Customized Topography-guided Photorefractive Keratectomy With the MEL-70 Platform and Mitomycin C to Correct Hyperopia After Radial Keratotomy

PURPOSE: To evaluate topography-guided photorefractive keratectomy (PRK) for correcting hyperopia and astigmatism after radial keratotomy (RK). METHODS., Prospective study of 12 consecutive patients (19 eyes) who were treated with topography-guided PRK with 0.02% mitomycin C using an Asclepion-Meditec MEL-70 excimer laser with a 9.5-mm ablation zone. All eyes were operated by the same surgeon and followed for 1 year. RESULTS: Thirteen eyes had complete epithelialization by day 7 and all eyes by day 10. At 1 year, uncorrected visual acuity was 20/25 or better in 42.1% of eyes and 20/40 or better in 68.4%. Preoperative mean spherical equivalent refraction was +3.80 +/- 2.47 diopters (D) and +0.24 +/- 2.36 D (P <.001) 1 year postoperative, with 47.4% of eyes being within +/- 1.00 D and 73.7% within +/- 2.00 D. Preoperative mean cylinder was -2.30 +/- 1.41 D and -0.62 +/- 0.73 D (P <.1001) 1 year postoperative. At 1 year, 68.4% of eyes gained at least 1 line of best-spectacle corrected visual acuity, 36.8% gained more than 1 line, and only 2 eyes lost 1 line (one due to corneal haze). Three eyes developed central haze. Mean regression from 6 to 12 months in these 3 eyes was +1.83 D and in the remaining 16 eyes was -0.50 D. CONCLUSIONS: Topography-guided PRK with mitomycin C was safe and reasonably effective for the treatment of hyperopia after RK [J Refract Surg. 2008;24:911-922.]

Synergistic effect of ethanol and mitomycin C on corneal stroma

PURPOSE: To investigate the combined effects of ethanol and mitomycin C (MMC) application on the corneal stroma of rabbits that underwent photorefractive keratectomy (PRK). METHODS: Twenty-four rabbits (24 eyes) underwent PRK to correct -9.00 diopters of myopia. Twelve eyes had ethanol application before removing the epithelium and 12 eyes had the epithelium manually removed without ethanol, Eyes in both groups had topical MMC 0.02% application for 12 seconds immediately after excimer laser ablation. Twelve rabbits were sacrificed at two time points-4 hours and 4 weeks after surgery-and immunohistochemistry was performed with TUNEL assay, alpha-smooth muscle actin (alpha-SMA), and DAPI. RESULTS: More TUNEL-positive cells were observed in the ethanol-treated group compared to the mechanical debridement group at 4 hours after surgery (P<.01). No significant difference in alpha-SMA-positive cells was detected, between the two groups at 4 weeks after sugery. However, decreased keratocyte density in the anterior stroma was more pronounced in the ethanol-treated group compared to the mechanical debridement (P<.02). CONCLUSIONS: Ethanol application for epithelial removal during PRK seems to produce a synergistic effect with MMC, resulting in fewer keratocytes in the anterior stroma of rabbit corneas treated with MMC and ethanol than in corneas treated with MMC alone after PRK.

Is the combination of mitomycin C, bleomycin and methotrexate effective as a neoadjuvant treatment for cervical cancer in women?

Objective: To determine the effectiveness of the combination of mitomycin C, bleomycin and methotrexate as a neoadjuvant treatment in preparation for surgical treatment of cervical cancer. Methods and Materials: Twenty-seven patients with carcinoma of the uterine cervix (stages exophytic IB2 and IIB-IIIB) who had not previously undergone any treatment received mitomycin C, bleomycin and methotrexate in five sessions, once every four weeks. Results: The objective response rate was approximately 81%, including 16 complete responses and six partial responses. Significant toxic effects were not observed. Responsive patients underwent surgery and remained without evidence of disease for the next 20 years. Unresponsive patients did not fare well and passed away within five years after treatment. Conclusion: Our data suggest that this strategy may be effective for advanced cases, enabling patients to receive surgical treatment.

Hormone therapy in Brazilian postmenopausal women with chronic hepatitis C: a pilot study

Design Fifty out of 336 postmenopausal patients with chronic infection with the hepatitis C virus were selected. The non-inclusion criteria were other chronic or systemic liver diseases, severe vascular diseases, autoimmune diseases or malignant tumors. The patients were randomized into two groups: the HT group with 25 patients to be given transdermal hormone therapy (50 mu g estradiol plus 170 mu g norethisterone/day) and the control group with the other 25 patients (no medication). Hepatic tests (alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total alkaline phosphatase, albumin, serum bilirubin) and hemostatic parameters (prothrombin time, factor V, fibrinogen) were evaluated at baseline and at 1, 4, 7 and 9 months of treatment. Results No significant changes in parameters were found in the comparison between the treated group and the controls, except for a decrease in total alkaline phosphatase (p = 0.002), presumably due to changes in bone remodelling. Conclusions There were no changes in liver function after a 9-month treatment with transdermal estradiol plus norethisterone in symptomatic postmenopausal patients with hepatitis C.

Influence of LH and high-density lipoprotein cholesterol (HDL-C) on metformin response in women with polycystic ovary syndrome

Objective: To search for predictors of metformin response in women with polycystic ovary syndrome (PCOS) through a detailed analysis of clinical and laboratory parameters. Study design: We designed a prospective study to investigate clinical and laboratory parameters to search for predictors of metformin response in women with PCOS. A total of 53 PCOS patients were given metformin 850 mg twice a day for 6 months, after which patients were classified as responders or non-responders. Parameters analyzed for comparison between the two groups were: plasma fasting insulin glucose/insulin ratio; oral glucose tolerance test (OGTT) with insulin (120 min); HOMA and QUICKI tests; total cholesterol and fractions, triglycerides; LH, FSH, estradiol, progesterone, testosterone, androstenedione, 17-OH progesterone, and DHEAS. Results: From all patients, 30(56.6%) were responders and 23(43.3%) were non-responders. Multinomial analysis showed that the positive response to metformin was associated with higher levels of basal LH (p = 0.038) and lower levels of high-density lipoprotein cholesterol (HDL-C) (p = 0.015). Conclusion: In weight-matched PCOS subjects, laboratory markers might predict the metformin response. Higher levels of basal LH and lower levels of HDL-C are correlated with a positive response to metformin treatment in PCOS subjects. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Cost-effectiveness analysis of a hypothetical hepatitis C vaccine compared to antiviral therapy

We propose a mathematical model to simulate the dynamics of hepatitis C virus (HCV) infection in the state of Sao Paulo, Brazil. We assumed that a hypothetical vaccine, which cost was taken to be the initial cost of the vaccine against hepatitis B exists and it is introduced in the model. We computed its cost-effectiveness compared with the anti-HCV therapy. The calculated basic reproduction number was 1.20. The model predicts that without intervention a steady state exists with an HCV prevalence of 3%, in agreement with the Current epidemiological data. Starting from this steady state three interventions were simulated: indiscriminate vaccination, selective vaccination and anti-HCV therapy. Selective vaccination proved to be the strategy with the best cost-effectiveness ratio, followed by indiscriminate vaccination and anti-HCV therapy.

Post-transplant recurrent hepatitis C: immunohistochemical detection of hepatitis C virus core antigen and possible pathogenic implications

Introduction: The mechanisms by which severe cholestatic hepatitis develops after liver transplantation are not fully understood. Reports on immunohistochemical distribution of hepatitis C virus (HCV) antigens are still scarce, but recently, HCV immunostaining was suggested for early diagnosis of cholestatic forms of recurrent hepatitis C in liver grafts. After purification, Rb246 pab anticore (aa1-68) yielded specific, granular cytoplasmic staining in hepatocytes. Signal amplification through the Envision-Alkaline Phosphatase System avoided endogenous biotin and peroxidase. Aims/Methods: Rb246 was applied to liver samples of explants of 12 transplant recipients, six with the most severe form of post-transplantation recurrence, severe cholestatic hepatitis (group 1) and six with mild recurrence (group 2). We also assessed immuno-reactivity at two time-points post-transplantation (median 4 and 22 months) in both groups. HCV-core Ag was semiquantified from 0 to 3+ in each time point. Serum HCV-RNA was also measured on the different time points by branched DNA. Results: In the early post-transplant time point, one patient had a mild staining (1+), two patients had a moderate staining (2+) and the other three had no staining in group 1, compared with five patients with no staining (0) and one patient with mild staining (1+) in group 2. Late post-transplant liver samples were available in nine patients, and two out of four samples in group 1 showed a mild staining, compared with no staining patients in five patients in group 2. Strikingly, on the explant samples, HCV immunostaining was strongly positive in group 1, and mildly positive in group 2. Two out of five samples showed 3+ staining, and three samples showed 2+ staining in group 1; two out of five samples showed no staining, two samples showed 1+ staining and one sample showed 2+ staining in group 2. Serum HCV-RNA was significantly higher in group 1, on both time-points post-transplantation. HCV-core Ag was not directly associated with serum HCV-RNA on the different time points. Conclusion: These preliminary results suggest that strong HCV immunostaining in the explant is predictive of more severe disease recurrence.

Anti-leishmanial effects of purified compounds from aerial parts of Baccharis uncinella C. DC. (Asteraceae)

Species of Baccharis exhibit antibiotic, antiseptic, wound-healing, and anti-protozoal properties, and have been used in the traditional medicine of South America for the treatment of several diseases. In the present work, the fractionation of EtOH extract from aerial parts of Baccharis uncinella indicated that the isolated compounds caffeic acid and pectolinaringenin showed inhibitory activity against Leishmania (L.) amazonensis and Leishmania (V.) braziliensis promastigotes, respectively. Moreover, amastigote forms of both species were highly sensible to the fraction composed by oleanolic + ursolic acids and pectolinaringenin. Caffeic acid also inhibited amastigote forms of L. (L.) amazonensis, but this effect was weak in L. (V.) braziliensis amastigotes. The treatment of infected macrophages with these compounds did not alter the levels of nitrates, indicating a direct effect of the compounds on amastigote stages. The results presented herein suggest that the active components from B. uncinella can be important to the design of new drugs against American tegumentar leishmaniases.

Prevalence and distribution of the GBV-C/HGV among HIV-1-infected patients under anti-retroviral therapy

Infection with GB virus C (GBV-C) or hepatitis G virus (HGV) is highly prevalent among HIV/AIDS patients. GBV-C/HGV viremia has not been associated with liver disease and seems to slow HIV disease progression. To study the GBV-C/HGV genotypes prevalence among HIV/AIDS patients and its association with HIV viral load (VL) and CD4+ lymphocyte counts. From February 2003 to February 2004, we analyzed 210 HIV-1-infected subjects who were on anti-retroviral therapy (ART). For 63 of them a PCR-nested to the non-coding 5` (5`NCR) region of the GBV-C/HGV was done, and for 49 a DNA direct sequencing was done. A phylogenetic analysis was performed by PHYLIP program. 63(30%) of the HIV-1-infected patients were co-infected with GBV-C/HGV. The phylogenetic analysis revealed the following genotypes (and respective relative frequencies): 1(10%), 2a (41%), 2b (43%), and 3 (6%). Co-infected patients presented lower HIV-1 VL and higher T CD4+ lymphocyte cells counts as compared with patients negative for GBV-C/HGV sequences (log = 4.52 vs. 4.71, p = 0.036), and T CD4+ lymphocyte counts (cells/mm(3) = 322.6 vs. 273.5, p = 0.081, respectively). T CD4+ cells counts equal to, or higher than, 200/mm(3) were significantly more common among co-infected patients than among HIV-infected-only patients (p = 0.042). The lowest T CD4+ cells counts were associated with genotype 1 and the highest with genotype 2b (p = 0.05). The GBV-C/HGV infection prevalence was 30% among HIV-1-infected subjects, and was associated with lower VL and higher CD4+ lymphocyte counts. GBV-C/HGV genotype 2b may be associated with better immunological response. Published by Elsevier B.V.

Exacerbation of Leishmania (Viannia) shawi infection in BALB/c mice after immunization with soluble antigen from amastigote forms

The present study aimed to evaluate the effects of immunization with soluble amastigote (AmaAg) and promastigote (ProAg) antigens from Leishmania (Viannia) shawi on the course of infection in BALB/c mice. After immunization with AmaAg, the challenged group showed greater lesion size and parasite load in the skin and lymph nodes, associated with diminished interleukin (IL)-2, IL-4, IL-10, interferon (IFN)-gamma and nitrate levels in the supernatant of lymph node cell cultures, together with increases in transforming growth factor (TGF)-beta concentrations and humoral immune response. In contrast, immunization with ProAg led to smaller lesion size with reduced numbers of viable parasites in the skin. Protection was associated with increases in IL-12, IFN-gamma, TGF-beta and nitrates and decreases in IL-4 and IL-10 levels. Concerning humoral immune response, a significant reduction in anti-leishmania immunoglobulin G was verified in the ProAg-challenged group. Analysis of these results suggests that AmaAg induced a suppressive cellular immune response in mice, favouring the spread of infection, whereas ProAg induced partial protection associated with increased cellular immune response.

A Sustained Virologic Response Is Durable in Patients With Chronic Hepatitis C Treated With Peginterferon Alfa-2a and Ribavirin

BACKGROUND & AIMS: A sustained virologic response (SVR) to therapy for hepatitis C virus (HCV) infection is defined as the inability to detect HCV RNA 24 weeks after completion of treatment. Although small studies have reported that the SVR is durable and lasts for long periods, it has not been conclusively shown. METHODS: The durability of treatment responses was examined in patients originally enrolled in one of 9 randomized multicenter trials (n = 1343). The study included patients who received pegylated interferon (peginterferon) alfa-2a alone (n = 166) or in combination with ribavirin (n = 1077, including 79 patients with normal alanine aminotransferase levels and 100 patients who were coinfected with human immunodeficiency virus and HCV) and whose serum samples were negative for HCV RNA (<50 IU/mL) at their final assessment. Patients were assessed annually, from the date of last treatment, for a mean of 3.9 years (range, 0.8-7.1 years). RESULTS: Most patients (99.1%) who achieved an SVR had undetectable levels of HCV RNA in serum samples throughout the follow-up period. Serum samples from 0.9% of the patients contained HCV RNA a mean of 1.8 years (range, 1.1-2.9 years) after treatment ended. It is not clear if these patients were reinfected or experienced a relapse. CONCLUSIONS: In a large cohort of patients monitored for the durability of an SVR, the SVR was maintained for almost 4 years after treatment with peginterferon alfa-2a alone or in combination with ribavirin. In patients with chronic hepatitis C infection, the SVR is durable and these patients should be considered as cured.

Monitoring of Group C Rotavirus in Children With Acute Gastroenteritis in Brazil: An Emergent Epidemiological Issue After Rotavirus Vaccine?

Group C rotavirus (GpCRV) has a worldwide distribution; however, its epidemiology and ecology are still unclear. Evidence for a possible zoonotic role has been postulated recently for Brazilian children strains. The aim of this study was to monitor GpCRV in children <= 15 years with acute gastroenteritis during the 2007-2010 national Brazilian rotavirus surveillance, and to undertake the molecular characterization of the major VP6 capsid protein. A total of 3,019 fecal samples were first screened for Group A rotavirus (GpARV). A total of 2,205 GpARV ELISA negative samples were tested further for the presence of GpCRV by SDS-PAGE, electronic microscopy, and RT-PCR for the VP6 gene. The genetic diversity of GpCRV was carried out by sequencing the VP6 gene. GpARV and GpCRV infections were detected in 24.6% (742/3,019) and 0.3% (8/3,019), respectively. The GpCRV detection rate increased from 0.2% (1/422) in 2007 to 1% (7/708) in 2008, and GpCRV cases were not detected in 2009 and 2010. The phylogenetic analysis indicated that the strains belonged to the human lineage, and showed a genetic relationship with the GpCRV strain from Japan isolated in 2009. None of the study sequences was related closely to animal GpCRV strains. This study provides further evidence that GpCRV is a minor cause of acute childhood gastroenteritis in Brazil, and does not suggest that GpCRV may assume epidemiological importance in the future, even after the introduction of a GpARV vaccine. In addition, the molecular analyses of the GpCRV samples in this study do not support the zoonotic hypothesis. J. Med. Virol. 83: 1631-1636, 2011. (C) 2011 Wiley-Liss, Inc.

Use of Inverted Fluoroscope`s C-arm During Endoscopic Treatment of Urinary Tract Obstruction in Pregnancy: A Practicable Solution to Cut Radiation

OBJECTIVES To describe the use of pulsed fluoroscopic guidance, to perform endoscopic procedures in pregnant women, by inverting the fluoroscope`s c-arm using a lead thyroid collar to shield the fetus from the direct X-ray beam. The use of radiation during treatment of pregnant patients with urolithiasis remains a recurring dilemma. METHODS Between May 2006 and December 2008, endoscopic treatment due to ureteral stones was attempted in 8 pregnant women. In all cases, we use an inverted fluoroscope`s c-arm during endoscopic treatment associated with 2 lead neck thyroid collars to shield the uterus, protecting the fetus from direct radiation. Indication for treatment was symptomatic ureteral stones unresponsive to medical treatment in 7 and persistent fever in 1. RESULTS Mean ureteral stone size was 8.1 +/- 4.8 mm, located in the left ureter in 5 (62.5%) cases. Three (37.5%) patients had stone located in the upper ureter, 2 (25%) in the middle ureter, and 3 (37.5) in the distal ureter. In 6 cases, ureteral stones were treated using the semi-rigid ureteroscope, whereas in 1 case a flexible ureteroscope was needed. One woman was treated with insertion of a double-J stent due to associated urinary infection. No women has early delivery related to the endoscopic procedure, and all neonates were perfectly normal. CONCLUSIONS We present a technique for endoscopic procedures in pregnant women inverting the fluoroscope`s c-arm and protecting the fetus from the direct X-ray beam. This practical approach should be specially considered when no portable ultrasound and radiologic assistance in available in the operating room. UROLOGY 75: 1505-1508, 2010. (c) 2010 Published by Elsevier Inc.