The use of fluorescence in situ hybridization in the diagnosis of hidden mosaicism: apropos of three cases of sex chromosome anomalies

FISH has been used as a complement to classical cytogenetics in the detection of mosaicism in sex chromosome anomalies. The aim of this study is to describe three cases in which the final diagnosis could only be achieved by FISH. Case 1 was an 8-year-old 46,XY girl with normal female genitalia referred to our service because of short stature. FISH analysis of lymphocytes with probes for the X and Y centromeres identified a 45,X/46,X,idic(Y) constitution, and established the diagnosis of Turner syndrome. Case 2 was a 21-month-old 46,XY boy with genital ambiguity (penile hypospadias, right testis, and left streak gonad). FISH analysis of lymphocytes and buccal smear identified a 45,X/46,XY karyotype, leading to diagnosis of mixed gonadal dysgenesis. Case 3 was a 47,XYY 19-year-old boy with delayed neuromotor development, learning disabilities, psychological problems, tall stature, small testes, elevated gonadotropins, and azoospermia. FISH analysis of lymphocytes and buccal smear identified a 47,XYY/48,XXYY constitution. Cases 1 and 2 illustrate the phenotypic variability of the 45,X/46,XY mosaicism, and the importance of detection of the 45,X cell line for proper management and follow-up. In case 3, abnormal gonadal function could be explained by the 48,XXYY cell line. The use of FISH in clinical practice is particularly relevant when classical cytogenetic analysis yields normal or uncertain results in patients with features of sex chromosome aneuploidy. Arq Bras Endocrinol Metab. 2012;56(8):545-51

The usefulness of acetic acid wash and chemiluminescent illumination (Vizilite) in the visualization of oral mucosal white lesions

A diligent and careful examination of the mouth and oral structures has been historically deficient in revealing premalignant and malignant oral lesions. Conventional screening practice for oral neoplastic lesions involves visual scrutiny of the oral tissues with the naked eye under projected incandescent or halogen illumination. Visualization is the principal strategy used to find patients with lesions at risk for malignant transformation; hence, any procedure which highlights neoplastic lesions should aid the clinician. This pilot study examined the usefulness of acetic acid wash and chemiluminescent light (Vizilite) in enhancing visualization of oral mucosal white lesions, and its ability to highlight malignant and potentially malignant lesions. Fifty five patients referred for assessment of a white lesion, were prospectively screened with Vizilite, and an incisional biopsy performed for a definitive diagnosis. The age, sex, and smoking status of all patients were recorded, and all lesions were photographed. The visibility, location, size, border, and presence of satellite lesions, were also recorded. The Vizilite tool enhanced intraoral visualization of 26 white lesions, but it could not distinguish between epithelial hyperplasia, dysplasia, or carcinoma. Indeed, all lesions appeared ‘‘aceto-white’’, regardless of the definitive diagnosis. On one occasion, Vizilite aided in the identification of a satellite lesion that was not observed by routine visual inspection. Vizilite appears to be a useful visualization tool, but it does not aid in the identification of malignant and potentially malignant lesions of the oral mucosa.

An examination of male and female odds ratios by BMI, cigarette smoking, and alcohol consumption for cancers of the oral cavity, pharynx, and larynx in pooled data from 15 case-control studies

Greater tobacco smoking and alcohol consumption and lower body mass index (BMI) increase odds ratios (OR) for oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers; however, there are no comprehensive sex-specific comparisons of ORs for these factors. We analyzed 2,441 oral cavity (925 women and 1,516 men), 2,297 oropharynx (564 women and 1,733 men), 508 hypopharynx (96 women and 412 men), and 1,740 larynx (237 women and 1,503 men) cases from the INHANCE consortium of 15 head and neck cancer case-control studies. Controls numbered from 7,604 to 13,829 subjects, depending on analysis. Analyses fitted linear-exponential excess ORs models. ORs were increased in underweight (< 18.5 BMI) relative to normal weight (18.5-24.9) and reduced in overweight and obese categories (a parts per thousand yen25 BMI) for all sites and were homogeneous by sex. ORs by smoking and drinking in women compared with men were significantly greater for oropharyngeal cancer (p < 0.01 for both factors), suggestive for hypopharyngeal cancer (p = 0.05 and p = 0.06, respectively), but homogeneous for oral cavity (p = 0.56 and p = 0.64) and laryngeal (p = 0.18 and p = 0.72) cancers. The extent that OR modifications of smoking and drinking by sex for oropharyngeal and, possibly, hypopharyngeal cancers represent true associations, or derive from unmeasured confounders or unobserved sex-related disease subtypes (e.g., human papillomavirus-positive oropharyngeal cancer) remains to be clarified.

A Sex-Specific Association between a 15q25 Variant and Upper Aerodigestive Tract Cancers

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35). Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case-control studies. Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08-1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95-1.09, P = 0.66; P-heterogeneity (P(het)) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12-1.34, P = 7 x 10(-6)) but not males (OR = 1.02, 95% CI = 0.97-1.08, P = 0.35; P(het) = 6 x 10(-4)). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (P(het) = 0.86). Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. Impact: Further research is warranted to elucidate the mechanisms underlying these observations. Cancer Epidemiol Biomarkers Prev; 20(4); 658-64. (C) 2011 AACR.

Oral lesions in 166 patients with cutaneous psoriasis: A controlled study

Objectives. This study was aimed to test if the frequency of oral lesions bears statistical correlation or not with the condition of cutaneous psoriasis. Study design. Two groups were examined, one made up of 166 patients with skin psoriasis and the other with the same number of individuals with a negative history of skin diseases (control group), matched by age, race, and sex. Patients with psoriasis were grouped according to their having localized or generalized forms of the disease. The oral mucosa was thoroughly examined in both groups. Data were analyzed using chi-square test, Fisher`s test, the odds ratio (OR) with a 95% confidence interval (CI), and the Ryan-Holm step-down Bonferroni procedure. The overall significance was set at P <= 0.05. Results. The oral lesions significantly associated with psoriasis were fissured tongue (FT, OR=2.7; 95% CI: 1.3-5.6), and geographic tongue (GT, OR=5.0; 95% CI: 1.5-16.8). Other factors analyzed, such as topical and/or systemic medication for treatment of psoriasis versus nontreated patients, and localized versus generalized forms of psoriasis presented no statistical association with the frequency of FT or GT lesions (P > 0.05). Conclusions. Patients with psoriasis presented no specific oral lesion different from those seen in the control group. Although further investigation is warranted to establish whether or not either FT or GT can be characterized as an oral expression of psoriasis, the present investigation did find for both these types of lesions that the frequency of each bore a statistically significant relation with the presence of cutaneous psoriasis.

Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men.

Background: Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition. Methods: We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections. Results: The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC-TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005). In the FTC-TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC-TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P=0.57). Conclusions: Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT00458393.) N Engl J Med 2010;363:2587-99.

Primary Oral Mucosal Melanoma: A Series of 35 New Cases From South America

Oral mucosal melanoma is rare and reported to be more aggressive than its cutaneous counterpart. Due to the rarity of this entity, data on epidemiology, tumor behavior, treatment, follow-up, and Survival of patients are mainly based oil single case reports. The few existing series of patients show that oral mucosa melanoma has its peak between 4 1 and 60 years of age, and male to female ratio is 2: 1. Preferred oral sites include hard palate and maxillary alveolar crests. Risk factors have not been clearly identified, and surgical treatment is still the treatment of choice for oral mucosal melanomas. The authors retrospectively studied 35 patients with primary melanoma of the oral cavity to report their clinical and pathological features, Such as age, sex, site of the tumor, metastasis, treatment, response to therapy, and Outcome. We found no significant sex predominance, and the mean age of the patients was 60.6 years, with a range From 9 to 91 years. The majority of the patients (71.42%) had palate commitment, and invasive histopathological aspect was observed in 80% of the specimens (grade 3). Long-distance metastasis was found in 60% of the cases. Fourteen patients were submitted to wide Surgical resections, with local relapse being observed in 11 of them (78.5%). The authors Suggest that improved outcome in oral malignant melanoma requires the development of new therapies and the prevention of distant metastasis.

Efficacy and Tolerability of Lodenafil Carbonate for Oral Therapy in Erectile Dysfunction: A Phase II Clinical Trial

Oral treatment with phosphodiesterase type 5 inhibitor (PDE5) is considered the first-line treatment for patients with erectile dysfunction (ED). Lodenafil carbonate (LC) is a novel PDE5. This is a phase II, prospective, randomized, double-blind, and placebo controlled clinical trial of LC. Efficacy end points were International Index of Sexual Function (IIEF) erectile domain, IIEF questions 3 and 4, and Sexual Encounter Profile (SEP) questions 2 and 3, before and after the use of LC or placebo. Seventy-two men older than 18 years, with ED for at least 6 months with stable sexual relationship were enrolled. Patients were randomized to placebo or LC 80 mg, 40 mg, or 20 mg and followed for 4 weeks. IIEF erectile domain scores before and after the use of medications were (mean +/- standard deviation [SD]): placebo: 11.9 +/- 3.4 and 12.6 +/- 5.5; LC 20 mg: 15.8 +/- 4.1 and 18.9 +/- 6.6; LC 40 mg: 11.9 +/- 4.4 and 15.4 +/- 8.1; LC 80 mg: 14.2 +/- 4.7 and 22.8 +/- 6.0 (anova P < 0.01). The SEP-2 scores before and after the use of medications were (Mean +/- SD): placebo: 71.0 +/- 33.1 and 51.2 +/- 43.1; LC 20 mg 70.3 +/- 34.2 and 75.5 +/- 31.5; LC 40 mg: 48.4 +/- 42.1 and 60.8 +/- 42.5; LC 80 mg: 68.6 +/- 33.5 and 89.6 +/- 26.0. The SEP-3 scores were: placebo 23.3 +/- 27.6 and 33.6 +/- 42.3; LC 20 mg: 32.3 +/- 38.9 and 51.2 +/- 41.7; LC 40 mg: 39.7 +/- 44.7 and 46.7 +/- 41.1; LC 80 mg* 17.2 +/- 29.5 and 74.3 +/- 36.4 (*P < 0.05 for difference to placebo). The drug was well tolerated. Adverse reactions were mild and self-limited and included headache, rhinitis, flushing, color visual disorders, and dyspepsia. This study showed that the dosage of 80 mg of LC was significantly more efficacious than placebo and well tolerated. Glina S, Toscano I, Gomatzky C, de Goes PM, Junior AN, de Almeida Claro JF, and Pagani E. Efficacy and tolerability of lodenafil carbonate for oral therapy in erectile dysfunction: A phase II clinical trial. J Sex Med 2009;6:553-557.

Oral manifestations after immune reconstitution in HIV patients on HAART

In order to verify possible association between immune reconstitution inflammatory syndrome (IRIS) and oral manifestations (OMs), we selected AIDS patients who had low CD4 count before the initiation of highly active antiretroviral therapy (HAART) and who returned three months later for therapy evaluation. The oral lesions observed three months after the initiation of HAART were evaluated and associated with the type of antiretroviral therapy (ART), CD4 count and HIV-RNA load levels (before and three months after HAART initiation). A total of 105 patients matched the selected criteria. Immune reconstitution (IR) was identified in 35.2%. Among these patients, the mean CD4 cell count rose from 105.97 to 330.29 and the mean viral load dropped from 168.005 (log 5.22) to 21.852 (log 4.33). There was no significant difference in age (P=0.78), sex (P=0.41) or previous history of ART (P=0.55) between IR and non-IR patients. In the IR group, the most common OM was. parotid enlargement (57.14%) (P=0.619), whereas in the non-IR group candidiasis (46.15%) was the most common OM. The results of our study suggest that the parotid gland enlargement found in the studied population might be an IRIS event, as it was found in patients with IR three months after the initiation of HAART.

Seeking SOCS and sex steroids

In seeking to explain why oral estrogen inhibits the GH-IGF-I axis, a recent study has unearthed a new way that steroid hormones can influence growth hormone action. This involves suppressors of cytokine signalling (SOCS), which offer a new level of understanding in signal control and crosstalk.

Dietary patterns and risk of oral cancer: a case-control study in São Paulo, Brazil

OBJECTIVE: To analyze the association between dietary patterns and oral cancer. METHODS: The study, part of a Latin American multicenter hospital-based case-control study, was conducted in São Paulo, Southeastern Brazil, between November 1998 and March 2002 and included 366 incident cases of oral cancer and 469 controls, frequency-matched with cases by sex and age. Dietary data were collected using a food frequency questionnaire. The risk associated with the intake of food groups defined a posteriori, through factor analysis (called factors), was assessed. The first factor, labeled "prudent," was characterized by the intake of vegetables, fruit, cheese, and poultry. The second factor, "traditional," consisted of the intake of rice, pasta, pulses, and meat. The third factor, "snacks," was characterized as the intake of bread, butter, salami, cheese, cakes, and desserts. The fourth, "monotonous," was inversely associated with the intake of fruit, vegetables and most other food items. Factor scores for each component retained were calculated for cases and controls. After categorization of factor scores into tertiles according to the distribution of controls, odds ratios and 95% confidence intervals were calculated using unconditional multiple logistic regression. RESULTS: "Traditional" factor showed an inverse association with cancer (OR=0.51; 95% CI: 0.32; 0.81, p-value for trend 0.14), whereas "monotonous" was positively associated with the outcome (OR=1.78; 95% CI: 1.78; 2.85, p-value for trend <0.001). CONCLUSIONS: The study data suggest that the traditional Brazilian diet, consisting of rice and beans plus moderate amounts of meat, may confer protection against oral cancer, independently of any other risk factors such as alcohol intake and smoking.

Oral health, hygiene practices and oral cancer

OBJECTIVE: To assess the association between oral health and hygiene practices and oral cancer. METHODS: Hospital-based case-control study in the metropolitan area of São Paulo, southeastern Brazil, from 1998 to 2002. A total 309 patients with squamous cell carcinoma of the mouth and the pharynx and 468 controls matched by sex and age were included in the study. Cases were recruited in seven reference hospitals and controls were selected in five out of the seven participating hospitals. Detailed information on smoking, alcohol consumption, schooling, oral health status and hygiene practices were obtained through interviews. Odds ratios (OR) and 95% confidence intervals (95% CI), adjusted by sex, age, schooling, smoking, alcohol consumption as well as the variables oral health status and hygiene practices were estimated using unconditional logistic regression analyses. RESULTS: The use of complete dental prosthesis was not associated with oral cancer but regular gum bleeding showed a strong association (OR 3.1; 95% CI 1.2-7.9). Those who never attended a dental visit were more likely to have oral cancer (OR 2.5; 95% CI 1.3-4.8). Daily mouthwash use showed a stronger association to pharynx (OR 4.7; 95% CI 1.8-12.5) than mouth cancer (OR 3.2; 95% CI 1.6-6.3). CONCLUSIONS: Gum bleeding, no dental care, and daily mouthwash use were factors associated with oral cancer regardless of tobacco and alcohol consumption.

Socioeconomic inequalities and changes in oral health behaviors among Brazilian adolescents from 2009 to 2012

OBJECTIVE To analyze oral health behaviors changes over time in Brazilian adolescents concerning maternal educational inequalities.METHODS Data from the Pesquisa Nacional de Saúde do Escolar(Brazilian National School Health Survey) were analyzed. The sample was composed of 60,973 and 61,145 students from 26 Brazilian state capitals and the Federal District in 2009 and 2012, respectively. The analyzed factors were oral health behaviors (toothbrushing frequency, sweets consumption, soft drink consumption, and cigarette experimentation) and sociodemographics (age, sex, race, type of school and maternal schooling). Oral health behaviors and sociodemographic factors in the two years were compared (Rao-Scott test) and relative and absolute measures of socioeconomic inequalities in health were estimated (slope index of inequality and relative concentration index), using maternal education as a socioeconomic indicator, expressed in number of years of study (> 11; 9-11; ≤ 8).RESULTS Results from 2012, when compared with those from 2009, for all maternal education categories, showed that the proportion of people with low toothbrushing frequency increased, and that consumption of sweets and soft drinks and cigarette experimentation decreased. In private schools, positive slope index of inequality and relative concentration index indicated higher soft drink consumption in 2012 and higher cigarette experimentation in both years among students who reported greater maternal schooling, with no significant change in inequalities. In public schools, negative slope index of inequality and relative concentration index indicated higher soft drink consumption among students who reported lower maternal schooling in both years, with no significant change overtime. The positive relative concentration index indicated inequality in 2009 for cigarette experimentation, with a higher prevalence among students who reported greater maternal schooling. There were no inequalities for toothbrushing frequency or sweets consumption.CONCLUSIONS There were changes in the prevalences of oral health behaviors during the analyzed period; however, these changes were not related to maternal education inequalities.

Oral Contraceptive Use and Clinical Outcomes in Patients with Multiple Sclerosis

Experimental and clinical data suggest a role of sex steroids in the pathogenesis of multiple sclerosis (MS). Scant information is available about the potential effect of oral contraceptive (OC) use on the prognosis of the disease. We aimed to evaluate this. The study population consisted of 132 women with relapsing-remitting MS before receiving disease modifying treatment and a mean disease duration 6.2 (SD 5.1) years. Three groups of patients were distinguished according to their OC behavior: [1] never-users, patients who never used OC [2] past-users, patients who stopped OC use before disease onset, and [3] after-users, those who used these drugs after disease onset. Multiple linear and logistic regression models were used to analyze the association between oral contraceptive use and annualized relapse rates, disability accumulation and severity of the disease. After-user patients had lower Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) values than never users (p<0.001 and p=0.002, respectively) and past users (p=0.010 and p=0.002, respectively). These patients were also more likely to have a benign disease course (MSSS<2.5) than never and past users together (OR: 4.52, 95%CI: 2.13-9.56, p<0.001). This effect remained significant after adjustment for confounders, including smoking and childbirths (OR: 2.97, 95%CI: 1.24, 6.54, p=0.011 and for MSSS β: -1.04; 95% C.I. -1.78, -0.30, p=0.006). These results suggest that OC use in women with relapsing-remitting MS is possible associated with a milder disabling disease course.