Vitamin D, bone mineral density and risk of fracture in people with intellectual disabilities.

BACKGROUND: People with intellectual disabilities (IDs) have very high rates of osteoporosis and fractures, to which their widespread vitamin D deficiency and other factors could contribute. We aimed to assess in people with IDs previously treated for vitamin D deficiency (1) long-term adherence to vitamin D supplementation and (2) bone mineral density (BMD), as an indicator for risk of fractures, according to vitamin D supplementation and other factors. METHOD: We recorded height, weight, medical, pharmacological, dietary and lifestyle assessment. Blood sample were taken for vitamin D and related analytes. dual-energy X-ray absorptiometry for BMD was performed. RESULTS: Of 51 study participants (mean [standard deviation, SD] age 51.5 [13.6] years, 57% male), 41 (80.4%) were taking vitamin D and 10 were not. Mean [SD] serum vitamin D was 81.3 [21.3] vs. 25.2 [10.2] nmol/L (P < 0.0001), respectively. Thirty-six participants underwent a dual-energy X-ray absorptiometry scan, which showed osteoporosis in 23.7% and osteopenia in 52.6%. Participants on vitamin D had higher BMD than those who were not, a statistically significant difference when confounders (lack of mobility and hypogonadism) were removed. BMD was significantly different according to mobility, particularly in wheelchair users, in whom hip BMD was 33% lower (P < 0.0001) than in participants with normal mobility. Participants still taking vitamin D showed a 6.1% increase in BMD at the spine (P = 0.003) after mean [SD] 7.4 [1.5] years vitamin D treatment. CONCLUSIONS: In people with IDs and previous vitamin D deficiency, BMD increases on long-term vitamin D supplementation. However, additional strategies must be considered for osteoporosis and fracture prevention in this population.

Comparison of Bayer Advia Centaur immunoassay results obtained on samples collected in four different Becton Dickinson Vacutainer tubes.

BACKGROUND: Medicines and Healthcare products Regulatory Agency's (MHRA's) Medical Device Alert MDA/2004/048 described bias in some endocrine test results obtained on a few immunoassay platforms, particularly the Bayer Advia Centaur instrument, when using blood specimens collected into Becton Dickinson (BD) Vacutainer SSTII Advance tubes. As users of BD tubes and the Advia Centaur instrument, we addressed our concerns about the quality of the results that we had previously reported by undertaking an independent study. METHOD: We compared the results of 15 immunoassays performed on Bayer Advia Centaur using blood specimens collected into four different BD Vacutainer tubes (plain, old and newly released BD SSTII Advance, and BD PSTII). RESULTS: Compared with plain tubes, old SSTII Advance tube results showed no bias for testosterone, CA15-3, follicle-stimulating hormone and folate assays, but gave a positive bias for cortisol and a negative bias for vitamin-B12. Compared with plain tubes, BD PSTII tubes gave no significant bias for thyroid function tests, prolactin, parathyroid hormone, and CA125, but gave a negative bias for steroid assays, and a positive bias for gonadotrophins. The results obtained using new BD SSTII Advance tubes were generally comparable with those on plain tubes. CONCLUSIONS: Only for cortisol did our findings support the bias described by MHRA. Based on our results, apart from vitamin-B12 and possibly cortisol, there may have been no significant influence on clinical decisions as a result of using the old BD SSTII Advance specimen tubes. New BD SSTII Advance tubes and plain tubes give generally comparable results. BD PSTII tubes should not be used for steroid hormone measurements on the Bayer Advia Centaur instrument.

Interleukin-6 and oligoclonal IgG synthesis in children with acute disseminated encephalomyelitis.

Interleukin-6 (IL-6) has a number of roles including recruitment of T lymphocytes and differentiation of B lymphocytes into IgG-secreting plasma cells. Furthermore, IL-6 is a neuropoietic cytokine with effects on neuronal differentiation, function and survival. We studied IL-6 concentrations in children with acute disseminated encephalomyelitis (ADEM; n = 14), and compared the values with those obtained from control patients with other inflammatory (OIND; n = 13) and non-inflammatory (NIND; n = 10) neurological disorders. Patients with ADEM had a significantly increased CSF IL-6 concentration compared with both OIND and NIND groups ( P < 0.01). Serum IL-6 was also increased in the ADEM group compared with the OIND group ( P < 0.05). CSF: serum IL-6 ratios were significantly increased in the ADEM group compared with the NIND group ( P < 0.05), suggesting an intrathecal production of IL-6 rather than its passive transfer across the blood-brain barrier alone. In ADEM, there was a significant correlation between an increased CSF IL-6 and an identical pattern of oligoclonal IgG synthesis in both serum and CSF ( P < 0.05). These results would suggest a role for IL-6 in the pathology of ADEM, and a possible direct link between an increased IL-6 and a proliferation of B lymphocytes with consequent IgG production.

Effects of thyroid status on insulin-like growth factor-I, growth hormone and insulin are modified by food intake.

Understanding the interactions between metabolic signals that regulate insulin-like growth factor-I (IGF-I) is crucial to a recognition of mechanisms that control mammalian growth. Thyroid hormones (THs) are essential for normal growth and development, and it has been suggested previously that they can modify circulating IGF-I concentrations. However, the fact that THs influence food intake, which can itself affect plasma IGF-I levels, has been ignored in previous studies. We have therefore investigated the effects of thyroid status on plasma IGF-I under conditions of controlled food intake in young growing pigs. Circulating IGF-I, growth hormone (GH) and insulin levels, were studied in hypo- and hyperthyroid animals on the same level of food intake as euthyroid controls. In addition, a separate group of hyperthyroid animals was given double the amount of food, in order to assess the influence of increased food intake, as would occur naturally in the hyperthyroid state. Hypothyroid animals and hyperthyroids with extra food had the greatest increase in body weight over the 3 weeks of treatment. These two groups had significantly higher circulating IGF-I and insulin concentrations than either the euthyroid or hyperthyroid animals on the same food intake. Integration of GH concentrations from samples taken every 20 min over a 9 h period showed that, by contrast with IGF-I and insulin levels, GH levels were significantly lower in hypothyroids and hyperthyroids on extra food compared with the euthyroids and the hyperthyroids on the same food intake. We conclude that the effects of thyroid status on IGF-I are mediated in part by the effects that THs have on energy balance, and that nutritional signals are capable of modifying the influence of thyroid status per se on circulating IGF-I concentrations.

Regulation of porcine skeletal muscle nuclear 3,5,3'-tri-iodothyronine receptor binding capacity by thyroid hormones: modification by energy balance.

Thyroid hormones have been implicated in the regulation of nuclear 3,5,3'-tri-iodothyronine (T3) receptor binding capacity (Bmax) but, despite numerous in vivo and in vitro studies, there is considerable controversy regarding their exact role. Since changes in thyroid status alter energy balance and hence may influence T3 receptor numbers, the effects of chronic hypothyroidism and T4 treatment have been studied in young pigs under conditions of controlled energy intake. Four groups of animals comprising a hypothyroid, a euthyroid and a hyperthyroid group, all on the same level of food intake, and a hyperthyroid group on twice the amount of food were used. After 3 weeks on the treatment regimes, both the hypothyroid animals on the same level of food intake and the hyperthyroid animals on twice the amount of food had significantly increased Bmax values (97% and 137% higher respectively) compared with euthyroid controls. However, there was no difference between controls and the hyperthyroid animals on the same level of food intake. In a second study, the effects of short-term treatment of euthyroid animals with T3 was investigated. Results showed that in two groups of controls that received intravenous saline, those on a higher food intake had higher Bmax values (76% increase). Intravenous T3 administration to animals on a low food intake did not change the receptor numbers. In none of the studies was there any change in the dissociation constant of the receptors as a result of different treatments. It is suggested that, at least in postnatal life, thyroid hormones per se have no significant effect on nuclear T3 receptor numbers in skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-term regulation of plasma IGF-I concentration by food intake in young growing pigs.

The short-term regulation of plasma insulin-like growth factor-I (IGF-I) concentration by food intake has been studied in 6-8 week old pigs, both within the thermally neutral zone (26 to 30 degrees C) and at a low (12 degrees C) environmental temperature. In animals at thermal neutrality, the plasma level of IGF-I increased significantly after feeding (p < 0.025 to < 0.01); the average maximum rise of 47% occurred at approximately 12h after the meal. When animals were acclimated to a low temperature and food intake was kept constant in relation to body weight, there was a decline in plasma IGF-I concentrations; values after 2-5 days of cold-acclimation were significantly lower than those before cold exposure (p < 0.05 to < 0.005). This effect of cold on plasma IGF-I was probably mediated by changes in energy balance, due to the increased metabolic demand associated with the low temperature. Animals living in the cold for 14 days, with a low fasting level of plasma IGF-I, showed a marked increase in IGF-I after a large meal; values at 8 or 12 h after food were twice as great as those immediately before or 4 h after feeding (p < 0.05 to < 0.005). It is concluded that in young growing animals, a rapid increase in circulating IGF-I levels can occur in response to food intake, at both thermally neutral and low temperatures, and that the peak in concentration may coincide with the anabolic effects of the meal.

Investigation of mechanisms mediating the increase in plasma concentrations of thyroid hormones after a meal in young growing pigs.

These studies investigated a number of possible mechanisms which could mediate the increase in plasma concentrations of thyroid hormones after a meal in young growing pigs. It has been established that in animals fed one meal a day, an immediate rise in plasma 3,5,3'-tri-iodothyronine (T3) and a slightly delayed increase in thyroxine (T4) levels are followed by a more sustained peak in both hormones several hours later. The increase in thyroid hormones involves both total and free T3 and T4, and there is no change in plasma albumin, the high-capacity thyroid hormone-binding protein in the pig. It has also been shown that the immediate rise in plasma T3 is not mediated either by an increase in plasma glucose concentration or by neural mechanisms associated with distension of the gastrointestinal tract. However, the finding that plasma T3 increases rapidly after feeding in thyroidectomized animals maintained on a replacement dose of T4 alone, indicates the source of T3 to be non-thyroidal. It is concluded that the rise in plasma thyroid hormones after a meal depends on the energy content of the food but not directly on the circulating glucose levels. The immediate increases in plasma T3 and T4 are probably due largely to a redistribution of the hormonal pools, and peripheral 5'-monodeiodination of T4 may also contribute significantly to the post-prandial rise in T3. The potential significance of these findings in relation to both the metabolic and growth-promoting effects of thyroid hormones is discussed.

Administration of 3,5,3'-triiodothyronine induces a rapid increase in enterocyte lactase-phlorizin hydrolase activity of young pigs on a low energy intake.

The rapid increase in plasma concentration of 3,5,3'-triiodothyronine (T3) which occurs after feeding may invoke changes in lactase-phlorizin hydrolase (LPH) activity of the small intestine. This hypothesis has been tested in 6-week-old pigs living at thermal neutrality (26 degrees C) on a low level of energy intake. Littermate pairs were infused with either saline or T3 at 30 min intervals over a 6 h period, 18-24 h after the last meal. The activity of LPH in mucosal homogenates increased significantly in test compared with control animals (P < 0.05; T3 37% > saline). This was a specific effect on LPH since there was no effect of T3 on the activity of sucrase-isomaltase. Further, it could not be attributed to changes in intestinal morphology since there were no differences in crypt depth, villus height or villus area between the two groups. Enzyme-cytochemical analysis indicated that administration of T3 increases LPH activity at all points along the villus axis, whereas there is no effect on alpha-glucosidase (combined sucrase-isomaltase and maltase) activities. These results indicate that there is unlikely to be a simple causal relation between the immediate increase in plasma T3 after feeding and the initial decline in LPH activity observed previously in young pigs living in a cold environment. By contrast, the subsequent increase in LPH activity could be under the direct control of the food-induced increase in plasma T3 concentration, and the present results suggest a potential role for T3 as an important short-term homeostatic regulator of LPH in the small intestine.

Short-term changes in the 3,5,3'-tri-iodothyronine nuclear receptor-binding capacity of porcine skeletal muscle following food intake.

The time-course of changes in the nuclear 3,5,3'-tri-iodothyronine (T3) receptor-binding capacity (Bmax) of longissimus dorsi muscle has been investigated in cold-acclimated young pigs after a single large meal. Measurement of Bmax values 4, 8, 12 and 24 h after feeding indicated a decline in receptor numbers after food intake with the lowest values occurring at 8 h. The receptor numbers then increased significantly, with the values at 12 h being more than 50% higher than those obtained at 8 h. The Bmax values reached their highest level 24 h after feeding. No significant changes in the dissociation constant were observed. Possible reasons for the changes in T3 receptor numbers are discussed and it is suggested that the increase in T3 receptor numbers 12-24 h after feeding may play a role in enhancing the thermogenic capacity of the tissues in response to food.

Variations in [3H]ouabain binding of porcine skeletal muscle associated with feeding.

The maximal ouabain binding capacity (Bmax) of longissimus dorsi muscle has been determined over a 24 h period in young pigs living at 12 degrees C. Animals were fed once a day and Bmax was estimated at 4, 8, 12 or 24 h after a large meal. Mean values of Bmax +/- S.E.M. (pmol ouabain/g wet wt muscle) of 548 +/- 78 and 556 +/- 57 at 4 and 24 h after feeding were significantly greater than those of 383 +/- 24 and 393 +/- 30 at 8 and 12 h after feeding (P less than 0.02). The extent to which these differences represent apparent or real changes in numbers of ouabain binding sites and, hence, in Na+,K(+)-ATPase concentration is discussed.

Dissociation between plasma concentrations of thyroxine and insulin-like growth factor-I.

The relation between plasma concentrations of thyroxine (T4) and insulin-like growth factor-I (IGF-I) has been examined in young, growing pigs under controlled conditions of energy intake. Compared with euthyroid controls, plasma levels of IGF-I were significantly elevated (P less than 0.005) both in hypothyroid animals on the same food intake and in hyperthyroid animals on double the food intake. There was however no increase in IGF-I in a hyperthyroid group on the control level of intake. Contrary to previous reports in which energy intake was not controlled, it is concluded that there is no simple correlation between plasma concentrations of T4 and IGF-I.