Carditis in Acute Rheumatic Fever in a High-Income and Moderate-Risk Country.

OBJECTIVE: To describe clinical presentation, electrocardiographic, and echocardiographic characteristics of carditis at the time of diagnosis of acute rheumatic fever (ARF) over a 13-year period. STUDY DESIGN: A single-center retrospective chart analysis was conducted involving all consecutive patients diagnosed with ARF between 2003 and 2015. Patient age, sex, clinical characteristics, recent medical history for group A streptococcal pharyngotonsillitis and antibiotic treatment, and laboratory, echocardiographic, and electrocardiographic findings were recorded. RESULTS: Of 98 patients (62 boys, mean age 8.81 ± 3.04 years), 59 (60.2%) reported a positive history of pharyngotonsillitis; 48 (49%) had received antibiotic (mean duration of treatment of 5.9 ± 3.1 days), and, among these, 28 (58.3%) had carditis. Carditis was the second most frequent finding, subclinical in 27% of patients. Mitral regurgitation was present in 49 of 56 patients (87.5%) and aortic regurgitation in 36/56 (64.3%) no stenosis was documented. CONCLUSIONS: ARF is still present in high-income countries and can develop despite primary prophylaxis, especially when given for a short course. Our findings highlight the need for 10 days of antistreptococcal treatment to prevent ARF. Echocardiography is important because 27% of cases with carditis were subclinical.

A network pharmacology approach to determine the synergetic mechanisms of herb couple for treating rheumatic arthritis.

PURPOSE: The purpose of this study was to investigate the therapeutic mechanism(s) of Clematis chinensis Osbeck/Notopterygium incisum K.C. Ting ex H.T (CN). METHODS: A network pharmacology approach integrating prediction of ingredients, target exploration, network construction, module partition and pathway analysis was used. RESULTS: This approach successfully helped to identify 12 active ingredients of CN, interacting with 13 key targets (Akt1, STAT3, TNFsf13, TP53, EPHB2, IL-10, IL-6, TNF, MAPK8, IL-8, RELA, ROS1 and STAT4). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that CN-regulated pathways were mainly classified into signal transduction and immune system. CONCLUSION: The present work may help to illustrate the mechanism(s) of action of CN, and it may provide a better understanding of antirheumatic effects.

A 2018 Approach to Combating Methotrexate Toxicity Folic Acid and Beyond.

Methotrexate (MTX) is the cornerstone to management across a variety of rheumatic diseases. Effective use and adherence to MTX treatment is dependent on toxicity prevention and management. The major deterrents to patient tolerability and adherence can include GI upset, hepatic transaminase elevation, stomatitis, hair loss, and CNS toxicity. Many rheumatologists are familiar with employing supplementation of folic acid and folinic acid, as well as a change from oral to subcutaneous (SC) MTX, to help combat MTX toxicity. There are, however, more potential strategies in a rheumatologist's armamentarium to ameliorate side effects and improve adherence, including vitamin A supplementation and dextromethorphan. Herein, we will provide a review of the literature (both rheumatologic and oncologic) and expert opinion in terms of managing methotrexate toxicity and improving adherence in rheumatic diseases.

An ultra-high performance liquid chromatographic-tandem mass spectrometric method for the determination of sinomenine in human plasma after transdermal delivery of the zhengqing fengtongning injection.

A sensitive, precise and selective ultra-high performance liquid chromatography method coupled with triple-quadrupole mass spectrometry was developed and validated for the determination of trace amounts of sinomenine (ng/mL) in minute volumes of human plasma. Fifty microliter plasma samples were precipitated using methanol to extract sinomenine. Separation was carried out on a C18 column with a water and acetonitrile mobile phase gradient with formic acid as an additive. The mass spectrometry data were obtained in the positive ion mode, and the transition of multiple reactions was monitored at m/z 330.2→181.0 for sinomenine quantification. The working assay range for sinomenine was linear from 0.1173 to 15.02 ng/mL with the lower limit of quantification of 0.1173 ng/mL. The precision and accuracy of the method was less than 15% in intra-day and inter-day experiments with a matrix effect of less than 6.5%. After validation, the quantitative method was applied to analyze sinomenine levels in human plasma after transdermal delivery of the Zhengqing Fengtongning Injection. The results showed that some samples contained sinomenine within the concentration range 0.4131-4.407 ng/mL.

Applying Manual Pressure before Benzathine Penicillin Injection for Rheumatic Fever Prophylaxis Reduces Pain in Children.

The purpose of this study was to evaluate the efficacy of applying manual pressure before benzathine penicillin injection and compare it with the standard injection technique in terms of reducing discomfort in children with rheumatic heart disease grouped by age and gender. This was a single-blind, randomized, crossover study. Fifty-one patients aged 7.1-19.9 years were recruited for this study carried out in the pediatric cardiology outpatient clinic. Twenty-nine were girls (56.9%). All subjects received an intramuscular injection of benzathine penicillin with manual pressure to one buttock or with the standard technique to the other buttock at 3-week intervals. The two techniques were used randomly. The subjects were blinded to the injection technique and a visual analogue scale was used after the procedure. Findings demonstrate that children experienced significantly less pain when they received injections with manual pressure (1.3 ± 0.9) compared with the standard injection (4.4 ± 1.6) technique. The perceived injection pain was negatively related to the age of the children in both techniques. Compared with boys, girls felt more pain, but the difference between each technique group according to gender was negligible. The application of manual pressure reduces pain in children under the stress of repeated intramuscular injections, which supports the suggestion that it should be used in routine practice. Manual pressure to the injection site is a simple, pain-reducing technique. Implementing this technique in routine practice may also promote adherence to the prophylaxis regimen, especially in children.

Anti-rheumatic potential of ethyl 2-(2-cyano-3-mercapto-3-(phenylamino) acrylamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate and its Co(II), Cu(II) and Zn(II) complexes.

Ethyl 2-(2-cyano-3-mercapto-3-(phenylamino)acrylamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [THBTD] and its [Co(THBTD]-H)Ac], [Cu(THBTD]-H)Ac]H2O and [Zn(THBTD)-H)Ac] complexes have been synthesized via the reaction of thiocarbamoyl derivatives with metal ions namely; Co(II), Cu(II) and Zn(II) acetate, respectively. The newly synthesized complexes were characterized by elemental analysis, spectral analysis (UV-Vis, IR, (1)H NMR and EPR), conductance, thermal analysis and magnetic moments. The in vivo collagen-adjuvant arthritis model in rats revealed significant antioxidant, analgesic and anti-rheumatic effects for [THBTD] and its copper complex.

Effect of dietary fat on intestinal inflammatory diseases.

Dietary fat has multiple roles on human health, and some dietary fat is used to treat organic diseases because of its anti-inflammatory effect. It is commonly accepted that omega-3 polyunsaturated fatty acid (PUFA) is beneficial on ischemic heart disease or rheumatic arthritis. On the contrary, effect of omega-3-PUFA on Crohn's disease remained controversial. That effect of omega-3 PUFA differs according to the location of inflamed intestine was hypothesized. To elucidate this hypothesis, to investigate the role of dietary fat on disease activity in different kind of murine models of intestinal inflammatory diseases was planned. The effect of omega-3 PUFA on small intestinal Crohn's disease model and large intestinal Crohn's disease model of mice. Chronic colitis model C57BL/6 mice received two cycles of dextran sodium sulfate solution treatment to induce chronic colitis. Feeding of omega-3 fat-rich diets exacerbated colitis with decrease in adiponectin expression. Chronic small intestinal inflammation model: SAMP1/Yit mice showed remarkable inflammation of the terminal ileum spontaneously. Feeding of omega-3 fat-rich diets for 16 weeks significantly ameliorated the inflammation of the terminal ileum. Enhanced infiltration of leukocytes and expression of mucosal addressin cell adhesion molecule-1 in intestinal mucosa was significantly decreased by omega-3 fat-rich diets treatment. Omega-3 PUFA has dual role, pro-/anti-inflammatory, on intestinal inflammatory diseases. The role of omega-3 fat and the potential for immunonutrition in inflammatory conditions of the gastrointestinal tract will be discussed.

A traditional Chinese medicine versus Western combination therapy in the treatment of rheumatoid arthritis: two-stage study protocol for a randomized controlled trial.

BACKGROUND: The common randomized controlled trial design has distinct limitations when applied to Chinese medicine, because Chinese medicine identifies and treats 'Chinese medicine patterns' rather than diagnosed diseases. Chinese medicine patterns are a group of associated symptoms, tongue appearances and pulse characteristics. These limitations could be overcome by developing new strategies to evaluate the effect of Chinese medicine. The idea behind pattern-based efficacy evaluations may optimize clinical trial design by identifying the responsiveness-related Chinese medicine patterns. METHODS/DESIGN: This is a two-stage multi-center trial of Chinese herbal medicine for the management of rheumatoid arthritis. The stage one trial is an open-label trial and aims to explore what groups of Chinese medicine information (such as symptoms) correlates with better efficacy, and the stage two trial is a randomized, controlled, double-blind, double-dummy clinical trial that incorporates the efficacy-related information identified in the stage-one trial into the inclusion criteria. DISCUSSION: The indication of a Chinese herbal formula is a specific Chinese medicine pattern and not a single disease and stratifying a disease into several patterns with a group of symptoms is a feasible procedure in clinical trials. This study is the first to investigate whether this approach in the design of Chinese herbal medicine trials can improve responses. TRIAL REGISTRATION: ChiCTR-TRC-10000989.

[From willow bark to acetylsalicylic acid]. / Fra pilebark til acetylsalicylsyre.

Acetylsalicylic acid is one of the most widely used drugs in the world. Its ancestry the salicylates, including salicin and salicylic acid, are found in the bark and leaves of the willow and poplar trees. The ancient Sumerians and Egyptians, as well as Hippocrates, Celsus, Pliny the Elder, Dioscorides and Galen used these natural products as remedies for pain, fever and inflammation. In the Middle Ages these remedies were used for fever and rheumatism by Hildegard of Bingen and Henrik Harpestreng. The first "clinical trial" was reported by Edward Stone in 1763 with a successful treatment of malarial fever with the willow bark. In 1876 the antirheumatic effect of salicin was described by T. MacLagan, and that of salicylic acid by S. Stricker and L. Riess. Acetylsalicylic acid was synthesized by Charles Gerhardt in 1853 and in 1897 by Felix Hoffmann in the Bayer Company. The beneficial effect of acetylsalicylic acid (Aspirin) on pain and rheumatic fever was recognized by K. Witthauer and J. Wohlgemuth, and the mechanism of action was explained in 1971 by John Vane. Today the antithrombotic effect of acetylsalicylic acid and new aspects of ongoing research demonstrates a still living drug.

Effect of benzathine penicillin treatment on antibiotic susceptibility of viridans streptococci in oral flora of patients receiving secondary prophylaxis after rheumatic fever.

OBJECTIVE: To assess the level of antibiotic resistance of viridans streptococci in the oral flora of children with a history of rheumatic fever, receiving long-term monthly intramuscular benzathine penicillin G prophylaxis. PATIENTS AND METHODS: Oral swabs from patients receiving monthly penicillin G prophylaxis for rheumatic fever were cultured and tested for viridans streptococci. The E-test was used to test susceptibility to penicillin G, clindamycin, clarithromycin and rifampin. Findings were compared with samples from healthy children who had not been exposed to antibiotic treatment for at least 2 months. RESULTS: Twenty-six patients and 20 control children were included in the study. Duration of intramuscular antibiotic treatment ranged from 5 months to 13.5 years. Sixty isolates of viridans streptococci species were obtained, with a similar distribution in the two groups. Intermediate resistance to penicillin (MIC 0.25-2 mg/L) was documented in 10 of the 32 isolates (31.2%) in the study group, and high resistance in none, compared to seven of 28 isolates (25%) with intermediate or high resistance in the control group (p=NS). All isolates in the study group and all but one in the control group were susceptible to clindamycin, and all isolates from both groups were susceptible to rifampin. One isolate (3.1%) in the study group and two (7.1%) in the control group were resistant to clarithromycin. CONCLUSION: Monthly Intramuscular penicillin prophylaxis has no effect on the antibiotic susceptibility of viridans streptococci in oral flora in children with a history of rheumatic fever, receiving secondary prophylaxis after rheumatic fever, regardless of the duration of treatment.

Adult-onset acute rheumatic fever: possible resurgence in southern Taiwan.

BACKGROUND: By the late 1980s, acute rheumatic fever (ARF) had become a rare disease in Taiwan. The low prevalence rate in this area is attributed to a better economic status, which has led to improved public health and adequate medical services. OBJECTIVES: The increasing number of patients with adult-onset ARF in the United States described in the literature prompted us to evaluate the cases diagnosed in our medical center. METHODS: A retrospective chart review was performed for patients with arthritis from July 1988 to October 2004. To be included, patients had to meet revised Jones criteria. RESULTS: Three adult patients with ARF have been diagnosed since June 2001, with no childhood ARF being diagnosed. All cases presented with migratory polyarthritis, whereas 1 had erythema marginatum and transient carditis. These patients responded well to treatment with antibiotics and nonsteroidal antiinflammatory drugs. CONCLUSIONS: Clinicians must provide careful assessment and treatment to patients presenting with acute pharyngitis. A possible resurgence of ARF can be eradicated by primary prevention of streptococcal pharyngitis.

Recurrent acute rheumatic fever: a forgotten diagnosis?

The incidence of acute rheumatic fever has seen a dramatic decline over the last 15 to 20 years in most developed countries and treatment of this disease has changed little since. The ease of travel and immigration and the cosmopolitan nature of many cities mean that occasionally the disease will come to the attention of clinicians not familiar with its presentation, resulting in delayed diagnosis and treatment. We present a case of recurrent acute rheumatic fever in a patient who was initially thought to be suffering from acute bacterial endocarditis on her previously diseased rheumatic aortic valve. This culminated in her undergoing urgent aortic valve replacement during a phase of the illness that should have been treated with high dose anti-inflammatory medication. Therefore, clinicians should be aware of this condition and include it in their differential diagnosis of the febrile patient with a previous history of rheumatic fever. We briefly discuss the diagnostic dilemma of patients suffering from this condition and in differentiating it from acute endocarditis.

[Primary acute rheumatic fever in juveniles from an organized community]. / Pervichnaia ostraia revmaticheskaia likhoradka u iunoshei, prebyvaiushchikh v usloviiakh organizovannogo kollektiva.

A closed population of juveniles was studied to follow-up manifestations of primary rheumatic fever. In line with other unfavourable factors, the onset of the disease within the first 6 months of the observation was due to cross streptococcal infection (foci of chronic nasopharyngeal infection were detected in 68.6% examinees, rheumatism debut after acute nasopharyngeal infection was in 91.0% patients). Persistence of streptococci was established in many blood counts in immunofluorescence reaction in 88.2% patients in acute disease, in more patients with lingering rheumatic process. Clinical manifestations include, aside from arthritis and rheumocarditis, frequent thyroid and gastrointestinal lesions. It is thought valid to raise the dose and duration of administration of penicillin in patients with primary rheumatic fever as it eradicates chronic infection foci, prevents recurrences, reduces the number of patients with a lingering course of the disease, with recurrences and valvular defects of the heart.