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ID PMID Title PublicationDate abstract
9451669 Intragastric distribution of nonsteroidal anti-inflammatory drug-related ulcers in patient 1997 Dec During the long-term administration of nonsteroidal anti-inflammatory drugs (NSAIDs), approximately 3% of patients have gastric ulcers develop in each year. Although much is known about the endoscopic characteristics of NSAID-induced gastric ulcers in patients with rheumatoid arthritis (RA), it is not clear where in the stomach NSAIDs induce ulcers in patients without RA. We looked at that question. During the 1-year study period, 29 patients with gastric ulcer, who had been taking NSAIDs regularly for more than 4 weeks mainly for osteoarthritis, were identified. Seventy-five patients with gastric ulcers who had not taken NSAID also were found. The sites of gastric ulcers of these two groups were quite different. The NSAID-induced ulcers mainly were found in the gastric antrum, whereas the majority of NSAID-unrelated ulcers were in the gastric corpus. We conclude that NSAID-induced ulcers in non-RA patients mainly are formed in the gastric antrum.
9364836 Anemia secondary to low erythropoietin in a patient with normal renal function. 1997 Nov Anemia with a relatively low erythropoietin level has been described in several medical conditions associated with chronic inflammatory diseases such as rheumatoid arthritis, cancer, sickle cell disease, chronic renal failure, acquired immunodeficiency syndrome, and severe autonomic nervous system failure. This case report describes the development of anemia with a relatively low erythropoietin level in a 65-year-old man with non-insulin-dependent diabetes mellitus, normal renal function, and negative hematologic, thyroid, and autoimmune disease work-ups. The serum erythropoietin level was 14 mU/mL (N: 10-20 mU/mL). The hemoglobin was 7.5 g/dL and the hematocrit was 24%. The patient was treated with recombinant erythropoietin at 50 U/kg subcutaneously three times weekly. The hemoglobin level increased over a 4-week period. When erythropoietin was stopped, the anemia recurred in 2 months. We conclude that the patient's anemia was caused by a relative lack of endogenous erythropoietin release. The exact mechanism of this anemia is unknown. We recommend including a test for erythropoietin level in the evaluation of any unexplained anemia.
12973428 Nonsteroidal antiinflammatory agents. 1999 Apr Since the synthesis of aspirin in 1897, aspirin-like or nonsteroidal antiinflammatory drugs (NSAIDs) have been the mainstay of therapy for rheumatoid arthritis. Although of diverse chemical structure, these drugs not only exhibit the same antipyretic, analgesic and antiinflammatory therapeutic actions, but they also manifest identical toxic actions on the gastric mucosa and the kidney. This indicated that a single pharmacological effect was responsible for the properties of NSAIDs, a theory that was confirmed by the epochal discovery by Vane in 1971, that inhibition of the enzyme-producing prostanoids (cyclooxygenase [COX]) produced both the therapeutic and side effects of aspirin-like drugs. However, at equivalent antiinflammatory doses, different NSAIDs exhibited different degrees of toxicity. The reason for this was resolved by the discovery that prostaglandins at sites of tissue damage were synthesized by an inducible COX (COX-2) formed by a gene distinct from that producing the constitutive enzyme (COX-1), responsible for the formation of prostaglandins that serve an essential physiological function. Modification of the structure of drugs showing a moderately selective effect on COX-2, and the elucidation of the crystal structure of both enzymes, has paved the way for the synthesis of NSAIDs that are highly selective for the inducible enzyme and which are, therefore, antiinflammatory without the typical side effects of the classical NSAIDs. The focus on COX-2 has also expanded our knowledge of the pathophysiological significance of prostanoids and raised the possibility of new uses for selective COX-2 inhibitors, for example, in colon cancer, premature labor and possibly Alzheimer's disease. However, the clinical effects of chronic administration of potent, selective COX-2 inhibitors must await the results of ongoing clinical trials.
12531004 Sleep and pain. 2001 Oct Noxious stimuli and painful disorders interfere with sleep, but disturbances in sleep also contribute to the experience of pain.Chronic paroxysmal hemicrania and possibly cluster headaches are related to REM sleep. Whereas headache is associated with snoring and sleep apnea, morning headaches are not specific for any primary sleep disorder. Nevertheless, the management of the sleep disorder ameliorates both morning headache and migraine.Noxious stimuli administered into muscles during slow-wave sleep (SWS) result in decreases in delta and sigma but an increase in alpha and beta EEG frequencies during sleep. Noise stimuli that disrupt SWS result in unrefreshing sleep, diffuse musculoskeletal pain, tenderness, and fatigue in normal healthy subjects. Such symptoms accompany alpha EEG sleep patterns that often occur in patients with fibromyalgia. The alpha EEG patterns include phasic and tonic alpha EEG sleep as well as periodic K alpha EEG sleep or frequent periodic cyclical alternating pattern. Moreover, alpha EEG sleep, as well as sleep-related breathing disorder and periodic limb movement disorder, occur in some patients with fibromyalgia, rheumatoid arthritis and osteoarthritis. Depression and not alpha EEG sleep are features of somatoform pain disorder. Disturbances in sleep, pain behaviour and psychological distress influence return to work in workers who have suffered a soft tissue injury, e.g. low back pain. Patients with irritable bowel disorder have disturbed sleep and have increased REM sleep. In conclusion, there is a reciprocal relationship between sleep quality and pain. The recognition of disturbed or unrefreshing sleep influences the management of painful medical disorders.
11523172 [Swallowing rehabilitation in two elderly patients with cerebral infarction]. 2001 Jul We report two cases of cerebral infarction in which swallowing function improved following swallowing rehabilitation. Patient 1 was an 82-year-old man, who was admitted due to rheumatoid arthritis and multiple cerebral infarction, suffering from aspiration pneumonia. The abnormality of swallowing was assessed by the water swallowing test and videofluorography. It has been reported that videofluorography is useful in the diagnosis of aspiration. Three weeks after the start of swallowing rehabilitation, the serum level of inflammatory markers and the chest X-ray had returned to normal. His score on the water swallowing test had improved. Patient 2 was a 68-year-old [correction of 62] man, who was admitted with severe hemiplegia, dysphagia and dysarthria. One month after the swallowing rehabilitation, videofluorography showed that the magnitude of aspiration into the trachea had decreased and the pooling of barium in the piriform sinus had disappeared. The patient could begin taking a little food by mouth. These results suggest that swallowing rehabilitation will be affect the clinical improvement of swallowing function and help preventing aspiration pneumonia in our hospital.
11395845 Biological basis of anemia. 2001 Apr Anemia is a frequent complication in cancer, occurring in more than 50% of patients with malignancies. Several factors can cause anemia in these patients, such as blood loss, hemolysis, bone marrow infiltration, hypersplenism, and nutrient deficiencies. However, in a considerable number of patients, no cause other than malignant disease itself can be implicated. This cancer-related anemia is similar to the anemia observed in other chronic diseases, such as rheumatoid arthritis and some chronic infections. The syndrome of anemia of chronic disease is characterized by a hyporegenerative, normocytic, normochromic anemia associated with reduced serum iron and transferrin saturation but elevated (or normal) ferritin levels. Cancer-related anemia results from activation of the immune and inflammatory systems, leading to increased release of tumor necrosis factor, interferon-gamma, and interleukin-1. The cytokine-mediated relative failure of erythropoiesis has been further investigated, and three different mechanisms of action are proposed: (1) impaired iron utilization; (2) suppression of erythroid progenitor cells differentiation; and (3) inadequate erythropoietin production. In addition, the life span of red blood cells is shortened in cancer-related anemia and production cannot compensate sufficiently for the shorter survival time. Administration of recombinant human erythropoietin (r-HuEPO, epoetin alfa) can not only correct inadequate endogenous erythropoietin production, but also can overcome the suppression of erythroid progenitor cells and impairment of iron mobilization.
11063088 Liposteroid therapy for refractory seizures in children. 2000 Oct Liposteroid is dexamethasone palmitate incorporated into liposomes and was developed as an anti-inflammatory drug for targeting therapy mainly for rheumatoid arthritis. Recently, it was reported that liposteroid might be effective for the treatment of West syndrome, with fewer side effects than those of corticotropin therapy. We describe three patients, a 2-month-old boy with early infantile epileptic encephalopathy, a 4-month-old girl with symptomatic West syndrome, and a 2-year-old girl with symptomatic localization-related epilepsy, whose refractory seizures were treated with liposteroid according to the original method reported by Yamamoto and colleagues in 1998. Uncontrollable seizures ceased completely in two patients and the seizure frequency decreased markedly in the other patient. Electroencephalograms revealed marked improvement in all patients. They showed no relapse of the seizures, and all showed no adverse effects except for mild brain shrinkage in one patient. Our experience with these three patients suggests that liposteroid therapy might be a new option for the treatment of refractory seizures in children, as well as for West syndrome.
11022117 Cell contact-mediated signaling of monocytes by stimulated T cells: a major pathway for cy 2000 Sep T lymphocytes are currently thought to play a pivotal part in the pathogenesis of chronic inflammatory diseases. However, the mechanism(s) by which they exert their pathogenic effect remain(s) elusive. Contact-mediated signaling of monocytes by stimulated T cells is a potent pro-inflammatory mechanism that triggers massive up-regulation of the pro-inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-alpha) that play an important part in chronic destructive diseases such as rheumatoid arthritis and multiple sclerosis. To date cell-cell contact is the only endogenous mechanism to be described that displays such an activity in monocyte-macrophages which are classically stimulated in vitro by bacterial products such as LPS or non-specific stimuli such as phorbol esters or poorly activated by soluble cytokines such as IFN-gamma. Since direct cellular contact occurs at the inflammatory site, we hypothesized that this mechanism is relevant to the pathogenesis of chronic inflammatory disorders. This review aims at summarizing the state of the art and importance of contact-mediated monocyte activation by stimulated T lymphocytes.
10838733 [Endocrinology 1998-1999]. 2000 Mar 15 In the cascade hormone--second messenger--cellular G-proteins (GTP binding proteins), impairment can occur also at the last step: Mutant G-proteins may amplify the response (e.g. hypophyseal and thyroid adenomas) or reduce it (pseudohypoparathyreosis, testitoxicosis). Other new group of diseases appears to be anexinopathy: Among anexins belong also lippocortins and impairments occur in the hemocoagulation. "Reverse endocrinology" is a process description when the recognition of receptor (called an "orphan receptor") comes earlier than that of the hormone: Such receptors are known for several steroid hormones, retinoids and eicosanoids and it appears they are important also in the metabolism of cholesterol. A single antigen--glutamic acid decarboxylase (GAD), can cause autoimmune disease as the immuno-dependent diabetes (IDDM). Treatment of the skin T-cell lymphoma by some retinoids can result in hypothyroidism. Retrotransposones are example of the human genome modification with yet unknown clinical manifestations. Hepatocytal growth factor reveals to be the hope for treatment of cirrhosis. Search for effective peroral insulin substitutes is at present based on testing of various metabolites of fungi. Antibodies against TNF (tumor necrosis factor) become tested as "anti-cytokine therapy" in patients with rheumatoid arthritis. Some other suggestions for new ways of treatment is also listed, including the intranasal administration of estradiol.
10548136 Medical illness in patients with schizophrenia. 1999 Research into the relationship between physical illness and schizophrenia has revealed that patients with schizophrenia may be at decreased risk for certain disorders, such as rheumatoid arthritis and allergies, but at increased risk for others, including substance abuse and polydipsia. Although such knowledge may ultimately help determine the underlying causes of schizophrenia, the principal concern of practicing clinicians should be to diagnose and treat medical comorbidity in individual patients. Nearly 50% of patients with schizophrenia have a comorbid medical condition, but many of these illnesses are misdiagnosed or undiagnosed. A fragmented health care system, lack of access to care, patient inability to clearly appreciate or describe a medical problem, and patient reluctance to discuss such problems all contribute to the lack of attention to medical problems in patients with schizophrenia. Psychiatrists and primary care practitioners who treat patients with schizophrenia should make an effort to uncover medical illnesses by using a structured interview or routine physical examination whenever a patient is seen for care.
10411375 Clinical aspects, outcome assessment, disease course, and extra-articular features of spon 1999 Jul Much has been written over the years regarding the clinical aspects and disease course of the spondyloarthropathies, but publications relating to outcome assessment that attempt to relate measures of process with outcome are few. Extra-articular features of the spondyloarthropathies, eg, uveitis, colitis, and aortitis, are well described, but in the past few years there has been an increasing interest in the incidence of osteoporosis in this group of patients, particularly those with ankylosing spondylitis. In rheumatoid arthritis functional indices have been developed, such as the Health Assessment Questionnaire score, which has been shown to be robust in monitoring response to therapy, but the situation is quite different in a condition such as ankylosing spondylitis. In the last few years a number of functional indices have been developed that are now beginning to be applied to monitor response to treatment in the spondyloarthropathies. The impact of ankylosing spondylitis in women is an area that has been neglected in the past, and a recent review addresses the effects of the disease on the reproductive capacity in women. This overall review of the past year's publications from the clinical aspects of ankylosing spondylitis confirms that clinical research still has much to contribute to this fascinating group of disorders.
10389502 Influence of cigarette smoking on Vitamin C, glutathione and lipid peroxidation status. 1998 Jan There has been a growing interest during recent years in the role of free radicals and lipid-peroxidation at tissue-level for the causation of cancer and other age-related diseases like atherosclerosis, rheumatoid arthritis, cataract etc. Free radicals and increased lipid peroxidation play a significant role for causation of human diseases by oxidative damage and functional degeneration of the tissues. Vitamin C, a well-known dietary antioxidant, and other enzymatic antioxidants like glutathione can protect the lipids of lipoproteins and other biomembranes against peroxidative damage by intercepting oxidants before they can attack the tissues. But cigarette smoking was found to affect the antioxidant protective action of Vitamin C, glutathione etc. A group of adult male smokers in this study were found to have lowered Vitamin 'C' & glutathione levels, but increased lipid-peroxide levels in their blood. Thus the increased pathogenicity of the smoking may also be due to indirect biochemical effect of enhanced oxidative stress by increased lipid-peroxidation and lowered Vitamin C & other antioxidants at tissue-level.
10332060 Microporous membrane drug delivery system for indomethacin. 1999 Jun 2 Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of rheumatoid arthritis for more than a decade. The high incidence and severity of side effects, which are dose-related and associated with long-term administration, have limited its use. This has led to the search for new delivery systems which can overcome the side effects by controlling the drug release. In this study, Indomethacin Extended Release Formulation was developed by pelletization using the method of extrusion/spheronization. The drug containing pellets were further coated to achieve the required release profile as per USP. Coating systems developed on the principle of microporous membrane drug delivery using soluble salt gave the best results.
10225705 Therapeutic cytapheresis for inflammatory bowel disease. 1998 May Cytapheresis therapy has recently been investigated as a treatment for several diseases, especially autoimmune related diseases such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease. The removal of leukocyte components has been performed by the centrifugal method; however, using fiber technology or column technology, leukocyte components can be removed simply, and these technologies are more effective than the centrifugal method in removing numbers of cells. Each of 3 types of leukocytapheresis methods removes a different kind of cell in its therapeutic principle. Thus, if we understand what kind of cells should be removed, we can choose the best method for removing leukocytes. For this reason, the authors propose an international standard for unifying names. The therapy that makes use of a centrifuge to selectively remove about 40% of neutrophils and more than 60% of lymphocytes may be called a lymphocyte removal therapy, lymphocytapheresis (LCA). Using cellulose acetate beads in a G-1 granulocyte removal column, granulocytes and monocytes are removed but not lymphocytes, so we suggest calling this granulocytapheresis (GCAP). In addition, using a leukocyte removal filter, the Cellsorba leukocyte removal filter, 99% of both granulocytes and monocytes and about 70% of lymphocytes are removed. We propose calling this leukocytapheresis (LCAP). In the near future, we hope that we will be able to select one of these methods for cytapheresis for each disease pathogenesis or cellular immune abnormality. Presently, a lot of research is on-going to analyze how cytapheresis is effective for the immune related diseases. The mechanism of cytapheresis will be clarified by investigators. We strongly believe that cytapheresis therapies offer good news to those patients suffering from incurable diseases as well as their physicians.
10219652 Oral tolerance in the treatment of inflammatory autoimmune diseases. 1999 Mar Oral tolerance refers to the oral administration of protein antigens, which induces a state of systemic nonresponsiveness specific for the fed antigen. This method of inducing immune non-responsiveness has been applied to the prevention and treatment of experimental animal models of autoimmune disease. Extensive research in this area over the past ten years has led to the conclusion that two mechanisms are operative in the mediation of oral tolerance--active suppression and clonal anergy/deletion. A number of factors have been identified that determine which mechanism of tolerance is operative--antigen dose, antigen form, and the timing of antigen administration. Work from these animal models has recently been extended into human clinical trials of multiple sclerosis, rheumatoid arthritis, diabetes, uveitis, and allergy, with differing degrees of success. In this review, a discussion is provided of the animal model systems where oral tolerance has been applied and the clinical trials where an oral tolerization approach has been attempted. Moreover, recent mechanistic studies are reviewed and a model proposed for the induction of oral tolerance.
10065357 Evaluation of Eudragit RS-PO and Ethocel 100 matrices for the controlled release of lobenz 1999 Feb Lobenzarit disodium is a drug for the treatment of rheumatoid arthritis. In this work, inert matrix tablets of lobenzarit disodium were prepared by direct compression using Ethocel 100 and Eudragit RS-PO as polymeric materials in different ratios. The obtained powder mixtures and tablets were evaluated from the rheological and technological points of view. The dissolution test was performed to evaluate the in vitro release kinetic of the matrices. The obtained dissolution profiles demonstrated that the matrices containing Eudragit RS-PO showed a slower release rate and therefore were more suitable for controlling the release of drug. The fit to the Higuchi model indicates that the drug release mechanism from these matrices was controlled by the diffusion step.
9814003 [Fibrinolytic system and a central retinal vein thrombosis]. 1998 On the basis of literature review the role of fibrinolysis in the pathogenesis of central retinal vein thrombosis is presented. It has been proved by many authors that fibrinolytic activity is depressed in patients with vascular thrombosis, due to increased levels of fibrinolytic inhibitors mainly plasminogen activator inhibitor (PAI 1), and/or decreased levels of tissue plasmogen activator (t-PA). Low levels of t-PA and increased levels of PAI-1 have been found in states of special risk of thrombosis: obesity, diabetes mellitus, postoperative states, rheumatoid arthritis, malignancies and other diseases such as Behcet's syndrome. In pregnancy susceptibility to thrombosis follows the presence in blood of PAI-2, an inhibitor of plasminogen activators secreted by the placenta. Therapy is based on the use of anticoagulants (e.g. heparin) and thrombolytic agents (e.g. streptokinase).
9703150 Thrombocytopenia after a single test dose of methotrexate. 1998 Aug Low dose methotrexate (MTX) can cause numerous gastrointestinal, pulmonary, central nervous system, and hematologic toxicities. Risk factors include folate deficiency, decreased renal function, older age, increased mean corpuscular volume or concomitant use of trimethoprim-sulphamethoxazole, probenecid, or nonsteroidal antiinflammatory drugs (NSAIDs). We describe a case of isolated thrombocytopenia after a single oral dose of MTX in a 36-year-old woman with sarcoidosis. She had rheumatoid arthritis and her only other medications included NSAIDs. One week after her first oral dose of 7.5 mg MTX, diffuse petechiae developed on her chest, abdomen, and extremities; she had a platelet count of 25,000/mm3. Nine days after discontinuation of both MTX and the NSAID, her platelet count increased to 189,000/mm3.
9073361 Resolution of recombinant human interleukin 10 from variants by recycling free flow focusi 1997 Mar 15 Recombinant human interleukin 10 (rhIL-10) is a potential human therapeutic agent for treating inflammatory bowel diseases and rheumatoid arthritis. The rhIL-10 molecule derived from Escherichia coli including bodies consists of two identical subunits forming a noncovalent dimer. Since the ability to separate rhIL-10 from closely related impurities was highly desirable, recycling free flow focusing (RFFF) was utilized for the purification process development of rhIL-10. Under nondenaturing conditions, RFFF was able to separate rhIL-10 from fractions enriched in rhIL-10 variants. Three major monomeric variants (A, B, and C) can be identified and quantitated by reversed phase HPLC. The isoelectric point (pI) of rhIL-10 was empirically determined to be 8.2 while that for the three variant populations were in the range 7.3-7.5. Knowledge of these pI's would potentially facilitate the optimization process for ion-exchange chromatography. Furthermore, the technique provided a mild and fast preparation procedure for obtaining the recombinant protein and its variants for further characterization, as evidenced in the separation of rhIL-1- from variant C by successive RFFF treatments.
9029043 Disposition and metabolism of tenidap in the rat. 1997 Feb Tenidap is a new antirheumatic drug currently undergoing clinical evaluation. It inhibits production and activity of cytokines in vivo and causes significant reductions in plasma markers of disease activity in rheumatoid arthritis. After the oral administration of C-14 labeled tenidap, bile, urine and plasma were examined by HPLC and atmospheric pressure tandem mass spectrometry. Label is excreted primarily in bile/feces and the remainder in urine, with good recoveries. Numerous metabolites were identified and the structures of most were confirmed by comparison with authentic synthetic samples. Hydroxylation in several positions on both the oxindole and thienyl rings of tenidap represents the major routes of metabolism; most of these metabolites are subsequently conjugated. The glucuronide of 5'-hydroxytenidap, excreted primarily in bile, is the major metabolite, constituting about one third of the oral dose recovered. Other pathways include dihydroxylation and methoxylation on the thienyl ring. An unusual reduction of hydroxytenidap took place, resulting in the formation of a novel thiolactone analog. Anaerobic incubation with rat cecal contents generated the thiolactone metabolite, suggesting the involvement of gut microflora.