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Biomedical subjects

M Ala-Houhala

Publications and source records attributed to M Ala-Houhala.

At least 19 recordsLinked to original sources

Serum tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of skeletal changes in prostate cancer.

Skeletal metastases are a significant problem in prostate cancer (PC). The patients are also exposed to treatment-related skeletal changes. This cross-sectional study evaluated a marker of bone resorption, TRACP 5b in relation to the standard analyte total alkaline phosphatase (tALP) as a marker of skeletal changes. Serum levels of TRACP 5b, tALP and PSA were measured in 130 prostate cancer patients. Comparison was made between patients with (BM+, n = 25) and without (BM-, n = 105) skeletal metastases, and between those treated with (n = 64) or without (n = 66) androgen deprivation (AD). Sensitivities and specificities were calculated for each marker and diagnostic accuracy was evaluated by ROC curve analysis. ROC curves indicated the superior accuracy of tALP, whereas TRACP 5b and PSA were comparable. With tALP the best combination of sensitivity (96%) and specificity of (91%) was reached at a cut-off point 224 U/L, the corresponding values were for TRACP 5b sensitivity (76%), specificity (89%) with a cut-off point 4.89 U/L, and for PSA sensitivity (65%), specificity (81%) at 23 ng/L for skeletal metastases. Patients treated with AD showed with increasing duration an increase in TRACP 5b values. TRACP 5b was less specific than tALP as a marker of skeletal metastases. TRACP 5b may have a role in the diagnostics of skeletal changes in PC with a focus on treatment-related skeletal changes.

Acid Phosphatase↗

Outcome of Henoch-Schoenlein nephritis with nephrotic-range proteinuria.

PATIENTS AND METHODS: All children with Henoch-Schoenlein glomerulonephritis (HSP-GN) and nephrotic-range proteinuria (> 40 mg/h/m2), treated at 5 university hospitals and in 1 central hospital in Finland during in 1990-1997, were analyzed retrospectively. The mean age of these 19 patients (8 girls, 11 boys) at the time of diagnosis was 9.9 years (range 4.6-15.1 years). A renal biopsy had been performed in all cases, giving findings according to the classification used in the International Study of Kidney Diseases in Children (ISKDC) of grade II (4 patients), grade III (10), grade IV (4) and grade V (1). Six patients underwent a second biopsy. RESULTS: The yearly incidence of nephrotic-range HSP-GN in Finland was 2 per 1 million children under 15 years of age. After a mean follow-up of 4.6 years (range 9 months-9.1 years), 3 patients (15.7%) had no signs of nephritis, 11 (57.9%) had proteinuria < 1 g/day or microscopic hematuria, 2 (10.5%) had proteinuria > 1 g/day, and 3 (15.7%) had developed ESRD or uremia. 47% of the patients needed medication for proteinuria at the time of the latest follow-up. The first kidney biopsy did not predict the outcome of HSP-GN, since all the patients with the poorest outcome had only ISKDC II-III findings in their first biopsy. CONCLUSION: According to our series, the morbidity in cases of HSP-GN with nephrotic-range proteinuria is high and a close clinical follow-up is needed. The treatment of HSP-GN patients should be based on the clinical presentation rather than on the biopsy findings.

Adolescent↗

Predictive factors associated with significant urinary tract abnormalities in infants with pyelonephritis.

BACKGROUND: Major urinary tract abnormalities are detected in 20 to 40% of infants with acute pyelonephritis (APN). Early detection of structural defects is essential for protecting the kidneys from reinfection and subsequent scarring. The purpose of this study was to investigate whether any factors present during the acute phase of infection could predict the presence of existing significant urinary tract abnormalities in infants. METHODS: A prospective study of 180 infants, aged 1 to 24 months, with APN was conducted. Blood and urine samples were collected. Renal ultrasound (US) was performed within 0 to 6 days from admission. Final diagnosis of the urinary tract anatomy was elucidated using the results of two or more radiologic imaging studies. RESULTS: Risk factors for the presence of significant urinary tract abnormalities in infants were pathogens other than Escherichia coli in urine [relative risk (RR) 3.4, 95% confidence interval (CI) 2.2 to 5.3; P = 0.001], positive blood culture (RR 2.3, 95% CI 1.3 to 4.0; P = 0.039), young age (1 to 6 months) (RR 2.2, 95% CI 1.3 to 3.9; P = 0.004), lack of papG adhesin genes of E. coli in urine (RR 2.1, 95% CI 1.2 to 3.9; P = 0.016) and abnormal renal US (RR 2.0, 95% CI 1.2 to 3.4; P = 0.008). CONCLUSIONS: Infants 1 to 6 months of age with APN caused by bacteria other than E. coli or by papG-negative E. coli strain, positive blood culture and abnormal renal US carry an increased risk for significant urinary tract abnormalities and need enforced follow-up.

Acute Disease↗

Renal follow up of premature infants with and without perinatal indomethacin exposure.

AIMS: To evaluate early childhood renal growth, structure, and function in children born at less than 33 weeks gestation and to investigate possible independent effects of perinatal indomethacin exposure. METHODS: A total of 66 children born at less than 33 weeks gestation, 31 of them with perinatal indomethacin exposure (study group) and 35 without (control group), were examined at 2-4 years of age. Serum cystatin C and protein; plasma creatinine, sodium, and potassium; urine protein, calcium:creatinine ratios, and alpha(1) microglobulin; and glomerular filtration rate (GFR) were determined. Renal sonography examinations were performed. RESULTS: The mean serum cystatin C concentrations were slightly higher in the control group than in the study group. Mean values of serum protein, and plasma creatinine and sodium did not differ between the groups, neither did median plasma potassium concentrations and urine protein:creatinine and calcium:creatinine ratios. None had tubular proteinuria. Abnormal GFR (<89 ml/min/1.73 m(2)) was found in one case in each group and renal structural abnormalities in five in each group. In logistic regression analysis the duration of umbilical artery catheter (UAC) use and furosemide treatment emerged as the significant independent risk factors for renal structural abnormalities. Furosemide treatment and assisted ventilation remained the risk factors associated with renal abnormalities in general-that is, functional and/or structural abnormal findings. CONCLUSION: Perinatal indomethacin does not seem to affect long term renal growth, structure, or function in children born at less than 33 weeks gestation. Duration of UAC use, furosemide treatment, and assisted ventilation may be correlated with later renal structural and functional abnormalities.

Blood Proteins↗

Genetic determinants of bone mineral content in premature infants.

Genetic determinants of bone mineral content in prematurely born children at 3 months and 9-11 years of age were studied. The findings suggest that multiple genes are involved in the regulation of site specific bone mass accumulation during childhood.

Absorptiometry, Photon↗

Identification of fifteen novel PHEX gene mutations in Finnish patients with hypophosphatemic rickets.

We have carried out a mutation screening of the PHEX gene in Finnish patients with hypophosphatemia. A total of 100% (5/5) of the familial HYP patients (X-linked hypophosphatemia) and 93% (14/15) of the sporadic cases were found to carry a mutation in the PHEX gene. We identified 18 mutations, of which 15 were novel. We report also a new polymorphism 46bp upstream of exon 16. Two families were segregating the same nonsense mutation in exon 1 (R20X), but since this mutation has been previously reported in three independent studies, we consider it to be a mutational hotspot rather than a Finnish founder mutation. We did not find PHEX gene mutations in two additional hypophosphatemia families in which the mode of inheritance was other than X-linked dominant. Also, no mutation could be detected in a patient with suspected oncogenic osteomalacia (OHO).

Child↗

Reference intervals for cystatin C in pre- and full-term infants and children.

Cystatin C is a non-glycated, 13-kDa basic protein produced by all nucleated cells. Recent studies have indicated that the plasma concentration of cystatin C is a better marker for glomerular filtration rate (GFR) than plasma creatinine, which is most commonly used for this purpose. We established reference values for plasma cystatin C in pre- or full-term infants and children. For comparison we also measured the creatinine concentration in the same samples. Cystatin C was measured by a commercially available immunoturbidimetric method with a Hitachi 704 analyzer in sera obtained from 58 pre-term infants, 50 full-term infants and 299 older children (132 girls, 167 boys, median age 4.17 years, range 8 days to 16 years). No sex differences were found. The pre-term infants had higher cystatin C concentrations (mean 1.88 mg/l, SD 0.36 mg/l) than the full-term (mean 1.70 mg/l, SD 0.26 mg/l, P=0.0145). The reference interval for pre-term infants calculated non-parametrically was 1.34-2.57 mg/l and for full-term infants 1.36-2.23 mg/l. The cystatin C concentration decreased rapidly after birth, and above 3 years of age did not depend on age. The reference interval for children 3-16 years of age calculated non-parametrically was 0.51-1.31 mg/l. Younger children (<1 year: 0.75-1.87 mg/l; 1-3 years: 0.68-1.60 mg/l) had slightly, but significantly, higher plasma cystatin C levels.

Adolescent↗

Cystatin C as a marker for glomerular filtration rate in pediatric patients.

Cystatin C is a non-glycated 13-kilodalton basic protein produced by all nucleated cells. The low molecular mass and the basic nature of cystatin C, in combination with its stable production rate, suggest that the glomerular filtration rate (GFR) is the major determinant of cystatin C concentration in the peripheral circulation. Recently published studies have shown that cystatin C correlates more strongly than creatinine with GFR measured using the 51Cr-EDTA clearance. The aim of this study was to evaluate serum cystatin C as a marker for GFR in children. GFR was determined on medical indications using the 51Cr-EDTA technique in pediatric patients (2-16 years) in our renal unit. Simultaneously their cystatin C and creatinine concentrations were also measured. Of our 52 patients, 19 had a reduced renal function (<GFR 89 ml/min per 1.73 m2) based on the 51Cr-EDTA clearance. The correlation of cystatin C with the isotopic measurement of GFR tended to be stronger (r=0.89, P=0.073) than that of creatinine (r=0.80). Receiver operating characteristic analysis showed that the diagnostic accuracy of cystatin C was better (P=0.037) than that of creatinine in discriminating between subjects with normal renal function and those with reduced GFR. This study demonstrates that serum cystatin C has an increased diagnostic accuracy for reduced GFR when compared with serum creatinine. Hence, cystatin C seems to be an attractive alternative for the estimation of GFR in children.

Adolescent↗

Congenital nephrotic syndrome.

Congenital nephrotic syndrome (CNS) can be caused by neonatal infections, renal diseases which exceptionally occur in early infancy and syndromes with a renal histology of DMS. The most common CNS is the Finnish-type (CNF), an autosomal recessively inherited disease characterized by intrauterine onset of massive proteinuria. The CNF gene has been localized to the long arm of chromosome 19, but the pathogenesis remains unclear. Forty-six CNF patients have been treated at our institution. The diagnosis was based on family history, severe proteinuria of intrauterine onset (serum albumin < 10 g/liter at presentation and urinary protein > 20 g/liter when serum albumin was corrected to > 15 g/liter), a large placenta (> 25% of birth wt), exclusion of other CNS-types and normal glomerular filtration rate during the first six months. Treatment included i.v. albumin substitution, optimal nutrition, thyroxine and anticoagulation. Forty-one patients had been nephrectomized bilaterally at a mean age of 1.2 years and after 3 to 25 months on peritoneal dialysis renal transplantation (Tx) had been performed on 34 who were a mean age of 2.2 years. Growth and development has been normal. Patient survival after Tx was 97%, graft survival 94%, 81% and 81% one, three and five years after Tx was (50% cadaver grafts). Mean GFR was 75 ml/min/1.73 m2 after three years, mean height SDS -1.42, and the nine oldest patients attend school in a normal class.

Humans↗

Alphacalcidol oral pulses are effective in secondary hyperparathyroidism prior to dialysis.

Secondary hyperparathyroidism in chronic renal failure (CRF) is due to the increased activity of parathyroid gland. The negative feedback control exerted by the vitamin D metabolite 1,25 (OH)2 D3 is lacking due to the deficiency of this metabolite in CRF. We have studied whether alphacalcidol given orally as thrice weekly evening pulses lowers parathyroid hormone (PTH) levels of children with CRF. Alphacalcidol 0.5-3.0 micrograms was given thrice weekly orally to a total of 22 children (mean age 5.6 years) with CRF; the dosis was adjusted according to PTH, ionized calcium and phosphate concentration. Serum PTH decreased significantly from a pretreatment level of 393 +/- 81 to 122 +/- 34 ng/l after 12 months, and stabilized at this level. Mean vitamin D metabolite concentrations were within normal range. 1,25 dihydroxyvitamin D did not increase during therapy while PTH decreased. The estimated creatinine clearance remained nearly the same (20 +/- 3 and 21 +/- 6 ml/min/ 1.73 m2). Growth remained low normal and bone mineral density did not decrease. Oral alphacalcidol pulse therapy for hyperparathyroidism in uremic children seemed to be easy and effective. The response is even better in inhibiting potential autonomous parathyroid hyperplasia if this treatment was started early. We conclude that feedback regulation of PTH with oral alphacalcidol pulse therapy is efficient in the treatment of hyperparathyroidism in children with CRF prior to dialysis.

Administration, Oral↗

Alphacalcidol oral pulses normalize uremic hyperparathyroidism prior to dialysis.

Alphacalcidol oral pulse therapy was given for secondary hyperparathyroidism to 22 children (mean age of 5.6 years) with renal insufficiency. At the beginning of the study, the glomerular filtration rate was < 50% of normal, serum intact parathyroid hormone (PTH) was > 100 ng/l and the serum phosphate and calcium concentrations were within the normal range. Alphacalcidol (0.5-3.0 micrograms) was given orally thrice weekly in the evening and adjusted according to PTH, ionized calcium and phosphate concentrations. Serum PTH (mean +/- SEM) decreased significantly from a pre-treatment level of 393 +/- 81 ng/l to 122 +/- 34 ng/l after 12 months, and stabilized at this level. Mean vitamin D metabolite concentrations were within the normal range. 1,25-Dihydroxyvitamin D did not increase during therapy, while PTH decreased. The estimated creatinine clearance remained almost unchanged (20 +/- 3 and 21 +/- 6 ml/min per 1.73 m2). Growth remained low normal (height standard deviation score -1.8 +/- 0.3 initially and -1.7 +/- 0.4 12 months later) and bone mineral density did not decrease. We concluded that feedback regulation of PTH with oral alphacalcidol pulse therapy is effective in the treatment of hyperparathyroidism in children with renal failure prior to dialysis.

Adolescent↗

25-Hydroxyvitamin D and vitamin D in human milk: effects of supplementation and season.

Breast-milk 25-hydroxyvitamin D (25-[OH]D) and vitamin D were measured in mothers supplemented with 2000 or 1000 IU (50 or 25 micrograms) of vitamin D/d or with no supplementation. Fore- and hindmilk samples were collected at two stages of lactation (8 and 15 or 20 wk after delivery) and at different seasons. Season affected the levels of 25-(OH)D and vitamin D. The 25-(OH)D levels were higher in hind- than in foremilk. Supplementation had no effect on vitamin D levels. Milk 25-(OH)D levels of mothers receiving either 1000 or 2000 IU (25 or 50 micrograms) vitamin D/d were significantly higher than those of unsupplemented mothers in February and April. In theory, supplementation with 2000 IU (50 micrograms) vitamin D should have increased the calculated antirachitic activity of the milk in winter to the levels of unsupplemented mothers in September; however, responses varied widely among individuals.

Breast Feeding↗

Double blind study on the need for vitamin D supplementation in prepubertal children.

Fifty-one healthy prepubertal schoolchildren were followed for 13 months in a double blind study. Twenty-four of them were supplemented with 400 IU of vitamin D2 5-7 times weekly, while 27 received a placebo. The children were examined in winter both at the beginning and at the end of the study, and in the middle of the study in autumn. Mean 25-hydroxyvitamin D levels in the supplemented group were significantly higher than those in the placebo group both in autumn and in winter, when the study ended. The vitamin D supplementation did not, however, affect other vitamin D metabolites, serum calcium, albumin, inorganic phosphorus, parathyroid hormone concentrations or alkaline phosphatase activity. Moreover, the supplementation caused no alterations in the weight or height gain or bone mineral content of the distal radius of the children, and thus subclinical rickets could not be shown.

Bone and Bones↗

Serum vitamin A levels in mothers and their breast-fed term infants with or without supplemental vitamin A.

Serum concentrations of vitamin A were measured in term infants (n = 72) and their mothers at delivery and after 20 weeks of breast-feeding (n = 48). During the 20 weeks the infants received either no supplemental vitamin A (but the mothers were given 3,000 IU vitamin A daily) (n = 16) or a daily vitamin A supplementation of 600 (n = 17) or 1,500 IU (n = 15). After 20 weeks of breast-feeding the vitamin A levels in the unsupplemented infants were similar to those at birth. The infants supplemented either with 600 or 1,500 IU had higher vitamin A serum levels than at birth (p less than 0.01), however, there was no difference between the two supplemented groups. During lactation, the serum vitamin A concentrations of the mothers increased significantly in all groups with or without vitamin A supplementation.

Breast Feeding↗