Raimar Weber

Oral lesions as predictors of highly active antiretroviral therapy failure in Brazilian HIV‐infected children

OBJECTIVES Evaluate the accuracy of HIV-related oral lesions to predict immune and virologic failure on HIV-infected children in use of highly active antiretroviral therapy (HAART). STUDY DESIGN Data for this cross-sectional analysis come from a longitudinal study being conducted through the HIV-AIDS Outpatient Unit, ENT Division, Hospital das Clinicas, Sao Paulo University Medical School. The study began in January 1990 and is still ongoing. The cut-off point for analyses purposes was December 2004. Subjects were 471 HIV-infected consecutive children attending the outpatient unit during this period, who enrolled regardless of medical or immunological status. The children have undertaken oral cavity examination, serum CD4(+) T-lymphocyte count, and, 271 of them, viral load measurement. Sensitivity, specificity, positive predictive value, negative predictive value and relative risk were calculated. RESULTS Oral lesions had moderate sensitivity, high specificity and positive predictive value to predict immune failure. It had low sensitivity and positive predictive value, and high specificity to predict virologic failure. DISCUSSION AND CONCLUSIONS Oral manifestations of HIV can be important markers for immune suppression and for virologic failure, in Brazilian children undergoing HAART.

Endoscopic ligation of the anterior ethmoidal artery: a cadaver dissection study

UNLABELLED Anterior ethmoidal artery (AEA) ligation may be necessary in cases of severe epistaxis not controllable with traditional therapy. Endoscopic endonasal ligation of the AEA is not used frequently; there are few studies in the literature for standardization of the endoscopic technique for this vessel. AIM To demonstrate the feasibility of periorbital AEA ligation in a transethmoidal endoscopic approach. METHODS A prospective study where 50 nasal cavities were dissected. After anterior ethmoidectomy and partial removal of lamina papyracea, the periorbital area was carefully dissected along a subperiosteal plane to identify the AEA. The vessel was exposed within the orbit and dissected. RESULTS Data on technical difficulties, complications, the learning curve and anatomical variations were gathered. CONCLUSION An endonasal endoscopic approach to the AEA within the orbit was shown to be feasible. Identifying the artery is not difficult, and this technique avoids external incisions. This approach appears to be an excellent alternative for approaching the AEA. Further clinical studies are needed to demonstarte the benefits of this technique.

AIDS and recurrent aphtous stomatitis

UNLABELLED The immunodeficiency state in HIV infected patients has been the cause of severe episodes of Recurrent Aphthous Stomatitis (RAS). AIM Our study aims to establish correlation between the manifestations of RAS and the immunosuppression state caused by HIV infection, through counting of CD4+ cells, CD8+ cells, CD4+:CD8+ cells ratio and viral load. STUDY DESIGN Series study. MATERIAL AND METHOD Ninety-four HIV infected patients (25 women and 69 men) with RAS were evaluated in the ENT Department of the University of Sao Paulo-Medical School from January 1998 to December 2003. The age ranged between 19 and 63 years (mean = 35.3 years). The patients were divided in two groups: AIDS group and HIV infected group. RESULTS The patients with AIDS and HIV infection presented, respectively, eight ulcers and two ulcers by outbreaks. Similarly, patients with major RAS presented smaller counting of cells CD8+, CD4+ and CD4+/CD8+ cells, and higher mean value of viral load than the patients with herpetiform and minor RAS. Between patients with minor and herpetiform RAS there were no statistical differences. CONCLUSIONS The emergence of the lesions, mainly in major RAS, is directly related to the immunological state of the HIV infected patient. These patients frequently present nutritional deficits and worsening in life style. Thus, diagnosis and treatment of RAS is a challenge that should not be neglected.

Correlation between histocompatibility antigens and recurrent aphthous stomatitis in the brazilian population

A Estomatite Aftoide Recorrente e uma doenca oral com incidencia em 20% da populacao mundial, caracterizada por ulceras mucosas de carater recidivante. O diagnostico baseiase principalmente na historia clinica do paciente. Hereditariedade pode ser um fator de risco para doenca, entretanto, os estudos disponiveis nao sao conclusivos quanto aos resultados obtidos, variando segundo a populacao estudada. OBJETIVO: Tipificar moleculas HLA de classe I e de classe II e avaliar a frequencia destas moleculas em pacientes brasileiros, portadores de Estomatite Aftoide Recorrente, comparando com grupo controle. MATERIAL E METODO: Este trabalho possui um desenho prospectivo, transverso e investigativo. Foram estudados 31 pacientes com suspeita diagnostica de Estomatite Aftoide Recorrente no periodo de fevereiro de 2004 a maio de 2006. Os pacientes foram submetidos a protocolo de exames e, daqueles que obedeceram aos criterios de inclusao, foi extraido o DNA e realizada a tipificacao HLA por Reacao de Polimerizacao em Cadeia. RESULTADO: Nos pacientes portadores de Estomatite Aftoide Recorrente do tipo minor encontramos as frequencias HLA A33 e B35 estatisticamente significantes. CONCLUSAO: As frequencias HLA-A33 e HLA-B35 podem estar associadas a Estomatite Aftoide Recorrente minor na populacao brasileira.

Aids e estomatite aftóide recidivante

The immunodeficiency state in HIV infected patients has been the cause of severe episodes of Recurrent Aphthous Stomatitis (RAS). AIM: Our study aims to establish correlation between the manifestations of RAS and the immunosuppression state caused by HIV infection, through counting of CD4+ cells, CD8+ cells, CD4+:CD8+ cells ratio and viral load. STUDY DESIGN: series study. MATERIAL AND METHOD: Ninety-four HIV infected patients (25 women and 69 men) with RAS were evaluated in the ENT Department of the University of Sao Paulo-Medical School from January 1998 to December 2003. The age ranged between 19 and 63 years (mean = 35.3 years). The patients were divided in two groups: AIDS group and HIV infected group. RESULTS: The patients with AIDS and HIV infection presented, respectively, eight ulcers and two ulcers by outbreaks. Similarly, patients with major RAS presented smaller counting of cells CD8+, CD4+ and CD4+/CD8+ cells, and higher mean value of viral load than the patients with herpetiform and minor RAS. Between patients with minor and herpetiform RAS there were no statistical differences. CONCLUSIONS: The emergence of the lesions, mainly in major RAS, is directly related to the immunological state of the HIV infected patient. These patients frequently present nutritional deficits and worsening in life style. Thus, diagnosis and treatment of RAS is a challenge that should not be neglected.

Impacto da Haart na prevalência de otite média crônica em crianças brasileiras infectadas pelo HIV

O advento de novas drogas anti-retrovirais como os inibidores de protease provocou mudancas sensiveis na morbidade e mortalidade de pacientes infectados pelo HIV. OBJETIVOS: Avaliar o impacto das novas drogas anti-retrovirais (Highly Active Anti-retroviral Therapy - HAART) na prevalencia de otite media cronica em populacao pediatrica infectada pelo HIV. METODOS: Analisamos os prontuarios de 471 criancas com idade entre zero e 12 anos e 11 meses portadoras de HIV atendidas no ambulatorio de AIDS de Clinica Otorrinolaringologica do HCFMUSP. As criancas foram divididas em dois grupos, de acordo com a faixa etaria: 0 a 5 anos e 11 meses e 6 a 12 anos e 11 meses, e classificadas como portadoras de otite media cronica, baseadas em achados de anamnese, otoscopia, audiometria e imitanciometria. As prevalencias de otite media cronica apresentadas e as contagens de linfocitos T CD4+ foram comparadas entre as criancas em uso ou nao de HAART. RESULTADOS: Das 459 criancas atendidas, 65 (14,2%) apresentavam otite media cronica. Observamos, nas criancas de 0 a 5 anos e 11 meses que o uso de HAART esteve associado a significante menor prevalencia de otite media cronica (p = 0,02), e maior contagem de linfocitos T CD4+ (p < 0,001). CONCLUSAO: O uso de HAART esteve associado a menor prevalencia da forma cronica de otite media entre criancas menores de 6 anos infectadas pelo HIV, provavelmente como consequencia do aumento promovido na contagem de linfocitos T CD4+.

Short and long term impact of adenotonsillectomy on the immune system.

UNLABELLED Palatine and pharyngeal tonsils are immune reactive lymphoid organs that manifest specific antibodies and B/T-cell activity to respond to a variety of antigens. They perform humoral and cellular immune functions. The possible effects of adenotonsillectomy upon the immune system remain controversial. OBJECTIVE To study the short and long-term impacts of tonsillectomy upon the cellular and humoral immunity of children. METHOD This longitudinal prospective study included 29 children referred to adenotonsillectomy for adenotonsillar hypertrophy. Serum IgA, IgM, and IgG and lymphocyte counts were analyzed at three points in time: before surgery, 1-2 months after surgery (short term), and 12-14 months after surgery (long term). RESULTS TCD4+ cell counts were significantly increased shortly after surgery. IgA and IgG values were significantly reduced in the long run, but were within normal ranges for this age group. CONCLUSION This study indicated that adenotonsillectomy does not pose negative short or long term impacts upon the cellular and humoral immunity of children submitted to the procedure.

HLA-DRB1*04:02, DRB1*08:04 and DRB1*14 alleles associated to pemphigus vulgaris in southeastern Brazilian population

We report here for the first time a strong association of the DRB1*08:04 allele and pemphigus vulgaris (PV) in a Brazilian highly admixed cohort. The authors recently performed a prospective case–control study, including 36 unrelated patients with PV from São Paulo, Brazil. All patients were diagnosed according to the standard criteria: (i) clinical features: a mucocutaneous blistering disorder; (ii) histopathology: a skin or a mucosal biopsy showing suprabasal acantholysis and clefting; and (iii) immunopathology: direct or indirect immunofluorescence to show IgG antibodies that bind to the intercellular spaces of the epidermis (1). Patients with neoplasia or paraneoplastic pemphigus (2) were not included. All patients were non-Jewish, and all except one patient had both parents and grandparents born in Brazil. DNA extraction was performed using the DTAB/CTAB method (3). Human leukocyte antigen (HLA) typing at the DRB1 locus was performed after DNA extraction using polymerase chain reaction (PCR) amplification with sequence-specific oligonucleotides (PCR-SSO) using LABType kits (One Lambda, Inc., Canoga Park, CA) (4, 5). HLA phenotypes were assigned to each individual based on the oligotyping results. Phenotypic and allelic frequencies were compared with those from a collected DNA bank of healthy volunteers donors registered in the national registry of bone marrow donors (REDOME) (6) from Sao Paulo, typed in the same laboratory between January 2008 and April 2009 using the same methods. One hundred sixty-two unrelated individuals were randomly chosen from the data bank (preserving the same ethnicity proportions of study group) and formed the control group. The allele frequencies found in the control group were similar to those reported by previous studies in samples of population from southeastern Brazil (7–9). Unlike other researchers, the authors of this study decided to not select individuals – cases or controls – from a homogeneous ethnic group, based on the premise that the Brazilian population is one of the most heterogeneous populations in the world as a result of five centuries of admixture between Europeans, Africans, and Amerindians, which produces, at the individual level, a significant dissociation of color and genomic ancestry (10). Moreover, evidence shows that the possible effect of population stratification is likely to be small in most situations and decreases as the number of admixed ethnicities increases (11, 12). Two-tailed Fisher’s exact test was used to detect significant deviations in allele frequency from controls; a P value ≤0.05 was considered a significant result. Odds ratios (OR) were calculated by the Woolf method (13) (or by the modified method described by Haldane (14)). Statistical analysis was performed using spss for Mac version 16.0 (SPSS Inc, Chicago, IL). A correction for multiple testing with the false discovery rate method (15, 16) was applied after the identification of alleles in PV patients displaying significant deviation in frequency from controls. The distribution of DRB1 genotypes in the patients and the controls was in Hardy–Weinberg equilibrium for patients (P = 0.82876) and for the controls (P = 0.83123). After correction for multiple comparisons, the null hypothesis was rejected for the association of PV with the alleles DRB1*04:02, DRB1*08:04, and DRB1*14, with OR (confidence interval 95%) 44.6 (19.2–103), 18.6 (8.3–41.7), and 4.8 (2.2–10.4), respectively. The authors report here for the first time a strong association of the DRB1*08:04 allele and PV in a Brazilian highly admixed cohort. Previous studies may have failed to identify this association because they did not include populations that have individuals of African origins. High-resolution typing of nearby loci DQA1 and DQB1 is necessary to differentiate if the association is inherent to the HLA-DRB1*08:04 allele or to a specific haplotype.

Haart impact on prevalence of chronic otitis media in Brazilian HIV-infected children

UNLABELLED The advent of new antiretroviral drugs such as protease inhibitors has generated sensible changes in morbity and mortality in HIV-infected patients. OBJECTIVES To evaluate the impact of Highly Active Antiretroviral Therapy (HAART) on the prevalence of chronic otitis media in HIV-infected pediatric population. METHODS We analyzed medical charts of 471 children aged zero to 12 years and 11 months with HIV infection from an Ambulatory of ENT and AIDS. Children were divided according to the age: 0 to 5 years and 11 months and 6 to 12 years and 11 months and classified as having chronic otitis media based on history, physical examination, audiologic and tympanometric data. Prevalence of chronic otitis media, as well as CD4+ lymphocyte count were compared between groups in use of HAART and the group without HAART. RESULTS Out of 459 children, 65 (14.2%) had chronic otitis media. We observed that in children aged 0 to 5 years and 11 months who were taking HAART there was significant lower prevalence of chronic otitis media (p=0.02). The use of HAART was associated to higher mean CD4+ lymphocyte count (p<0.001). CONCLUSION The use of HAART was associated to reduction in prevalence of chronic otitis media in HIV infected children, probably due to increase in mean CD4+ lymphocyte count.

Caracterização da voz do indivíduo portador de obesidade mórbida

RACIONAL: A obesidade e doenca cronica e grave com crescimento alarmante em todo o mundo e de interesse na saude publica. Existe alteracao no comportamento vocal destes pacientes e ele e pouco estudado. OBJETIVO: Caracterizar prospectivamente a voz de individuos portadores de obesidade morbida comparando-a com a de nao obesos. METODOS: Estudo prospectivo de 45 individuos adultos voluntarios, 14 homens e 31 mulheres com idade media de 43 anos variando de 20 a 63 anos. Todos apresentavam IMC acima de 35 Kg/m2 constituindo o grupo em estudo (GO) Para cada individuo do GO foi selecionado tambem um individuo adulto voluntario, proveniente da populacao geral do ambulatorio de otorrinolaringologia com IMC abaixo de 30 Kg/m2, constituindo o grupo controle (GN). Os criterios de exclusao foram diagnostico de lesoes neoplasicas malignas em cabeca e pescoco ou operacoes previas da regiao orofaringea. Fooram submetidos a exame laringologico e a gravacao da voz. Tambem submeteram-se a avaliacao subjetiva perceptivo-auditiva da qualidade vocal, atraves da escala GIRBAS e a aspereza, o estrangulamento no final das. A analise acustica foi realizada objetivamente utilizando os softwares Vox Metria versao 4.0.47 e PRAAT, fornecendo a frequencia fundamenta, jitter, shimmer, ruido e tempo maximo fonatorio. RESULTADOS: Observou-se que os grupos foram homogeneos em relacao ao sexo, idade, tabagismo e altura, mas significativamente diferentes em relacao ao peso e IMC (P<0,001). Os achados laringoscopicos em ambos os grupos mostraram que 26,7% dos obesos tinham laringoscopia alterada contra 13,3% dos nao obesos. Sinais laringeos sugestivos de RLF foram significativos para o GO (P<0,042). A analise perceptivo-auditiva revelou que o grau da disfonia, a instabilidade, a rouquidao, a soprosidade, a astenia, a tensao e a aspereza tiveram alteracoes altamente significantes para o GO (P=0,001 ou 002). O estrangulamento ao final das emissoes, bem como a ressonância da producao vocal foi significante (P=0,001) comprometendo o GO. Na analise acustica notou-se que o jitter, shimmer, ruido e o tempo maximo fonatorio apresentaram significância alta comprometendo o GO. CONCLUSAO: A voz do individuo portador de obesidade morbida apresenta alteracoes significantes quanto as caracteristicas vocais em relacao aos individuos nao obesos, caracterizando a voz do obeso como rouca, soprosa, instavel, estrangulada e com tempos maximos fonatorios reduzidos.