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Biomedical subjects

J Mustonen

Publications and source records attributed to J Mustonen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Renal findings and glomerular pathology in diabetic subjects.

BACKGROUND: To describe the relationship between proteinuria, hematuria, and renal insufficiency, on one hand, and glomerular pathology, on the other hand, in a consecutive biopsy series of diabetic patients. SUBJECTS AND METHODS: All diabetic subjects (n = 200) biopsied from 1979 to 1995 at Tampere University Hospital were identified in retrospect. The clinician-based indication (any unexplained renal finding) for renal biopsy was consistent during the years and was: proteinuria alone in 68%; combined with hematuria in 10%; with renal insufficiency in 10%; with both in 9%, and with isolated hematuria or renal failure in 3%. One third of the subjects had proteinuria of >/=3 g/24 h and 16% a serum creatinine level of >/=200 microM. Glomerulopathy was found in 171 specimens and defined as nodular diabetic (group A), diffuse diabetic (group B) and primary (group C). The 24-hour urinary protein excretion rate [mean (range)] was 3.5 (1.6-6.9), 1.0 (0.5-3.5), and 3.6 (1.1-6.6) g in groups A, B and C, respectively (ANOVA p = 0.001). The corresponding serum creatinine values [mean (SD)] were 175 (115), 105 (142) and 169 (138) microM (p = 0.001). RESULTS: Nodular diabetic glomerulopathy was found in 40%, diffuse diabetic glomerulopathy in 42% and primary glomerulopathy in 18%. A primary glomerulopathy was found in any indication and in both types of diabetes (prevalence range 14-26%). The best multivariate logistic regression model obtained (chi(2) = 13.5, p = 0.008) in predicting the presence of diabetic glomerulosclerosis (group A + B) in contrast to a primary glomerulopathy (group C) included retinopathy (p = 0.04), renal insufficiency (p = 0.03), hematuria (p = 0.12) and type of diabetes (p = 0.10). CONCLUSION: In this series of diabetic subjects, biopsied due to proteinuria, hematuria and not severe renal insufficiency, 18% had evidence of a primary glomerulopathy.

Adult↗
PubMed2000

Angiotensin-converting enzyme insertion/deletion polymorphism and prognosis of IgA nephropathy.

BACKGROUND/AIM: Well-known factors for a poor prognosis in IgA nephropathy (IgAN) are hypertension, proteinuria, and renal insufficiency at the time of diagnosis. Also hypertriglyceridemia and hyperuricemia seem to play a role in the progression of IgAN. Angiotensin-converting enzyme (ACE) gene I/D polymorphism has been associated with cardiovascular diseases and with progression of IgAN. We, therefore, investigated the contribution of ACE gene I/D polymorphism in the prognosis of IgAN and its association with the other risk factors affecting the prognosis. METHODS: A total of 168 patients with IgAN were followed up for 6-17 (median 11) years from renal biopsy with respect to progression of renal disease defined as elevation of serum creatinine above 125 microM (1.4 mg/dl) in men or 105 microM (1.2 mg/dl) in women and over 20% from the baseline level. In addition to serum creatinine, the urinary protein excretion was evaluated at the time of renal biopsy and at the assessment visit at the end of the follow-up period. RESULTS: During the follow-up period, 26 (15%) patients showed progression of renal disease. Patients with ACE genotype II had a more favorable course than those with genotypes ID or DD. Although there were no significant differences among the ACE genotypes with respect to proteinuria > or =1 g/24 h at the time of renal biopsy, proteinuria > or =1 g/24 h was more frequent in patients with genotypes ID or DD than in those with genotype II at the end of the follow-up period. No associations were found between hypertension, serum lipids or serum urate, and ACE genotypes. CONCLUSIONS: Our results show that patients with ACE genotype II have a more favorable prognosis than those with genotypes ID/DD. Secondly, proteinuria (> or =1 g/24 h) found in patients with genotype II at diagnosis may improve, while in patients with genotypes ID/DD it is a more constant feature.

Adolescent↗
PubMed2000

Complement activation in nephropathia epidemica caused by Puumala hantavirus.

BACKGROUND AND AIM: Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome caused by Puumala hantavirus. There is considerable variability in the clinical severity of NE. Its pathogenesis is largely unknown and data on complement activation in NE are scant. We sought here to establish how the complement system behaves during NE and whether the variation in the clinical outcome is related to the activation of complement. PATIENTS AND METHODS: The complement component levels and complement activation products and the clinical course of 25 hospital-treated acutely ill NE patients were studied. RESULTS: Complement activation was observed in 23 patients. In 10 patients the complement system was activated mainly through the alternative route, in 6 mainly through the classical route and in 5 through both the alternative and the classical route. An elevated soluble terminal complex SC5b-9 was the most sensitive indicator of complement activation (17 out of 25 patients). Two patients had only an elevated SC5b-9 value and 2 had no complement activation. The C4d/C4 maximal ratio was significantly higher in patients with clinically severe NE compared to the mild or moderate disease groups. CONCLUSION: Our results show that complement activation is common in NE. Although both pathways are usually activated, the classical pathway activation by immune complexes or directly by viral components is associated with a severe clinical course of NE.

Adolescent↗
PubMed2000

Hemodialysis causes changes in dynamic vectorcardiographic ischemia monitoring parameters.

AIMS: The aim of this study was to establish whether changes in parameters reflecting myocardial ischemia QRS vector difference (QRS-VD), ST change vector magnitude (STC-VM) and ST vector magnitude (ST-VM6) during hemodialysis (HD) registered by MIDA (myocardial infarction dynamic analysis) are related to changes in blood volume (BV), extracellular water (ECW) and blood biochemistry. PATIENTS AND METHODS: Fifteen hemodialysis (HD) patients were studied. Computerized vectorcardiography was used for on-line dynamic analysis of ST segment and QRS complex changes. BV changes were monitored non-invasively and continuously with the CRIT-LINE instrument. Bioelectric impedance analysis (BIA) was used for ECW estimation. Blood samples were taken before and after hemodialysis for hemoglobin (B-Hb), hematocrit (B-Hcr), sodium (P-Na), chloride (P-Cl), magnesium (P-Mg), potassium (P-K), ionized calcium (P-iCa), phosphate (P-Pi) and astrup measurement. RESULTS: During dialysis treatment QRS-VD, ST-VM6 and STC-VM did not change in parallel. According to the linear mixed model, no statistically significant changes were noted in ST-VM6 during dialysis (time effect p = 0.5635). On the other hand, QRS-VD and STC-VM showed a statistically significant linear trend (time effect for QRS-VD p = 0.0001 and for STC-VM p = 0.0004). Changes in both ECW and BV affected the change in QRS-VD and in STC-VM. CONCLUSION: During HD treatment changes in the vectorcardiographic ischemia monitoring parameters QRS-VD and STC-VM are mostly related to ECW and BV changes and may give a false positive impression of myocardial ischemia. The ST-VM6 trend is less markedly influenced by volume changes.

Adult↗
PubMed1999

Analysis of puumala hantavirus genome in patients with nephropathia epidemica and rodent carriers from the sites of infection.

Reverse transcription-polymerase chain reaction (RT-PCR) followed by sequence and phylogenetic analyses were used to study specimens from nine Finnish nephropathia epidemica (NE) patients admitted to hospital during the epidemic in winter 1996-1997. Blood samples from six patients were found to be positive for the partial M- and/or S-segment sequences of Puumala hantavirus (PUUV). Analyses of these sequences (nt 2168-2610 for the M segment, and nt 819-1082 for the S segment) revealed six distinct PUUV strains showing highest similarity to previously described PUUV strains from Finland: 90-95% for the S segment, and 90-99% for the M segment. Accordingly, on the phylogenetic trees calculated for both viral segments, all six human strains were placed within the Finnish genetic lineage of PUUV. Attempts were made to trace five RT-PCR-positive patients to local bank voles (Clethrionomys glareolus) infected with wild-type PUUV, and for two patients a comparative analysis of human- and rodent-originated viral sequences was undertaken. Whereas in the first case the differences between the sequences were substantial (5. 7% for the S segment, and 10.8%, for the M segment), in the other case the M segment sequence recovered from the clinical specimen was 100% identical to three sequences recovered from rodent lungs, and the S sequences differed by one silent substitution only. This is the first finding of virtually identical PUUV sequences in an NE patient and a natural rodent host from the site of infection.

Adolescent↗
PubMed1999

Small bowel T cells, HLA class II antigen DR, and GroEL stress protein in IgA nephropathy.

BACKGROUND: Previous studies suggest that intestinal mucosa may be involved in the pathogenesis of IgA nephropathy (IgAN). To further clarify this involvement, we investigated whether or not IgAN patients have small bowel mucosal findings suggestive of inflammation and stress. METHODS: Seventeen patients with IgAN underwent gastroscopic examination. Fresh small bowel biopsy specimens were frozen, and in cryosections, the proportion of alphabeta and gammadelta receptors bearing T cells and CD3+ T cells were quantitated immunohistochemically. The expression of HLA class II antigen DR (HLA-DR) and human GroEL stress-protein homologue was similarly quantitated. In an avidin-biotin peroxidase technique, the following monoclonal primary antibodies were used: anti-beta-chain (betaF1), anti-delta-chain (TCRdelta1), anti-CD3 (Leu4), anti-constant fragment of HLA-DR (L243), and anti-GroEL (ML30). Twenty-nine patients who had undergone gastroscopy because of dyspepsia served as controls. RESULTS: In all specimens, the mucosal architecture was normal. The amount of gammadelta T cells and the total amount of T cells, as indicated by CD3+ positivity, were both significantly increased in IgAN. The number of alphabeta T cells was also higher in the IgAN patients. Villous epithelium of the IgAN patients disclosed a significant increase in the expression of HLA-DR antigen and GroEL stress protein. CONCLUSIONS: Our results suggest that ongoing small bowel inflammation and stress are present in IgAN. Despite normal morphology, there is reason to believe that the small bowel mucosa is involved in the pathogenesis of IgAN.

Adult↗
PubMed1999

QRS amplitude and volume changes during hemodialysis.

BACKGROUND: According to several studies the QRS amplitude of the ECG increases during hemodialysis. The detailed background to this phenomenon has not been defined. Two main mechanisms have been suggested: myocardial ischemia and volume changes. New noninvasive technologies make possible a comparison of QRS complex changes synchronously with myocardial ischemia and extracellular water (ECW)/blood volume (BV) changes during hemodialysis. METHODS: In this study hemodialysis-related changes in body weight, biochemical blood variables, BV, ECW, ST segment and QRS complex were analyzed in 15 patients (age 36-76, time on dialysis 0-6 years) undergoing chronic hemodialysis treatment. QRS complex and ST segment changes were measured using a dynamic vectorcardiographic monitoring system. The ECG parameters measured were QRS vector difference (QRS-VD) and ST vector magnitude (ST-VM6). Bioimpedance analysis was used to detect changes in the ECW. Continuous measurement of BV changes was implemented using an on-line optical reflection method based on the reflection of infrared light by erythrocyte membranes. Blood hemoglobin (B-Hb), hematocrit (B-Hcr), plasma sodium (P-Na), chloride (P-Cl), magnesium (P-Mg), potassium (P-K), ionized calcium (P-iCa), phosphate (P-Pi), creatinine (P-Crea) and urea (S-Urea) were monitored. RESULTS: The mean QRS-VD increase during the dialysis session was almost fourfold (372 +/- 300%) from 4.16 +/- 2. 40 to 15.60 +/- 7.0 microVs (p < 0.001). This change was due to a change in amplitude, since the duration of the QRS complex did not alter significantly. The correlation between the changes in QRS-VD and body weight from the start to the end of the dialysis session was moderate and statistically significant (r = -0.55, p < 0.05). The correlation between the changes in QRS-VD and ECW varied from r = -0.67 to -0.97, being statistically significant in all patients (p < 0.001). The correlation between BV and QRS-VD was assessed at one minute intervals during the dialysis and varied from r = -0.22 to -0. 98, being significant in 14 of the 15 patients (p < 0.001). Significant ST segments alterations (ST-VM6 elevation > 100 microV) did not occur during dialysis. Laboratory parameters reflecting volume and osmotic changes during hemodialysis correlated with QRS-VD change: B-Hcr (r = 0.56, p < 0.05), B-Hb (r = 0.63, p < 0.05), P-Na (r = 0.62, p < 0.05) and S-Urea (r = -0.62, p < 0.05). CONCLUSIONS: The increase in QRS complex amplitude during hemodialysis is correlated to reduced ECW. The mechanism involved is most probably augmentation of electrical resistance of the tissues around the heart caused by loss of interstitial fluid.

Adult↗
PubMed1999

Retinopathy is independently related to microalbuminuria in type 2 diabetes mellitus.

UNLABELLED: AIM, SUBJECTS AND METHODS: To evaluate whether microalbuminuria is related to retinopathy in type 2 diabetes, we studied a sample of 125 known diabetic subjects with a mean disease duration of 11 years (range 5-22 years), aged 46-71 years, by ophthalmoscopy, fundus photography and fluoresceine angiography. Urinary albumin excretion rate (UAER) was measured by nephelometry and the fractional clearance of albumin, i.e. in relation to creatinine was calculated from spot samples. The subjects were classified into groups based on the UAER/24 h. RESULTS: Microalbuminuria was present if UAER was 30-300 mg/24 h and overt nephropathy when UAER > or = 300 mg/24 h. Background (> or = 2 microaneurysms or > or = 2 hemorrhages or > or = 1 more advanced lesions, except proliferative changes) and proliferative retinopathies were found in 21% and in 3%, respectively. Subjects with microalbuminuria (p = 0.026) and overt nephropathy (p = 0.002) had more frequently background retinopathy than their counterparts with a normal UAER (chi2-test). A multivariate logistic regression model was obtained for background retinopathy (chi2 = 37.5, p = 0.0000039, OR 14.9, correct prediction of negative outcome in 97% and of positive outcome in 30.4%) including the following variables. The fractional clearance of albumin independently explained background retinopathy (OR 3.9, 95% CI 1.3-12, p = 0.028). Insulin therapy (p = 0.0017), diabetes duration (p = 0.048), blood glucose at 2 h in standard oral glucose tolerance test (p = 0.009) and low fasting serum HDL cholesterol (p = 0.023) also independently explained retinopathy. Age, gender, BMI, systolic blood pressure, ACE inhibitor therapy, fasting serum total cholesterol and triglyceride, blood glucose or insulin, hemoglobin A1c, glucagon-stimulated C peptide response, glomerular filtration rate or smoking habits did not independently explain retinopathy. CONCLUSION: We conclude that microalbuminuria is related to background retinopathy in type 2 diabetes.

Aged↗
PubMed1998

Pathogenesis of puumala and other hantavirus infections.

Hantaviruses are rodent/insectivore-borne negative-stranded RNA viruses which belong to the Bunyaviridae family. They do not cause any symptomatic disease in their adult carrier rodents, but in humans they are aetiologic agents of haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), both associated with a significant mortality. In cell culture hantaviruses do not cause cytopathic effects and the mechanisms of disease in man are not well understood. Increased capillary permeability is a central phenomenon in the pathogenesis of hantavirus infections. Although the viruses have in vivo a predilection for endothelial cells, it is presumed that inflammatory mediators of the host immune response play a significant role in the capillary leak that may produce abrupt hypotension and shock in severely ill patients. Mediators released by activated macrophages including NO and TNF-alpha are considered important. The pathogenesis of renal failure in HFRS also awaits to be resolved. This review summarises what is known about these phenomena and discusses also the molecular basis of the putative virulence factors of hantaviruses. Finally, the genetic predisposition and HLA association with severe Puumala virus infection will be discussed. Copyright 1998 John Wiley & Sons, Ltd.

Journal Article↗
PubMed1998

Association of HLA B27 with benign clinical course of nephropathia epidemica caused by Puumala hantavirus.

Both the severe course of nephropathia epidemica (NE) caused by Puumala hantavirus, and the fast progression of human immunodeficiency virus (HIV) disease, are associated with the HLA B8 DRB1*0301 haplotype. As HLA B27, on the contrary, is associated with the slow progression of HIV disease, we wanted to test whether the same is true for NE. Only six (8%) NE patients, half the figure expected, had the HLA B27 allele in 74 randomly selected hospital-treated patients. All six had a benign overall clinical course of NE; none had any severe complications, the severity of renal failure was also mild, and the treatment time at the hospital was half that needed for HLA B27- patients (P = 0.004). Patients who were HLA B27 had maximal blood leucocyte count > 10.000 x 10(9)/L (P = 0.020) more often, probably reflecting differences in immune response. Thus, similar HLA associations can be found in both HIV infection and NE caused by Puumala virus.

Adult↗
PubMed1998

High-producer allele of tumour necrosis factor-alpha is part of the susceptibility MHC haplotype in severe puumala virus-induced nephropathia epidemica.

The biallelic polymorphisms in the tumour necrosis factor-alpha (TNF-alpha) gene promoter region were studied in patients with nephropathia epidemica (NE). The rarer TNF2 allele, associated with a high TNF-alpha producer phenotype, was more frequently found in hospitalized NE patients (42%) than in healthy controls (15%; p=0.0064). The putative role of TNF2 as an independent risk factor for NE is discussed.

Alleles↗
PubMed1998

Nephrotic syndrome, hyperreninemia and multiple transplant renal arterial stenoses in a patient with diabetes.

Nine months after cadaveric renal transplantation the nephrotic syndrome developed in a patient with insulin-dependent diabetes. Renal biopsy ruled out tissue lesions induced by cyclosporine, chronic rejection, recurrence of diabetic kidney disease and de novo glomerulopathies. Captopril-enhanced nephrography and a high plasma renin response suggested renal artery disease. Angiography revealed five intrarenal arterial stenoses. Four were successfully dilated with a prompt diuretic response and diminished proteinuria. Late angiography showed a moderate restenosis in two of the dilated arteries. Due to persistent proteinuria, elevated blood pressure and higher serum creatinine levels than at nadir after transplantation low-dose ACE inhibitor therapy was started. This normalized proteinuria, blood pressure and serum creatinine levels. This beneficial response to combined renal artery balloon angioplasty and medical treatment has been sustained for 2.5 years.

Diabetes Mellitus, Type 1↗
PubMed1998

Foveal optical modulation transfer function of the human eye at various pupil sizes.

We determined the foveal optical modulation transfer functions of the human eye (O) for pupil sizes of 1-8 mm by using two simple psychophysical techniques. O as a function of spatial frequency f could be described by exp[-(f/fc)n] at any pupil size in our data as well as in the data available in the literature [J. Physiol. (London) 186, 558 (1966); Opt. Acta 21, 395 (1974); Vision Res. 33, 15 (1993); J. Opt. Soc. Am. A 11, 246 (1994)]. When all these estimates of fc and n were pooled the parameters were found to depend on the pupil diameter as fc = 16.6 - 1.49p and n = exp(0.840/p - 0.318). This result indicates that at 1 mm O(f) is close to the diffraction-limited system.

Contrast Sensitivity↗
PubMed1998

Serum ionized versus total magnesium in patients with intestinal or liver disease.

In serum, magnesium exists in three fractions: protein-bound, complex-bound and free ionized form. Only the free ionized fraction is biologically active. Until recently, only the measurement of serum total magnesium has been in clinical use. Now, commercially available instruments using new ion-selective electrodes for Mg++ have made possible the reliable measurement of serum ionized magnesium in clinical practice. For the measurement of serum ionized magnesium we used a magnesium-selective electrode installed in a six-channel electrolyte analyzer. We compared the use of ionized versus total magnesium measurement in 52 patients with intestinal disease, 54 with liver disease, and in 75 healthy control subjects. In the patients with alcoholic liver disease both serum ionized and total magnesium were lower, and in those with inflammatory bowel disease slightly higher than in control subjects. The correlation coefficient between serum ionized and total magnesium was r=0.87 (p<0.001) in the patients, and r=0.75 (p<0.001) in the controls. In the patient group the fraction of ionized magnesium in the total was negatively related to the serum albumin level (r=-0.41, p<0.001). Serum total magnesium was below the reference range in 30 out of 150 measurements, serum ionized magnesium in only 9 out of 150 measurements, respectively. Thus, 21 cases with low total but normal ionized magnesium (two thirds of hypomagnesemia according to serum total magnesium) were false positive. Total magnesium measurement may overestimate the incidence of hypomagnesemia when significant hypoalbuminemia is present. Measurement of serum ionized magnesium instead of total magnesium may therefore be of advantage in evaluating patients with hypoalbuminemia and when hypomagnesemia is expected.

Adolescent↗
PubMed1997

Cardiac sympathetic denervation in patients with coronary artery disease without previous myocardial infarction.

Myocardial infarction damages sympathetic nerve fibers coursing through the infarct zone. In this study we investigated whether coronary artery disease without myocardial infarction results in sympathetic denervation. We examined 12 patients without a history of previous myocardial infarction and 19 postinfarction patients. 1-123 metaiodobenzylguanidine (MIBG) and technetium-99m sestamibi (MIBI) single-photon emission tomography were conducted at rest to determine the extent of denervated myocardium and the extent of myocardium with reduced perfusion, respectively. In addition, myocardial perfusion during exercise was assessed with MIBI. A MIBG or MIBI defect was determined as being regional uptake of < or =30% of the maximal myocardial activity. All but 1 patient without previous infarction had MIBG defects. MIBG defects (10.3 +/- 8.5% of left ventricular mass) were significantly larger than MIBI defects at rest (2.4 +/- 3.2%, p <0.001) and during exercise (4.8 +/- 6.1%, p <0.05). In multiregression analysis, the size of an MIBG defect was associated with severity of coronary stenoses (> or =90% of lumen diameter; p <0.05), but not with age, number of significant stenoses (> or =50% of lumen diameter), left main disease, functional class, left ventricular ejection fraction, angina pectoris, maximal ST depression, or mean workload during exercise test. MIBG and MIBI defects were significantly larger in patients with severe coronary stenoses than in patients with moderate stenoses (50% to 89% of lumen diameter) (16.4 +/- 8.9% vs 6.0 +/- 5.2% [p <0.05] and 5.0 +/- 3.1% vs 0.6 +/- 1.3% [p <0.001], respectively). The size of MIBG (16.1 +/- 8.9%) and MIBI defects (7.3 +/- 6.5%) at rest in postinfarction patients did not differ from patients with severe stenoses. Our study demonstrates that cardiac adrenergic tissue is very sensitive to ischemia and that regional cardiac sympathetic denervation can occur in patients with stable coronary artery disease without previous myocardial infarction.

Adult↗
PubMed1997

Perinuclear antineutrophil cytoplasmic antibody in rheumatoid arthritis: a marker of severe disease with associated nephropathy.

OBJECTIVE: To evaluate the clinical significance of antineutrophil cytoplasmic antibodies (ANCA) in patients with rheumatoid arthritis (RA), and especially in those with clinically suspected or histologically proven nephropathy. METHODS: A total of 246 RA patients with (n = 149) and without (n = 97) histologically proven (n = 99) or clinically suspected (n = 50) nephropathy were studied for the presence of ANCA by immunofluorescence and enzyme immunoassay. RESULTS: Perinuclear ANCA (pANCA) were found in 52 (21%) of the 246 patients. Patients with clinically suspected or histologically proven nephropathy were significantly more frequently positive for pANCA (30% versus 7%; P < 0.00005) and had significantly higher mean (+/- SD) pANCA log titers (103 +/- 5.6 versus 27 +/- 3.0; P = 0.0011) than patients without clinically evident renal disease. Positivity for pANCA was associated with clinical and laboratory findings indicating severe basic disease and increased inflammatory activity. Irrespective of this association, pANCA acted as a significant and independent predictor of RA-associated nephropathy. CONCLUSION: Perinuclear ANCA in RA indicate severe disease with increased inflammatory activity. There is an especially strong and independent association between pANCA and RA-associated nephropathy.

Adolescent↗