Management of Patients With Rheumatoid Arthritis in Latin America A Consensus Position Paper From Pan-American League of Associations of Rheumatology and Grupo Latino Americano De Estudio de Artritis Reumatoide

Objective: A consensus meeting of representatives of 18 Latin-American and Caribbean countries gathered in Renaca, Chile, for 2 days to identify problems and provide recommendations for the care of patients with rheumatoid arthritis (RA) in Latin America, a region where poverty and other health priorities make the efforts to provide effective and high quality care difficult. This report includes recommendations for health professionals, patients, and health authorities in Latin America, with an emphasis oil education and therapeutic issues. Methods: Fifty-one rheumatologists (list available only online on the JCR website) from 18 Latin-American and Caribbean countries with a special interest in RA participated in the consensus meeting. Participants were experts identified and appointed by the National Societies of Rheumatology affiliated with the Pan-American League of Associations for Rheumatology (PANLAR) and by the Grupo Latino Americano De Estudio de Artritis Reumatoide (GLADAR)-an independent group of Latin American rheumatologist researchers were also invited to the meeting. Eight topics were identified as priorities: patient, community and allied health professional education, health policy and decision making, programs for early detection and appropriate treatment of RA, role of classic disease modifying antirheumatic drugs (DMARDs), role of biologic therapy, and drug safety surveillance. To reach consensus, a survey with questions relevant to the topic of interest was sent to all participants before the meeting. During a 2 day meeting, the answers of the survey were reviewed and discussed by each group, with final recommendations on action items. Results: The specific topic of the survey was answered by 86% of the participants and 68% of them answered the entire survey. It was agreed that RA and rheumatic diseases which are currently not but should be public health priorities in Latin America, because of their prevalence and impact on quality of life. Conclusions: Strategic areas identified as priorities for our region included: early diagnosis and access to care by multidisciplinary teams, creation of databases to identify infections with the use of biologic agents in RA which are relevant to Latin America, and overall efforts to improve the care of RA patients in accordance with international standards. Implementation of educational programs aimed to improve self-management for patients with RA was also considered crucial.

Bacterial triggers and autoimmune rheumatic diseases

Autoimmune rheumatic diseases are generally considered as a multifactorial aetiology, mainly genetic susceptibility combined with environmental triggers of which bacteria are considered one of the most prominent. Among the rheumatic diseases where bacterial agents are more clearly involved as triggers are: reactive arthritis (ReA), rheumatic fever (RF) and Lyme disease. The role of bacterial infections in inducing other seronegative spondyloarthritis and antiphospholipid antibody syndrome has been hypothesized but is still not proven. The classic form of ReA is associated with the presence of HLA-B27 and is triggered by the urethritis or enteritis causing pathogens Chlamydia trachomatis and the enterobacteria Salmonella, Shigella, and Yersinia, respectively. But several other pathogens such as Brucella, Leptospira, Mycobacteria, Neisseria, Staphylococcus and Streptococcus have also been reported to cause ReA. RF is due to an autoimmune reaction triggered by an untreated throat infection by Streptococcus pyogenes in susceptible individuals. Carditis is the most serious manifestation of RF and HLA-DR7 is predominantly observed in the development of valvular lesions. Lyme disease is a tick-transmitted disease caused by the spirochete Borrelia burgdorferi. Knowledge is limited about how this spirochete interacts with human tissues and cells. Some data report that Borrelia burgdorferi can manipulate resident cells towards a pro- but also anti-inflammatory reaction and persist over a long period of time inside the human body or even inside human cells.

Transanal endorectal pull-through in children with Hirschsprung`s disease-technical refinements and comparison of results with the Duhamel procedure

Purpose: Transanal endorectal pull-through (TEPT) has drastically changed the treatment of Hirschsprung`s disease (HD). A short follow-up of children Submitted to TEPT reveals results that are similar to the classic transabdominal pull-through procedures. However, few reports compare the late results of TEPT with transabdominal pull-through procedures with respect to complication rates and the fecal continence. The aims of the present work are to describe some technical refinements that we introduced in the procedure and to compare the short and long-term outcome of TEPT with the outcomes of a group of patients with HD who previously underwent the Duhamel procedure. Methods: Thirty-five patients who underwent TEPT were prospectively studied and compared to a group of 29 patients who were treated with colostomy followed by a classical Duhamel pull-through. The main modifications introduced in the TEPT group were no preoperative colon preparation, operation conducted under general anesthesia in addition to regional sacral anesthesia, use of only one purse-string Suture in the rectal mucosa before transanal submucosal dissection, and no use of retractors and electrocautery during file submucosal dissection. Results: The most frequent early complications of TEPT group were perineal dermatitis (22.8%) and anastomotic strictures (8.6%). The comparison with patients who underwent Duhamel procedure revealed no difference in the incidence of preoperative enterocolitis, the patients of the TEPT group were younger at the time of diagnosis and of surgery, they had shorter operating times, and they began oral feeding more quickly after the operation. The incidence of wound infection was lower in the TEPT group. Moreover, the TEPT and Duhamel groups showed no difference in the incidences of mortality, postoperative partial continence, and total incontinence. Although the incidences of complete continence and postoperative enterocolitis were not different, a tendency to the increased incidence in the TEPT group was observed. Conclusions: This study further supports the technical advantages, the simplicity, and the decreased incidence of complications of a primary TEPT procedure when compared to a classical form of pull-through. Sonic technical refinements are described, and no preoperative colon preparation was necessary for the patients studied here. The results show that the long-term outcomes of the modified TEPT procedure are generally better than those obtained with classical approaches. Published by Elsevier Inc.

Functional growth hormone (GH) receptors and GH are expressed by preimplantation mouse embryos: A role for GN in early embryogenesis?

The results of this study challenge the widely held view that growth hormone (GH) acts only during the postnatal period. RNA phenotyping shows transcripts for the GH receptor and GH-binding protein in mouse preimplantation embryos of all stages from fertilized eggs (day 1) to blastocysts (day 4). An antibody specific to the cytoplasmic region of the GH receptor revealed receptor protein expression, first in two-cell embryos, the stage of activation of the embryonic genome (day 2), and in all subsequent stages, In cleavage-stage embryos this immunoreactivity was localized mainly to the nucleus, but clear evidence of membrane labeling was apparent in blastocysts. GH receptor immunoreactivity was also observed in cumulus cells associated with unfertilized oocytes but not in the unfertilized oocytes. The blastocyst receptor was demonstrated to be functional, exhibiting the classic bell-shaped dose-response curves for GH stimulation of both 3-O-methyl glucose transport and protein synthesis. Maximal stimulation of 40-50% was seen for both responses at less than 1 ng/ml recombinant GH, suggesting a role for maternal GK. However mRNA transcripts for GH were also detected from the morula stage (day 3) by using reverse transcription-PCR, and GH immunoreactivity was seen in blastocysts. These observations raise the possibility of a paracrine/autocrine GH loop regulating embryonic development in its earliest stages.

Endemic and opportunistic infections in Brazilian solid organ transplant recipients

OBJECTIVE To evaluate the frequency and clinical features of endemic and other opportunistic infections in liver or kidney transplant recipients in four transplant centres in different geographical areas of Brazil. METHODS Retrospective analysis of medical and laboratory records of four transplant centres on endemic and other opportunistic infections in liver or kidney transplant recipients. Analyses were performed with spss statistical software. RESULTS From 2001 to 2006, 1046 kidney and 708 liver transplants were registered in all centres. The average age was 42 years. Among 82 (4.7%) cases with infections, the most frequent was tuberculosis (2.0%), followed by systemic protozoal infections (0.7%), toxoplasmosis (0.4%) and visceral leishmaniasis (0.3%). Systemic fungal infections occurred in 0.6%, of which 0.4% were cryptococcosis and 0.2% were histoplasmosis. Dengue was the only systemic viral infection and was registered in two cases (0.1%), of which one was classified as the classic form and the other as dengue haemorrhagic fever. Nocardiosis was described in one case (0.05%). The infectious agents most frequently associated with diarrhoea were Blastocystis sp., Schistosoma mansoni and Strongyloides stercoralis. CONCLUSIONS Opportunistic Infections in transplant patients have a wide spectrum and may vary from asymptomatic to severe infections with high mortality. A better understanding of the epidemiology of endemic pathogens and clinical manifestations can contribute to the establishment of an early diagnosis as well as correct treatment aimed at decreasing morbidity and mortality.

Clinical and pathologic prognostic factors for curative resection for pancreatic cancer

Background. Pancreatic cancer is the fifth leading cause of cancer-related deaths in the world. Operative resection is the only therapeutic option with curative potential for this disease. Objective. The aim of the present study was to correlate clinical and pathologic parameters with survival in patients submitted to pancreatic resection for pancreatic adenocarcinoma. Methods. Surgical resection with curative intent (R0 and R1 resections) was performed in 65 pancreatic cancer patients between 1990 and 2006. The overall results of surgical treatment were retrospectively analyzed and compared with the clinicopathologic features of these patients. Results. Pylorus-preserving pancreatoduodenectomy was performed in 37 patients (56.9%), classic resection in 35.4%, distal pancreatectomy in 4.6% and total pancreatectomy in 3.6%. The inhospital mortality was 5% (three patients). Postoperative complications occurred in 28 patients (43%). Mean survival and five-year survival rate after curative resection were 27 months and 9.0%, respectively. Sex, TNM stage, tumor differentiation, neural invasion, tumor size and involvement of resection margin were significant prognostic factors on univariate analysis. Multivariate analysis showed tumor differentiation and neural invasion as prognostic factors. Conclusion. Patients with pancreatic cancer, even those with poor prognostic factors should be given the opportunity of surgical resection with curative intent.

Coordinated expression of ER, PR and HER2 define different prognostic subtypes among poorly differentiated breast carcinomas

Aims: Histological grade is one of the most important prognostic factors in breast carcinomas, but poorly differentiated neoplasms still have quite heterogeneous biological behaviour, since they can be genetically classified as basal-like, HER2+ or even luminal. The aim was to analyse the frequency of oestrogen receptor (ER), progesterone receptor (PR) and HER2 expression profiles among breast carcinomas with < 10% tubular formation, and their correlation with classic prognostic factors. Methods and results: One hundred and thirty-four samples of paraffin-embedded tumours were studied retrospectively. The tumours were classified in to four groups by their ER/PR/HER2 profile: (i) ER+ and/or PR+ but HER2-; (ii) ER+ and/or PR+ and HER2+; (iii) ER- and/or PR- but HER2+; and (iv) ER-, PR- and HER2- (triple-negative). The histological features of triple-negative and HER2+ carcinomas overlap. The only difference was the expression of basal cytokeratins (basal CK), which was more frequent among triple-negative carcinomas. Basal-CK expression defined a more aggressive group of tumours, according to the pathological features, regardless of the immunohistochemical profile. Conclusions: Group 1 and 2 tumours (ER+ and/or PR+ tumours with or without HER2 expression) were not statistically different, suggesting that poorly differentiated carcinomas with hormone receptors correspond to the luminal B type of tumour. Among poorly differentiated breast carcinomas, the classic profile associated with basal-CK identifies distinct subtypes equivalent to those seen by genetic classification.

Genetic Polymorphisms of Matrix Metalloproteinases: Susceptibility and Prognostic Implications for Prostate Cancer

Purpose: Prostate cancer is the most common tumor in males in Brazil. Single nucleotide polymorphisms have been demonstrated to exist in the promoter regions of matrix metalloproteinase genes and they are associated with the development and progression of some cancers. We investigated the correlation between MMP1, 2, 7 and 9 polymorphisms with susceptibility to prostate cancer, and classic prognostic parameters of prostate cancer. Materials and Methods: Genomic DNA was extracted using conventional protocols. The DNA sequence containing the polymorphic site was amplified by realtime polymerase chain reaction using TaqMan (R) fluorescent probes. Results: For the MMP1 gene the polymorphic allele was more common in the control group than in the prostate cancer group (p <0.001). For the MMP9 gene the incidence of the polymorphic homozygote genotype was higher in the prostate cancer group (p <0.001). For higher stage tumors (pT3) a polymorphic allele in the MMP2 gene was more common (p = 0.026). When considering Gleason score, the polymorphic homozygote genotype of MMP9 was more common in Gleason 6 or less tumors (p = 0.003), while a polymorphic allele in the MMP2 gene was more common in Gleason 7 or greater tumors (p = 0.042). Conclusions: MMP1 and MMP2 may protect against prostate cancer development and MMP9 may be related to higher risk. In contrast, MMP9 polymorphism was associated with a lower Gleason score and MMP2 polymorphism was associated with nonorgan confined disease.

The effects of human herpesvirus 8 infection and interferon-gamma response in cutaneous lesions of Kaposi sarcoma differ among human immunodeficiency virus-infected and uninfected individuals

Background Kaposi sarcoma (KS) is associated with human herpesvirus 8 (HHV-8). The cutaneous immune response in this tumour is not well established and a better understanding is necessary. Objectives To evaluate the HHV-8 expression and immune response in cutaneous lesions of classic KS (CKS) and AIDS-associated KS (AIDS-KS). Methods We performed a quantitative immunohistochemical study of cells expressing HHV-8 latency-associated nuclear antigen (LANA), CD4, CD8 and interferon (IFN)-gamma in skin lesions from patients with CKS and AIDS-KS (with or without highly active antiretroviral therapy, HAART). Results CKS showed higher LANA expression compared with AIDS-KS, regardless of HAART. We also found higher LANA expression in nodules compared with patch/plaque lesions. The tissue CD4+ cell proportion was lower in AIDS-KS patients without HAART than in patients with CKS. In CKS lesions, CD4+ and CD8+ cells expressed IFN-gamma, as shown by double immunostaining. AIDS-KS presented low numbers of IFN-gamma-expressing cells. CD8+ cell numbers were similar in all groups, which appeared unrelated to the clinical or epidemiological type of KS. Conclusions. Our quantitative data on the pattern of KS lesions in selected groups of patients, as shown by in situ immune response, demonstrated a CD4+ T-cell involvement associated with IFN-gamma, an environment of immune response-modified human immunodeficiency virus (HIV) infection. In our sample, the promotion of KS in patients without HIV appears to be related to higher HHV-8 load or virulence than in those with AIDS. This higher resistance may be explained by a sustained immune response against this herpesvirus, that is only partially restored but effective after HAART.

Comparison of renal transplantation outcomes in children with and without bladder dysfunction. A customized approach equals the difference

Purpose: We examined the development of urological abnormalities in a group of pediatric renal transplant recipients. Materials and Methods: We reviewed 211 patients younger than 19 years who underwent 226 renal transplants. Three groups of patients were studied-136 children with end stage renal disease due to a nonurological cause (group 1), 56 children with a urological disorder but with an adequate bladder (group 2a) and 19 children with lower urinary tract dysfunction and/or inadequate bladder drainage (group 2b). A total of 15 children in group 2b underwent bladder augmentation (ureterocystoplasty in 6, enterocystoplasty in 9), 2 underwent continent urinary diversion, 1 underwent autoaugmentation and 1 underwent a Mitrofanoff procedure at the bladder for easier drainage. Kidney transplantation was performed in the classic manner by extraperitoneal access, and whenever possible the ureter was reimplanted using an antireflux procedure. Results: At a mean followup of 75 months 13 children had died, 59 grafts were lost and 15 children had received a second transplant. Two patients in group 2a required a complementary urological procedure to preserve renal function (1 enterocystoplasty, 1 vesicostomy). A total of 12 major surgical complications occurred in 226 kidney transplants (5.3%), with a similar incidence in all groups. The overall graft survival at 5 years was 75%, 74% and 84%, respectively, in groups 1, 2a and 2b. Conclusions: With individualized treatment children with severely inferior lower urinary tract function may undergo renal transplantation with a safe and adequate outcome.

Fabry Disease in Hemodialysis Patients in Southern Brazil: Prevalence Study and Clinical Report

Background. Fabry disease (FD) is a lysosomal storage disorder caused by a deficiency of -Galactosidase A (-Gal A). Fabry nephropathy typically progresses throughout the fifth decade to end-stage renal disease (ESRD), requiring hemodialysis and/or kidney transplantation. Objective. To estimate the prevalence of FD among ESRD males on hemodialysis treatment in Rio Grande do Sul, the southernmost state of Brazil. Methods. Screening for -Gal A activity was performed by a dried blood spot (normal reference value: 1.5 nmoles/hour/mL). Positive screening results were confirmed by plasma -Gal A activity assay (reference value: 3.3 nmoles/hour/mL). Results. Five hundred fifty-eight male patients on hemodialysis were evaluated. Of these, only two had low -Gal A activity and were diagnosed with Fabry disease (0.36%). One of these, age 42, had left ventricular hypertrophy and renal manifestations of Fabry disease without the classic symptoms. The other, age 46, had the classical manifestations of angiokeratomas, acroparesthesias, hypohidrosis, and ocular opacities. Conclusions. Although the prevalence of Fabry disease was very low in our study (0.36%), routine screening of male hemodialysis patients would enable earlier identification of many other affected relatives in their families who might benefit from specific clinical treatment.

Segmental amplification of MLL gene associated with high expression of AURKA and AURKB genes in a case of acute monoblastic leukemia with complex karyotype

We report a case of acute monoblastic leukemia showing a jumping translocation with the MLL gene in a 17-year-old male. Classic cytogenetic and spectral karyotyping revealed a complex karyotype, and fluorescence in situ hybridization (FISH) demonstrated amplification of the MLL gene followed by translocation to chromosomes 15q, 17q, and 19q. In addition, molecular analyses showed a high expression of AURKA and AURKB genes. It is already known that overexpression of Aurora kinases is associated with chromosomal instability and poor prognosis. The formation of jumping translocations is a rare cytogenetic event and there is evidence pointing toward preferential involvement of the heterochromatin region of donor chromosomes and the telomere ends of recipient chromosomes. Jumping translocation with the MLL gene rearrangement is an uncommon phenomenon reported in leukemia cytogenetics. (C) 2010 Elsevier Inc. All rights reserved.