Discordance in the development of peripheral and autonomic neuropathy during vincristine therapy.
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Biomedical subjects
Publications and source records attributed to J Mustonen.
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The clinical course of mesangial glomerulopathy with IgM deposits (IgM-nephropathy) was studied in 54 patients. The initial manifestations of the disease were nephrotic syndrome in 18, proteinuria in 21, proteinuria together with hematuria in 4 and isolated hematuria in 11 patients. The nephrotic syndrome was steroid-responsive in 60% of cases and of these 80% were steroid-dependent. During a 5-year postbiopsy follow-up 3 patients went into terminal uremia and in 6 more patients a milder renal insufficiency was observed. Three patients were rebiopsied and in 2 of these the second biopsy specimen disclosed typical focal and segmental glomerulosclerosis. Hematuria was a favorable sign, as no patient with hematuria showed progressive impairment of renal function. The prevalence of hypertension in the whole material was 37%. At close of follow-up 35% of all patients were in clinical remission. It is suggested that IgM-nephropathy associated with abundant proteinuria or the nephrotic syndrome represents a distinct disorder from that associated with hematuria. While the nephrotic type often manifested itself with a morphologic change and a tendency to develop renal insufficiency, the hematuric type showed female predominance, a high tendency to spontaneous clinical remission and a favorable clinical course.
We studied the effect of one haemodialysis treatment on the plasma concentrations of intact parathyroid hormone (PTH), total immunoreactive PTH (determined with an antibody against the mid-molecular part of the hormone), and ionised calcium in 25 patients on maintenance dialysis for chronic renal failure. During dialysis the calcium concentration in the external fluid was 1.75 mmol/l, which led to an increase in the plasma ionised calcium concentration from 1.23 +/- 0.07 mmol/l (mean +/- SD) at commencement of dialysis to a final 1.35 +/- 0.07 mmol/l (P less than 0.001). The plasma concentration of intact PTH decreased from 27.4 +/- 26.3 pmol/l to 13.0 +/- 19.1 pmol/l (P less than 0.001) during the treatment. Total immunoreactive PTH did not change, reflecting poor dialysability of PTH and PTH fragments. We also compared the dialysis-induced changes in the plasma concentrations of intact PTH and ionised calcium with those induced by a calcium infusion test. We conclude that in the majority of dialysis patients, one haemodialysis treatment with a relatively high external fluid calcium concentration can be used to assess the suppressibility of secondary hyperparathyroidism.
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Left ventricular systolic and diastolic function was studied using systolic time intervals and echocardiography in 19 male and 17 female patients with Type 1 (insulin-dependent) diabetes, 24 male and 15 female patients with Type 2 (non-insulin-dependent) diabetes and 24 male and 24 female control subjects. The subjects for the present study were selected from a population based study in which 117 Type 1 and 510 Type 2 diabetic patients and 649 non-diabetic subjects were originally examined. After exclusions, none of the subjects had any evidence of coronary heart disease, hypertension or other diseases known to affect left ventricular function. There were no consistent differences in systolic time intervals or echocardiographic variables of systolic function between patients with Type 1 diabetes and non-diabetic control subjects; but patients with Type 2 diabetes showed an increased fractional shortening. Female patients with Type 2 diabetes showed an increased left ventricular mass not explicable by hypertension. Isovolumic relaxation period was longer in male (86 +/- 3 ms; mean +/- SEM) and female patients (84 +/- 6 ms) with Type 2 diabetes than in male (76 +/- 3 ms; p less than 0.05) and female (71 +/- 3 ms; p less than 0.05) control subjects. Peak diastolic filling rate was lower in female patients with Type 1 diabetes (12.8 +/- 0.8 cm/s, p less than 0.05) and in male (11.5 +/- 0.8 cm/s; p less than 0.01) and female patients (11.5 +/- 0.6 cm/s; p less than 0.001) with Type 2 diabetes as compared to male (14.4 +/- 0.7 cm/s) and female (14.9 +/- 0.5 cm/s) control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Quantitative electrocardiographic (ECG) and vectorcardiographic (VCG) analysis was carried out in 113 newly diagnosed, middle-aged, non-insulin-dependent diabetics (61 men, 52 women) and 125 non-diabetic control subjects (56 men, 69 women) in order to explore changes attributable to non-coronary heart disease (diabetic cardiomyopathy) in diabetics. Diabetic men had a prolonged PQ interval and women a more negative P-terminal force and a more leftward frontal QRS axis than their non-diabetic counterparts, but no other significant differences we found between diabetic and non-diabetic subjects in various quantitative ECG and VCG variables when the effect of confounding factors (age, obesity, coronary heart disease, hypertension, drugs) was taken into account. The more negative P-terminal force and left axis deviation in diabetic women could be explained by a concomitant left ventricular hypertrophy among them. Non-insulin-dependent (type 2) diabetes, which is commonly preceded by a long duration of asymptomatic hyperglycaemia, is not associated, early in its clinical course, with major ECG and VCG abnormalities suggestive of diabetic cardiomyopathy.
Left ventricular function was evaluated noninvasively before and three months after starting insulin treatment in nine patients (mean age 61.8 years, range 51-68 years) with non-insulin dependent diabetes showing an impaired insulin secretion capacity. After starting insulin treatment, fasting blood glucose decreased from 12.9 +/- 0.5 mmol/l (mean +/- SEM) to 9.8 +/- 1.2 mmol/l (p = 0.03), but the decrease of glycosylated haemoglobin Alc was not significant (9.0 +/- 0.4% vs. 8.3 +/- 0.6%). On systolic time intervals, PEP/LVET ratio improved from 0.44 +/- 0.03 to 0.37 +/- 0.02 (p = 0.03). On M-mode echocardiography, E-F slope became steeper (89 +/- 6 mm/sec vs. 103 +/- 8 mm/sec; p = 0.01) but no significant changes were observed in other variables reflecting diastolic or systolic function. On equilibrium radionuclide angiocardiography, the left ventricular ejection fraction at rest was similar before and after starting insulin treatment (48.6 +/- 3.2% vs. 49.2 +/- 2.8%) but during peak exercise the left ventricular ejection fraction improved significantly (51.0 +/- 5.3% vs. 59.9 +/- 4.7%; p = 0.02). The change of PEP/LVET ratio correlated significantly with the changes of blood glucose and glycosylated haemoglobin Alc levels, but the correlation between these metabolic variables and the change of left ventricular ejection fraction during exercise did not reach statistical significance. In conclusion, the left ventricular function improved concomitantly with improved metabolic control after starting insulin treatment in middle-aged patients with non-insulin-dependent diabetes having an impairment in insulin secretion capacity. This finding suggests that metabolic factors are involved in the left ventricular dysfunction observed in diabetes.
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We studied the parathyroid function in patients with advanced renal failure by determining their plasma concentrations of ionized calcium (iCa), intact parathyroid hormone (PTH) and its inactive metabolites (PTH-MM). The suppressibility of the parathyroidism was studied with a calcium infusion test. The intact PTH values of the nondialysis and dialysis patients did not statistically differ from each other. The concentrations of PTH-MM were, however, higher in the dialysis patients than in the nondialysis patients (p less than 0.05). The ratio of PTH-MM to intact PTH was lowest in healthy reference subjects and highest in dialysis patients (p less than 0.01), and did not correlate with the degree of intact PTH elevation in the patient groups. The calcium infusion test was carried out on 15 patients. All showed suppression in the elevated plasma intact PTH concentration and in 6 the intact PTH value normalized. The PTH-MM value did not normalize in any of the patients. During oral calcium treatment the degree of intact PTH suppression at an achieved concentration of plasma iCa was predictable from the infusion test. Three patients were parathyroidectomized after the calcium infusion test. In 2 of these elevated intact PTH normalized within 24 h while in 1 no change took place. In this latter case on clinical improvement was noted. We conclude that the determination of plasma intact PTH concentration especially of combined with plasma iCa value is a reliable means of studying the hyperparathyroidism associated with chronic renal failure.
Oral poliovirus vaccine was used to immunize 51 patients with IgA glomerulonephritis and 44 healthy controls. The patients showed an enhanced antibody response compared to controls. This was apparent in a higher frequency of strong increases in neutralizing antibody titres during the course of immunization as well as higher levels of virus-specific IgA-class antibodies. IgG-class antibodies showed similar activity in both groups. In patients the neutralizing antibodies correlated with the virus-specific IgA-class antibodies, suggesting that the IgA-antibodies synthesized by the patients are functionally competent antibodies.
The excreted fraction of filtered sodium (FeNa) was examined in 54 patients with acute intrinsic renal failure in whom renal biopsy was performed to determine the morphology of the acute renal disease. In patients with acute tubulointerstitial nephritis oliguric patients had almost constantly elevated FeNa values, whereas in non-oliguric patients with acute tubulointerstitial nephritis this was observed in less than half. The five patients with acute extracapillary glomerulonephritis had an FeNa greater than 1. FeNa values were low, especially in non-oliguric patients who had mild impairment of renal function. The presence of a high FeNa value correlated significantly with severe morphological tubular changes observed on renal biopsy. We conclude that patients with acute tubulointerstitial nephritis cannot be distinguished from those with acute glomerulonephritis by FeNa, as in both types of acute nephritis the FeNa test shows both low and elevated values.
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The relationship of blood pressure to fasting and postglucose serum insulin and lipid levels was examined in 133 (70 men, 63 women) newly diagnosed, non-insulin-dependent diabetic patients and 144 (62 men, 82 women) non-diabetic control subjects. In addition, the frequency of left ventricular hypertrophy by ECG criteria and left ventricular mass determined by M-mode echocardiography in diabetic patients were compared to that in non-diabetic subjects. Fasting serum insulin showed a significant correlation with systolic and diastolic blood pressure levels in male non-diabetic subjects, but not in male and female diabetic or in female non-diabetic subjects. Postglucose serum insulin levels showed no significant correlations with systolic or diastolic blood pressure levels in men, but in female diabetic and non-diabetic subjects significant correlations were found in particular with systolic blood pressure level. The correlations between serum insulin and blood pressure levels could not be accounted for by obesity. In male and female diabetic subjects serum triglycerides correlated positively with systolic and diastolic blood pressure levels even after adjustment for obesity. No significant difference was found in the prevalence of left ventricular hypertrophy based on ECG criteria between diabetic and non-diabetic subjects, but female diabetic subjects showed in echocardiography an increased left ventricular mass related to body surface area compared to their non-diabetic counterparts. Elevated systolic blood pressure and high postglucose serum insulin levels showed an independent, significant association with left ventricular mass in female diabetic subjects.
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.
To test the hypothesis that rheumatoid factor (RF) protects against (immune complex mediated) renal disease, patients with rheumatoid arthritis (RA; 48 with nephropathy of various types, 35 without renal disease) and systemic lupus erythematosus (SLE; 35 with and 17 without nephritis) were evaluated for the presence and titre of RF. There was no correlation between RF and nephropathy in RA, whereas in SLE RFs were almost exclusively seen in patients without nephropathy. This result supports the above hypothesis for lupus nephropathy but not for RA associated renal disease, and it may be explained by a more pronounced role for immune complexes in SLE and interference of RFs with the complexes.
Renal biopsy specimens from 39 patients with rheumatoid arthritis and clinical signs of renal disease disclosed a mild mesangial glomerulopathy in more than 1 in 4 cases. Almost all patients had deposits of immunoglobulin and complement in the mesangial lesions. This type of glomerulopathy was the most common cause of hematuria and was also frequently encountered in proteinuric patients. Clinically it was not possible to distinguish between mesangial and membranous nephropathy.
A single dose of inactivated mumps virus vaccine was administered to male patients with IgA glomerulonephritis (IgA-GN), IgM glomerulonephritis (IgM-GN) and to healthy males. Antibodies to mumps virus were determined using an enzyme-linked immunosorbent assay. Patients with IgA-GN showed a higher and more sustained IgG and IgA antibody response compared to patients with IgM-GN or healthy controls. Before vaccination, patients with IgM-GN had higher levels of IgG antibodies than the controls or those with IgA-GN. However, the IgA antibody and IgG responses after vaccination were low. IgM antibody responses did not vary among the groups studied. It is concluded that patients with IgA-GN are high responders for IgA and IgG antibody production. Patients with IgM-GN are low responders, especially for IgA antibody.
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