01-6.69). We conclude that 1) PCOS women are at significantly increased risk for IGT and type 2 diabetes mellitus at all weights and at a young age; 2) these prevalence rates are similar in 2 different populations of PCOS women, suggesting that PCOS may be a more important risk factor than ethnicity or race for glucose intolerance in young women; and 3) the American Diabetes Association diabetes diagnostic criteria failed to detect a significant number of PCOS women with diabetes by postchallenge glucose values.

Effects of the ovarian cycle on sympathetic neural outflow during static exercise.

We compared reflex responses to static handgrip at 30% maximal voluntary contraction (MVC) in 10 women (mean age 24.1 +/- 1.7 yr) during two phases of their ovarian cycle: the menstrual phase (days 1-4) and the follicular phase (days 10-12). Changes in muscle sympathetic nerve activity (MSNA; microneurography) in response to static exercise were greater during the menstrual compared with follicular phase (phase effect P = 0.01). Levels of estrogen were less during the menstrual phase (75 +/- 5.5 vs. 116 +/- 9.6 pg/ml, days 1-4 vs. days 10-12; P = 0.002). Generated tension did not explain differences in MSNA responses (MVC: 29.3 +/- 1.3 vs. 28.2 +/- 1.5 kg, days 1-4 vs. days 10-12; P = 0.13). In a group of experiments with the use of 31P-NMR spectroscopy, no phase effect was observed for H+ and H2PO-4 concentrations (n = 5). During an ischemic rhythmic handgrip paradigm (20% MVC), a phase effect was not observed for MSNA or H+ or H2PO-4 concentrations, suggesting that blood flow was necessary for the expression of the cycle-related effect. The present studies suggest that, during static handgrip exercise, MSNA is increased during the menstrual compared with the follicular phase of the ovarian cycle.

Maintained exercise pressor response in heart failure.

The impact of forearm blood flow limitation on muscle reflex (metaboreflex) activation during exercise was examined in 10 heart failure (HF) (NYHA class III and IV) and 9 control (Ctl) subjects. Rhythmic handgrip contractions (25% maximal voluntary contraction, 30 contractions/min) were performed over 5 min under conditions of ambient pressure or with +50 mmHg positive pressure about the exercising forearm. Mean arterial blood pressure (MAP) and venous effluent hemoglobin (Hb) O2 saturation, lactate and H+ concentrations ([La] and [H+], respectively) were measured at baseline and during exercise. For ambient contractions, the increase (Delta) in MAP by end exercise (DeltaMAP; i.e., the exercise pressor response) was the same in both groups (10.1 +/- 1.2 vs. 7.33 +/- 1.3 mmHg, HF vs. Ctl, respectively) despite larger Delta[La] and Delta[H+] for the HF group (P < 0.05). With ischemic exercise, the DeltaMAP for HF (21.7 +/- 2.7 mmHg) exceeded that of Ctl subjects (12.2 +/- 2.8 mmHg) (P < 0.0001). Also, for HF, Delta[La] (2.94 +/- 0.4 mmol) and Delta[H+] (24.8 +/- 2.7 nmol) in the ischemic trial were greater than in Ctl (1.63 +/- 0.4 mmol and 15.3 +/- 2.8 nmol; [La] and [H+], respectively) (P < 0.02). Hb O2 saturation was reduced in Ctl from approximately 43% in the ambient trial to approximately 27% with ischemia (P < 0.0001). O2 extraction was maximized under ambient exercise conditions for HF but not for Ctl. Despite progressive increases in blood perfusion pressure over the course of ischemic exercise, no improvement in Hb O2 saturation or muscle metabolism was observed in either group. These data suggest that muscle reflex activation of the pressor response is intact in HF subjects but the resulting improvement in perfusion pressure does not appear to enhance muscle oxidative metabolism or muscle blood flow, possibly because of associated increases in sympathetic vasoconstriction of active skeletal muscle.