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Biomedical subjects

P Lips

Publications and source records attributed to P Lips.

At least 145 records · Page 8Linked to original sources

Lower mobility and markers of bone resorption in the elderly.

Immobilization may lead to severe bone loss. Physical activity decreases with age and lower mobility might influence bone loss. We have evaluated the degree of mobility and parameters of bone turnover in 70 residents of a nursing home (mean age +/- SD 81 +/- 9 years) and 68 residents of an old people's home (mean age +/- SD 84 +/- 6 years). The mobility was assessed with a standing and walking score from 1 (severely disabled) to 5 (standing/walking without help). When the subjects were arranged according to increasing walking score from 1 to 5, fasting urinary hydroxyproline/creatinine ratio gradually decreased from 31 +/- 19 to 14 +/- 5 mumol/mmol (P less than 0.001). There was also a significant linear decrease of fasting urinary calcium/creatinine ratio, and serum calcium concentration and a significant increase of serum albumin and 1,25-dihydroxyvitamin D concentrations with increasing walking score. These data indicate that lower mobility in the elderly leads to higher bone resorption, which may suppress the formation of 1,25-dihydroxyvitamin D.

Aged↗

Percutaneous transcatheter embolization of symptomatic renal angiomyolipomas: a report of four cases.

Successful percutaneous transcatheter embolization of renal angiomyolipoma is reported in four female patients. The angiomyolipomas measured more than 4 cm in diameter. Three patients had severe haemorrhage and one patient had a growing angiomyolipoma in a solitary kidney. This patient had percutaneous transcatheter embolization to prevent further deterioration of kidney function. Three patients had multiple renal angiomyolipomas as part of tuberous sclerosis. Two of them had selective transcatheter embolization of more than one angiomyolipoma. After embolization, one patient had partial loss of kidney function and one patient developed an abscess that could successfully be drained percutaneously under ultrasound guidance. The following conclusions can be drawn. All patients with tuberous sclerosis should be screened for renal angiomyolipomas. All symptomatic renal angiomyolipomas and all angiomyolipomas that measure more than 4 cm in diameter require treatment. Embolization should be considered as a primary therapeutic modality for multiple angiomyolipomas.

Adult↗

The effect of cross-gender hormonal treatment on bone metabolism in male-to-female transsexuals.

A deficiency of sex hormones leads in both sexes to increased bone loss, and hormonal substitution can prevent this. The effect of the change of hormonal environment on bone metabolism in transsexuals is unknown. Transilial bone biopsies were obtained from 23 male-to-female transsexuals (mean age +/- SD, 38.0 +/- 11.7 years) after estrogen (ethinylestradiol, 100 micrograms/day) and antiandrogen treatment (cyproterone acetate, 100 mg/day) for 8-41 months. Histomorphometric data were compared with those from 11 healthy men (39.6 +/- 9.4 years). There was no difference in bone volume, bone surface, or trabecular thickness between transsexuals and controls. Eroded surface and osteoclast number were not different between the groups. The osteoid volume, surface, and thickness were significantly lower in the transsexuals than in the controls. The mineral apposition rate and adjusted apposition rate were normal, but mineralizing surface and bone formation rate were suppressed in the transsexuals compared with data reported from the literature. The results indicate that antiandrogen and estrogen treatment in male-to-female transsexuals may suppress bone turnover and is not associated with bone loss.

Adult↗

Perimenopausal bone mass and risk factors.

We studied the effect of menopausal status and risk factors on lumbar bone mineral density (BMD) and metacarpal cortical thickness (MCT) in 286 women of 46-55 years of age. Body mass index (height/weight) was measured and the family history of osteoporosis, reproductive history, menopausal status, calcium intake, amount of physical activity and the consumption of tobacco and alcohol were assessed. Lumbar BMD and MCT decreased substantially in the perimenopausal and postmenopausal period. In the premenopausal women a significant (P = 0.03) lower lumbar BMD was observed in the lowest tertile of calcium intake (less than or equal to 900 mg/day) compared to the highest tertile (greater than or equal to 1200 mg/day). This difference was not apparent in the peri- and postmenopausal women. This suggests that dietary calcium intake is more important in the development and/or maintenance of peak bone mass, than in the modulation of postmenopausal bone loss. Apart from menopausal status and low calcium intake, no other significant determinant of bone mass could be identified. We conclude, therefore, that the assessment of risk factor status is not an efficient tool for the identification of perimenopausal women with low bone mass.

Bone Density↗

Pharmacokinetics of 24,25-dihydroxyvitamin D3 in humans.

Pharmacokinetic properties of pharmacological doses of 24,25-dihydroxyvitamin-D3 [24,25(OH)2D3] were determined in healthy volunteers. Four male subjects received 25 micrograms of 24,25(OH)2D3 as an intravenous bolus injection. Plasma concentrations of 24,25(OH)2D3, 25-hydroxyvitamin D and 1,25-dihydroxy-vitamin D were monitored during 14 days. In addition, serum ionized calcium, total calcium, inorganic phosphate, albumin, creatinine and intact hPTH(1-84) were measured during 14 days. The concentration-time curve of 24,25(OH)2D3 could be described by a two-exponential curve with half-lives of 3.0 +/- 0.9 hrs and 8.2 +/- 2.9 days (mean +/- SD). The volume of distribution was 0.19 +/- 0.02 liters/kg. None of the mentioned biochemical parameters, except serum 24,25(OH)2D3, changed markedly. In 18 subjects suffering from primary hyperparathyroidism, taking 25 micrograms of 24,25(OH)2D3 daily during three months, an average plateau level of 39 +/- 12 nmol/l of serum was observed. Bioavailability as estimated from this plateau level was approximately 70%.

24,25-Dihydroxyvitamin D 3↗

Adult hypophosphataemic osteomalacia with Fanconi syndrome presenting in a patient with neurofibromatosis.

A patient is described with neurofibromatosis, increasing walking problems and low back pain. Initially, osteoporosis or pressure caused by a neurofibroma was suspected. However, the progressively increasing alkaline phosphatase activity and hypophosphataemia found during laboratory investigations led to metabolic studies which revealed proximal tubular dysfunction. A bone biopsy showed severe osteomalacia. A diagnosis of hypophosphataemic osteomalacia was made based on the Fanconi-syndrome. The association between hypophosphataemic osteomalacia and neurofibromatosis may be akin to the relationship between this type of osteomalacia and mesenchymal tumours, which has been noticed several times in the literature. The underlying mechanism is unknown.

Fanconi Syndrome↗

Quantification of strontium in plasma and urine with flameless atomic absorption spectrometry.

This analytical method for determination of Sr in plasma and urine involves flameless atomic absorption spectrophotometry (FAAS). Drying, charring, and atomization were optimized with respect to temperature, temperature ramp, and duration for Sr in dilute HNO3 and Sr in plasma diluted 20-fold with dilute HNO3. Calibration curves (r greater than 0.995) were linear in the concentration range 5-250 micrograms/L for Sr in various media, with intercepts negligibly small except for the calibration curves in 1:1-diluted plasma and undiluted urine. The estimated detection limits for Sr in 20-fold-diluted plasma and 50-fold-diluted urine were 2 and 3 micrograms/L, respectively. Endogenous Sr in plasma and urine was estimated at 16 (SD 8) micrograms/L and 158 (SD 26) micrograms/L (n = 6), respectively. Intra- and interassay CVs were 9.1% and 5.3% for 20-fold-diluted plasma at a Sr concentration of 25 micrograms/L, and 6.9% and 4.8% at a concentration of 250 micrograms/L. The respective CVs were 8.2% and 1.2% for 50-fold-diluted urine at the low concentration, and 4.0% and 4.6% at the high concentration. In a pharmacokinetic pilot study of 2.5 mmol of Sr orally administered to a healthy volunteer, the peak plasma concentration of Sr, 4.4 mg/L, decayed bi-exponentially [t1/2, alpha = 24 h, t1/2, beta = 77 h]; the estimated first-order absorption rate constant was 0.005 min-1; and the observed decay (day 0-6) of the urinary Sr/creatinine ratio closely paralleled the plasma decay [t1/2 = 70 h].

Administration, Oral↗

Accelerated vertebral bone loss in relation to the menopause: a cross-sectional study on lumbar bone density in 286 women of 46 to 55 years of age.

Bone mineral density (BMD) of the lumbar spine was measured in 286 women (46-55 years of age) using dual photon absorptiometry. The women were classified in three categories: premenopausal, perimenopausal and postmenopausal. The postmenopausal group was subdivided according to the number of years since the last uterine bleeding. With multiple linear regression analysis of lumbar BMD on age and menopausal status, an acceleration of bone loss was observed during the perimenopausal period and the following first two postmenopausal years. No significant bone loss was detected in relation to age or during the later postmenopausal years. Applying both an additive and a multiplicative model of bone loss, the mean perimenopausal bone loss was 0.061 gram-equivalents hydroxyapatite (geqHA)/cm2 and 6.4%, respectively. In the first 2 postmenopausal years the mean bone loss was 0.044 geqHA/cm2 and 5.1% per year. These results suggest a substantial menopause related acceleration of lumbar bone loss in a relatively short time span with its onset in the perimenopausal period.

Bone and Bones↗

The effect of vitamin D supplementation on vitamin D status and parathyroid function in elderly subjects.

Vitamin D deficiency is common in the elderly and may lead to secondary hyperparathyroidism, cortical bone loss, and hip fractures. The effect of vitamin D supplementation for 1 yr was studied in 72 people living in a nursing home and 70 people living in an aged people's home. The subjects were randomized into 3 groups: control, and 400 or 800 IU vitamin D3/day. The initial vitamin D status of each subject was classified as deficient or borderline [serum 25-hydroxyvitamin D (25OHD) less than 30 nmol/L] in 79% and adequate (serum 25OHD greater than or equal to 30 nmol/L) in 21%. Serum 25OHD concentrations increased about 3-fold in both groups receiving vitamin D supplementation. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations increased slightly but significantly, and the increase was inversely related to the initial serum 25OHD concentration. Serum intact PTH-(1-84) concentrations decreased about 15% during supplementation in both nursing home and aged people's home residents, whereas serum osteocalcin significantly decreased in the nursing home residents only. We conclude that a vitamin D3 supplement of 400 IU/day adequately improves vitamin D status in elderly people and increases 1,25-(OH)2D concentrations in those with vitamin D deficiency. Supplementation decreases parathyroid function and may depress bone turnover to some degree.

Aged↗

Improvements in the simultaneous determination of calcidiol and calcitriol in human serum or plasma.

Technical improvements have been applied to reduce the time required for the determination of calcidiol and calcitriol in serum or plasma. The modifications include the use of Sep-Pak C18 cartridges for the extraction of calciol metabolites from serum instead of a classical liquid/liquid extraction, a considerable shortening of the HPLC purification time compared with our previously described method, and the application of HPLC with UV detection at 254 nm of calcidiol as an alternative to the usual competitive protein binding methods. In none of the 199 samples where calcidiol was determined by HPLC did we observe a detectable peak of ercalcidiol. Quantitation of calcidiol by HPLC and competitive protein binding was compared in 5 series of assays. The correlation between the two methods was 0.99. The average slope of the linear regression line when the HPLC values were plotted versus the competitive protein binding values was 1.14. The average intercept was 0.19 nmol/l. The mean within-run coefficient of variation for calcidiol in these series was 5% for the competitive protein binding method, and 4% for HPLC method. Between-run coefficients of variation were 6% and 12% for the competitive protein binding and for the HPLC method, respectively. Within-run and between-run coefficients of variation for calcitriol were 6% and 15%, respectively.

Calcifediol↗

Determinants of vitamin D status in patients with hip fracture and in elderly control subjects.

The factors that influence vitamin D status were investigated in 125 patients with hip fracture and in 74 elderly control subjects. The serum concentrations of 25-hydroxyvitamin D [25(OH)D] varied with sunshine score and were paralleled by serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. The control subjects showed a higher sunshine score and higher serum 24(OH)D levels than the patients with hip fracture. Dietary vitamin D intake was similar in both groups (mean 115 IU/d). A positive correlation between vitamin D intake and serum 25(OH)D was observed in the patients with low sunshine exposure. It appeared from this relation that dietary vitamin D intake should be approximately 300 IU/d to maintain an adequate serum (25(OH)D concentration. Vitamin D status was very poor in patients who were institutionalized before hip fracture. Multiple regression analysis on serum 25(OH)D confirmed the primary role of sunshine exposure as determinant of vitamin D status. The principal determinants of serum 1,25(OH)2D were serum 25(OH)D, serum creatinine, and serum phosphate.

Aged↗

An analysis of bone structure in patients with hip fracture.

The prevalence of osteoporosis in patients with hip fracture is not well defined. We performed a histomorphometric analysis of bone structural parameters in transilial biopsies of 39 patients with hip fracture (21 cervical, 18 trochanteric), 23 patients with one or more vertebral crush fractures and 20 control subjects. Trabecular bone volume (TBV) and trabecular surface density (Sv) were significantly lower in trochanteric than in cervical fractures. Mean trabecular plate thickness (MTPT), mean wall thickness (MWT) and TBV were significantly lower in trochanteric fractures than in the control group. Vertebral crush fractures are mainly characterized by a decreased TBV and Sv. There was a strong positive correlation between MWT and MTPT in trochanteric fractures suggesting that the decreased trabecular thickness in this group is due to decreased osteoblastic apposition. Trochanteric fractures are associated with serious osteoporosis, whereas cervical fractures constitute a more heterogeneous group. The osteoporosis of trochanteric fractures is characterized by significant trabecular thinning, whereas that of vertebral fractures is mainly associated with loss of trabecular plates.

Biopsy↗

Long-term use of magnesium hydroxide as a phosphate binder in patients on hemodialysis.

The long-term use of magnesium hydroxide [Mg(OH)2] as a phosphate binder was investigated in 18 patients on chronic hemodialysis. All patients received a basal treatment with oral calcium carbonate. Vitamin D supplements were not used. In period I each patient ingested aluminum hydroxide [Al(OH)3], in period II Mg(OH)2 and in period III Mg(OH)2 and Al(OH)3 together. During period II and III a dialysate devoid of Mg was used. Mg(OH)2 doses were adjusted to prevent severe hypermagnesemia and diarrhea. The mean dose of Mg(OH)2 in period II was 2.4 +/- 0.6 and in period III 2.6 +/- 1.2 g/day. Serum phosphate increased significantly in period II and fell again in period III. Despite a halving of the Al(OH)3 dose in period III, serum Al was similar in period I and period III (55.8 +/- 19.1 vs 57.1 +/- 27.3 microg/l). Parathyroid hormone (PTH) concentration fell in period II and decreased even further in period III. We conclude that oral Mg(OH)2 may reduce the required Al(OH)3 dose, however, without an effect on serum Al concentration. The observed suppression of parathyroid activity needs further study.

Aluminum Hydroxide↗

Bone metabolism in rheumatoid arthritis compared with postmenopausal osteoporosis.

Calcium and bone metabolism in 29 rheumatoid arthritis (RA) patients were compared with those in 27 postmenopausal osteoporotic patients. Signs of vitamin D deficiency were found in 20 RA patients, including 12 who took recommended amounts of vitamin D in their diets and were exposed to sufficient sunlight, and in none of the osteoporotic patients. There were no signs of malabsorption. In six out of 15 patients we found increased liver enzyme activity, which may have a role in vitamin D metabolism. We propose the influence of non-steroidal anti-inflammatory drugs (NSAIDs) on vitamin D metabolism in the liver as a possible explanation.

Arthritis, Rheumatoid↗

Absence of effect of 24,25-dihydroxyvitamin D3 in primary hyperparathyroidism.

Nineteen patients with primary hyperparathyroidism were treated with 25 micrograms 24,25-dihydroxyvitamin D3 or placebo daily for 3 months according to double-blind cross-over protocol. Serum immunoreactive PTH, total and ionized calcium, urinary calcium excretion, tubular reabsorption of phosphate/glomerular filtrate, and urinary hydroxyproline excretion did not change significantly. Serum 24,25-dihydroxyvitamin D3 levels increased significantly from 1.4 +/- 2.2 (SD) nmol/liter to 38 +/- 11 nmol/liter during the treatment period. Serum 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 levels did not change. We conclude that pharmacological doses of 24,25-dihydroxyvitamin D3 have no suppressive effect on parathyroid function in primary hyperparathyroidism.

24,25-Dihydroxyvitamin D 3↗

Clinical implications of estimation of intact parathyroid hormone (PTH) versus total immunoreactive PTH in normal subjects and hyperparathyroid patients.

We describe a clinical study comparing the value of measurements of intact human PTH [hPTH(1-84)] and total PTH immunoreactivity [hPTH-(1-84) plus fragments]. A two-step immunochemical method was used to separate plasma hPTH-(1-84) from all circulating PTH fragments. The first step involved extraction and concentration of plasma PTH using solid phase antiamino-terminal PTH antibodies. After elution, the PTH immunoextract was analyzed using a sensitive mid- and C-region immunoassay. Complete separation in the immunoextraction step was proven by Sephadex G-75 gel filtration. hPTH-(1-84) values in fasting patients showed a clear distinction between those with primary hyperparathyroidism and those with nonparathyroid hypercalcemia, in contrast with small overlap in total immunoreactive PTH values. The hPTH-(1-84) values increased faster and more substantially in response to long EDTA and calcium infusion tests, compared with total PTH immunoreactivity, in normal subjects. Infusion of EDTA (10 mg/kg BW) in 5 min) elicited a readily measurable response of hPTH-(1-84) between 5 and 10 min after starting the infusion. Ingestion of 1000 mg calcium caused a decrease in hPTH-(1-84) in 1 h or less. More than 50% of patients with terminal renal failure had normal hPTH-(1-84) values despite elevated total immunoreactive PTH concentrations. We conclude that the two-step hPTH-(1-84) assay is more specific and sensitive than most regional PTH assays. Measurements of hPTH-(1-84) levels may identify disorders of parathyroid function at an early stage and provide a useful tool for the study of parathyroid physiology.

Administration, Oral↗

The effect of trauma on serum concentrations of vitamin D metabolites in patients with hip fracture.

In a previous study we observed lower serum concentrations of 25(OH)D, 24,25(OH)2D, and 1,25(OH)2D in patients with hip fracture than in aged control subjects. In order to evaluate the effect of trauma on vitamin D metabolite levels, we measured serum concentrations of vitamin D binding protein (DBP) in 118 patients with hip fracture and 71 aged control subjects. Serum DBP was lower in the patients than in the controls (mean +/- SD 315 +/- 60 vs 371 +/- 44 mg/l, P less than 0.001). Serum DBP correlated positively with serum total protein, albumin, alpha 2-globulin, and the vitamin D metabolite levels in the patients. When correcting for differences in serum DBP, serum 25(OH)D and 24,25(OH)2D still were significantly lower in patients than in controls, whereas serum 1,25(OH)2D was not. The free 1,25(OH)2D index (10(5) x molar ratio 1,25(OH)2D/DBP) was lower in patients than in controls, but the level of significance was marginal. This difference was not significant when patients and controls with impairment of renal function were excluded. It is concluded that the difference in serum 25(OH)D and 24,25(OH)2D between patients and controls is largely preexistent. However, the lower serum 1,25(OH)2D in the patients is mainly caused by the trauma. The free 1,25(OH)2D concentrations are almost similar in the two groups when renal function is normal.

25-Hydroxyvitamin D 2↗