Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been proposed as a possible candidate for involvement in the pathophysiology of bipolar disorder ( BD). To determine whether an association exists between the BDNF Val66Met genotype and morphometric abnormalities of the brain regions involved in memory and learning in BD and healthy subjects. Forty-two BD patients and 42 healthy subjects were studied. Interactions between BDNF Val66Met genotype and diagnosis in gray ( GM) volumes were analyzed using an optimized voxel-based morphometry technique. Declarative memory function was assessed with the California Verbal Learning Test II. Left and right anterior cingulate GM volumes showed a significant interaction between genotype and diagnosis such that anterior cingulate GM volumes were significantly smaller in the Val/Met BD patients compared with the Val/Val BD patients (left P = 0.01, right P = 0.01). Within-group comparisons revealed that the Val/Met carriers showed smaller GM volumes of the dorsolateral prefrontal cortex compared with the Val/Val subjects within the BD patient (P = 0.01) and healthy groups (left P = 0.03, right P = 0.03). The Val/Met healthy subjects had smaller GM volumes of the left hippocampus compared with the Val/Val healthy subjects (P<0.01). There was a significant main effect of diagnosis on memory function (P = 0.04), but no interaction between diagnosis and genotype was found (P = 0.48). The findings support an association between the BDNF Val66Met genotype and differential gray matter content in brain structures, and suggest that the variation in this gene may play a more prominent role in brain structure differences in subjects affected with BD. Neuropsychopharmacology (2009) 34, 1904-1913; doi: 10.1038/npp.2009.23; published online 18 March 2009

Elevation of Uterine Basal Tone and Fetal Heart Rate Abnormalities After Labor Analgesia A Randomized Controlled Trial

OBJECTIVE: To estimate the effects of combined spinal-epidural and traditional epidural analgesia on uterine basal tone and its association with the occurrence of fetal heart rate (FHR) abnormalities. METHODS: Seventy-seven laboring patients who requested pain relief during labor were randomly assigned to combined spinal-epidural (n=41) or epidural analgesia (n=36). Uterine contractions and FHR were recorded 15 minutes before and after analgesia. Uterine tone was evaluated with intrauterine pressure catheter. Primary outcomes were the elevation of baseline uterine tone and occurrence of FHR prolonged decelerations or bradycardia after analgesia. The influence of other variables such as oxytocin use, hypotension, and speed of pain relief were estimated using a logistic regression model. RESULTS: The incidence of all outcomes was significantly greater in the combined spinal-epidural group compared with epidural: uterine hypertonus (17 compared with 6; P=.018), FHR abnormalities (13 compared with 2; P<.01), and both events simultaneously (11 compared with 1; P<.01). Logistic regression analysis showed the type of analgesia as the only independent predictor of uterine hypertonus (odds ratio 3.526, 95% confidence interval 1.21-10.36; P=.022). For the occurrence of FHR abnormalities, elevation of uterine tone was the independent predictor (odds ratio 18.624, 95% confidence interval 4.46-77.72; P<.001). Regression analysis also found a correlation between decrease on pain scores immediately after analgesia and the estimated probability of occurrence of hypertonus and FHR abnormalities. CONCLUSION: Combined spinal-epidural analgesia is associated with a significantly greater incidence of FHR abnormalities related to uterine hypertonus compared with epidural analgesia. The faster the pain relief after analgesia, the higher the probability of uterine hypertonus and FHR changes. CLINICAL TRIAL REGISTRATION: Umin Clinical Trials Registry, http://www.umin.ac.jp/ctr/index.htm, UMIN000001186

High prevalence of pituitary magnetic resonance abnormalities and gene mutations in a cohort of Brazilian children with growth hormone deficiency and response to treatment

Data were retrospectively collected from 69 Brazilian patients (45 boys) with growth hormone deficiency (GHD) who received exogenous growth hormone (GH) for a median duration of 4 years (range 1-13 years). Forty-two patients had multiple pituitary hormone deficiencies and 27 had isolated GHD. Peak GH was <7 ng/ml (IRMA) or <3.2 ng/ml (IFMA) after two stimulation tests.. Therapy was started at median age of 10.0 years (range 2.2-21.6 years), bone age of 5.8 years (0.5-13.5 years) and height standard deviation score -4.4 (range -9.3 to -1.6). MRI revealed pituitary abnormalities in 87% of patients. Homozygous mutations in PROP-1, GHRH-R, GH-1 or HESX-1 genes were found in 12 patients. Mean height velocities were 3.3 pretreatment and 10.3, 7.8, 7.4 and 6.4 cm/yr, respectively, during 1-4 years of treatment with GH. In conclusion, the high prevalence (96%) of genetic and/or pituitary abnormalities probably reflects the stringent diagnostic criteria used, and GH replacement resulted in significant catch-up growth.

Intra- and inter-observer reliability of MRI examination of intervertebral disc abnormalities in patients with cervical myelopathy

Purpose: Intervertebral cervical disc herniation (CDH) is a relatively common disorder that can coexist with degenerative changes to worsen cervicogenic myelopathy. Despite the frequent disc abnormalities found in asymptomatic populations, magnetic resonance imaging (MRI) is considered excellent at detecting cervical spine myelopathy (CSM) associated with disc abnormality. The objective of this study was to investigate the intra- and inter-observer reliability of MRI detection of CSM in subjects who also had co-existing intervertebral disc abnormalities. Materials and methods: Seven experienced radiologists reviewed twice the MRI of 10 patients with clinically and/or imaging determined myelopathy. MRI assessment was performed individually, with and without operational guidelines. A Fleiss Kappa statistic was used to evaluate the intra- and inter-observer agreement. Results: The study found high intra-observer percent agreement but relatively low Kappa values on selected variables. Inter-observer reliability was also low and neither observation was improved with operational guidelines. We believe that those low values may be associated with the base rate problem of Kappa. Conclusion: In conclusion, this study demonstrated high intra-observer percent agreement in MR examination for intervertebral disc abnormalities in patients with underlying cervical myelopathy, but differing levels of intra- and inter-observer Kappa agreement among seven radiologists. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside

Chantler PD, Nussbacher A, Gerstenblith G, Schulman SP, Becker LC, Ferrucci L, Fleg JL, Lakatta EG, Najjar SS. Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside. Am J Physiol Heart Circ Physiol 300: H1914-H1922, 2011. First published March 4, 2011; doi:10.1152/ajpheart.01048.2010.-The coupling between arterial elastance (E(A); net afterload) and lea ventricular elastance (E(LV); pump performance), known as E(A)/E(LV), is a key determinant of cardiovascular performance and shifts during exercise due to a greater increase in E(LV) versus E(A). This normal exercise-induced reduction in E(A)/E(LV) decreases with advancing age. We hypothesized that sodium. nitroprusside (SNP) can acutely ameliorate the age-associated deficits in E(A)/E(LV). At rest and during graded exercise to exhaustion, EA was characterized as end-systolic pressure/stroke volume and E(LV) as end-systolic pressure/end-systolic volume. Resting E(A)/E(LV): did not differ between old (70 +/- 8 yr. n = 15) and young (30 +/- 5 yr. n = 17) subjects because of a tandem increase in E(A) and E(LV) in older subjects. During peak exercise, a blunted increase in E(LV) in old (7.8 +/- 3.1 mmHg/ml) versus young (11.4 +/- 6.5 mmHg/ml) subjects blunted the normal exercise-induced decline in E(A)/E(LV) in old (0.25 +/- 0.11) versus young (0.16 +/- 0.05) subjects. SNP administration to older subjects lowered resting E(A)/E(LV) by 31% via a reduction E(A) (10%) and an increase in E(LV) (47%) and lowered peak exercise E(A)/E(LV) (36%) via an increase in E(LV) (68%) without a change in E(A). Importantly, SNP attenuated the age-associated deficits in E(A)/E(LV) and E(LV) during exercise, and at peak exercise E(A)/E(LV) in older subjects on drug administration did not differ from young subjects without drug administration. In conclusion, some age-associated deficiencies in E(A)/E(LV), E(A), and E(LV), in older subjects can be acutely abolished by SNP infusion. This is relevant to common conditions in older subjects associated with a significant impairment of exercise performance such as frailty or heart failure with preserved ejection fraction.

The expression of Delta NTP73, TATP73 and TP53 genes in acute myeloid leukaemia is associated with recurrent cytogenetic abnormalities and in vitro susceptibility to cytarabine cytotoxicity

TP73 encodes for two proteins: full-length TAp73 and Delta Np73, which have little transcriptional activity and exert dominant-negative function towards TP53 and TAp73. We compared TATP73 and Delta NTP73 expression in acute myeloid leukaemia (AML) samples and normal CD34(+) progenitors. Both forms were more highly expressed in leukaemic cells. Amongst AML blasts, TATP73 was more expressed in AML harbouring the recurrent genetic abnormalities (RGA): PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11, whereas higher Delta NTP73 expression was detected in non-RGA cases. TP53 expression did not vary according to Delta NTP73/TATP73 expression ratio. Leukaemic cells with higher Delta NTP73/TATP73 ratios were significantly more resistant to cytarabine-induced apoptosis.

High expression of AURKA and AURKB is associated with unfavorable cytogenetic abnormalities and high white blood cell count in patients with acute myeloid leukemia

In the present study, we analyzed AURKA and AURKB gene expression in 70 acute myeloid leukemia (AML) patients. There was no difference between leukemic samples and bone marrow mononuclear cells (BMMCs, n = 8) or CD34(+) progenitors (n = 10) from healthy donors. High white blood cells (WBC) counts were observed in the AURKA(+) and AURKB(+) groups, but no significant differences regarding age, gender, platelet counts or frequency of FLT3-ITD mutations. AURKA, but not AURKB, expression was independently associated with high WBC counts (OR: 3.15, 95% CI 1.07-9.24, p = 0.03). Moreover, the majority of cases that overexpressed AURKA and AURKB presented unfavorable cytogenetic abnormalities (p < 0.001). In conclusion, we described a significant association between overexpression of AURKA/B and cytogenetics findings in AML, which may be relevant to new therapeutic approaches, based on Aurora kinase inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.

Changes in facial morphology after adenotonsillectomy in mouth-breathing children

Background. Morphological and dentofacial alterations have been attributed to impaired respiratory function. Objective. To examine the influence of mouth breathing (MB) on children facial morphology before and after adenoidectomy or adenotonsillectomy. Methods. Thirty-three MB children who restored nasal breathing (NB) after surgery and 22 NB children were evaluated. Both groups were submitted to lateral cephalometry, at time 1 (T1) before and at time 2 (T2) 28 months on average postoperatively. Results. Comparison between the MB and NB groups at T1 showed that mouth breathers had higher inclination of the mandibular plane; more obtuse gonial angle; dolichofacial morphology; and a decrease in the total and inferior posterior facial heights. Twenty-eight months after the MB surgical intervention, they still presented a dolichofacial morphologic pattern. During this period, MB altered the face growth direction and decreased their mandible plane inclination, with reduction in the SN.GoGn, PP.MP, SNGn, and ArGo.GoMe parameters as well as an increase in BaN.PtGn. Conclusion. After the MB rehabilitation, children between 3 and 6 years old presented significant normalization in the mandibular growth direction, a decrease in the mandible inclination, and an increase in the posterior facial height. Instead, they still persisted with a dolichofacial pattern when compared with nasal breathers.

Detection of Bartonella spp. in neotropical felids and evaluation of risk factors and hematological abnormalities associated with infection

Although antibodies to Bartonella henselae have been described in all neotropical felid species, DNA has been detected in only one species, Leopard us wiedii. The aim of this study was to determine whether DNA of Bartonella spp. could be detected in blood of other captive neotropical felids and evaluate risk factors and hematological findings associated with infection. Blood samples were collected from 57 small felids, including 1 Leopard us geoffroyi, 17 L wiedii, 22 Leopardus tigrinus, 14 Leopardus pardalis, and 3 Puma yagouaroundi; 10 blood samples from Panthera onca were retrieved from blood banks. Complete blood counts were performed on blood samples from small felids, while all samples were evaluated by PCR. DNA extraction was confirmed by amplification of the cat GAPDH gene. Bartonella spp. were assessed by amplifying a fragment of their 16S-23S rRNA intergenic spacer region; PCR products were purified and sequenced. For the small neotropical felids, risk factors [origin (wild-caught or zoo-born), gender, felid species, and flea exposure) were evaluated using exact multiple logistic regression. Hematological findings (anemia, polycythemia/hyperproteinemia, leukocytosis and leukopenia) were tested for association with infection using Fisher`s exact test. The 635 bp product amplified from 10 samples (10/67 = 14.92%) was identified as B. henselae by sequencing. Small neotropical felid males were more likely to be positive than females (95% CI = 0.00-0.451, p = 0.0028), however other analyzed variables were not considered risk factors (p > 0.05). Hematological abnormalities were not associated with infection (p > 0.05). This is the first report documenting B. henselae detection by PCR in several species of neotropical felids. (C) 2009 Elsevier B.V. All rights reserved.

Squamous Cell Carcinoma of the Tongue and Floor of the Mouth: Analysis of Survival Rate and Independent Prognostic Factors in the Amazon Region

Oral squamous cell carcinoma (OSCC) accounts for more than 95% of all malignant neoplasms in the oral cavity. Although several studies have shown the epidemiology of this cancer in Brazil, there do not seem to be any studies that describe the prognostic factors related to OSCC in the Amazon region. Therefore, the aim of this study was to determine the survival rate and prognostic significance of different factors in patients from this region affected by OSCC. Data from 85 patients with histologically confirmed squamous cell carcinoma of the tongue and floor of the mouth identified from the Ofir Loyola Hospital archives were collected and analyzed using univariate (log-rank test) and multivariate (Cox proportional hazard model) tests. The overall 5-year survival rate was found to be 27%. Univariate analysis showed that the 5-year survival rate was significantly higher for younger (<= 45 y) female patients, patients with T1-2 tumors and clinically clear neck nodes (N0), patients with early stage cancers (AJCC stage I-II), and patients treated with surgical procedures. However, multivariate analysis showed that the 5-year survival rate was significantly higher only in the younger patients and those who underwent surgical treatment. The age of the patient at the moment of diagnosis and treatment with surgical procedures were the only independent prognostic factors that affected the 5-year survival rate of the patients in this region.

Oral and Dental Abnormalities in Barber-Say Syndrome

A previously unreported case of Barber Say syndrome is described with special attention to dental manifestations. A 7-year-old female with multiple congenital anomalies such mammary gland hypoplasia, hypertrichosis, ectropion, and redundant skin was seen at the School of Dentistry of the University of Sao Paulo. Oral examination revealed macrostomia, broad alveolar ridges, gingival fibromatosis, taurodontism, delayed tooth eruption, and malocclusion. Dental treatment included gingivoplasty and orthodontic treatment. (C) 2010 Wiley-Liss, Inc.

Tooth abnormalities and soft tissue alterations in patients with G/BBB syndrome

OBJECTIVE: The G/BBB syndrome is an X-linked recessive disorder characterized by eye anomalies, laryngotracheoesophageal cleft, congenital heart disease, genitourinary anomalies and gastrointestinal disorders. Patients may also present cleft lip and palate, high-arched palate and thin upper lip. This study aimed to investigate the occurrence of tooth abnormalities and soft tissue changes in patients with G/BBB syndrome. DESIGN: Cross-sectional. SUBJECTS AND METHODS: Twenty-one patients with G/BBB syndrome were analyzed as to the presence of tooth abnormalities and soft tissue alterations. MAIN OUTCOME MEASURES: The prevalence of tooth agenesis and supernumerary teeth was compared to patients without morphofunctional alterations, matched for gender and age. RESULTS: All patients had complete cleft lip and palate; 95.23% of patients presented tooth abnormalities, mainly hypoplastic alterations, with predominance of alterations of number, followed by alterations of structure, shape and position. The frequency of tooth agenesis and supernumerary teeth was significantly higher compared with the control group; 11 patients presented incisiform supernumerary teeth in the mandibular anterior region. Ankyloglossia was observed in 11 of 21 patients. CONCLUSION: The presence of mandibular anterior supernumerary teeth and ankyloglossia should be investigated in the clinical evaluation of patients with suspected diagnosis of the G/BBB syndrome. Oral Diseases (2008) 14, 747-753

Tooth abnormalities and soft tissue changes in patients with velocardiofacial syndrome

Objective. The objective of this study was to investigate the prevalence of tooth abnormalities and soft tissue changes in patients with velocardiofacial syndrome. Study design. Twenty-six patients with velocardiofacial syndrome were examined to investigate the presence of tooth abnormalities and soft tissue alterations. The occurrence of tooth agenesis and supernumerary teeth was compared to patients without morphofunctional alterations, matched for gender and age. Results. Of all patients, 76.92% exhibited at least one tooth abnormality, with predominance of hypoplastic alterations, especially represented by hypodevelopment of the lingual cusp of mandibular first premolars and enamel opacities. The occurrence of tooth agenesis and supernumerary teeth was similar in both study and control groups. Conclusion. the present results suggest an association between hypodevelopment of the lingual cusp of mandibular first premolars and enamel opacities, yet these findings still require corroboration. Future studies should further investigate these aspects in larger samples compared to control groups, as well as employing molecular genetics techniques.

Caries-preventive Efficacy and Retention of a Resin-modified Glass lonomer Cement and a Resin-based Fissure Sealant: A 3-year Split-mouth Randomised Clinical Trial

Purpose: This prospective clinical trial compared the retention rate and caries-preventive efficacy of two types of sealant modalities over a 3-year period. Materials and Methods: Using a split-mouth randomised design, 1280 sealants were randomly applied on sound permanent second molars of 320 young patients aged between 12 and 16 years. Half of the teeth (n = 640) were sealed with a resin-modified glass ionomer cement (RMGIC) (Vitremer (TM), 3M ESPE) and the other half (n = 640) with a conventional light-cure, resin-based fissure sealant (LCRB) (Fluoroshield (R), Dentsply Caulk). Teeth were evaluated at baseline, 6-, 12-, 18-, 24-, 30- and 36-month intervals with regard to retention and new caries development. Results: On the sealed occlusal surfaces after 3 years, 5.10% of RMGIC and 91.08% of LCRB sealants were totally intact and 6.37% of RMGIC and 7.65% of LCRB sealants were partially intact. New caries lesions were found in 20.06% of RMGIC sealed occlusal surfaces, compared to 8.91% for LCRB sealants. Conclusions: The findings of the present clinical study suggest that RMGIC should be used only as a transitional sealant that can be applied to newly erupting teeth throughout the eruptive process, whereas LCRB sealants are used to successfully prevent occlusal caries lesions once an effective rubber dam can be achieved. It can be concluded that there are differences between the RMGIC and LCRB sealants over a 3-year period in terms of the retention rate and caries-preventive efficacy. RMGIC can serve as a simple and economic sealing solution, however provisional. Due to its poor retention rate, periodic recalls are necessary, even after 6 months, to eventually replace the lost sealant.