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Biomedical subjects

J Mustonen

Publications and source records attributed to J Mustonen.

At least 19 recordsLinked to original sources

Left ventricular function and dimensions in newly diagnosed non-insulin-dependent diabetes mellitus.

Left ventricular (LV) function and dimensions were assessed with Doppler and M-mode echocardiography in 26 men and 17 women with newly diagnosed non-insulin-dependent diabetes mellitus, and in 13 healthy control men and 13 women. The diabetic men had lower peak filling rate normalized to mitral stroke volume than the control men (mean +/- standard error of the mean, 4.2 +/- 0.1 vs 4.9 +/- 0.3 stroke volume/s, p less than 0.01). The diabetic women had increased LV mass (102 +/- 12 vs 86 +/- 8 g/m2, p less than 0.01) and decreased fractional shortening (34 +/- 1 vs 38 +/- 1%, p less than 0.05) when compared with control women. At 3 and 15 months, 23 diabetic men and 15 women were reexamined. Concomitantly with decreasing blood glucose levels, fractional shortening improved mainly during the first 3 months and was significantly higher in both diabetic men (36 +/- 2 vs 30 +/- 2%, p less than 0.05) and women (38 +/- 1 vs 34 +/- 1%, p less than 0.05) at 15 months than at baseline. In the diabetic men, peak filling rate increased from 4.3 +/- 0.1 stroke volume/s at baseline to 4.8 +/- 0.2 stroke volume/s at 15 months (p less than 0.05). At 15 months, peak filling rate was correlated (r = 0.61, p less than or equal to 0.001) with autonomic nervous function assessed as heart rate variability during deep breathing test in diabetic men who also showed an inverse correlation between LV hypertrophy and heart rate variability throughout the follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

HLA-DP region gene polymorphism in primary IgA nephropathy: no association.

Many features suggest that a genetically mediated abnormality of the IgA immune response is central in the pathogenesis of IgA nephropathy (IgAN). Candidate disease susceptibility genes include those encoding the MHC class II antigens, HLA-DR, -DQ, and -DP, and we have recently described an HLA-DQB1 association in IgAN. Polymorphisms of the HLA-DP region loci have been shown to associate with autoimmune diseases which share immunological features with IgAN; coeliac disease (CD) and dermatitis herpetiformis (DH). We have therefore examined restriction fragment length polymorphisms (RFLPs) of the DP alpha and DP beta chain genes (DPA1 and DPB1 respectively) in IgAN, and have studied three caucasoid populations (North, Mid, Southern Europe) to determine whether ethnic variation in genetic susceptibility exists. DNA was extracted from blood (IgAN, UK n = 89, Italy n = 75, Finland n = 49; Controls, UK n = 99, Italy n = 54, Finland n = 45), and studied by Southern blot hybridization techniques using the restriction enzymes BgI II and Msp I and cDNA 32P-labelled DPA1 and DPB1 probes respectively. The frequency distribution of the DPA1 and DPB1 fragments was similar between the three caucasoid IgAN patient groups compared to their respective controls. There was no association of DPA1 or DPB1 RFLPs with clinical features. These results suggest that HLA-DP region genes are not important in conferring disease susceptibility to IgAN and do not influence clinical disease expression. Moreover, different immunogenetic mechanisms operate in IgAN, CD, and DH.

Glomerulonephritis, IGA

Autonomic nervous function and its relationship to cardiac performance in middle-aged diabetic patients without clinically evident cardiovascular disease.

Autonomic nervous function was evaluated in 36 patients with insulin-dependent diabetes mellitus (IDDM), 39 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 48 control subjects, all without clinically evident cardiovascular disease. Valsalva ratio and heart rate variation during deep breathing were lower in both diabetic groups than in the control group. Autonomic nervous function score (ANFS) was more abnormal in patients with IDDM than in control subjects, but was not significantly increased in patients with NIDDM. There was a negative correlation between ANFS and left ventricular diastolic filling evaluated by echocardiography or peak heart rate during exercise in both diabetic groups. There were no correlations between ANFS and left ventricular systolic function at rest or during exercise in any of the groups. In conclusion, autonomic nervous function was abnormal in middle-aged diabetic patients, and it was associated with impaired left ventricular diastolic filling at rest and decreased heart rate response to exercise, but not with left ventricular systolic function.

Analysis of Variance

Noninvasive detection of cardiac sympathetic nervous dysfunction in diabetic patients using [123I]metaiodobenzylguanidine.

The association between clinical autonomic dysfunction and myocardial MIBG accumulation was investigated. The study groups comprised 6 male diabetic patients with autonomic neuropathy (ANP+ group), 6 male diabetic patients without autonomic neuropathy (ANP-group), and 6 male nondiabetic control subjects. The mean age was comparable in all groups, and the subjects had no evidence of coronary heart disease. Reduced heart-rate variation in a deep-breathing test was used as a criterion for autonomic neuropathy. Immediately after injection, the peak net influx rate of MIBG to myocardium was significantly (P less than 0.05) reduced in both diabetic groups. At 6 hr after MIBG injection, the MIBG uptake of the myocardium was significantly (P less than 0.05) smaller in the ANP+ group than in the control group. In the ANP- group, the MIBG uptake of the myocardium was between that of the ANP+ group and that of the control group. Our data show that reduced myocardial MIBG accumulation is associated with autonomic dysfunction in diabetic patients, but it can occur to a lesser extent also in diabetic patients without apparent autonomic neuropathy. The measurement of the myocardial MIBG accumulation is a promising new method to detect cardiac sympathetic nervous dysfunction in diabetic patients.

3-Iodobenzylguanidine

Acute effect of dialysate calcium concentration and intravenous vitamin D3 on the secretion of parathyroid hormone in hemodialysis patients.

We studied the suppression of intact parathyroid hormone (PTH) in ten patients on chronic hemodialysis using different calcium concentrations of dialysate. Secondly, giving i.v. vitamin D3 at commencement of dialysis we investigated whether 1 alpha (OH)D3 or 1,25(OH)2D3 acutely modifies the responsiveness of the parathyroid gland to the suppressive effect of increased serum calcium. Dialysis with high-calcium dialysate (1.75 mmol/l) reverted the plasma PTH to normal limits. Lower-calcium dialysate (1.5 mmol/l) induced only a partial suppression of hyperparathyroidism. We found no differences in the suppression of hyperparathyroidism whether 1 alpha (OH)D3 or 1,25(OH)2D3 was given at the beginning of the dialysis or not. We conclude that the suppressibility of hyperparathyroidism in dialysis patients can be evaluated by different calcium concentrations of dialysate, and that i.v. vitamin D3 does not acutely modify the responsiveness of the parathyroid gland to the effect of calcium.

Aged

Acute effects of calcium carbonate and citrate on secondary hyperparathyroidism in chronic renal failure.

Two grams of elemental calcium as carbonate or citrate were given after an overnight fast to 14 patients with advanced renal failure (serum creatinine 759 +/- 365 mumol/l, mean +/- SD). The suppressibility of their hyperparathyroidism was confirmed with a calcium infusion test. Both calcium citrate and carbonate increased significantly plasma ionized calcium (6.8 and 4.5%, respectively) and total calcium (9.3 and 6.0%), p less than 0.001. In the majority of the patients, calcium citrate but not carbonate increased plasma calcium sufficiently to induce the suppression of hyperparathyroidism. The decrease of plasma intact parathyroid hormone was 35.9 +/- 24.8% (mean +/- SD); p less than 0.001) after calcium citrate and 9.2 +/- 18.9% (mean +/- SD; NS) after calcium carbonate.

Calcium

Mesangial glomerulopathy in rheumatoid arthritis patients. Clinical follow-up and relation to antirheumatic therapy.

23 patients (16 women, 7 men) with rheumatoid arthritis (RA) and renal biopsy-proven mesangial glomerulopathy (MGP) were followed for 4-117 months (median 42) in order to evaluate the clinical course of their renal disease. Urinalysis was made, and 24-hour urine protein excretion and serum creatinine were determined. At the time of renal biopsy, the clinical renal findings of the patients were isolated hematuria (n = 10), isolated proteinuria (n = 6) and hematuria combined with proteinuria (n = 7). Hematuria persisted and renal function remained normal in all patients with isolated hematuria. A possible association between the presence of hematuria and the use of antirheumatic drugs was not established in this study. Proteinuria was clinically closely associated with the use of antirheumatic drugs in 9 out of 13 cases (6 with gold sodium thiomalate, 2 with D-penicillamine and 1 with auranofin) suggesting that antirheumatic drugs are important contributors to proteinuria in these patients. Renal function, although initially reduced in some patients, remained stable in all but 1 patient with IgA glomerulonephritis who developed the nephrotic syndrome and died of uremia. In conclusion, the clinical course of MGP in RA patients is benign in most patients. Moreover, this nephropathy may not represent a clinical entity. Proteinuria was related to antirheumatic drugs in most patients whereas microhematuria was constant even after stopping the antirheumatic drugs.

Adult

Effect of enalapril on plasma atrial natriuretic peptide in late recovery phase of acute myocardial infarction.

A 12 week randomised, double blind, placebo controlled study on the effect of enalapril (5-20 mg daily) on the concentration of plasma atrial natriuretic peptide level and activity of the sympathetic nervous system and renin angiotensin system was done on 27 patients who had suffered an uncomplicated acute myocardial infarction two to six months earlier. None of our patients needed drug treatment for heart failure, but their exercise capacity was markedly limited. Plasma neurohormone concentrations at baseline and after 12 weeks of treatment were also compared with those of healthy controls. Concentrations of plasma atrial natriuretic peptide concentrations remained high throughout the study in those patients on beta-blockers. Enalapril treatment had no definite effect on the concentrations of plasma atrial natriuretic peptide or other neurohormone.

Aldosterone

Autonomic nervous system function in Baltic myoclonus epilepsy.

Baltic myoclonus epilepsy (BME) is a neurodegenerative disease characterized by tonic-clonic seizures, myoclonus and a progressive course. The aim of the present study was to assess the clinical symptoms and signs of possible involvement of the autonomic nervous system (ANS) and objectively evaluate autonomically mediated cardiovascular reflexes in this syndrome. Fifteen patients with BME and 14 healthy control subjects were studied. Thirteen (87%) of the patients had symptoms suggesting ANS dysfunction. The most common symptoms were postural dizziness and sweating disturbances. The heart rate variation during deep breathing was lower in patients than in controls. The heart rate response and systolic blood pressure response during tilting were similar in both groups. Our results suggest a mild parasympathetic hypofunction and an intact sympathetic function in ambulatory patients with BME.

Adult

Immunoglobulin heavy chain switch region gene polymorphisms in glomerulonephritis.

Much evidence suggests that primary IgA nephropathy (IgAN) and idiopathic membranous nephropathy (MN) are immune complex mediated diseases. Moreover, genetic factors may play an important role in their pathogenesis. Recently, restriction fragment length polymorphisms (RFLPs) of the immunoglobulin heavy chain genes have been described which appear to associate with glomerulonephritis. We have studied RFLPs of the switch region of the IgM (S mu) and IgA1 (S alpha 1) heavy chain in MN and IgAN. DNA obtained from British Caucasoids with IgAN (N = 75), MN (N = 43), and normal controls (N = 73), was digested with the restriction enzyme Sac1, and studied using Southern blot techniques and hybridization with a 32P labelled DNA probe homologous to S mu. This probe detects RFLPs at the S mu and S alpha 1 loci. The genotypic and allelic frequencies of the S mu and S alpha 1 alleles in IgAN and MN was similar to normal controls. Caucasoid subjects with IgAN from Northern and Southern Europe (Finland and Italy, respectively) were also studied to determine whether an ethnic variation in genetic susceptibility to IgAN exists. The frequency of the S mu and S alpha 1 alleles was similar between the patient groups and their respective local healthy controls. These results do not support the recent findings of an association with RFLPs of the S mu and S alpha 1 loci in IgAN and MN, and suggest that the immunoglobulin heavy chain switch region genes are not important in conferring disease susceptibility to IgAN or MN.

Blotting, Southern

Immunological comparison of patients with rheumatoid arthritis with and without nephropathy.

Serum immunoglobulins IgG, IgA, and IgM, serum complement components C3 and C4, circulating immune complexes, antinuclear antibodies, and rheumatoid factor were measured in 56 patients with rheumatoid arthritis (RA) and nephropathy (23 with mesangial glomerulopathy; 13 with membranous glomerulonephritis; and 20 with amyloidosis) and 35 patients with RA without nephropathy (controls). Renal immunofluorescence findings in patients with mesangial glomerulopathy were compared with the serologic data. There were no differences in the occurrence of rheumatoid factor, antinuclear antibodies, and circulating immune complexes and the concentrations of serum complement C3 and C4 between various RA nephropathy groups and controls. Serum IgA and IgM concentrations were significantly higher in patients with mesangial glomerulopathy and amyloidosis than in controls. In patients with mesangial glomerulopathy glomerular IgM, IgA, and C3 were the most prominent findings in immunofluorescence examination. The serum IgA concentration was significantly higher in those patients with mesangial glomerulopathy with mesangial IgA deposits than in those without (4.97 (SD 1.03) g/l v 2.07 (1.21) g/l). The highest serum IgA concentrations (5.08 (1.39) g/l) were seen in the four patients with IgA glomerulonephritis. The prevalence of IgA glomerulonephritis in the renal biopsy material of the patients with RA was 5%, which possibly differs little from that seen in the general population. The results suggest that circulating immune complexes may not have any major role in the pathogenesis of various nephropathy types in patients with RA, contrary to their role in most extra-articular manifestations of RA.

Adult

Clinical significance of autoantibodies against neutrophil cytoplasmic components in patients with renal disease.

The diagnostic significance of anticytoplasmic autoantibodies (ANCA) was studied in 71 renal patients. The ANCA test was positive in 67% of patients with Wegener's granulomatosis (WG), in 35% of those with a simultaneous renal and respiratory tract disease but not diagnosed as WG and in 22% of patients with a renal disease associated with unspecific collagenosis/vasculitis. Among WG patients ANCA positivity clearly correlated with the presence of active renal disease. Interestingly, both ANCA-positive and -negative patients were encountered in the group with acute renal failure and acute extracapillary glomerulonephritis associated with diffuse pulmonary infiltrates. The diagnostic and clinical significance of the ANCA test in these cases remains for the present obscure. In the majority of the ANCA-positive renal patients with respiratory tract abnormalities, the antibodies showed diffuse cytoplasmic staining and were mostly of the IgG class, of both IgG and IgM classes in some cases and of IgG, IgM and IgA classes in 1 patient. In patients with unspecific vasculitis/collagenosis the level of ANCA was rather low, and the distribution of different isotypes resembled that of patients with respiratory symptoms. A certain isotype of ANCA or staining pattern did not mark out any clinicopathologic subgroup among the patients. Our findings indicate that the clinical picture of ANCA-positive patients varies considerably and the ANCA test may not be as specific a marker of WG as previously suggested.

Autoantibodies

Glomerular IgA deposits in patients with celiac disease.

Glomerular immunopathology was studied in 25 patients with newly diagnosed celiac disease. None had clinical signs of renal disease. Glomeruli were obtained by fine-needle aspiration biopsy. The specimens were processed and studied by indirect immunofluorescence for immunoglobulins and complement. Mesangial IgA was found in 8 of the patients. It occurred occasionally together with slight IgG or IgM, but C3 was not seen in these patients. IgA-class circulating immune complexes (CIC), antireticulin antibodies (ARA), antigliadin antibodies (AGA), and rheumatoid factor (RF) occurred significantly more often in the patients with mesangial IgA than in the 17 patients having no mesangial IgA. The patients with mesangial IgA also had significantly higher mean levels of serum IgA, IgA-ARA and IgA-AGA than those without. The results suggest that glomerular mesangial deposits of IgA occur frequently in untreated celiac disease and that they are in some way associated with circulating IgA-class antibodies and immune complexes. In this situation IgA seems to be deposited without being able to induce clinically overt glomerulonephritis, a circumstance that may be related to the lack of complement in the deposits.

Adolescent

Proteinuria and haematuria are frequently present in patients with lung cancer.

The aim of the study was to ascertain whether there is an increased occurrence of proteinuria and/or haematuria among lung cancer patients. As a control group we selected patients with bronchial asthma treated at the same hospital and during the same period as the lung cancer patients. The study comprised a retrospective part, where observations were made at two hospitals on 166 and 284 lung cancer patients. Proteinuria was observed in 9% and 13% and haematuria in 5% and 9% of these patients. The prevalences were significantly greater than among the asthmatic patients. This result prompted a prospective case-control study involving 150 consecutive patients with lung cancer and asthma, respectively. Twelve patients in the cancer group and one asthmatic patient had a daily urine protein excretion exceeding 100 mg (P less than 0.004); haematuria was noted in 14 and one, respectively (P less than 0.002). We conclude that the occurrence of proteinuria and haematuria is unexpectedly increased among patients with lung cancer.

Aged