Cross sectional investigation of the effects of inhaled corticosteroids on bone density and bone metabolism in patients with asthma

BACKGROUND: Bone mineral density has been reduced in patients with asthma taking inhaled corticosteroids in some cross sectional studies and this could be important if treatment is continued for several decades. The possibility of confounding by age, menopausal status, physical activity and, especially, past oral steroid use has not been excluded in most studies. The present study was designed to assess the magnitude of any reduction in bone mineral density in relation to inhaled steroid use after adjusting for these factors. METHODS: Bone mineral density (BMD), vertebral fractures, and markers of bone metabolism (serum osteocalcin, procollagen peptide I, bone-specific alkaline phosphatase, and urinary deoxypyridinoline cross links) were measured in 81 patients with asthma age 20-40 years; 34 patients (19 men) who had never had inhaled or systemic steroids and 47 (19 men) who had taken inhaled steroids for at least five years with limited exposure to systemic steroids in the past. Data relating to past medication use, physical activity, smoking, and other confounding factors were collected by questionnaire. The relation between inhaled steroid dose and duration and BMD was assessed by linear regression analysis, accounting for potential confounders including weight, exercise, and oral steroid use. RESULTS: The 47 patients taking an inhaled steroid had a mean current dose of 620 micrograms/day (range 100-3000 micrograms), a mean duration of use of 7.8 years, and had had a mean of 0.85 courses of prednisolone in the past. There was no significant difference in mean BMD values between those who were and those who were not on inhaled steroids in men or women. However, on multivariate analysis, cumulative inhaled steroid dose was associated with a reduction in posterior-anterior (P-A) and lateral lumbar spine bone mineral density in women, equivalent to a 0.11 standard deviation reduction in bone density per 1000 micrograms/day inhaled steroid per year after adjustment for potential confounding factors (95% CI for P-A spine 0.01 to 0.22; for lateral spine 0.02 to 0.21). Previous oral steroid use was not an important confounding factor in these patients. Inhaled steroid use was not related to BMD at the wrist or hip in women or at any skeletal site in men. Women taking an inhaled steroid had lower levels of serum osteocalcin than those not taking them, although this was not dose related. Inhaled steroid use was not associated with differences in other markers of bone metabolism in men or women or with the presence of vertebral fractures. CONCLUSIONS: Although an effect of confounding factors cannot be excluded entirely in a cross sectional study, our findings are in keeping with an effect of inhaled steroid therapy in reducing bone density in the spine in women and provide an estimate of the magnitude of this effect.


     

The Transfer of Polystyrene Microspheres from the Gastrointestinal Tract to the Circulation after Oral Administration in the Rat

Factors relating to the transfer of latex microspheres of 0·87 μm mean diameter from the gastrointestinal tract (GIT) to the circulation have been investigated. The rapidity of appearance and the number of particles increased when the volume of water used as a suspending vehicle was increased. This was probably due to barrier cell integrity being compromised so that the movement of particles across the enterocytes would be enhanced. Particles were swept into these channels by the waterflow. The tonicity of the fluid was important as isotonic and hypertonic saline were not as affective as water in transferring particles. Particles were transferred from GIT segments adjacent to the stomach which may in part explain the rapid appearance of particles in the circulation. Particle uptake was blocked by cytochalasin B which suggests an active component may also be involved.     

Simplifying superovulation and intrauterine insemination treatment: evidence and clinical decision making

It is not always possible to develop a well-powered, randomized controlled trial (RCT) that will control for all possible variables to compare various treatment protocols. In the absence of evidence, it is reasonable to rely on physiologic principles, empiric observation, and, when possible, the results of an RCT to evaluate critical parts of a treatment protocol. On the basis of these principles, it is clear that a single IUI after mild superovulation done anywhere between 32 and 40 hours after hCG administration is an effective if not an efficacious treatment for idiopathic or mild male factor infertility.     

Copper radionuclides and radiopharmaceuticals in nuclear medicine

The chemistry, radiochemistry, radiobiology, and radiopharmacology of radiopharmaceuticals containing copper radionuclides are reviewed. Copper radionuclides offer application in positron emission tomography, targeted radiotherapy, and single photon imaging. The chemistry of copper is relatively simple and well-suited to radiopharmaceutical application. Current radiopharmaceuticals include biomolecules labelled via bifunctional chelators primarily based on cyclic polyaminocarboxylates and polyamines, and pyruvaldehyde-bis(N⁴-methylthiosemicarbazone) (PTSM) and its analogues. The chemistry of copper, of which only a fraction has yet been exploited, is likely to be applied more fully in the future.     

Continuous arteriovenous haemofiltration in the treatment of tumour lysis syndrome

The management of tumour lysis syndrome remains problematic despite the rigorous use of preventative measures. Continuous arteriovenous haemofiltration (CAVH) is well suited to its use in both the prevention and treatment of metabolic abnormalities and renal insufficiency associated with tumour lysis. We report the successful use of CAVH in the treatment of a patient with tumour lysis syndrome.     

A ribonuclease inhibitor expresses anti-angiogenic properties and leads to reduced tumor growth in mice.

Our experiments were designed to determine whether recombinant ribonuclease inhibitor (RNasin) could inhibit angiogenesis and reduce tumor growth in adult mice. We used the Fajardo disc angiogenesis assay as the primary means of measuring new blood vessel growth. This assay measures the penetration of cells into a polyvinyl alcohol sponge with a central core of ELVAX-coated sponge containing test substances. Cell penetration was reduced to 29.3% of control (phosphate-buffered saline; heat-inactivated RNasin) values. Endothelial cell influx was measured by lectin staining and confirmed by culturing cells isolated from sponges by collagenase treatment. RNasin also reduced the augmented reaction evoked by either basic fibroblast growth factor (bFGF) or sodium orthovanadate. To confirm the anti-angiogenic activity of RNasin, Hydron-coated polyvinyl sponges containing bFGF or bFGF plus RNasin were implanted into adult mouse corneas. bFGF induced a strong angiogenic response that was almost completely inhibited by RNasin. RNasin-containing ELVAX-coated sponges implanted subcutaneously underneath an intradermal inoculum of C755 mammary tumor cells caused significant reduction in tumor growth (P < 0.005). The antitumor effect of RNasin correlated with its effect on tumor-induced neovascularization, suggesting that the ability of RNasin to affect tumor growth was due to its ability to inhibit angiogenesis.     

The 1986 McCollum award lecture. Fuel-mediated teratogenesis during early organogenesis: the effects of increased concentrations of glucose, ketones, or somatomedin inhibitor during rat embryo culture

Whole rat embryos were explanted at head-fold, late pre-somite stage (day 9.5 of gestation) and cultured in rat sera varyingly supplemented with glucose (3, 6, 9, or 12 mg/mL), D,L sodium beta-hydroxybutyrate (2, 4, 8, or 16 mM), or both (6 mg/mL D-glucose plus 8 mM beta-hydroxybutyrate). During 48 h culture, increasing glucose alone or beta-hydroxybutyrate alone effected growth retardation and faulty neural and extraneural organogenesis in dose-dependent fashion. Synergistic dysmorphogenic effects occurred when minimally teratogenic concentrations of glucose and beta-hydroxybutyrate were combined. Sera from diabetic animals containing somatomedin inhibitor bioactivity were also able to produce growth retardation and major developmental lesions in presence of amounts of glucose and ketones which of themselves were not teratogenic. Thus, aberrant fuels and fuel-related products can impair growth and organogenesis in early post-implantation embryo. Such fuel-mediated teratogenesis may be multifactorial and include possibilities for synergistic and additive interactions.