Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases

Background Despite the WHO recommendation that the 2010-2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus there is no consistent data regarding its immunogenicity and safety in a large autoimmune rheumatic disease (ARD) population. Methods 1668 ARD patients (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, psoriatic arthritis (PsA), Behcet`s disease (BD), mixed connective tissue disease, primary antiphospholipid syndrome (PAPS), dermatomyositis (DM), primary Sjogren`s syndrome, Takayasu`s arteritis, polymyositis and Granulomatosis with polyangiitis (Wegener`s) (GPA)) and 234 healthy controls were vaccinated with a non-adjuvanted influenza A/California/7/2009(H1N1) virus-like strain flu. Subjects were evaluated before vaccination and 21 days post-vaccination. The percentage of seroprotection, seroconversion and the factor increase in geometric mean titre (GMT) were calculated. Results After immunisation, seroprotection rates (68.5% vs 82.9% p < 0.0001), seroconversion rates (63.4% vs 76.9%, p < 0.001) and the factor increase in GMT (8.9 vs 13.2 p < 0.0001) were significantly lower in ARD than controls. Analysis of specific diseases revealed that seroprotection significantly reduced in SLE (p < 0.0001), RA (p < 0.0001), PsA (p=0.0006), AS (p=0.04), BD (p=0.04) and DM (p=0.04) patients than controls. The seroconversion rates in SLE (p < 0.0001), RA (p < 0.0001) and PsA (p=0.0006) patients and the increase in GMTs in SLE (p < 0.0001), RA (p < 0.0001) and PsA (p < 0.0001) patients were also reduced compared with controls. Moderate and severe side effects were not reported. Conclusions The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. (ClinicalTrials.gov #NCT01151644)

HLA-DR in Brazilian patients with polyarteritis nodosa (PAN) and microscopic polyangiitis (MPA)

The aim of this study was to evaluate the frequency and clinical associations of HLA-DR alleles in Brazilian Caucasian patients with polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA). We evaluated 29 Caucasian patients with vasculitis classified as PAN or MPA according to the American College of Rheumatology (ACR) 1990 Criteria, Chapel Hill Consensus Conference (CHCC) nomenclature for vasculitis and EULAR recommendations for conducting clinical studies in systemic vasculitis. HLA-DR alleles were typed using polymerase chain reaction-amplified DNA, hybridized with sequence-specific low resolution primers. DNA obtained from 59 Caucasian healthy blood donors were used as control. In order to evaluate if a specific HLA may have influence on the clinical profile of those diseases, we also divided the patients according to Birmingham vasculitis score (BVAS) and Five-Factors Score (FFS) at the time of diagnosis. Increased frequency of HLA-DRB1*16 (p = 0.023) and DRB4*01 (p = 0.048) was found in patients with higher disease activity at the time of diagnosis (BVAS >= 22). Patients with less severe disease (FFS = 0) had a higher frequency of HLA-DRB1*03 (p = 0.011). Patients with gastrointestinal tract involvement had significantly increased frequency of HLA-DRB1*11 or B1*12 (p = 0.046), B1*13 (p = 0.021) and B3 (p = 0.008). In contrast, patients with renal disease, had higher frequency of DRB1*15 or DRB1*16 (p = 0.035) and B5 (p = 0.035). In the subgroup of patients with MPA, increased frequency of HLA-DRB1*15 was found in patients with BVAS >= 22 (p = 0.038) and FFS >= 1 (p = 0.039) suggesting that this allele is associated with more aggressive disease. Antineutrophil cytoplasmic antibodies (ANCA) negative MPA patients had significantly increased frequency of HLA-DRB1*11 or DRB1*12 when compared to ANCA positive patients (p = 0.023). Our results suggest that HLA-DR alleles may influence PAN and MPA clinical expression and outcome and that in MPA they participate in the mechanisms involved in the development to ANCA.

Wegener`s granulomatosis: experience from a Brazilian tertiary center

Most epidemiological studies with Wegener`s granulomatosis (WG) patients are based on populations from the Northern hemisphere, whereas very few studies have been conducted in Southern hemisphere populations, particularly from South America. The authors performed a large retrospective, demographic study including clinical and laboratory profiles of 134 consecutive WG patients seen at one Brazilian center from 1999 to 2009. Mean age at initial WG diagnosis was 43.4 +/- 15.5 years, and mean disease duration was 8.6 +/- 6.6 years. Sixty-four (47.8%) patients were male and a total of 113 (84.3%) subjects were white. Ear/nose/throat involvement occurred in 85.8%. The classic lung and renal involvement were observed in 77.6% and 75.4%, respectively, followed by ocular (35.8%), musculoskeletal (33.4%), cutaneous (29.1%), neurological (20.1%), cardiac (11.2%), and genitourinary involvement in 2.2% of cases. Cytoplasmic pattern-antineutrophil cytoplasmic antibody was detected in 83 (61.9%) cases. Ten (7.5%) individuals presented limited forms of WG. Classic therapy with corticosteroids and cyclophosphamide was used in 97 cases (72.4%). There were no cases of tuberculosis or Pneumocystis jiroveci pneumonia, but cutaneous herpes zoster occurred in eight (6.0%) individuals. There were 29 deaths (21.6%). Eighteen patients died of septic shock (mainly bacterial pneumonia), whereas four died of alveolar hemorrhage, four of myocardial infarction, and three of other causes. In summary, our data from a very large retrospective and descriptive study mirrored the main clinical features of WG described in other countries, demonstrating that they may serve as a reference for South American populations.

ASSOCIATION BETWEEN SADDLE NOSE DEFORMITY AND RETRO-ORBITAL MASS IN WEGENER`S GRANULOMATOSIS

Objectives: The relationship between saddle nose deformity (SND) in Wegener`s granulomatosis (WG) and other clinical features, including retro-orbital mass formation (ROM), has been poor described. Therefore, this relationship was analyzed retrospectively from 2000 to 2010. Patients and Methods: Eighteen consecutive WG patients with SND diagnosed by computed tomography were matched to 36 WG patients without SND (control group) for gender, age at WG diagnosis and disease duration. Results: No difference was found between the two groups in relation to WG type (limited and systemic forms), ethnicity, laboratory features, constitutional symptoms or clinical manifestations, including upper respiratory tract, and treatment, except for ROM (33.3 vs. 2.8% in SND(+) and SND(-) groups, respectively; p=0.004) and subglottic stenosis (22.2 vs. 2.8%; p=0.038). However, on multivariate analysis, only ROM (OR 17.15; 95% CI 1.11-265.52) was statistically associated to SND. In addition, in more than half of the cases, SND manifested prior to ROM. Conclusions: Results of this prospective analysis showed that SND was strongly associated to ROM in WG. Since early diagnosis and aggressive treatment of orbital involvement could lead to better prognosis, the presence of SND warrants additional vigilance.

EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria

Objectives To validate the previously proposed classification criteria for Henoch-Schonlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA). Methods Step 1: retrospective/prospective webdata collection for children with HSP, c-PAN, c-WG and c-TA with age at diagnosis <= 18 years. Step 2: blinded classification by consensus panel of a representative sample of 280 cases. Step 3: statistical (sensitivity, specificity, area under the curve and.-agreement) and nominal group technique consensus evaluations. Results 827 patients with HSP, 150 with c-PAN, 60 with c-WG, 87 with c-TA and 52 with c-other were compared with each other. A patient was classified as HSP in the presence of purpura or petechiae (mandatory) with lower limb predominance plus one of four criteria: (1) abdominal pain; (2) histopathology (IgA); (3) arthritis or arthralgia; (4) renal involvement. Classification of c-PAN required a systemic inflammatory disease with evidence of necrotising vasculitis OR angiographic abnormalities of medium-/small-sized arteries (mandatory criterion) plus one of five criteria: (1) skin involvement; (2) myalgia/muscle tenderness; (3) hypertension; (4) peripheral neuropathy; (5) renal involvement. Classification of c-WG required three of six criteria: (1) histopathological evidence of granulomatous inflammation; (2) upper airway involvement; (3) laryngo-tracheo-bronchial involvement; (4) pulmonary involvement (x-ray/CT); (5) antineutrophilic cytoplasmic antibody positivity; (6) renal involvement. Classification of c-TA required typical angiographic abnormalities of the aorta or its main branches and pulmonary arteries (mandatory criterion) plus one of five criteria: (1) pulse deficit or claudication; (2) blood pressure discrepancy in any limb; (3) bruits; (4) hypertension; (5) elevated acute phase reactant. Conclusion European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society propose validated classification criteria for HSP, c-PAN, c-WG and c-TA with high sensitivity/specificity.

Gingival Manifestations of Orofacial Granulomatosis

Background: Orofacial granulomatosis is a clinical entity presenting with swelling of the facial and/or oral tissues in association with histologic evidence of noncaseating granulomatous inflammation. Labial swelling is the most common finding. Compromise of the gingival and periodontal tissues may occur but has rarely been described in the literature. Our objective was to characterize granulomatous gingivitis in patients with orofacial granulomatosis. Observations: The study included 29 cases of orofacial granulomatosis seen in our clinic between January 1, 1989, and December 31, 2006. Of these 29, 5 had clinical evidence of gingival tumefaction and underwent gingival biopsy. Histologic examination of all the gingival biopsy specimens showed noncaseating granulomas, edema of the superficial lamina propria, and a chronic inflammatory infiltrate consisting predominantly of lymphocytes and multinucleated giant cells. Treatment options included anti-inflammatory therapy associated with periodontal care. Conclusion: Gingival tumefaction with histologic evidence of granulomatous inflammation may occur in orofacial granulomatosis and might be more common than reported in the literature.

Reconstruction of bony facial contour deficiencies with polymethylmethacrylate implants: case report

Facial trauma can be considered one of the most serious aggressions found in the medical centers due to the emotional consequences and the possibility of deformity. In craniofacial surgery, the use of autologous bone is still the first choice for reconstructing bony defects or irregularities. When there is a shortage of donor bone or a patient refuses an intracranial operation, alloplastic materials such as polymethylmethacrylate (PMMA) can be used. The PMMA prosthesis can be pre-fabricated, bringing advantages such as reduction of surgical time, easy technical handling and good esthetic results. This paper describes the procedures for rehabilitating a patient with PMMA implants in the region of the face, recovering the facial contours and esthetics of the patient.

Craniofacial characteristics of Caucasian and Afro-Caucasian Brazilian subjects with normal occlusion

OBJECTIVE: The objective of this study was to compare the skeletal, dental and soft tissue characteristics of Caucasian and Afro-Caucasian Brazilian subjects with normal occlusion and to evaluate sexual dimorphism within the groups. MATERIAL AND METHODS: The sample comprised lateral cephalograms of untreated normal occlusion subjects, divided into 2 groups. Group 1 included 40 Caucasian subjects (20 of each sex), with a mean age of 13.02 years; group 2 included 40 Afro-Caucasian subjects (20 of each sex), with a mean age of 13.02 years. Groups 1 and 2 and males and females within each group were compared with t tests. RESULTS: Afro-Caucasian subjects presented greater maxillary protrusion, smaller upper anterior face height and lower posterior face height, larger upper posterior face height, greater maxillary and mandibular dentoalveolar protrusion as well as soft tissue protrusion than Caucasian subjects. The Afro-Caucasian female subjects had less mandibular protrusion and smaller total posterior facial height and upper posterior facial height than males. CONCLUSIONS: Brazilian Afro-Caucasian subjects have greater dentoalveolar and soft tissue protrusion than Brazilian Caucasian subjects, with slight sexual dimorphism in some variables.

Pulpotomies with portland cement in human primary molars

Two clinical cases in which Portland cement (PC) was applied as a medicament after pulpotomy of mandibular primary molars in children are presented. Pulpotomy using PC was carried out in two mandibular first molars and one mandibular second molar, which were further followed-up. At the 3, 6 and 12-month follow-up appointments, clinical and radiographic examinations of the pulpotomized teeth and their periradicular area revealed that the treatments were successful in maintaining the teeth asymptomatic and preserving pulpal vitality. Additionally, the formation of a dentin bridge immediately below the PC could be observed in the three molars treated. PC may be considered as an effective alternative for primary molar pulpotomies, at least in a short-term period. Randomized clinical trials with human teeth are required in order to determine the suitability of PC before unlimited clinical use can be recommended.

Segmental LeFort I osteotomy for treatment of a class III malocclusion with temporomandibular disorder

This article reports the case of a 19-year-old young man with Class III malocclusion and posterior crossbite with concerns about temporomandibular disorder (TMD), esthetics and functional problems. Surgical-orthodontic treatment was carried out by decompensation of the mandibular incisors and segmentation of the maxilla in 4 pieces, which allowed expansion and advancement. Remission of the signs and symptoms occurred after surgical-orthodontic intervention. The maxillary dental arch presented normal transverse dimension. Satisfactory static and functional occlusion and esthetic results were achieved and remained stable. Three years after the surgical-orthodontic treatment, no TMD sign or symptom was observed and the occlusal results had not changed. When vertical or horizontal movements of the maxilla in the presence of moderate maxillary constriction are necessary, segmental LeFort I osteotomy can be an important part of treatment planning.

Evaluation of superficial microhardness in dental enamel with different eruptive ages

This study evaluated the superficial microhardness of enamel in teeth at different posteruptive ages (before eruption in the oral cavity, 2-3 years after eruption, 4-10 years after eruption and more than 10 years after eruption). The study sample was composed of 134 specimens of human enamel. One fragment of each tooth was obtained from the flattest central portion of the crown to produce specimens with 3 x 3 mm. The enamel blocks were minimally flattened out and polished in order to obtain a flat surface parallel to the base, which is fundamental for microhardness testing. Microhardness was measured with a microhardness tester and a Knoop diamond indenter, under a static load of 25 g applied for 5 seconds. Comparison between the superficial microhardness obtained for the different groups was performed by analysis of Student's t test. The results demonstrated that superficial microhardness values have a tendency to increase over the years, with statistically significant difference only between unerupted enamel and that with more than 10 years after eruption. According to the present conditions and methodology, it was concluded that there were differences between the superficial micro-hardness of specimens at different eruptive ages, revealing an increasing mineralization. However, this difference was significant only between unerupted specimens and those with more than 10 years after eruption.

Comparison of periodontal parameters in individuals with syndromic craniosynostosis

Craniosynostosis syndromes are characterized by premature closure of one or more cranial sutures, associated with other malformations, the most frequent of which are the Crouzon and Apert syndromes. Few studies in the literature have addressed the oral health of these individuals. The purpose of this study was to compare the periodontal status of individuals with Apert, Crouzon, Pfeiffer and Saethre-Chotzen syndromes before toothbrushing and compare the efficiency of plaque removal before and after mechanical toothbrushing. The probing depth, plaque index (according to Löe and O'Leary), clinical attachment level, gingival index (according to Silness and Löe) and amount of keratinized mucosa were evaluated before toothbrushing, and the O'Leary plaque index was assessed before and immediately after toothbrushing, on the same day, in 27 individuals aged 11 to 36 years. There was statistically significant difference in the mean probing depth and clinical attachment level among regions (p=0.00; p=0.01, respectively). The gingival index did not reveal statistically significant differences. With regard to the plaque index, the left region exhibited higher plaque index values than the right and anterior regions. No significant results were found in the analysis of keratinized mucosa. Comparison of the O'Leary plaque index before and after toothbrushing revealed statistically significant difference for all syndromes except for the Pfeiffer syndrome (p<0.05). In conclusion, there was no difference in the periodontal status among individuals with syndromic craniosynostosis. The posterior region was more affected than the anterior region as to the presence of plaque, loss of insertion and probing depth. Individuals with Pfeiffer syndrome exhibited greater toothbrushing efficiency than individuals with the other craniosynostosis syndromes.

Correlation between margin fit and microleakage in complete crowns cemented with three luting agents

Microleakage can be related to margin misfit. Also, traditional microleakage techniques are time-consuming. This study evaluated the existence of correlation between in vitro margin fit and a new microleakage technique for complete crowns cemented with 3 different luting agents. Thirty human premolars were prepared for full-coverage crowns with a convergence angle of 6 degrees, chamfer margin of 1.2 mm circumferentially, and occlusal reduction of 1.5 mm. Ni-Cr cast crowns were cemented with either zinc phosphate (ZP) (S.S. White), resin-modified glass-ionomer (RMGI) (Rely X Luting Cement) or a resin-based luting agent (RC) (Enforce). Margin fit (seating discrepancy and margin gap) was evaluated according to criteria in the literature under microscope with 0.001 mm accuracy. After thermal cycling, crowns were longitudinally sectioned and microleakage scores at tooth-cement interface were obtained and recorded at ×100 magnification. Margin fit parameters were compared with the one-way ANOVA test and microleakage scores with Kruskal-Wallis and Dunn's tests (alpha=0.05). Correlation between margin fit and microleakage was analyzed with the Spearman's test (alpha=0.05). Seating discrepancy and marginal gap values ranged from 81.82 µm to 137.22 µm (p=0.117), and from 75.42 µm to 78.49 µm (p=0.940), respectively. Marginal microleakage scores were ZP=3.02, RMGI=0.35 and RC=0.12 (p<0.001), with no differences between RMGI and RC scores. The correlation coefficient values ranged from -0.27 to 0.30 (p>0.05). Conclusion: Margin fit parameters and microleakage showed no strong correlations; cast crowns cemented with RMGI and RC had lower microleakage scores than ZP cement.

Fracture resistance of weakened roots restored with composite resin and glass fiber post

This study evaluated the fracture resistance of weakened roots restored with glass fiber posts, composite resin cores and complete metal crowns. Thirty maxillary canines were randomly divided into 3 groups of 10 teeth each: teeth without weakened roots (control); teeth with partially weakened roots (PWR) and teeth with and largely weakened roots (LWR). The control group was restored with glass fiber posts and a composite resin core. Teeth in the PWR and LWR groups were flared internally to standardized dimensions in order to simulate root weakness. Thereafter, the roots were partially filled with composite resin and restored in the same way as in the control group. The specimens were exposed to 250,000 cycles in a controlled chewing simulator. All intact specimens were subjected to a static load (N) in a universal testing machine at 45 degrees to the long axis of the tooth until failure. Data were analyzed by one-way ANOVA and Dunnett's test for multiple comparisons (p=0.05). There were statistically significant difference differences (p<0.01) among the groups (control group = 566.73 N; PWR = 409.64 N; and LWR = 410.91 N), with significantly higher fracture strength for the control group. There was no statistically significant difference (p>0.05) between the weakened groups. The results of this study showed that thicker root dentin walls significantly increase the fracture resistance of endodontically treated teeth.

Communicative and psycholinguistic abilities in children with phenylketonuria and congenital hypothyroidism

The Neonatal Screening for Inborn Errors of Metabolism of the Association of Parents and Friends of Special Needs Individuals (APAE) - Bauru, Brazil, was implanted and accredited by the Brazilian Ministry of Health in 1998. It covers about 286 cities of the Bauru region and 420 collection spots. Their activities include screening, diagnosis, treatment and assistance to congenital hypothyroidism (CH) and phenylketonuria (PKU), among others. In 2005, a partnership was established with the Department of Speech-Language Pathology and Audiology, Bauru School of Dentistry, University of São Paulo, Bauru, seeking to characterize and to follow, by means of research studies, the development of the communicative abilities of children with CH and PKU. OBJECTIVE: The aim of this study was to describe communicative and psycholinguistic abilities in children with CH and PKU. MATERIALS AND METHODS: Sixty-eight children (25 children aged 1 to 120 months with PKU and 43 children aged 1 to 60 months with CH) participated in the study. The handbooks were analyzed and different instruments were applied (Observation of Communication Behavior, Early Language Milestone Scale, Peabody Picture Vocabulary Test, Gesell & Amatruda's Behavioral Development Scale, Portage Operation Inventory, Language Development Evaluation Scale, Denver Developmental Screening Test, ABFW Child Language Test-phonology and Illinois Test of Psycholinguistic Abilities), according to the children's age group and developmental level. RESULTS: It was observed that the children with PKU and CH at risk for alterations in their developmental abilities (motor, cognitive, linguistic, adaptive and personal-social), mainly in the first years of life. Alterations in the psycholinguistic abilities were also found, mainly after the preschool age. Attention deficits, language and cognitive alterations were more often observed in children with CH, while attention deficits with hyperactivity and alterations in the personal-social, language and motor adaptive abilities were more frequent in children with PKU. CONCLUSION: CH and PKU can cause communicative and psycholinguistic alterations that compromise the communication and affect the social integration and learning of these individuals, proving the need of having these abilities assisted by a speech and language pathologist.