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.

Otitis media with effusion and dental occlusion: is there any relationship?

Aim Auditory tube dysfunction is one of the aetiological causes of otitis media. Studies suggest a correlation between otitis media with effusion and dental malocclusion. Our goal was to determine any correlation between dental malocclusion and otitis media with effusion in children with chronic upper airway obstruction due to tonsil and adenoid enlargement. Materials and methods This prospective study evaluated 52 children with otitis media with effusion and 48 without, aged 4.2 to 10.8 years. A questionnaire was answered by the parents about breast or bottle-feeding and bad oral habits. Malocclusion was diagnosed according to Angle`s classification for molar relationships in Classes I, II and III, posterior and anterior cross bite, open and deep bite, and overjet. Results and conclusion The results suggested no correlation between dental malocclusion and otitis media with effusion. Other potential confounders, such as breast or bottle-feeding and oral habits were also not correlated.

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.

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.

GIANT FUSIFORM ANEURYSM ARISING FROM FENESTRATED POSTERIOR CEREBRAL ARTERY AND BASILAR TIP VARIATION: CASE REPORT

OBJECTIVE: A giant fusiform aneurysm in the posterior cerebral artery (PCA) is rare, as is fenestration of the PCA and basilar apex variation. We describe the angiographic and surgical findings of a giant fusiform aneurysm in the P1-P2 PCA segment associated with PCA bilateral fenestration and superior cerebellar artery double origin. CLINICAL PRESENTATION: A 26-year-old woman presented with a 2-month history of visual blurring. Digital subtraction angiography showed a giant (2.5 cm) fusiform PCA aneurysm in the right P1-P2 segment. The 3-dimensional view showed a caudal fusion pattern from the upper portion of the basilar artery associated with a bilateral long fenestration of the P1 and P2 segments and superior cerebellar artery double origin. INTERVENTION: Surgical trapping of the right P1 -P2 segment, including the posterior communicating artery, was performed by a pretemporal approach. Angiograms performed 3 and 13 months after surgery showed complete aneurysm exclusion, and the PCA was permeated and filled the PCA territory. Clinical follow-up at 14 months showed the patient with no deficits and a return to normal life. CONCLUSION: To our knowledge, this is the first report of a giant fusiform aneurysm of the PCA associated with P1-P2 segment fenestration and other variations of the basilar apex (bilateral superior cerebellar artery duplication and caudal fusion). Comprehension of the embryology and anatomy of the PCA and its related vessels and branches is fundamental to the decision-making process for a PCA aneurysm, especially when parent vessel occlusion is planned.

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.

Antenatal steroid and tracheal occlusion restore vascular endothelial growth factor receptors in congenital diaphragmatic hernia rat model

OBJECTIVE: Investigate the effects of antenatal steroids and tracheal occlusion on pulmonary expression of vascular endothelial growth factor receptors in rats with nitrofen-induced congenital diaphragmatic hernia. STUDY DESIGN: Fetuses were exposed to nitrofen at embryonic day 9.5. Subgroups received dexamethasone or were operated on for tracheal occlusion, or received combined treatment. Morphologic variables were recorded. To analyze vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2 expression, we performed Western blotting and immunohistochemistry. Morphologic variables were analyzed by analysis of variance and immunohistochemistry by Kruskal-Wallis test. RESULTS: Congenital diaphragmatic hernia decreased body weight, total lung weight, and lung-to-body weight ratio. Tracheal occlusion increased total lung weight and lung-to-body weight ratio (P < .05). Fetuses with congenital diaphragmatic hernia had reduced vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2 expression, whereas steroids and tracheal occlusion increased their expression. Combined treatment increased expression of receptors, but had no additive effect. CONCLUSION: Vascular endothelial growth factor signaling disruption may be associated with pulmonary hypertension in congenital diaphragmatic hernia. Tracheal occlusion and steroids provide a pathway for restoring expression of vascular endothelial growth factor receptors.

Surgical management of glomus jugulare tumors: a proposal for approach selection based on tumor relationships with the facial nerve Clinical article

Object. The goal of this paper is to analyze the extension and relationships of glomus jugulare tumor with the temporal bone and the results of its surgical treatment aiming at preservation of the facial nerve. Based on the tumor extension and its relationships with the facial nerve, new criteria to be used in the selection of different surgical approaches are proposed. Methods. Between December 1997 and December 2007, 34 patients (22 female and 12 male) with glomus jugulare tumors were treated. Their mean age was 48 years. The mean follow-up was 52.5 months. Clinical findings included hearing loss in 88%, swallowing disturbance in 50%, and facial nerve palsy in 41%. Magnetic resonance imaging demonstrated a mass in the jugular foramen in all cases, a mass in the middle ear in 97%, a cervical mass in 85%, and an intradural mass in 41%. The tumor was supplied by the external carotid artery in all cases, the internal carotid artery in 44%, and the vertebral artery in 32%. Preoperative embolization was performed in 15 cases. The approach was tailored to each patient, and 4 types of approaches were designed. The infralabyrinthine retrofacial approach (Type A) was used in 32.5%; infralabyrinthine pre- and retrofacial approach without occlusion of the external acoustic meatus (Type B) in 20.5%; infralabyrinthine pre- and retrofacial approach with occlusion of the external acoustic meatus (Type C) in 41 W. and the infralabyrinthine approach with transposition of the facial nerve and removal of the middle ear structures (Type D) in 6% of the patients. Results. Radical removal was achieved in 91% of the cases and partial removal in 9%. Among 20 patients without preoperative facial nerve dysfunction, the nerve was kept in anatomical position in 19 (95%), and facial nerve function was normal during the immediate postoperative period in 17 (85%). Six patients (17.6%) had a new lower cranial nerve deficit, but recovery of swallowing function was adequate in all cases. Voice disturbance remained in all 6 cases. Cerebrospinal fluid leakage occurred in 6 patients (17.6%), with no need for reoperation in any of them. One patient died in the postoperative period due to pulmonary complications. The global recovery, based on the Karnofsky Performance Scale (KPS), was 100% in 15% of the patients, 90% in 45%, 80% in 33%, and 70% in 6%. Conclusions. Radical removal of glomus jugulare tumor can be achieved without anterior transposition of the facial nerve. The extension of dissection, however, should be tailored to each case based on tumor blood supply, preoperative symptoms, and tumor extension. The operative field provided by the retrofacial infralabyrinthine approach, or the pre- and retrofacial approaches. with or without Closure of the external acoustic meatus, allows a wide exposure of the jugular foramen area. Global functional recovery based on the KPS is acceptable in 94% of the patients. (DOI: 10.3171/2008.10.JNS08612)

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.

Age and gender influence on maximal bite force and masticatory muscles thickness

The present study aimed investigate the age and gender influence on maximal molar bite force and at outlining the criteria for normal masticatory muscle development in a sample of 177 Brazilian Caucasian dentate individuals aged 7-80 years divided into five age groups: I(7-12 years), II (13-20 years), III (21-40 years), IV (41-60 years), and V (61-80 years). Except for Group V, which comprised nine women and eight men, all groups were equally divided in respect to gender (20 M/20 F). Bite force was recorded with a mouth-adapted 1000 N dynamometer and the highest out of three records was regarded as the maximal bite force. The data were submitted to multivariate statistical analysis (SPSS 17.0 p < 0.05). Effects of group and gender were found, but no interactions between them. The ANOVA showed significant differences between groups bilaterally. Bonferroni`s test showed that group I had significantly lower bite force means at both sides as compared to all groups, except group V. No differences were found between the left and right sides. In all the groups, gender was found to be a significant factor associated with maximal bite force. A global comparison including all the subjects and measures showed that the means of men were approximately 30% higher than those of women, within-group comparisons yielded similar results in all groups. Muscle thickness was measured with a SonoSite Titan ultrasound tool using a high-resolution real-time 56 mm/10 MHz linear-array transducer. Three ultrasound images were obtained from the bilateral masseter and temporal muscles at rest and at maximal voluntary contraction. The means of the three measures in each clinical condition were analyzed with multivariate statistical analysis (SPSS 17.0 p < 0.05). A gradual increase in thickness of the masseter and temporal muscles was found both at rest and maximal voluntary contraction for groups I to IV, whereas a decrease in muscle thickness was observed in group V. Multivariate analysis showed that in both conditions there was an effect of group and gender. The study of the development of the stomatognathic system in relation to age and gender can provide useful data for the identification of normal and impaired functioning patterns. The results of this study indicate that age and gender are associated with structural and functional alterations in the muscles of the stomatognathic system. (C) 2010 Elsevier Ltd. All rights reserved.

Parafoveal letter recognition at reduced contrast in normal aging and in patients with risk factors for AMD

Background Patients with early age-related maculopathy ( ARM) do not necessarily show obvious morphological signs or functional impairment. Many have good visual acuity, yet complain of decreased visual performance. The aim of this study was to investigate the aging effects on performance of parafoveal letter recognition at reduced contrast, and defects caused by early ARM and normal fellow eyes of patients with unilateral age-related macular degeneration (nfAMD). Methods Testing of the central visual field (8 radius) was performed by the Macular Mapping Test (MMT) using recognition of letters in 40 parafoveal target locations at four contrast levels (5, 10, 25 and 100%). Effects of aging were investigated in 64 healthy subjects aged 23 to 76 years (CTRL). In addition, 39 eyes (minimum visual acuity of 0.63; 20/30) from 39 patients with either no visible signs of ARM, while the fellow eye had advanced age-related macular degeneration (nfAMD; n=12), or early signs of ARM (eARM; n=27) were examined. Performance was expressed summarily as a ""field score"" (FS). Results Performance in the MMT begins to decline linearly with age in normal subjects from the age of 50 and 54 years on, at 5% and 10% contrast respectively. The differentiation between patients and CTRLs was enhanced if FS at 5% was analyzed along with FS at 10% contrast. In 8/12 patients from group nfAMD and in 18/27 from group eARM, the FS was statistically significantly lower than in the CTRL group in at least one of the lower contrast levels. Conclusion Using parafoveal test locations, a recognition task and diminished contrast increases the chance of early detection of functional defects due to eARM or nfAMD and can differentiate them from those due to aging alone.

Spontaneous Interblink Time Distributions in Patients with Graves` Orbitopathy and Normal Subjects

PURPOSE. To determine the shape of spontaneous interblink time interval distributions obtained in a long observation period in normal subjects and patients with Graves` orbitopathy. METHODS. The magnetic search coil technique was used to register the spontaneous blinking activity during 1 hour of video observation of two groups of 10 subjects each (normal controls aged 27-61 years, mean +/- SD = 46.0 +/- 13.6; patients with Graves` orbitopathy aged 33-61 years, mean +/- SD +/- 46.7 +/- 8.9). The spontaneous blink rate of each subject was calculated for the entire period of observation and for 56 five-minute bins. Histograms of the interblink time interval were plotted for each measurement of blink rate. RESULTS. Neither the overall mean blink rate (controls, 19.8 +/- 4.9; Graves`, 17.6 +/- 5.4) nor the interblink time (controls, 5.2 +/- 3.1, Graves`, 7.9 +/- 3.5) differed between the two groups. There was a large variation of both measurements when the 5-minute bins were considered. The interblink time distribution of all subjects was highly positively skewed when the 1-hour period was measured. A significant number of the 5-minute bin distributions deviated from the overall pattern and became symmetric. CONCLUSIONS. The normal blinking process is characterized by highly positively skewed interblink time distributions. This result means that most blinks have a short time interval, and occasionally a small number of blinks have long time intervals. The different patterns of distribution described in the early literature probably represent artifacts because of the small samples analyzed. (Invest Ophthalmol Vis Sci. 2011;52:3419-3424) DOI:10.1167/iovs.10-7060

Evaluation of the performance of normal elderly in a limb praxis protocol: Influence of age, gender, and education

Limb praxis can be influenced by age, gender, and education. The present Study investigated the influence of these variables on gesture production by healthy elderly Subjects. We evaluated 96 individuals divided into two age groups (60-74 and 75-88 years). Each group contained 48 men and 48 women and was subdivided into four groups according to education: illiterates and 1-3, 4-7, and 8 or more years of education. Individuals were requested to carry Out tasks oil verbal command and imitation. There were no differences between the performance of men and women, while older individuals performed worse than their younger counterparts. Regarding educational level, three major groups emerged: illiterates, individuals with 1-7 years of education, and those with 8 or more years of education. In conclusion, age and education significantly influenced the performance of individuals in limb praxis tests. (JINS, 2009, 157 618-622.)