Ultrasound Measurements for the Prediction of Osteoporotic Fractures in Elderly People

In this prospective study we investigated the predictive value of quantitative ultrasound (QUS) measurements and other potential predictors of osteoporotic fractures in the elderly. During a 1-year period, 710 participants (132 men and 578 women), aged 70 years and older (mean age ± SD: 82.8 ± 5.9), were recruited from seven homes and apartment houses for the elderly. QUS measurements (broadband ultrasound attenuation (BUA) and speed of sound (SOS)) were assessed with a clinical bone densitometer. A structured questionnaire was used to collect information on other potential predictors. Follow-up of fractures was done each half year by telephone interviews. During the study period (median follow-up 2.8 years, maximum 3.7 years), 30 participants had a first hip fracture and 54 suffered from a first other nonspinal fracture. Cox regression analyses, adjusted for age and sex, showed that the relative risk (RR) of hip fracture for each standard deviation reduction was 2.3 (95% CI, 1.4–3.7) for BUA and 1.6 (95% CI, 1.1–2.3) for SOS. Slightly weaker relationships were found for any fracture (BUA: RR, 1.6; 95% CI, 1.2–2.1; SOS: RR, 1.3; 95% CI, 1.0–1.6). Multivariable analyses identified low BUA values and immobility as the strongest predictors for hip fractures and any fracture. Female gender proved to be the strongest predictor for other nonspinal fractures. It can be concluded that QUS measurements can predict the risk for hip fracture and any fracture in elderly people. Received: 23 July 1998 / Accepted: 19 November 1998     

Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos

In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture environment differs from in-vivo conditions in that the oxygen concentration is higher, and in such conditions the mouse embryos show a higher concentration of reactive oxygen species (ROS) in simple culture media. ROS are believed to cause damage to cell membranes and DNA fragmentation in somatic cells. This study was conducted to ascertain the level of H2O2 concentration within embryos and the morphological features of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31 fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was obtained from the IVF-embryo transfer programme. The relative intensity of H2O2 concentrations within embryos was measured using 2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence imaging and DNA fragmentation was observed with transmission electron microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations were significantly higher in fragmented embryos (72.21 +/- 9.62, mean +/- SEM) compared to non-fragmented embryos (31.30 +/- 3.50, P < 0.05) and unfertilized oocytes (30.75 +/- 2.67, P < 0.05). Apoptosis was observed only in fragmented embryos, and was absent in non-fragmented embryos. Electron microscopic findings confirmed apoptotic bodies and cytoplasmic condensation in the fragmented blastomeres. We conclude that there is a direct relationship between increased H2O2 concentration and apoptosis, and that further studies should be undertaken to confirm these findings.      

From gene to disease; from the RET gene to multiple endocrine neoplasia types 2A and 2B, sporadic and familial medullary thyroid carcinoma, Hirschsprung disease and papillary thyroid carcinoma]

The RET gene encodes a receptor tyrosine kinase involved in normal and neoplastic development of neural crest cell lineages. Activating RET mutations are present in patients with multiple endocrine neoplasia types 2A and 2B (MEN2A, 2B) and in familial medullary thyroid carcinoma (FMTC) patients, whereas inactivating RET mutations are found in patients with Hirschsprung (HSCR) disease. In particular for MEN2A and FMTC, the clinical management largely depends on the specific mutation found.     

Determination of the solute removal index for urea by using a partial spent dialysate collection method

In 22 hemodialysis patients, during a dialysis session, the solute removal index (SRI) for urea obtained from the use of a partial spent dialysate collection method was compared with that derived from the use of a total spent dialysate collection technique. The partial spent dialysate collection method was used to harvest a small representative sample of the total spent dialysate. The volumes of spent dialysate collected by the partial and the total spent dialysate collection methods were 1.7 +/- 0.4 L and 129.6 +/- 15.3 L, respectively. The total amount of urea nitrogen removed by dialysis as estimated by the partial spent dialysate collection method was similar to that determined by the total spent dialysate collection approach. As a result, the SRI value for urea obtained by the partial spent dialysate collection method (namely, 63% +/- 8%) correlated very well (r = 0.95, P < 0.001) with that derived by the total spent dialysate collection technique (namely, 62% +/- 8%). Our data suggest that it is feasible to use a simple partial spent dialysate collection method to obtain SRI results in patients treated with hemodialysis.     

Impact of vertebral deformities, osteoarthritis, and other chronic diseases on quality of life: a population-based study

Vertebral deformities and spinal osteoarthritis are common disorders in elderly persons and are associated with back pain, impaired physical functioning, and loss of quality of life. The objectives of this study were to assess the impact of vertebral deformities and osteoarthritis on quality of life in a population-based sample, and to compare this with the impact of six other important chronic diseases on quality of life. The study was performed as a substudy of the Longitudinal Aging Study Amsterdam. Vertebral deformities and osteoarthritis were assessed by spinal radiographs; chronic diseases were assessed by self-report; quality of life was estimated by the SF-12, EQ-5D (EuroQol) and Qualeffo-41 (n=336). In univariate analyses, severe osteoporosis of the vertebrae significantly worsened the physical component summary scale of the SF-12 and the total score of Qualeffo-41, while osteoarthritis of the spine did not significantly reduce quality of life. The other chronic diseases reduced quality of life, although not all changes reached statistical significance. In multivariate analyses, severe osteoporosis of the vertebrae, cardiac disease, peripheral arterial disease, and diabetes mellitus significantly reduced quality of life. In conclusion, most persons in an elderly population suffer from one or more chronic diseases, and therefore experience loss of quality of life. After adjustment for age, sex, and other chronic diseases, severe osteoporosis of the vertebrae, cardiac disease, peripheral arterial disease, and diabetes mellitus significantly reduced quality of life in the general population.     

Stimulation and suppression of intact parathyroid hormone (PTH1–84) in normal subjects and hyperparathyroid patients

OBJECTIVE: Because of an overlap between serum PTH values in healthy controls and hyperparathyroid patients we sought to evaluate a short stimulation and suppression test for differentiating the two groups. SUBJECTS: Subjects were 34 patients with primary hyperparathyroidism (PHPT) and 25 healthy controls. DESIGN: After stimulation with intravenous EDTA (10 mg/kg body weight in 5 minutes) blood samples were obtained for up to 15 minutes. After an oral calcium dose of 1 g, blood samples were obtained at 1 and 2 hours. After an intravenous calcium dose (2.5 mg/kg body weight in 30 seconds), blood samples were obtained serially for 20 minutes. MEASUREMENT: Serum PTH(1-84) was measured by a double antibody technique. RESULTS: The intravenous EDTA test resulted in an average 2.6-fold increase of serum PTH(1-84) in hyperparathyroid patients, whereas it increased 10.5-fold in controls. A response was absent in three of 23 patients. There was an overlap in results between patients with mild hyperparathyroidism and controls. The oral calcium dose decreased serum PTH(1-84) in patients to 0.73 and in controls to 0.55 of the basal value, but six of 15 patients and two of 12 controls did not respond. The intravenous calcium test resulted in a drop of serum PTH(1-84) in hyperparathyroid patients to 0.51 and in control subjects to 0.40 of the basal value, and non-responders were not observed. There was a strong correlation between the responses to the EDTA and the calcium infusion tests in the patients (r = 0.97, P less than 0.01). Fasting serum calcium and serum PTH(1-84) showed a positive correlation in PHPT patients (r = 0.75, P less than 0.001) and a negative correlation in control subjects (r = -0.41, P less than 0.05). Based on these relationships, hyperparathyroid patients and controls could be completely separated. CONCLUSION: The wide range of responses to stimulation and suppression tests and the correlation between these responses in hyperparathyroid patients indicate various degrees of autonomy. As the response to these tests is less marked in patients than in controls and both groups still overlap, these tests are not useful for the diagnosis of primary hyperparathyroidism.     

No effect of the long-acting somatostatin analogue octreotide in patients with insulinoma

The efficacy of subchronic (3 weeks) treatment with the long-acting somatostatin analogue octreotide was studied in four patients with symptomatic benign insulinoma. No clinical or biochemical effect on serum glucose, insulin, C-peptide or glucagon was observed in all four patients despite clearly detectable serum levels of octreotide. The resistance to octreotide therapy in these patients might be explained by the absence of somatostatin analogue receptors on their tumours.