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Biomedical subjects

J Mustonen

Publications and source records attributed to J Mustonen.

At least 55 records · Page 3Linked to original sources
PubMed1997

Changes in autonomic nervous function during the 4-year follow-up in middle-aged diabetic and nondiabetic subjects initially free of coronary heart disease.

OBJECTIVES: To study the changes in autonomic nervous function during the 4-year follow-up period in diabetic patients and to investigate factors predicting autonomic nervous dysfunction. DESIGN: A 4-year follow-up study. SETTING: At baseline the study subjects without known cardiovascular disease were recruited from a large group of diabetic and nondiabetic subjects selected randomly from a baseline population. SUBJECTS: Middle-aged control subjects (n = 44), patients with insulin-dependent diabetes mellitus (n = 32) and patients with non-insulin-dependent diabetes mellitus (n = 32) were studied at baseline and after the 4-year follow-up. INTERVENTIONS: Autonomic nervous function tests and exercise test at baseline and after the 4-year follow-up. RESULTS: At the baseline, heart rate variation during deep breathing was significantly lower in patients with insulin-dependent diabetes (13.0 +/- 1.2 beats min-1; P < 0.05) and in patients with non-insulin-dependent diabetes (12.9 +/- 1.5 beats min-1; P < 0.05) than in control subjects (16.6 +/- 1.1 beats min-1). At baseline, autonomic nervous function score was significantly higher indicating disturbed autonomic nervous function in patients with insulin-dependent diabetes (1.74 +/- 0.19; P < 0.01) than in control subjects (1.24 +/- 0.14), but the difference was not significant between control subjects and patients with non-insulin-dependent diabetes (1.47 +/- 0.12). During the follow-up, autonomic nervous function score increased in patients with non-insulin-dependent diabetes to 2.00 +/- 0.21 (P < 0.001, as compared to baseline), but did not change in patients with insulin-dependent diabetes (1.77 +/- 0.18) or control subjects (1.22 +/- 0.12). In both diabetic groups, the deterioration of autonomic nervous function score during the 4-year follow-up was associated with poor glycaemic control at baseline. Clinical manifestation of coronary heart disease was found in three (7%) control subjects, 12 (37%; P < 0.001) patients with insulin-dependent diabetes and 11 (34%; P < 0.01) patients with non-insulin-dependent diabetes mellitus at follow-up examination. Autonomic nervous function was more abnormal in those insulin-dependent diabetic patients with coronary heart disease than those without. CONCLUSIONS: During the 4-year follow-up the impairment in autonomic nervous function occurred mainly in patients with noninsulin-dependent diabetes. Poor glycaemic control appears to be an important determinant of the progression of autonomic nervous dysfunction in diabetes.

Aged↗
PubMed1997

Antibody reactivity against thyroid peroxidase and myeloperoxidase in autoimmune thyroiditis and systemic vasculitis.

Potential cross-reactivity between thyroid peroxidase (TPO) and myeloperoxidase (MPO) molecules was evaluated by analysing the binding of 199 TPO antibody- and MPO antibody-positive sera to TPO and MPO molecules. Sera from six patients with autoimmune thyroiditis (AITD) and four patients with systemic vasculitis (SV) with different TPO-MPO antibody findings were then chosen for further analyses. All six patients with AITD had TPO antibodies in enzyme immunoassay (EIA) and four of them had simultaneously MPO antibodies in EIA. In AITD patients antibody binding to TPO could not be inhibited by adding native MPO to the serum diluent, suggesting that the possible cross-reactive epitopes were exposed in the denaturated MPO molecule. Similarly, the MPO ab reactivity of patients with systemic vasculitis could not be inhibited by native TPO. To study whether TPO and MPO antibodies recognize linear epitopes, the binding of antibodies to synthetic TPO and MPO peptides was analysed. Several TPO and MPO peptides were reactive, including peptides reacting with both TPO and MPO antibody-positive sera. One of the most cross-reactive peptides contained AA 586-601 in TPO, showing also particularly high AA homology (88%) with MPO (AA 594-609). The results suggest that TPO and MPO molecules contain cross-reactive epitopes that are exposed in denaturated molecules and may thus cause false positive antibody findings in solid phase EIA assays.

Amino Acid Sequence↗
PubMed1997

The influence of peritoneal dialysis and the use of subcutaneous and intraperitoneal insulin on glucose metabolism and serum lipids in type 1 diabetic patients.

BACKGROUND: Intraperitoneally administered insulin is regarded as the most physiological replacement therapy, leading to lower peripheral insulin concentrations and equal or better glycaemic control than subcutaneous insulin. This two-part study was undertaken to evaluate the effect of CAPD, as well as the use of subcutaneous vs. intraperitoneal insulin on insulin sensitivity, glycaemic control and serum lipids in type 1 diabetes. METHODS: Eleven patients with type 1 diabetes mellitus and chronic renal failure participated the studies. Glycated haemoglobin (HbA1c), euglycaemic hyperin-sulinaemic clamp, serum lipids, and patient well-being were measured. During CAPD all patients were first treated with subcutaneous insulin and then with intraperitoneal insulin. The metabolic studies were repeated after both treatment periods for at least 3 months. Metabolic studies were performed on six of the patients also before initiation of CAPD. RESULTS: HbA1c rose after the initiation of CAPD from 8.85 +/- 0.54% to 9.58 +/- 0.66%, NS) and improved after changing from subcutaneous to intraperitoneally administered insulin (from 9.49 +/- 0.43% to 8.13 +/- 0.39%, P < 0.01). Insulin dose increased by 15% after initiation of CAPD and 128% after switching from subcutaneous to intraperitoneal insulin. Glucose disposal rate enhanced by 39% (P = 0.05) and 14% respectively (P < 0.01). Initiation of CAPD had no significant effects on serum lipids but intraperitoneally administered insulin reduced HDL cholesterol and increased LDL/HDL ratio significantly. CONCLUSIONS: Intraperitoneal insulin therapy offers better glycaemic control and insulin sensitivity than subcutaneous insulin. Deterioration of HbA1c after initiation of CAPD while patients remained on subcutaneous insulin may be partly due to absorbed energy from the dialysate. Intraperitoneal insulin therapy seems to have detrimental effects on serum lipids. The clinical significance in modifying the risk of atherosclerosis remains unclear.

Adult↗
PubMed1997

Renal and cardiovascular predictors of 9-year total and sudden cardiac mortality in non-insulin-dependent diabetic subjects.

BACKGROUND: The objective was to evaluate the impact of urinary albumin excretion rate (UAER), glomerular filtration rate (GFR) and subclinical autonomic neuropathy (SANP) on 9-year total (TM) and sudden cardiac mortality (SCM) in recently diagnosed (< 1 year; RD; n = 150) and known (mean duration 11 years; KD; n = 146) NIDDM subjects. METHODS: The study was prospective and controlled (n = 150). Mortality predictors were analysed by logistic regression analysis. The dependent variables were TM and SCM, the predictors were UAER, GFR, SANP, age, gender, BMI, mean arterial pressure (MAP), fasting serum cholesterol, HDL-cholesterol, triglycerides, insulin, haemoglobin A1c, diabetes duration, QTc-interval (ECG), coronary heart disease (CHD), peripheral vascular disease (PVD), cerebrovascular disease (CVD), congestive heart failure (CHF), antihypertensive therapy, and smoking habits. RESULTS: CHD predicted TM and SCM in both RD (P = 0.041 and 0.029) and KD (P = 0.034 and 0.006). PVD predicted TM and SCM in KD only (P = 0.001 and 0.003). CVD predicted TM and SCM in RD only (P = 0.001 and 0.017). In RD male gender (P = 0.049), fasting serum cholesterol (P = 0.007) and CHF (P = 0.001) predicted TM and in kDa haemoglobin A1c (P = 0.004), age (P = 0.001) and MAP (P = 0.014) predicted TM. Serum triglycerides predicted SCM in both RD and kDa (P = 0.001 and 0.003). SANP predicted TM (P = 0.009) and SCM (P = 0.044) in KD only. GFR (inverse value) predicted TM and SCM (P = 0.04 and 0.027) in kDa only. The UAER did not predict mortality in the diabetic subjects. CONCLUSION: SANP and a slightly reduced GFR still in the normal range predicted mortality in KD. Microalbuminuria (30 < UAER < 300 mg/24 h) did not independently predict 9-year mortality in the NIDDM subjects studied.

Adult↗
PubMed1997

Mesangial glomerulonephritis as an extra-articular manifestation of rheumatoid arthritis.

Mesangial glomerulonephritis (MesGN) is a frequent renal biopsy finding in patients with rheumatoid arthritis (RA) presenting with haematuria and/or proteinuria. The purpose of this study was to describe the mesangial immunofluorescence (IF) findings in 37 such RA patients, and to correlate the nature of the glomerular immunodeposits with clinical data, levels of serum immunoglobulins and the concentrations of serum rheumatoid factors (RFs). The serological findings in RA patients with MesGN were correlated with those of RA patients matched for age, sex and duration of RA, but without clinically evident renal disease. The most characteristic mesangial IF finding in 37 RA patients with MesGN was IgM observed in 29 specimens (78%). IgA (n = 16) and C3 (n = 15) deposits were also frequently found, whereas C1q (n = 3) and IgG (n = 2) deposits were only occasionally seen. Two main patterns of IF findings could be classified. (1) Granular IgM deposits as a sole or main finding (IgM GN; 25 specimens). The intensity of the mesangial IgM deposits did not correlate with the duration or severity of RA nor with the levels of serum immunoglobulins. However, a significant correlation with the intensity of mesangial IgM deposits and the levels of serum IgM class RF was observed. (2) Granular IgA deposits usually together with the complement component C3, i.e. IgA glomerulonephritis (IgA GN; nine specimens). The intensity of mesangial IgA deposits correlated significantly with the duration and severity of RA, and especially with serum IgA levels. Both RA patients with IgA GN or IgM GN were associated with a more frequent occurrence and higher titres of serum RFs when compared with the RA patients without nephropathy. The clinicopathological correlations and the association with RF support the concept that MesGN is related to the basic rheumatoid disease, and it should be regarded as an extra-articular manifestation of RA.

Adult↗
PubMed1997

Puumala hantavirus genome in patients with nephropathia epidemica: correlation of PCR positivity with HLA haplotype and link to viral sequences in local rodents.

Reverse transcription-PCR was used to analyze specimens from 20 Finnish nephropathia epidemica (NE) patients hospitalized during the period from October 1994 to January 1995. Blood and/or urine sediment specimens from seven patients were found to be positive for the genome sequences of Puumala hantavirus (PUU). PCR positivity of the specimens from the patients correlated well with the HLA-DRB1*0301 and HLA B8 alleles, which previously were shown to associate with severe courses of NE. Genetic analysis of the partial M-and/or S-segment sequences obtained from three severely ill NE patients revealed three PUU strains related to but distinct from previously reported strains from Finland. The M-segment sequence of PUU from bank voles trapped near the probable site of infection for one of the patients showed 98.2% identity to that of the PUU strain obtained from the patient, suggesting a link between wild-type PUU from the natural focus and the NE case. The S-segment sequences from the patient and the bank voles, however, showed substantially lower identity (95.8%). As this difference in diversity for M and S genes (1.8 and 4.2%) is atypical for PUU genetic drift, one possibility is that the strain acquired at the putative place of infection is a reassortant one.

Adult↗
PubMed1997

Evaluation of the calcium-PTH axis and renal handling of phosphate by calcium and citrate clamp techniques in normal subjects and in patients with heavy proteinuria.

We studied the effect of induced hyper- and hypocalcemia on parathyroid function and renal handling of phosphate in healthy subjects (n = 10) and in patients with heavy proteinuria, mean 5.6 +/- 1.9 g/24 hours (n = 5). We used calcium and citrate clamp techniques. Hypercalcemia was rapidly induced by calcium infusion and maintained for 120 min, and correspondingly, hypocalcemia by citrate infusion. The suppression of intact PTH secretion during calcium clamp was similar (to the level of < or = 0.8 pmol/l) in both groups. The response of the parathyroid glands to hypocalcemia was similar in normal subjects and proteinuric patients. Both groups showed a peak of PTH secretion at 10 min, 18.9 +/- 6.7 pmol/l in healthy subjects and 20.4 +/- 7.4 pmol/l in patients. The peak levels were 4.8-7.2 times and 4.0-6.7 times the baseline level, respectively. Thereafter the plasma PTH concentration declined to a fairly constant steady-state level (twice the baseline level) in spite of maintained hypocalcemia. The area under the curve of the plasma concentrations of intact PTH at various times (AUC0-120) was 890 +/- 324 pmol/l/min in normal subjects and 989 +/- 331 pmol/l/min in proteinuric patients, the difference between the groups being again not significant. The renal threshold phosphate concentration (TmPO4/GFR) increased during calcium infusion and decreased during citrate infusion in both groups. During recovery from hypocalcemia PTH levels were lower than during hypocalcemic induction at corresponding serum calcium levels. Using calcium and citrate clamp techniques, we found that the response of the parathyroid glands in acute and maintained hypercalcemia and hypocalcemia, and renal phosphate handling in patients with heavy proteinuria was not different from that of healthy subjects.

Adult↗
PubMed1996

Cytokines, adhesion molecules, and cellular infiltration in nephropathia epidemica kidneys: an immunohistochemical study.

Puumala hantavirus-induced nephropathia epidemica (NE) is an important cause for an acute reversible renal failure in Scandinavia, European Russia, and the Balkans. The characteristic histopathological renal finding is an acute tubulointerstitial nephritis. Mild to massive proteinuria, hematuria, and a rise in the serum creatinine level are typically seen. The pathogenetic mechanisms of NE kidney failure are incompletely understood. Therefore we studied the infiltrating cell populations and local expression of cytokines and growth factors in the kidney during the acute disease. Results of the histological and immunohistological studies of eight kidney biopsies show mild to moderate interstitial infiltration of lymphocytes, plasma cells, monocytes/macrophages, and polymorphonuclear leukocytes, mainly eosinophilic granulocytes and neutrophils. An increased expression of the cytokines tumor necrosis factor-alpha, transforming growth factor-beta, and platelet-derived growth factor was seen at the same sites mainly in the peritubular area of the distal nephron. Concomitantly also at the same locations expression of the endothelial adhesion molecules ICAM-1, VCAM, and PECAM was seen. Light microscopic changes in tubuli were common. Interestingly, despite the often massive transient proteinuria, no marked changes were seen in the glomeruli of NE kidneys. No evidence of Puumala virus was found in the kidney biopsies.

Adult↗
PubMed1996

Measurement of myocardial accumulation of 123I-metaiodobenzylguanidine for studying cardiac autonomic neuropathy in diabetes mellitus.

The association of myocardial 123I-metaiodobenzylguanidine (MIBG) accumulation and autonomic neuropathy, as well as factors known to affect autonomic nervous function, were studied in a group of 12 diabetic patients representing different degrees of autonomic failure. The early myocardial uptake phase of 123I-MIBG was measured by calculating the peak net influx rate for the first 30 min after the 123I-MIBG injection and by single photon emission computed tomography (SPECT) imaging 1 h after the injection. The retainment of 123I-MIBG in the myocardium was measured using SPECT imaging 6 h after the injection, and myocardial uptake and the myocardium/liver uptake ratio were calculated. The 6-h myocardium/liver uptake ratio of 123I-MIBG was significantly (p < 0.05) lower in the diabetic patients with clinically evident autonomic neuropathy compared with those without autonomic neuropathy. Greater body mass index was associated with lower peak net influx rate and 1-h myocardial uptake of 123I-MIBG, and greater diastolic blood pressure was associated with lower 1-h myocardial uptake of 123I-MIBG, whether or not the patients had diabetic autonomic neuropathy. In conclusion, reduction in the 6-h myocardium/liver uptake ratio of 123I-MIBG is related to diabetic autonomic neuropathy. Because the early 123I-MIBG accumulation in myocardium is reduced in diabetic patients with greater body mass index and diastolic blood pressure, irrespective of autonomic neuropathy, our results encourage the use of the late myocardial accumulation of 123I-MIBG for studying sympathetic neuropathy in the diabetic heart.

3-Iodobenzylguanidine↗
PubMed1996

Genetic susceptibility to severe course of nephropathia epidemica caused by Puumala hantavirus.

Nephropathia epidemica (NE) caused by Puumala hantavirus is one type of hemorrhagic fever with renal syndrome (HFRS). There is considerable variability in the clinical severity of NE. Many infections are subclinical but the disease can even be fatal. We questioned whether the wide spectrum in the outcome of NE is dependent, on host-related immunological factors by determining the major histocompatibility complex markers (MHC) in 74 adult patients with NE. Patients with the most severe course of the disease had a very high frequency of HLA B8, C4A*Q0, and DRB1*0301 alleles. HLA B8 was found in all 7 (100%) patients with shock and in 9 of the 13 (69%) patients who required dialysis, versus in only 25 of 74 (34%) in the entire population, and in 14 of 93 (15%) controls. In addition, various other clinical findings pointing to a severe form of NE were found to be associated with these alleles. Interestingly, the same MHC alleles are risk factors for various autoimmune diseases. This is the first study where a certain HLA haplotype is found to be associated with the clinical course of an acute viral disease or acute nephritis.

Acute Kidney Injury↗
PubMed1996

Subcutaneous and intraperitoneal insulin therapy in diabetic patients on CAPD.

We evaluated in a cross-over manner the consequences of subcutaneously and intraperitoneally given insulin on glucose control, insulin sensitivity, and serum lipids in 8 type I diabetic patients on continuous ambulatory peritoneal dialysis (CAPD). The patients were treated with both subcutaneous and intraperitoneal insulin for at least three months. After each period, metabolic studies were performed. Despite significantly improved glycemic control (Hb A1c 10.00 +/- 0.38% after subcutaneous and 8.40 +/- 0.36% after intraperitoneal insulin, p = 0.01), serum lipids showed unfavorable changes. High-density lipoprotein (HDL)-cholesterol was significantly lower (1.28 +/- 0.18 mmol/L vs 0.88 +/- 0.06 mmol/L, p = 0.03) and low-density lipoprotein (LDL)/HDL-cholesterol ratio was higher (p = 0.025) during intraperitoneal insulin. Total cholesterol, LDL-cholesterol, and triglycerides were higher during intraperitoneal insulin administration. Severe hypoglycemic episodes were more common during subcutaneous than intraperitoneal insulin. It is concluded that, although intraperitoneal insulin administration offers significantly better glycemic control and insulin sensitivity than subcutaneous insulin, the effect of serum lipids is more disadvantageous possibly via a direct effect of insulin on the liver.

Adult↗
PubMed1996

Pulmonary involvement in nephropathia epidemica: radiological findings and their clinical correlations.

Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome (HFRS) normally taking a benign clinical course. The etiologic agent, Puumala hantavirus is genetically closely related to Sin Nombre virus, which causes a frequently lethal febrile syndrome with pulmonary involvement (hantavirus pulmonary syndrome, HPS). HPS is characterized by acute respiratory distress, non-cardiogenic pulmonary edema and severe and hypotension, but usually no significant renal involvement. Pulmonary involvement and respiratory symptoms also occur in NE. To understand the mechanisms of pulmonary involvement in NE, we studied the clinical records and chest X-rays of 125 hospital-treated acutely ill NE patients. Twenty-eight percent of the patients had disease-related changes in their chest radiographs. Pleural effusion and atelectasis were the most common X-ray findings, whereas frank pulmonary edema was rare. The patients with pathologic X-ray findings had a more marked hypoproteinemia (lowest measured serum protein concentration 54 +/- 1 g/l) than those with normal X-ray (62.1 +/- 0.9 g/l, p < 0.001) and leukocytosis (highest measured blood leukocyte count 14.1 +/- 0.9 x 10(9)/l vs. 10.6 +/- 0.6 x 10(9)/l, p < 0.001) and more severe renal insufficiency (highest measured serum creatinine 590 +/- 60 mumol/l vs. 356 +/- 29 mumol/l, p < 0.05). Hypoproteinemia best predicted the occurrence of abnormal chest X-ray findings in NE. This suggests, that capillary leakage and inflammation may play a role in the pathogenesis of NE lung involvement, similarly as in HPS. Differently from HPS, the fluid volume overload associated with renal insufficiency seemed to contribute strongly to the chest X-ray changes in NE.

Case-Control Studies↗
PubMed1995

Neural modulation transfer function of the human visual system at various eccentricities.

We measured r.m.s. contrast sensitivity as a function of retinal illuminance at various spatial frequencies within 3-37 deg of eccentricity in the nasal visual field. In dim light contrast sensitivity increased in proportion to the square root of retinal illuminance obeying the DeVries-Rose law but in bright light contrast sensitivity was independent of luminance following Weber's law. Critical retinal illuminance (Ic) marking the transition between the laws was found to be independent of grating area but proportional to the spatial frequency squared at all eccentricities, in agreement with the Van Nes-Bouman law of foveal vision. In addition, the proportionality constant was found to be independent of eccentricity and similar to that of the fovea. According to our contrast detection model of human vision the modulation transfer function (PMTF) of the neural visual pathways squared is directly proportional to the critical retinal illuminance. On this basis our result means that PMTF is similar, i.e. equal to spatial frequency across the visual field, thus attenuating low spatial frequencies relatively more than high spatial frequencies. Hence, up to the spatial cut-off frequency determined by the lowest neural sampling density of each retinal location the neural modulation transfer function is independent of visual location.

Adult↗
PubMed1995

Comparison of intraperitoneal and subcutaneous insulin administration on insulin sensitivity and serum lipids in type I diabetic patients on continuous ambulatory peritoneal dialysis treatment.

1. The metabolic effects of intraperitoneal and subcutaneous insulin delivery were compared in a cross-over manner in six C-peptide-negative diabetic patients with end-stage renal disease on continuous ambulatory peritoneal dialysis. Each treatment period lasted at least 3 months. Hyperinsulinaemic euglycaemic clamp was performed and glucose turnover assessed using [3-(3)H]glucose as a tracer. 2. During intraperitoneal delivery the daily insulin dose was 2.4 times higher than during subcutaneous administration and glycaemic control was significantly better (HbA1c 7.63% +/- 0.46% and 9.52% +/- 0.51% during intraperitoneal and subcutaneous insulin respectively, P < 0.01). The number of hypoglycaemic episodes was lower during intraperitoneal insulin than during subcutaneous therapy. 3. Intraperitoneal insulin resulted in an enhanced glucose disposal rate (P < 0.01) and reduced fasting hepatic glucose production (P < 0.01). High-density lipoprotein-cholesterol decreased and the ratio of low-density lipoprotein/high-density lipoprotein-cholesterol increased significantly (P < 0.05) during intraperitoneal insulin delivery. 4. The results suggest that intraperitoneal insulin, while resulting in better glycaemic control and improved insulin sensitivity than subcutaneous insulin, increases serum triacylglycerol and total cholesterol and reduces high-density lipoprotein-cholesterol, possibly via a direct effect on the liver.

Adult↗