Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 69-year-old woman with a 6-year history of rheumatoid arthritis treated solely with an orally administered NSAID had slowly progressing persistent mild abdominal pain and diarrhea, accompanied with marked sing of inflammation as well as hypoproteinemia due to protein-losing gastroenteropathy. Examinations of the large intestine revealed variously shaped ulcerative lesions, centered around the left hemicolon, as well as luminal narrowing. The course of the disease and the shape of the lesions strongly suggested involvement of rheumatoid vasculitis; oral administration of prednisolone was effective.
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PMID:Rheumatoid arthritis accompanied by colonic lesions. 1077 27

Rheumatoid arthritis (RA) is a chronic disease affecting 0.8% of the population. Nonsteroidal anti-inflammatory drugs reduce the pain and inflammation of RA and improve mobility but do not slow the progression of joint damage. Disease-modifying antirheumatic drugs (DMARDs), which limit potentially irreversible joint damage, may influence the course of disease progression. This review describes the recently approved DMARD leflunomide, an isoxazole-based immunomodulator. Unlike other DMARDs, leflunomide arrests the growth of activated lymphocytes by inhibiting the enzyme dihydroorotate dehydrogenase, a critical link in the production of uridine monophosphate. Leflunomide is rapidly metabolized to the active major metabolite A77 1726, which is responsible for the drug's pharmacologic activity. Leflunomide has exerted inhibitory activity in animal models of RA. Its clinical efficacy has been demonstrated in a number of controlled trials. In two multinational 52-week studies and two 24-week studies, all leflunomide-treated patients received an initial loading dose of 100 mg for 3 days, followed by 20 mg/d. The effects on the signs and symptoms of RA were evaluated using the American College of Rheumatology (ACR) 20 responder index, tender and swollen joint counts and scores, patients' and physician's global assessments, and pain intensity index. Erosions and joint-space narrowing were assessed by radiography. Compared with placebo, leflunomide significantly improved the signs and symptoms of RA (41%-64% improvement) by ACR 20 responder criteria (P < 0.001). Leflunomide, methotrexate, and sulfasalazine were equally effective in terms of symptom outcomes. In terms of retarding the progression of disease, leflunomide was significantly superior to placebo, with no consistent difference from methotrexate or sulfasalazine. In a trial using a combination of leflunomide and methotrexate therapy, 53% of patients were responders by ACR 20 criteria. Adverse effects in RA patients receiving leflunomide included diarrhea, elevated liver enzymes, alopecia, and rash. Additional adverse events occurring with a frequency >5% included allergic reaction, asthenia, abdominal pain, back pain, and hypertension, among others. Thus leflunomide may be used in selected RA patients (ie, those starting RA therapy for the first time or failing earlier DMARD therapy). However, the product labeling requires monthly monitoring of liver enzymes until stable concentrations are reached. Other labeled warnings include a risk of immunosuppression and an increased risk of fetal death or teratogenic effects in pregnant women. Methotrexate, which is also hepatotoxic, is usually the initial DMARD recommended for use in patients with aggressive RA.
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PMID:Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis. 1089 Feb 56

A fifteen-year-old boy was admitted to our hospital because of lower abdominal pain, watery diarrhea and mucobloody stool. Two years before admission, he was diagnosed to have Still's disease presenting with polyarthritis, sore throat, remittent fever and typical skin rash. He had been treated with non-steroidal anti-inflammatory agents, oral prednisolone and low-dose methotrexate. Although he was almost free of symptoms during the next two years, serum C-reactive protein (CRP) levels continued to be elevated moderately. He began to complain of lower abdominal pain and loose stool in May 1997 and came down with mucous-bloody diarrhea in June. Laboratory data on admission showed an elevated level of serum CRP (13.9 mg/dl). The biopsy of the stomach, ileum, sigmoid colon and rectum revealed the deposition of amyloid protein of AA type, which confirmed the diagnosis of secondary amyloidosis. The dose of prednisolone was increased and dimethyl sulfoxide per os or rectum was instituted, which improved his gastro-intestinal symptoms to some extent. However, fever, arthritis and diarrhea recurred along with tapered prednisolone dosage. In addition to gastro-intestinal symptoms, arrhythmia and proteinuria appeared. These symptoms were considered to reflect general deposition of amyloid in his body. He is now on immunosuppressive agent and high-dose prednisolone. Several studies report the higher frequency of gamma-allele of SAA 1 gene in the cases of rheumatoid arthritis with AA-amyloidosis than in those without. In the patient presented here, molecular biological analysis revealed that his SAA 1 gene was composed of beta- and gamma-allele. The presence of gamma-allele in his SAA 1 gene might be one of the factors that predisposed him for generalized deposition of amyloid protein in such a short period of time.
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PMID:[Rapidly progressed secondary amyloidosis in a patient with Still's disease with gamma-allele in his SAA 1 gene]. 1092 Jun 89

Rheumatoid vasculitis is a relatively uncommon complication of rheumatoid arthritis (RA). It shows wide variety of extra-articular features including skin and neurologic involvement, but rarely shows gastrointestinal involvement. We describe a 79-old-man of rheumatoid vasculitis manifesting as small bowel multiple ulcerations accompanied by perforation of the descending colon diverticulum. The patient was admitted to our hospital with rectal bleeding and severe anemia. He had had rheumatoid arthritis for more than 10 years with treatment of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose prednisone. Upper endoscopy or colonoscopy revealed no evidence of bleeding. Suddenly he developed cramping abdominal pain, and emergency operation was performed. Segments of the descending colon and small bowel were resected to reveal perforation of the descending diverticulum and severe multiple ulcer of small bowel. The pathological examination showed multiple ulcerations of the small intestine was caused by vasculitis.
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PMID:[Rheumatoid vasculitis with multiple intestinal ulcerations: report of a case]. 1092 Jun 90

The present report describes and expands the clinical and genetic spectrum of the autoinflammatory disorder, tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS). A total of 20 mutations have been identified since our initial discovery of 6 missense mutations in TNF receptor super family 1A (TNFRSF1A) in 1999. Eighteen of the mutations result in amino acid substitutions within the first 2 cysteine-rich domains (CRDs) of the extracellular portion of the receptor. A single splicing mutation also affects the first CRD by causing the insertion of 4 amino acids. Haplotype analysis of the most commonly occurring and ethnically heterogeneous mutation, R92Q, demonstrates an ancient founder; however, analysis of the T50M mutation, another commonly occurring mutation in Irish and Scottish families, does not, suggesting that T50M is a recurring mutation. Mutations that result in cysteine substitutions demonstrate a higher penetrance of the clinical phenotype (93% versus 82% for noncysteine residue substitutions), and also increase the probability of developing life-threatening amyloidosis (24% versus 2% for noncysteine residue substitutions). Retrospective and prospective evaluation of more than 50 patients, representing 10 of the 20 known mutations, allows us to expand and better define the clinical spectrum of TRAPS. Recurrent episodes of fever, myalgia, rash, abdominal pain, and conjunctivitis that often last longer than 5 days are the most characteristic clinical features of TRAPS. Defective shedding of TNFRSF1A can only partially explain the pathophysiologic mechanism of TRAPS, since some mutations have normal shedding. Consequently, other mechanisms may be mediating the observed phenotype. We are currently investigating other possible mechanisms using stable and transiently transfected cell systems in vitro, as well as developing a knockin mouse model. Preliminary data suggest that etanercept may be effective in decreasing the severity, duration, and frequency of symptoms in TRAPS patients. Additionally, it provides a viable therapeutic alternative to glucocorticoid therapy, which has numerous serious, long-term adverse effects. Two clinical trials are being conducted to evaluate the efficacy of etanercept in decreasing the frequency and severity of symptoms in TRAPS. Lastly, we have summarized data that R92Q and P46L, and probably as yet undiscovered substitutions, represent very low penetrance mutations that may play a much larger role in more broadly defined inflammatory diseases such as rheumatoid arthritis. Our laboratories are currently undertaking both clinical and basic research studies to define the role of these mutations in more common inflammatory diseases.
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PMID:The TNF receptor-associated periodic syndrome (TRAPS): emerging concepts of an autoinflammatory disorder. 1235 31

Whipple disease is an uncommon chronic bacterial infection due to Tropheryma whipplei. Clinical manifestations are protean (joint pain, fever, weight loss, abdominal pain, lymphadenopathies), and the diagnosis is often delayed. Although previously considered a late manifestation of Whipple disease, neurological involvement is now frequently the initial clinical manifestation and represents the greatest risk for long-term disability. All patients should be treated and monitored as if they had central nervous system disease even if they are asymptomatic. Neurological manifestations include dementia (56 percent), abnormalities of eye movements (33p. cent), involuntary movements (28 percent), seizures, hypothalamic dysfunction, myelopathy, ataxia and psychiatric manifestations. Uveitis, retinitis, optic neuritis and papilloedema may be found. 80 percent of the reported cases of neuro-Whipple had associated systemic symptoms or signs but many patients are presenting without concurrent intestinal manifestation. Thus, the disease may remain undiagnosed or misdiagnosed, as rheumatoid arthritis or sarcoidosis. Traditionally, the diagnostic procedure of choice is biopsy of the duodenal mucosa by demonstrating PAS-positive foamy macrophages. However, not all cases have small bowel infiltration and tissue obtained from sites clinically affected may be helpful. CT and MR images of the central nervous system are normal or not specific: atrophic changes, mass lesions, focal abnormalities and hydrocephalus. The application of a PCR assay against Tropheryma whipplei has transformed the diagnosis. Positive results have been obtained from several tissues and from CSF and PCR is more sensitive than other techniques. All patients must be treated with antibiotics which cross the blood-brain barrier. Most agree that initial treatment with a combination of parenteral penicillin and streptomycin for at least 14 days is appropriate, thereafter cotrimoxazole orally 3 times a day for at least one and probably for two years. Third generation cephalosporins, rifampicin and chloramphenicol have been used successfully. PCR is recognized to be a useful tool for monitoring progress but it is sometimes difficult to reverse established neurological defects.
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PMID:[Neurological manifestations of Whipple disease]. 1240 8

Thalidomide has several targets and mechanisms of action: a hypnosedative effect, several immunomodulatory properties with an effect on the production of TNF-alpha and the balance between the different lymphocyte subsets and an antiangiogenic action. Thalidomide has been used in several cutaneous inflammatory disorders (e.g., erythema nodosum leprosum in lepromatous leprosy, cutaneous lupus erythematosus and severe aphtosis), cancers (e.g., relapsed/refractory multiple myeloma, malignant melanoma and systemic signs in cancer) and inflammatory conditions (e.g., Crohn's disease and rheumatoid arthritis). Several side effects are associated with thalidomide. Some are major, such as teratogenicity, peripheral neuropathy and deep vein thrombosis. Somnolence and rash are frequently reported when thalidomide is used at higher doses as an anticarcinogenic agent and can lead to dose reduction or treatment discontinuation depending on severity. Minor side effects include abdominal pain and endocrine disturbances. To prevent the teratogenicity, use of thalidomide is strictly controlled in western countries with close adherence to a birth control programme. Close monitoring for early development of peripheral neuropathy is also recommended.
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PMID:Thalidomide: an old drug with new clinical applications. 1468 Apr 61

In patients with systemic lupus erythematosus(SLE), interstitial cystitis(lupus cystitis) is an uncommon, but important manifestation. We report two Japanese patients with lupus cystitis. Case 1 was a 49-year-old woman diagnosed as having rheumatoid arthritis and membranous nephropathy. She was treated with prednisolone(5 mg daily). Case 2 was a 41-year-old woman also diagnosed as having rheumatoid arthritis previously and treated with a non-steroidal anti-inflammatory drug. Both cases presented abdominal pain, vomiting, dysuria and frequency of micturition. We diagnosed these cases as SLE on the basis of arthritis, renal disorder(proteinuria and hematuria), and positive antinuclear and anti-dsDNA antibodies. In addition, bilateral hydronephrosis was found in both cases. Thus, they were also diagnosed as probable lupus cystitis. The patients were treated with one cycle of methylprednisolone pulse therapy. Thereafter they were treated with 60 mg/day of prednisolone and their symptoms resolved promptly. Furthermore, no abnormal finding was found by abdominal ultrasonography and/or the intravenous pyelogram after therapy. Renal biopsies were performed and both cases showed lupus glomerulopathy (case 1: WHO class Vb, case II: WHO class IVb). Abdominal pain and/or dysuria, which is common in SLE patients, requires further examinations to evaluate the lupus cystitis.
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PMID:[Two cases of lupus cystitis complicated by lupus nephritis treated successfully with steroid therapy]. 1473 94

A 66-year old female suffering from rheumatoid arthritis was treated with methotrexate and intra-articular steroid injections. She had gone through pulmonary tuberculosis at the age of 2 years, also, surgery had been performed 2 years ago because of perforated sigmoid diverticulitis. The patient now presented with episodes of abdominal pain and diarrhea as well as occasional night sweats. Laboratory investigation (normal BSR, CRP and white blood cell counts) did not indicate the presence of an inflammatory process, such as reoccurrence of diverticulitis. However, leukocyturia was repetitively found in this patient with the conventional urine culture yielding no significant bacterial growth. Further urine investigation did not indicate infection with Chlamydia trachomatis or Neisseria gonorrhoeae. Ziehl Neelson stains of morning urinary samples did not show acid-fast rods, however, Mycobacterium tuberculosis was finally isolated by culture. Thus, urogenital tuberculosis was finally diagnosed in this patient. Infection, hematogenic dissemination, and spontaneous remission of pulmonary tuberculosis had occurred more than 60 years ago. After a long latent period, reactivation of tuberculosis happened during drug-induced immunosuppression. The patient was successfully treated with an anti-tuberculosis triple-drug therapy during 2 months followed by a double-drug therapy during 4 months.
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PMID:[Unexpected complication in an elderly lady suffering from rheumatoid arthritis]. 1505 56

Nabumetone is a nonsteroidal anti-inflammatory prodrug, which exerts its pharmacological effects via the metabolite 6-methoxy-2-naphthylacetic acid (6-MNA). Nabumetone itself is non-acidic and, following absorption, it undergoes extensive first-pass metabolism to form the main circulating active metabolite (6-MNA) which is a much more potent inhibitor of preferentially cyclo-oxygenase (COX)-2. The three major metabolic pathways of nabumetone are O-demethylation, reduction of the ketone to an alcohol, and an oxidative cleavage of the side-chain occurs to yield acetic acid derivatives. Essentially no unchanged nabumetone and < 1% of the major 6-MNA metabolite are excreted unchanged in the urine from which 80% of the dose can be recovered and another 10% in faeces. Nabumetone is clinically used mainly for the management of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) to reduce pain and inflammation. The clinical efficacy of nabumetone has also been evaluated in patients with ankylosing spondylitis, soft tissue injuries and juvenile RA. The optimum oral dosage of nabumetone for OA patients is 1 g once daily, which is well tolerated. The therapeutic response is superior to placebo and similar to nonselective COX inhibitors. In RA patients, nabumetone 1 g at bedtime is optimal, but an additional 0.5-1 g can be administered in the morning for patients with persistent symptoms. In RA, nabumetone has shown a comparable clinical efficacy to aspirin (acetylsalicylic acid), diclofenac, piroxicam, ibuprofen and naproxen. Clinical trials and a decade of worldwide safety data and long-term postmarketing surveillance studies show that nabumetone is generally well tolerated. The most frequent adverse effects are those commonly seen with COX inhibitors, which include diarrhoea, dyspepsia, headache, abdominal pain and nausea. In common with other COX inhibitors, nabumetone may increase the risk of GI perforations, ulcerations and bleedings (PUBs). However, several studies show a low incidence of PUBs, and on a par with the numbers reported from studies with COX-2 selective inhibitors and considerably lower than for nonselective COX inhibitors. This has been attributed mainly to the non-acidic chemical properties of nabumetone but also to its COX-1/COX-2 inhibitor profile. Through its metabolite 6-MNA, nabumetone has a dose-related effect on platelet aggregation, but no effect on bleeding time in clinical studies. Furthermore, several short-term studies have shown little to no effect on renal function. Compared with COX-2 selective inhibitors, nabumetone exhibits similar anti-inflammatory and analgesic properties in patients with arthritis and there is no evidence of excess GI or other forms of complications to date.
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PMID:Nabumetone: therapeutic use and safety profile in the management of osteoarthritis and rheumatoid arthritis. 1545 29


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