Impact of Clomiphene Citrate on the Steroid Profile in Dysmetabolic Men with Low Testosterone Levels.

Clomiphene citrate (CC) in male hypogonadism increases testosterone (T) and estrogen levels by stimulating pituitary gonadotropin release. Our group confirmed these hormonal changes in a randomized, cross-over, double-blind trial of CC versus placebo in addition to metformin, conducted in 21 obese dysmetabolic men with low T levels. However, we hypothesize that based on its mechanism of action, CC may directly or indirectly affect adrenal steroidogenesis. The aim of this sub-study was to better understand the changes in steroid levels and metabolism induced by CC treatment. We assessed 17α-hydroxypregnelone (17αOH-P5), dehydroepiandrosterone (DHEA), progesterone (P4), 17α-hydroxyprogesterone (17αOH-P4), androstenedione (A), T, dihydrotestosterone (DHT), estrone (E1), 17ß-estradiol (E2), 11-deoxycortisol (11 S), cortisol (F), and cortisone (E) by LC-MS/MS, and corticosteroid binding globulin (CBG) by ELISA, before and after each treatment. In addition, free-F and steroid product/precursor ratios were calculated. We observed a significant change in serum levels induced by CC compared with placebo for 17αOH-P4, DHT, T, E2, E1, F, E, and CBG, but not free-F. In addition, compared to placebo, CC induced higher 17αOH-P4/P4, E2/E1, 17αOH-P4/17αOH-P5, A/17αOH-P4, T/A, E1/A, F/11 S, and F/E ratios. Therefore, besides the CC stimulating effect on testis steroidogenesis, our study showed increased F, E, but not free-F, levels, indicating changes in steroid metabolism rather than adrenal secretion stimulation. The steroid profiling also revealed the CC stimulation of the Δ5 rather than the Δ4 pathway, thus indicating considerable testicular involvement in the increased androgen secretion.

A New Reliable Method for Evaluating Gallbladder Dynamics: The 3-Dimensional Sonographic Examination.

OBJECTIVES: The purpose of this study was to compare conventional 2-dimensional (2D) B-mode sonography with 3-dimensional (3D) sonography for assessing gallbladder volume and contractility. METHODS: Gallbladder volume and contractility were evaluated in 32 healthy volunteers after fasting and abstinence from smoking for 8 hours and after a standardized balanced liquid meal. The gallbladder was evaluated with 2D sonography (with the use of the ellipsoid method) and with 3D sonography using a volumetric matrix probe. Both measurements were made by an operator who was skilled in sonography and an unskilled operator. The group of volunteers was subdivided into 2 subgroups including 16 participants, which represented the "2 moments" of acquisition by the techniques, particularly for the unskilled operator. RESULTS: The postprandial volumes obtained with 3D sonography were significantly lower in comparison to the volumes obtained with 2D sonography (P= .013), and there was a significant difference between the measurements made by the skilled and unskilled operators only for 2D sonography (P< .001), whereas between the 2 moments of acquisition by the 3D technique, there was no significant difference. The reproducibility of the technique for evaluation of gallbladder volumes was higher for 3D sonography than 2D sonography, particularly for the postprandial evaluation. CONCLUSIONS: The new 3D sonographic method using a volumetric matrix probe is a simple, reliable, and more reproducible technique than conventional 2D sonography, even if performed by an unskilled operator, and it allows a reliable stimulation test for a gallbladder dynamic study.

Standardized uptake values of (68)Ga-DOTANOC PET: a promising prognostic tool in neuroendocrine tumors.

UNLABELLED: Despite the fact that several studies have been published regarding the prognostic factors of neuroendocrine tumors (NETs), there are some cases in which available data are not sufficient to predict disease progression and to define a correct therapeutic approach. To our knowledge, the role of maximum standardized uptake value (SUVmax) as a prognostic factor has never been studied in NET patients. Therefore, we prospectively investigated whether (68)Ga-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-octreotide ((68)Ga-DOTANOC) PET SUVmax could be used as an accurate noninvasive marker for disease prognosis. METHODS: Forty-seven patients with NETs were studied with (68)Ga-DOTANOC PET. All patients underwent a baseline visit and laboratory and radiologic examinations. Follow-up was performed in all cases. RESULTS: SUVmax was significantly higher in patients with pancreatic NET and in those with well-differentiated NETs. Moreover, SUVmax was significantly higher in patients with an elevated expression of 2A-somatostatin receptor. During the follow-up, the disease was stable or presented a partial response in 25 patients, and in 19 cases the disease progressed. The patients with stable disease or a partial response had an SUVmax significantly higher than did those in the progressive disease group, with the best cutoff ranging from 17.9 to 19.3. At univariate and multivariate analysis, the significant positive prognostic factors were well-differentiated NET, an SUVmax of 19.3 or more, and a combined treatment with long-acting somatostatin analogs and radiolabeled somatostatin analogs. CONCLUSION: We demonstrated, for the first time to our knowledge, that (68)Ga-DOTANOC PET SUVmax correlates with the clinical and pathologic features of NETs and is also an accurate prognostic index.

Blunt abdominal trauma: diagnostic performance of contrast-enhanced US in children--initial experience.

PURPOSE: To prospectively compare the sensitivity and specificity of ultrasonography (US) with those of contrast material-enhanced US in the depiction of solid organ injuries in children with blunt abdominal trauma, with contrast-enhanced computed tomography (CT) as the reference standard. MATERIALS AND METHODS: The study protocol was approved by the ethics board, and written informed consent was obtained from parents. US, contrast-enhanced US, and contrast-enhanced CT were performed in 27 consecutive children (19 boys, eight girls; mean age, 8.9 years +/- 2.8 [standard deviation]) with blunt abdominal trauma to determine if solid abdominal organ injuries were present. Sensitivity, specificity, agreement, accuracy, number of lesions correctly identified, and positive and negative predictive values were determined for US and contrast-enhanced US, as compared with contrast-enhanced CT. RESULTS: In 15 patients, contrast-enhanced CT findings were negative. Contrast-enhanced CT depicted 14 solid organ injuries in 12 patients. Lesions were in the spleen (n = 7), liver (n = 4), right kidney (n = 1), right adrenal gland (n = 1), and pancreas (n = 1). Contrast-enhanced US depicted 13 of the 14 lesions in 12 patients with positive contrast-enhanced CT findings and no lesions in the patients with negative contrast-enhanced CT findings. Unenhanced US depicted free fluid in two of 15 patients with negative contrast-enhanced CT findings and free fluid, parenchymal lesions, or both in eight of 12 patients with positive contrast-enhanced CT findings. Overall, the diagnostic performance of contrast-enhanced US was better than that of US, as sensitivity, specificity, and positive and negative predictive values were 92.2%, 100%, 100%, and 93.8%, respectively. CONCLUSION: Contrast-enhanced US was almost as accurate as contrast-enhanced CT in depicting solid organ injuries in children.

Ultrasound assessment of vascularization of the thickened terminal ileum wall in Crohn's disease patients using a low-mechanical index real-time scanning technique with a second generation ultrasound contrast agent.

OBJECTIVE: To prospectively evaluate the vascularization of the thickened terminal ileum in Crohn's disease patients using contrast enhanced ultrasound (CEUS) and to compare the clinical activity measured by the Crohn's disease activity index (CDAI) with the CEUS findings. PATIENTS AND METHODS: Forty-eight of 104 consecutive patients (17 females and 31 males, aged 42.4+/-13.8 years) with a thickened terminal ileum at sonography were recruited for the study. CEUS examinations were performed using a real-time low mechanical index harmonic ultrasound technique after intravenous injection of a second generation contrast agent. We used two parameters to assess the vascularization of the bowel wall: a semi-quantitative method, the pattern of enhancement (which is the description of the arrangement of the enhanced layer in the bowel wall) and a quantitative method, the E/W ratio (which is the ratio between the major thickness of the enhanced layer, E, and the thickness of the entire wall section, W). In order to assess the accuracy of the CEUS findings in discriminating between active and inactive patients according to CDAI values (>150 and < or =150, respectively), the patterns of enhancement (four patterns) were dichotomized in two groups and an E/W ratio cutoff value was calculated to differentiate between poor and abundant bowel wall enhancement. RESULTS: The CEUS findings, namely the pattern of enhancement and the E/W ratio (best cutoff value ranging between 0.43 and 0.47), had a sensitivity of 81.0% and 81.0%, respectively, a specificity of 63.0% and 55.6%, respectively, a positive predictive value of 63.0% and 58.6%, respectively, and a negative predictive value of 81.0% and 78.9%, respectively, in distinguishing patients with active and inactive disease. CONCLUSIONS: CEUS assessment of diseased bowel wall vascularization may be a sensitive tool for the detection of inflammatory activity.

Does gabexate mesilate affect serum concentrations of acute phase proteins after endoscopic retrograde cholangiopancreatography examination?

BACKGROUND/AIMS: To explore the possibility that the preventive effect of gabexate mesilate on endoscopic retrograde cholangiopancreatography-related acute pancreatitis may be mediated by its modulation of acute phase proteins. METHODOLOGY: Thirty consecutive patients who underwent endoscopic retrograde cholangiopancreatography were randomly assigned to receive 1g of gabexate mesilate (13 patients) or a placebo (17 patients) by continuous i.v. infusion starting 30 minutes before the endoscopy session and continuing for 12 hours afterward. In all patients, C-reactive protein, serum amyloid A and interleukin 6 serum concentrations were determined before endoscopy and 4, 8, 12 and 24 hours afterward. RESULTS: Interleukin 6 basal serum concentrations were not statistically different between patients who had been treated with gabexate mesilate and those who had received the placebo (P = 0.279), whereas C-reactive protein (P = 0.033) and serum amyloid A (P = 0.022) basal values were significantly lower in the gabexate mesilate group than in the placebo group. Compared to basal values, serum interleukin 6 concentrations significantly increased at 4 (P = 0.048) and at 8 (P = 0.025) hours; the increase of serum interleukin 6 concentrations was not significant at 12 (P = 0.092), but became significant at 24 (P = 0.025) hours. C-reactive protein and serum amyloid A serum concentrations increased significantly only at 12 (P = 0.001, P = 0.012, respectively) and 24 (P < 0.001, P = 0.013, respectively) hours. The modifications of serum concentrations of interleukin 6, C-reactive protein and serum amyloid A were not significantly different between the gabexate mesilate and the placebo groups. CONCLUSIONS: Gabexate mesilate does not affect serum concentrations of acute phase proteins after endoscopic retrograde cholangiopancreatography examination and it is able to prevent acute pancreatitis related to endoscopic retrograde cholangiopancreatography via a different mechanism than that explored in this study.