Assessment of adrenal function in cirrhotic patients: salivary cortisol should be preferred.

BACKGROUND & AIMS: Adrenal insufficiency is a common disorder among cirrhotic patients. Adrenal function is usually assessed with serum total cortisol assays. Free cortisol (active fraction) represents only 10% of serum total cortisol, the remaining 90% being linked to cortisol-binding globulin (CBG) and albumin. In cirrhotic patients, the synthesis of these proteins is reduced, which could lead to an overestimation of the prevalence of adrenal insufficiency. Salivary cortisol assessment adequately reflects free cortisol plasma concentration. However, this method has never been validated in cirrhotic patients. The objectives of this report were to assess the following parameters by a prospective observational study: (1) correlation between salivary, serum total and free cortisol, (2) adrenal insufficiency prevalence using salivary and serum assays, (3) parameters associated with a discrepancy between both tests, and (4) adrenal insufficiency risk factors among cirrhotic patients. METHODS: Salivary and serum total cortisol were assessed before and 1h following an injection of corticotropin (250 microg) in patients hospitalized for cirrhosis complications without shock. CBG was measured and free cortisol was assessed by the Coolens formula. RESULTS: Eighty-eight patients were included in the study (Child-Pugh C: 68.2%). Free cortisol was more strongly correlated with salivary than with serum total cortisol (Spearman coefficient=0.91 vs. 0.76, respectively, p<0.001). Among included patients, 9.1% had adrenal insufficiency according to salivary cortisol and 33.0% had adrenal insufficiency according to serum total cortisol (p=0.001). Hypoalbuminemia was the only factor associated with a discrepancy between the results of both tests. Adrenal insufficiency risk factors were ascites and low HDL-cholesterol plasma concentration. CONCLUSION: Using serum total cortisol assays overstate adrenal insufficiency prevalence among cirrhotic patients, mainly because of inaccurate concentrations related to hypoalbuminemia. Salivary cortisol assays should be preferably used in these patients.

Thoracoscopic removal of mediastinal parathyroid glands: a critical appraisal of an emerging technique.

OBJECTIVE: To retrospectively evaluate the feasibility of thoracoscopic removal of mediastinal parathyroids. SUMMARY BACKGROUND DATA: Mediastinal exploration to resect ectopic parathyroid(s) is needed in approximately 2% of cases in hyperparathyroidism. Recent advances in thoracoscopic surgery allow for a minimally invasive treatment. METHODS: From 1999 through 2007, 13 patients affected by primary hyperparathyroidism (11 females, mean age 60 years, range: 22-88) underwent thoracoscopic removal of mediastinal parathyroids. Scintigraphy produced positive results in 11 of 13 cases, computed tomography scan in 9 of 10, parathyroid hormone venous sampling in 10 of 10 patients, and magnetic resonance imaging in 5 of 7. Right thoracoscopic access was used in 9 patients, left in 4. Postoperative outcome was analyzed. RESULTS: Thoracoscopy enabled retrieval of mediastinal parathyroids in 10 of 13 (78%) cases. Mean operating time was 92 minutes (range: 50-240). One procedure (8%) was converted. No perioperative deaths/major complications occurred. Mild complications occurred in 2 of 13 (15%) patients (pneumothorax/pneumonia, transient recurrent nerve palsy). Mean hospital stay was 4.7 days (range: 2-15). At a mean follow-up of 73 months (range: 16-105), parathyroid hormone and calcium venous concentrations were high in 3 patients. Unsuccessful procedures were related to doubtful or non-concordant preoperative localization. CONCLUSIONS: The thoracoscopic approach for mediastinal parathyroidectomy is feasible and safe. An accurate preoperative work-up should be standardized to avoid useless procedures. In case of negative preoperative localization of the abnormal gland, thoracoscopy should not be adopted as a diagnostic tool.

Comparison of fifteen immunoassays for the measurement of serum MUC-1/CA 15-3 in breast cancer patients.

BACKGROUND: Quality control results for serum MUC-1/CA 15-3 assays have always shown large discrepancies. METHODS: This multicentre study of 15 methods (labelled M1-M15) measured coded sera from 35 patients with breast cancer without recurrence (group 1), 46 patients at 1st metastasis (group 2), and 39 patients with advanced metastases (group 3). Results were compared using parametric statistics, ANOVA, principal component analysis, and receiver operating characteristic (ROC) curves. RESULTS: Mean MUC-1/CA 15-3 concentrations varied widely (75.1-303.0 U/mL, 24.8%) among methods. The false positive (FP) rate for group 1 was 8/521 (1.5%); for group 2 and group 3 false negative (FN) results were 21/680 (3.1%) and 11/583 (1.9%), respectively. Using the ROC cut-offs, we found no FPs for group 1 and no FNs for group 3. However, group 2 showed 16 FNs. All p-values for Pearson's correlation were <0.0001 between methods, except for M11. When comparing methods using different antibodies, discordance rates reached a maximum of 15.2%. Principal component analysis revealed a grouping of methods using: CanAg monoclonal antibodies (mAbs) (M2, M7 and M12); Centocor/Fujirebio mAbs (M3-M6, M8-M10, M14-M15) and Biomira mAbs (M1 and M13); and Centocor/Fujirebio mAbs (M11). CONCLUSIONS: Results were more consistent among methods using the same antibody type. Principal component analysis showed that antibody type was the strongest determinant of immunoassay results.

Maternal biochemical serum screening for Down syndrome in pregnancy with human immunodeficiency virus infection.

OBJECTIVE: To estimate the influence of human immunodeficiency virus (HIV) infection and antiretroviral therapy on maternal serum markers levels and the false-positive rate with biochemical maternal serum screening for Down syndrome. METHODS: We performed a 1:1 matched case-control study comparing 132 HIV-infected women with single pregnancy to controls selected among non-HIV-infected women matched on geographical origin and fetal sex. RESULTS: Of HIV-infected women, 47.7% were receiving antiretroviral therapy. Groups did not differ in multiples of the median (MoM) levels of total human chorionic gonadotrophin. The MoM alpha fetoprotein level did not differ between total HIV-infected women and control women but was significantly lower for untreated HIV-positive women compared with control women (0.91 compared with 1.03 MoM, P<.01) and compared with treated HIV-positive women (0.91 compared with 1.18 MoM, P<.01). The false-positive rate of biochemical screening did not differ between groups. CONCLUSION: Untreated HIV infection is associated with lower maternal serum alpha fetoprotein levels. Nevertheless, the false-positive rate of double-marker second-trimester Down syndrome serum screening did not appear to be affected in our sample of HIV-infected women, whether women were receiving antiretroviral therapy at the time of the test or not.

Neurological consequences of vitamin B12 deficiency and its treatment.

In developed countries, the vitamin B12 deficiency usually occurs in children exclusively breast-fed, whose mothers are vegetarians, causing low stores of vitamin B12. Symptoms of vitamin B12 deficiency appear during the second trimester of life and include failure to thrive, lethargy, hypotonia, and arrest or regression of developmental skills. A megaloblastic anemia can be present. One half of the infants exhibit abnormal movements before the start of treatment with intramuscular cobalamin, which disappear 1 or 2 days after. More rarely, movement disorders appear a few days after treatment, whereas neurological symptoms are improving. These abnormal movements can last for 2 to 6 weeks. If not treated, vitamin B12 deficiency can cause lasting neurodisability. Therefore, efforts should be directed to preventing deficiency in pregnant and breast-feeding women on vegan diets and their infants by giving them vitamin B12 supplements. When preventive supplementation has failed, one should recognize and treat quickly an infant presenting with failure to thrive and delayed development.

Effects of aspirin and clopidogrel on plasma brain natriuretic peptide in patients with heart failure receiving ACE inhibitors.

BACKGROUND: By inhibiting prostaglandins, aspirin may be deleterious in heart failure (HF) and/or may counteract angiotensin-converting enzyme (ACE) inhibitor efficacy. Conversely, clopidogrel has no effect on prostaglandin metabolism. AIM: To investigate the effect of aspirin and clopidogrel on brain natriuretic peptide (BNP) levels in HF patients treated with ACE inhibitors. METHODS: 36 patients with stable HF (65+/-13 years, 24 males/12 females, NYHA class II to IV, ejection fraction <40%, 13 with coronary disease, all treated with ACE inhibitors) were enrolled in this prospective, double-blind study and randomised to aspirin 325 mg/day or clopidogrel 75 mg/day for 14 days. BNP was determined at day 0 and day 14. RESULTS: 19 patients were randomised to aspirin and 17 to clopidogrel. Baseline characteristics were similar in both groups. BNP levels increased in the aspirin group from day 0 to day 14 (107+/-103 to 144+/-149 pg/ml, p=0.04) whereas clopidogrel had no effect (104+/-107 and 97+/-99 pg/ml respectively, p=0.61). CONCLUSION: This study demonstrates an adverse effect of aspirin 325 mg/day on BNP plasma levels in HF patients treated with ACE inhibitors. In contrast clopidogrel 75 mg/day had no effect.

Plasma levels and expression of vascular endothelial growth factor-A in human localized prostate cancer.

Although the impact of vascular endothelial growth factor (VEGF) is clearly established in advanced prostate cancer (PCa), its role in localized PCa remains to be determined. The aim of our study was to analyse the plasma levels of VEGF-A and the expression of VEGF-A in prostatic tissue in a population of patients with localized PCa. We measured the preoperative plasma levels of VEGF-A in 100 patients undergoing radical prostatectomy (RP) for clinically-localized PCa. After intervention, we determined the expression of VEGF-A in all RP specimens using immunohistochemistry. We found no association between plasma levels of VEGF-A and the established prognostic factors of PCa. Moreover, there was no association between plasma levels of VEGF-A and the expression of VEGF-A in prostatic tissue. On the contrary, there was a strong correlation between the expression of VEGF-A in PCa tissue and the Gleason score of cancer: the expression of VEGF-A was significantly higher in patients with a high Gleason score on RP specimen (p=0.01). Our results suggest that the expression of VEGF may have a prognostic impact in clinically-localized PCa.

Selective use of fetal fibronectin detection after cervical length measurement to predict spontaneous preterm delivery in women with preterm labor.

OBJECTIVE: The purpose of this study was to determine whether selective use of fetal fibronectin detection after ultrasound measurement of cervical length predicts preterm delivery in symptomatic patients better than either indicator alone. STUDY DESIGN: This prospective blinded study performed both tests on 359 women hospitalized for preterm labor between 18 and 34 completed weeks' gestation. The primary outcome was preterm delivery before 35 weeks'gestation. RESULTS: Among the 359 women included, 48 (13.4%) delivered before 35 weeks' gestation. The sensitivity, specificity, and positive and negative predictive values of cervical length < or = 25 mm were 75%, 63%, 24%, and 94%, respectively, and of fetal fibronectin > or = 50 ng/mL, 63%, 81%, 33%, and 93%. Fetal fibronectin detection was significantly (P < .001) more specific than cervical length measurement. For selective use of fetal fibronectin detection after cervical length measurement, the test was considered positive if cervical length was < or = 15 mm or if cervical length was between 16 and 30 mm with fetal fibronectin > or = 50 ng/mL. The predictive values of this test were not significantly different from those of fetal fibronectin detection (67%, 81%, 36%, and 94%). This strategy could have avoided 200 fibronectin tests. CONCLUSION: Selective use of fetal fibronectin detection after cervical length measurement is more specific than cervical length and as effective as fetal fibronectin assays in the entire population of women in preterm labor for predicting preterm birth.

[The level of evidence for the use of biomarkers in the early detection of prostate cancer]. / Les niveaux de preuve des biomarqueurs utilisés pour la détection précoce des cancers de la prostate.

To systematically review the evidence for the use of PSA and other biomarkers in the early detection of prostate cancer, we searched PubMed for clinical trials and studies assessing PSA and other biomarkers in the early detection of prostate cancer, published between 2000 and May 2013 that included >200 subjects. The level of evidence (LOE) for clinical utility was evaluated using the tumor marker utility grading system. A total of 84 publications, corresponding to 70 trials and studies were selected for inclusion in this review. We attributed a level of evidence (LoE) of IA to PSA for early PCa detection, but we do not recommend its use in mass screening. Emerging biomarkers were assessed in prospective case-control and cohort studies: PCA3 (n=3); kallikreins (n=3); [-2]proPSA (n=5); fusion oncogenes (n=2). These studies used biopsy results for prostate cancer to determine specificity and sensitivity, but they did not assess the effect on PCa mortality. The LoE attributed was III-C. PSA can be used for early prostate cancer detection but mass screening is not recommended. Studies on other biomarkers suggest that they could be used, individually or in combination, to improve the selection of patients with elevated PSA levels for biopsy, but RCTs assessing their impact on prostate cancer management and mortality are needed. A better use of available tests is possible for men at risk in order to maximize the risk-benefit ratio.

Pro PSA : a "pro cancer" form of PSA?

Pro PSA, the precursor of PSA, is an inactive 244-amino acid protein secreted by prostatic cells. Pro PSA, a distinct molecular form of free PSA in serum, includes native as well as several truncated forms. Clinical studies have recently provided evidence that pro PSA is associated with prostate cancer (PCa). The truncated (-2) pro PSA form accounts for only 6-19% of free PSA in the serum of patients without PCa, but it represents up to 25-95% of free PSA in that of PCa patients. In the PSA range of 2-10 ng/ml, it has been suggested that pro PSA may be useful to detect PCa, and to spare 10-20% of unnecessary prostate biopsies. However, only scant information about the role of pro PSA is available to date, and its real impact on PCa detection remains to be determined. Furthermore, it is questionnable whether pro PSA could be predictive of tumor recurrence of PCa after therapy. Prospective clinical studies with long term followup are needed to clarify this point.

Midnight salivary cortisol for the initial diagnosis of Cushing's syndrome of various causes.

We assessed the value of midnight salivary cortisol for the initial diagnosis of Cushing's syndrome. Sixty-three patients with various causes of Cushing's syndrome (37 with Cushing's disease, 17 with adrenal Cushing's syndrome, and nine with ectopic ACTH syndrome) and 54 control subjects with simple obesity were studied. All patients with Cushing's syndrome excreted more than 90 microg urinary free cortisol (UFC)/d (248 nmol/d), and all controls excreted less than 90 microg/d UFC. All patients with Cushing's syndrome had a midnight salivary cortisol concentration above 2.0 ng/ml (5.52 nmol/liter), whereas only three controls did so [2.0 ng/ml (5.52 nmol/liter); 2.05 ng/ml (5.66 nmol/liter); and 3.6 ng/ml (9.96 nmol/liter)]. This cut-off provides a sensitivity of 100% and a specificity of 96%. In patients with Cushing's syndrome, midnight salivary cortisol concentrations were correlated with UFC collected over the same period of time (0800-0800 h). Salivary cortisol measurements taken every 4 h showed a typical lack of circadian variation. The daily measurement of midnight salivary cortisol concentrations for 2 wk or more in five other out-patients (with obvious Cushing's disease, subclinical adrenal Cushing's syndrome, suspected Cushing's syndrome, pituitary incidentaloma, and prolactinoma) demonstrated the clinical utility of this factor. Measuring midnight salivary cortisol is an easy and noninvasive means of diagnosing hypercortisolism. Its diagnostic accuracy is identical to, if not better than, that of previously described gold standards.

Comparative response of EPO and soluble transferrin receptor at high altitude.

PURPOSE: Soluble transferrin receptor (sTfR) classically raises with increased erythropoiesis, along with the rise in erythropoietin (EPO). However, the specific effect of altitude-induced erythropoiesis on sTfR remains poorly documented. This study investigated the response of sTfR during high-altitude exposure in human and verified that sTfR was related to EPO response in this case. METHODS: EPO, sTfR, red cell volume (RCV), ferritin, and iron intake were measured during: 1) experiment A (N = 8, 31 d at 5000-8848 m), at sea level (SL), and at the simulated altitude of 5000, 6000, 7000, and 8000 m; and 2) during experiment B (N = 10, 7 d at 4350 m), at SL, after 3, 5, and 7 d at 4350 m and 1-2 d after return to SL (RSL). RESULTS: In experiment A, progressive decompression from SL to 8000 m induced a large parallel rise in EPO (33.8-fold) and sTfR (5.9-fold), whereas ferritin was dramatically decreased and iron intake reduced. RCV was increased after 31 d of decompression. In experiment B, EPO peaked at day 3 at 4350 m, then declined later at altitude and returned to baseline values at RSL, whereas sTfR progressively rose at altitude (+86%) and remained elevated during RSL (+64%). Ferritin progressively declined at 4350 m, whereas iron intake was unchanged. RCV was not enhanced after exposure to 4350 m. CONCLUSION: In summary, sTfR mirrors EPO response for a given level of altitude hypoxia but differs from EPO response during transitory phases, such as early acclimatization or reoxygenation. Analysis of sTfR may therefore account for altitude-related erythropoiesis, at a time when EPO is blunted.

[B-type natriuretic peptide for the diagnostic and prognostic assessment in cardiology. Its interest and perspectives of application]. / Le peptide B natriurétique pour l'évaluation diagnostique et pronostique en cardiologie. Intérêt pratique et perspectives d'applications.

A HORMONE REVEALING VENTRICULAR DYSFUNCTION: B-type natriuretic peptide or Brain natriuretic peptide (BNP) is a neurohormone secreted by the ventricular myocytes in response to volume expansion and pressure overload. It is a sensitive marker of ventricular dysfunction in symptomatic and asymptomatic patients, and its dosage is correlated with the severity of the dysfunction. INDICATION FOR ITS DOSAGE IN HEART FAILURE: Since the results of recent studies, many authors recommend its routine use in heart failure, in order to confirm the diagnosis in difficult cases, assess severity, prognosis and the efficacy of treatment. Such use requires that the results of these studies be known and that the threshold value be adapted according to the age, concomitant diseases and indication of the dosage. OTHER AFFECTIONS: Its diagnostic and prognostic interest in acute coronary syndromes and hypertension is presently being studied.

Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients.

Drug-induced hypersensitivity syndrome (DIHS), also called drug rash with eosinophilia and systemic symptoms (DRESS), is a severe reaction usually characterized by fever, rash, and multiorgan failure, occurring 1-8 weeks after drug introduction. It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release, although no consensus has been reached as to its etiology. The skin, hematopoietic system, and liver are frequently involved. DIHS can mimic severe sepsis, viral infection, adult-onset Still disease (AOSD), or lymphoproliferation.We describe 24 consecutive patients with DIHS who were hospitalized between September 2004 and March 2008. Criteria for inclusion in this observational study were suspected drug reaction, eosinophilia >or=500/microL and/or atypical lymphocytes, involvement of at least 2 organs (skin being 1 of them), with suggestive chronology and exclusion of other diagnoses. Our cohort of 12 women and 12 men had a median age of 49 years (range, 22-82 yr), and 11 had skin phototype V or VI. Patients with mild or no rash were immunocompromised (7/24)- defined as treatment with prednisone (>or=10 mg/d) and another immunosuppressant drug, or human immunodeficiency virus infection. All patients were febrile (>38 degrees C), 14 had localized or generalized edema, 7 had pharyngitis, 8 had lymphadenopathy, 22 had hepatitis, 4 had nephritis, 2 had noninfectious and nonlithiasic angiocholitis or cholecystitis. Ten patients were hypotensive, 5 of whom had associated laboratory signs and/or imaging findings suggestive of acute myocardial dysfunction. Half of the patients had hemogram abnormalities, including eosinophilia. Nine DIHS patients fulfilled the Fautrel criteria for AOSD diagnosis, including glycosylated ferritin <20% in 4/11, with or without laboratory characteristics of hemophagocytosis. Twenty DIHS episodes occurred during the less sunny months of October to March.We determined 25-hydroxyvitamin D3 (25[OH]D3) levels in 18 patients and found that 9 patients had vitamin D deficiency (<25 nmol/L or <10 microg/L) and 5 had vitamin D insufficiency (25-50 nmol/L). Moreover, 25(OH)D3 levels were inversely correlated with ferritin values. After culprit-drug withdrawal, outcomes were favorable for all patients, including those with cardiac abnormalities under slow tapering of glucocorticoids.We recommend looking for the frequent but underdiagnosed hypersensitivity myocarditis with noninvasive diagnostic tools, such as N-terminal probrain natriuretic peptide, and promptly withdrawing the culprit drug and starting glucocorticoids. Vitamin D deficiency might be a DIHS risk or severity factor, especially for patients with high skin phototype and during the winter. Because DIHS clinical and laboratory patterns share similarities with AOSD and hemophagocytosis, DIHS should be included in their differential diagnoses.

Chronic dietary exposure to a low-dose mixture of genistein and vinclozolin modifies the reproductive axis, testis transcriptome, and fertility.

BACKGROUND: The reproductive consequences and mechanisms of action of chronic exposure to low-dose endocrine disruptors are poorly understood. OBJECTIVE: We assessed the effects of a continuous, low-dose exposure to a phytoestrogen (genistein) and/or an antiandrogenic food contaminant (vinclozolin) on the male reproductive tract and fertility. METHODS: Male rats were exposed by gavage to genistein and vinclozolin from conception to adulthood, alone or in combination, at low doses (1 mg/kg/day) or higher doses (10 and 30 mg/kg/day). We studied a number of standard reproductive toxicology end points and also assessed testicular mRNA expression profiles using long-oligonucleotide microarrays. RESULTS: The low-dose mixture and high-dose vinclozolin produced the most significant alterations in adults: decreased sperm counts, reduced sperm motion parameters, decreased litter sizes, and increased post implantation loss. Testicular mRNA expression profiles for these exposure conditions were strongly correlated. Functional clustering indicated that many of the genes induced belong to the "neuroactive ligand-receptor interactions" family encompassing several hormonally related actors (e.g., follicle-stimulating hormone and its receptor). All exposure conditions decreased the levels of mRNAs involved in ribosome function, indicating probable decreased protein production. CONCLUSIONS: Our study shows that chronic exposure to a mixture of a dose of a phytoestrogen equivalent to that in the human diet and a low dose-albeit not environmental-of a common anti-androgenic food contaminant may seriously affect the male reproductive tract and fertility.

Serum levels of vascular endothelial growth factor in patients undergoing prostate biopsy for suspicion of prostate cancer.

OBJECTIVES: To analyze the correlation between serum levels of vascular endothelial growth factor (VEGF) and biopsy findings in patients with a suspicion of prostate cancer. METHODS: Serum levels of VEGF were measured on frozen, archival serum obtained before prostate biopsy in 47 patients with clinical and/or biologic suspicion of prostate cancer. VEGF-A levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The prostate biopsies showed cancer in 27 patients (group 1) and benign tissue in the remaining 20 patients (group 2). No statistically significant difference was found between the two groups in age, digital rectal examination findings, total prostate-specific antigen (PSA) levels, free PSA levels, and complexed PSA levels. The mean prostate volume was significantly lower in group 1 (45.5 g versus 53.9 g; P = 0.04), and the mean percentage of free PSA (free PSA/total PSA) was significantly lower in group 1 (11.3% versus 19%; P = 0.0003). Serum VEGF-A levels were not significantly different between the two groups. The mean VEGF level was 90.6 pg/mL in group 1 and 107.9 pg/mL in group 2 (P = 0.55). Multivariate analysis showed that VEGF-A levels were not predictive of prostate cancer. CONCLUSIONS: Our findings suggest that serum VEGF-A is not helpful to predict prostate cancer in patients with clinical and/or biologic suspicion of prostate cancer.

Long-term impact of a restrictive laboratory test ordering form on tumor marker prescriptions.

OBJECTIVE: To evaluate the long-term impact of an intervention designed to reduce the ordering of three tumor markers frequently prescribed for gastroenterologic diseases (carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 19-9). METHODS: A prospective study with time series analysis in a teaching hospital. Local clinical guidelines were developed and implemented through a new order form, designed as a reminder to the physician, restricting the ordering of laboratory tests. Ratios between the number of markers ordered and number of admissions were recorded during a 3-month period before and after intervention in the whole hospital and monthly on a 4-year period in two wards of the hospital (Department of Gastroenterology and Department of Internal Medicine). To evaluate the appropriateness of tumor marker orders, audits were performed on a sample of order forms, before and after (1 month and 2 years after) the implementation of the new order form. RESULTS: The analysis of covariance showed a significant effect of the intervention in the hospital (p < .01), and in the Departments of Gastroenterology (p < .01) and Internal Medicine (p < .007). The decrease of tumor marker orders ranged from 25% (Internal Medicine Department) to 55% (whole hospital). A similar decrease was observed for the three studied markers. The appropriateness of prescriptions increased from 54.6% before to 73.6% after the implementation of the new order form, but decreased to 52.9% 2 years after intervention. CONCLUSIONS: Providing a reminder to clinicians through a specific order form represents an inexpensive and easy way to implement guidelines on use of laboratory tests.

Percentile curves of serum estradiol levels during controlled ovarian stimulation in 905 cycles stimulated with recombinant FSH show that high estradiol is not detrimental to IVF outcome.

BACKGROUND: High, normal and poor responders are usually defined by reference to subjectively selected estradiol E2 levels at days 4-6 and the day of hCG administration (d-hCG). The purpose of this study was to use E2 percentile curves from day 5 until d-hCG to determine high, normal and poor responders, and to predict IVF outcome. METHODS: In this retrospective study, 762 patients underwent 905 cycles with a GnRH agonist/recombinant FSH short protocol. They were divided into three groups according to their age. Percentile E2 curves according to E2 levels were plotted. High responders were those patients with E2 levels above the 90th percentile, normal responders had E2 between the 10th and 90th percentiles, and poor responders had E2 below the 10th percentile. RESULTS: IVF outcome, expressed as number of oocytes, total embryos obtained and number of high grade embryos, was significantly better for patients with E2 above the 90th percentile at d-hCG for the three age groups and at day 5 for group A (<35 years). Pregnancy rates were higher for high responders, but the difference did not reach statistical significance. CONCLUSIONS: Percentile curves can be useful in controlled ovarian stimulation cycles to define high, normal and poor responders, and also to predict IVF outcome.

Brain natriuretic peptide: A marker of myocardial dysfunction and prognosis during severe sepsis.

OBJECTIVE: To investigate the value of brain natriuretic peptide plasma levels as a marker of systolic myocardial dysfunction during severe sepsis and septic shock. DESIGN: Prospective observational study. SETTING: Intensive care unit. PATIENTS: A total of 34 consecutive patients with severe sepsis (nine patients) or septic shock (25 patients) without previous cardiac, respiratory, or chronic renal failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Myocardial systolic performance was assessed by fractional area contraction (FAC) using echocardiography performed on days 2 (FACD2) and 8. Plasma levels of brain natriuretic peptide were measured at days 1-4 and 8 after the beginning of severe sepsis. Among 34 patients (Simplified Acute Physiology Score II, 43 +/- 2.5), 15 (44%) presented with initial myocardial dysfunction (FACD2 < 50%). Lungs were the origin of sepsis in 65% of patients. The 28-day mortality was 29%. Comparisons were performed between patients with (FACD2 < 50%) and without (FACD2 > or = 50%) myocardial dysfunction. Plasma levels of brain natriuretic peptide were significantly higher in patients with FACD2 < 50% than in those with FACD2 > or = 50% (p <.05) from day 2 to day 4. Brain natriuretic peptide levels were also significantly higher on days 2 and 3 in patients who died during their intensive care unit stay (p <.05). CONCLUSIONS: Systolic myocardial dysfunction is present in 44% of patient with severe sepsis or septic shock. In this setting, brain natriuretic peptide seems useful to detect myocardial dysfunction, and high plasma levels appear to be associated with poor outcome of sepsis, but further studies are needed.