CC chemokine ligand 3 and receptors 1 and 5 gene expression in recurrent aphthous stomatitis

Objective. The aim of this study was to investigate the local and systemic expression of CC-chemokine ligand 3 (CCL3) and its receptors (CCR1 and CCR5) in tissue samples and peripheral blood mononuclear cells of recurrent aphthous stomatitis (RAS) patients. Study Design. This case-control study enrolled 29 patients presenting severe RAS manifestations and 20 non-RAS patients proportionally matched by sex and age. Total RNA was extracted from biopsy specimens and peripheral blood mononuclear cells for quatitative reverse-transcription polymerase chain reaction. The data obtained by relative quantification were evaluated by the 2(-Delta Delta Ct) method, normalized by the expression of an endogenous control, and analyzed by Student t test. Results. The results demonstrated overexpression in RAS tissue samples of all of the chemokines evaluated compared with healthy oral mucosa, whereas the blood samples showed only CCR1 overexpression in RAS patients. Conclusions. These findings suggest that the increased expression of CCL3, CCR1, and CCR5 may influence the immune response in RAS by T(H)1 cytokine polarization. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:93-98)

Gram-negative osteomyelitis: clinical and microbiological profile

Introduction: Despite the growing interest in the study of Gram-negative bacilli (GNB) infections, very little information on osteomyelitis caused by GNB is available in the medical literature. Objectives and methods: To assess clinical and microbiological features of 101 cases of osteomyelitis caused by GNB alone, between January 2007 and January 2009, in a reference center for the treatment of high complexity traumas in the city of Sao Paulo. Results: Most patients were men (63%), with median age of 42 years, affected by chronic osteomyelitis (43%) or acute osteomyelitis associated to open fractures (32%), the majority on the lower limbs (71%). The patients were treated with antibiotics as inpatients for 40 days (median) and for 99 days (median) in outpatient settings. After 6 months follow-up, the clinical remission rate was around 60%, relapse 19%, amputation 7%, and death 5%. Nine percent of cases were lost to follow-up. A total of 121 GNB was isolated from 101 clinical samples. The most frequently isolated pathogens were Enterobacter sp. (25%), Acinetobacter baumannii (21%) e Pseudomonas aeruginosa (20%). Susceptibility to carbapenems was about 100% for Enterobacter sp., 75% for Pseudomonas aeruginosa and 60% for Acinetobacter baumannii. Conclusion: Osteomyelitis caused by GNB remains a serious therapeutic challenge, especially when associated to nonfermenting bacteria. We emphasize the need to consider these agents in diagnosed cases of osteomyelitis, so that an ideal antimicrobial treatment can be administered since the very beginning of the therapy. (C) 2012 Elsevier Editora Ltda. All rights reserved.

Modulation transfer function and optical quality after bilateral implantation of a+3.00 D versus a+4.00 D multifocal intraocular lens

PURPOSE: To determine whether the improvement in intermediate vision after bilateral implantation of an aspheric multifocal intraocular lens (IOL) with a +3.00 diopter (D) addition (add) occurs at the expense of optical quality compared with the previous model with a +4.00 D add. SETTING: Department of Ophthalmology, University of Sao Paulo, Sao Paulo, Brazil. DESIGN: Prospective randomized double-masked comparative clinical trial. METHODS: One year after bilateral implantation of Acrysof Restor SN6AD1 +3.00 D IOLs or Acrysof Restor SN6AD3 +4.00 D IOLs, optical quality was evaluated by analyzing the in vivo modulation transfer function (MTF) and point-spread function (expressed as Strehl ratio). The Strehl ratio and MTF curve with a 4.0 pupil and a 6.0 mm pupil were measured by dynamic retinoscopy aberrometry. The uncorrected and corrected distance visual acuities at 4 m, uncorrected and distance-corrected near visual acuities at 40 cm, and uncorrected and distance-corrected intermediate visual acuities at 50 cm, 60 cm, and 70 cm were measured. RESULTS: Both IOL groups comprised 40 eyes of 20 patients. One year postoperatively, there were no statistically significant between-group differences in the MTF or Strehl ratio with either pupil size. There were no statistically significant between-group differences in distance or near visual acuity. Intermediate visual acuity was significantly better in the +3.00 D IOL group. CONCLUSION: Results indicate that the improvement in intermediate vision in eyes with the aspheric multifocal +3.00 D add IOL occurred without decreasing optical quality over that with the previous version IOL with a +4.00 D add.

Differential expression of toll-like receptor mRNAs in recurrent aphthous ulceration

BACKGROUND: Toll-like receptors (TLR) are membrane proteins that recognize conserved molecules derived from bacterial, viral, fungal or host tissues. They are responsible for promoting the production of cytokines and chemokines, increasing the expression of costimulatory molecules and influencing the T Helper response (Th) toward either a Th1 or Th2 profile, thereby modulating the regulatory T cell response and controlling the integrity of the epithelial barrier. The key factors responsible for increased susceptibility to recurrent aphthous ulceration (RAU) are unclear, and because TLRs are involved in both immune regulation and control of the epithelial barrier, a deficiency in TLR activity is likely to cause increased susceptibility. METHODS: We investigated the gene expression of TLRs one through 10 in tissue samples and peripheral blood mononuclear cells (PBMC) of RAU patients in comparison to healthy controls using real-time quantitative reverse transcription PCR. RESULTS: The analysis of mRNA expression levels in oral lesion showed significant (P < 0.01) overexpression of the TLR2(similar to 6-fold) gene and decreased expression of the TLR3 (similar to 5-fold) and TLR5 (similar to 6-fold) genes in comparison with healthy oral mucosa. The analysis of mRNA expression in PBMC indicated a down-regulation of TLR5 gene expression in the cells from RAU patients (P < 0.05; similar to 2-fold). CONCLUSION: Our results support the hypothesis that a subset of RAU patients has fewer TLR expression that have been tentatively implicated in antiinflammatory effects. This derangement of TLR gene expression may cause an overlay exuberant inflammation reaction in situations where normal individuals are resistant. J Oral Pathol Med (2012) 41: 8085

Association between mannose-binding lectin and interleukin-1 receptor antagonist gene polymorphisms and recurrent vulvovaginal candidiasis

Objective The influence of functional polymorphisms in the genes coding for mannose-binding lectin (MBL) and interleukin-1 receptor antagonist (IL-1ra) on recurrent vulvovaginal candidiasis (RVVC) were examined in an urban Brazilian population. Methods DNA was isolated from buccal swabs of 100 women with RVVC and 100 control women and tested by gene amplification for a single nucleotide polymorphism in codon 54 of the MBL2 gene and for a length polymorphism in intron 2 of the IL1RN gene. Genotype and allele frequencies were compared between groups. Results The frequency of the variant MBL2 B allele, associated with reduced circulating and vaginal MBL concentrations, was 27.0% in RVVC and 8.5% in control women (p < .0001). The MBL2 B, B genotype was present in 12% of RVVC patients and 1% of controls (p = .0025). The IL1RN 2 allele frequency, associated with the highest level of unopposed IL-1 beta activity, was 24.0% in RVVC and 23.4% in controls. The IL1RN genotype distribution was also similar in both groups. Conclusion Carriage of the MBL2 codon 54 polymorphism, but not the IL1RN length polymorphism, predisposes to RVVC in Brazilian women.

BF Integrase Genes of HIV-1 Circulating in Sao Paulo, Brazil, with a Recurrent Recombination Region

Although some studies have shown diversity in HIV integrase (IN) genes, none has focused particularly on the gene evolving in epidemics in the context of recombination. The IN gene in 157 HIV-1 integrase inhibitor-naive patients from the Sao Paulo State, Brazil, were sequenced tallying 128 of subtype B (23 of which were found in non-B genomes), 17 of subtype F (8 of which were found in recombinant genomes), 11 integrases were BF recombinants, and 1 from subtype C. Crucially, we found that 4 BF recombinant viruses shared a recurrent recombination breakpoint region between positions 4900 and 4924 (relative to the HXB2) that includes 2 gRNA loops, where the RT may stutter. Since these recombinants had independent phylogenetic origin, we argue that these results suggest a possible recombination hotspot not observed so far in BF CRF in particular, or in any other HIV-1 CRF in general. Additionally, 40% of the drug-naive and 45% of the drug-treated patients had at least 1 raltegravir (RAL) or elvitegravir (EVG) resistance-associated amino acid change, but no major resistance mutations were found, in line with other studies. Importantly, V151I was the most common minor resistance mutation among B, F and BF IN genes. Most codon sites of the IN genes had higher rates of synonymous substitutions (dS) indicative of a strong negative selection. Nevertheless, several codon sites mainly in the subtype B were found under positive selection. Consequently, we observed a higher genetic diversity in the B portions of the mosaics, possibly due to the more recent introduction of subtype F on top of an ongoing subtype B epidemics and a fast spread of subtype F alleles among the B population.

Polymorphisms in antithrombin and in tissue factor pathway inhibitor genes are associated with recurrent pregnancy loss

Recurrent pregnancy loss (RPL) is a multifactorial condition. The effect of antithrombin (SERPINC1), protein C (PROC), thrombomodulin (THBD) and tissue factor pathway inhibitor (TFPI) single nucleotide polymorphisms (SNPs) on the risk of RPL is thus far unknown. Our objective was to determine the association of SNPs in the above mentioned genes with RPL. We included 117 non-pregnant women with three or more consecutive losses prior to 20 weeks of pregnancy without a previous history of carrying a fetus to viability, and 264 healthy fertile non-pregnant women who had at least two term deliveries and no known pregnancy losses. The PROC (rs1799809 and rs1799808), SERPINC1 (rs2227589), THBD (rs1042579) and TFPI (rs10931292, rs8176592 and rs10153820) SNPs were analysed by Real Time PCR. Genotype frequencies for PROC 2418A > G, PROC 2405C > T, THBD 1418C > T, TFPI (T-33C and TFPI C-399T) SNPs were similar in cases and controls. The carriers of SERPINC1 786A allele (GA + AA genotypes) had an increased risk for RPL (odds ratio [OR]: 1.77, 95% confidence interval [CI]: 1.05-3.00, p=0.034) while women carrying the TFPI-287C allele (TC + CC genotypes) had a protection effect on having RPL (OR: 0.46, 95% CI: 0.26 - 0.83, p=0.009). The TCC haplotype for TFPI T-33C/TFPI T-287C/TFPI C-399T SNPs was less frequent in cases (5.7%) than in controls (11.6%) (OR: 0.45, 95% CI: 0.23 - 0.90, p=0.025). In conclusion, our data indicate that SERPINC1 786G > A variant increases the risk for RPL, while TFPI T-287C variant is protective; however, further studies are required to confirm our findings.

Does Adjunctive Chemotherapy Reduce Remission Rates Compared to Cortisone Alone in Unifocal or Multifocal Histiocytosis of Bone?

Langerhans cell histiocytosis (LCH) is a rare disorder that can affect almost any organ, including bone. Treatment options include local corticosteroid infiltration in isolated bone lesions and oral corticosteroids and chemotherapy in multifocal bone lesions. Several studies show local corticosteroid injection in unifocal bone lesions heal in more than 75% of patients with minimal side effects. Therefore, it is unclear whether chemotherapy adds materially to the healing rate. We therefore compared overall survival, remission rate, and recurrence rate in patients with bone LCH treated with chemotherapy and corticosteroids or corticosteroids alone. We retrospectively reviewed the records of 198 patients with LCH since 1950. Median age at diagnosis was 5 years, male-to-female ratio was 1.33, and the most frequent symptom was local pain (95%). We recorded the disease presentation, demographics, treatment, and clinical evolution of each patient. Minimum followup was 4 months (median, 24 months; range, 4-360 months). The survival rate of the systemic disease group was 76.5% (65 of 85) while the survival rate in the unifocal and multifocal bone involvement groups was 100% at a median 5-year followup. All patients with unifocal bone involvement and 40 of 43 (93%) with multifocal bone involvement had complete remission. One of 30 patients with multifocal bone involvement treated with chemotherapy and oral corticosteroids did not achieve remission whereas two of six receiving only corticosteroids did not achieve remission. Our observations suggest intralesional corticosteroid injection without adjunctive chemotherapy achieves remission in unifocal bone LCH but may not do so in multifocal single-system bone involvement. Larger series would be required to confirm this observation. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes

Recurrent chromosomal translocations underlie both haematopoietic and solid tumours. Their origin has been ascribed to selection of random rearrangements, targeted DNA damage, or frequent nuclear interactions between translocation partners; however, the relative contribution of each of these elements has not been measured directly or on a large scale. Here we examine the role of nuclear architecture and frequency of DNA damage in the genesis of chromosomal translocations by measuring these parameters simultaneously in cultured mouse B lymphocytes. In the absence of recurrent DNA damage, translocations between Igh or Myc and all other genes are directly related to their contact frequency. Conversely, translocations associated with recurrent site-directed DNA damage are proportional to the rate of DNA break formation, as measured by replication protein A accumulation at the site of damage. Thus, non-targeted rearrangements reflect nuclear organization whereas DNA break formation governs the location and frequency of recurrent translocations, including those driving B-cell malignancies.

Cochleovestibular nerve involvement in multifocal fibrosclerosis

Objectives: To report a case of multifocal fibrosclerosis with a nine-year follow up, and to discuss this disease's radiological appearance and management. The disease is a rare systemic disorder of unknown cause characterised by fibrous proliferation involving multiple anatomical sites. Case report: A 50-year-old woman presented with histological findings characterised by similar inflammatory processes involving the meninges, pituitary gland, peritoneum, retroperitoneum and orbits, prompting a search for a common pathophysiology. A diagnosis of multifocal fibrosclerosis was postulated. Symptom improvement was noted after treatment with prednisone and azathioprine. Conclusion: This is the first documented case of involvement of the cochleovestibular nerve in a patient with multifocal fibrosclerosis. The rare association between fibrotic diseases and masses showing various clinical patterns should be kept in mind by otolaryngologists, and imaging performed to investigate for multifocal fibrosclerosis. However, diagnosis can only be confirmed with tissue biopsy and histopathological examination.

Prevention of recurrent herpes labialis outbreaks through low-intensity laser therapy: a clinical protocol with 3-year follow-up

Conselho Nacional de Pesquisa e Desnsenvolvimento Tecnologico (CNPq)

Radiologic findings of osteoarticular infection in paracoccidioidomycosis

To report the radiological abnormalities of osteoarticular involvement in paracoccidioidomycosis (PCM). After institutional board approval, the medical records and conventional radiology findings of 19 patients with osseous PCM were retrospectively reviewed. Number, distribution, and lesion characteristics were evaluated in consensus by two experienced musculoskeletal radiologists. The mean age of patients was 16.1 years (range 4-49 years), 11 male and eight female. MSK involvement was the only or the primary presentation of the disease in eight of 19 patients (42.1%). In total, 51 focal bone lesions were detected, being 41 in long bones. In long bones lesions, 19 of 41 (46.4%) were metaphyseal, 12 of 41 (29.3%) meta-epiphyseal, and 12 of 41 (29.3%) diaphyseal. The most common presentation was a geographic osteolytic bone lesion (62.7%), without marginal sclerosis (82.4%) and without periosteal reaction (90.2%). Articular involvement was present in six of 19 patients (31.6%), being two cases of primary arthritis. All encountered bone lesions were osteolytic. Metaphyseal or meta-epiphyseal osteomyelitis of a long bone was the most prevalent osteoarticular manifestation of paracoccidioidomycosis. PCM osteoarticular involvement could be solitary or multifocal, occurs almost exclusively in the acute/subacute clinical form, and it is more common in children and in juvenile patients. Axial skeleton involvement, arthritis, or a disseminated osseous pattern of infection may occasionally occur in this fungal disease.

Multifocal pattern electroretinography for the detection of neural loss in eyes with permanent temporal hemianopia or quadrantanopia from chiasmal compression

Aims To evaluate the ability of multifocal transient pattern electroretinography (mfPERG) to detect neural loss and assess the relationship between mfPERG and visual-field (VF) loss in eyes with chiasmal compression. Methods 23 eyes from 23 patients with temporal VF defects and band atrophy of the optic nerve and 21 controls underwent standard automated perimetry and mfPERG using a stimulus pattern of 19 rectangles, each consisting of 12 squares. The response was determined for the central rectangle, for the nasal and temporal hemifields (eight rectangles each) and for each quadrant (three rectangles) in both patients and controls. Comparisons were made using variance analysis. Correlations between VF and mfPERG measurements were verified by linear regression analysis. Results Mean +/- SD mfPERG amplitudes from the temporal hemifield (0.50 +/- 0.17 and 0.62 +/- 0.32) and temporal quadrants (superior 0.42 +/- 0.21 and 0.52 +/- 0.35, inferior 0.51 +/- 0.23 and 0.74 +/- 0.40) were significantly lower in eyes with band atrophy than in controls (0.78 +/- 0.24, 0.89 +/- 0.28, 0.73 +/- 60.26, 0.96 +/- 0.36, 0.79 +/- 0.26 and 0.91 +/- 0.31, respectively). No significant difference was observed in nasal hemifield measurements. Significant correlations (0.36-0.73) were found between VF relative sensitivity and mfPERG amplitude in different VF sectors. Conclusions mfPERG amplitude measurements clearly differentiate eyes with temporal VF defect from controls. The good correlation between mfPERG amplitudes and the severity of VF defect suggests that mfPERG may be used as an indicator of ganglion cell dysfunction.

Comparison of the reliability of multifocal visual evoked cortical potentials generated by pattern reversal and pattern pulse stimulation

This study compared the effectiveness of the multifocal visual evoked cortical potentials (mfVEP) elicited by pattern pulse stimulation with that of pattern reversal in producing reliable responses (signal-to-noise ratio >1.359). Participants were 14 healthy subjects. Visual stimulation was obtained using a 60-sector dartboard display consisting of 6 concentric rings presented in either pulse or reversal mode. Each sector, consisting of 16 checks at 99% Michelson contrast and 80 cd/m² mean luminance, was controlled by a binary m-sequence in the time domain. The signal-to-noise ratio was generally larger in the pattern reversal than in the pattern pulse mode. The number of reliable responses was similar in the central sectors for the two stimulation modes. At the periphery, pattern reversal showed a larger number of reliable responses. Pattern pulse stimuli performed similarly to pattern reversal stimuli to generate reliable waveforms in R1 and R2. The advantage of using both protocols to study mfVEP responses is their complementarity: in some patients, reliable waveforms in specific sectors may be obtained with only one of the two methods. The joint analysis of pattern reversal and pattern pulse stimuli increased the rate of reliability for central sectors by 7.14% in R1, 5.35% in R2, 4.76% in R3, 3.57% in R4, 2.97% in R5, and 1.78% in R6. From R1 to R4 the reliability to generate mfVEPs was above 70% when using both protocols. Thus, for a very high reliability and thorough examination of visual performance, it is recommended to use both stimulation protocols.