Importance of serum phosphate in elderly patients with diabetes mellitus

BACKGROUND Metabolic disturbances including changes in serum calcium,magnesium or phosphate(P) influence the prevalence of type 2 diabetes mellitus(DM).We assessed the importance of serum P in elderly patients with type 2 DM vs nondiabetes mellitus(non-DM) in relation to renal function.AIM To determine the association between serum P and serum glucose or insulin resistance in diabetic and non-diabetic patients.METHODS One hundred-ten subjects with a mean age of 69.02±14.3 years were enrolled.Twenty-nine of the participants had type 2 DM(26.4%).The incidence of hypertension,smoking and receiving vitamin D(vitD) derivates were recorded.The participants were classified by both estimated glomerular filtration rate(eGFR) and albuminuria categories according to the Kidney Disease Improving Global Outcomes 2012 criteria.RESULTS We divided the patients in two groups according to the P cut-off point related to DM value.A comparison between high and low P showed that body mass index30.2±6.3 vs 28.1±4.6(P=0.04),mean glucose 63.6 vs 50.2(P=0.03),uric acid 6.7±1.6 vs 6.09±1.7(P=0.05),mean intact-parathyroid hormone 68.06 vs 47.4(P=0.001),systolic blood pressure 147.4±16.7 vs 140..2±16.1(P=0.02),mean albuminuria 63.2 vs 50.6(P=0.04) and eGFR 45.6±22.1 vs 55.4±21.5(P=0.02)were significantly different.χ~2 tests showed a significant association between high P and DM,hypertension,receiving vitD,smoking and eGFR stage(χ~2=6.3,P=0.01,χ~2=3.9,P=0.03,χ~2=6.9,P=0.009,χ~2=7.04,P=0.01 and χ~2=7.36,P=0.04,respectively).The adjusted model showed that older age,female gender and increased body mass index were significant predictors of type 2 DM when entering the covariates.CONCLUSION High serum P contributes to vascular and metabolic disturbances in elderly patients with type 2 DM and renal impairment.     

Effect of long-term calcitonin administration on steroid-induced osteoporosis after cardiac transplantation.

BACKGROUND: Early, rapid bone loss and fractures after cardiac transplantation are well-documented complications of steroid administration; therefore, we undertook this study on the effects of long-term calcitonin on steroid-induced osteoporosis. METHODS: Twenty-three heart transplant recipients on maintenance immunosuppression with cyclosporine, mycophenolate mofetil and prednisone were retrospectively studied. All patients received long-term prophylactic treatment with elemental calcium and vitamin D. Twelve (52.2%) patients also received long-term intranasal salmon calcitonin, whereas 11 (47.8%) received none. Bone mineral density and vertebral fractures were assessed at yearly intervals. Statistical comparisons between each group's bone loss during the first year and in the early (1 to 3 years), intermediate (4 to 6 years) and late (7+ years) post-transplantation periods were done. RESULTS: Lumbar spine bone loss was significant during the early follow-up period in the group not receiving calcitonin (0.744 +/- 0.114 g/cm(2) vs 0.978 +/- 0.094 g/cm(2) [p = 0.002]). The calcitonin group showed bone mineral density (BMD) levels within normal average values throughout the study period. BMD increased in the no-calcitonin group during the intermediate (4 to 6 years) and late (7+ years) follow-up periods, with values approaching normal average and no significant difference between the 2 groups (0.988 +/- 0.184 g/cm(2) vs 0.982 +/- 0.088 g/cm(2) [p = 0.944] and 0.89 +/- 0.09 g/cm(2) vs 1.048 +/- 0.239 g/cm(2) [p = 0.474], respectively). CONCLUSIONS: Prophylactic treatment with intranasal salmon calcitonin prevents rapid bone loss associated with high-dose steroids early after cardiac transplantation. Long-term administration does not seem warranted in re-establishing BMD.     

The renin-aldosterone axis in patients with diabetes insipidus

OBJECTIVE The objective of the present study was to investigate the renin-aldosterone axis in neurogenic diabetes insipidus in man, in view of the fact that profound abnormalities of this axis have been described in experimental animals with congenital neurogenic diabetes insipidus. DESIGN AND PATIENTS Nine patients with neurogenic diabetes insipidus and 11 healthy subjects (controls) were examined under basal conditions, following the standard 8-hour water deprivation test and 1 hour after a subsequent oral rehydration. MEASUREMENTS Plasma and urine osmolalities were determined by freezing point depression, plasma sodium and potassium by a method using an ion-selective electrode, plasma AVP, Cortisol, aldosterone and plasma renin activity by radioimmunoassay. RESULTS Plasma renin activities under basal conditions were significantly higher in patients with diabetes insipidus than in controls (mean ± SEM 23.4 ± 6.6 vs 7.8 ± 1.2 ng/ I min). In the diabetes insipidus group, water deprivation caused a twofold Increase in plasma renin activities (48 ± 13.8 ng/l min), while in the control group plasma renin activity levels were not significantly altered (10.2 ± 1.2 ng/l min). Rehydration did not alter plasma renin activity levels in either group (patients 50.4 ± 13.2, controls 9.0 ± 2.4 ng/l min). Plasma aldosterone concentrations under basal conditions did not differ between the two groups (patients 302.4 ± 37, controls 326.4 ± 36.5 pmol/l) and did not change in patients with diabetes insipidus after water deprivation or rehydration (307.5 ± 67.2 and 385.5 ± 91 pmol/l, respectively). Conversely, controls showed a significant decrease in plasma aldosterone levels after dehydration (201 ± 27.9 pmol/l), which was attributed to the circardian variation in aldosterone secretion, as shown by a parallel decrease in plasma Cortisol levels. CONCLUSIONS Patients with diabetes insipidus are hyper-reninaemic, probably because of chronic volume contraction. There is a dissociation between renin and aldosterone in patients with diabetes insipidus under basal conditions, which is exaggerated during water deprivation.     

Late left ventricular diastolic flow propagation velocity determined by color M-mode Doppler in the assessment of diastolic dysfunction.

BACKGROUND: Early color M-mode Doppler flow propagation (Ep) through the left ventricle (LV) has been proposed as a useful noninvasive index for assessing LV relaxation, whereas data concerning late velocity propagation (Ap) is lacking. METHODS: We studied 51 patients with delayed relaxation (group I) and 50 with pseudonormal filling pattern (group II). Another 51 aged-matched healthy persons served as the control group. RESULTS: Patients showed increased left atrial dimensions, atrial wave of the pulmonary vein flow, and Ap, and reduced LV ejection fraction, Ep, and Ep/Ap ratio compared with the control group. Patients in group II revealed increased left atrial dimensions (P =.001), atrial wave of the pulmonary vein flow (P <.001), and Ep/Ap ratio (P <.001), and reduced LV ejection fraction and Ap (P <.001) compared with group I. Regression analysis showed that the strongest independent variable distinguishing normal from pseudonormal filling pattern was the Ep/Ap ratio. CONCLUSION: Ap evaluation offers a new diagnostic diastolic index, especially in the field of the pseudonormal pattern where the separation from normal is difficult.     

Autoimmune hepatitis type 1 and primary biliary cirrhosis have distinct bone marrow cytokine production

We have recently reported differences in the hematopoiesis between autoimmune hepatitis type 1 (AIH-1) and primary biliary cirrhosis (PBC). In view of the notion that cytokines are regulators of hematopoiesis, we investigated in our tertiary center the cytokine production in the bone marrow (BM) of the same consecutive cohort of patients (13 AIH-1, 13 PBC, 10 healthy and 7 patients with cirrhosis due to chronic hepatitis B). Interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) were determined in the supernatants of long-term BM cultures by ELISAs. IL-4, TNF-alpha and TGF-beta were found significantly increased in the BM of PBC patients compared to AIH-1 and both control groups. AIH-1 patients had significantly higher BM IL-10 compared to PBC patients and higher IL-10, IL-4 and TNF-alpha compared to controls. BM IFN-gamma was significantly higher in PBC and AIH-1 patients compared to controls. In AIH-1 patients, IL-10 was positively correlated with CD34+, CD34+/CD38- and CD34+/CD38+ cell proportions. In conclusion, the BM cytokine microenvironment of PBC and AIH-1 patients differs significantly compared to that of healthy individuals and cirrhotic patients of non-autoimmune etiology. Differences were also found between patients with PBC and AH-1. The implication of BM in the pathogenesis of autoimmune liver diseases is possible and needs further investigation.     

Applying spatial distribution analysis techniques to classification of 3D medical images

OBJECTIVE: The objective of this paper is to classify 3D medical images by analyzing spatial distributions to model and characterize the arrangement of the regions of interest (ROIs) in 3D space. METHODS AND MATERIAL: Two methods are proposed for facilitating such classification. The first method uses measures of similarity, such as the Mahalanobis distance and the Kullback-Leibler (KL) divergence, to compute the difference between spatial probability distributions of ROIs in an image of a new subject and each of the considered classes represented by historical data (e.g., normal versus disease class). A new subject is predicted to belong to the class corresponding to the most similar dataset. The second method employs the maximum likelihood (ML) principle to predict the class that most likely produced the dataset of the new subject. RESULTS: The proposed methods have been experimentally evaluated on three datasets: synthetic data (mixtures of Gaussian distributions), realistic lesion-deficit data (generated by a simulator conforming to a clinical study), and functional MRI activation data obtained from a study designed to explore neuroanatomical correlates of semantic processing in Alzheimer's disease (AD). CONCLUSION: Performed experiments demonstrated that the approaches based on the KL divergence and the ML method provide superior accuracy compared to the Mahalanobis distance. The later technique could still be a method of choice when the distributions differ significantly, since it is faster and less complex. The obtained classification accuracy with errors smaller than 1% supports that useful diagnosis assistance could be achieved assuming sufficiently informative historic data and sufficient information on the new subject.     

Meta-analysis of the association of beta2-adrenergic receptor polymorphisms with asthma phenotypes

BACKGROUND: Two common polymorphisms of the beta2-adrenergic receptor gene (Arg16Gly and Gln27Glu ) have been extensively studied for their possible association with asthma-related phenotypes, but the results of individual studies have been inconclusive. OBJECTIVE: We aimed to integrate quantitatively the available evidence on the association of the Arg16Gly and the Gln27Glu polymorphisms with asthma, nocturnal asthma, asthma severity, and bronchial hyperresponsiveness. METHODS: Meta-analysis of case-control and cohort studies using random effects models. RESULTS: A total of 28 studies were included in the meta-analysis. The summary estimates suggested that neither the Gly16 nor the Glu27 allele contributes to asthma susceptibility overall (odds ratio [OR], 1.01; 95% CI, 0.90-1.13; and OR, 0.95; 95% CI, 0.83-1.09, respectively) or to bronchial hyperresponsiveness (OR, 0.90; 95% CI, 0.77-1.05; and OR, 1.07; 95% CI, 0.94-1.22, respectively). There was a strong association of Gly16 with nocturnal asthma (OR, 2.20; 95% CI, 1.56-3.11) and a less strong association with severe or moderate rather than milder asthma (OR, 1.42; 95% CI, 1.04-1.94). No such effects were seen for the Glu27 allele (OR, 1.02; 95% CI, 0.74-1.40; and OR, 0.82; 95% CI, 0.59-1.14, respectively). Moreover, there was evidence that Gly16 homozygotes had a much higher risk for nocturnal asthma (OR, 5.15; 95% CI, 2.44-10.84) and asthma severity (OR, 2.84; 95% CI, 1.62-4.96) than the Arg16 homozygotes. CONCLUSION: The Gly16 allele of the beta2-adrenergic receptor gene predisposes to nocturnal asthma, and this may also explain the association with asthma severity. Neither polymorphism modulates the risk for bronchial hyperresponsiveness or mild asthma.     

Reporting of conflicts of interest in guidelines of preventive and therapeutic interventions

Background

Guidelines published in major medical journals are very influential in determining clinical practice. It would be essential to evaluate whether conflicts of interests are disclosed in these publications. We evaluated the reporting of conflicts of interest and the factors that may affect such disclosure in a sample of 191 guidelines on therapeutic and/or preventive measures published in 6 major clinical journals (Annals of Internal Medicine, BMJ, JAMA, Lancet, New England Journal of Medicine, Pediatrics) in 1979, 1984, 1989, 1994 and 1999.

Results

Only 7 guidelines (3.7%) mentioned conflicts of interest and all were published in 1999 (17.5% (7/40) of guidelines published in 1999 alone). Reporting of conflicts of interest differed significantly by journal (p=0.026), availability of disclosure policy by the journal (p=0.043), source of funding (p < 0.001) and number of authors (p=0.004). In the entire database of 191 guidelines, a mere 18 authors disclosed a total of 24 potential conflicts of interest and most pertained to minor issues.

Conclusions

Despite some recent improvement, reporting of conflicts of interest in clinical guidelines published in influential journals is largely neglected.