Rheumatoid Arthritis: Latin America

Mantell LL, Parrish WR, Ulloa L. · St. John's University College of Pharmacy, Jamaica, NY 11439, USA. · Shock. · Pubmed #16369179 No free full text.

Abstract: High-mobility group box (HMGB)-1 was recently identified as a lethal mediator of severe sepsis and represents a novel group of intracellular proteins that function as inflammatory cytokines when released into the extracellular milieu. From a clinical perspective, extracellular HMGB-1 can cause multiple organ failure and contribute to the pathogenesis of diverse disorders including sepsis, cardiovascular shock, rheumatoid arthritis, diabetes, and cancer. HMGB-1 has been proven to be a successful therapeutic target in experimental models of diverse infectious and inflammatory diseases, and these findings have renewed the clinical interest of specific cytokine inhibitors. However, little is known about the molecular mechanisms underlying the cytokine activity of HMGB-1 and its contribution to infection and inflammation. This article analyzes the value of HMGB-1 as a therapeutic target for the treatment of diverse infectious and inflammatory disorders and its interest for human clinical trials.

Llanos C, Soto L, Sabugo F, Bastías MJ, Salazar L, Aguillón JC, Cuchacovich M. · Departamento de Medicina, Hospital Clínico, Universidad de Chile. · Rev Med Chil. · Pubmed #16311703 links to  free full text

Abstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects 0.8% of the world population, it affects the synovial membrane of joints and the clinical presentation encompasses a wide spectrum, ranging from a mild to a severe and erosive disease that causes joint and cartilage destruction which finally provokes irreversible structural damage and patient disability. In the last years, there have been important advances in the pathogenesis of this disease, the efforts have been concentrated on pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha). This protein guides numerous events in the synovial and systemic inflammatory process and is encoded in the Major Histocompatibility Complex (MHC), one of the most polymorphic of the genome. Polymorphisms affecting the TNFalpha gene and its regulatory regions are associated with RA prevalence and course. There is a possible association between these polymorphisms and the clinical response to the use of monoclonal antibodies anti-TNFalpha. The possibility that the determination of genotypes -238 and -308 may have prognostic and therapeutic consequences is debated nowadays.

Castro GW, Appenzeller S, Bertolo MB, Costallat LT. · Unit of Rheumatology, Department of Internal Medicine, State University of Campinas, Campinas, Brazil. · Clin Rheumatol. · Pubmed #16308666 No free full text.

Abstract: The authors report a case of a woman with pulmonary hypertension secondary to rheumatoid arthritis, whose treatment with azathioprine resulted in normalization of pulmonary artery pressure and resolution of clinical symptoms. Different etiologies for pulmonary hypertension are discussed and literature review is presented.

Riedemann JP, Muñoz S, Kavanaugh A. · Department of Rheumatology and Clinical Epidemiology, Faculty of Medicine, Universidad de la Frontera, Temuco, Chile. · Clin Exp Rheumatol. · Pubmed #16273788 No free full text.

Abstract: OBJECTIVE: To evaluate the diagnostic properties and predictive value of the second generation of anti-CCP antibodies (anti-CCP2) in rheumatoid arthritis (RA) patients. METHODS: A systematic review of the published literature between January 2002 and June 2005 was performed. Data were extracted regarding the sensitivity and specificity of anti-CCP2 antibodies in making an accurate diagnosis of RA, predicting future development of RA, and predicting future radiological damage in RA patients. In addition, the prevalence of CCP2 antibodies in patients with other rheumatic diseases was examined. RESULTS: Among 38 studies initially identified, 27 provided information on the use of anti-CCP2 testing. Diagnostic properties were assessed in 13 studies; reported sensitivities ranged from 14.4% to 96%, and specificities from 88.9% to 100%. Odds ratios (OR) for the future development of RA varied from 15.9 among previously healthy individuals to 37.8 among a group of patients with undifferentiated arthritis. Several studies suggested that the presence of anti-CCP2 antibodies is highly predictive of current radiographic damage and further damage progression. CONCLUSIONS: Anti-CCP2 has a low sensitivity to be used as a screening test. However, a positive test is highly specific for RA. In addition, anti-CCP2 appears to be highly predictive of the future development of RA in both normal individuals and patients with undifferentiated arthritis. Finally, the presence of anti-CCP2 antibodies appears to predict radiographic damage and progression among patients with RA.

Aguillón JC, Cruzat A, Contreras-Levicoy J, Dotte A, Pesce B, Aravena O, Salazar L, Catalán D, Abello P, Aguirre A, Llanos C, Cuchacovich M. · Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile. · Rev Med Chil. · Pubmed #16163436 links to  free full text

Abstract: The use of biological agents such as etanercept, infliximab, adalimumab and anakinra has been recently approved for the treatment of rheumatoid arthritis. All are effective controlling signs and symptoms and inhibiting disease progression. To overcome the problems generated by their high costs and possible participation in reactivating latent infections, other therapeutic tools are being developed. Gene therapy using expression vectors carrying genes coding for specific proteins, may interfere in key points involved in the pathogenesis of the disease. Intra-articular administration of cDNA coding for soluble TNF receptors, IL-1, or IL-1Ra decreases signs of the disease in animal models. Vectors, expressing inhibitors of signal transduction pathways involving to NF-kB and JAK-STAT-3, are effective in modulating joint inflammation in mice. The use of antigen-pulsed antigen presenting cells or dendritic cells (DC) bound to apoptosis-inducing molecules, specifically eliminates autoreactive T cells. Other novel approach attempts the development of T regulatory-inducing tolerogenic DC-based vaccines that inhibit autoreactive T cells, through the secretion of suppressing cytokines or by other mechanisms to be elucidated. Oral tolerance induction to auto-antigens is also a successful experimental strategy under study. Current research aims to control peripheral tolerance in rheumatoid arthritis patients.

Camargo JF, Tobón GJ, Fonseca N, Diaz JL, Uribe M, Molina F, Anaya JM. · Rheumatology Unit, Clínica Universitaria Bolivariana, Medellin, Colombia, South America. · Lupus. · Pubmed #15864918 No free full text.

Abstract: Autoimmune rheumatic diseases (AIRD) are not uncommon in the general population and up to one third of hospitalized patients with AIRD may need admission to intensive care unit (ICU). This paper describes the causes of admission, the clinical features and outcome of 24 AIRD patients admitted to a medical ICU from a third level hospital. Thirteen patients had systemic lupus erythematosus (54.2%), three rheumatoid arthritis (12.5%), three pulmonary renal syndrome (12.5%), two dermatopolymyositis (8.3%), two scleroderma (8.3%) and one antiphospholipid syndrome (4.2%). The main causes for ICU admission were rheumatic disease flare-up (37.5%), infection (37.5%) and complications derived from rheumatic disease (29.1%). Mortality during ICU stay was 16.7% (four patients). Excluding shock requiring vasopressor support, no statistical difference was found between survivors and nonsurvivors; although there was a trend to higher test severity scores (APACHE II, ODIN) in nonsurvivors. Our results reveal a lower mortality rate in AIRD patients admitted to the ICU than reported previously. Severity scores such as APACHE II are predictors of mortality in patients with AIRD in the ICU.

Bezerra MC, Carvalho JF, Prokopowitsch AS, Pereira RM. · Departamento de Reumatologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. · Braz J Med Biol Res. · Pubmed #15785827 links to  free full text

Abstract: Rheumatoid arthritis is characterized by the presence of inflammatory synovitis and destruction of joint cartilage and bone. Tissue proteinases released by synovia, chondrocytes and pannus can cause cartilage destruction and cytokine-activated osteoclasts have been implicated in bone erosions. Rheumatoid arthritis synovial tissues produce a variety of cytokines and growth factors that induce monocyte differentiation to osteoclasts and their proliferation, activation and longer survival in tissues. More recently, a major role in bone erosion has been attributed to the receptor activator of nuclear factor kappa B ligand (RANKL) released by activated lymphocytes and osteoblasts. In fact, osteoclasts are markedly activated after RANKL binding to the cognate RANK expressed on the surface of these cells. RANKL expression can be upregulated by bone-resorbing factors such as glucocorticoids, vitamin D3, interleukin 1 (IL-1), IL-6, IL-11, IL-17, tumor necrosis factor-alpha, prostaglandin E2, or parathyroid hormone-related peptide. Supporting this idea, inhibition of RANKL by osteoprotegerin, a natural soluble RANKL receptor, prevents bone loss in experimental models. Tumor growth factor-beta released from bone during active bone resorption has been suggested as one feedback mechanism for upregulating osteoprotegerin and estrogen can increase its production on osteoblasts. Modulation of these systems provides the opportunity to inhibit bone loss and deformity in chronic arthritis.

Correa PA, Tobón GJ, Citera G, Cadena J, Schneeberger E, Camargo JF, Maldonado-Cocco JA, Anaya JM. · Unidad de Biología Celular e Inmunogenética, Corporación para Investigaciones Biológicas, Medellín, Colombia. · Biomedica. · Pubmed #15495594 No free full text.

Abstract: The specificity and sensitivity of anti-cyclic citrullinated peptide antibodies (anti-CCP) was examined in Latin-American patients with rheumatoid arthritis (RA). The variables considered included: 1) relation with the activity of disease, 2) extra-articular manifestations (EAM), 3) synthesis of cytokines (IL-4, IL-10, IL-12, TNF-alpha, and IFN-gamma) and IgM and IgA rheumatoid factor (RF), and 4) the association with HLA-DRB1 polymorphism. Seventy-nine RA patients were assessed (69 with established RA, and 10 with recent-onset RA not receiving any treatment), 56 with ankylosing spondylitis (AS), 25 with systemic lupus erythematosus (SLE), 50 with primary Sjögren's syndrome (pSS), and 10 healthy individuals. Of the 69 patients with established RA, 36 were reexamined 2 years later. The activity of the RA was measured by criteria adopted by the American College of Rheumatology. Anti-CCP2, RF and cytokines levels were determined by ELISA. HLA genotypes were established by first, PCR sequence amplification using sequence-specific primers and then, complete sequencing of the product. Anti-CCP antibodies were observed in 96% of patients with RA during the first evaluation and in 86% at the second evaluation (p = 0.12). No significant change in antibody titre was observed between the two evaluations (131 +/- 58.7 and 130.6 +/- 67.1 IU, respectively). The overall sensitivity and specificity was 94% and 92%, respectively; however, at titres > 60 IU, the values were 84% and 95%, respectively. The anti-CCP likelihood ratio positive test was 12 and the likelihood ratio negative test was 0.06. The positive predictive value was 87%, and the negative predictive value was 96%. Anti-CCP antibodies were observed in 12% of SLE and pSS patients, in 2% of AS patients, and in 10% of healthy controls. In RA patients, these antibodies were not associated with the activity of disease, EAM or HLA-DRB1 alleles; no significant correlation was observed between antibody titre and cytokines level. Although anti-CCP antibodies have potential as a diagnostic tool for RA, they are not useful for monitoring clinical activity or predicting the clinical course of disease. Antibody synthesis is HLA-DRB1 independent and not correlated with Th1/Th2 cytokines.

Pardo A, Selman M. · Facultad de Ciencias, Universidad Nacional Autónoma de México and Instituto Nacional de Enfermedades Respiratorias, Apartado Postal 21-630, Coyoacan, México, DF, CP 04000, Mexico. · Int J Biochem Cell Biol. · Pubmed #15474975 No free full text.

Abstract: The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that play a key role in both physiological and pathological tissue remodeling. Human fibroblast collagenase (MMP-1) was the first vertebrate collagenase purified as a protein and cloned as a cDNA, and is considered the prototype for all the interstitial collagenases. It is synthesized as a zymogen where N-terminal residues are removed by proteolysis and shares with other MMPs a catalytic domain and a carboxy terminal domain with sequence similarity to hemopexin. Importantly, MMP-1 should be considered a multifunctional molecule since it participates not only in the turnover of collagen fibrils in the extracellular space but also in the cleavage of a number of non-matrix substrates and cell surface molecules suggesting a role in the regulation of cellular behaviour. Furthermore, an extensive body of evidence indicates that MMP-1 plays an important role in diverse physiologic processes such as development, tissue morphogenesis, and wound repair. Likewise, it seems to be implicated in a variety of human diseases including cancer, rheumatoid arthritis, pulmonary emphysema and fibrotic disorders, suggesting that its inhibition or stimulation may open therapeutic avenues.

Mysler E. · OMI, Buenos Aires, Argentina. · Int J Clin Pract. · Pubmed #15311562 No free full text.

Abstract: Lumiracoxib, a new selective COX-2 inhibitor, has been recently approved in England and Mexico for the treatment of acute and chronic pain. Although it is the fifth COX-2 inhibitor to come to the market, it has a unique structure that could prove to be important in the adverse event profile. Double blind randomised trials have proved its efficacy in acute pain, dysmenorrhea, rheumatoid arthritis and osteoarthritis. Its gastrointestinal safety profile has been studied in multiple trials. The main clinical trail, therapeutic arthritis research and gastrointestinal event trial, has as primary end point: perforations, obstructions and bleeding and as secondary end points: cardiovascular, renal and hepatic safety profile. The results of this trial will probably change the way we look at selective COX-2 inhibitors.

Richaud-Patin Y, Soto-Vega E, Jakez-Ocampo J, Llorente L. · Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga #15, Tlalpan, 14000 Mexico City, Mexico. · Autoimmun Rev. · Pubmed #15110230 No free full text.

Abstract: Multidrug resistance-1 (MDR-1) is characterized by overfunction of P-glycoprotein (P-gp), a pump molecule that decreases intracellular drug concentration by effluxing them from the intracellular space. Broad ranges of structurally unrelated compounds are transported by P-gp, including antineoplastic agents, HIV protease inhibitors, prednisone, gold salts, methotrexate, colchicine as well as several antibiotics. In contrast, many other compounds such as calcium channel blockers (verapamil) and immunosupressors (cyclosporine-A) are able to inhibit P-gp function. The P-gp role in therapeutic failures has been extensively studied in cancer; however, there is little information regarding MDR-1 phenotype in autoimmune disorders. It has been reported that an increased number of lymphocytes are able to extrude P-gp substrates in rheumatoid arthritis, immune thrombocytopenic purpura and systemic lupus erythematosus, the patients with poor response to treatment being the ones that exhibit the highest values. This may be due, at least in part, to a simultaneous long-term usage of several drugs that induce P-gp function. Since abnormally activated cell compartments characterize autoimmune diseases, it is possible that those cells are the ones that exhibit drug resistance. The study of drug resistance mechanisms in autoimmunity may be helpful for the optimization of the current therapeutic schemes through their combination with low doses of P-gp inhibitors.

Cardinali DP, García AP, Cano P, Esquifino AI. · Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. · Curr Drug Targets Immune Endocr Metabol Disord. · Pubmed #15032620 No free full text.

Abstract: Our perception of the function of the pineal gland and its hormone melatonin has attained a new dimension during the last decade. Through melatonin, the pineal becomes a principal organ present in vertebrates involved in the control of rhythmic adaptations to daily and seasonal cycles. Melatonin is synthesized and secreted during the dark period of the light/dark cycle. The rhythmic nocturnal melatonin secretion is directly generated by the circadian clock and is entrained to a 24-hour period by the light-dark cycle. The periodic secretion of melatonin may be used as a circadian mediator to any system than can "read" the message. Melatonin acts as an arm of the circadian clock, giving a time-related signal to a number of body functions; one of them is the circadian organization of the immune response. This review discusses melatonin role in rheumatoid arthritis. Animal studies employing Freund's complete mycobacterial adjuvant (FCA) as a model of rheumatoid arthritis are described. Immune and neuroendocrine circadian rhythms were examined in FCA-injected rats, both in the preclinical phase of arthritis (2-3 days after FCA injection) as well as in the acute phase of the disease (18 days after FCA injection). In arthritic rats, the 24-h organization of immune and neuroendocrine responses becomes altered. Significant effects of immune response on diurnal rhythmicity of adenohypophysial and hypophysiotropic hormones occurred in arthritic rats. Melatonin treatment prevented alteration of 24-h rhythms of serum ACTH, prolactin and luteinizing hormone in rats injected with FCA. In addition, melatonin treatment prevented alteration of the 24-h variation in hypothalamic monoamine transmitter turnover during the preclinical phase of Freund's adjuvant arthritis in rats. A comparison between the inflammatory and immune responses elicited by physiological and pharmacological doses of melatonin in FCA arthritis is reported. Pinealectomized rats exhibited a significantly less pronounced inflammatory response, which was restored to normal by a low melatonin dose (0.3 microg/ml of drinking water), whereas a high melatonin dose (30 microg/ml) that resulted in a 50-60-fold increase in plasma melatonin, augmented the inflammatory and immune response. These results should be considered in the light of recent reports that rheumatoid arthritis patients have increased nocturnal plasma levels of melatonin and that their synovial macrophages respond to melatonin with an increased cytokine production.

Aguillón JC, Contreras J, Dotte A, Cruzat A, Catalán D, Salazar L, Molina MC, Guerrero J, López M, Soto L, Salazar-Onfray F, Cuchacovich M. · Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile. · Rev Med Chil. · Pubmed #15022409 No free full text.

Abstract: The fusion of a murine B cell and a myeloma cell generates a hybridoma that produces monoclonal antibody (mAb). These murine mAb induce the HAMA (human anti-mouse antibodies) response. Murine mAb have been modified by genetic engineering, producing molecules with a higher proportion of human protein. At present, chimeric, humanized and fully human mAb are available. mAb block interactions between target molecules and their ligands or trigger the lyses of mAb-coated tumor cells. Numerous mAb have been developed using the recombinant DNA technology and several are available in the market. Trastuzumab, against HER2/neu, is useful in breast cancer; rituximab, against CD20 in B lymphocytes is useful in lymphoma; alemtuzumah, against CD52 is used in lymphoma and leukemia; daclizumab and basiliximab block the IL-2 receptor interaction and reduce acute rejection in kidney transplantation; abciximab, an antagonist of GPIIb/IIIa platelet receptor, is used in patients undergoing acute coronary syndromes. In autoimmunity diseases, blocking tumor necrosis factor by infliximab and adalimumab has demonstrated excellent results. Thus, infliximab is useful in the treatment of rheumatoid arthritis (RA), Crohn's disease and ulcerative colitis while adalimumab is the first fully human mAb available for RA. Infliximab and adalimumab reduce signs and symptoms in RA and they also interfere with progression of joint damage. Finally, the direct benefits of antagonist treatment can occur at the expense of a major adverse effect in some other biological function.

Garavito G, Malagón C, Ramírez LA, De La Cruz OF, Uribe O, Navarro E, Iglesias A, Martínez P, Jaraquemada D, Egea E. · Universidad Autónoma de Barcelona, Barcelona, España. · Biomedica. · Pubmed #14582328 No free full text.

Abstract: Oligotypes of the human leukocyte antigen HLA Class II, DRB1 alleles were characterized at the molecular level in a group of Colombian children suffering juvenile rheumatoid arthritis (JRA). The distribution of these alleles was examined in a group of Colombian mestizo children (genetic admixture of Amerindians, Europeans and Africans) suffering from clinically distinct JRA subsets in order to detect HLA allele frequency differences in patients with different JRA subsets. A group of 65 patients with JRA and 65 controls were characterized for the subtypes of the HLA-DRB1 alleles using polymerase chain reaction with sequence-specific oligonucleotide probes (PCR-SSOP). The oligotyping protocol recommended by the 12th International Histocompatibility Workshop held in St. Malo, Paris, in 1996, was used. Subtype HLA-DRB1*1104 was the allele most strongly associated with susceptibility to JRA (Fisher's p = 0.013, odds ratio (OR) = 16.79, etiologic fraction (EF) = 0.93). HLA-DRB1*1602 was also associated with susceptibility to a lesser degree (Fisher's p = 0.016, OR = 8.98, EF = 0.88). HLA-DRB1 alleles participating in JRA protection were HLA-DRB1*1501 (preventive fraction (PF) = 0.466, p = 0.005) and HLA DRB1*1402 (PF = 0.49, p = 0.009). The relationship between some HLA-DRB1 alleles and clinical features was also compared. The presence of rheumatic factor was associated with the alleles HLA-DRB1*0407 (p = 0.05, OR = 11.2, EF = 0.45) and HLA-DRB1*1302 (p = 0.02, OR = 22.8, EF = 0.63). There was also an association between HLA-DRB1*0701 (p = 0.001, OR = 58, EF = 0.73) with expressing ANA +. We found that in the oligoarticular subset, the allele HLA-DRB1*1104 (p = 0.0034, OR = 41.53, EF = 0.97) was the one expressed most commonly. In the poliarticular group, the alleles most frequently expressed were HLA-DRB1*0404 (Fisher's p = 0.012, OR = 8.75, EF = 0.88). In patients with systemic JRA, the HLA-DRB1*1602 allele (p = 0.005, OR = 21.33, EF = 0.95) was most frequent. These results suggested that the MHC genes of mestizo children influence not only the clinical expression of the disease, but also the susceptibility to its development.

Cordner S, De Ceulaer K. · University Hospital of the West Indies, Jamaica. · Curr Opin Rheumatol. · Pubmed #12496509 No free full text.

Abstract: Patients with sickle cell disease often seek treatment for rapid periorbital swelling due to infarction of the orbital bones. Because of resulting orbital compression syndrome, treatment with corticosteroids and antibiotics is advisable. If spinal tuberculosis occurs in patients with sickle cell anemia, radiologic signs will be a combination of the two conditions. The diagnosis of juvenile rheumatoid arthritis is usually delayed in patients with sickle cell disease. Sulphasalazine is the disease-modifying drug of choice for treating juvenile rheumatoid arthritis, because it also reduces the adhesiveness of sickled red cells. TNF-alpha inhibitors may also be useful for treating these patients. A volumetric method to determine the size and special distribution of the necrotic lesions of the femoral head has been developed using magnetic resonance imaging scans. With this method it will be easier to determine which early lesions require core decompression, or which ones should be treated conservatively. Osteomyelitis can be differentiated from bone infarction with the use of segmental radionuclide bone-marrow and bone scans. Reduction in frequency of painful crises can be achieved by increasing fetal hemoglobin with the use of hydroxyurea. The treatment of the actual pain requires decisions about the analgesics that are used as well as the route of their administration. Ketorolac monotherapy is likely to fail in the presence of an initial high pain score or with involvement of four or more pain sites.

Aguillón JC, Cruzat A, Cuenca J, Cuchacovich M. · Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Sección de Reumatología, Departamento de Medicina, Hospital Clínico. · Rev Med Chil. · Pubmed #12434654 No free full text.

Abstract: Cytokine unbalance is responsible for the pathogenesis of diverse inflammatory, autoimmune and infectious diseases, and Tumor Necrosis Factor Alpha (TNF alpha), among other cytokines, plays a central role. TNF alpha production can be regulated at the transcriptional, post-transcriptional, and translational levels. Variability in the promoter and coding regions of the TNF alpha gene may modulate the magnitude of its secretory response. Up to date, several single nucleotide polymorphisms (SNPs) have been identified in the human TNF alpha gene promoter. One of these, is a guanine to adenine transition at position -308, that generates the TNF1 and TNF2 alleles, respectively. The TNF2 allele is associated to a high in vitro TNF expression, and it has also been linked to an increased susceptibility and severity, for a variety of illnesses, such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, Alzheimer disease and cerebral malaria among others. It is also associated with a higher septic shock susceptibility and mortality. The investigation of polymorphisms within the TNF alpha cluster will be important in understanding the role of TNF alpha regulation in specific diseases.

León-Sarmiento FE, Carpintero de Jimeno M. · Unidad de Neurología y Neurociencias Aplicadas, Departamento de Medicina Interna y Ciencias Básicas, Facultad de Salud, UIS-Universidad Industrial de Santander, Bucaramanga, Colombia. · Rev Neurol. · Pubmed #12389174 links to  free full text

Abstract: AIMS: To analyse the pros and cons of the etiopathogenic aspects of the different clinical entities that, over the years, have been found to be associated with the so called human retroviruses in order to propose possible etiological alternatives. METHOD: Since research on retroviruses began there has been a tendency to blame these elements for a number of clinical entities, the most important of which include Aids, tropical spastic paraparesis (TSP), fungoid mycosis, Sjogren's syndrome and T cell leukaemia. Yet many patients and scientific publications point out the existence of a large number of clinical and laboratory inconsistencies, which suggests that the so called cofactors associated with all these entities are far more likely to be the real generators of these public health problems. Among these, we pay special attention to environmental toxins, of which a prototypical example is the group of neuromycotoxins. There are several ways these can enter the organism of an individual exposed to them (through food, breathing and intravenously) or, worse still, they can be generated endogenously in immunosuppressed individuals. CONCLUSION: The possibility of some cofactors being the real causes behind a large number of entities considered to be Aids, TSP, Sjogren s syndrome, fungoid mycosis or T cell leukaemia, among others, regardless of their retroviral serological state, is becoming more and more likely and scientifically plausible. All these facts should be researched in much greater depth to determine their real dimensions, which would therefore enable us to face the future with better means of prevention, diagnosis and treatment at our disposal.

Hilário MO, Terreri MT. · Alameda dos Anapurus, 1370 ap 144, 04087-004 São Paulo, Brazil. · Best Pract Res Clin Rheumatol. · Pubmed #12387812 No free full text.

Abstract: Rheumatic fever resulting from group A beta-haemolytic Streptococcus infection continues to be a prevalent disease and an important cause of morbidity and mortality in developing countries. Molecular mimicry and CD4 T lymphocytes, interleukins and adhesion molecules play a crucial role in the pathogenesis of this disease. Arthritis, followed by carditis and chorea, are the main manifestations of the disease. Evidence of asymptomatic carditis has been increasing; however, abnormality identified by echo-Doppler evaluation is not considered as a criterion for diagnosis of rheumatic carditis. Benzathine penicillin is still the best therapeutic option for the treatment of streptococcal infection and secondary prophylaxis, due to its efficacy and low cost.

Teixeira RA, Martinelli Filho M, Benvenuti LA, Costa R, Pedrosa AA, Nishióka SA. · Heart Institute, Medical School, University of São Paulo, São Paulo, SP, Brazil. · Arq Bras Cardiol. · Pubmed #12163948 links to  free full text

Abstract: Chloroquine has been widely used in rheumatological treatment, but potential severe side effects require careful follow-up. Cardiac damage is not a common consequence, but its clinical relevance has not yet been described. We report the case of a 58-year-old woman with rheumatoid arthritis, in whom chronic chloroquine use resulted in major irreversible cardiac damage. She presented with syncopal episodes due to complete atrioventricular block confirmed by electrophysiological study whose changes were concluded to be irreversible and a permanent pacemaker was indicated. Endomyocardial biopsy was also performed to search for histopathological and ultrastructural cardiac damage. We also reviewed the 22 cases of chloroquine-induced cardiopathy described to date as well as its pathophysiology.

Soto-Rojas AE, Kraus A. · Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Vasco de Quiroga #15, Tlalpan, 14000 México City, D.F., México. · Arch Med Res. · Pubmed #11886706 No free full text.

Abstract: Sjögren syndrome (SS) is an inflammatory disease of the exocrine glands. Although not always present, signs and symptoms of dry eyes and xerostomia are characteristic features of SS. Oral dryness is one of the most important data of patients with SS. Several sets of criteria have been published; however, there is no definitive agreement concerning which is the most useful. In addition to its various clinical manifestations, lack of understanding of the causes of SS delays prompt diagnosis. Histologically, the salivary gland shows a characteristic lymphocytic infiltrate, which is implicated in the destruction of gland cells. Saliva performs an important role in maintaining and protecting oral health. Deficient quality and quantity of saliva have a detrimental consequence for dental and oral health. In some patients, appropriate information regarding dry mouth care is not offered because most professionals either neglect or ignore adequate attention to oral health. Therefore, lack of treatment is frequent. Medical and dental studies that focus on the oral aspects of diagnosis, consequences, and treatment of SS are commented on. Diagnostic methods used for the oral component are also reviewed. The role of the oral tests developed to diagnose SS is assessed, especially tests used by the majority of criteria. Impairment of salivary secretion increases the risk of developing oral diseases; the therapeutic modalities designed to ameliorate these damages by increasing salivary output or by substitution of saliva are reviewed. We discuss published prevention techniques to diminish dental, periodontal, and soft tissue infections.

Caviglia HA, Fernandez-Palazzi F, Galatro G, Perez-Bianco R. · Haemophilia Foundation, Department of Orthopaedics, Buenos Aires, Argentina. · Haemophilia. · Pubmed #11564141 No free full text.

Abstract: Rifampicin is an antibiotic that has been currently used for the treatment of noninfectious articular lesions with satisfactory results. The first experience was performed with patients who presented rheumatoid arthritis, and later with haemophilic patients. The clinical experience of three haemophilia centres which used rifampicin for the treatment of chronic haemophilic synovitis is presented here. The protocols were different. It was observed that rifampicin is more effective when it is used in small joints (elbows and ankles), than when used in bigger ones (knees), and that a high number of injections predicts failure. Mention is also made of experimental studies in animals where it was shown that the healing pattern of rifampicin is similar to that of NSAIDs.

Ortiz Z, Shea B, Suarez Almazor M, Moher D, Wells G, Tugwell P. · Sucre 3280, 7th Floor, Apt. 26, Buenos Aires, Argentina, 1428. · Cochrane Database Syst Rev. · Pubmed #10796393 No free full text.

Abstract: OBJECTIVES: To assess the effects of folic acid and folinic acid in reducing the mucosal and gastrointestinal (GI) and haematologic side effects of low-dose of Methotrexate (MTX) in patients with Rheumatoid Arthritis (RA) and to determine whether or not folate supplementation alters MTX efficacy. SEARCH STRATEGY: We searched the Cochrane Controlled Clinical Trial's Register (CCTR), the Cochrane Musculoskeletal Group Specialized Register and Medline up to and including June 1999, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). We also handsearched the following: (i) bibliographic references; (ii) current contents of the last 6 months; (iii) abstracts of the rheumatology meetings; and (iv) all issues of four journals; Journal of Rheumatology, Arthritis & Rheumatism, Clinical and Experimental Rheumatology, and British Journal of Rheumatology. All languages were included. Principal investigators were also contacted in order to look for unpublished literature. SELECTION CRITERIA: We selected all double-blind, randomized, placebo-controlled, clinical trials (RCTs), in which adult RA patients were treated with a low dose of MTX (<20 mg / week) concurrently with folate supplementation. DATA COLLECTION AND ANALYSIS: Two observers extracted the data and assessed the quality of the trials. (BS, Z0) The overall treatment effect across trials was calculated using a fixed effect model. Disease activity was evaluated using standardized mean differences to ensure comparability across outcome measures. Results are presented with 95% Confidence Inervals (95% CI). Subgroup analyses were conducted evaluating different doses and sensitivity analysis looking at the quality of the trials. Publication bias was assessed with an inverted funnel plot technique. Heterogeneity of the trials was measured using a standard chi square test. Costs per month in different countries were compared. MAIN RESULTS: Of the 12 trials retrieved, 7 met the inclusion criteria. The total sample included 307 patients, of which 147 were treated with folate supplementation, 80 patients with folinic acid and 67 patients with folic acid. A 79% reduction in mucosal and GI side effects was observed for folic acid [OR = 0.21 (95% CI 0.10 to 0.44)]. For folinic acid, a clinically but non-statistically significant reduction of 43% was found [OR = 0. 57 (95% CI 0.28 to 1.15)]. No major differences were observed between low and high doses of folic or folinic acid. Haematologic side effects could not be analyzed, since details of each haematologic side effect by patients were not provided. No consistent differences in disease activity parameters were observed when comparing placebo and folic or folinic acid at low or high doses, although patients on high dose folinic acid had an increase in the number of tender joints, but not swollen joints. Large differences in costs across countries were found, but folinic acid was more expensive in all. REVIEWER'S CONCLUSIONS: The results support the protective effect of folate supplementation in reducing MTX side effects related to the oral and GI systems. We could not determine if folic was different from folinic acid. Therefore, for folinic acid to be considered cost-effective it must be found more effective than folic acid at reducing MTX side effects.

Coronato S, Di Girolamo W, Salas M, Spinelli O, Laguens G. · Cátedra de Patología B, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina. · Medicina (B Aires). · Pubmed #10684171 No free full text.

Abstract: Hsp (Heat shock proteins) are a family of constitutive proteins of all pro and eukariotic cells that play different physiological roles: they promote the folding (acquisition of tertiary structure) assembly, translocation and secretion of newly synthesized polypeptides and participate in the removal or repairing of denatured proteins acting as molecular chaperons. This family of proteins is composed by numerous members grouped according to their molecular weight. When cells are subjected to different stresses such as hyperthermic shock, radiation, toxins, viral infections, etc., Hsp are overexpressed. In this way, they exert a cytoprotective effect, making the cells resistant to apoptosis. In humans, Hsp are overexpressed in cancer cells from ovary, endometrium, breast, prostate, digestive tract, etc. In some cases, overexpression is correlated with an unfavorable outcome because these proteins could favour metastatic disease. Some authors associate them not only with proliferation but also with differentiation of the neoplastic tissue. Recent studies show their influence in resistance to chemotherapeutic drugs. In autoimmune diseases like rheumatoid arthritis, Hsp can suppress the inflammatory response. Nevertheless, their role in the immune system has not been well established.

Ramos-e-Silva M, Carneiro SC. · Section of Dermatology, HUCFF-UFRJ, School of Medicine, Universidade Federal do Rio de Janeiro, Brazil. · Clin Dermatol. · Pubmed #10631528 No free full text.

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Shinzato M, Yamamoto J, Hirata CE, Goldberg AC, Yoshinari NH, Bonfá E. · School of Medicine, University of São Paulo, Brazil. · Postgrad Med J. · Pubmed #10621881 links to  free full text

Abstract: We report the case of a 40-year-old woman with diffuse uveitis, sensorineural hearing loss and cerebrospinal fluid pleocytosis as features of Vogt-Koyanagi-Harada syndrome who developed symmetric polyarthritis and stiffness of small and large joints, in addition to rheumatoid arthritis. Although their target tissues are distinct, both diseases have a possible autoimmune origin strongly associated with HLA-DRB4.