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Biomedical subjects

D Thiébaud

Publications and source records attributed to D Thiébaud.

At least 37 records · Page 2Linked to original sources
PubMed1996

Segmental body composition assessed by bioelectrical impedance analysis and DEXA in humans.

The present study assessed the relative contribution of each body segment to whole body fat-free mass (FFM) and impedance and explored the use of segmental bioelectrical impedance analysis to estimate segmental tissue composition. Multiple frequencies of whole body and segmental impedances were measured in 51 normal and overweight women. Segmental tissue composition was independently assessed by dual-energy X-ray absorptiometry. The sum of the segmental impedance values corresponded to the whole body value (100.5 +/- 1.9% at 50 kHz). The arms and legs contributed to 47.6 and 43.0%, respectively, of whole body impedance at 50 kHz, whereas they represented only 10.6 and 34.8% of total FFM, as determined by dual-energy X-ray absorptiometry. The trunk averaged 10.0% of total impedance but represented 48.2% of FFM. For each segment, there was an excellent correlation between the specific impedance index (length2/impedance) and FFM (r = 0.55, 0.62, and 0.64 for arm, trunk, and leg, respectively). The specific resistivity was in a similar range for the limbs (159 +/- 23 cm for the arm and 193 +/- 39 cm for the leg at 50 kHz) but was higher for the trunk (457 +/- 71 cm). This study shows the potential interest of segmental body composition by bioelectrical impedance analysis and provides specific segmental body composition equations for use in normal and overweight women.

Absorptiometry, Photon↗
PubMed1996

Randomized phase II trial comparing different doses of the bisphosphonate ibandronate in the treatment of hypercalcemia of malignancy.

PURPOSE: To evaluate the hypocalcemic effect and safety of three different doses of the bisphosphonate ibandronate in tumor-associated hypercalcemia, and to identify factors predicting response. PATIENTS AND METHODS: One hundred seventy-four cancer patients with a serum calcium level greater than 2.7 mmol/L (10.8 mg/dL) were enrolled onto the trial. If hypercalcemia persisted after fluid repletion, patients were randomly assigned to treatment with 0.6 mg, 1.1 mg, and 2.0 mg of ibandronate. Response, defined as restoration of normocalcemia, was evaluated by an intent-to-treat analysis. RESULTS: One hundred seventy-three (99%) patients were assessable for toxicity and 151 (87%) for efficacy. The administration of 0.6 mg (group A), 1.1 mg (group B), or 2.0 mg (group C) of ibandronate led to response rates of 44%, 52%, and 67%, respectively. Significantly more patients in group C responded than in group A (P = .0276). Of the various parameters examined, only the initial serum calcium level (P < .0001; odds ratio, 0.083) and the dose of ibandronate (P = .0162; odds ratio, 2.094) correlated with response. One hundred ninety-five adverse events (AEs) were reported, 99 classified as serious and 96 as nonserious. Three serious and sixteen nonserious AEs were considered related to ibandronate treatment. The three serious AEs were one case with thrombocytopenia, one with nausea, and one with fever. CONCLUSION: Ibandronate therapy led to a dose-dependent reduction in serum calcium levels. The response to ibandronate treatment correlated negatively with the initial serum calcium level and positively with the dose administered. A dose of 2 mg was necessary to achieve a response rate comparable to that in previous studies with the bisphosphonates pamidronate and clodronate. Because the incidence of drug-associated AEs was low, a dose escalation of ibandronate can be recommended for further clinical trials.

Adult↗
PubMed1996

Influences of body weight, body composition, and substrate oxidation rate on resting postabsorptive glucose production and gluconeogenesis.

OBJECTIVE: To determine the influence of body weight, fat mass, and fat distribution on resting endogenous glucose production in healthy lean and overweight individuals. DESIGN: measurements were performed in the resting postabsorptive state in individuals receiving an unrestricted diet. SETTING: Institute of Physiology of Lausanne University. MEASUREMENTS: resting post absorptive glucose production, glycogenolysis and gluconeogenesis; resting energy expenditure and net substrate oxidation. RESULTS: Endogenous glucose production was positively correlated with body weight, lean body mass, energy expenditure and carbohydrate oxidation. Gluconeogenesis was positively correlated with net lipid oxidation and energy expenditure, and negatively correlated with net carbohydrate oxidation. No correlation with body fat or fat distribution was observed. CONCLUSIONS: Gluconeogenesis shows a large interindividual variability. Net lipid oxidation and not body fat appears to be a major determinant of gluconeogenesis.

Adult↗
PubMed1995

The diagnostic value of urinary pyridinium cross-links of collagen, serum total alkaline phosphatase, and urinary calcium excretion in neoplastic bone disease.

Bone metastases strongly affect skeletal metabolism by both their growth and their paracrine activities. However, so far no specific laboratory marker has been found to signal the spread of neoplastic disease to bone. We performed a cross-sectional study of 153 cancer patients and an equal number of healthy controls matched for sex and age, in which we determined serum levels of calcium and total alkaline phosphatase (TAP) as well as the fasting urinary excretion of calcium (uCa) and of the collagen cross-links pyridinoline (uPYD) and deoxypyridinoline (uDPD). The aim of the study was to analyze the diagnostic validity of the biochemical parameters measured with regard to neoplastic bone involvement. In the cancer group, 98 patients had overt bone metastases, as judged from radiographic and radioisotopic bone imaging. The remaining 55 patients were also in an advanced stage of disease, but there was no evidence of malignant bone involvement. In comparison to healthy controls, patients both with and without metastatic bone disease had significantly higher levels of TAP, uPYD, and uDPD (P < 0.0001). Only in cancer patients with bone metastases was the median serum calcium level higher than in the healthy controls (P < 0.02). uCa was the same in cancer patients and the control group. Within the collective of cancer patients, individuals with skeletal metastases had higher levels of serum calcium (P < 0.05), TAP (P < 0.01), and uPYD and uDPD (both P < 0.0001), than patients without evidence of malignant bone disease. uCa did not differ between the 2 groups of cancer patients. The cancer patients were then stratified into 4 subgroups according to the serum calcium level (< or = 2.6 mmol/L >) and the absence or evidence of bone metastases. This stratification revealed that in patients with bone metastases, uPYD and uDPD levels were similar in normocalcemic and hypercalcemic subjects, whereas in hypercalcemic patients, uCa levels significantly exceeded those in normocalcemic patients. When the efficacy of TAP, uCa, uPYD, and uDPD in discriminating between patients with and without bone metastases was evaluated by use of receiver-operating characteristic curves and stepwise multivariate regression analysis, uPYD was found to have the highest diagnostic validity. Using 50 mumol PYD/mol creatinine (i.e. the upper limit of normal range) as the cut-off level, the sensitivity of uPYD was 88.7%, whereas the specificity was only 41.8% (odds ratio, 5.598; 95% confidence interval, 2.547-12.306).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

[Prevention of osteoporosis and role of densitometry].

Osteoporosis is a major public health problem in countries with aging populations, resulting in excess morbidity and mortality. Osteoporosis is defined as a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with the consequent increase in bone fragility and susceptibility to fractures. Therefore, the bone loss that precedes fractures is a continuous process that is often mostly irreversible in the aging. The most efficient method of preventing fractures is the prevention of bone loss. The measurement of bone mass and other skeletal characteristics can effectively identify women at high risk for fractures. The measurement of bone mass which can be carried out by osteo-densitometry is now widely available. It is the only clinical data that can provide accurate assessment of individual fracture risk. Treatments exist that will preserve bone mass and presumably reduce fracture risk; therefore there is a place for screening of patients at high risk of fractures. Many studies have shown recently that a reduced bone mass (at least 1 standard deviation below normal) was associated with a more than 100% increased risk of fracture. Thus the initial assessment of bone mass can be used to estimate future fracture risk and to start prevention measures for high risk patients. Primary prevention can be initiated during the adolescence to optimize peak bone mass. Later in life, secondary prevention can prevent excessive bone loss and more specific treatments can prevent postmenopausal and age related bone demineralization. Strategies of prevention should be promoted and validated as general health care strategies.

Absorptiometry, Photon↗
PubMed1994

Effects of treatment of malignancy-associated hypercalcemia on serum parathyroid hormone-related protein.

Parathyroid hormone-related protein (PTHrP) is the primary mediator of hypercalcemia in patients with malignancy-associated hypercalcemia. We conducted this study to examine the effects of treatment with a bisphosphonate on serum PTHrP. We analyzed 41 episodes of hypercalcemia occurring in 38 patients: 22 patients received alendronate, and 16 were treated with pamidronate. At baseline, 29 patients had an increased serum PTHrP (group I) and 9 had low or undetectable levels (group II). The two groups did not differ significantly in baseline hypercalcemia (3.26 versus 3.41 mM) or the response of serum calcium to therapy. Serum calcium was normalized in 88% of group I and 70% of group II patients. Lowering of the mean calcium level was not associated with a change in the level of PTHrP in group I patients (40.2 versus 36.7 pgEq/ml) or group II patients. We also analyzed data on serum PTH and 1,25-(OH)2D in 20 of the patients. Serum PTH rose with treatment in group I patients (9.7-40.2 pg/ml, p < 0.05), as did the serum 1,25-(OH)2D (19.1-32.4 pg/ml, p < 0.001). Similarly, treatment of group II patients was associated with an increase in serum PTH (9.8-37.2 pg/ml) and serum 1,25-(OH)2D (22.9-40.2 pg/ml). The individual increases in 1,25-(OH)2D levels associated with therapy could not be predicted from the level of PTHrP or the changes in levels of serum calcium or PTH. Our data show that effective treatment of malignancy-associated hypercalcemia is not associated with a consistent change in serum levels of PTHrP. Therapy is associated with a variable increase in the serum levels of PTH and 1,25-(OH)2D.

Alendronate↗
PubMed1994

Regulation of collagen type I and biglycan mRNA levels by hormones and growth factors in normal and immortalized osteoblastic cell lines.

Growth factors, such as transforming growth factor beta (TGF-beta) and insulin-like growth factors (IGF) I and II, have been shown to exert anabolic effects on bone cells in vitro. Hormones, such as PTH and probably insulin and growth hormone, were recently shown to stimulate bone formation in vivo as well. The aim of the present study was to assess by northern blots, which were quantitated by densitometry, the effects of these anabolic growth factors and hormones in two osteogenic cell populations: CRP 10/30 cells, a clonal cell population derived from primary rat calvarial cells, and IRC 10/30-myc cells, which were established from CRP 10/30 by immortalization. Transcripts for alpha 1(I) collagen, biglycan, osteonectin, osteopontin, and osteocalcin were detected in both cell populations, which is consistent with the phenotype expressed by mature osteoblasts. There were no difference in the basal expression of bone matrix mRNAs between the two cell populations. PTH increased alpha 1(I) collagen mRNA levels in both osteoblastic cells but had no effect on the biglycan transcripts. Neither insulin nor growth hormone affected mRNA levels of either matrix protein after 24 h exposure. All three growth factors, TGF-beta, IGF-I, and IGF-II, increased alpha 1(I) collagen transcripts in a time- and dose-dependent manner in both cell populations. Biglycan mRNA levels were enhanced in both osteoblastic lines only by IGF-I and IGF-II, but not TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Two years' effectiveness of intravenous pamidronate (APD) versus oral fluoride for osteoporosis occurring in the postmenopause.

Bisphosphonates seem to be effective as antiresorptive agents in the prevention and treatment of osteoporosis. However, the optimal dose and route of administration as well as the specific effects on cortical or trabecular bone have not been clarified. To compare pamidronate (APD) with fluoride (F) in the therapy of postmenopausal osteoporosis, 32 osteoporotic women were treated for 2 years either with APD (30 mg as a single intravenous infusion over 1 h every 3 months, n = 16, mean age 65 years) or with fluoride orally (20-30 mg F/day, n = 16, mean age 67 years) in an open study. Both groups received 1 g calcium and 1000 U vitamin D per day, but no estrogens or other drugs acting on bone. Both groups showed the same initial mean number of fractures per patient (2.8 and 2.7). Bone densitometry was performed every 6 months at three sites: lumbar spine and hip with dual-energy X-ray absorptiometry (BMD), distal forearm with single photon absorptiometry and lumbar spine with quantitative computed tomography. Biochemical assessment was performed in blood and urine every 3 months. Lumbar BMD (g/cm2, mean +/- SEM) increased from 0.632 (+/- 0.030) at time 0 to 0.696 (+/- 0.028) at 24 months in the APD group (p < 0.001), and from 0.684 (+/- 0.025) to 0.769 (+/- 0.028) in the fluoride group (p < 0.001). Femoral neck BMD increased significantly from 0.558 (+/- 0.025) to 0.585 (+/- 0.025) (p < 0.01) in the APD group, whereas it did not change in the fluoride group.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Direct evidence of a parathyroid related protein gradient between the mother and the newborn in humans.

Umbilical cord plasma has increased parathormone (PTH)-like bioactivity in comparison with that in maternal plasma, but suppressed PTH levels. Previous attempts to detect elevated levels of PTHrP(1-34) in the umbilical cord were unsuccessful, whereas PTHrP was detected by immunohistochemistry in both fetal parathyroid glands and placental membranes. At the time of delivery, plasma samples were drawn simultaneously from 47 normal mothers (mean age, 26 years) and from the umbilical cord of 25 female and 22 male newborns and assessed for calcium adjusted for albumin, magnesium, creatinine, intact PTH and PTHrP. PTHrP was measured using a new 2-site immunoradiometric assay recognizing separately 1-40 and 60-72 residues with a sensitivity of 0.3 pmol/l. Mean (+/- S.D.) plasma calcium values were 2.35 +/- 0.10 in the mothers versus 2.63 +/- 0.12 mmol/l in the newborns (P < 0.001). PTH values were significantly higher in the mothers, as expected (22.3 +/- 14.8 vs. 6.2 +/- 0.9 pg/ml). In contrast, PTHrP values were significantly higher in the newborns (1.50 +/- 0.39 versus 0.84 +/- 0.28 pmol/l, P < 0.001). Only 1/47 mother had a PTHrP level higher than her child (0.9 vs. 0.8 pmol/l). Only 10/47 mothers had PTHrP higher than 1 pmol/l whereas only 1/47 newborn had a value below 1 pmol/l. There was no correlation between Ca and PTHrP in either group. Serum creatinine values were all within the normal range. Serum magnesium levels were not different between the mothers and the children.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1993

Methylpentylaminopropylidenebisphosphonate (BM 21.0955): a new potent and safe bisphosphonate for the treatment of cancer-associated hypercalcemia.

Bisphosphonates have been shown to be effective in lowering serum calcium levels in patients with cancer-associated hypercalcemia. 1-Hydroxy-3-(methylpentylamino)propylidenebisphosphonate (BM 21.0955) was developed as a third generation bisphosphonate and has been recently proven effective in animals and in patients with Paget's disease or tumor osteolysis. Thirty-six patients with cancer-associated hypercalcemia were treated with increasing doses (0.2-2.0 mg) of BM 21.0955 by single i.v. infusion over 4 h in a phase I trial. Six patients were rejected from analysis due to concomitant treatment with other bisphosphonates or chemotherapy. After rehydration and infusion of BM 21.0955 the mean serum calcium levels fell significantly (P < 0.001), from 3.29 +/- 0.49 mmol/l to 3.04 +/- 0.44 mmol/l until day 2 and normalized on day 6 (2.66 +/- 0.33 mmol/l). Serum calcium was reduced in all patients and normalized in 16. No symptomatic hypocalcemia occurred. Mean serum creatinine decreased significantly (P < 0.01), from 1.25 +/- 0.58 mg/dl (day 0) to 1.05 +/- 0.37 mg/dl (day 6). The mean urinary calcium/creatinine concentration fell significantly (P < 0.001), from 1.90 +/- 1.16 mM/mM (day 0) to 0.37 +/- 0.34 mM/mM/l (day 6). There were no subjective drug-related side effects during or after the infusion. Thirteen patients had elevations of morning body temperature above 38 degrees C. This was due to confirmed infections in five patients and possibly drug- or tumor-related in the other eight. We conclude from these preliminary results that a single infusion of BM 21.0955 is an effective and safe way to treat cancer-associated hypercalcemia.

Aged↗
PubMed1992

[Moderate Paget's disease treated with pamidronate (APD): experience in 43 patients with a single 60 mg infusion of varying duration of 1-to-24 hours].

Pamidronate disodium (APD) given as a single 60 mg intravenous infusion over 24 hours was shown to be an effective treatment for Paget's disease of bone. To further improve the feasibility of a simple treatment that ensures compliance in elderly outpatients (pts), we investigated the effectiveness of a single 60 mg APD intravenous infusion given over 8 hours (12 pts), 4 hours (9 pts) and 1 hour (10 pts) compared with that over 24 hours (12 pts). Infusion rate of APD was 7.5, 15 and 60 mg/h respectively, in comparison with 2.5 mg/h previously. Clinical improvement and biochemical remission were observed in all patients. Side effects, limited to mild transient fever and local transient increase in bone pain, occurred in 9 patients (2-3 pts in each group). There was no difference in the fall of plasma alkaline phosphatase and of urinary hydroxyproline between the 4 infusion rates. Plasma alkaline phosphatase (U/l, mean +/- SEM) decreased from 263 +/- 34 to 110 +/- 8 (1 h infusion), from 251 +/- 26 to 102 +/- 9 (4 h), from 237 +/- 23 to 95 +/- 9 (8 h) and from 256 +/- 29 to 97 +/- 7 (24 h), from day 0 to day 180 respectively (all p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Plicamycin and pamidronate in symptomatic tumor-related hypercalcemia: a prospective randomized crossover trial.

We have conducted a randomized crossover comparative trial of a single-dose course of disodium (3-amino-1-hydroxypropylidene) bisphosphonate pentahydrate (pamidronate) and plicamycin in 48 patients with a first occurrence of tumor-related hypercalcemia. All patients had hypercalcaemia-associated symptoms and serum-calcium levels (corrected for total protein) greater than or equal to 2.80 mmol/l. Pamidronate and plicamycin were given concurrently with rehydration immediately after diagnosis of hypercalcaemia was made. Both agents lowered serum calcium levels significantly within 1 week, with 88% of the evaluable patients in the pamidronate group and 45% of those in the plicamycin group achieving normocalcemia (p less than 0.01). In the patients who received pamidronate, the duration of normocalcemia was longer (p less than 0.05) and there was a significant decrease in serum creatinine (p less than 0.05). Vomiting occurred in 8 of 22 evaluable patients (36%) who received plicamycin, but in none of 25 evaluable patients who received pamidronate (P less than 0.01). Phlebitis occurred at the infusion site in more of the pamidronate-treated patients (P less than 0.05). Hypocalcemia, which occurred in 8 of 25 evaluable patients (32%) in the pamidronate group and in 1 of 22 of those (5%) in the plicamycin group, was either clinically asymptomatic or mild, except in one pamidronate-treated patient. Overall, pamidronate was found to be more effective and better tolerated than plicamycin, thereby confirming results of previous studies that showed pamidronate to be an effective, simple, and safe agent for the relief of the morbidity associated with tumor-related hypercalcemia.

Adult↗
PubMed1991

[Prevalence of risk factors for osteoporosis and distribution of calciuria and hydroxyprolinuria in an elderly population of a general practice. Results of a survey among 32 practitioners of the Vaud and Fribourg districts].

169 postmenopausal women and 84 male patients aged over 59 years from the outpatient consultations of 32 general practitioners were examined. The most frequently encountered risk factors for osteoporosis were low physical activity (41% of women, 27% of men), low intake of dairy products (37%/21%), smoking (11%/22%), while the particularly relevant risk factors were more rare, such as corticotherapy (7%/9%) and early menopause (17%). The risk factors were not more frequent than in 550 persons of the same age screened among the Swiss general population in another study. The same group of persons also yielded reference values for urinary calcium and hydroxyproline in the fasting urine, which are both considered as markers of bone turnover and as potential tools for screening osteoporosis. The urinary values were independent of age, body mass index, calcium intake, and the duration of the postmenopausal period. They were different from those found in 38 patients with Paget's disease, 66 patients with malignant hypercalcemia and 25 with bone metastasis from breast cancer. Calcium and hydroxyproline excretion are expressed as a ratio of urinary creatinine. Percentiles 10 and 90 of urinary calcium are 0.058 and 0.363 mmol/mmol (male) and 0.062 and 0.523 mmol/mmol (women). Percentiles 10 and 90 for urinary hydroxyproline are 0.006 and 0.024 mmol/mmol (male) and 0.010 and 0.025 mmol/mmol (women).

Aged↗
PubMed1991

Treatment of bone metastases from breast cancer and myeloma with pamidronate.

28 patients with progressing painful bone metastases (18 breast cancer, 9 myeloma and 1 low grade lymphoma) received pamidronate 60 mg by 24 h continuous infusion for at least 2 courses (range 2-12). In patients urinary calcium and hydroxyproline excretion significantly decreased in relation to diminution of bone resorption. 9 of 18 breast cancer patients and 8 of 9 evaluable patients with myeloma had symptomatic improvement. Sclerotic areas of previously lytic lesions appeared in 8 breast cancer patients and in 1 myeloma patient. Transient fever developed in 1 patient and local phlebitis in 2. Among the 28 patients, 15 did not receive any anticancer treatment or have any change of the anticancer therapy during pamidronate administration. Of 7 with breast cancer, 4 had an improvement of symptoms and 4 sclerosis on radiographs. Impressive control of symptoms was the major feature of 8 myeloma patients, but only 1 had radiographic sclerosis.

Adult↗