Inhibition of bone turnover by milk intake in postmenopausal women

Increased postmenopausal bone turnover leads to bone loss and fragility fracture risk. In the absence of osteoporosis, risk preventive measures, particularly those modifying nutritional lifestyle, are appropriate. We tested the hypothesis that milk supplementation affects bone turnover related to biochemical markers in a direction that, in the long term, may be expected to reduce postmenopausal bone loss. Thirty healthy postmenopausal women aged 59.3 (SD 3.3) years were enrolled in a prospective crossover trial of 16 weeks. After a 4-week period of adaptation with diet providing 600 mg calcium plus 300 mg ingested as 250 ml semi-skimmed milk, participants were maintained during 6 weeks under the same 600 mg calcium diet and randomized to receive either 500 ml semi-skimmed milk, thus providing a total of 1200 mg calcium, or no milk supplement. In the next 6 weeks they were switched to the alternative regimen. At the end of the each period, i.e. after 4, 10 and 16 weeks, blood and urinary samples were collected. The changes in blood variables between the periods of 6 weeks without and with milk supplementation were: for parathyroid hormone, -3.2 pg/ml (P=0.0054); for crosslinked telopeptide of type I collagen, -624 pg/ml (P<0.0001); for propeptide of type I procollagen, -5.5 ng/ml (P=0.0092); for osteocalcin, -2.8 ng/ml (P=0.0014). In conclusion, a 6-week period of milk supplementation induced a decrease in several biochemical variables compatible with diminished bone turnover mediated by reduction in parathyroid hormone secretion. This nutritional approach to postmenopausal alteration in bone metabolism may be a valuable measure in the primary prevention of osteoporosis.     

Effects of Air Pollution on Adults with Chronic Obstructive Pulmonary Disease

Few studies have been conducted on the effects of air pollution on patients with chronic obstructive pulmonary disease (COPD). During a 14-mo period, 39 Parisian adults with severe COPD were monitored by their physicians. Daily levels of 4 air pollutants were provided by an urban air-quality network. Exacerbation of COPD was associated only with ozone (O₃) (odds ratio [OR] = 1.44 for a 10-μg/m³ increase in O₃; 95% confidence interval [Cl] = 1.14, 1.82), with a lag of 2-3 days. The effect of O₃ was greater in patients whose carbon dioxide pressure (PaCO₂) was higher than 43 mm Hg (OR = 1.83; 95% Cl = 1.36, 2.47) vs. those with a lower PaCO₂ (OR = 1.26; 95% Cl = 0.90, 1.77). The effect of O₃ was unchanged, regardless of the maintenance medications used. The only air pollutant to which patients with severe COPD were particularly sensitive was O₃.     

Single-Molecule hsTnI and Short-Term Risk in Stable Patients With Chest Pain

Background

Evaluation of stable symptomatic outpatients with suspected coronary artery disease (CAD) may be challenging because they have a wide range of cardiovascular risk. The role of troponin testing to assist clinical decision making in this setting is unexplored.

Variations in Digestive Physiology of Rats After Short Duration Flights Aboard the US Space Shuttle

The purpose of this work was to assess the influence of microgravity on several endogenous and microbial parameters of digestive physiology. On the occasion of two Spacelab Life Sciences missions, SLS-1 (a 9-day space flight) and SLS-2 (a 14-day space flight), Sprague-Dawley rats flown aboard the US space shuttle were compared to age-matched ground-based controls. In both flights, exposure to microgravity modified cecal fermentation: concentration and profile of short-chain fatty acids were altered, whereas urea and ammonia remained unchanged. Only in SLS-1 was there an induction of intestinal glutathione-S-transferase. Additional analyses in SLS-2 showed a decrease of hepatic CYP450 and of colonic goblet cells containing neutral mucin. After a postflight recovery period equal to the mission length, only modifications of the hepatic and intestinal xenobiotic metabolizing enzymes still persisted. These findings should help to predict the alterations of digestive physiology and detoxification potential likely to occur in astronauts. Their possible influence on health is discussed.     

Calcium-sensing receptor autoantibodies are relevant markers of acquired hypoparathyroidism

We investigated the presence of autoantibodies (aAbs) directed against the parathyroid gland in 17 patients with spontaneous isolated acquired hypoparathyroidism. Fourteen patients with acquired hypoparathyroidism (AH) associated with type I or II autoimmune polyendocrinopathy syndrome were also tested in comparison with a control group of 68 subjects without AH, including patients with other autoimmune diseases and healthy blood donors. aAbs against parathyroid tissue were screened using an indirect immunofluorescence technique on primate parathyroid tissue and human parathyroid adenoma. aAbs against the calcium-sensing receptor (CaSR) were analyzed using an immunoblotting assay with the recombinant extracellular domain of the human CaSR as antigen. Seven of the 31 patients with AH were positive for CaSR aAbs. Five of the positive sera were obtained from the group with isolated AH. The two other positive sera were from patients with autoimmune polyendocrinopathy syndrome. The sensitivity of the immunoblotting technique was higher than that of both the radioimmunological test using the extracellular domain of the CaSR and the indirect immunofluorescence technique. There were no positive sera in the control group. In conclusion, using an immunoblotting assay, we demonstrate the presence of CaSR aAbs in about one third of the patients with isolated AH, pointing out the value of detecting such aAbs to assess the autoimmune origin of the disease.     

Differential diagnosis on the autism spectrum: Theorizing an “Ordinary Autism”

ObjectivesData on the prevalence of Autism Spectrum Disorder (ASD) reveal several clinical evolutions inducing new psychiatric definitions and diagnostic practices. Thus, autism has shifted from being a rare syndrome with severe clinical forms to a new paradigm: the paradigm of “ordinary” or “invisible” autism, in terms of the frequency and the intensity of the disorders. These changes incorporate new populations into our conception of autism, with new phenotypes that pose theoretical and clinical challenges to clinicians. In response, we propose the hypothesis — based on psychoanalytic theories of psychic structures — of an “ordinary autism” as a definition of a non-prototypical autistic psychic functioning that falls outside the DSM diagnostic framework. This idea seems to provide us new theoretical references that nourish our practices as well as fundamental research.MethodFirst, we will review the nosographic mutations of the DSM-5 and their implications for non-prototypical psychic modes of functioning of autistic people that may not be contained within the autism spectrum's blurry boundaries — especially for the adult population without intellectual delay and in the case of complicated differential diagnosis for clinical and societal reasons. Next, we will discuss the definition of “ordinary” or “invisible” autism in a psychoanalytic structural model, as a possible epistemological orientation for identifying and designing practice with the clinical heterogeneity of autism outside the boundaries of psychiatric ASD.ResultsThe autistic population targeted by the DSM-5 criteria is different from that previously defined by DSM-IV. This leads to two consequences: on the one hand, autistic modes of functioning are not limited to individuals who have been diagnosed with Autism Spectrum Disorders as defined by the DSM-5; thus individuals with autism do not have access to the diagnosis of ASD or are given other diagnoses. The alternative diagnoses proposed by the DSM-5 that attempt to correct this diagnostic exclusion — such as Social (Pragmatic) Communication Disorder — are unsatisfactory. Therefore, there is an entire segment of the autistic population that has subclinical, non-prototypic autistic manifestations or more subtle phenomena discernible in the broader autistic phenotype or sub-threshold autism spectrum that does not have access to the ASD diagnosis and raises differential diagnostic issues. On the other hand, it appears that the autism spectrum brings together extremely different entities and false positives such as schizophrenia and schizophrenic spectrum personality disorders under one diagnostic rubric. Then, the differential problem appears central: both at the theoretical level and in diagnostic practices. The recognition of these limits should encourage us to promote research and clinical applications on this subject. One solution that we envisage is to be found in an extension of Maleval's structural psychoanalytical model: we propose the notion of “ordinary autism” — an echo of ordinary psychosis — to define attenuated or compensated non-prototypical autistic phenotypes, increasingly frequent and with fewer “extraordinary” phenomenological expressions than the classic cases of autism which now call into question the relationship between the normal and the pathological.Discussion“Ordinary autism” seems to offer clinicians the opportunity to formalize the new contemporary and extensive clinical reality of autism. This term situates itself within a theoretical model whose current and future developments might help us respond to clinical and diagnostic issues, but also to therapeutic and societal ones. We propose to continue on the path of the operationalization of these theoretical models in order to identify autistic structural constants that could be found throughout the “ordinary” clinic of autism and could serve as differentiating tools for diagnosis as well as a support in developing and refining therapeutic practices.ConclusionWe conclude that there is an urgent need to conceive of “ordinary autism” to provide us with reference points to respond to new clinical issues, but also to reintroduce respect for the autistic person in his or her subjectivity to the center of our therapeutic practices.     

Design features of the Avasimibe and Progression of coronary Lesions assessed by intravascular UltraSound (A-PLUS) clinical trial

Background Although statins have been shown to be beneficial in the management of hyperlipidemia and the reduction of cardiovascular morbidity and mortality, rates of major cardiovascular events remain high despite their use. Inhibition of the acyl coenzyme A: cholesterol acyltransferase (ACAT) enzyme in the arterial wall may prevent excess accumulation of cholesteryl esters in macrophages. In addition to ACAT inhibitor monotherapy, combination of a statin with an ACAT inhibitor may be a promising approach to further prevent the progression of atherosclerosis. Methods This report describes the design and methodologic features of a double-blind, randomized, placebo-controlled trial to assess the effect of the ACAT inhibitor avasimibe at 50-, 250-, and 750-mg daily dosages on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients receive background lipid-lowering therapy when necessary. The study population consists of patients with at least one 20% to 50% diameter stenosis in a coronary artery with a reference diameter of ≥2.5 mm. IVUS and coronary angiography are performed at baseline and repeated at 24 months. The primary study end point is the change from baseline in plaque volume in a 30-mm segment of the coronary artery assessed by 3-dimensional IVUS. Several other IVUS and angiographic end points are measured. Conclusions The Avasimibe and Progression of coronary Lesions assessed by intravascular UltraSound (A-PLUS) trial is among the first large imaging trials to use IVUS as a primary end point and assesses the effects of the ACAT inhibitor avasimibe on atherosclerosis progression. (Am Heart J 2002;144:589-96.)