Quasispecies of hepatitis C virus genotype 1 and treatment outcome with Peginterferon and Ribavirin

The majority of patients with chronic hepatitis C fail to respond to antiviral therapy. The genetic basis of this resistance is unknown. The quasispecies nature of HCV may have an important implication concerning viral persistence and response to therapy. The HCV nonstructural 5A (NS5A) protein has been controversially implicated in the inherent resistance of HCV to interferon (IFN) antiviral therapy. To evaluate whether the NS5A quasispecies pre-treatment composition of HCV 1a/1b is related to responsiveness to combined pegylated interferon (PEG-IFN) and Ribavirin therapy, detailed analyses of the complete NS5A were performed. Fifteen full-length NS5A clones were sequenced from 11 pretreatment samples of patients infected with genotype 1 HCV (3 virological sustained responders, 4 non-responders, and 4 end-of-treatment responders). Our study could not show a significant correlation between the mean number of mutations in HCV NS5A before treatment and treatment outcome, and the phylogenetic construction of complete NS5A sequences obtained from all patients failed to show any clustering associated with a specific response pattern. No single amino acid position was associated with different responses to therapy in any of the NS5A regions analyzed, and mutations were clustered downstream the ISDR, primarily in the V3 region. We observed that the CRS and NLS regions of the NS5A protein were conflicting for some variables analyzed, although no significant differences were found. If these two regions can have antagonistic functions, it seems viable that they present different mutation profiles when compared with treatment response. The patient sample that presented the lowest genetic distance values also presented the smallest number of variants, and the most heterogeneous pattern was seen in the end-of-treatment patients. These results suggest that a detailed molecular analysis of the NS5A region on a larger sample size may be necessary for understanding its role in the therapy outcome of HCV 1a/1b infection. (C) 2008 Elsevier B.V. All rights reserved.

On Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcome

Background:Hepatitis C is a disease spread throughout the world. Hepatitis C virus (HCV), the etiological agent of this disease, is a single-stranded positive RNA virus. Its genome encodes a single precursor protein that yields ten proteins after processing. NS5A, one of the non-structural viral proteins, is most associated with interferon-based therapy response, the approved treatment for hepatitis C in Brazil. HCV has a high mutation rate and therefore high variability, which may be important for evading the immune system and response to therapy. The aim of this study was to analyze the evolution of NS5A quasispecies before, during, and after treatment in patients infected with HCV genotype 3a who presented different therapy responses.Methods:Viral RNA was extracted, cDNA was synthesized, the NS5A region was amplified and cloned, and 15 clones from each time-point were sequenced. The sequences were analyzed for evolutionary history, genetic diversity and selection.Results:This analysis shows that the viral population that persists after treatment for most non-responder patients is present in before-treatment samples, suggesting it is adapted to evade treatment. In contrast, the population found in before treatment samples from most end-of-treatment responder patients either are selected out or appears in low frequency after relapse, therefore changing the population structure. The exceptions illustrate the uniqueness of the evolutionary process, and therefore the treatment resistance process, in each patient.Conclusion:Although evolutionary behavior throughout treatment showed that each patient presented different population dynamics unrelated to therapy outcome, it seems that the viral population from non-responders that resists the treatment already had strains that could evade therapy before it started. © 2013 Bittar et al.

Long-term outcome of penile fracture treatment

Objectives: Penile fracture is a rare injury, usually resulting from direct trauma to the erect penis during sexual intercourse. Our goal was to evaluate the best diagnostic methods and the late complications following surgical treatment of penile fracture. Material and Methods: We studied retrospectively 11 patients with penile fracture in a period of 10 years (1985-1995). Results: In 55% of the cases, the injury occurred during sexual intercourse. All patients presented with a very suggestive clinical picture (pain, detumescence and hematoma) and only 2 were submitted to further investigation (ultrasonography) to confirm the diagnosis. Only one patient had urethral bleeding and therefore was submitted to retrograde urethrogram, which confirmed urethral injury. All patients were treated by immediate surgery, through a circular subcoronal incision and degloving of the penis to allow a thorough exploration. All patients had a tunica albuginea tear that was promptly repaired, and 2 patients (18%) had associated urethral injury (one had no symptoms) that was also repaired. All patients did very well after surgery and only one had a mild curvature, which did not hinder intercourse during follow-up (18 months). Conclusions: Penile fracture has very typical clinical signs and, therefore, further investigation is usually unnecessary. Early surgical treatment is associated with a low incidence of late complications.

Studying the satisfaction of patients on the outcome of an aesthetic dermatological filler treatment

Background: Many factors contribute to extend productive life in the modern world. Competition makes people worry about physical appearance, mosftly in respect to facial and skin aging. This has motivated new developments in cosmetic dermatology and the need of evaluating patient satisfaction with the new proposed treatments. Poll questionnaire has been used for such evaluation, and the analysis of the electroencephalogram (EEG) mapping obtained while the patient answers the satisfaction questionnaire may render the results less subjective. Objectives: The purpose of this paper is to study the satisfaction of a group of 33 women (mean age, 44.years) treated with hyaluronic acid filling of nasolabial folding or lips, combining the EEG brain mapping and questionnaire techniques. Methods: At the third month of evaluation, two networked personal computers were used for the EEG recording and for presenting the patient with a questionnaire about her well-being feeling; self-evaluation of her face; her satisfaction with the results of the aesthetic treatment; how the family, friends, and people at work evaluated the result of the treatment; and her decision to repeat the treatment and to recommend it to friends and family. Results: Poll results showed that patients were feeling well and were satisfied with the results of the aesthetic treatment. Furthermore, the regression EEG mappings showed patients to be satisfied with their appearance and with the treatment involving similar brain areas. Conclusion: Patients decided to undergo the treatment because they were already considering it (54%) or because they were dissatisfied with their lips or nasolabial folding (52%). The fact that the treatment was free of charge solidified the decision. Patients consider themselves as good-looking and they wanted to preserve such a condition. © 2008 Wiley Periodicals, Inc.

Efficacy of surgical versus conservative treatment in esophageal perforation: a systematic review of case series studies

PURPOSE: To evaluate the efficacy of surgical treatment for esophageal perforation. METHODS: A systematic review of the literature was performed. We conducted a search strategy in the main electronic databases such as PubMed, Embase and Lilacs to identify all case series. RESULTS: Thirty three case series met the inclusion criteria with a total of 1417 participants. The predominant etiology was iatrogenic (54.2%) followed by spontaneous cause (20.4%) and in 66.1% the localization was thoracic. In 65.4% and 33.4% surgical and conservative therapy, respectively, was considered the first choice. There was a statistically significance different with regards mortality rate favoring the surgical group (16.3%) versus conservative treatment (21.2%) (p<0.05). CONCLUSION: Surgical treatment was more effective and safe than conservative treatment concerning mortality rates, although the possibility of bias due to clinical and methodological heterogeneity among the included studies and the level of evidence that cannot be ruled out.

Alcoholic women and men: a comparative study of social and familial aspects and outcome

Objetivos: A proporção de ocorrência de alcoolismo em homens e mulheres tem uma variação de 14:1 até 2:1, mostrando a necessidade de estudos específicos para a população feminina. O objetivo deste estudo foi analisar o perfil e a evolução de alcoolistas, segundo gênero e gravidade da dependência. Métodos: Realizou-se um estudo longitudinal retrospectivo de 114 homens e 57 mulheres alcoolistas (CID-10), inscritos no ambulatório da Faculdade de Medicina de Botucatu, no período de 1990-1994 e avaliados até julho de 1997. Utilizou-se um questionário semi-estruturado, e, para avaliação da gravidade do alcoolismo, o Short Alcohol Dependence Data. Resultados/Conclusões: Os principais resultados mostraram que a estrutura familiar estava comprometida com: relacionamento difícil para 55,6% das mulheres e 65,7% dos homens; violência familiar em 74,1% das mulheres e 61,1% dos homens. As mulheres iniciaram a ingestão mais tarde que os homens (p=0,01), em geral com seus cônjuges (p=0,00). Não houve diferença de evolução no tratamento entre os gêneros. Os principais fatores associados à melhor resposta ao tratamento, independentemente do sexo, foram: nível de gravidade de dependência do álcool (dependentes leves e moderados apresentaram 5,59 vezes mais chances de melhorar do que os dependentes graves); ser praticante de alguma religião (2,3 vezes mais chances de melhora do que os pacientes que não eram praticantes); e tempo de seguimento no programa, negativamente correlacionado a chances de melhora (0,68 vezes menos chances de melhora que aqueles que permaneceram por tempo menor em tratamento).

Lethal photosensitization and guided bone regeneration in treatment of peri-implantitis: an experimental study in dogs

The purpose of this study was to evaluate the effect of lethal photosensitization and guided bone regeneration (GBR) on the treatment of ligature-induced peri-implantitis in different implant surfaces. The treatment outcome was evaluated by clinical and histometric methods. A total of 40 dental implants with four different surface coatings (10 commercially pure titanium surface (cpTi); 10 titanium plasma-sprayed (TPS); 10 acid-etched surface; 10 surface-oxide sandblasted) were inserted into five mongrel dogs. After 3 months, the animals with ligature-induced peri-implantitis were subjected to surgical treatment using a split-mouth design. The controls were treated by debridment and GBR, while the test side received an additional therapy with photosensitization, using a GaAlAs diode laser, with a wavelength of 830 nm and a power output of 50 mW for 80 s (4 J/cm(2)), and sensitized toluidine blue O (100 mu g/ml). The animals were sacrificed 5 months after therapy. The control sites presented an earlier exposition of the membranes on all coating surfaces, while the test group presented a higher bone height gain. Re-osseointegration ranged between 41.9% for the cpTi surface and 31.19% for the TPS surface in the test sites; however differences were not achieved between the surfaces. The lethal photosensitization associated with GBR allowed for better re-osseointegration at the area adjacent to the peri-implant defect regardless of the implant surface.

Treatment of gingival recession: Comparative study between subepithelial connective tissue graft and guided tissue regeneration

Background: Various procedures have been proposed to treat gingival recession, but few studies compare these procedures to each other. The purpose of this study was to evaluate a clinical comparison of subepithelial connective tissue graft (SCTG) and guided tissue regeneration (GTR) with a collagen membrane in the treatment of gingival recessions in humans. Methods: Twenty-four defects were treated in 12 patients who presented canine or pre-molar Miller Class I and/or II bilateral gingival recessions. Both treatments were performed in all patients, and clinical measurements were obtained at baseline and 18 months after surgery. These clinical measurements included gingival recession height (GR), root coverage (RC), probing depth (PD), keratinized tissue width (KT), and final esthetic result. Results: Both SCTG and GTR with a bioabsorbable membrane and bone graft demonstrated significant clinical and esthetic improvement for gingival recession coverage. The SCTG group was statistically significantly better than GTR for height of GR (SCTG = 0.2 mm, GTR = 1.12 mm, P = 0.02) and KT (SCTG = 4.58 mm, GTR = 2.5 mm, P <0.0001). However, PD was statistically significantly better for GTR than SCTG treatment (GTR = 1.66 mm, SCTG = 1.00, P = 0.01). The 2 procedures were statistically similar in root coverage (SCTG = 95.6%, GTR = 84.2%, P = 0.073). The esthetic condition after both treatments was satisfactory (P = 0.024). Conclusions: It was concluded that the gingival recessions treated with the SCTG group were superior for GR, RC, and KT clinical parameters, while GTR demonstrated better PD reduction. The final esthetic results were similar using both techniques.

Subgingival utilization of a 1% chlorhexidine collagen gel for the treatment of periodontal pockets. A clinical and microbiological study.

This study evaluates the effect of subgingival irrigation with a 1% chlorhexidine collagen gel in periodontal pockets as an adjunct procedure to scaling and root planing (SRP). Thirty-seven sites with probing depth (PD) of 5-7 mm and BANA positive in 6 patients with chronic periodontal disease were selected. Sites were assigned to different treatment groups consisting of SRP only (group 1), SRP + irrigation with collagen gel (group 2), or SRP + irrigation with collagen gel containing 1% chlorhexidine (group 3). Subgingival irrigation was performed after initial SRP and at 7, 14 and 21 days. Clinical measurements including PD, plaque index (PI), gingival index (GI), gingival recession (GI), bleeding on probing (BOP) and clinical attachment level (CAL) were performed at the selected sites at baseline, 60 and 90 days and the BANA test was performed on plaque samples from the same sites at baseline and 90 days. There was an improvement in clinical parameters in all groups with a significantly greater decrease in GI and bleeding in the chlorhexidine group. There was a greater reduction of BANA positive sites in groups 2 and 3. The authors concluded that 1% chlorhexidine collagen gel is a promising adjunct to SRP in the treatment of adult periodontitis.

Gelatinous polyethylene in the treatment of the anophthalmic cavity

PURPOSE: Gelatinous polyethylene (GP) has been used as an orbital implant to evaluate volume maintenance and tissue reaction in the anophthalmic socket in a rabbit model. METHODS: Twenty-eight Norfolk white rabbits underwent unilateral evisceration with placement of 2ml GP (GP group - 16 animals) or 2ml 0.9% sodium chloride solution (Control group - 12 animals). Animal behavior, postoperative tissue response and socket conditions were evaluated. The animals were sacrificed at 7, 15, 30 and 60 days after the surgery and the bulbs were enucleated; volume maintenance and histopathological evaluation were done in the enucleated bulbs. The results were submitted to statistical analysis. RESULTS: All animals showed normal behavior. The orbital volume maintenance was better in the GP group. Histopathology in the GP animals showed mild tissue inflammation throughout the evaluation period and a thin pseudocapsule formation surrounding the orbital implant material. CONCLUSION: The clinical findings, good orbital volume maintenance and mild inflammatory tissue response make GP a good choice to replace the lack of volume in anophthalmic socket reconstruction.

Treatment Effects Produced by Fränkel Appliance in Patients with Class II, Division 1 Malocclusion

The purpose of this investigation was to evaluate the dentoalveolar and skeletal cephalometric changes produced by the Fränkel appliance in individuals with a Class II, division 1 malocclusion. Lateral cephalograms of 44 patients of both sexes were divided in two groups of 22 each. The control group was comprised of untreated Class II children with an initial mean age of eight years and seven months who were followed without treatment for a period of 13 months. The Fränkel group had an initial mean age of nine years and was treated for a mean period of 17 months. Lateral cephalometric headfilms of each patient were obtained at the beginning and end of treatment. The Fränkel appliance produced no significant changes in maxillary growth during the evaluation period, while a statistically significant increase in mandibular length was observed. The maxillomandibular relationship improved mostly because of an increase in mandibular length. In addition, there were no statistically significant differences in the craniofacial growth direction between the Fränkel and the control group, both showing a slight downward rotation of the palatal plane. The Fränkel appliance produced a labial tipping of the lower incisors and a lingual inclination of the upper incisors as well as a significant increase in mandibular posterior dentoalveolar height. It was concluded that the main effects of the Fränkel appliance during this time period were mostly dentoalveolar with a smaller but significant skeletal mandibular effect.

Surgical treatment of metachronous metastases in different organs following radical nephrectomy

Renal clear cell carcinoma (RCCC) is a neoplasia resistant to radio and chemotherapy, with surgical treatment being the procedure that is recognized for its curative treatment. This case report demonstrates the success of an aggressive surgical treatment for consecutive and late metachronous metastases following radical nephrectomy. Case report: Asymptomatic 50-year old man. During a routine examination, an incidental mass was found by renal ultrasonography. He underwent right radical nephrectomy due to RCCC in June 1992. During the follow-up metastases were evidenced in cerebellum on the seventh year, and in left lung and pancreas on the eighth year following the radical nephrectomy, with all of them successfully treated by surgical excision. Comments: The surgical excision of consecutive and late metachronous metastases in different organs arising from RCCC is feasible, being a good therapeutic alternative in selected cases.

Effect of the Clinical Application of the GaA1As Laser in the Treatment of Dentine Hypersensitivity

Objective: The aim of this study was to evaluate the effectiveness of the clinical use of the gallium-aluminum-arsenium (GaAlAs) laser at the maximum and minimum energies recommended by the manufacturer for the treatment of dentine hypersensitivity. Background Data: Dentine hypersensitivity (DH) is a response to a stimulus that would not usually cause pain in a healthy tooth. It is characterized by sharp pain of short duration from the denuded dentin. Its etiology is unknown. The dentin only begins to show sensitivity when exposed to the buccal environment. This exposure can result after removal of the enamel and/or dental cement, or after root denudation. Different treatments are proposed for this disorder. Materials and Methods: In this study, 25 patients, with a total number of 106 cases of DH, were treated with GaAlAs low-level laser therapy (LLLT). 65% of the teeth were premolars; 14% were incisors and molars; 6.6% were canines. The teeth were irradiated with 3 and 5 J/cm 2 for up to six sessions, with an interval of 72 h between each application, and they were evaluated initially, after each application, and at 15 and 60 days follow-up post-treatment. Results: The treatment was effective in 86.53% and 88.88% of the irradiated teeth, respectively, with the minimum and maximum energy recommended by the manufacturer. There was a statistically significant difference between DH and after a follow-up of 60 days for both groups. The difference among the energy maximum and minimum was not significant. Conclusion: The GaAlAs low-level laser was effective in reducing initial DH. A significant difference was found between initial values of hypersensitivity and after 60 days follow-up post-treatment. No significant difference was found between minimum (3 J/cm 2) and maximum (5 J/cm 2) applied energy.

Apert syndrome: Analysis of associated brain malformations and conformational changes determined by surgical treatment

Apert Syndrome, also called acrocephalosyndactylia type 1, is characterized by craniostenosis with early fusion of sutures of the vault and/ or cranial base, associated to mid-face hypoplasia, symmetric syndactylia of the hands and feet and other systemic malformations. CNS malformations and intracranial hypertension are frequently observed in these patients. Early surgical treatment aims to minimize the deleterious effects of intracranial hypertension. Fronto-orbital advancement, the usual surgical technique, increases the intracranial volume and improves the disposition of encephalic structures previously deformed by a short skull. This study analyzes CNS alterations revealed by magnetic resonance in 18 patients presenting Apert Syndrome, and the conformational alterations in the encephalic structures after surgical treatment. The patients' age in February 2001 ranged from 14 to 322 months (m=107). Image study included brain magnetic resonance showing ventricular enlargement in five cases (27.8%), corpus callosum hypoplasia in five cases (27.8%), septum pellucidum hypoplasia in five cases (27.8%), cavum vergae in two cases (11.1%) and, arachnoid cyst in the posterior fossa in two cases (11.1%). Absence of CNS alterations was noted in 44.4% of cases. A corpus callosum morphologic index was established by dividing its height by its length, which revealed values that ranged from 0.4409 to 1.0237. The values of this index were correlated to the occurrence or absence of surgical treatment (p=0.012; t=2.83). Data analysis allowed the conclusion that the corpus callosum morphologic measure quantified the conformational alterations of the cerebral structures determined by the surgical treatment.

Argon laser for treatment of benign eyelid tumors

Small lesions located in the skin might be treated using the laser system. The purpose of this is to report the therapy of benign eyelid tumors using argon laser. Forty-four benign eyelid tumors were treated using argon blue-green laser with spot size of 500 μm, power from 1000 to 1200 mW and 0.3 second exposure time. The eyelid tumors were located mainly in the upper eyelid (65.9%) and the skin tag was the most frequent treated lesion (43.2%). The average number of laser shots to treat the lesions was 165. There was not observed any complication and all patients were satisfied with the results. The authors are considering the argon laser a benefit therapeutic method to treat benign tumors located in the eyelids.