Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients. (57/22207)

OBJECTIVE: To retrospectively analyze the clinical symptoms, laboratory findings, and outcomes in patients with microscopic polyangiitis (MPA) who were enrolled in various clinical trials conducted by the French Vasculitis Study Group. METHODS: A cohort of 85 patients meeting the Chapel Hill criteria for MPA participated in the study. Seventy-one of them were included in prospective therapeutic trials. Eighty-one diagnoses were biopsy proven. In the other patients, diagnosis was based on clinical findings. RESULTS: Forty-seven men and 38 women, with a mean +/- SD age of 56.8 +/- 14.6 years, met the criteria for MPA. Their main clinical symptoms were renal manifestations (78.8%), weight loss (72.9%), skin involvement (62.4%), fever (55.3%), mononeuritis multiplex (57.6%), arthralgias (50.6%), myalgias (48.2%), hypertension (34.1%), lung involvement (24.7%; alveolar hemorrhage 11.8%), and cardiac failure (17.6%). The mean +/- SD serum creatinine level before treatment was 2.59 +/- 2.96 mg/dl; 47 patients had renal insufficiency (serum creatinine > 1.36 mg/dl). Eight patients underwent dialysis at the time of diagnosis, and long-term dialysis was necessary for 10 patients. Antineutrophil cytoplasmic antibodies (ANCA) were present in 38 of 51 patients (74.5%), of whom 33 had a perinuclear staining pattern (pANCA) and 5 had a cytoplasmic pattern. Antibodies to proteinase 3 were present in 4 patients and antibodies to myeloperoxidase were detected in 31, as determined by enzyme-linked immunosorbent assay. Of the 30 patients who underwent renal and celiac angiography, 4 had microaneurysms. Of the 29 patients (34.1%) who had relapses, 8 died during or after the relapse. During followup, 28 of the 85 patients (32.9%) died. The mean +/- SD duration of followup of the group was 69.9 +/- 60.6 months. Deaths were less frequent when patients had been treated with steroids and immunosuppressive drugs (13 patients [24.1%]) than with steroids alone (15 patients [48.4%]) (P < 0.01). The 5-year survival rate was 74%. CONCLUSION: This study demonstrated that MPA is a multisystemic disease in which renal symptoms are frequent, but the disease is also associated with general symptoms, arthritis, mononeuritis multiplex, and other manifestations that are also seen in various vasculitides. The rarity of abnormal angiogram findings and the high frequency of pANCA are characteristic of MPA. In most cases, the outcome is comparable with those of other systemic vasculitides, but relapses are frequent.  (+info)

Changes in joint cartilage aggrecan after knee injury and in osteoarthritis. (58/22207)

OBJECTIVE: To determine the concentrations of aggrecan fragments in synovial fluid from patients with knee joint injury, osteoarthritis (OA), or acute pyrophosphate arthritis (PPA; pseudogout), and to test their relative reactivity with the 846 epitope, a putative marker of cartilage aggrecan synthesis. METHODS: Samples of knee joint fluid from 385 patients and 9 healthy-knee volunteers were obtained in a cross-sectional study. Study groups were acute PPA/ pseudogout (n = 60), anterior cruciate ligament (ACL) rupture (n = 159), meniscus lesion (n = 129), and primary knee OA (n = 37). The 846 epitope on aggrecan was assayed by competitive solution-phase radioimmunoassay. Aggrecan fragments were assayed by enzyme-linked immunosorbent assay using a monoclonal antibody (1-F21). Cartilage oligomeric matrix protein (COMP), C-propeptide of type II collagen (CPII), bone sialoprotein, matrix metalloproteinases 1 and 3, and tissue inhibitor of metalloproteinases 1 were previously quantified by immunoassays. RESULTS: Reactivity of the 846 epitope was increased in all study groups compared with the reference group, and was highest in patients with primary OA. The median levels (in microg fetal aggrecan equivalents/ml) of the epitope were 0.28 (range 0.24-0.47) in the reference group, 0.48 (range 0.26-1.32) in PPA/pseudogout, 0.61 (range 0.12-2.87) in ACL rupture, 0.53 (range 0.22-3.02) in meniscus lesion, and 0.68 (range 0.31-4.31) in primary OA. The 846 epitope reactivity per microg aggrecan fragments in the joint fluid was higher in late-stage OA than in early-stage OA. Epitope 846 reactivity correlated positively with several markers of matrix turnover, particularly with COMP (r(s) = 0.421) and CPII (r(s) = 0.307). CONCLUSION: The observed differences in 846 epitope reactivity in synovial fluid, and its concentration in relation to aggrecan and other markers of matrix turnover, were consistent with marked ongoing changes in aggrecan turnover after joint injury and in the development of OA. OA is thus a disease characterized by dynamic changes in tissue macromolecule turnover, which is reflected by measurable changes in aggrecan epitopes in the synovial fluid.  (+info)

Epidemiological analysis of site relationships of synchronous and metachronous multiple primary cancers in the National Cancer Center, Japan, 1962-1996. (59/22207)

BACKGROUND: Multiple primary cancer (MPC) has been recognized as a problem commonly encountered in routine medical practice. A study of MPC is necessary not only to provide insights into the etiology of cancer, but also to provide information for effective medical care by clinical oncologists. METHODS: A cohort of 49,751 cancer patients who were admitted to the National Cancer Center Hospital between 1962 and 1996 was used to study the site relationship of MPC. Logistic and Poisson regression analyses using an internal reference group within the cohort were applied for the calculation of the prevalence odds ratio (POR) for site relationships of synchronous MPC and the incidence rate ratio (IRR) for those of metachronous MPC. RESULTS: Three site combinations with elevated risks for both synchronous and metachronous MPCs, eight with elevated risk for synchronous MPC, five with elevated risk for metachronous MPC and six with decreased risk for synchronous MPC were identified with statistical significance. Among them, the increased risk of metachronous stomach cancer following lymphoma and myeoloma (POR = 1.0 and 1.1, P > 0.05; IRR = 2.5, P < 0.05) and the inverse site-correlation of synchronous MPC between [trachea, bronchus and lung] and other sites of the upper aerodigestive tract [lip, oral cavity and pharynx] (POR = 0.5 and 0.3, P < 0.05) and esophagus (POR = 0.7 and 0.3, P < 0.05) have not been reported previously. CONCLUSIONS: Our results suggest that interventions for lymphoma and myeloma might affect the development of subsequent stomach cancer and additional etiological factors other than tobacco smoking are associated with the development of cancer in the upper aerodigestive tract.  (+info)

Serum levels of ochratoxin A in healthy adults in Tuscany: correlation with individual characteristics and between repeat measurements. (60/22207)

Ochratoxin A (OTA), a mycotoxin widely contaminating staple foods and beverages, has been classified as a "possible human carcinogen (Group 2B)" by the IARC. Serum levels of OTA were measured in a group of 138 healthy adults (age, 35-65 years) living in the area surrounding Florence (Tuscany, central Italy) and detected in all but four samples (97%). After the exclusion of one subject with a peak value of 57.2 ng/ml, OTA levels ranged between 0.12 and 2.84 ng/ml, with mean and median values of 0.56 and 0.48 ng/ml, respectively. OTA levels were significantly higher in men than in women (0.64 versus 0.50) and correlated positively with height. A strong association was found with the season in which blood samples were obtained, with summer values higher than autumn values. On the other hand, OTA levels tended to be negatively associated with blood pressure, either systolic or diastolic; no association was evident with age, weight, body mass index, and smoking history. The associations with height and season persisted in a multivariate regression analysis. A subgroup of subjects provided a repeat blood sample approximately 1 year later. The Spearman correlation coefficient between 68 pairs of original and repeat measurements was practically null (r = 0.05). Only two subjects (2.9%) had OTA levels of >1 ng/ml on both occasions. These results suggest that OTA contamination is widespread in foods consumed by this population, in agreement with previous reports from Italy and other countries. A strong seasonal variation, which possibly differs from year to year, was observed. OTA serum levels are a short-term biomarker with a high within-subject variability; therefore they have limited use at the individual level but can be used to characterize populations or subgroups of subjects. Additional analyses are needed to explore the dietary determinants of OTA levels in this population.  (+info)

Who bears the burden of Medicaid drug copayment policies? (61/22207)

This DataWatch examines the impact of Medicaid prescription drug copayment policies in thirty-eight states using survey data from the 1992 Medicare Current Beneficiary Survey. Findings indicate that elderly and disabled Medicaid recipients who reside in states with copay provisions have significantly lower rates of drug use than their counterparts in states without copayments. After controlling for other factors, we find that the primary effect of copayments is to reduce the likelihood that Medicaid recipients fill any prescription during the year. This burden falls disproportionately on recipients in poor health.  (+info)

Molecular evolution of swine vesicular disease virus. (62/22207)

Phylogenetic analysis was used to examine the evolutionary relationships within a group of coxsackie B viruses that contained representatives of the major serotypes of this group and 45 isolates of swine vesicular disease virus (SVDV) from Asia and Europe. Separate analyses of sequence data from two regions of the viral genomes encoding the VP1 and 3BC genes both revealed that the SVDV belonged to a single monophyletic group which could be clearly distinguished from all other sampled coxsackieviruses. Regression analysis revealed that within the SVDV clade at least 80% of the synonymous variation in evolutionary divergence between isolates was explained by time, indicating the existence of an approximate molecular clock. Calibration of this clock according to synonymous substitutions per year indicated the date of occurrence of a common ancestor for the SVDV clade to be between 1945 and 1965.  (+info)

Determinants of an impaired quality of life five years after coronary artery bypass surgery. (63/22207)

OBJECTIVE: To identify determinants of an inferior quality of life (QoL) five years after coronary artery bypass grafting (CABG). SETTING: University hospital. PARTICIPANTS: Patients from western Sweden who underwent CABG between 1988 and 1991. MAIN OUTCOME MEASURES: Questionnaires for evaluating QoL before CABG and five years after operation. Three different instruments were used: the Nottingham health profile (NHP), the psychological general wellbeing index (PGWI), and the physical activity score (PAS). RESULTS: 2121 patients underwent CABG, of whom 310 died during five years' follow up. Information on QoL after five years was available in 1431 survivors (79%). There were three independent predictors for an inferior QoL with all three instruments: female sex, a history of diabetes mellitus, and a history of chronic obstructive pulmonary disease. Multivariate analysis showed that a poor preoperative QoL was a strong independent predictor for an impaired QoL five years after CABG. An impaired QoL was also predicted by previous disease. CONCLUSIONS: Female sex, an impaired QoL before surgery, and other diseases such as diabetes mellitus are independent predictors for an impaired QoL after CABG in survivors five years after operation.  (+info)

Quality of life four years after acute myocardial infarction: short form 36 scores compared with a normal population. (64/22207)

OBJECTIVES: To assess the impact of myocardial infarction on quality of life in four year survivors compared to data from "community norms", and to determine factors associated with a poor quality of life. DESIGN: Cohort study based on the Nottingham heart attack register. SETTING: Two district general hospitals serving a defined urban/rural population. SUBJECTS: All patients admitted with acute myocardial infarction during 1992 and alive at a median of four years. MAIN OUTCOME MEASURES: Short form 36 (SF 36) domain and overall scores. RESULTS: Of 900 patients with an acute myocardial infarction in 1992, there were 476 patients alive and capable of responding to a questionnaire in 1997. The response rate was 424 (89. 1%). Compared to age and sex adjusted normative data, patients aged under 65 years exhibited impairment in all eight domains, the largest differences being in physical functioning (mean difference 20 points), role physical (mean difference 23 points), and general health (mean difference 19 points). In patients over 65 years mean domain scores were similar to community norms. Multiple regression analysis revealed that impaired quality of life was closely associated with inability to return to work through ill health, a need for coronary revascularisation, the use of anxiolytics, hypnotics or inhalers, the need for two or more angina drugs, a frequency of chest pain one or more times per week, and a Rose dyspnoea score of >/= 2. CONCLUSIONS: The SF 36 provides valuable additional information for the practising clinician. Compared to community norms the greatest impact on quality of life is seen in patients of working age. Impaired quality of life was reported by patients unfit for work, those with angina and dyspnoea, patients with coexistent lung disease, and those with anxiety and sleep disturbances. Improving quality of life after myocardial infarction remains a challenge for physicians.  (+info)