[Presidency of the Society of Nephrology: passing the baton from France to Switzerland].
Explore the source record for details and available documents.
Administrative Personnel↗
Biomedical subjects
P Jaeger
Publications and source records attributed to P Jaeger.
[Video-assisted theloscopic electroincision of a high teat stenosis].
Results of surgery of high teat stenosis remained disappointing until nowadays. The aim of this pilot study was to elaborate a new theloscopic surgical resection. A 5.5 year old swiss milk cow was suspected to have posttraumatic high teat stenosis. Diagnosed was ascertained by teat sonography. Animal was sedated and local anesthesia was performed at the base of the teat. After a teat side incision, resectoscope was introduced. Stenosis was electro-divided under continuity saline-solution irrigation and coagulation of bleeding vessels. After a follow-up period of 4 months, the cow was milked without residual. No intercurrent infections occurred. There were no signs of recurrence in the control teat sonography. Theloscopic electroresection of teat stenosis is a possible new, surgical, minimal invasive, option, to treat high teat stenosis.
Animals↗
[Differential osteoporosis diagnosis in the woman].
Bone mineral density of a woman in the second half of her life depends on the amount of bone made during growth and its subsequent rate of loss. Although the rate of bone loss did receive more attention in the study of pathogenesis of osteoporosis, it is becoming increasingly clear that insufficient accumulation of skeletal mass by young adulthood predisposes a person to low bone mass and subsequently to fractures later in life as age related and menopause-related bone loss ensue. In this article we 1) explain the role of inadequate peak bone mass as a major risk factor for osteoporosis and 2) give an overview of factors leading to osteoporosis by decreasing bone mass. Special emphasis has been put on iatrogenic osteoporosis which is frequently neglected because of the fact that the responsible agents often are not known as to be deleterious to the skeleton: among others, glucocorticoids, thyroid hormones and antiepileptics adversely affect bone.
Adult↗
Incidence and direct medical costs of hospitalizations due to osteoporotic fractures in Switzerland.
The objective of this study was to estimate the annual direct medical costs of hospitalizations due to osteoporotic fractures in Switzerland. Days of hospital stay in 1992 were quantified using the casuistic of the medical statistics department of VESKA (Vereinigung Schweizerischer Krankenhäuser, the Swiss Hospital Association), which covers 43% of all hospital beds of that country. Number and incidence of total hospitalizations due to fractures were calculated by extrapolating to 100% the 43% VESKA-selected sample. To estimate number and incidence of hospitalizations due to osteoporotic fractures, internationally accepted age-specific osteoporosis attribution rates were applied. According to the latter the probability of a fracture being caused by osteoporosis increases with age. Mean length of stay for all fractures was calculated (= total hospital days divided by number of cases). By multiplying these mean lengths of stay by the number of osteoporosis-related fracture cases, the number of bed-days due to osteoporotic fractures was calculated. To compare the direct medical costs of hospitalization due to osteoporosis with those due to other frequent diseases, days of hospital stay caused by chronic obstructive pulmonary disease (COPD), stroke, acute myocardial infarction and breast cancer were estimated using the same methodology. A total estimate of 63,170 (f: 33,596, m: 29,574) hospitalizations due to fractures (and other osteoporosis-related diagnoses) was calculated, thus leading to overall annual incidence rates of hospitalizations for fractures of 950/100,000 women and 877/100,000 men. In women, 548,615 hospital days were found to be caused by osteoporosis, 353,654 days by COPD, 352,062 days by stroke, 200,669 days by breast carcinoma and 131,331 days by myocardial infarction. In men, COPD caused more hospitalization days (537,164) than myocardial infarction (196,793), stroke (180,524) or osteoporosis (152,857). Taking a mean price for a hospital day in Switzerland of 845 Swiss francs, the annual costs of acute hospitalizations due to osteoporosis and its complications were approximately 600 million Swiss francs (f: 464, m: 130 million Swiss francs) in 1992. We conclude that there is enough economic evidence to justify wide-scale interventions against osteoporosis in Switzerland.
Adolescent↗
Three-dimensional primary stability of cementless femoral stems.
OBJECTIVE: This study investigates by means of a new bone-prosthesis interface motion detector whether conceptual design differences of femoral stems are reflected in their primary stability pattern. DESIGN: An in vitro experiment using a biaxial materials testing machine in combination with three-dimensional motion measurement devices was performed. BACKGROUND: Primary stability of uncemented total hip replacements is considered to be a prerequisite for the quality of bony ongrowth to the femoral stem. Dynamic motion as a response to loading as well as total motion of the prosthesis have to be considered under quasi-physiological cyclic loading conditions. METHODS: Seven paired fresh cadaveric femora were used for the testing of two types of uncemented femoral stems with different anchoring concepts: CLS stem (Spotorno) and Cone Prosthesis (Wagner). Under sinusoidal cyclic loading mimicking in vivo hip joint forces a new measurement technique was applied allowing for the analysis of the three-dimensional interface motion. RESULTS: Considerable differences between the two prostheses could be detected both in their dynamic motion and total motion behaviour. Whereas the CLS stem, due to the wedge-shaped concept, provides smaller total motions, the longitudinal ribs of the Cone prostheses result in a substantially smaller dynamic motion. CONCLUSIONS: The measuring technique provided reliable and accurate data illustrating the three-dimensional interface motion of uncemented femoral stems.
Journal Article↗
Effect of sex and age on bone mass, body composition and fuel metabolism in humans.
The mechanism(s) governing the gain of upper-body fat and its relationship to the decrease in bone mass with age is still unclear. Therefore, four groups of subjects matched for weight, height, and body mass index (n = 119; 60 women, 59 men), but differing in age (above and below 50 y) and sex were investigated using dual energy x-ray absorptiometry (DXA) to assess body composition (bone, lean, and fat mass as well as its distribution) and indirect calorimetry to determine resting fuel metabolism. Fat mass of trunk and arms (P < 0.01), but not legs, increased with advancing age in males, resulting in a continuous increase in the ratio of upper- to lower-body fat (r = 0.45, P < 0.001). In contrast, total fat mass remained stable in women, irrespective of menopause, but a redistribution of fat occurred with advancing age (r = 0.43, P < 0.001), resulting in a higher upper- to lower-body fat ratio (P < 0.05) in older than in younger women. Total lean soft-tissue mass of all segments of the body was greater in men than in women irrespective of age (P < 0.001), and lower in the older groups than in the younger ones irrespective of sex. In males, but not females, lean soft-tissue mass in arms and legs decreased (r = 0.57, P < 0.001), whereas the ratio of total fat to lean soft-tissue mass increased (r = 0.53, P < 0.001) with age. Bone mineral content correlated with total body fat in both groups of women and in young males (r > 0.5, P < 0.001), but not in older males. With advancing age, the proportion of lean soft-tissue mass occupied by total skeleton declined in women (n = 59, P < 0.001), but remained stable in males. Resting energy expenditure decreased with age in both sexes. Protein and carbohydrate oxidation were similar in all four groups of subjects. Total fat oxidation and fat oxidation per kilogram of lean soft-tissue mass decreased with age (r > 0.36, P < 0.01) in males, but not in females, whereas it increased with increasing fat mass in females (r > 0.32, P < 0.03), but not in males. In contrast, fat oxidation per kilogram of fat mass decreased with fat mass in males (r = 0.61, P < 0.001), but not in females. Our results suggest that aging affects body composition and fuel metabolism differently in each gender, leading to reduced fat oxidation and accumulation of upper-body fat with loss of striated muscle in men, and to an increased ratio of upper- to lower-body fat and bone loss in women, the latter depending on fat mass.
Absorptiometry, Photon↗
Metabolic evaluation of patients with recurrent idiopathic calcium nephrolithiasis.
BACKGROUND: Metabolic evaluation in recurrent idiopathic calcium renal stone-formers (RCSF) was analysed with respect to the following questions: (1) do three 24-h urines provide more diagnostic accuracy in the metabolic evaluation of RCSF than 1 or 2 urines?; (2) does time after stone event influence the diagnostic yield?; (3) is urine composition at weekends different from that at mid-week?; (4) what are the prevalences of the most important risk factors (RF) of idiopathic calcium nephrolithiasis, i.e. low volume (LV), hypercalciuria (HC), hyperoxaluria (HO), hyperuricosuria (HU), hypocitraturia (Hypo-Cit), and hypomagnesiuria (Hypo-Mg)?; and (5) do male RCSF differ from females with respect to urinary RFs? METHODS: Seventy-five RCSF (59 men, 16 women) collected three 24-h urines (U1-3) while on free-choice diet. To account for possible variations in lifestyle and diet, U1 and U3 had to be collected midweek and U2 at a weekend. RESULTS: When considering all three urines together (U1 + U2 + U3), the number of RF abnormalities/patient was 2.8 +/- 0.1, higher than numbers of any combination of two urines or of any single urine (P = 0.0001 for all comparisons). The number of RF abnormalities also rose with time after stone event, from 0.8 +/- 0.1 (range 0-4) in U1 to 1.1 +/- 0.1 (range 0-4) in U3 (P = 0.011 vs U1). Whereas all other RF did not change between collections, urine volume was lower in U2 (1793 +/- 90 ml) than in U1 (2071 +/- 97 ml, P = 0.0001 vs U2) and U3 (1946 +/- 97 ml, P = 0.046 vs U2). At least 1 abnormality was found in 85.3% of all RCSF, and multiple abnormalities occurred in 47%. The most frequent RF was HC (39%), followed by HO and LV (32% each), Hypo-Cit (29%), HU (23%) and Hypo-Mg (19%). Males more often had Hypo-Cit (P < 0.001) and Hypo-Mg (P < 0.01) than females, whereas HO was more frequent in female RCSF (P < 0.025 vs males). CONCLUSIONS: Diagnostic accuracy of metabolic evaluation in RCSF increases both with the number of urines collected and the time passing after a stone event. Urines collected at weekends differ from those of the week only by their lower volumes. Abnormalities of RF for calcium nephrolithiasis can be detected in 85.3% of RCSF, and HC is the most common RF both in male and female RCSF.
Adult↗
Long-term influence of different postmenopausal hormone replacement regimens on serum lipids and lipoprotein(a): a randomised study.
OBJECTIVE: To assess the influence of three different postmenopausal hormone replacement therapies on levels of serum lipids and lipoprotein(a) [Lp(a)]. DESIGN: Open, randomised, controlled study. PARTICIPANTS: One hundred and forty healthy, early postmenopausal women. INTERVENTIONS: The women were randomised to receive continuous 17 beta-oestradiol, either orally (2 mg daily; n = 35) or transdermally (50 micrograms daily; n = 35), plus 10 mg dydrogesterone daily for 14 days of each 28-day cycle; or 2.5 mg tibolone daily (n = 35). Thirty-five untreated women acted as controls. MAIN OUTCOME MEASURES: Fasting blood samples were analysed at baseline, 6, 12 and 24 months for low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, very low density lipoprotein (VLDL), total cholesterol, triglycerides, lipoprotein(a)[Lp(a)], apolipoproteins A-1, A-2 and B, fibrinogen, and antithrombin factor III. RESULTS: At 24 months oral oestradiol increased mean HDL cholesterol (7%; 95% CI 1-14), compared with no change in the transdermal group and a decrease of 26.8% in the tibolone group (95% CI 22.9-30.5); oral oestradiol decreased mean LDL cholesterol (11.8%; 95% CI 6.3-19), compared with no change in the tibolone group. Changes in apolipoprotein A-1 and B showed a similar pattern to HDL and LDL cholesterol, respectively. Oral oestradiol increased serum triglycerides (30%; 95% CI 18-42) after 24 months, compared with no change in the tibolone and transdermal oestradiol groups. Tibolone decreased serum Lp(a) by 36.6% after 24 months (95% CI 8.3-56.2), oral oestradiol decreased levels by 29.4% (95% CI 2-51.1), compared with no change in the transdermal oestradiol group. CONCLUSIONS: Oral and to a lesser extent transdermal oestradiol when sequentially combined with dydrogesterone, showed a beneficial influence on serum lipids regarding the cardiovascular disease risk, which was not seen with tibolone. The significance of Lp(a) levels on cardiovascular disease risk remains to be determined.
Administration, Cutaneous↗
Aromatase deficiency in a female who is compound heterozygote for two new point mutations in the P450arom gene: impact of estrogens on hypergonadotropic hypogonadism, multicystic ovaries, and bone densitometry in childhood.
We report on a female who is compound heterozygote for two new point mutations in the CYP19 gene. The allele inherited from her mother presented a base pair deletion (C) occurring at P408 (CCC, exon 9), causing a frameshift that results in a nonsense codon 111 bp (37 aa) further down in the CYP19 gene. The allele inherited from her father showed a point mutation from G-->A at the splicing point (canonical GT to mutational AT) between exon and intron 3. This mutation ignores the splice site and a stop codon 3 bp downstream occurs. Aromatase deficiency was already suspected because of the marked virilization occurring prepartum in the mother, and the diagnosis was confirmed shortly after birth. Extremely low levels of serum estrogens were found in contrast to high levels of androgens. Ultrasonographic follow-up studies revealed persistently enlarged ovaries (19.5-22 mL) during early childhood (2 to 4 yr) which contained numerous large cysts up to 4.8 x 3.7 cm and normal-appearing large tertiary follicles already at the age of 2 yr. In addition, both basal and GnRH-induced FSH levels remained consistently strikingly elevated. Low-dose estradiol (E2) (0.4 mg/day) given for 50 days at the age of 3 6/12 yr resulted in normalization of serum gonadotropin levels, regression of ovarian size, and increase of whole body and lumbar spine (L1-L4) bone mineral density. The FSH concentration and ovarian size returned to pretreatment levels shortly (150 days) after cessation of E2 therapy. Therefore, we recommend that affected females be treated with low-dose E2 in amounts sufficient to result in physiological prepubertal E2 concentrations using an ultrasensitive estrogen assay. However, E2 replacement needs to be adjusted throughout childhood and puberty to ensure normal skeletal maturation and adequate adolescent growth spurt, normal accretion of bone mineral density, and, at the appropriate age, female secondary sex maturation.
Adult↗
Prevention of postmenopausal bone loss using tibolone or conventional peroral or transdermal hormone replacement therapy with 17beta-estradiol and dydrogesterone.
Postmenopausal bone loss can be prevented by continuous or intermittent estradiol (E2) administration. Concomitant progestogen therapy is mandatory in nonhysterectomized women to curtail the risk of endometrial hyperplasia or cancer. However, the recurrence of vaginal bleeding induced by sequential progestogen therapy in addition to continuous estrogen administration is one of the reasons for noncompliance to hormone replacement therapy (HRT). Tibolone, a synthetic steroid with simultaneous weak estrogenic, androgenic, and progestational activity, which does not stimulate endometrial proliferation, has recently been proposed for the treatment of climacteric symptoms. To compare the efficacy of conventional oral and transdermal HRT with that of tibolone in the prevention of postmenopausal bone loss, 140 postmenopausal women (age, 52 +/- 0.6 years; median duration of menopause, 3 years) were enrolled in an open 2-year study. Volunteers had been offered a choice between HRT and no therapy (control group, CO). Patients selecting HRT were randomly allocated to one of the following three treatment groups: TIB, tibolone, 2.5 mg/day continuously, orally; PO, peroral E2, 2 mg/day continuously, plus sequential oral dydrogesterone (DYD), 10 mg/day, for 14 days of a 28-day cycle; TTS, transdermal E2 by patch releasing 50 microg/day, plus DYD as above. Bone densitometry of the lumbar spine, upper femur, and whole body was performed using dual-energy X-ray absorptiometry at baseline, and then 6, 12, 18, and 24 months after initiation of therapy. One hundred and fifteen women (82%) completed the 2 years of the study. The dropout rate was similar in each group. Over 2 years, bone preservation was observed in all three treatment groups as compared with controls, without significant differences among treatment regimens. In conclusion, tibolone can be regarded as an alternative to conventional HRT to prevent postmenopausal bone loss.
Absorptiometry, Photon↗
The relative importance of vertebral bone density and disc degeneration in spinal flexibility and interbody implant performance. An in vitro study.
STUDY DESIGN: An in vitro biomechanical investigation in the human lumbar spine focuses on the functional significance of vertebral bone density and intervertebral disc degenerations. OBJECTIVE: To determine that interrelationship between vertebral bone density and intervertebral disc degeneration, their effect on normal spine motion, and their significance in the biotechnical performance of interbody fixation techniques. SUMMARY OF BACKGROUND DATA: A relationship between vertebral bone density and intervertebral disc degeneration has been suggested, but a definitive relationship has not been established. The effect of vertebral bone density and intervertebral disc degeneration on interbody stabilization remains unknown despite the rapidly increasing use of this surgical method for patients with chronic low back pain. METHODS: The vertebral bone density and intervertebral disc degeneration of 72 functional spinal units were determined using dual energy x-ray absorptiometry scans and macroscopic grading, respectively. A three-dimensional flexibility test was performed on 24 functional spinal units in the intact and stabilised conditions. The compressive behavior of the bone-implant interface was evaluated in 48 functional spinal units. RESULTS: The vertebral bone density in moderately degenerated disc was significantly lower than at all other levels of intervertebral disc degeneration. Increasing intervertebral disc degeneration resulted in more axial rotation and less lateral bending. In flexion-extension and lateral bending, better vertebral bone resulted in significantly better stabilization. This trend was observed also in axial compression in which higher failure loads were observed with greater bone densities. CONCLUSION: The authors conclude a significant relationship exists between bone density and disc degeneration, bone density is a highly important factor in the performance of interbody stabilization, and disc degeneration, is of moderate importance in signal motion.
Biomechanical Phenomena↗
Evidence for preservation of cortical bone mineral density in patients on continuous ambulatory peritoneal dialysis.
It is still unclear whether dialysis modality, i.e., continuous ambulatory peritoneal dialysis (CAPD) versus hemodialysis (HD) specifically affects bone mineral density (BMD). To answer this question, 34 patients on HD and 25 on CAPD were matched for age, sex, height, and body weight with 125 normal subjects. BMD was measured using dual-energy X-ray absorptiometry (DXA; Hologic QDR 1000/W) at the lumbar spine (trabecular bone), the femoral neck (mixed cortical and trabecular bone), the distal tibial diaphysis (cortical bone), and the epiphysis (trabecular bone) in all subjects. No significant difference for blood hemoglobin, albumin, total and ionized calcium, intact parathyroid hormone (PTH) or phosphorus concentrations, as well as for alkaline phosphatase activity, failed renal allograft, prior steroid therapy, prior parathyroidectomy, duration of uremia, or of dialysis was found between patients on HD and those on CAPD. However, the residual daily urine volume and renal function at the time of the absorptiometry were higher in CAPD than in HD patients (p < 0.05) as well as the mean dialysate calcium concentration during dialysis, the blood bicarbonate concentration, and the residual renal function at the initiation of dialysis (p < 0.01, p < 0.05, and p < 0.005, respectively). In contrast, the total dose of calcium carbonate was lower in CAPD than in HD patients (p < 0.01). Results of BMD were expressed as Z scores (the number of standard deviations from the appropriate mean of BMD of 623 healthy subjects adjusted for age and sex). At the lumbar spine, no significant difference with respect to BMD was observed between the three groups. At the femoral neck and tibial epiphysis, HD patients had lower BMD (p < 0.001) than normal controls, whereas no difference was observed between HD and CAPD patients. At tibial diaphysis, patients on HD had lower BMD (p < 0.001) than patients on CAPD and than normal controls, with the values being similar in patients on CAPD and in normal controls. The results remained identical after exact matching of HD (n = 25) and CAPD (n = 25) patients for dialysis duration (1.9 +/- 0.3 and 1.7 +/- 0.3 years, respectively). Multiple regression analysis revealed significant negative correlations between Z scores at the lumbar spine (p < 0.05), femoral neck (p < 0.02), tibial diaphysis (p < 0.005), and tibial epiphysis (p < 0.05) on the one hand and plasma alkaline phosphatase activity on the other. The Z score at tibial diaphysis was also correlated with residual renal function at the initiation of dialysis (p < 0.05). In conclusion, this study provides evidence for the preservation of cortical bone with CAPD as opposed to HD. The higher residual renal function observed in the former treatment modality might account, at least in part, for this finding.
Bone Density↗
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↗
Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis.
To determine the effects of long-term daily oral alendronate sodium (ALN) on bone mass in postmenopausal women with osteoporosis, 19 centers enrolled 516 postmenopausal women aged 45-80 years with spine bone mineral density (BMD) at least 2.5 SD below the mean for young premenopausal women in a 3-year, double-blind, placebo-controlled study. Subjects were randomly allocated to one of four treatment groups: placebo; alendronate, 5 or 10 mg/day for 3 years; or alendronate, 20 mg/day for 2 years followed by 5 mg/day for the 3rd year. All patients received 500 mg/day of supplemental calcium to ensure adequate calcium intake. BMD was measured by dual-energy X-ray absorptiometry at several skeletal sites. Nonsignificant mean decreases in BMD of the spine, femoral neck, and trochanter of 0.6, 0.7, and 0.4%, respectively, occurred in the placebo group at 3 years. Relative to placebo-treated patients, spine BMD increased by 5.4%, 7.4%, and 8.4% in the 5, 10, and 20/5 mg ALN groups, respectively. Increases at the femoral neck were 3.5%, 5.5%, and 4.3%, and those at the trochanter were 5.1%, 7.2%, and 7.2%, respectively. Thus, efficacy of 10 and 20/5 mg ALN was similar, whereas the 5 mg dose was less effective. BMD continued to increase over the entire 3-year study duration in the ALN-treated groups and, compared with the other dosage groups, 10 mg ALN produced the largest gains in BMD during the 3rd year. Changes in biochemical markers of bone turnover and mineral homeostasis confirmed the effect of ALN to decrease bone turnover to a new steady-state level. The safety and tolerability of ALN were comparable with those of placebo. In summary, 10 mg daily oral ALN given for 3 years significantly and progressively increases bone mass and is a generally well-tolerated treatment for osteoporosis in postmenopausal women.
Administration, Oral↗
Effect of regular physical training on age-associated alteration of body composition in men.
Body composition changes with increasing age in men, in that lean body mass decreases whereas fat mass increases. Whether this altered body composition is related to decreasing physical activity or to the known age-associated decrease in growth hormone secretion is uncertain. To address this question, three groups of healthy men (n = 14 in each group), matched for weight, height and body mass index, were investigated using dual-energy X-ray absorptiometry, indirect calorimetry and estimate of daily growth hormone secretion [i.e. plasma insulin-like growth factor I (IGF-I-) levels]. Group 1 comprised young untrained subjects aged 31.0 +/- 2.1 years (mean +/- SEM) taking no regular physical exercise; group 2 consisted of old untrained men aged 68.6 +/- 1.2 years; and group 3 consisted of healthy old men aged 67.4 +/- 1.2 years undergoing regular physical training for more than 10 years with a training distance of at least 30 km per week. Subjects in group 3 had for the past three years taken part in the 'Grand Prix of Berne', a 16.5-km race run at a speed of 4.7 +/- 0.6 min km-1 (most recent race). Fat mass was more than 4 kg higher in old untrained men (P < 0.01, ANOVA) than in the other groups (young untrained men, 12.0 +/- 0.9 kg; old untrained men, 16.1 +/- 1.0 kg; old trained men, 11.0 +/- 0.8 kg), whereas body fat distribution (i.e. the ratio of upper to lower body fat mass) was similar between the three groups. The lean mass of old untrained men was more than 3.5 kg lower (P < 0.02, ANOVA) than in the other two groups (young untrained men, 56.4 +/- 1.0 kg; old untrained men, 52.4 +/- 1.0 kg; old trained men, 56.0 +/- 1.0 kg), mostly because of a loss of skeletal muscle mass in the arms and legs (young untrained men, 24.0 +/- 0.5 kg; old untrained men 20.8 +/- 0.5 kg; old trained men, 23.6 +/- 0.7 kg; P < 0.01, ANOVA). Resting metabolic rate per kilogram lean mass decreased with increasing age independently of physical activity (r = -0.42, P < 0.005). Fuel metabolism was determined by indirect calorimetry at rest. Protein oxidation was similar in the three groups. Old untrained men had higher (P < 0.001) carbohydrate oxidation (young untrained men, 13.2 +/- 1.0 kcal kg-1 lean mass; old untrained men, 15.2 +/- 1.3 kcal Kg-1; old trained men, 7.8 +/- 0.8 kcal kg-1), but lower (P < 0.05, ANOVA) fat oxidation (young untrained men, 10.1 +/- 1.2 kcal kg-1 lean mass; old untrained men, 6.5 +/- 1.0 kcal kg-1; old trained men, 13.7 +/- 1.0 kcal kg-1) than the other two groups. Mean plasma IGF-I level in old trained men was higher than in old untrained men (P < 0.05), but was still lower than that observed in young untrained men (P < 0.005) (young untrained men, 236 +/- 24 ng mL-1; old untrained men, 119 +/- 13 ng mL-1; old trained men, 166 +/- 14 ng mL-1). In summary, regular physical training in older men seems to prevent the changes in body composition and fuel metabolism normally associated with ageing. Whether regular physical training in formerly untrained old subjects would result in similar changes awaits further study.
Absorptiometry, Photon↗
Systemic interleukin-2 modulates the anti-idiotypic response to chimeric anti-GD2 antibody in patients with melanoma.
The induction of human antimouse antibodies (HAMA) and human anti-idiotypic (anti-Id) responses in cancer patients receiving therapeutic monoclonal antibody (mAb) may limit the effectiveness of the administered mAb. This report evaluates the influence of systemic interleukin-2 (IL-2) on the anti-Id response to anti-disialoganglioside (anti-GD2) antibody given as treatment for patients with melanoma. Twenty-eight patients with melanoma received combined immunotherapy with anti-GD2 antibody and IL-2 at 1.5 x 10(6) U/m2/day given 4 days/week. The anti-GD2 antibody [murine 14.G2a mAb; dose levels of 2-5 mg/m2/day (4 patients); or human-mouse chimeric 14.18 (ch14.18) antibody; dose levels of 2-10 mg/m2/day (24 patients)] was scheduled to be given for 5 days either before, during, or after initial systemic IL-2 treatment. All four patients who received murine 14.G2a developed HAMA anti-isotype antibodies (660-1,000 ng/ml) as well as measurable anti-Id antibodies. All three patients who received initial treatment with ch14.18 alone developed a strong anti-Id antibody response after IL-2 was started 1 week later. The serum level of anti-Id antibody decreased during subsequent ch14.18 infusions, suggesting that the anti-Id antibody may be binding the administered ch14.18. In contrast, measurable anti-Id antibody was detected in only 3 of 14 patients who received IL-2 before, during, and after initial ch14.18 administration. Two of four patients receiving systemic IL-2 before and during initial ch14.18 infusions, and two of three patients receiving systemic IL-2 concurrent with initial ch14.18 infusions developed anti-Id antibodies. These data suggest that the anti-Id response to chimeric anti-GD2 antibody is influenced by the timing of systemic IL-2 in relation to antibody administration and can be suppressed by systemic treatment with IL-2 given before, during, and after the antibody administration.
Adjuvants, Immunologic↗
No evidence of osteopenia 5 to 8 years after ileal orthotopic bladder substitution.
PURPOSE: The use of bowel segments as bladder substitutes may result in chronic, impaired vitamin D and calcium metabolism, and ultimately in bone demineralization. MATERIALS AND METHODS: Bone metabolism was examined in 14 patients who lived for 5 to 8 years with an ileal low pressure bladder substitute after radical cystectomy for bladder cancer. Bone mineral density was measured using dual energy x-ray absorptiometry of the total skeleton, lumbar spine, femoral neck, and tibial epiphysis and diaphysis. Laboratory studies included serum levels of 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, intact parathyroid hormone, plasma alkaline phosphatase, electrolytes, creatinine and blood gas analysis. RESULTS: Bone mineral density was normal in all patients. There was no evidence of deficient vitamin D stores. There was a tendency toward slightly elevated serum creatinine values in patients with preexisting impaired renal function, including 1 who also had slight acidosis. No patient had hyperchloremia. CONCLUSIONS: We found no evidence of osteomalacia, osteoporosis or significant metabolic acidosis in 14 patients with an ileal bladder substitute for 5 to 8 years. However, it is not known whether the absence of osteopenia would also apply to patients with poor renal function, to those not followed meticulously and, thus, at risk for major long-term functional or metabolic disturbances from the ileal bladder substitute or to patients with orthotopic bladder substitutes made from longer or other bowel segments than we used.
Acidosis↗
Genetic versus environmental factors in renal stone disease.
The dietary habits of renal stone formers appear to differ from those of the general population. Renal stone formers seem to eat more oxalate, more flesh protein and less vegetable fibres than their normal counterparts. Often their urine volume is low. These are environmental factors which govern nephrolithiasis. Subtle underlying defects are detected not infrequently in these patients; for example, medullary sponge kidneys, abnormally structured macromolecular inhibitors of calcium oxalate crystallization (nephrocalcin and Tamm-Horsfall protein), incomplete distal renal tubular acidosis, deficient activation of pyridoxine, defective intestinal absorption of citrate, excessive production of interleukin-1 by monocytes, subtle primary hyperparathyroidism, heterozygosity for cystinuria, and, discovered more recently, abnormal chloride channels along the nephron. Many of these defects are inheritable, but carriers of the trait are not always active stone formers. The opinion forwarded in this review is that combinations of the environmental and of the underlying or genetic defects are required to trigger renal stone disease.
Aged↗