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Biomedical subjects

I Ala-Houhala

Publications and source records attributed to I Ala-Houhala.

16 recordsLinked to original sources
PubMed2002

Skeletal deposition of clodronate is related to parathyroid function and bone turnover in dialysis patients.

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.

Adult↗
PubMed2001

Polymorphism of the cytokine genes in hospitalized patients with Puumala hantavirus infection.

BACKGROUND: Nephropathia epidemica (NE) is a mild type of haemorrhagic fever with renal syndrome caused by Puumala (PUU) hantavirus. The clinical course of NE varies from asymptomatic to fatal. The aim of this study was to establish whether polymorphisms in the cytokine genes are associated with susceptibility to and outcome of NE. METHODS: The genotypes of the genes of tumour necrosis factor alpha (TNFalpha), interleukin-1alpha (IL-1alpha), IL-1beta and IL-1 receptor antagonist (IL-1RA) were analysed by polymerase chain reaction in 87 subjects, all hospital-treated for serologically confirmed acute NE. The control group comprised 400 healthy blood donors. Nineteen out of these 400 (5%) controls were PUU virus-seropositive. RESULTS: IL-1RA allele 2 and IL-1beta (base exchange polymorphism at position -511) allele 2 were strongly associated with each other in both groups. NE patients were more often IL-1RA-2 negative/IL-1beta-2 negative than PUU-seronegative blood donors (38 vs 27%, odds ratio 1.65, 95% confidence interval 1.0-2.7). However, there were no differences in the clinical severity of NE between the IL-1RA-2 negative/IL-1beta-2 negative and the other patients. The other allele frequencies studied evinced no statistically significant differences between the groups. Thirty-three out of 87 (38%) patients and 121 out of 381 (32%) seronegative controls were carriers of the high-producer genotype TNF2 allele. Several parameters showed the clinical course of NE to be more severe in TNF2 carriers than in non-carriers. CONCLUSIONS: These data suggest that non-carriage of the IL-1RA allele 2 and IL-1beta (-511) allele 2 may contribute to susceptibility to NE. Furthermore, TNFalpha polymorphism seems to be associated with the outcome of NE.

Adolescent↗
PubMed2001

Reference intervals for the markers of proteinuria with a standardised bed-rest collection of urine.

Reference intervals for markers of proteinuria or glomerular charge selectivity were measured in 61 healthy female and 61 healthy male individuals. Timed bed-rest and daytime collections were used to assess significance of preanalytical variability of results. Bed-rest collections are advisable for research on renal damage, whereas in routine care, robust protein/creatinine ratios work as practical estimates of protein excretion rates, the correlations to excretion rates improving with increasing proteinuria. For glomerular charge selectivity, pancreatic/salivary isoamylase clearance ratio showed lower within-subject biological variation than IgG/IgG4 clearance ratio, allowing more accurate classification into normal and reduced charge selectivity. With our method, the lower 2.5% reference intervals for isoamylase clearance ratio were 1.1 in men and 1.9 in women.

Acetylglucosaminidase↗
PubMed2000

Renal function and blood pressure five years after puumala virus-induced nephropathy.

BACKGROUND: Nephropathia epidemica (NE) is a mild form of hemorrhagic fever with renal syndrome caused by Puumala hantavirus. Its long-term prognosis is considered favorable. Some reports suggest, however, that a previous hantavirus infection increases the risk of hypertension. METHODS: We studied 46 previously healthy subjects (26 males and 20 females, mean age of 44 years) who had serologically confirmed NE three to seven years previously, and 38 healthy, seronegative controls (22 males and 16 females, mean age of 44 years). Ambulatory blood pressure (ABP) was monitored. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by 51CrEDTA and 131I-hippurate clearances, respectively. The filtration fraction (FF) was calculated. Quantitative 24-hour urinary protein excretion (UprotE) and timed overnight urinary excretion of alpha1-microglobulin were measured. RESULTS: The NE patients had a higher mean ambulatory systolic BP than the controls (123 +/- 13 vs. 117 +/- 9 mm Hg, P = 0. 008). GFR and FF were increased in patients compared with controls (GFR, 120 +/- 20 vs. 109 +/- 14 mL/min/1.73 m2, P = 0.006; FF, 19 +/- 3 vs. 18 +/- 3%, P = 0.030), but ERPF did not differ between the groups. The patients also had higher UPE than the controls (median 0. 18 g/day, range 0.12 to 0.38 vs. median 0.14 g/day, range 0.09 to 0. 24, P < 0.001, respectively). The overnight urinary excretion rate of alpha1-microglobulin exceeded 7 microg/min in nine patients. CONCLUSION: Three to seven years after NE, the patients had higher GFR and FF, more proteinuria, and higher ambulatory systolic BP compared with the healthy controls. NE may thus cause mild renal lesions and alterations in BP in some patients.

Acute Kidney Injury↗
PubMed1999

Pharmacokinetics of clodronate in haemodialysis patients.

BACKGROUND: Clodronate is a bisphosphonate used in the treatment of hypercalcaemia of various aetiologies. The major route of elimination of clodronate is renal excretion. The aim of the study was to derive data for the adjustment of dosage in haemodialysis patients. METHODS: The pharmacokinetic parameters describing the fate of an intravenous infusion of 300 mg clodronate disodium were studied in 10 haemodialysis patients. Clodronate disodium in serum, urine and dialysate samples was analysed by capillary gas chromatography with mass-selective detection. RESULTS: Of the 300 mg clodronate infused, 159 mg (53%) was excreted into dialysate within 4 h. Clearance by haemodialysis (CLD) was 87.8+/-16.2 ml/min, accounting for 84% of total serum clearance (CLtot). Non-renal, non-dialysis clearance (CL(NRD)) represents the removal of the drug via other routes than dialysis or kidneys. The greatest CL(NRD) was observed in patients with most severe hyperparathyroidism. There was a positive correlation between CL(NRD) and plasma intact PTH concentration. CONCLUSIONS: According to the present findings, standard haemodialysis removes clodronate effectively from the circulation, and total clearance in haemodialysis patients on a dialysis day is not very different from that in healthy subjects. The regimen of dosing intravenous clodronate in hypercalcaemia can also be used in haemodialysis patients. The portion of clodronate eliminated by routes other than via dialysate or kidneys, i.e. predominantly via skeletal deposition, was related to the severity of hyperparathyroidism.

Aged↗
PubMed1999

Proteinuria and renal function during and after acute urinary retention.

PURPOSE: Benign prostatic hyperplasia is the most common neoplasm as well as the main cause of bladder outlet obstruction in men. It may progress to involve a risk of urinary retention. We investigated the effects of acute urinary retention on renal function. MATERIALS AND METHODS: We evaluated renal function using biochemical markers in 25 men with a mean age of 69 years in whom an episode of acute urinary retention a mean of 31 hours in duration was due to bladder outlet obstruction. Patients were followed for 6 months after acute retention was relieved. Patients were not known to have had any renal disease previously. RESULTS: During acute urinary retention at presentation, and after 1 and 6 months we noted albuminuria in 100, 92 and 54% of patients, elevated alpha 1-microglobulin excretion in 54, 39 and 58%, and elevated beta 2-microglobulin excretion in 17, 19 and 9%. Serum creatinine or creatinine clearance did not predict proteinuria. All parameters became normal at 6 months in only 2 cases. CONCLUSIONS: Acute urinary retention affects glomerular and tubular renal function. After acute urinary retention was relieved increased glomerular permeability and tubular damage persisted in the majority of patients. This condition may have been partially due to previous long-term bladder outlet obstruction. Our findings stress the importance of the rapid recognition and treatment of acute urinary retention.

Acute Disease↗
PubMed1998

Effect of intravenous calcitriol on cardiac systolic and diastolic function in patients on hemodialysis.

The systolic and diastolic function of the heart of hemodialysis (HD) patients and the effect of intravenous vitamin D therapy on cardiac function was studied by Doppler and digitized M-mode echocardiography in 10 HD patients before and after 3-4.5 months of calcitriol therapy. Calcitriol was administered intravenously 1-3 times a week at a dose of 1-2 microg after the dialysis sessions. Ten age- and sex-matched healthy controls were also examined echocardiographically. Before calcitriol therapy cardiac wall thicknesses (interventricular septum, posterior wall) and left ventricle (LV) dimensions (end diastolic, end systolic) were greater, and LV diastolic (peak late diastolic velocity, peak early diastolic velocity/peak late diastolic velocity ratio, isovolumic relaxation time) and systolic (fractional shortening) function was impaired in HD patients as compared to controls. The LV posterior wall thickness was related to plasma parathyroid hormone (PTH; r = 0. 70, p = 0.01) in the patients. Calcitriol therapy raised serum ionized Ca from 1.23+/-0.04 to 1.33 +/- 0.04 mmol/l and reduced PTH from 41.1+/-10.7 to 34.2+/-11.7 pmol/l (29+/-11%). Calcitriol therapy did not cause any significant changes in cardiac function in the whole patient group. However, in a subgroup of 5 patients with severe but controllable hyperparathyroidism (PTH >3 times upper normal margin) the LV dimensions and systolic function improved (LV end systolic dimension from 39.0 +/- 4.0 to 31.3 +/- 2.9 mm, p = 0. 03; LV end diastolic dimension from 57.7 +/- 3.1 to 53.4 +/- 3.0 mm, p = 0.06; fractional shortening from 33 +/- 4 to 42 +/- 3%, p = 0. 03). The diastolic indices improved also, but not significantly. In conclusion, left ventricle hypertrophy and systolic and diastolic dysfunction was observed in HD patients. Intravenous calcitriol therapy improved cardiac function in patients with severe secondary hyperparathyroidism.

Adult↗
PubMed1990

Effects of exercise on glomerular passage of macromolecules in patients with diabetic nephropathy and in healthy subjects.

The effects of exercise on glomerular permeability were investigated in 12 proteinuric insulin-dependent diabetic patients and in 12 healthy controls by measuring the fractional protein and dextran clearances at rest and after exercise. Exercise significantly reduced the glomerular filtration rate (GFR) and the renal plasma flow (RPF) and markedly increased the filtration fraction (FF) in both diabetics and controls. The fractional clearances of albumin and IgG increased significantly during exercise in diabetics. Exercise also significantly increased the fractional clearance of albumin in healthy controls. The changes in the fractional protein clearances correlated significantly with the changes in the FF. In diabetics the fractional dextran clearances of molecules with a radius greater than or equal to 4.8 nm were significantly elevated after exercise. This was not found in healthy controls. It is concluded that exercise increases glomerular permeability by influencing the renal haemodynamics. Probably partial depletion of negative charges on the glomerular capillary wall plays a role in exercise-induced proteinuria in both healthy and diabetic subjects. In addition, the altered glomerular permeability during exercise is associated with increased size of the filtering pores in diabetic nephropathy.

Adult↗
PubMed1990

Interrelations of blood pressure, glomerular filtration rate, protein clearances and sodium excretion in patients with glomerulonephritis and diabetic nephropathy.

The roles of blood pressure and glomerular filtration rate in the renal handling of albumin, beta 2-microglobulin and sodium were studied by partial correlation analysis in 22 patients with glomerulonephritis and in 25 patients with diabetic nephropathy. The analysis showed that in these proteinuric patients blood pressure may have an independent role in the regulation of albumin excretion in both diseases. Fractional beta 2-microglobulin clearance and fractional excretion of sodium correlated significantly in both diseases. In the diabetic patients this correlation remained strong after removing the effect of blood pressure, whereas in the patients with glomerulonephritis control of blood pressure clearly decreased the correlation. This reflects differences in the renal handling of sodium and beta 2-microglobulin in patients with diabetic nephropathy and glomerulonephritis.

Adult↗
PubMed1987

Fractional dextran and protein clearances in glomerulonephritis and in diabetic nephropathy.

The renal clearance of dextran and protein of different molecular sizes has been measured in 42 proteinuric patients with diabetes and glomerulonephritis. In both patient groups the fractional low molecular (radii 3.0-3.6 nm) dextran clearances were significantly decreased whereas the fractional high molecular (radii 5.1-7.8 nm) dextran clearances were increased as compared with the controls. A porosity/charge index was constructed by calculating the ratio of fractional clearances of neutral to anionic macromolecules (theta D3.6/theta ALB, theta D5.1/theta IgG). In diabetic patients the relation between the fractional clearances of neutral and anionic macromolecules was dependent on glomerular filtration rate. It seems likely that the altered glomerular permeability in diabetic nephropathy is associated with a decrease of charge as renal function deteriorates. In glomerulonephritis the process is different and there is a high degree of variation from case to case.

Adolescent↗
PubMed1987

Intravenously administered frusemide increases glomerular permeability.

1. The effects of frusemide on glomerular permeability were investigated in eight proteinuric patients by measuring the fractional protein and dextran clearances and correlating these observations with changes in renal haemodynamics. 2. Frusemide increased significantly the fractional albumin and IgG clearances. The fractional dextran clearances of molecules with a radius greater than or equal to 5.4 nm also increased significantly after frusemide injection. Pretreatment with indomethacin partly inhibited the increments in clearances of macromolecules. 3. The changes in the fractional protein clearances correlated significantly with those of inulin clearance There was also a high degree of correlation between the changes in fractional protein clearances and prostanoid excretion. 4. The data obtained suggest that frusemide increases glomerular permeability by influencing the effective pores of the glomerular capillary wall. The increased permeability possibly is due to changes in prostanoid synthesis.

Adolescent↗
PubMed1979

Cellular immunity in renal diseases.

Cellular immune reactivity was studied in 78 patients with various forms of renal disease by skin testing with four recall antigens and a lymphocyte transformation test with tuberculin PPD and leucoagglutinin. Patients with S-creatine greater than or equal to 230 micromol/l as well as those with chronic pyelonephritis who had S-creatinine values below 230 micromol/l had significantly lower skin reactions than the controls to streptokinase-streptodornase, parotitis and PPD. Glomerulonephritic patients with S-creatinine values below 230 micromol/l had normal skin reactivity. Lymphocyte transformation tests showed decreased reactivity only in patients with S-creatinine level greater than or equal to 230 micromol/l. The results suggest an association of chronic pyelonephritis with a defective efferent, nonspecific arm of cellular immunity.

Adult↗