Multidrug resistance-1 (MDR-1) in rheumatic autoimmune disorders. Part I: Increased P-glycoprotein activity in lymphocytes from rheumatoid arthritis patients might influence disease outcome.

BACKGROUND: Multidrug resistance (MDR) is characterized by overexpression of P-glycoprotein, a pump molecule that decreases intracellular drug concentrations by increasing drug efflux from cells. OBJECTIVE: To look for correlations between clinical status and P-glycoprotein activity and/or TNF-alpha mRNA levels in patients with rheumatoid arthritis. METHODS: Sixteen patients were studied. Based on response to therapy, eight were refractory and eight nonrefractory to treatment. Findings were compared to those in 24 healthy controls. Flow cytometry was used to evaluate P-glycoprotein activity in peripheral blood mononuclear cells isolated by gradient centrifugation and incubated with the P-glycoprotein substrate daunorubicin. TNF-alpha mRNA levels were determined using quantitative PCR. RESULTS: Patients with rheumatoid arthritis showed an increased number of lymphocytes with high P-glycoprotein activity (p = 0.0001) as compared to the normal controls. P-glycoprotein activity was higher in the refractory than in the non-refractory patient subgroup (p = 0.006). Also, TNF-alpha mRNA levels were markedly higher in the refractory subgroup than in the nonrefractory subgroup, and were undetectable in the normal controls. CONCLUSIONS: Enhanced P-glycoprotein activity may be closely related to an unfavorable clinical course and a poor response to treatment. Increased TNF-alpha expression and chronic exposure to various drugs, including glucocorticoids, may contribute to increase P-glycoprotein activity. Both high P-glycoprotein activity and excessive amounts of TNF-alpha seem associated with poor outcome in rheumatoid arthritis.

Mycobacterium tuberculosis infection in patients with systemic rheumatic diseases. A case-series.

OBJECTIVE: To describe the clinical characteristics of patients with systemic rheumatic diseases and tuberculosis. A retrospective case series from 1987 to 1994, drawn from a tertiary-care hospital in Mexico City, was studied. RESULTS: Thirty patients were included (20 women, 10 men), with mean age of 39.8 years (range 14-66), and a mean duration of the systemic rheumatic disease of 44 months (1-372). The rheumatic diseases included systemic lupus erythematosus (SLE) (n = 13), rheumatoid arthritis (7), polymyositis or dermatomyositis (5), and other diseases (5). During the six months previous to the diagnosis of tuberculosis, 22 patients had received corticosteroids, and 13 others immunosuppressants. Mycobacterium tuberculosis was isolated from 18 patients. Pulmonary tuberculosis was found in 10 patients, and extrapulmonary tuberculosis in 20, seven of these with miliary disease. SLE was seen in 6 of the patients with miliary tuberculosis. The clinical manifestations were: fever (67%), weight loss (67%), diaphoresis (60%), cough and sputum (53%), lymph node enlargement (43%), and dyspnea (33%). Sixteen patients had an abnormal chest film. Of 18 patients tested by PPD RT-2, 8 had an induration > 10 mm. Patients were initially treated with 3 or 4 anti-tuberculosis drugs for 15 days to 6 months, followed by 6 to 10 months of isoniazid plus rifampicin. Three relapsed, and 2 died of respiratory failure. CONCLUSIONS: This case series showed a particular pattern of tuberculosis in patients with systemic rheumatic diseases.

Tuberculosis prophylaxis in patients with steroid treatment and systemic rheumatic diseases. A case-control study.

OBJECTIVE: The aim of this study was to assess the impact of isoniazid prophylaxis in patients with systemic rheumatic diseases who attended a teaching hospital in Mexico City between 1987 and 1992. METHODS: In this case-control study, patients with systemic rheumatic diseases and tuberculosis (cases) were compared with patients with systemic rheumatic diseases without tuberculosis (controls). The groups were matched by year of hospital admission and rheumatic disease. Clinical charts were reviewed for: 1) isoniazid prophylaxis, defined as the administration of isoniazid 300 mg/day for 6 or more months in patients with exposure to steroids (prophylaxis with isoniazid was defined as complete, incomplete or any prophylaxis); 2) exposure to steroids: defined as the administration of prednisone > 15 mg/day (or its equivalent of another steroid) for 3 or more months before tuberculosis or recruitment into the study; 3) exposure to immunosuppressants, defined as the administration of any dose of azathioprine, methotrexate, cyclophosphamide, and/or 6-mercaptopurine, before tuberculosis in the cases or recruitment date in the controls; 4) reactivity to PPD; and 5) other relevant variables. RESULTS: Twenty cases and 66 controls were studied. A 70% decrease in the risk of developing tuberculosis was found among patients who received any prophylaxis with isoniazid as compared to controls: OR 0.31, 95% CI 0.09-0.98, p = 0.03. A 97% decrease was seen in those patients who received complete prophylaxis: OR 0.034, 95% CI 0.0001-0.216, p < 0.0001. The protective effect of complete prophylaxis persisted even after controlling for other potential confounders, such as age, gender, rheumatic disease, duration of rheumatic symptoms, and exposure to steroids and/or immunosuppressants. CONCLUSION: The results of this study suggest that in countries with a high prevalence of tuberculosis the use of isoniazid (300 mg/day for 6 months) in rheumatic patients with exposure to prednisone (> 15 mg/day for three or more months) may be useful to prevent tuberculosis, independently of the results of the PPD reactivity test. However, a controlled clinical trial will be required to confirm these results.

Risk factors for operative morbidity in patients with systemic lupus erythematosus: an analysis of 63 surgical procedures.

The surgical morbidity rate of patients with Systemic Lupus Erythematosus is considered very high; however, the experience in the literature is small. This study will determine the rate of surgical morbidity and the existence of predictive factors in patients with such a disease. The medical records of 53 patients with Systemic Lupus Erythematosus who underwent 63 major operations were analyzed retrospectively. The rate and causes of operative morbidity were registered. Univariate and multivariate statistical analysis was performed to ascertain the existence of predictive factors for morbidity. The overall morbidity and mortality were 16% and 6% respectively. Lymphopenia, hypoalbuminemia, increased SGOT and SGPT, urgent indication of operation, the physical status of the American Society of Anesthesiology, as well as a shorter duration of Systemic Lupus Erythematosus showed a significant correlation with operative morbidity in the univariate analysis; high blood urea nitrogen showed marginal significance. Physical status, urgent indication, and blood urea nitrogen remained as significant variables with the multivariate logistic regression analysis. The surgical morbidity rate of these patients may be lower than previously estimated. The physical status, urgency of operation, and level of blood urea nitrogen seemed to be the most useful independent predictors for surgical morbidity risk in patients with Systemic Lupus Erythematosus.

[Iatrogenic trends as indicator of clinical competence in courses of specialization in medicine]. / Tendencias iatrogénicas como indicador de competencia clínica en los cursos de especialización en medicina.

Iatrogenesis, understood here as an unfavourable effect to the health of patients provoked by the medical institution, has risen little interest in the researchers of the health area in spite of its growing presence. The present study had the aim of exploring the iatrogenic behavior of 659 recently graduated physicians by a questionnaire composed by clinical cases which described diagnostic and/or therapeutic situations that required the making of decisions. The questionnaire consisted of 600 general medical knowledge questions of which 112 explored commission of iatrogenic behavior. The group showed a iatrogenicity index of 39.5% ranging between 15.2% and 74.1%. When this iatrogenicity index was compared to that of global medical knowledge (600 questions) no correlation was found. It is concluded that the "iatrogenicity" index of this group is high and lacks correlation with the global medical knowledge. This suggests that the individualized and careful use of the diagnostic and therapeutic resources suitable for specific situations in patients does not receive sufficient emphasis during the teaching-learning process nor does it play a prominent role within the priorities of knowledge that are learned in the school of medicine. The need to deepen our understanding of the iatrogenic behavior of the physicians at different levels of their professional training is emphasized.

Deforming arthropathy of the hands in systemic lupus erythematosus.

Forty-one of 858 patients with systemic lupus erythematosus (SLE) developed clinical deformity of their hands. This deformity was clinically and radiologically different from that found in 40 patients with classical or definite rheumatoid arthritis (RA), and tended to appear early in the course of disease. Characteristics of this arthropathy included nonerosive carpal collapse; exceptional erosion of the styloid processes; Z deformity of the thumb; nonerosive ulnar deviation and subluxation of MCP joints; parametacarpophalangeal joint hook formation; scant and asymmetric joint erosions; and swan neck deformity of the fingers. Most of these changes seemed to be due to involvement of the ligaments rather than to the destructive effect of synovitis. Patients with SLE with deforming arthropathy had a higher frequency of rheumatoid factor positivity, sicca symptoms and antibodies to native DNA, whereas they had lower incidence of facial rash and photosensitivity than did those without. Other manifestations did not differ. We propose that most patients with SLE with deforming arthropathy belong to a subset of SLE rather than representing the coexistence of SLE and RA.

Changes in anti-lymphocyte and anti-Ia antibodies during pregnancy in systemic lupus erythematosus.

Anti-lymphocyte antibodies reactive with monocyte-depleted lymphocytes, T cells, or B cells were studied in 43 nonpregnant and 23 pregnant systemic lupus erythematosus (SLE) patients. Anti-Ia specificity was assayed in an enzyme-linked immunosorbent assay system. No difference in mean lymphocytotoxicity was noted between pregnant and nonpregnant SLE patients; however, anti-Ia lymphocyte antibody associated with disease activity was lower (P less than 0.01) in pregnant than in nonpregnant SLE patients. Lymphocytotoxic or anti-Ia antibody activity did not reliably predict the outcome of individual pregnancies.

Fatal pulmonary hemorrhage in systemic lupus erythematosus. Occurrence without hemoptysis.

We describe 12 patients with systemic lupus erythematosus (SLE) who developed massive pulmonary hemorrhage with very active disease. Other causes of pulmonary bleeding were excluded. Eleven of the 12 patients died, but only 4 had hemoptysis. Massive pulmonary hemorrhage should be suspected, even in the absence of hemoptysis, in severely ill patients with lupus who develop acute respiratory distress with bilateral pulmonary infiltrates and a drop in hemoglobin of 3 or more g/dl. Because of the deadly nature of this complication of SLE, when it is suspected, intensive corticosteroid and immunosuppressive treatment should be instituted.

A multi-systemic disease (lupus-like) preceding bronchioloalveolar carcinoma.

A patient with a multi-systemic disease (lupus-like) that preceded the onset of a bronchioloalveolar carcinoma is described, and a brief review of the literature is presented. We suggest that this tumor be listed among the neoplasms responsible for multi-systemic diseases with lupus-like characteristics.

Involvement of the urinary bladder in systemic lupus erythematosus. A pathologic study.

Urinary bladder histologic changes were found in 16 of 35 necropsies from systemic lupus erythematosus (SLE) patients in whom adequate material was available for study. These included interstitial cystitis (n = 11), hemorrhage (n = 9), congestion (n = 7), vasculitis (n = 5), and perivenular infiltrate (n = 4). Abnormalities were found in only 5 of 30 control necropsies from patients with other diseases and in 4 of them these were hemorrhagic and chiefly due to indwelling catheters. SLE patients with histologic bladder changes were found to have pulmonary hemorrhage more frequently than those without. This suggests a common pathogenetic mechanism between interstitial cystitis and pulmonary hemorrhage in SLE.

Immunologic studies in patients with Takayasu's arteritis. II. Effects of serum on lymphocyte functions in vitro.

Natural lymphocytotoxic antibodies, circulating immune complexes and their effect on in vitro blast transformation of normal cells were studied in 24 patients with Takayasu's arteritis. Sera with Takayasu's arteritis lacked lymphocytotoxic antibodies, had an inhibitory effect on the formation of EA and EAC rosettes and interfered with normal lymphocyte function in vitro. The absence of lymphocytotoxic antibodies, together with the other epidemiological and histocompatibility studies, would support the notion that Takayasu's arteritis and temporal arteritis are two distinct entities.