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Biomedical subjects

R Takkinen

Publications and source records attributed to R Takkinen.

12 recordsLinked to original sources
PubMed1998

High-calcium intake abolishes hyperoxaluria and reduces urinary crystallization during a 20-fold normal oxalate load in humans.

BACKGROUND: The aim of the study was to test whether increasing dietary calcium intake lowers intestinal oxalate absorption and thereby prevents hyperoxaluria and urinary crystallization during a 20-fold normal oxalate load in healthy subjects. METHODS: Fourteen healthy male volunteers (age 23-44 years, BMI 21.5-27.7 kg/m2) collected 24-h urines while on free-choice diet as well as on two standardized diets. The latter contained 2545 kcal, 2500 ml of mineral water, 102 g of protein, 13.6 g of sodium chloride and 2220 mg of oxalate (approximately 20-fold content of an average diet). Subjects were studied twice while on the standardized diet, once while eating a normal amount of calcium (1211 mg/day, oxalate-rich diet), and once while eating 3858 mg of calcium/day (calcium and oxalate-rich diet). RESULTS: Compared with the free-choice diet (322+/-36 micromol/d), UOx x V increased to 780+/-72 micromol/d on the oxalate-rich diet (P=0.001) and fell again to 326+/-31 micromol/d on calcium and oxalate-rich diet (P=0.001 vs oxalate-rich diet). Urinary glycolate (a metabolic precursor of Ox) always remained below the upper limit of the normal range and did not change between different diets, indicating that changes in UOX x V reflect respective variations in intestinal absorption of Ox. Uca x V was 4.60+/-0.45 mmol/d on the free-choice diet and 3.20+/-0.32 mmol/d on the oxalate-rich diet (P=0.011 vs free-choice diet); it increased to 7.28+/-0.74 mmol/d on the calcium- and oxalate-rich diet (P=0.001 vs free-choice and oxalate-rich diets). As indicated by the AP (CaOx) index (Tiselius), urinary supersaturation did not vary significantly between the three diets. In freshly voided morning urines (studied in 8/14 subjects) on the oxalate-rich diet, CaOx crystals or crystal aggregates of up to 80 microm diameter were found in 5/8 urines, whereas this never occurred on the free-choice diet and only t once on the calcium- and oxalate-rich diet. CONCLUSION: . Increasing calcium intake while eating Ox-rich food prevents dietary hyperoxaluria and reduces CaOx crystallization in healthy subjects. This further illustrates that dietary counseling to idiopathic calcium-stone formers should ensure sufficient calcium intake, especially during oxalate-rich meals.

Adult↗
PubMed1996

PTH-related protein is released into the mother's bloodstream during lactation: evidence for beneficial effects on maternal calcium-phosphate metabolism.

Recent studies have indicated that parathyroid hormone-related protein (PTHrP) may have important actions in lactation, affecting the mammary gland, and also calcium metabolism in the newborn and the mother. However, there are as yet no longitudinal studies to support the notion of an endocrine role of this peptide during nursing. We studied a group of 12 nursing mothers, mean age 32 years, after they had been nursing for an average of 7 weeks (B) and also 4 months after stopping nursing (A). It was assumed that changes occurring between A and B correspond to the effect of lactation. Blood was assayed for prolactin (PRL), PTHrP (two-site immunoradiometric assay with sheep antibody against PTHrP(1-40), and goat antibody against PTHrP(60-72), detection limit 0.3 pmol/l), intact PTH (iPTH), ionized calcium (Ca2+), 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), alkaline phosphatase (alkP), as well as for creatinine (Cr), protein, phosphorus (P), and total calcium (Ca). Fasting 2-h urine samples were analyzed for Ca excretion (CaE) and renal phosphate threshold (TmP/GFR). PRL was significantly higher during lactation than after weaning (39 +/- 10 vs. 13 +/- 9 micrograms/l; p = 0.018) and so was PTHrP (2.8 +/- 0.35 vs. 0.52 +/- 0.04 pmol/l; p = 0.002), values during lactation being above the normal limit (1.3 pmol/l) in all 12 mothers. There was a significant correlation between PRL and PTHrP during lactation (r = 0.8, p = 0.002). Whole blood Ca2+ did not significantly change from A (1.20 +/- 0.02 mmol/l) to B (1.22 +/- 0.02, mmol/l), whereas total Ca corrected for protein (2.18 +/- 0.02 mmol/l) or uncorrected (2.18 +/- 0.02 mmol/l) significantly rose during lactation (2.31 +/- 0.02 mmol/l, p = 0.003 and 2.37 +/- 0.03 mmol/l, p = 0.002, respectively). Conversely, iPTH decreased during lactation (3.47 +/- 0.38 vs. 2.11 +/- 0.35 pmol/l, A vs. B, p = 0.02). Serum-levels of 25(OH)D3 and 1,25(OH)2D3 did not significantly change from A to B (23 +/- 2.3 vs. 24 +/- 1.9 ng/ml and 29.5 +/- 6.0 vs. 21.9 +/- 1.8 pg/ml, respectively). Both TmP/GFR and P were higher during lactation than after weaning (1.15 +/- 0.03 vs. 0.86 +/- 0.05 mmol/l GF, p = 0.003 and 1.25 +/- 0.03 vs. 0.96 +/- 0.05 mmol/l, p = 0.002, respectively) as was alkP (74.0 +/- 7.1 vs. 52.6 +/- 6.9 U/l, p = 0.003). CaE did not differ between A and B (0.015 +/- 0.003 vs. 0.017 +/- 0.003 mmol/l GF, A vs. B, NS). We conclude that lactation is accompanied by an increase in serum PRL. This is associated with a release of PTHrP into the maternal blood circulation. A rise in total plasma Ca ensues, probably in part by increased bone turnover as suggested by the elevation of alkP. PTH secretion falls, with a subsequent rise of TmP/GFR and plasma P despite high plasma levels of PTHrP.

Adult↗
PubMed1996

Effect of calcium-channel blockers on calcium-phosphate metabolism in patients with end-stage renal disease.

BACKGROUND: After EDTA-induced hypocalcaemia, healthy volunteers treated with diltiazem display more severe hyperparathyroidism than subjects on felodipine studied under identical conditions. Therefore patients with end-stage renal disease (ESRD) and severe secondary hyperparathyroidism might be particularly sensitive to this side-effect. METHODS: To test this hypothesis, seven patients with ESRD on chronic haemodialysis (3 women and 4 men) with serum levels of intact PTH ranging from 204 to 675 pg/ml were studied both before and during the first 180 min of haemodialysis against a dialysate with low calcium concentration (0.75 mmol/l, n = 6 and 1 mmol/l, n = 1) under the following three experimental conditions: control, felodipine (10 mg/day) and diltiazem (120 mg b.i.d.). RESULTS: At onset of dialysis, plasma phosphorus level was higher on diltiazem (2.03 +/- 0.08 mM) than on felodipine (1.64 +/- 0.10, P < 0.02), and on the latter it was lower than in control condition (1.88 +/- 0.16, P < 0.02). As a probable consequence, blood ionized calcium concentration was lower on diltiazem (1.14 mM +/- 0.02, mean +/- SEM) than on felodipine (1.2 +/- 0.03, P < 0.05) or in control condition (1.17 +/- 0.01, NS). There was a trend for intact PTH to be higher on diltiazem (324 +/- 47 pg/ml) than on felodipine (246 +/- 55) or in control condition (305 +/- 49) and 1,25-dihydroxyvitamin D was higher indeed on diltiazem (6.70 +/- 0.92 pg/ml) than on felodipine (4.75 +/- 0.91, P < 0.02) or control (3.87 +/- 0.62, P < 0.05). Area under the curve PTH over the first 60 min of dialysis was higher by 16 +/- 7% on diltiazem than on felodipine (P < 0.05). CONCLUSIONS: While on diltiazem rather than on felodipine, patients with ESRD display higher plasma phosphorus levels, and slightly aggravate the degree of severity of hyperparathyroidism recorded during haemodialysis against low-calcium dialysate. The long-term effect of this new observation remains to be evaluated.

Aged↗
PubMed1995

Renal mass and serum calcitriol in male idiopathic calcium renal stone formers: role of protein intake.

To determine whether chronic overconsumption of protein might increase renal mass and cause up-regulation of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D] production, 57 male recurrent idiopathic calcium stone formers (RCSF), 29 with hypercalciuria (HCSF; urinary calcium x V, > 7.50 mmol/day) and 28 with normocalciuria (NCSF), were compared with 15 healthy male controls (C) while consuming a free choice diet. Renal mass in RCSF was measured by the sum of the surface areas of right and left kidneys (square centimeters) on plain films of the abdomen by a computer-assisted sonic stylus; in C, renal mass was assessed sonographically. Serum intact PTH and 1,25-(OH)2D were measured radioimmunometrically. In HCSF, urinary phosphate x V (35.9 +/- 1.2 mmol/day) was higher than that in NCSF (29.3 +/- 1.3 mmol/day; P = 0.0009) or C (28.7 +/- 1.8 mmol/day; P = 0.005); urinary creatinine x V (16.5 +/- 0.5 mmol/day) was also higher in HCSF than in NCSF (15.0 +/- 0.5 mmol/day; P = 0.024) or C (13.8 +/- 0.6 mmol/day; P = 0.002). For identical blood levels of ionized calcium and phosphate, the 1,25-(OH)2D/PTH concentration ratio (an index of regulation of 1,25-(OH)2D production) was higher in HCSF (6.5 +/- 1.0) than in NCSF (4.0 +/- 0.3; P = 0.005). In addition, the sum of the surface areas of right and left kidneys was increased in HCSF (163.4 +/- 2.9 cm2) compared with that in NCSF (140.5 +/- 3.1 cm2; P = 0.0001), and it positively correlated with urinary phosphate x V (r = 0.429; P = 0.001) as well as with urinary creatinine x V (r = 0.294; P = 0.026); no such correlation was noted in C. Calcitriol levels were positively related to renal mass in RCSF (r = 0.316; P = 0.018), but not in C. Finally, urinary calcium x V positively correlated with the serum calcitriol/PTH concentration ratio only in RCSF (r = 0.388; P = 0.003). These findings suggest that protein overconsumption may cause an increase in renal mass and up-regulate calcitriol production in some male RCSF, an effect that would subsequently cause "idiopathic" hypercalciuria.

Adult↗
PubMed1995

Effect of oral calcium loading on intact PTH and calcitriol in idiopathic renal calcium stone formers and healthy controls.

The calciuric response after an oral calcium load (1000 mg elemental calcium together with a standard breakfast) was studied in 13 healthy male controls and 21 recurrent idiopathic renal calcium stone formers, 12 with hypercalciuria (UCa x V > 7.50 mmol/24 h) and nine with normocalciuria. In controls, serum 1,25(OH)2 vitamin D3 (calcitriol) remained unchanged 6 h after oral calcium load (50.6 +/- 5.1 versus 50.9 +/- 5.0 pg/ml), whereas it tended to increase in hypercalciuric (from 53.6 +/- 3.2 to 60.6 +/- 5.4 pg/ml, P = 0.182) and fell in normocalciuric stone formers (from 45.9 +/- 2.6 to 38.1 +/- 3.3 pg/ml, P = 0.011). The total amount of urinary calcium excreted after OCL was 2.50 +/- 0.20 mmol in controls, 2.27 +/- 0.27 mmol in normocalciuric and 3.62 +/- 0.32 mmol in hypercalciuric stone formers (P = 0.005 versus controls and normocalciuric stone formers respectively); it positively correlated with serum calcitriol 6 h after calcium load (r = 0.392, P = 0.024). Maximum increase in urinary calcium excretion rate, delta Ca-Emax, was inversely related to intact PTH levels in the first 4 h after calcium load, i.e. more pronounced PTH suppression predicted a steeper increase in urinary calcium excretion rate. Twenty-four-hour urine calcium excretion rate was inversely related to the ratio of delta calcitriol/deltaPTHmax after calcium load (r = -0.653, P = 0.0001), indicating that an abnormally up-regulated synthesis of calcitriol and consecutive relative PTH suppression induce hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Assessment of parathyroid gland function: predictive value of a nomogram].

Recent developments in measurement of intact parathormone (PTH) has enabled to generate a nomogram for parathyroid function. Blood levels of PTH can thus be interpreted in relation to calcemia. Intact PTH and calcium were assayed in blood from 99 healthy subjects studied under fasting conditions; 26 subjects were also studied during hyper- and hypocalcemia, induced by calcium and EDTA infusions, respectively. Serum levels of intact PTH which had been obtained in 99 patients were then analysed retrospectively by comparison with the nomogram. Patients whose intact PTH levels lie above the normal zone of the nomogram produce too much PTH relative to the blood calcium level (hyperparathyroidism); those falling under the normal zone produce too little (hypoparathyroidism).

Adolescent↗
PubMed1994

Risk factors for low urinary citrate in calcium nephrolithiasis: low vegetable fibre intake and low urine volume to be added to the list.

Risk factors for low urinary citrate excretion were assessed in 34 consecutive male recurrent idiopathic calcium stone formers (RCSF) who collected two 24-h urines while on free-choice diet. Overt hypocitraturia (hypo-cit) was defined as UCit x V < 1.70 mmol/day, and 'low' citraturia (low-cit) as UCit x V between 1.70 and 2.11 mmol/day. Twenty-three RCSF had normocitraturia (normo-cit), six low-cit and five hypo-cit. UCit x V positively correlated with urine volume (VOLUME, r = 0.44, P = 0.009), vegetable fibre intake (fibers, r = 0.46, P = 0.009) and GI-alkali absorption (alkali, r = 0.47, P = 0.006), and volume, fibres and alkali tended to be lower among RCSF with low-/hypo-cit. A 3-day NH4Cl loading test (0.95 mEq/kg BW daily in 3 doses) was performed in RCSF as well as in 14 age-matched healthy male controls (C). On a plot of urine pH versus serum bicarbonate, 10 of 11 RCSF with low-/hypo-cit, but only six of 23 with normo-cit (P = 0.0004) fell off the normal range, indicating incomplete RTA. Two or more risk factors simultaneously occurred in only four of 23 RCSF with normo-cit, but in eight of 11 with low-/hypo-cit (P = 0.002). In conclusion, incomplete RTA is the most prevalent risk factor for low-/hypo-cit in RCSF, and decreases in vegetable fibres and urine volume emerge as two new risk factors for low urinary CIT.

Acidosis, Renal Tubular↗
PubMed1994

Altered parathyroid gland function in severely immunocompromised patients infected with human immunodeficiency virus.

Several endocrine functions have been found disturbed in patients with acquired immunodeficiency syndrome (AIDS). However, no information is available on parathyroid function in these patients. Six patients with AIDS and 10 healthy volunteers underwent an EDTA infusion to induce hypocalcemia and stimulate PTH secretion. A group of 6 severely ill patients with malignancies was studied at baseline and served as additional controls for the effect of a severe disease per se. Baseline values showed that mean serum intact PTH concentration was lower in patients infected with the human immunodeficiency virus than in healthy volunteers (P < 0.04) as well as in patients with malignancies (P = 0.004). Whole blood calcium also tended to be lower in patients with the human immunodeficiency virus than in both control groups, the difference reaching the limit of statistical significance for the healthy controls only (P < 0.04). Mean serum magnesium, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations were similar in both groups. Throughout the entire EDTA stimulation procedure, i.e. at any blood calcium concentration, serum intact PTH concentration remained lower in patients with AIDS than in healthy control subjects (P < 0.04, analysis of variance for repeated measurements). Basal and maximal secretion of PTH is reduced in patients with AIDS. The mechanisms underlying this finding remain speculative.

Acquired Immunodeficiency Syndrome↗
PubMed1993

[Urinary specific gravity--comparative measurements using reagent strips and refractometer in 340 morning urine samples].

The specific gravity of urine (SG) indicates the number and weight of solute particles in urine; its measurement is helpful in interpreting proteinuria detected by dipstick tests and in monitoring adequate hydration in patients with nephrolithiasis. Four methods for measuring SG or osmolality of urine are currently available (depression of the freezing-point, urometry, refractometry, cation exchange on a reagent strip). Using a recently developed reagent strip, we have measured SG in morning urines of 340 non-selected outpatients and compared the results with SG measurements by refractometry of the same urines. In 86.2% of all urines, a good positive correlation between SG measured by reagent strip and refractometry was noted (r = 0.913, p = 0.0001). In 13.8% of the urines, however, the SG measured by reagent strip deviated by more than +/- 5 from the value obtained by refractometry; in 90% of these urines, glucosuria (reagent strip values too low or too high), proteinuria (values too high), or bacteriuria/leukocyturia (values too low or too high) could be found. In alkaline urine (pH > 7.0), SG values obtained by reagent strip have to be corrected by +5.

Female↗
PubMed1993

Relative hypoparathyroidism and calcitriol up-regulation in hypercalciuric calcium renal stone formers--impact of nutrition.

The issue of secondary hyperparathyroidism in idiopathic hypercalciuria (IH) was addressed in 61 male idiopathic calcium stone formers (SF) who underwent metabolic evaluation on a free-choice diet as well as bone mineral density (BMD) measurements by dual-energy X-ray absorptiometry. They were divided into hypercalciurics (HCSF, n = 30, UCa X V > 7.5 mmol/day) and normocalciurics (NCSF, n = 31, UCa X V < 7.5 mmol/day). At identical blood Ca2+ levels, parathyroid hormone (PTH) was lower in HCSF (25.3 +/- 1.8 pg/ml) than in NCSF (31.4 +/- 1.8 pg/ml, p = 0.017). Since neither fasting urinary hydroxyproline nor pyridinoline/deoxypirdinoline excretions nor BMD values were different between HCSF and NCSF, chronic bone dissolution as the cause of relative hypoparathyroidism in HCSF could be excluded. Despite lower PTH in the face of similar phosphate, Ca2+ and IGF-1 blood levels, however, serum 1,25-dihydroxyvitamin D3 (calcitriol) concentrations were slightly (though not significantly) higher in HCSF than in NCSF (52.8 +/- 3.2 vs. 47.3 +/- 2.9 pg/ml, p = NS), and calcitriol/PTH ratio was elevated in HCSF (2.52 +/- 0.29) vs. NCSF (1.66 +/- 0.15, p = 0.001). Creatinine clearance, significantly higher in HCSF than in NCSF (113 +/- 4 vs. 92 +/- 3 ml/min/1.73 m2, p = 0.0001), was positively correlated with excretion rates of urinary markers of both protein and NaCl intake. Since serum calcitriol levels were positively correlated with creatinine clearance (r = 0.350, slope = 0.288, p = 0.006), up-regulation of calcitriol synthesis with subsequent relative hypoparathyroidism in HCSF is-at least partly-explained by exaggerated protein and sodium consumption.

Absorptiometry, Photon↗
PubMed1993

Diltiazem stimulates parathyroid hormone secretion in vivo whereas felodipine does not.

The impact of two calcium channel blockers of different structure, diltiazem and felodipine, on PTH secretion was studied under hyper- and hypocalcemic conditions. Six healthy volunteers were investigated before and after treatment with felodipine, then after treatment with diltiazem. Under each of these three conditions, they received first a calcium infusion (0.109 mmol/kg over 130 min). Blood was drawn every 5-10 min for measurements of Ca2+ and intact PTH concentrations, and urine was collected over the infusion periods for measurements of calcium and creatinine. Basal levels of Ca2+ and intact PTH concentrations were similar under the three conditions. During calcium infusion, Ca2+ increased linearly from 1.27 to 1.51 mmol/L during the control period. Based on the whole response curve, Ca2+/time, this rise was less marked (P < 0.002) during each of the calcium channel blocker periods than under control conditions, although the three values of urinary calcium excretion were similar. In addition, PTH secretion was less suppressed on diltiazem than on felodipine therapy or during the control period (P < 0.04). During EDTA infusion, Ca2+ decreased in a linear way from 1.27 to 1.07 mmol/L during the control period. Based on the whole response curve, Ca2+/time, this decrease was more marked during felodipine than during diltiazem treatment or in the control period (P < 0.001). Although Ca2+ concentrations did not differ between the control and diltiazem periods, PTH levels were 1.3-fold higher (P < 0.0001) during diltiazem, but similar in the control and felodipine periods. These data demonstrate that diltiazem, but not felodipine, stimulates PTH secretion in vivo in man, with a maximal effect observed under hypocalcemic conditions.

Adult↗