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.

Comparative epidemiology of chronic fatigue syndrome in Brazilian and British primary care: prevalence and recognition

Background Although fatigue is a ubiquitous symptom across countries, clinical descriptions of chronic fatigue syndrome have arisen from a limited number of high-income countries. This might reflect differences in true prevalence or clinical recognition influenced by sociocultural factors. Aims To compare the prevalence, physician recognition and diagnosis of chronic fatigue syndrome in London and Sao Paulo. Method Primary care patients in London (n=2459) and Sao Paulo n=3914) were surveyed for the prevalence of chronic fatigue syndrome. Medical records were reviewed for the physician recognition and diagnosis. Results The prevalence of chronic fatigue syndrome according to Centers for Disease Control 1994 criteria was comparable in Britain and Brazil, 2.1% v. 1.6% (P=0.20). Medical records review identified 11 diagnosed cases of chronic fatigue syndrome in Britain, but none in Brazil (P<0.001). Conclusions The primary care prevalence of chronic fatigue syndrome was similar in two Culturally and economically distinct nations. However, doctors are unlikely to recognise and label chronic fatigue syndrome as a discrete disorder in Brazil. The recognition of this illness rather than the illness itself may be culturally induced.

Interaction between Tobacco and Alcohol Use and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (psi) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (psi = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases < 45 years, 73% for cases > 60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases. (Cancer Epidemiol Biomarkers Prev 2009;18(2):541-50)

Alcohol and tobacco, and the risk of cancers of the upper aerodigestive tract in Latin America: a case-control study

Cancers of the upper aerodigestive tract (UADT; including oral cavity, pharynx, larynx and oesophagus) have high incidence rates all over the world, and they are especially frequent in some parts of Latin America. However, the data on the role of the major risk factors in these areas are still limited. We have evaluated the role of alcohol and tobacco consumption, based on 2,252 upper aerodigestive squamous-cell carcinoma cases and 1,707 controls from seven centres in Brazil, Argentina, and Cuba. We show that alcohol drinkers have a risk of UADT cancers that is up to five times higher than that of never-drinkers. A very strong effect of aperitifs and spirits as compared to other alcohol types was observed, with the ORs reaching 12.76 (CI 5.37-30.32) for oesophagus. Tobacco smokers were up to six times more likely to develop aerodigestive cancers than never-smokers, with the ORs reaching 11.14 (7.72-16.08) among current smokers for hypopharynx and larynx cancer. There was a trend for a decrease in risk after quitting alcohol drinking or tobacco smoking for all sites. The interactive effect of alcohol and tobacco was more than multiplicative. In this study, 65% of all UADT cases were attributable to a combined effect of alcohol and tobacco use. In this largest study on UADT cancer in Latin America, we have shown for the first time that a prevailing majority of UADT cancer cases is due to a combined effect of alcohol and tobacco use and could be prevented by quitting the use of either of these two agents.

The awareness of chronic fatigue syndrome: A comparative study in Brazil and the United Kingdom

Objective: While in many Western affluent countries there is widespread awareness of chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), little is known about the awareness of CFS/ME in low- and middle-income countries. We compared the awareness of CFS in Brazil and the United Kingdom. Methods: Recognition and knowledge of CFS were assessed among 120 Brazilian specialist doctors in two major university hospitals using a typical case vignette of CFS. We also surveyed 3914 and 2435 consecutive attenders in Brazilian and British primary care clinics, respectively, concerning their awareness of CFS. Results: When given a typical case vignette of CFS, only 30.8% [95% confidence interval (CI), 22.7-39.9%] of Brazilian specialist doctors mentioned chronic fatigue or CFS as a possible diagnosis, a proportion substantially lower than that observed in Western affluent countries. Similarly, only 16.2% (95% CI, 15.1-17.4%) of Brazilian primary care attenders were aware of CFS, in contrast to 55.1% (95% CI, 53.1-57.1%) of their British counterparts (P <.001). This difference remained highly significant after controlling for patients` sociodemographic and socioeconomic characteristics (P <.001). Conclusions: The awareness of CFS was substantially lower in Brazil than the United Kingdom. The observed difference may influence patients` help-seeking behavior and both doctors` and patients` beliefs and attitudes in relation to fatigue-related syndromes. Attempts to promote the awareness of CFS should be considered in Brazil, but careful plans are required to ensure the delivery of sound evidence-based information. (c) 2008 Elsevier Inc. All rights reserved.

CHOREA IN A CHILD WITH CHURG-STRAUSS SYNDROME

Introduction: Churg-Strauss syndrome (CSS) is a systemic granulomatous vasculitis rarely described in children, particularly associated with neurological involvement, exceptionally chorea. To our knowledge there are only 35 children and adolescent patients with CSS described in the literature. During a 25-year period 5283 patients were followed up at the Pediatric Rheumatology Unit of our University Hospital and only one (0.02%) presented CSS. Case report: A 7-year-old boy suffered from severe asthma, eosinophilia, history of allergy, recurrent non-fixed pulmonary infiltrates, several nodular lesions in both lungs and maxillary sinusitis. Transthoracic biopsy of the right lung revealed necrotizing extravascular eosinophilic infiltrates and the diagnosis of CSS was established. During the follow-up he had persistent vasculitis skin lesions and hemichorea. Despite the treatment with immunosuppressive drugs and intravenous immunoglobulin, he died because of pulmonary abscess and sepsis. Discussion: A rare case of CSS with chorea was reported, reinforcing the possibility of this disease in children with asthma, allergic rhinitis, hypereosinophilia and cutaneous vasculitis.

TNF receptor-associated periodic syndrome (TRAPS): Description of a novel TNFRSF1A mutation and response to etanercept

TRAPS is the most common of the autosomal dominant periodic fever syndromes. It is caused by mutations in the TNFRSF1A gene, which encodes for the type 1 TNF-receptor (TNFR1). We describe here a Brazilian patient with TRAPS associated to a novel TNFRSF1A de novo mutation and the response to anti-TNF therapy. The patient is a 9-year-old girl with recurrent fevers since the age of 3 years, usually lasting 3 to 7 days, and recurring every other week. These episodes are associated with mild abdominal pain, nausea, vomiting and generalized myalgia. Recurrent conjunctivitis and erysipela-like skin lesions in the lower limbs also occur. Laboratory studies show persistent normocytic normochromic anemia, thrombocytosis, elevated erythrocyte sedimentation rate and C-reactive protein. IgD levels are normal. Mutational screening of TNFRSF1A revealed the association of a novel C30F mutation with the common R92Q low-penetrance mutation. The R92Q mutation is seen in 5% of the general population and is associated with an atypical inflammatory phenotype. The patient had a very good response to etanercept, with cessation of fever and normalization of inflammatory markers. Our report expands the spectrum of TNFRSF1A mutations associated with TRAPS, adding further evidence for possible additive effects of a low-penetration R92Q and cysteine residue mutations, and confirms etanercept as an efficacious treatment alternative.

The spectrum of autoantibodies in IPEX syndrome is broad and includes anti-mitochondrial autoantibodies

IPEX syndrome is a congenital disorder of immune regulation caused by mutations in the FOXP3 gene, which is required for the suppressive function of naturally arising CD4 + CD25 + regulatory T cells. In this case series we evaluated serum samples from 12 patients with IPEX syndrome for the presence of common autoantibodies associated with a broad range of autoimmune disorders. We note that 75% of patients (9/12) had 1 or more autoantibodies, an incidence far above the cumulative rate observed in the general population. The range of autoantibodies differed between patients and there was no predominant autoantibody or pattern of autoantibodies present in this cohort. Surprisingly, one patient had high-titer anti-mitochondrial antibodies (AMA) typically associated with primary biliary cirrhosis (PBC) although the patient had no signs of cholestasis. PBC is a well-characterized autoimmune disease that occurs primarily in women and includes the serological hallmarks of serum AMA and elevated IgM which were both present in this patient. PBC is virtually absent in children with the exception of one reported child with interleukin 2 receptor a (CD25) deficiency which is associated with an IPEX-like regulatory T cell dysfunction. Based on the present data and the available literature we suggest a direct role for CD4 + CD25 + regulatory T cells in restraining B cell autoantibody production and that defects in regulatory T cells may be crucial to the development of PBC. (C) 2010 Elsevier Ltd. All rights reserved.

Decreased AIRE Expression and Global Thymic Hypofunction in Down Syndrome

The Down syndrome (DS) immune phenotype is characterized by thymus hypotrophy, higher propensity to organ-specific autoimmune disorders, and higher susceptibility to infections, among other features. Considering that AIRE (autoimmune regulator) is located on 21q22.3, we analyzed protein and gene expression in surgically removed thymuses from 14 DS patients with congenital heart defects, who were compared with 42 age-matched controls with heart anomaly as an isolated malformation. Immunohistochemistry revealed 70.48 +/- 49.59 AIRE-positive cells/mm(2) in DS versus 154.70 +/- 61.16 AIRE-positive cells/mm(2) in controls (p < 0.0001), and quantitative PCR as well as DNA microarray data confirmed those results. The number of FOXP3-positive cells/mm(2) was equivalent in both groups. Thymus transcriptome analysis showed 407 genes significantly hypoexpressed in DS, most of which were related, according to network transcriptional analysis (FunNet), to cell division and to immunity. Immune response-related genes included those involved in 1) Ag processing and presentation (HLA-DQB1, HLA-DRB3, CD1A, CD1B, CD1C, ERAP) and 2) thymic T cell differentiation (IL2RG, RAG2, CD3D, CD3E, PRDX2, CDK6) and selection (SH2D1A, CD74). It is noteworthy that relevant AIRE-partner genes, such as TOP2A, LAMNB1, and NUP93, were found hypoexpressed in DNA microarrays and quantitative real-time PCR analyses. These findings on global thymic hypofunction in DS revealed molecular mechanisms underlying DS immune phenotype and strongly suggest that DS immune abnormalities are present since early development, rather than being a consequence of precocious aging, as widely hypothesized. Thus, DS should be considered as a non-monogenic primary immunodeficiency. The Journal of Immunology, 2011, 187: 3422-3430.

Sensory Gating Scales and Premonitory Urges in Tourette Syndrome

Sensory and sensorimotor gating deficits characterize both Tourette syndrome (TS) and schizophrenia. Premonitory urges (PU) in TS can be assessed with the University of Sao Paulo Sensory Phenomena Scale (USP-SPS) and the Premonitory Urge for Tics Scale (PUTS). In 40 subjects (TS: n = 18; healthy comparison subjects [HCS]: n = 22), we examined the relationship between PU scores and measures of sensory gating using the USP-SPS, PUTS, Sensory Gating Inventory (SGI), and Structured Interview for Assessing Perceptual Anomalies (SIAPA), as well symptom severity scales. SGI, but not SIAPA, scores were elevated in TS subjects (p < 0.0003). In TS subjects, USP-SPS and PUTS scores correlated significantly with each other, but not with the SGI or SIAPA; neither PU nor sensory gating scales correlated significantly with symptom severity. TS subjects endorse difficulties in sensory gating and the SGI may be valuable for studying these clinical phenomena.

Effects of topiramate or naltrexone on tobacco use among male alcohol-dependent outpatients

Background: A high smoking prevalence has been registered among alcoholics. It has been pointed out that alcoholic smokers may have a more severe course and greater severity of alcoholism. This study aims at comparing smoking and non-smoking alcoholics in terms of treatment outcomes and verifying the efficacy of topiramate and naltrexone to decrease the use of cigarettes among alcoholic smokers. Methods: The investigation was a double-blind, placebo-controlled, 12-week study carried out at the University of Sao Paulo, Brazil. The sample comprised 155 male alcohol-dependent outpatients (52 nonsmokers and 103 smokers). 18-60 years of age, with an International Classification of Diseases (ICD-10) diagnosis of alcohol dependence. After a 1-week detoxification period, the patients randomly received placebo, naltrexone (50 mg/day) or topiramate (up to 300 mg/day). Only the alcoholic smokers who adhered to the treatment were evaluated with reference to the smoking reduction. Results: Cox regression analysis revealed that the smoking status among alcoholics increased the odds of relapse into drinking by 65%, independently of the medications prescribed, using the intention-to-treat method. Topiramate showed effectiveness to reduce the number of cigarettes smoked when compared to placebo among adherent patients (mean difference =7.91, p < 0.01). There were no significant differences between the naltrexone group and the placebo group. Conclusions: The results of this study confirm that the treatment is more challenging for smoking alcoholics than for non-smoking ones and support the efficacy of topiramate in the smoking reduction among male alcoholic smokers who adhered to the treatment. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

The role of alcoholic beverage preference in the severity of alcohol dependence and adherence to the treatment

The severity of dependence on alcohol and the efficacy of diverse types of treatments for alcoholism have been the subject of various researches. This study focused on the types of beverages preferentially consumed by alcohol-dependent outpatients and their effects on the severity of dependence and therapeutic outcomes. Our sample comprised 153 patients, 18-60 years of age, with an International Classification of Diseases (ICD-10) diagnosis of alcohol dependence, who were randomly divided into three different groups to receive topiramate (up to 300 mg/day), naltrexone (50 mg/day), or placebo during 12 weeks of follow-up. Spirits and beer were the main beverages consumed. At the start of this research, the group of spirits drinkers showed higher severity of alcohol dependence, higher craving for alcohol, more frequent history of treatments for alcoholism, and lower income than the group of beer preference drinkers. During the study, beer preference drinkers demonstrated higher adherence to the treatment, independently of the types of medications prescribed (P = .02, odds ratio, 2.46, 95% confidence interval, 1.17-5.19). This study suggests that the severity of dependence and the adherence to the treatment can be factors that set apart beer drinkers from spirits drinkers. As the compliance with the treatment for alcoholism was lower among spirits preference drinkers, a more intensive model of treatment would be necessary. (C) 2009 Elsevier Inc. All rights reserved.

Comparing topiramate with naltrexone in the treatment of alcohol dependence

To compare the efficacy of topiramate with naltrexone in the treatment of alcohol dependence. The investigation was a double-blind, placebo-controlled, 12-week study carried out at the University of Sao Paulo, Brazil. A total of 155 patients, 18-60 years of age, with an International Classification of Diseases (ICD-10) diagnosis of alcohol dependence. After a 1-week detoxification period, patients were assigned randomly to receive topiramate (induction to 300 mg/day), naltrexone (50 mg/day) or placebo. Time to first relapse (consumption of > 60 g ethyl alcohol), cumulative abstinence duration and weeks of heavy drinking. In intention-to-treat analyses, topiramate was statistically superior to placebo on a number of measures including time to first relapse (7.8 versus 5.0 weeks), cumulative abstinence duration (8.2 versus 5.6 weeks), weeks of heavy drinking (3.4 versus 5.9) and percentage of subjects abstinent at 4 weeks (67.3 versus 42.6) and 8 weeks (61.5 versus 31.5), but not 12 weeks (46.2 versus 27.8). Results remained significant after controlling for Alcoholics Anonymous attendance, which was higher in topiramate than in other groups. There were no significant differences between naltrexone versus placebo or naltrexone versus topiramate groups, but naltrexone showed trends toward inferior outcomes when compared to topiramate. The results of this study support the efficacy of topiramate in the relapse prevention of alcoholism. Suggestive evidence was also obtained for superiority of topiramate versus naltrexone, but this needs to be verified in future research with larger sample sizes.