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Rheumatic fever and rheumatic heart disease.

Rheumatic heart disease poses a major challenge to public health and is the most prevalent heart disease in children. The major determinants of rheumatic fever and rheumatic heart disease are poverty, malnutrition, overcrowding, poor housing, and a shortage of health-care resources. Although cost-effective strategies for the prevention and control of these diseases are available, they remain underutilized in most developing countries. A World Health Organization Expert Consultation reviewed the current scientific knowledge of rheumatic fever and rheumatic heart disease, as well as medical and public-health practices, and revised the Jones diagnostic criteria for rheumatic fever and rheumatic heart disease. This revision facilitates the diagnosis of: primary episodes of rheumatic fever, recurrent attacks of rheumatic fever in patients with or without rheumatic heart disease, rheumatic chorea, insidious onset rheumatic carditis and chronic rheumatic heart disease. The present report provides practical recommendations for an evidence-based approach to the prevention and management of rheumatic fever and rheumatic heart disease. It also provides practical guidance for implementing cost-effective programmes for controlling these diseases. The report will be of interest to clinicians, policy-makers and public-health professionals.

Adolescent↗

[Rheumatic fever and rheumatic heart disease].

Rheumatic heart disease, the sequel of acute rheumatic fever, is a very common cause of cardiovascular mortality and morbidity all over the world, and is the predominant indication for cardiac surgery in the industrialized countries. Diagnosis of rheumatic chronic carditis may sometimes be difficult because valvular regurgitation may not always be detected by routine clinical auscultation. A recent report from the World Health Organization Expert Committee recognizes the usefulness of echocardiography Doppler in providing supporting evidence for diagnosis of rheumatic carditis in the presence of equivocally pathological murmur, and recommends that patients with subclinical carditis should be managed as rheumatic heart disease until proven otherwise, because the disease still represents a major health problem. The aim of this review is to give an update on the disease by underlining changes made by the World Health Organization on disease diagnosis and patient management.

Adolescent↗

Rheumatic heart disease.

Rheumatic heart disease seems in many ways emblematic of an older era in medicine, without any prospects of new development or change in the current era. Many new findings have come to light in the past few years regarding this illness, which has a relatively low prevalence in the United States. Not only have the diagnostic Jones criteria for acute rheumatic fever changed, but substantial advances have been made in the use of penicillin prophylaxis for recurrent rheumatic attacks, the use of mitral valve repair or reconstruction for rheumatic mitral regurgitation, the management of rheumatic, aortic, and mitral valve disease, and the application of balloon commissurotomy for mitral stenosis. This review details some of these advances.

Adolescent↗

Dilemmas in the management of rheumatic heart disease.

Rheumatic heart disease (RHD) is a major health care problem in India and will continue to be so for few more decades. As there is no vaccine against RHD, it is difficult to control the disease. Besides RHD, most children have other preventable ailments as well. Hence the schools, specially for the poor, must act as primary and preventive health care centres. Prevention of RHD starts with school prophylaxis. Primary, secondary and tertiary prophylaxis play their roles afterwords. After the heart valves have been damaged, tertiary prevention might minimise further damage. For mitral stenosis, closed mitral valvotomy (CMV), open mitral valvotomy (OMV) and interventional mitral valvotomy (IMV) are the different options but none is curative. Valve replacement poses many problems and therefore valvotomy is deferred as far as possible. Mild or moderate mitral regurgitation (MR) is best treated medically. For more advanced disease repair or replacement is the option. For aortic stenosis (AS), valvotomy may be preferred to replacement wherever feasible and for aortic regurgitation (AR) repair is not yet well established. In combined mitral and aortic valve disease it is important to assess both the valves carefully and try to repair one or both the valves and to avoid double valve replacement as far as possible. Once the heart valve is damaged any treatment is palliative, hence all efforts should be directed towards prevention of RHD. Indian Medical Association can play a major role in this endeavour and help children in India to grow up free from RHD.

Adult↗

[Immunohistochemical study of thymus in patients with congenital heart disease or rheumatic heart disease].

A series monoclonal antibodies were used to study the intrathymic distribution of T and B cells and the process of intrathymic differentiation of T cells on frozen sections of 14 patients' thymuses by a more sensitive immunohistochemical method. The observation indicated that most of the cortical lymphocytes reacted with Leu 1, Leu 2 a, Leu 3 a and Leu 4 antibodies, thus indicating coexpression of multiple antigen on cortical lymphocytes. In cortex, the numbers of Leu 1 and Leu 4 positive cells were less than medulla. In contrary, the numbers of Leu 2 a and Leu 3 a positive cells in the cortex were more than the medulla: and the medullary thymocytes showed segregation into Leu 2 a+ Leu 3 a- and Leu 3 a+ Leu 2 a- subsets. The ANAE+ and AIG 3+ cells were almost limited to the medulla. Hence, the staining profile of medulla approximated the staining pattern of peripheral T cell subsets, which were programmed for their respective role as helper and suppressor cells. Our results supported the conclusion that the mature T cells presented in the medulla were derived from the immature cells in the cortex. In addition, the expression of Leu 7 was not only limited to the NK cells scattered in the medulla, but also found at the cortical-septa border. On the other hand, a small number of B lymphocytes scattered in the medulla stained with Leu 14, OKB-2, BA-1 and IgM antibodies. The Hassall's corpuscles were cross reaction with the B cell antibodies mentioned above; while the epithelial cells in thymic parenchyma were only stained with IgM antibody. Based on these findings we conclude that the human thymus predominantly consist of T cells, but it also contains a fraction of B cells and epithelial cells.

Adolescent↗

Advances in potential M-protein peptide-based vaccines for preventing rheumatic fever and rheumatic heart disease.

Rheumatic fever (RF) and rheumatic heart disease (RHD) are postinfectious complications of an infection (or repeated infection) with the Gram-positive bacterium, Streptococcus pyogenes (also known as group A streptococcus, GAS). RF and RHD are global problems and affect many indigenous populations of developed countries and many developing countries. However, RF and RHD are only part of a larger spectrum of diseases caused by this organism. The development of a vaccine against GAS has primarily targeted the abundant cell-surface protein called the M-protein. This review focuses on different M-protein-based-subunit vaccine approaches and the different delivery technologies used to administer these vaccine candidates in preclinical studies.

Amino Acid Sequence↗

Myocardial metal content in patients who expired from cyanotic congenital heart disease and acute rheumatic heart disease.

The importance of metals in normal and pathologic cardiovascular function has been recognized. Significant derangements in myocardial Ca2+, Mg2+, and Cu2+ have been reported in ischemic heart injury. We studied 3 groups of hearts: 1) fifteen specimens obtained from patients who had no heart disease, 2) nine specimens from patients who had expired from cyanotic congenital heart disease, and 3) ten specimens from patients who had expired from acute rheumatic heart disease with carditis and severe heart failure. None of the patients had undergone cardiac surgery. Left ventricular lateral wall Mg2+, Ca2+, Cu2+, and Zn2+ contents were measured by atomic absorption spectrometry. The results showed a significant decrease in myocardial Mg2- (Group I 177.06 +/- 32.71; Group II 155.66 +/- 14.79; Group III 149.00 +/- 13.29, p less than 0.05 and p less than 0.01, respectively), and Cu2+ contents (Group I 3.22 +/- 0.37; Group II 2.94 +/- 0.22; Group III 2.56 +/- 0.32, p less than 0.02 and p less than 0.001, respectively), and a rise in myocardial Ca2+ content (Group I 36.06 +/- 10.72; Group II 43.22 +/- 7.01; Group III 46.30 +/- 4.85, p = not significant, and p less than 0.01, respectively). The myocardial Zn2+ content did not change significantly (Group I 26.53 +/- 3.99; Group II 26.00 +/- 4.15; Group III 26.40 +/- 3.53). The myocardial Mg2+/Ca2+ ratio was reduced markedly in both groups (Group I 5.328 +/- 1.879; Group II 3.685 +/- 0.735; Group III 3.135 +/- 0.291, p less than 0.001 for both Groups II and III vs Group I). The latter results correlated closely with the myocardial Mg2+/Ca2+ ratios reported in experimental models in peri-infarction zones. Thus, the myocardium of patients who had expired from cyanotic congenital heart disease and acute rheumatic carditis is jeopardized by ischemia, with metal contents similar to the border areas in myocardial infarction.

Acute Disease↗

Morphometric analysis of fossa ovalis in rheumatic heart disease.

BACKGROUND: Rheumatic heart disease is an important cause of valvular disease in India, with resultant alterations in the interatrial septum and fossa ovalis. Morphometric details of fossa ovalis may help in its localization during transseptal catheterization so as to prevent complications. METHODS AND RESULTS: Autopsy heart specimens of rheumatic heart disease (n=30) and non-cardiac death (n=30) patients between 15-45 years of age were studied as case and control group, respectively. The dimensions of fossa ovalis and interatrial septum were measured. The ratio of area of fossa ovalis to septum was calculated. Case group showed a significant increase in surface area of septum and fossa as compared to control group. The septal area was significantly increased in 15-30 years and 31-45 years groups, specially females in the former group. The fossa area was increased only in 31-45 years age group. The ratio of area of fossa to septum was not statistically altered in cases versus controls. Case group, specially females of 15-30 years, showed a significant horizontal orientation of fossa as compared to controls. Cases having both mitral and aortic stenosis showed highest increase in the areas of fossa and septum, as also the most horizontal orientation of fossa. CONCLUSIONS: The enlargement of the septal area begins at an early age in rheumatic heart disease along with initial hemodynamic and valvular alterations. There is a categorical horizontal orientation of fossa ovalis in these cases. Varying dynamics in stenotic and regurgitant valves leads to varying morphological changes in dimensions of fossa ovalis and septum.

Adolescent↗

Replacement of mitral, aortic, and pulmonary valves for rheumatic heart disease.

Rheumatic disease of the pulmonary valve has been documented at autopsy. Most of the reported cases of calcified pulmonary valves are associated with congenital heart disease. A unique case of rheumatic aortic and mitral valve disease associated with calcific pulmonary stenosis is presented. Prosthetic replacement of all three involved valves was carried out successfully. This is believed to be the first reported triple valve replacement of its kind.

Aortic Valve↗

MHC class II alleles in Mexican patients with rheumatic heart disease.

BACKGROUND: Rheumatic heart disease (RHD) is an autoimmune sequel of group A streptococcal infection that has been associated with the presence of some major histocompatibility complex (MHC) genes. Thus, the aim of the present study was to investigate the role of class II alleles in the genetic susceptibility to RHD in Mexican patients and establish the relationship of these alleles with the pattern of valve damage. METHODS: HLA-DR, -DQA1 and -DQB1 allele frequencies were determined by PCR-SSO reverse dot blot and PCR-SSP in 98 Mexican Mestizo patients with RHD and 99 healthy controls. Patients were divided into mitral valve damage (n=46), multivalvular lesion (n=49) and aortic damage (n=3). RESULTS: RHD patients presented an HLA-DR16 increased frequency (pC=0.009, OR=3.9) and a decreased HLA-DR11 frequency (pC=0.018) when compared to healthy controls. HLA-DR16 subtyping showed that DRB1*1602 was the DR16 allele increased in patients (pC=0.007, OR=5.3). Haplotype analysis showed increased frequency of DR16-DQA1*0501-DQB1*0301 in RHD patients when compared to healthy controls (pC=0.011). HLA-DR16 frequency remained significantly increased on patients with multivalvular lesion (pC=0.004, OR=4.8). CONCLUSIONS: Our data suggest an important participation of Amerindian autochthonous HLA-DR16 (DRB1*1602) allele and DR16-DQA1*0501-DQB1*0301 haplotype as markers for RHD genetic susceptibility in the Mexican Mestizo population. HLA-DR16 allele could also play an important role in determining the pattern of valve damage on these patients.

Adolescent↗

Restriction in the usage of variable beta regions in T-cells infiltrating valvular tissue from rheumatic heart disease patients.

Rheumatic Heart Disease (RHD) is a delayed consequence of a pharyngeal infection with group A streptococcus (GAS), usually ascribed to a cross-reactive immune response to the host's cardiac tissues. Several GAS proteins have been reported to be superantigens, also raising the possibility that T cells in RHD could be driven by superantigens. We therefore analysed the variable beta (V beta) repertoire of T cells infiltrating heart valves from chronic RHD patients undergoing elective valvular surgery. We analysed 15 valve specimens from patients with longstanding quiescent RHD and control valves from four non-rheumatic individuals. Total RNA was extracted from fresh valve tissue and employed to amplify 22 V beta genes by RT-PCR. In valvular tissue, a restricted number of only 2 to 9 V beta regions were detected as opposed to the findings in control valves. In 8 RHD valves, the expression of V beta1, 2, 3, 5.1, 7, 8, 9 or 14 was marked. These V beta regions have been related to GAS superantigens. Our results evidence the presence of a restricted set of T lymphocytes in valvular tissue from a majority of patients with chronic RHD and suggest that valvular sequelae in these patients might be related to a local antigen or superantigen driven inflammatory process that persists even many years after the initial triggering event.

Adult↗

Molecular evidence for antigen-driven immune responses in cardiac lesions of rheumatic heart disease patients.

Rheumatic heart disease (RHD) is a sequel of post-streptococcal throat infection. Molecular mimicry between streptococcal and heart components has been proposed as the triggering factor of the disease, and CD4(+) T cells have been found predominantly at pathological sites in the heart of RHD patients. These infiltrating T cells are able to recognize streptococcal M protein peptides, involving mainly 1-25, 81-103 and 163-177 N-terminal amino acids residues. In the present work we focused on the TCR beta chain family (TCR BV) usage and the degree of clonality assessed by beta chain complementarity-determining region (CDR)-3 length analysis. We have shown that in chronic RHD patients, TCR BV usage in peripheral blood mononuclear cells (PBMC) paired with heart-infiltrating T cell lines (HIL) is not suggestive of a superantigen effect. Oligoclonal T cell expansions were more frequently observed in HIL than in PBMC. Some major BV expansions were shared between the mitral valve (Miv) and left atrium (LA) T cell lines, but an in-depth analysis of BJ segments usage in these shared expansions as well as nucleotide sequencing of the CDR3 regions suggested that different antigenic peptides could be predominantly recognized in the Miv and the myocardium. Since different antigenic proteins probably are constitutively represented in myocardium and valvular tissue, these findings could suggest a differential epitope recognition at the two lesional heart sites after a common initial bacterial challenge.

Adolescent↗