The effectiveness for prevention of tuberculosis in patients with inflammatory rheumatic diseases treated with TNF inhibitors.

BACKGROUND: New biologic therapies blocking TNF undoubtly constitute a considerable advancement in the management mentioned diseases, but are also associated with higher risk of activation of tuberculosis. METHODS: An assessment of tuberculosis activation rate in the group of patients with rheumatoid arthritis, juvenile idiopatic arthritis, ankylosing spondylitis and psoriatic arthritis threated by anti-TNF inhibitors since January 1st 2001 to June 30th 2007 in Slovakia and went in for special anti-tuberculosis screening before start of therapy. RESULTS: A total 537 rheumatic patients received the anti-TNF therapy. There were 346 rheumatoid arthritis patients, 68 juvenile idiopatic arthritis patients, 71 patients suffered from ankylosing spondylitis and 52 from psoriatic arthritis. Duration of anti-TNF therapy was 843 of patient-years. Infliximab took 203 patients with duration of therapy 348 patient-years, etanercept 201 patients with duration of therapy 331 patient-years and adalimumab 133 patients with duration of therapy 164 patient-years. The activation of tuberculosis reached the incidence 0.37% (2 cases for 537 patients) representing 0.237 cases for 100 patient-years. Both patients had extrapulmonary forms of tuberculosis which was in one patient disseminated, but they fully recovered after the anti-TNF drugs were stopped and chemotherapy was completed. CONCLUSION: Our results demonstrate a low incidence of tuberculosis activation during anti-TNF treatment in patients with inflammatory rheumatic diseases in the Slovak Republic and confirm the high effectiveness ours specified complex screening measures (Tab. 3, Ref. 13). Full Text (Free, PDF) www.bmj.sk.

[Gastroduodenal complications associated with non-steroidal anti-inflammatory drugs in Slovak Republic: results of one-year prospective study]. / Podiel gastroduodenálnych komplikácií vo vzt'ahu k liecbe nesteroidovými antiflogistikami v Slovenskei republike: rocná prospektívna stúdia.

The aim of the one-year prospective study was to estimate the prevalence of non-steroidal anti-inflammatory drugs using in patients with symptomatic gastroduodenal ulcers, the upper gastrointestinal bleeding and perforation (PUB--perforation, ulcer, bleeding). Among of 326 patients with PUB, prevalence of non-steroidal anti-inflammatory drugs using was 60%. In the group of 194 patients with non-steroidal antiinflammatory drugs induced PUB, 49% patients took aspirin, 38% non-aspirin non-steroidal anti-inflammatory drugs and 13% their combination. Low dosing aspirin (daily dosis < or =200 mg) was associated with PUB in 21% of patients. Age higher than 60 years and women had statisticaly signiticant higher prevalence of non-steroidal anti-inflammatory drugs induced PUB.

[Seroprevalence of Helicobacter pylori in rheumatoid arthritis and its relationship to pharmacotherapy]. / Séroprevalencia Helicobacter pylori pri reumatoidnej artritíde a jej vzt'ah k farmakoterapii.

GOAL: To find out a serology prevalence of Helicobacter pylori (Hp) infection in patients suffering from rheumatoid arthritis (RA) and to investigate its relationship to pharmacotherapy modes. METHOD: To determine Hp IgG class and IgA class antibodies by ELISA method in hospitalised patients with active RA according to ACR criteria (1987). RESULTS: 137 patients with RA were examined--20 men, 117 women, an average age was 54.6 +/- 13.1, an average length of RA in these patients was 12.46 +/- 9.75, positive RF/LFT had 88% of patients. Hp ELISA IgG antibodies were confirmed in 57% (78/137) of patients with RA, Hp ELISA IgA antibodies were confirmed in 60% of examined patients (82/137), and IgG + IgA antibodies simultaneously were found in 51% (70/137) of examined patients. A comparison of basic demographic data, specific parameters of the disease, and clinical signs has not confirmed any differences between groups of Hp positive and Hp negative patients. Patients with both types of Hp antibodies (IgG + IgA) had more frequent signs of RA in other places than joints (p = 0.046). RA patients with anti-Hp IgG antibodies more frequently used anticoagulation drugs (p = 0.029) while patients with anti-Hp IgA antibodies more frequently used methotrexate (p = 0.01). CONCLUSIONS: Results point out more frequent incidence of Hp IgA antibodies in RA patients treated with methotrexate and more frequent incidence of both IgG and IgA antibodies in patients with RA signs in other places than joints.

Liquid chromatographic method development for determination of fungicide epoxiconazole enantiomers by achiral and chiral column switching technique in water and soil.

High-performance liquid chromatography (HPLC) in both chiral isocratic and achiral-chiral column switching mode was employed for optimization of separation conditions, separation and determination of fungicide epoxiconazole in real samples. Two enantiomers of commercially available triazole fungicide epoxiconazole (BAS 480 F), first registered in 1993, were resolved for the first time on a microcrystalline cellulose triacetate (MCTA). A low-cost home-packed chiral column (150x3 mm, 15-25 microm, MCTA, Merck) enabled baseline enantiomeric resolution of two enantiomers of the fungicide epoxiconazole produced commercially. The effects of concentration of organic modifiers (methanol, ethanol) in mobile phase, flow-rate and temperature were studied. The isocratic chiral HPLC method allows determination of the enantiomers in tap and surface water within the range 1-1000 mg/l by direct injection (20 microl) of the sample. Using the achiral (C18)-chiral (MCTA) column-switching technique and 1-ml sample volume, injection of 0.050 mg/l of epoxiconazole enantiomers can be conveniently determined by UV detection at 230 nm. The same method applied to methanolic soil extracts allows determination of 0.2 mg/kg of epoxiconazole enantiomers in addition to the other 10 commonly used pesticides in fortified soils.

Alzheimer's disease, inflammation and non-steroidal anti-inflammatory drugs.

Alzheimer's disease (AD) is a degenerative disease of the brain, which causes dementia. The disease is characterised by three main pathogenic factors: senile plaques, neurofibrillary tangles and inflammation. the participation of the local inflammatory reaction is confirmed especially by the results of studies dealing with activated microglia, reactive astrocytes, complement system, cytokines, reactive mediators of oxygen and nitrogen (free radicals), all of which participate significantly in inflammatory processes. These inflammatory markers are locally produced by brain cells, and occur in close proximity of beta-amyloid and tau protein deposits. Moreover, some epidemiologic and pilot clinical studies have proven that long-term administration of anti-inflammatory drugs have a protective effect on the onset of AD. Out of them, non-steroidal anti-inflammatory drugs (NSAIDs) are most extensively investigated medicaments. Despite some contradictory findings, the prevalent majority of these studies prove that long-term application of anti-inflammatory treatment can delay the onset, or at least slow down the progression of AD, namely in people between 65 and 75 years of age. The most appropriate prophylactic effect seems to be achieved by specific inhibitors of cyclooxygenase-2 (COX-2), namely celecoxib and rofecoxib. These preparations protect the gastrointestinal tract better than classical NSAIDs which inhibit both isoenzymes--COX-1 and COX-2. COX-2 is expressed in higher concentrations in the degenerating cells of the brain and this excessive expression can be decreased by selective inhibitors. The latter decrease also the excessive activation of some transcription factors (PPARgama and the nuclear factor kapa-B), which are responsible for the initiation of transcription of a number of pro-inflammatory genes. The selective inhibitors COX-2 can thereby have an anti-inflammatory effect operating on several levels. (Tab. 1, Fig. 1, Ref. 75.)

Nonsteroidal antiinflammatory drug-induced mucosal lesions of the upper gastrointestinal tract and their relationship to Helicobacter pylori.

The aim of the present study was to determine the prevalence of Helicobacter pylori infection in a group of patients hospitalized at the clinic of rheumatology who presented peptic ulcers and erosions associated with nonsteroidal antiinflammatory drugs (NSAIDs). Of a group of 4,256 hospitalized patients receiving therapy with NSAIDs, 221 patients with persistent dyspepsia underwent endoscopic examination of the upper segment of the gastrointestinal tract. Among them, mucosal abnormalities in the stomach and duodenum were confirmed in 69 patients. H. pylori was found in 42% (29/69) of the examined patients. Peptic ulcers were confirmed in 19 patients. Localization was gastric in 12 patients and duodenal in seven. H. pylori was found in only 17% of the patients (2/12) with gastric ulcers, but in as many as 86% (6/7) of those with duodenal ulcers. Patients with H. pylori taking NSAIDs were at higher risk of developing duodenal mucosal abnormalities, both ulcers (OR: 10.17; 95% CI: 1.08-23.88, p = 0.013) and erosions (OR: 2.67; 95 CI: 1.94-3.66, p = 0.001). Concomitant administration of corticoids and NSAIDs did not increase the risk of gastrotoxicity in patients with positive finding of H. pylori (OR: 0.32; 95% CI: 0.1-0.96). In conclusion, a close association was found between H. pylori infection and duodenal ulcers and erosions, but not between gastric ulcers and gastric erosions in a group of patients hospitalized for rheumatic diseases and undergoing NSAID therapy.

[Treatment of erosive gastropathy caused by nonsteroidal anti-inflammatory agents using low doses of antacids]. / Liecba erozívnej gastropatie vyvolanej nesteroidovými antiflogistikami nízkodávkovanými antacídami.

In an open clinical, endoscopy controlled study involving 31 patients with erosive NSAIDs-induced gastropathy without Helicobacter pylori infection, the effect of low dose of antacids (120 mmol/l) with aluminium oxide and magnesium oxide (Maalox) administered for 4 weeks was followed. The administration of NSAIDs was not interrupted during the time of treatment. Healing rate of the gastric erosions after four weeks reached 65% (20/31) and endoscopic score in the gastric mucosa proved significant improvement (0.97 +/- 0.49 compared to 0.07 +/- 0.25, p < 0.01). Our results suggest efficacy of low dose antacids containing aluminium in the treatment of NSAIDs-induced gastric erosions.

Nabumetone induces less gastrointestinal mucosal changes than diclofenac retard.

The aim of the study was to compare the efficacy and the effects on the mucosa of the gastrointestinal tract (GIT) of nabumetone and diclofenac retard in patients with osteoarthritis (OA). An open, multicentre, randomised, comparative, endoscopy-blind parallel group study included 201 patients with nabumetone and 193 patients with diclofenac retard suffering from moderate to severe OA of the knee or hip joint. Twelve clinical efficacy variables were assessed and a portion of the population underwent gastroduodenoscopy. All patients exhibited significant improvement in pain severity and pain relief (p < 0.001 and p < 0.0001, respectively) but there were no differences between the groups for all the efficacy variables. Eleven per cent of patients on nabumetone and 19% on diclofenac experienced GIT side-effects. Sixty-nine patients with nabumetone and 61 with diclofenac underwent gastroduodenoscopy. The differences in the mucosal grade for the oesophagus, stomach and duodenum at baseline were not significant. In the oesophagus there were significantly less changes after treatment with nabumetone (p = 0.007) than with diclofenac; there were similar findings in the stomach (p < 0.001) but the difference in the duodenum was not significant. This study indicates that nabumetone and diclofenac retard have similar efficacy in the treatment of OA, but nabumetone has significantly fewer GIT side-effects.

[Treatment and prevention of gastrointestinal complications caused by non-steroidal antiphlogistic agents]. / Liecba a prevencia gastrointestinálnych komplikácií vyvolaných nesteroidovými antiflogistikami.

The aim of our study is to give a survey of the most efficient methods for treatment and prevention of non-steroidal anti-inflammatory drug (NSAID)-induced gastrointestinal adverse in cases when antiphlogistic treatment cannot be discontinued due to active and progressive joint disease. Analysis of published studies shows that, the proton pump inhibitors (omeprazole) are the most efficient agents in treatment of gastric and duodenal ulcers induced by NSAIDs. The analysis shows a reliable effect of prostaglandin analogues (misoprostol) as well. Prostaglandin analogues (misoprostol) proved the most effective in treatment of gastric erosions. Prophylaxis of adverse gastrointestinal mucosal abnormalities can be primary or secondary. Secondary prevention is intended for patients with gastrointestinal symptoms or those treated for mucosal defects (ulcer, erosions). The standard prevention using H2-antagonists or sucralphate does not provide sufficient protection against NSAID in these patients, but omeprazole reduces the chance of a peptic lesion relapse. Primary prevention is intended for patients with a higher risk of gastrointestinal complications (age above 60, history of peptic ulcer, a higher dose of NSAID, simultaneous treatment with glucocorticoids or anticoagulants). Diclofenac with misoprostol and nabumetone reduce the incidence of gastroduodenal ulcers and their complications in short-term as well long-term studies. Meloxicam reduces the incidence of gastroduodenal mucosal abnormalities is short-term studies. Nimesulide is associated with a lower incidence of adverse gastrointestinal events, but the fact is that, reliable data on gastroduodenal ulcer incidence reduction or their complications are not available.

[Takayasu arteritis and the algodystrophic syndrome]. / Takayasuova arteritída a algodystrofický syndróm.

Algodystrophic syndrome represents a group of symptoms involving pain and oedema of the affected extremity, with movement disorders, vegetative and vasomotor disturbances and focal osteoporosis development. The key role in the pathogenesis of the syndrome plays intensive and prolonged stimulation of pain receptors. The authors present a case report of 47 years old woman with Takayasu's arteritis complicated by skin defects on right instep and sole with consequent development of algodystrophic syndrome on both lower extremities. Combined influence of both types of nociceptive stimuli is demonstrated, ischaemic-obstruction of peripheral arteries and alterative-skin defects. (Fig. 3, Ref. 13.)

[Famotidine in the treatment of gastropathy induced by non-steroidal antirheumatic agents]. / Famotidín v liecbe gastropatie vyvolanej nesteroidnými antireumatikami.

In an open clinical endoscopically controlled study in 30 consecutive patients with rheumatic diseases complicated by the ulcerative and erosive form of gastroduodenopathy induced by non-steroidal antiinflammatory drugs and oesophagitis, after four weeks treatment with oral famotidine (one dose of 40 mg/day) confirmed a significant improvement of the mean oesophageal (0.67 +/- 1.06 vs. 0.03 +/- 0.18, p rrr 0.01) gastric 2.10 +/- 1.49 vs. 0.63 +/- 0.85, p rrr 0.001) and duodenal mucosal score (1.80 +/- 1.52 vs. 0.43 +/- 0.82, p rrr 0.001). After four weeks treatment 71% lesions (5/7) in the oesophagus were cured, 77% gastric lesions (10/13) and 75% duodenal lesions (9/12). Treatment with non-steroid antirheumatics proceeded.

[Congenital atransferrinemia]. / Kongenitale Atransferrinämie.

Congenital atransferrinemia was first diagnosed at the age of 11 months in a now 27-year-old woman. Until she was aged 14 years treatment with human transferrin was irregular and, as it turned out, inadequate. But since then she has regularly received human transferrin (1 g monthly) and deferoxamine (500 mg twice weekly). Despite this she developed haemosiderosis affecting heart, liver, hypophysis, thyroid and the locomotor apparatus. This case report demonstrates the need of early diagnosis and treatment of congenital atransferrinemia to prevent the mentioned complications.

[HLA antigens and primary prolapse of the mitral valve]. / HLA antigény a primárny prolaps mitrálnej chlopne.

The authors present results of investigation of antigens of the HLA system in primary mitral valvular prolapse. The investigated group of patients was formed by 23 not related patients with primary mitral valvular prolapse. (15 women, 8 men, aged 18-55 years) where HLA antigens of loci A, B and C were assessed. They found a significantly increased frequency of antigen HLA-B35 in the patients (56.52%), as compared with the population (18.33%, x2 = 18.48, Pcorr less than 0.01). The measure of the observed relationship is expressed by the relative risk value--RR = 5.81. The difference in the frequency of the other HLA antigens was not statistically significant.

Joint hypermobility in primary mitral valve prolapse patients.

Twenty-seven patients with echocardiographic evidence of primary mitral valve prolapse (MVP) were tested for the presence of joint hypermobility using the criteria of Beighton and Horan. In the examined group, joint hypermobility was found in 14 patients (52%). This occurrence was statistically significant. In patients with simultaneous occurrence of MVP and articular hypermobility we have found a number of pathologic arthrologic manifestations, such as arthralgias, synovitic reactions, distortions, low back pain, and others. In patients with articular hypermobility, there were increased functions of antigen B 35.