Total Exposure and Exposure Rate Effects for Alcohol and Smoking and Risk of Head and Neck Cancer: A Pooled Analysis of Case-Control Studies

Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter duration was less deleterious than fewer cigarettes/day for a longer duration. Estimates of EOR/pack-year were homogeneous across sites, while the effects of cigarettes/day varied, indicating that the greater laryngeal cancer risk derived from differential cigarettes/day effects and not pack-years. EOR/drink-year estimates increased through 10 drinks/day, suggesting that greater drinks/day for a shorter duration was more deleterious than fewer drinks/day for a longer duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied by site, while drinks/day effects were homogeneous, indicating that the greater pharyngeal/oral cavity cancer risk with alcohol consumption derived from the differential effects of drink-years and not drinks/day.

Low human papillomavirus prevalence in head and neck cancer: results from two large case-control studies in high-incidence regions

Background Recent studies support an important role for human papillomavirus (HPV) in a subgroup of head and neck squamous cell carcinomas (HNSCC). We have evaluated the HPV deoxyribonucleic acid (DNA) prevalence as well as the association between serological response to HPV infection and HNSCC in two distinct populations from Central Europe (CE) and Latin America (LA). Methods Cases (n = 2214) and controls (n = 3319) were recruited from 1998 to 2003, using a similar protocol including questionnaire and blood sample collection. Tumour DNA from 196 fresh tissue biopsies was analysed for multiple HPV types followed by an HPV type-specific polymerase chain reaction (PCR) protocol towards the E7 gene from HPV 16. Using multiplex serology, serum samples were analysed for antibodies to 17 HPV types. Statistical analysis included the estimation of adjusted odds ratios (ORs) and the respective 95% confidence intervals (CIs). Results HPV16 E7 DNA prevalence among cases was 3.1% (6/196), including 4.4% in the oropharynx (3/68), 3.8% in the hypopharynx/larynx (3/78) and 0% among 50 cases of oral cavity carcinomas. Positivity for both HPV16 E6 and E7 antibodies was associated with a very high risk of oropharyngeal cancer (OR = 179, 95% CI 35.8-899) and hypopharyngeal/laryngeal cancer (OR = 14.9, 95% CI 2.92-76.1). Conclusions A very low prevalence of HPV DNA and serum antibodies was observed among cases in both CE and LA. The proportion of head and neck cancer caused by HPV may vary substantially between different geographical regions and studies that are designed to evaluate the impact of HPV vaccination on HNSCC need to consider this heterogeneity.

Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report

Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging. Regional cerebral blood flow (rCBF) at rest was measured twice using (99m)Tc-ECD SPECT in 10 treatment-naive patients with SAD. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping. Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001), reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (p < 0.001, uncorrected), and increased ECD uptake in the right posterior cingulate gyrus (p < 0.001, uncorrected). These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.

Validation of the University of Sao Paolo Sensory Phenomena Scale: Initial Psychometric Properties

Introduction: Although obsessions and compulsions comprise the main features of obsessive-compulsive disorder (OCD), many patients report that their compulsions are preceded by a sense of ""incompleteness"" or other unpleasant feelings such as premonitory urges or a need perform action`s until feeling ""just right."" These manifestations have been characterized as Sensory Phenomena (SP). The current study presents initial psychometric data for a new scale designed to measure SP. Methods: Seventy-six adult OCD subjects were probed twice. Patients were assessed with an open clinical interview (considered as the ""gold standard"") and with the following standardized instruments: Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders, Yale-Brown Obsessive-Compulsive Scale, Dimensional Yale-Brown Obsessive-Compulsive Scale, Yale Global Tic Severity Scale, Beck Anxiety Inventory, and Beck Depression Inventory. Results: SP were present in 51 OCD patients (67.1%). Tics were present in 16 (21.1%) of the overall sample. The presence of SP was significantly higher in early-onset OCD patients. There were no significant differences in the presence of SP according to comorbidity with tics or gender. The comparison between the results from the open clinical interviews and the University of Sao Paulo Sensory Phenomena Scale (USP-SPS) showed an excellent concordance between them, with no significant differences between interviewers. The inter-rater reliability between the expert raters for the USP-SPS was high, with K=.92. The Pearson correlation coefficient between the SP severity scores given by the two raters was .89. Conclusion: Preliminary results suggest that the USP-SPS is a valid and reliable instrument for assessing the presence and severity of SP in OCD subjects. CNS Spectr. 2009;14(6):315-323

Validity of the self reporting questionnaire-20 in epidemiological studies with older adults

This study examined the validity of the self-reporting questionnaire (SRQ-20) in a population-based survey with older adults in Sao Paulo, Brazil. The study sample consisted of 2,008 individuals aged 65 years or more who were living in an economically disadvantaged area of the city. The geriatric mental state (GMS) was used as the gold standard for the assessment of common mental disorders (CMD). The optimal SRQ-20 threshold for case definition was 4/5 (sensitivity = 76.1%, specificity = 74.6%, area under ROC curve = 0.82). Women, older participants and those with lower income were more likely to be misclassified by the questionnaire. The inclusion of older persons with dementia or psychosis did not change the ability of the SRQ-20 to identify cases of CMD. The SRQ-20 may be a useful instrument to be used in large epidemiological studies in resource-poor settings for the identification of cases of depression and anxiety in later life. The performance of the SRQ-20 among older adults was similar to that observed with the adult population in Brazil.

Molecular and ultrastructural studies of the fibrotic lesions of bovine focal proliferative fibrogranulomatous panniculitis (Lechiguana)

This work aimed to investigate some aspects related to the pathogenicity of Lechiguana, a bovine fibroproliferative lesion characterized by rapid collagen accumulation. Light and transmission electron microscopy and in situ hybridization studies were performed in order to elucidate the fibrogenic activity of this lesion. The characterization of fibroblastic plasticity in the lesion was done by immunohistochemical study for alpha-smooth-muscle cell actin. The ovoid-shaped cells presented positive reaction for alpha-smooth-muscle cell actin in their cytoplasm and, at the electron-microscopic level demonstrated basal lamina-like material adjacent to the external surface and collagen fibrils that corresponded to a cell population phenotypically similar to the myofibroblast. We also investigated alpha 1 collagen type I mRNA at different times of evolution of Lechiguana lesions, using isotopic and non-isotopic in situ hybridization. The results strongly suggest the involvement of a myofibroblast-like cell population that expresses mRNA for type I collagen and is probably associated with the increase of collagen deposition.

Ventilation Distribution Studies Comparing Technegas and ""Gallgas"" Using (68)GaCl(3) as the Label

Ventilation distribution can be assessed by SPECT with Technegas. This study was undertaken in piglets with different degrees of ventilation inhomogeneity to compare PET using (68)Ga-labeled pseudogas or ""Gallgas"" with Technegas. Methods: Twelve piglets were studied in 3 groups: control, lobar obstruction, and diffuse airway obstruction. Two more piglets were assessed for lung volume (functional residual capacity). Results: In controls, SPECT and PET images showed an even distribution of radioactivity. With lobar obstruction, the absence of ventilation of the obstructed lobe was visible with both techniques. In diffuse airway obstruction, SPECT images showed an even distribution of radioactivity, and PET images showed more varied radioactivity over the lung. Conclusion: PET provides detailed ventilation distribution images and a better appreciation of ventilation heterogeneity. Gallgas with PET is a promising new diagnostic tool for the assessment of ventilation distribution.

A Palliative Prognostic Score for Terminally Ill Children and Adolescents With Cancer

Background. The loss of a child is considered the hardest moment in a parent`s life. Studies addressing length of survival under pediatric palliative care are rare. The aim of this study was to improve a survival prediction model for children in palliative care, as accurate information positively impacts parent and child preparation for palliative care. Procedure. Sixty-five children referred to a pediatric palliative care team were followed from August 2003 until December 2006. Variables investigated (also included in previous studies) were: diagnosis, home care provider, presence of anemia, and performance status score given by the home care provider. Clinical variables such as symptom number were also used to test the score`s ability to pre-validated using the above variables. The number of symptoms at transition to palliative care does not improve the score`s predictive ability. The sum of the single scores gives an overall score for each patient, dividing the population into three groups by probability of 60-day survival: Group A 80.0%, Group B 38.0%, and Group C 28.5% (P < 0.001). Conclusion. A pediatric palliative care score based on easily accessible variables is statistically significant in multivariate analysis. Factors that increase accuracy of life expectancy prediction enable adequate information to be given to patients and families, contributing to therapeutic decision-making issues. Pediatr Blood Cancer. 2010;55:1167-1171. (C) 2010 Wiley-Liss, Inc.

Functional Disability in Alzheimer Disease A Validation Study of the Brazilian Version of the Disability Assessment for Dementia (DAD-Br)

Background: The assessment of activities of daily living (ADL) is important both for the diagnosis and staging of dementia. The objective of this study was to verify the applicability and validity of the Brazilian version of the Disability Assessment for Dementia (DAD-Br). Methods: The DAD was applied to caregivers of 89 patients with probable Alzheimer disease (AD) and to 40 elderly individuals without cognitive impairment (controls). We assessed the construct validity of the scale and its diagnostic accuracy (sensitivity, specificity, and predictive value). In addition, intergroup and intragroup analyses were conducted to characterize patient performance on basic and instrumental ADL and to determine underlying deficits (initiation, planning, or effective execution). Results: AD patients and controls had mean ages of 76.4 +/- 6.9 years and 74.5 +/- 7.3 years (P = 0.08), respectively. Mean Mini-Mental State Examination scores were 17.4 +/- 5.0 and 26.1 +/- 5.1 (P < 0.001) and scores on the DAD were 68.4 +/- 19.0 and 99.8 +/- 0.9 (P < 0.001), for patients and controls, respectively. The DAD scale showed good internal consistency (Cronbach alpha = 0.77) and correlation with the Mini-Mental State Examination (r = 0.44; P < 0.001). The AD group did better on basic ADL than on instrumental ADL (P < 0.001). As expected, controls did not exhibit significant deficits on the items evaluated. Conclusion: The Brazilian version of the DAD is an adequate and reliable tool for assessing functional ability in AD patients.

Validation of a Cutoff Value on Echo Doppler Analysis to Replace Right Heart Catheterization During Pulmonary Hypertension Evaluation in Heart Transplant Candidates

Background. Heart transplantation (OHT) has traditionally been contraindicated in the presence of severe pulmonary hypertension (PH), as detected by right heart catheterization. Noninvasive methods are still not reliably accurate to make this evaluation. Objectives. Determine the efficacy of echo Doppler analysis for the diagnosis of severe PH. Methods. One hundred thirty patients (mean age = 42 +/- 15 years, 82 men) showed severe left ventricular dysfunction (mean ejection fraction = 29 +/- 12%; functional class III-IV). We excluded patients with atrial fibrillation, heart failure secondary to congenital disease, and valvulopathy. The pulmonary parameters defined as severe PH were: systolic pulmonary artery pressure (sPAP) >= 60 mm Hg; a mean transpulmonary gradient >= 15; or pulmonary vascular resistance >= 5 Wood units. Patients underwent a right heart catheterization using a Swan-Ganz catheter to measure hemodynamic parameters and to noninvasively estimate right-sided pressures from spectral Doppler recordings of tricuspid regurgitation velocity (right ventricular systolic pressure [RVsP]). A Pearson correlation of sPAP was obtained with RVsP by; the sensitivity of RVsP for the diagnosis of PH was determined by a receiver operating characteristic (ROC) curve. Results. A good correlation between sPAP and RVsP was obtained by Pearson correlation analysis (r = 0.64; 95% confidence interval [CI] 0.50-0.75; P < .001). The ROC curve analysis showed a sensitivity of 100%, a specificity of 37.2%, (95% CI 0.69-0.83, P < .0001) of a RVsP < 45 mm Hg (cutoff) on the exclusion of severe PH. Conclusions. The cutoff of RVsP < 45 mm Hg, on noninvasive echo Doppler evaluation of PH is an efficient method to replace invasive heart catheterization in OHT candidates.

Clinical and biochemical studies in mucopolysaccharidosis type II carriers

The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty-two women at risk to be a carrier, with a mean age of 34.1 years (range 16-57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non-carriers. All women evaluated were clinically healthy, and their levels of urinary GAGs were within normal limits. Median plasma and leukocyte IDS activities found among carriers were significantly lower than the values found for non-carriers; there was, however, an overlap between carriers` and non-carriers` values. Our data suggests that MPS II carriers show lower plasma and leukocyte IDS activities but that this reduction is generally associated neither with changes in levels of urinary GAGs nor with the occurrence of clinical manifestations.