Epidemiological and ethical aspects of multiplex autoantibody testing.

Arrays are one of the technologies able to detect autoantibodies by measuring simultaneously many thousands of markers from a unique biological sample. The main purpose of a diagnostic test is making an early and accurate diagnosis. From a statistical point of view, multiple testing increases the probability of false positive and false negative results. Some correction methods are available to account for this problem for instance family-wise error rate or false discovery rate. From an ethical point of view, the decision to accept or decline a test not requested has to be made autonomously. Some people may seek clarification about tests and implications of their choices. A scarcity of proven measures to reduce mortality has to be considered too. Reasons may also include avoidance of psychological harm or anxiety. Moreover, protection of confidentiality and privacy has to be respected. In conclusion, the fact that testing is optional and that surveillance advice can be offered on the basis of risk alone without a test should be discussed in the consultation. The implication of a positive test result should be discussed to make a decision about the degree to which early treatment of the condition is better than late (or no) treatment.

Physical activity and bone mineral density in Italian middle-aged women.

Osteoporosis is a major health issue in post-menopausal women on account of the association between low bone mineral density and fractures. A role of physical activity in the prevention and treatment of low bone mineral density is possible but still unclear. The relationship between low spine bone mineral density measured by means of dual photon absorptiometry at lumbar spines, and levels of past and recent physical activity has been assessed by means of a population-based screening study carried out on 1373 women (age 40-64 years) in the North-East of Italy. Physical activity at work and in leisure time was investigated for three specific periods of life: at age 12, between 15 and 19 years (during bone formative years), and in the recent years prior to the interview (30-39 or 50-59 years). Data were analysed comparing low versus high bone mineral density tertile (i.e., 458 and 461 women, respectively), after controlling for other known contributory factors in the development of osteoporosis. A positive association emerged with leisure time physical activity, with significant trends at age 15-19 (odds ratio (OR) for low versus high tertile of leisure time activity: 1.4, 95% confidence interval (CI): 0.8-2.4) and at most recent age (OR: 1.7, 95% CI: 1.1-2.6). Risk trends with occupational physical activity were less clear and non-statistically significant. The present Southern European cross-sectional study lends further support to the possibility that past and recent physical activity helps increasing bone mineral density in middle-aged women. Although the most beneficial type and intensity level of exercise has yet to be determined, the present results provide further evidence that participation in even moderate exercise programs should be encouraged.

Menopause, menstrual and reproductive history, and bone density in northern Italy.

STUDY OBJECTIVE: To analyse the relationship between menstrual and reproductive factors and the risk of low bone mineral density (BMD). DESIGN: This was a population based screening programme carried out between 1991 and 1993 among 1373 perimenopausal women in northern Italy by means of dual photon absorptiometry at the lumbar spine. MAIN RESULTS: BMD was strongly related to the age at menopause. In comparison with women reporting menopause below 45 years of age, the odds ratios (OR) of being in the lowest compared with the highest BMD tertile were 0.7 (95% confidence interval (CI) 0.3,1.5) and 0.3 (95% CI 0.1,0.8), respectively, in those with menopause at age 45-49 and above 50 years: the trend in risk was significant. Likewise, the risk of being in the lowest tertile increased with years since the menopause. Compared with women who reported they had undergone the menopause less than two years before interview, the OR of being in the lowest BMD tertile were 2.1 (95% CI 1.1,4.3), 2.3 (95% CI 1.1, 5.0), and 5.7 (95% CI 2.5,12.9) respectively in women who reported menopause 2-5, 6-9, and > or = 10 years earlier. The protective effect on bone density of late age at menopause was observed in different strata of years since menopause. Likewise, the increasing risk of a low BMD with increasing years since the menopause was evident in strata of different age at menopause. No relationships were observed between BMD and the age at menarche, characteristics of menstrual cycles, and the duration of menses. Likewise, no association emerged between reproductive history, including parity and age at first pregnancy, and BMD. CONCLUSIONS: In this Italian population the risk of being in the lowest BMD tertile decreased with increasing age at menopause and increased with years since menopause. No relationships emerged between BMD and other menstrual characteristics or reproductive factors.

The influence of body size, smoking, and diet on bone density in pre- and postmenopausal women.

We studied the determinants of low bone mineral density, using data from a population-based screening program of osteoporosis carried out among 1,373 women (age 40-64 years) in the province of Pordenone, Italy, by means of dual photon absorptiometry of the lumbar spine. Menopause had a major effect on bone mineral density. Age had little influence before menopause. In multivariate linear regression analyses, weight was the strongest predictor of bone mineral density in pre- as well as postmenopausal women. After the inclusion in a single model of a term for current weight, weight at ages 12 and 30 years explained some additional variance, whereas high waist-to-hip ratio (an indicator of central adiposity) had no influence. Smoking 15 or more cigarettes per day entailed a small increased risk of osteoporosis, but this effect, independent of weight, appeared to be restricted to premenopausal women. No food or micronutrient that we examined was predictive of bone mineral density, nor was coffee or alcoholic beverage intake.

Double catheterization of the internal jugular vein for hemodialysis: indications, techniques, and clinical results.

Central vascular catheters are used to access the central vascular system in both acute and chronic uremic patients undergoing hemodialysis. Among different approaches, the internal jugular vein seems to have less adverse effects. We describe our long-term experience with a two-catheter system. Percutaneous jugular vein cannulation was performed using Medcomp silicone rubber catheters. The study included 108 patients undergoing hemodialysis. One- and 2-year survival was 93 and 91%, respectively; 36 died because of unrelated causes. Blood flow rate was 284 mL/min; venous pressure at 1 year was 90 mm Hg. Complications included accidental withdrawal (6), dysfunction (4), catheter clotting (11), mediastinal hematoma (2), pneumothorax (1), and sepsis (7). Good long-term survival and a low complication rate make this system a safe and reliable method of access for long-term hemodialysis.

Fusarium peritonitis in peritoneal dialysis: report of two cases.

This report describes two cases of peritoneal dialysis-related peritonitis caused by Fusarium species which have been incriminated in a variety of disease conditions. Treatment with 5-Fluorocytosine was unsuccessful, but removal of the catheter resulted in a rapid resolution of the infections.

Close genetic linkage between HLA and renal glycosuria.

Renal glycosuria is an inherited disorder of renal tubule function in which significant amounts of glucose are excreted in the urine in the simultaneous presence of normal blood glucose levels. Renal glucose titration analyses and HLA genotypes were performed in 5 unrelated affected families with a total of 25 patients and 40 healthy relatives. In each family the gene responsible for renal glycosuria segregates with the HLA complex suggesting a close genetic linkage. 2 cases carry intra-HLA recombinant haplotypes; in these subjects our findings indicate that the abnormal gene is closer to the HLA-A locus than the HLA-B locus. No HLA-A, HLA-B or HLA-C specific antigen is selectively increased among the 5 unrelated families affected with renal glycosuria.

Is renal glycosuria a benign condition?

HLA typing and a range of autoantibodies were evaluated in five families affected with type A renal glycosuria. HLA typing demonstrates that this inherited disease is controlled by an autosomal dominant gene located on chromosome six in close genetic linkage with the HLA complex. All affected family members have significant titres of autoantibodies to nuclear antigens, native DNA, smooth muscle, mitochondria, liver antigens, thyroglobulin, thyroid microsomes and renal tubule brush border with variable association. This suggests that renal glycosuria is a complex HLA-linked disease with increased susceptibility to multiple autoantibody production and this urges caution with respect to its classical definition as a benign condition.