Benefits of the Intermittent Use of 6-Mercaptopurine and Methotrexate in Maintenance Treatment for Low-Risk Acute Lymphoblastic Leukemia in Children: Randomized Trial From the Brazilian Childhood Cooperative Group Protocol ALL-99

Purpose To describe event-free survival (EFS) and toxicities in children with low-risk acute lymphoblastic leukemia (ALL) assigned to receive either continuous 6-mercaptopurine (6-MP) and weekly methotrexate (MIX) or intermittent 6-MP with intermediate-dose MTX, as maintenance treatment. Patients and Methods Between October 1, 2000, and December 31, 2007, 635 patients with low-risk ALL were enrolled onto Brazilian Childhood Cooperative Group for ALL Treatment (GBTLI) ALL-99 protocol. Eligible children (n=544) were randomly allocated to receive either continuous 6-ME/MIX (group 1, n 272) or intermittent 6-MP (100 mg/m(2)/d for 10 days, with 11 days resting) and MIX (200 mg/m(2) every 3 weeks; group 2, n = 272). Results The 5-year overall survival (OS) and EFS were 92.5% +/- 1.5% SE and 83.6% +/- 2.1% SE, respectively. According to maintenance regimen, the OS was 91.4% +/- 2.2% SE (group 1) and 93.6% +/- 2.1% SE (group 2; P=.28) and EFS 80.9% +/- 3.2% SE (group 1) and 86.5% +/- 2.8% SE (group 2; P=.089). Remarkably, the intermittent regimen led to significantly higher EFS among boys (85.7% v 74.9% SE; P=027), while no difference was seen for girls (87.0% v 88.8% SE; P=.78). Toxic episodes were recorded in 226 and 237 children, respectively. Grade 3 to 4 toxic events for groups 1 and 2 were, respectively, 273 and 166 for hepatic dysfunction (P=.002), and 772 and 636 for hematologic episodes (P=.005). Deaths on maintenance were: seven (group 1) and one (group 2). Conclusion The intermittent use of 6-MP and MIX in maintenance is a less toxic regimen, with a trend toward better long-term EFS. Boys treated with the intermittent schedule had significantly better EFS.

Advantages and Pitfalls of the Polymerase Chain Reaction in the Diagnosis of Esophageal Ulcers in AIDS Patients

HIV-1-infected patients frequently have opportunistic esophageal infections which, when associated with severe immunodeficiency, can be attributed to unusual pathogens. The clinical presentation of several esophageal diseases is similar and the best method for a specific diagnosis of these patients has not been well defined. To evaluate the role of the polymerase chain reaction (PCR) in the etiologic definition of esophageal ulcers in HIV-1-infected patients, 96 esophageal biopsies from 79 HIV-1-infected patients were processed by PCR using specific primers for cytomegalovirus (CMV), herpes virus (HSV), human papilloma virus (HPV), HIV-1, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Treponema pallidum, and Haemophilus ducreyi. The PCR results were compared to the histopathologic results. Seventy-nine patients were studied (mean age: 34 years; 62% men; median CD4 + T cell = 103.59 cells/mu l (range 1-795.2 cells/mu l). The most common endoscopic findings were as follows: esophageal candidiasis (37.1%), esophageal ulcers (24.7%), esophagitis (11.2%), and lugol-negative areas (10.1%). The histopathologic findings in the esophageal ulcers (22 biopsies) were non-specific inflammation (31.8%), HSV (36.4%), Candida (13.6%), CMV (13.6%), or HPV disease (4.5%). In the esophageal ulcer biopsies, the PCR results were negative in 27.6% of cases, and positive for HIV (65.5%), CMV (31%), HPV (20.7%), HSV (10.3%), and H. ducreyi (6.9%). The histopathologic examination did not identify a pathogen or identified only Candida in 15 biopsies of esophageal ulcers. PCR was positive in ten (66.7%) and negative in five (33.3%) of these biopsies (idiopathic ulcers). PCR detected: HIV (53.3%), CMV (20%), HPV (13.3%), and H. ducreyi (6,7%). PCR detected more etiologic agents in esophageal ulcers than histopathology and was able to detect unusual pathogens. On the other hand, sometimes more than one pathogen was detected in the esophageal ulcers, making it difficult to reach an accurate diagnosis. This finding indicates the need for more studies to evaluate the benefit of this method in the routine evaluation of esophageal ulcer biopsies in HIV-1-infected patients.

Tumor necrosis factor region polymorphisms are associated with AIDS and with cytomegalovirus retinitis

Background: The tumor necrosis factor (TNF) gene is located within the highly polymorphic major histocompatibility complex region, exhibiting the -308 CA promoter region polymorphism and six microsatellites (TNFa-f) spanning the region nearby the TNF locus. Objective: In the present Study, we evaluated the frequency of -308 CA and TNFa-e polymorphisms and respective haplotypes (in chromosomal sequence: TNFd-TNFe-308GA-TNFc-TNFa-TNFb), in 222 patients with AIDS, 52 of whom exhibited cytomegalovirus retinitis, and in 202 healthy HIV-negative individuals. Method: TNF microsatellite and single nucleotide polymorphism typings were performed by PCR followed by polyacrylamide gel electrophoresis. Results: The TNF-308A allele and the 4-3-C-2-7-1 haplotype were associated with susceptibility to AIDS, whereas the TNFb4 allele and the 3-3-C-1-11-4 haplotype were associated with protection against AIDS development. The TNFc2 allele and the 4-1-G-2-2-1 haplotype, which contains the TNFc2 allele, were associated with cytomegalovirus retinitis. Conclusion: This study highlights that polymorphic sites spanning the region nearby the TNF locus are associated with AIDS per se and with cytomegalovirus retinitis in AIDS patients. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study

Objective To evaluate if two different measures of synovial activation, baseline Hoffa synovitis and effusion synovitis, assessed by MRI, predict cartilage loss in the tibiofemoral joint at 30 months follow-up in subjects with neither cartilage damage nor tibiofemoral radiographic osteoarthritis of the knee. Methods Non-contrast-enhanced MRI was performed using proton density-weighted fat-suppressed sequences in the axial and sagittal planes and a short tau inversion recovery sequence in the coronal plane. Hoffa synovitis, effusion synovitis and cartilage status were assessed semiquantitatively according to the WORMS scoring system. Included were knees that had neither radiographic osteoarthritis nor MRI-detected tibiofemoral cartilage damage at the baseline visit. The presence of Hoffa synovitis was defined as any grade = 2 (range 0-3) and effusion synovitis as any grade = 2 (range 0-3). Logistic regression was performed to examine the relation of the presence of either measure to the risk of cartilage loss at 30 months adjusting for other potential confounders. Results Of 514 knees included in the analysis, the prevalence of Hoffa synovitis and effusion synovitis at the baseline visit was 8.4% and 10.3%, respectively. In the multivariable analysis, baseline effusion synovitis was associated with an increased risk of cartilage loss. No such association was observed for baseline Hoffa synovitis. Conclusions Baseline effusion synovitis, but not Hoffa synovitis, predicted cartilage loss. The findings suggest that effusion synovitis, a reflection of inflammatory activity including joint effusion and synovitic thickening, may play a role in the future development of cartilage lesions in knees without osteoarthritis.

Prevalence and risk factors of metabolic syndrome in Brazilian and Italian obese adolescents: a comparison study

Background: Metabolic syndrome (MS) prevalence between different populations in obese adolescents is scanty to date. Objective: To compare the MS prevalence and related risk factors in Brazilian and Italian obese adolescents. Methods: A total of 509 adolescents (110 Brazilian, 399 Italian), aged 15-19 years. Anthropometric characteristics, triglycerides (TG), total, low-density lipoprotein (LDL)-, high-density lipoprotein (HDL)-cholesterol, fasting plasma glucose (FPG), insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and blood pressure were measured. Results: Age, body mass index (BMI) and BMI z-score were not significantly different between the two subgroups. BMI z-score, TG, FPG, HOMA-IR and systolic blood pressure (SBP) were significantly higher in boys than in girls both in Brazilian and Italian adolescents, while HDL-cholesterol levels were lower in boys than in girls. No significant differences were observed in BMI, LDL and total-cholesterol and DBP in two genders and groups. Insulin, FPG, HOMA-IR and TG were significantly higher, while LDL-cholesterol and SBP were significantly lower in Brazilian than in Italian subjects, both in males and females. HDL and total-cholesterol and diastolic blood pressure (DBP) were not significantly different between the two subgroups and genders. MS prevalence was higher in Brazilian than in Italian obese boys (34.8 vs. 23.6%, p < 0.001) and girls (15.6 vs. 12.5%, p < 0.01). The most frequently altered parameter was HOMA-IR both in subjects with MS (100% in Brazilian and 81.8% in Italian) and without MS (42.9% and 11.7%). Conclusion: Metabolic syndrome represents a worldwide emerging health problem in different ethnical populations, the alterations of the risk factors related to MS (different in their prevalence between different subgroups) being strictly linked to the degree of obesity.

Panretinal photocoagulation versus PRP plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy (IBeHi study)

Purpose: To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab on best corrected visual acuity (BCVA) and total area of fluorescein leakage from active new vessels (NVs) in patients with high-risk proliferative diabetic retinopathy (PDR). Methods: We carried out a prospective study of patients with high-risk PDR and no prior laser treatment who were randomly assigned to receive PRP (PRP group) or PRP plus intravitreal injection of 1.5 mg of bevacizumab (PRP-plus group). In all patients, the PRP was administered at two time-points (weeks 1 and 3), with the intravitreal bevacizumab delivered at the end of the second laser episode in the PRP-plus group. Standardized ophthalmic evaluation including Early Treatment Diabetic Retinopathy Study BCVA as well as stereoscopic fundus photography and fluorescein angiography were performed at baseline and at weeks 4, 9 (+/- 1) and 16 (+/- 2). Main outcome measures included changes in BCVA and in total area of fluorescein leakage from active NVs. Results: Twenty-two (n = 30 eyes) consecutive patients completed the 16-week follow-up. There was no significant difference between the PRP and PRP-plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active NVs or BCVA. No significant difference in BCVA was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-plus group compared with the PRP group at weeks 4, 9 and 16 (p < 0.001). No major adverse events were identified. Conclusions: In the short-term, the adjunctive use of intravitreal bevacizumab with PRP was associated with a greater reduction in the area of active leaking NVs than PRP alone in patients with high-risk PDR.

Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study

Objectives To introduce a comprehensive and reliable scoring system for the assessment of whole-knee joint synovitis based on contrast-enhanced (CE) MRI. Methods Multicenter Osteoarthritis Study (MOST) is a cohort study of people with, or at high risk of, knee osteoarthritis (OA). Subjects are an unselected subset of MOST who volunteered for CE-MRI. Synovitis was assessed at 11 sites of the joint. Synovial thickness was scored semiquantitatively: grade 0 (< 2 mm), grade 1 (2-4 mm) and grade 2 (> 4 mm) at each site. Two musculoskeletal radiologists performed the readings and inter-and intrareader reliability was evaluated. Whole-knee synovitis was assessed by summing the scores from all sites. The association of Western Ontario and McMaster Osteoarthritis Index pain score with this summed score and with the maximum synovitis grade for each site was assessed. Results 400 subjects were included (mean age 58.8 +/- 7.0 years, body mass index 29.5 +/- 4.9 kg/m(2), 46% women). For individual sites, intrareader reliability (weighted kappa) was 0.67-1.00 for reader 1 and 0.60-1.00 for reader 2. Inter-reader agreement (kappa) was 0.67-0.92. For the summed synovitis scores, intrareader reliability (intraclass correlation coefficient (ICC)) was 0.98 and 0.96 for each reader and inter-reader agreement (ICC) was 0.94. Moderate to severe synovitis in the parapatellar subregion was associated with the higher maximum pain score (adjusted OR (95% CI), 2.8 (1.4 to 5.4) and 3.1 (1.2 to 7.9), respectively). Conclusions A comprehensive semiquantitative scoring system for the assessment of whole-knee synovitis is proposed. It is reliable and identifies knees with pain, and thus is a potentially powerful tool for synovitis assessment in epidemiological OA studies.

Subchondral Cystlike Lesions Develop Longitudinally in Areas of Bone Marrow Edema-like Lesions in Patients with or at Risk for Knee Osteoarthritis: Detection with MR Imaging-The MOST Study

Purpose: To assess the association of prevalent bone marrow edema-like lesions (BMLs) and full-thickness cartilage loss with incident subchondral cyst-like lesions (SCs) in the knee to evaluate the bone contusion versus synovial fluid intrusion theories of SC formation. Materials and Methods: The Multicenter Osteoarthritis study is a longitudinal study of individuals who have or are at risk for knee osteoarthritis. The HIPAA-compliant protocol was approved by the institutional review boards of all participating centers, and written informed consent was obtained from all participants. Magnetic resonance images were acquired at baseline and 30-month follow-up and read semiquantitatively by using the Whole-Organ Magnetic Resonance Imaging Score system. The tibiofemoral and patellofemoral joints were subdivided into 14 subregions. BMLs and SCs were scored from 0 to 3. Cartilage morphology was scored from 0 to 6. The association of prevalent BMLs and full-thickness cartilage loss with incident SCs in the same subregion was assessed by using logistic regression with mutual adjustment for both predictors. Results: A total of 1283 knees were included. After adjustment for full-thickness cartilage loss, prevalent BMLs showed a strong and significant association with incident SCs in the same subregion, with an odds ratio of 12.9 (95% confidence interval [CI]: 8.9, 18.6). After adjustment for BMLs, prevalent full-thickness cartilage loss showed a significant but much less important association with incident SCs in the same subregion (odds ratio, 1.4; 95% CI: 1.0, 2.0). There was no apparent relationship between severity of full-thickness cartilage loss at baseline and incident SCs. Conclusion: Prevalent BMLs strongly predict incident SCs in the same subregion, even after adjustment for full-thickness cartilage loss, which supports the bone contusion theory of SC formation. (C) RSNA, 2010

Thyroid gland and cerebella lesions: New risk factors for sudden cardiac death in schizophrenia?

People with schizophrenia show a two to threefold increased risk to die prematurely than those without schizophrenia. Patients` life style, suicide, premature development of cardiovascular disease, high prevalence of metabolic syndrome and sudden cardiac death are well-known causes of the excess mortality. The exact pathophysiological cause of sudden death in schizophrenia is unknown, but it is likely that cardiac arrhythmia and respiratory abnormalities play potential role. Some antipsychotics may be associated with cardiovascular adverse events (e.g., QT interval prolongation) and lesions in specific brain regions, such as cerebella may be associated with respiratory abnormalities, suggesting that metabolic and brain dysfunction could lead to sudden cardiac death in patients with schizophrenia. However, exact knowledge regarding the association of these findings and schizophrenia is lacking. As subclinical hyperthyroidism has been linked with increased risk of cardiovascular disease and cerebella progressive atrophy has been observed in patients with schizophrenia, we propose in this paper that subclinical thyroid dysfunction and cerebella volume loss could be considered as new risk factor for sudden cardiac death in schizophrenia. (C) 2010 Elsevier Ltd. All rights reserved.

Clinical and Fiberoptic Endoscopic Evaluation of Swallowing in Robin Sequence Treated With Nasopharyngeal lntubation: The Importance of Feeding Facilitating Techniques

Objective: To evaluate oral feeding capacity, the swallowing process, and risk for aspiration, both clinically and during fiberoptic endoscopic evaluation of swallowing, in infants with isolated Robin sequence treated exclusively with nasopharyngeal intubation and feeding facilitating techniques. Design: Longitudinal and prospective study. Setting: Hospital de Reabilitacao de Anomalies Craniofaciais, University of Sao Paulo, Bauru, Brazil. Patients: Eleven infants with isolated Robin sequence, under 2 months of age, treated with nasopharyngeal intubation. Interventions: Feeding facilitating techniques were applied in all infants throughout the study period. The infants were evaluated clinically and through fiberoptic endoscopic evaluation of swallowing at first, second, and, if necessary, third week of hospitalization (T1, T2, T3). The mean volume of ingested milk was registered during clinical evaluation, and events were registered during feeding. Results: The respiratory status of all infants was improved after nasopharyngeal intubation; 72% of them presented risk for aspiration during fiberoptic endoscopic evaluation of swallowing at T1. This risk was less frequent when thickened milk was given to the infants and at subsequent evaluations (T2 and T3). Conclusions: Nasopharyngeal intubation aids in stabilizing the airway in isolated Robin sequence, but it does not relate directly to feeding. The risk for aspiration was present in most of the infants, mainly during the first week of hospitalization, and improved within a few weeks, after the use of feeding facilitating techniques.

Cutaneous mycoflora and CD4:CD8 ratio of cats infected with feline immunodeficiency virus

This study was designed to compare cutaneous mycoflora isolation and CD4+:CD8+ ratio in feline immunodeficiency virus (FIV)-infected cats with that in FIV-uninfected cats. Sixty cats were examined. Twenty-five were Fly-infected cats and 35 were RV-uninfected cats. All 60 cats were FeLV-negative. Fungi were speciated and immunophenotyping of peripheral CD4+ and CD8+ T lymphocytes was performed. At least one fungal colony was isolated from 22/25 (88%) FIV-infected cats. Among the FIV-uninfected cats fungal colonies were recovered from 13/35 (37%) specimens. Dermatophytes were recovered from 2/25 (8%) FIV-infected cats (one Microsporum gypseum, one Microsporum can is) and 3/35 (8.5%) FIV-uninfected cats (M gypseum). Malassezia species was the most commonly isolated organism from both groups of cats (51.6%). Malassezia species was more commonly isolated from FIV-infected cats than RV-uninfected cats (84% vs 28.6%). The CD4+ to CD8+ lymphocyte ratio for FIV-infected cats was significantly lower than the CD4+ to CD8+ ratio in the FIV-uninfected cats. The CD4+ to CD8+ lymphocyte ratio for FIV-infected cats with cutaneous overall fungal isolation was significantly lower than the CD4:CD8 lymphocyte ratio in the FIV-infected cats but without cutaneous fungal isolation. We can conclude that immunologic depletion due to retroviral infection might represent a risk factor to cutaneous fungal colonization in cats. (C) 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Risk factors associated with leptospirosis in dairy goats under tropical conditions in Brazil

Serum samples from 248 adult dairy goats from 13 flocks with lowered fertility farmed in the Rio de Janeiro region of Brazil were examined for Leptospira antibodies by MAT with 24 serovars, cut off 100. A questionnaire was completed for each herd. Antibodies were detected in 20.8% of these goats, mainly to serovar Hardjo. Risk factors associated with seroprevalence to leptospirosis were the frequency of professional veterinary supervision (OR = 2.35), climate (OR = 2.63) and grazing for more than 2 h a day. Flock factors as size, type of milking and offering of food supplementation, as well as the location and topography, the type of animal housing or the presence of silos did not significantly affect seroprevalence. We suggest that a successful control program for goat leptospirosis should include a complete investigation of herd management practices, which could influence in the occurrence of the infection. (C) 2007 Elsevier Ltd. All rights reserved.

Detection of Bartonella spp. in neotropical felids and evaluation of risk factors and hematological abnormalities associated with infection

Although antibodies to Bartonella henselae have been described in all neotropical felid species, DNA has been detected in only one species, Leopard us wiedii. The aim of this study was to determine whether DNA of Bartonella spp. could be detected in blood of other captive neotropical felids and evaluate risk factors and hematological findings associated with infection. Blood samples were collected from 57 small felids, including 1 Leopard us geoffroyi, 17 L wiedii, 22 Leopardus tigrinus, 14 Leopardus pardalis, and 3 Puma yagouaroundi; 10 blood samples from Panthera onca were retrieved from blood banks. Complete blood counts were performed on blood samples from small felids, while all samples were evaluated by PCR. DNA extraction was confirmed by amplification of the cat GAPDH gene. Bartonella spp. were assessed by amplifying a fragment of their 16S-23S rRNA intergenic spacer region; PCR products were purified and sequenced. For the small neotropical felids, risk factors [origin (wild-caught or zoo-born), gender, felid species, and flea exposure) were evaluated using exact multiple logistic regression. Hematological findings (anemia, polycythemia/hyperproteinemia, leukocytosis and leukopenia) were tested for association with infection using Fisher`s exact test. The 635 bp product amplified from 10 samples (10/67 = 14.92%) was identified as B. henselae by sequencing. Small neotropical felid males were more likely to be positive than females (95% CI = 0.00-0.451, p = 0.0028), however other analyzed variables were not considered risk factors (p > 0.05). Hematological abnormalities were not associated with infection (p > 0.05). This is the first report documenting B. henselae detection by PCR in several species of neotropical felids. (C) 2009 Elsevier B.V. All rights reserved.

Human directed aggression in Brazilian domestic cats: owner reported prevalence, contexts and risk factors

Aggression by cats towards humans is a serious behavioural, welfare and public health problem, although owners may believe it is an inevitable part of cat ownership. There has been little scientific investigation of the risk factors associated with this problem. One hundred and seven owners in the Sao Paulo region of Brazil, took part in a survey aimed at investigating the perceived prevalence of the problem, defining the most common contexts of human directed aggression and identifying associated potential risk factors. Human directed aggression occurred in 49.5%, of cats and was most commonly associated with situations involving petting and play, followed by protection of a resource, when startled, when observing an unfamiliar animal and least commonly when unfamiliar people were present. Pedigree status, neuter status, a history of early trauma, sensitivity to being stroked, the absence of other cats in the home, relationship with other animals, level of background activity at home, access to the outside and tendency to be alone (meaning tendency to staying far from the family members) were all associated with an increased risk in one or more context. However, sex, age, age when acquired, source of pet, attachment to a specific household member, type of domestic accommodation, relationship with another cat if present and contact with other animals did not appear to increase the risk. The results suggest sensitivity to being stroked and background levels of stress in the home are the most pervasive risk factors, and future research should aim to investigate these factors further. These data are of relevance when advising owners about the risk and development of this problem. (C) 2009 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Prevalence and risk factors for anti-Toxoplasma gondii antibodies in goats of the Serido Oriental microregion, Rio Grande do Norte state, Northeast region of Brazil

The prevalence and risk factors for anti-Toxoplasma gondii antibodies were investigated in goats of the Serido Oriental microregion, Rio Grande do Norte state, Northeast region of Brazil. Three hundred and sixty-six blood samples from goats collected by jugular venopuncture were used. For the serologic diagnosis of Toxoplasma gondii infection, the indirect fluorescent-anti body test (IFAT) with cut-off value 1:64 was carried out. The prevalence of anti-T. gondii antibodies was 30.6% [95% CI = 25.9-35.6%] with titers ranging from 1:64 to 1: 16,384. The multivariate logistic regression analysis showed that the risk factors associated to anti-T. gondii antibodies were presence of cats in the herd, extensive/semi-intensive management systems and lack of mineral supplementation. (c) 2008 Elsevier B.V. All rights reserved.