We studied 71 patients with acute Yersinia infection for the occurrence of pathologic urinary and renal findings. Transient proteinuria and/or microhematuria was found in 17 patients (24%) and slightly elevated serum creatinine in seven patients (10%). Renal biopsy was done in two patients and revealed mild mesangial glomerulonephritis in both cases. One of these patients had IgA glomerulonephritis and Reiter's syndrome. Pyuria occurred in 16 patients (23%) and was frequently associated with Reiter's syndrome. Seventy-three patients with acute intrinsic renal failure were studied for the occurrence of acute Yersinia infection by determining Yersinia antibodies by ELISA. One out of 13 patients with acute glomerulonephritis but none of 60 patients with acute tubulointerstitial renal disease had acute Yersinia infection. Acute Yersinia infection seems to be rarely an etiologic factor in acute intrinsic renal failure. Our results indicate that transient proteinuria, microhematuria, pyuria or impaired renal function are frequent findings in patients with acute Yersinia infections. However, glomerulonephritis seems to be a rather infrequent and mild complication of acute Yersinia infection.

Systemic lupus erythematosus, an autoimmune disorder which predominantly affects young women, is frequently complicated by renal involvement. Lupus nephritis (LN) is characterized by immune-complex mediated glomerular and tubulointerstitial inflammation Ieading to chronic renal insufficiency in up to 30% affected patients. In patients with suspected lupus nephritis, renal biopsy may be used to confirm the diagnosis and determine appropriate therapy. The ISN/RPS classification of LN represents a significant advance over the 1982 WHO scheme. The treatment of lupus nephritis often consists of a period of intensive immunosuppressive therapy (induction therapy) followed by a period of less intensive maintenance therapy. The established treatment of lupus nephritis with cyclophosphamide and steroids has improved the outcome of LN but is burdened with significant adverse effects. Results of clinical studies showed that mycophenolate mofetil is equally effective with fewer toxic complications than standard therapy, but its long-term efficacy is not yet known. New therapeutic agents (biologic drugs) targeted to the pathogenetic mechanism of the disease are promissing improved efficacy with less toxicity. Despite recent advances, treatment of lupus nephritis remains a challenging clinical problem.

Objective: To assess the mortality and causes of death in a cross-sectional population-based study of 1042 patients with rheumatoid arthritis ( RA).Methods: In 1988, 604 RA patients [ 470 females ( F), 134 males ( M)] and 457 age- and sex-matched controls ( 352 F, 105 M) were examined prospectively ( participants) and 438 ( 183 F, 81 M) non-participant RA patients retrospectively. In 1999, vital status and causes of death were determined. Mortality in the total RA population was compared to that in the general population, and that among participant RA patients to their matched controls.Results: A total of 384 (37%) RA patients and 71 (16%) controls died. RA patients had increased mortality compared to the general population ( standardized mortality ratios SMR 2.64) or controls (1.71). This was observed in both sexes. Over 40% of deaths in all groups were due to cardiovascular diseases. RA patients were at increased risk of dying of urogenital, gastrointestinal, respiratory and cardiovascular diseases, infections, and cancers when compared to the general population or controls.Conclusions: Our results show that a cross-sectional cohort of RA patients had an increased risk of death from various causes.

OBJECTIVES:To determine whether plasma matrix metalloproteinase 9 (MMP-9) and MMP9 (-1562C-->T) polymorphism have an effect on the disease phenotype in primary Sjogren's syndrome (pSS).METHODS:Plasma MMP-9 concentrations and polymorphism of the MMP9 gene were analysed in 66 patients with pSS. These data were studied in relation to the clinical data of the patients. The genetic data of patients were compared with the data of 66 healthy subjects.RESULTS:Plasma MMP-9 was higher in patients with definite pSS than in patients with possible pSS. This association was principally caused by higher plasma MMP-9 in patients with a positive Schirmer test and keratoconjunctivitis sicca. pSS patients with purpura, SS-A autoantibodies and RF had significantly lower plasma MMP-9 than patients without these characteristics. The overall MMP9 (-1562C-->T) allele frequencies were similar in patients and control subjects. The frequency of the allele T was higher in patients without Raynaud's phenomenon than in the control group.CONCLUSIONS:MMP9 (-1562C-->T) could not be used for risk assessment in pSS. The presence of the rarer allele T may decrease the risk of Raynaud's phenomenon in pSS. High plasma MMP-9 is indicative of definite pSS but may paradoxically have a preventive effect on the eruption of purpura and on the development of autoantibody reaction in pSS.

BACKGROUND: Apolipoprotein E (apoE) polymorphism plays a central role in lipid metabolism, but has recently also been suggested to regulate inflammation, as judged by levels of serum C-reactive protein (CRP). OBJECTIVE: To establish whether polymorphism of the apoE genes affects susceptibility to primary Sjogren's syndrome (pSS), degree of inflammation or age of onset of pSS. METHODS: ApoE genotype distribution and allelic frequencies were analysed using PCR and the TaqMan system in 63 Finnish Caucasian patients with pSS and in 64 healthy controls matched for sex, ethnic origin and area of residence. The clinical and immunological data on the pSS patients were analysed in relation to the apoE genotypes. RESULTS: There was no difference between pSS patients and controls in apoE genotype and allelic frequencies. The apoE epsilon4 allele was significantly associated with early onset of pSS in the entire population and in female patients (Kaplan-Meier log rank test, P = 0.0407 and P = 0.0168, respectively). The average age (+/- S.D.) of onset of pSS in all apoE epsilon4 allele carriers was 46 +/- 12 and in other genotypes it was 53 +/- 10 yr (P = 0.031, t-test). ApoE polymorphism was not associated with signs of inflammation evaluated by such markers as concentration of plasma CRP, plasma interleukin-6, plasma TNF-alpha, immunoglobulin G and haemoglobin, or leucocyte count or ESR. CONCLUSIONS: ApoE polymorphism does not affect susceptibility to pSS or levels of plasma inflammatory indices in patients with pSS. However, a clear association prevails between apoE epsilon4 and early onset of pSS.

Aims and Methods: Mortality among RA patients and controls was analyzed with special attention to renal disease in population-based material (originally screened in 1988) of 604 patients with RA (470 females, 134 males) and 457 age- and sex-matched controls (352 females, 105 males). In the original RA population, isolated hematuria (HU) was observed in 54, isolated proteinuria (PU) in 27, combined hematuria and proteinuria (HUPU) in 7, chronic renal failure (CRFtot) in 36 and isolated chronic renal failure without HU or PU (CRFisol) in 15 patients. Among the controls, HU was observed in 39, PU in 11, CRFtot in 32 and CRFisol in 16 subjects. HUPU was not observed in any of the controls. Microalbuminuria (20–200 µg/min) was observed in 34 RA patients and in 27 controls. Histologically confirmed amyloidosis was found in 13 RA patients and mesangial glomerulonephritis (MesGN) in 17 patients. The mortality was evaluated in 1999 from data of the Statistical Office of Finland. Statistical analysis was performed by Cox regression analysis. Results: Mortality was significantly increased in the RA population as compared to controls: hazard ratio (HR) 1.78 (95% CI 1.34–2.31) for all RA patients; HR 2.12 (1.52–2.94) for females; HR 1.15 (0.75–1.77) for males. In the RA material, increased mortality was detected in patients with HUPU (HR 4.45; 1.54–12.84), PU (HR 3.54; 1.88–6.65), CRFtot (HR 3.74; 2.55–5.56) or microalbuminuria (HR 2.77; 1.64–4.69) when compared to those with normal clinical renal findings, whereas HU (HR 1.49; 0.88–2.52), CRFisol (HR 1.71; 0.82–3.54), bacteriuria (HR 0.96; 0.35–2.59) or pyuria (HR 0.65; 0.09–4.65) did not predict mortality. Renal amyloidosis was associated with an over twofold mortality rate (HR 2.31; 1.03–5.15), whereas mortality was within expected limits in RA patients with MesGN (HR 1.61; 0.49–5.24). Conclusion: Our results show that nephropathy presenting with combined hematuria and proteinuria, proteinuria, microalbuminuria or histologically confirmed amyloidosis is associated with increased mortality in RA patients, whereas mortality is within expected limits in those with isolated hematuria or mesangial glomerulonephritis.

Patients benefit from surgical seclusion of atrial septal defect but have excessive cardiovascular morbidity after the operation. We evaluated haemodynamics and looked for abnormalities of cardiac structures and function late after surgical seclusion of the defect. Serum N-terminal natriuretic peptide measurement and transthoracic and transoesophageal echocardiography were performed in 61 patients aged 43±15 years (mean±standard deviation) 21±5 years after surgery. The findings were compared with 67 control subjects. The patients had higher serum N-terminal atrial natriuretic peptide concentration than the control subjects (0.40±0.32 vs. 0.24±0.12 nmol/l, P=0.0001). Peptide levels correlated with current age (P=0.0001) and age at operation (P=0.0014), but not with age in the control subjects. In the patients, echocardiography measurements of cardiac dimensions correlated with hormone levels (atrial natriuretic peptide concentration with left atrial end-systolic diameter (P=0.042), left ventricular end-diastolic (P=0.021) and end-systolic diameter (P=0.042). There were only 10 patients (16%) without any abnormality in echocardiography. Their peptide concentration was 0.25±0.18 nmol/l (P=not significant compared to the control subjects). The association between increasing N-terminal atrial peptide levels and operation age together with echocardiography findings support the clinical consensus of treating atrial septal defect patients in their childhood and adolescence.

Objective and methods : To investigate the significance of mannan-binding lectin (MBL) gene alleles in patients with primary Sjögren's syndrome (pSS). Genotypes were determined in 65 pSS patients and 138 controls. Results : No difference in MBL genotype or allele frequencies was detected between the pSS patients and controls. However, when the effect of MBL genotypes on the diagnostic findings in pSS patients was assessed, none of the eight patients with 52/w genotype fulfilled four (definite) Californian criteria (P= 0.007). Among these eight the Chisholm-Mason histological grade was f 3 in only three (P= 0.017). Furthermore, the MBL concentration was lower in patients with 52/w genotype compared to those with wild-type (w/w) genotype (P= 0.035). Conclusion : Our findings suggest that MBL structural gene polymorphisms do not influence on susceptibility to pSS. However, MBL may be associated with salivary gland destruction in pSS, and its concentration may be comparable with the intensity of inflammatory reaction. Further studies are warranted to clarify the possible mechanisms involved.

Purpose: To evaluate renal US findings in patients with nephropathia epidemica (NE) and to determine whether changes in these findings are related to the clinical course of NE. Material and Methods: Renal US was undertaken in 23 hospital-treated NE patients during the acute phase of their disease (first study). The second US study was performed 3–6 months later. Results: The resistive index (RI) was abnormal in 12 patients and fluid collections (perirenal, pleural, pericardial, ascites) were found in 13 patients in the first study. Renal length decreased in every patient, cortical parenchymal thickness in 19 patients and RI in 18 patients from the first to the second studies. The mean change was significant in all parameters. Increased RI and presence of fluid collections in the first study as well as a greater change in length and RI between the first and the second studies were associated with high maximum daily urine excretion, substantial change in body weight between the anuric and polyuric phases, high maximum serum creatinine and urea concentration, high blood leukocyte count and low hematocrit value. Conclusion: Renal US changes occurred in every patient with NE. The severity of the findings was associated with fluid volume overload and degree of clinical renal insufficiency.

AIMS:The present study was undertaken to assess the role of isolated ultrafiltration (UF phase) and hemodialysis with minimal ultrafiltration (HD phase) in changes in parameters reflecting myocardial ischemia: QRS vector difference (QRS-VD), ST change vector magnitude (STC-VM) and ST vector magnitude (ST-VM6) registered by MIDA (myocardial infarction dynamic analysis).PATIENTS AND METHODS:Twelve patients on maintenance hemodialysis were first ultrafiltrated for 2.5 h without dialysis (UF) followed by a 2.5-hour session of hemodialysis with minimal ultrafiltration (HD). Computerized vectorcardiography (VCG) was used for on-line dynamic analysis of ST segment and QRS complex changes. Blood volume (BV) changes were monitored non-invasively and continuously with the CRIT-LINE instrument. Whole-body bioelectric impedance analysis (BIA) was used for extracellular water (ECW) estimation.RESULTS:During the UF phase QRS-VD and STC-VM showed a statistically significant increasing linear trend (time effect for both QRS-VD and STC-VM p < 0.0001, while no changes were noted in ST-VM6; time effect p = 0.986). During the HD phase none of these parameters changed (time effect for QRS-VD p = 0.855, for STC-VM p = 0.275 and for ST-VM6 p = 0.976). During the UF, phase changes in QRS-VD were in close relation to those in ECW.CONCLUSION:Isolated ultrafiltration leads to an increase in the VCG ischemia monitoring parameters QRS-VD and STC-VM. The increase of QRS-VD is related to changes in ECW. Hemodialysis with minimal ultrafiltration has no effect on VCG ischemia monitoring parameters.

Purpose: To evaluate renal US findings in patients with nephropathia epidemica (NE) and to determine whether changes in these findings are related to the clinical course of NE.Material and Methods: Renal US was undertaken in 23 hospital-treated NE patients during the acute phase of their disease (first study). The second US study was performed 3-6 months later.Results: The resistive index (RI) was abnormal in 12 patients and fluid collections (perirenal, pleural, pericardial, ascites) were found in 13 patients in the first study. Renal length decreased in every patient, cortical parenchymal thickness in 19 patients and RI in 18 patients from the first to the second studies. The mean change was significant in all parameters. Increased RI and presence of fluid collections in the first study as well as a greater change in length and RI between the first and the second studies were associated with high maximum daily urine excretion, substantial change in body weight between the anuric and polyuric phases, high maximum serum creatinine and urea concentration, high blood leukocyte count and low hematocrit value.Conclusion: Renal US changes occurred in every patient with NE. The severity of the findings was associated with fluid volume overload and degree of clinical renal insufficiency.

AIMS:Bisphosphonates inhibit osteoclastic bone resorption, and in the future, they may also have a role in the therapy of renal osteodystrophy. Our aim was to study whether the severity of hyperparathyroidism has an effect on the clearance of clodronate via routes other than dialysis or kidneys (nonrenal, non-dialysis clearance, CL(NRD)), which most likely represents the deposition of the drug in the skeleton.METHODS:We studied 31 dialysis patients (9 female/22 male, aged 28 - 79, median 58 years), 18 on hemodialyis (HD) and 13 on peritoneal dialysis (PD). HD patients were studied on a non-dialysis day. An intravenous infusion of 300 mg clodronate was given during 60 min at 8:00 a.m. Blood, urine and PD fluid samples were collected for 1 + 24 h, and pharmacokinetic parameters were calculated.RESULTS:In PD patients, 7% of the infused drug was excreted into PD fluid within 24 h, and in those HD or PD patients with residual diuresis 11% was excreted via the kidneys. The highest CL(NRD) was seen in patients with the most severe hyperparathyroidism. There was a positive correlation between CL(NRD) and plasma intact PTH (r = 0.79, p < 0.001). CL(NRD) was also related to the serum levels of bone markers PINP (procollagen type I N-terminal propeptide, r = 0.81, p < 0.001), osteocalcin (r = 0.65, p < 0.001) and ICTP (type I collagen cross-linked telopeptide, r = 0.68, p < 0.001). However, even in the patients with normal PTH, more than one-third of the infused drug was taken up by bone.CONCLUSION:In dialysis patients, the skeletal deposition of clodronate is related to bone turnover being highest in severe hyperparathyroidism. However, even in the case of low turnover, the uptake of the drug in bone takes place in amounts that might be clinically significant.

BACKGROUND:Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism may cause hyperhomocysteinemia, which affects the vascular endothelium and may induce occlusive vascular disease (OVD). Hypertension thickens small-sized arterial walls and attenuates intramural blood flow. Such OVD can be studied in retinal angiograms as a decrease in the arterio-venous ratio (AVR). Diabetes, by altering microvascular structure and function, in many ways modifies this AVR.OBJECTIVE:To assess whether MTHFR gene polymorphism (C677T) by causing hyperhomocysteinemia affects the retinal AVR in type 2 diabetic and non-diabetic subjects.METHODS:Eighty-four recently diagnosed (< 1 year) type 2 diabetic and 115 non-diabetic subjects were included in the study. Retinal fluoresceine angiograms were recorded and the mean AVR was calculated by measuring transverse vessel diameters at 6 locations. The mean AVR was used as a marker of OVD. The MTHFR VV, VA and AA genotypes were determined by PCR and plasma homocysteine by high-pressure liquid chromatography.RESULTS:In the diabetic subjects with the VV, VA and AA genotypes, the plasma homocysteine levels were 16.5 +/- 7, 12.5 +/- 4.6 and 11.3 +/- 4.9 microM, respectively (p = 0.008, ANCOVA). The corresponding values in controls were 14.6 +/- 3.8, 13.7 +/- 5.7 and 11.6 +/- 4.4 (p = 0.08). Correspondingly, in the diabetic subjects, the AVR values were 0.71 +/- 0.07, 0.75 +/- 0.07 and 0.73 +/- 0.1 (p = NS, ANOVA) and in the control subjects they were 0.8 +/- 0.14, 0.81 +/- 0.12 and 0.76 +/- 0.09 (p = NS, ANOVA). Multiple linear regression analysis (best model chi2 = 18.2, R2 = 0.10, p < 0.001) showed that AVR was related to diastolic blood pressure (t = -3.7, p < 0.001) and GFR (t = -2.2, p = 0.03). There was no relation between the AVR and plasma homocysteine levels.CONCLUSION:In the present study of recently diagnosed type 2 diabetic and non-diabetic subjects, MTHFR gene polymorphism (C677T mutation) slightly affected the plasma homocysteine level but did not alter the arterio-venous ratio.

OBJECTIVESTo determine whether plasma interleukin-6 (IL-6) and G/C base exchange polymorphism at position -174 of the IL6 gene have an effect on the clinical manifestations of primary Sjögren's syndrome (pSS).METHODSLevels of circulating IL-6 protein and polymorphism of the IL6 gene were analysed in 66 patients with pSS and in 400 healthy subjects. These data were studied in relation to clinical data on the pSS patients.RESULTSPlasma IL-6 was elevated in pSS patients compared with healthy controls. pSS patients with coeliac disease, pulmonary fibrosis or alveolitis or peripheral nervous system symptoms had significantly higher IL-6 levels than patients without these manifestations. IL-6 levels increased in parallel with the histological grade of minor salivary gland biopsy and the number of pSS criteria fulfilled. IL6 allele frequencies were similar in patients and normal subjects. Plasma IL-6 levels were regulated by the IL6 genotype in pSS patients.CONCLUSIONSThe G/C polymorphism of the IL6 gene does not predispose patients to pSS, but the circulating IL-6 concentration is related to specific manifestations of the disease and the levels of IL-6 are regulated by the IL6 promoter polymorphism in pSS.

OBJECTIVE:To determine whether the haplotypes formed on the basis of single-base-exchange polymorphisms at positions -1082, -819, or -592 of the interleukin-10 (IL-10) gene predispose subjects to primary Sjögren's syndrome (SS).METHODS:The frequency of IL-10 polymorphisms was analyzed in 62 patients with primary SS and in 400 healthy subjects. These data were assessed for correlations with the concentration of IL-10 in the plasma.RESULTS:The frequency of the IL-10 GCC haplotype (G at position -1082, C at position -819, and C at position -592 of the IL-10 gene) was increased (P < 0.05, odds ratio [OR] 1.90, 95% confidence interval [95% CI] 0.955-3.62) and the frequency of the ACC haplotype decreased (P < 0.05, OR 0.443, 95% CI 0.257-0.764) in primary SS patients compared with healthy controls. Moreover, the frequency of the ATA haplotype was similar in primary SS patients and healthy controls, but the incidence of the GCC/ATA genotype was elevated in the primary SS patients (P < 0.05, OR 2.19, 95% CI 1.19-4.03). The concentration of plasma IL-10 was significantly higher in patients carrying the GCC haplotype than in non-carriers of GCC.CONCLUSION:These results suggest that the presence of the GCC haplotype or the GCC/ATA genotype and the absence of the ACC haplotype of the IL-10 gene are associated with an increased susceptibility to primary SS. This effect is probably mediated by the increased capability to produce IL-10 among carriers of the GCC haplotype.

Purpose: To describe a specific imaging pattern of hepatic fatty change typical of diabetic patients on continuous ambulatory peritoneal dialysis (CAPD) treated with intraperitoneal (i.p.) insulin. Material and Methods: Liver ultrasound was applied in 16 CAPD patients with insulin-dependent diabetes mellitus. Presence of hepatic subcapsular steatosis and maximum thickness of the fatty layer were recorded. Liver MR examination was made of 1 patient found to have extensive subcapsular steatosis. Results: Hepatic ultrasound revealed a typical pattern of subcapsular steatosis ("coating-of-fat") in 7/8 patients treated with i.p. insulin. None (0/8) of the diabetic CAPD patients treated with subcutaneous insulin had subcapsular steatosis. Conclusion: Hepatic subcapsular steatosis is specific to CAPD patients on i.p. insulin treatment. To our knowledge this is the first report to describe imaging findings in this particular form of hepatic fatty change.

Objective-To evaluate outcome in a cohort of Finnish patients with primary Sjogren's syndrome (pSS).Methods-Clinical and laboratory data from the time of diagnosis and follow up were collected from 110 patients with pSS (107 women, three men) diagnosed in 1977-1992 in central Finland. The standardised incidence ratio for cancers was determined as the ratio of the observed number of cases to the expected number based on regional population rates. Eighty one of the 93 patients still alive were interviewed, and clinical and laboratory examinations performed in 1994-1997.Results-The mean (SD) erythrocyte sedimentation rate (33 (22) v 45 (28) mm/1st h), serum IgG (18.8 (7.4) v 22.5 (8.5) g/l), and serum IgM (1.6 (1.1) v 2.0 (1.2) g/l) at the control visit were significantly (p<0.0001) lower than those at baseline. A similar change was observed in a subgroup of patients never treated with glucocorticosteroids or disease modifying antirheumatic drugs. Three non-Hodgkin's lymphomas were diagnosed (standardised incidence ratio 13; 95% confidence interval 2.7 to 38). In a logistic regression model, the patients with pSS with subsequent lymphoma were found to have higher baseline levels of serum (2) microglobulin than the others (odds ratio 1.9; 95% confidence interval 1.1 to 3.4).Conclusion-The results suggest that mean concentrations of serum IgG and IgM in patients with pSS decline with time, possibly reflecting diminishing inflammatory activity. As in previous studies, the incidence of non-Hodgkin's lymphomas in this cohort of patients with pSS was significantly higher than in the reference population.