Comparison of Quantitative Imaging Devices and Subjective Optic Nerve Head Assessment by General Ophthalmologists to Differentiate Normal From Glaucomatous Eyes

Purpose: To compare the ability of Subjective assessment of optic nerve head (ONH) and retinal nerve fiber layer (RNFL) by general ophthalmologists and by a glaucoma expert with objective measurements by optical coherence tomography (Stratus OCT, Carl Zeiss Meditec Inc), confocal scanning laser ophthalmoscope (HRT III; Heidelberg Engineering, Heidelberg. Germany), and scanning laser polarimetry (GDx enhanced corneal compensation; Carl Zeiss Meditec Inc, Dublin, CA) in discriminating glaucomatous and normal eyes. Methods: Sixty-one glaucomatous and 57 normal eyes or 118 subjects Were included in the study. Three independent general ophthalmologists and I glaucoma expert evaluated ONH stereo-photographs. Receiver operating characteristic curves were constructed for each imaging technique and sensitivity at fixed specificity was estimated. Comparisons or areas under these curves (aROCs) and agreement (k) were determined between stereophoto grading and best parameter from each technique. Results: Best parameter from each technique showed larger aROC (Stratus OCT RNFL 0.92; Stratus OCT ONH vertical integrated area = 0.86; Stratus OCT macular thickness = 0.82; GDx enhanced corneal compensation = 0.91, HRT3 global cup-to-disc ratio = 0.83; HRT3 glaucoma probability score numeric area score 0.83) compared with stereophotograph grading by general ophthalmologists (0.80) in separating glaucomatous and normal eyes. Glaucoma expert stereophoto grading provided equal or larger aROC (0.92) than best parameter of each computerized imaging device. Stereophoto evaluated by a glaucoma expert showed better agreement with best parameter of each quantitative imaging technique in classifying eyes either as glaucomatous or normal compared with stereophoto grading by general ophthalmologists, The combination Of Subjective assessment of the optic disc by general ophthalmologists with RNFL objective parameters improved identification of glaucoma patients in a larger proportion than the combination of these objective parameters with Subjective assessment of the optic disc by a glaucoma expert (29.5% vs. 19.7%, respectively). Conclusions: Diagnostic ability of all imaging techniques showed better performance than subjective assessment of the ONH by general ophthalmologists, but not by It glaucoma expert, Objective RNFL measurements may provide improvement in glaucoma detection when combined with subjective assessment of the optic disc by general ophthalmologists or by a glaucoma expert.

Metabolism of triglyceride-rich lipoproteins and lipid transfer to high-density lipoprotein in young obese and normal-weight patients with polycystic ovary syndrome

Objective: To clarify whether the metabolism of triglyceride-rich lipoproteins and lipid transfer to high-density lipoprotein (HDL) are altered in patients with polycystic ovary syndrome (PCOS). Design: Case control study. Setting: Endocrinology clinics. Patient(s): Eight normal-weight (NW) and 15 obese (013) patients with PCOS were compared with 10 NW and 10 Ob women without PCOS paired for age and body mass index. Intervention(s): Determination of triglyceride-rich lipoprotein metabolism and lipid transfer to HDL. Main Outcome Measure(s): Participants were injected triglyceride-rich emulsions labeled with (14)C-cholesteryl esters and (3)H-triglycerides and the fractional clearance rate (FCR, in min(-1)) of labels was determined. Lipid transfer from artificial nanoemulsions to HDL was performed by incubating radioactively labeled lipid nanoemulsions with plasma during 1 hour, followed by radioactive counting of HDL-containing supernatant after chemical precipitation. Result(s): Lipolysis estimated by triglyceride FCR was equal in PCOS groups (NW = 0.043 +/- 0.032, Ob = 0.033 +/- 0.009) and respective controls (NW = 0.039 +/- 0.015, Ob = 0.044 +/- 0.019). However, the remnant removal as estimated by cholesteryl ester FCR was reduced in both PCOS groups (NW = 0.005 +/- 0.006, Ob = 0.005 +/- 0.005) compared with controls (NW = 0.016 +/- 0.006, Ob = 0.011 +/- 0.072). Lipid transfer rates were not different among groups, but triglyceride transfer rates were positively correlated with homeostasis model assessment estimate of insulin resistance in PCOS. Conclusion(s): PCOS patients showed decreased removal of atherogenic remnants even when fasting glucose was <100 mg/dL. This reinforces the usefulness of the measures taken to prevent cardiovascular events in PCOS patients. (Fertil Steril (R) 2010;93:1948-56. (C)2010 by American Society for Reproductive Medicine.)

Quantitative Analysis of Placental Vasculature by Three-Dimensional Power Doppler Ultrasonography in Normal Pregnancies From 12 to 40 Weeks of Gestation

Evaluate the distribution and variation of placental vascular indices according to gestational age and placental volume. From March to November 2007, three-dimensional (3D)-power Doppler ultrasound was performed in 295 normal pregnancies from 12 to 40 weeks of gestation. Using the same preestablished settings for all patients, power Doppler was applied to the placenta and placental Volume was obtained by the rotational technique (VOCAL(TM)). The 3D-power histogram was used to determine the placental vascular indices: vascularization index (VI), flow index (FI) and vascularization-flow index (VFI). The placental vascular indices were then plotted against gestational age and placental volume. All placental vascular indices showed constant distribution throughout gestation. A tendency for a reduction in placental vascular indices with increased placental volume was observed, but was only statistically significant when placental FI was considered (p < 0.05). All placental vascular indices estimated by 3D-power Doppler ultrasonography presented constant distribution throughout gestation, despite the increase in placental volume according to gestational age. (C) 2008 Elsevier Ltd. All rights reserved.

Placental Volumes Measured by 3-Dimensional Ultrasonography in Normal Pregnancies From 12 to 40 Weeks` Gestation

Objective. The purpose of this study was to construct nomograms of placental volumes according to gestational age and estimated fetal weight. Methods. From March to November 2007, placental volumes were prospectively measured by ultrasonography in 295 normal pregnancies from 12 to 40 weeks` gestation and correlated with gestational age and estimated fetal weight. Inclusion criteria were healthy women, singleton pregnancies with normal fetal morphologic characteristics on ultrasonography, and confirmed gestational age by first-trimester ultrasonography. Results. The mean placental volume ranged from 83 cm(3) at 12 weeks to 427.7 cm(3) at 40 weeks. Linear regression yielded the following formula for the expected placental volumes (ePV) according to gestational age (GA): ePV` (cm(3)) = -64.68 + 12.31 x GA (r = 0.572; P < .001). Placental volumes also varied according to estimated fetal weight (EFW), and the following mathematical equation was also obtained by linear regression: ePV = 94.19 + 0.09 x EFW (r = 0.505; P < 0.001). Conclusions. Nomograms of placental volumes according to gestational age and estimated fetal weight were constructed, generating reference values.

Diagnostic model based on Raman spectra of normal, hyperplasia and prostate adenocarcinoma tissues in vitro

This study evaluated the use of Raman spectroscopy to identify the spectral differences between normal (N), benign hyperplasia (BPH) and adenocarcinoma (CaP) in fragments of prostate biopsies in vitro with the aim of developing a spectral diagnostic model for tissue classification. A dispersive Raman spectrometer was used with 830 nm wavelength and 80 mW excitation. Following Raman data collection and tissue histopathology (48 fragments diagnosed as N, 43 as BPH and 14 as CaP), two diagnostic models were developed in order to extract diagnostic information: the first using PCA and Mahalanobis analysis techniques and the second one a simplified biochemical model based on spectral features of cholesterol, collagen, smooth muscle cell and adipocyte. Spectral differences between N, BPH and CaP tissues, were observed mainly in the Raman bands associated with proteins, lipids, nucleic and amino acids. The PCA diagnostic model showed a sensitivity and specificity of 100%, which indicates the ability of PCA and Mahalanobis distance techniques to classify tissue changes in vitro. Also, it was found that the relative amount of collagen decreased while the amount of cholesterol and adipocyte increased with severity of the disease. Smooth muscle cell increased in BPH tissue. These characteristics were used for diagnostic purposes.

The frequency of human papillomavirus findings in normal oral mucosa of healthy people by PCR

The human papillomavirus (HPV) is a DNA virus, which belongs to papillomaviridae family, being of low and high risk, which infect the skin and mucous membranes and can induce benign and malign tumor formation. In the oral mucosa they have been associated with oral papilloma, focal epithelial hyperplasia, leucoplakia and oral neoplasia. Aim: to study the frequency of HPV finding in oral mucosa of normal people. Materials and methods: Prospective study, cross-sectional cohort. One hundred volunteers, young adults, healthy, aged between 20 and 31 years, university students with no history, no complains, without oral or oropharyngeal lesions. They were submitted to a questionnaire with questions regarding HPV infection epidemiology. The samples were harvested by brushing and analyzed by PCR. Results: The results were negative for HPV in all samples. Conclusion: It seems we had high social and economical class individuals, with nutrition rich in carotenoyds and vitamin C, low smoking and alcohol consumption and heterosexual habits with predominant monogamy and regular use of condoms.

Normal metabolite levels in the left dorsolateral prefrontal cortex of unmedicated major depressive disorder patients: A single voxel (1)H spectroscopy study

Few proton magnetic resonance spectroscopy ((1)H spectroscopy) studies have investigated the dorsolateral prefrontal cortex (DLPFC), a key region in the pathophysiology of major depressive disorder (MDD). We used (1)H spectroscopy to verify whether MDD patients differ from healthy controls (HQ in metabolite levels in this brain area. Thirty-seven unmedicated DSM-IV MDD patients were compared with 40 HC. Subjects underwent a short echo-time (1)H spectroscopy examination at 1.5 T, with an 8-cm(3) single voxel placed in the left DLPFC. Reliable absolute metabolite levels of N-acetyl aspartate (NAA), phosphocreatine plus creatine (PCr+Cr), choline-containing compounds (GPC+PC), myo-inositol, glutamate plus glutamine (Glu+Gln), and glutamate were obtained using the unsuppressed water signal as an internal reference. Metabolite levels in the left DLPFC did not statistically differ between MDD patients and HC. We found an interaction between gender and diagnosis on PCr+Cr levels. Male MDD patients presented lower levels of PCr+Cr than male HC, and female MDD patients presented higher levels of PCr+Cr than female HC. Moreover, length of illness was inversely correlated with NAA levels. These findings suggest that there is not an effect of diagnosis on the left DLPFC neurochemistry. Possible effects of gender on PCr+Cr levels of MDD patients need to be further investigated. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

The Incapacity of the Surgeon to Identify NASH in Bariatric Surgery Makes Biopsy Mandatory

Nonalcoholic steatohepatitis (NASH) is a morbid condition highly related to obesity. It is unclear if the macroscopic liver appearance correlates with the histopathologic findings. The goal of this prospective study was to determine the relationship between the intraoperative liver appearance and the histopathologic diagnosis of NASH in morbidly obese subjects undergoing bariatric surgery. We also aimed to determine variables that could predict NASH preoperatively. Consecutive 51 subjects undergoing bariatric surgery without evidence of other liver disease underwent intraoperative liver biopsy. An intraoperative liver visual (macroscopic and tactile examination) was recorded. The liver aspect was compared with the liver histologic findings. Histological assessment was categorized into two groups: NASH and non-NASH (including normal histology and simple steatosis). Clinical and biochemical parameters were obtained from the patient databases and were compared between groups to identify preoperatively predictive factors of NASH. From 51 patients, only one presented totally normal histology. Forty-three (86.2%) presented simple steatosis, and seven (13.7%) were classified as NASH. Clinical parameters were not different between groups. At biochemical analysis, only VLDL cholesterol level was significantly higher in the NASH group (p = 0.037) but yet within the normal range. Association between macroscopic liver appearance and the presence of histological NASH is poor (sensitivity of 14%, specificity of 56%, positive predictive value of 5%, and negative predictive value of 80%). No predictor of NASH was found. Surgeons` evaluation could not identify NASH individuals. Routine liver biopsy during bariatric operations is mandatory to differentiate NASH and nonalcoholic fatty liver disease.

Abnormal methylation at the KvDMR1 imprinting control region in clinically normal children conceived by assisted reproductive technologies

Genomic imprinting alterations have been shown to be associated with assisted reproductive technologies (ARTs) in animals. At present, data obtained in humans are inconclusive; however, some epidemiological studies have demonstrated an increased incidence of imprinting disorders in children conceived by ARTs. In the present study, we focused on the effect of ARTs [IVF and intracytoplasmic sperm injection (ICSI)] on the epigenetic reprogramming of the maternally methylated imprinting control region KvDMR1 in clinically normal children. Qualitative and quantitative methylation at KvDMR1 were assessed by the methylation-specific PCR approach and by the methylation-sensitive enzymatic digestion associated with real-time PCR method, respectively. DNA was obtained from peripheral blood of 12/18 and umbilical cord blood and placenta of 6/18 children conceived by IVF or ICSI. The methylation patterns observed in this group were compared with the patterns observed in 30 clinically normal naturally conceived children (negative controls) and in 3 naturally conceived Beckwith-Wiedemann syndrome patients (positive controls). Hypomethylation at KvDMR1 was observed in 3/18 clinically normal children conceived by ARTs (2 conceived by IVF and 1 by ICSI). A discordant methylation pattern was observed in the three corresponding dizygotic twins. Our findings corroborate the hypothesis of vulnerability of maternal imprinting to ARTs. Furthermore, the discordant methylation at KvDMR1 observed between dizygotic twins could be consequent to one of the following possibilities: (i) a differential vulnerability of maternal imprints among different embryos; or (ii) epimutations that occurred during gametogenesis resulting in the production of oocytes without the correct primary imprint at KvDMR1.

Factors determining normal adult height in girls with gonadotropin-dependent precocious puberty treated with depot gonadotropin-releasing hormone analogs

Context: Several factors can affect adult height (AH) of patients with gonadotropin-dependent precocious puberty (GDPP) treated with depot GnRH analogs. Objective: Our objective was to determine factors influencing AH in patients with GDPP treated with depot GnRH analogs. Patients: A total of 54 patients (45 girls) with GDPP treated with depot GnRH analog who reached AH was included in the study. Design: Univariate and multivariate analyses of the factors potentially associated with AH were performed in all girls with GDPP. In addition, clinical features of the girls who attained target height (TH) range were compared with those who did not. Predicted height using Bayley and Pinneau tables was compared with attained AH. Results: In girls the mean AH was 155.3 +/- 6.9 cm (-1.2 +/- 1 SD) with TH range achieved by 81% of this group. Multiple regression analysis revealed that the interval between chronological age at onset of puberty and at the start of GnRH analog therapy, height SD scores (SDSs) at the start and end of therapy, and TH explained 74% of AH variance. The predicted height at interruption of GnRH therapy, obtained from Bayley and Pinneau tables for average bone age, was more accurate than for advanced bone age in both sexes. In boys the mean AH was 170.6 +/- 9.2 cm (-1 +/- 1.3 SDS), whereas TH was achieved by 89% of this group. Conclusions: The major factors determining normal AH in girls with GDPP treated with depot GnRH analogs were shorter interval between the onset of puberty and start of therapy, higher height SDS at the start and end of therapy, and TH. Therefore, prompt depot GnRH analog therapy in properly selected patients with GDPP is critical to obtain normal AH.

Evaluation of mild hyperhomocysteinemia during the development of atherosclerosis in apolipoprotein E-deficient and normal mice

We focused on the effect of mild hyperhomocysteinemia (HHcy) on the development of atherosclerosis, using apolipoprotein E-deficient (apoE(-/-)) and normal mice. Mice received diets enriched in methionine with low or high levels of folate, B(12) and B(6) (diets B and C, respectively), and diet only with low levels of folate, B(12) and B(6) (diets D), to induce mild HHcy. Normal mice fed on diets B, C and D presented mild HHcy, but they did not develop atherosclerotic lesions after 24 weeks of diet. In addition, increased endoplasmic reticulum stress was present in normal mice fed on diet B, compared to others groups. ApoE(-/-) mice fed on diet B for 20 weeks presented the greatest atherosclerotic lesion area at the aortic sinus than other groups. These results suggest that the methionine may have a toxic effect on endothelium, and the B-vitamins addition on diet may have a protective effect in the long term, despite the increase on homocysteine levels. Mild HHcy accelerated the development of atherosclerosis in apoE(-/-) mice, and supplementation with B-vitamins is important for prevention of vascular disease, principally in the long term. (C) 2010 Elsevier Inc. All rights reserved.

A new proctoscope for transanal endoscopic operations

Transanal access is one of many currently used procedures for rectal cancer treatment. The techniques used for local excision include conventional transanal excision, posterior access, therapeutic colonoscopy and transanal endoscopic approaches. The aim of the present study was to present a new surgical proctoscope for the endoscopic transanal excision of rectal lesions. A cylindrical proctoscope with a diameter of 4 cm was devised and built. The end inserted into the anus has a bevelled aspect and rounded borders, allowing correct exposure of the anal lesion. The rectoscope is fixed to the anal border with surgical thread through perforations in the external end. A base screw holds a fibre-light which illuminates the operative field. Part of the equipment is a guide which is positioned inside the rectoscope on insertion into the anus. In operations utilizing this proctoscope, 17 adenomas, 25 adenocarcinomas, 1 carcinoid and 1 endometrioma were excised. The diameter of the lesions varied from 1 to 6 cm. The range of procedures that are possible with this new proctoscope are similar to those achieved with conventional techniques which, however, require more expensive equipment. Hence, the present study demonstrates that this newly devised low-cost proctoscope is an efficient tool for the transanal endoscopic excision of rectal lesions.

Enantioselective Determination of Mexiletine and Its Metabolites p-Hydroxymexiletine and Hydroxymethylmexiletine in Rat Plasma by Normal-Phase Liquid Chromatography-Tandem Mass Spectrometry: Application to Pharmacokinetics

Mexiletine (MEX), hydroxymethylmexiletine (HMM) and P-hydroxy-mexiletine (PHM) were analyzed in rat plasma by LC-MS/MS. The plasma samples were prepared by liquid-liquid extraction using methyl-tert-butyl ether as extracting solvent. MEX, HMM, and PHM enantiomers were resolved on a Chiralpak (R) AD column. Validation of the method showed a relative standard deviation (precision) and relative errors (accuracy) of less than 15% for all analytes studied. Quantification limits were 0.5 ng ml(-1) for the MEX and 0.2 ng ml(-1) for the HMM and PHM enantiomers. The validated method was successfully applied to quantify the enantiomers of MEX and its metabolites in plasma samples of rats (n = 6) treated with a single oral dose of racemic MEX. Chirality 21:648-656, 2009. (C) 2008 Wiley-Liss, Inc.