66 research outputs found
Identifying older diabetic patients at risk of poor glycemic control
BACKGROUND: Optimal glycemic control prevents the onset of diabetes complications. Identifying diabetic patients at risk of poor glycemic control could help promoting dedicated interventions. The purpose of this study was to identify predictors of poor short-term and long-term glycemic control in older diabetic in-patients. METHODS: A total of 1354 older diabetic in-patients consecutively enrolled in a multicenter study formed the training population (retrospective arm); 264 patients consecutively admitted to a ward of general medicine formed the testing population (prospective arm). Glycated hemoglobin (HbA1c) was measured on admission and one year after the discharge in the testing population. Independent correlates of a discharge glycemia ≥ 140 mg/dl in the training population were assessed by logistic regression analysis and a clinical prediction rule was developed. The ability of the prediction rule and that of admission HbA1c to predict discharge glycemia ≥ 140 mg/dl and HbA1c > 7% one year after discharge was assessed in the testing population. RESULTS: Selected admission variables (diastolic arterial pressure < 80 mmHg, glycemia = 143–218 mg/dl, glycemia > 218 mg/dl, history of insulinic or combined hypoglycemic therapy, Charlson's index > 2) were combined to obtain a score predicting a discharge fasting glycemia ≥ 140 mg/dl in the training population. A modified score was obtained by adding 1 if admission HbA1c exceeded 7.8%. The modified score was the best predictor of both discharge glycemia ≥ 140 mg/dl (sensitivity = 79%, specificity = 63%) and 1 year HbA1c > 7% (sensitivity = 72%, specificity = 71%) in the testing population. CONCLUSION: A simple clinical prediction rule might help identify older diabetic in-patients at risk of both short and long term poor glycemic control
Entropy-driven liquid-liquid separation in supercooled water
Twenty years ago Poole et al. (Nature 360, 324, 1992) suggested that the
anomalous properties of supercooled water may be caused by a critical point
that terminates a line of liquid-liquid separation of lower-density and
higher-density water. Here we present an explicit thermodynamic model based on
this hypothesis, which describes all available experimental data for
supercooled water with better quality and with fewer adjustable parameters than
any other model suggested so far. Liquid water at low temperatures is viewed as
an 'athermal solution' of two molecular structures with different entropies and
densities. Alternatively to popular models for water, in which the
liquid-liquid separation is driven by energy, the phase separation in the
athermal two-state water is driven by entropy upon increasing the pressure,
while the critical temperature is defined by the 'reaction' equilibrium
constant. In particular, the model predicts the location of density maxima at
the locus of a near-constant fraction (about 0.12) of the lower-density
structure.Comment: 7 pages, 6 figures. Version 2 contains an additional supplement with
tables for the mean-field equatio
Poorly controlled type 2 diabetes is accompanied by significant morphological and ultrastructural changes in both erythrocytes and in thrombin-generated fibrin: implications for diagnostics
We have noted in previous work, in a variety of inflammatory diseases, where iron dysregulation occurs, a strong
tendency for erythrocytes to lose their normal discoid shape and to adopt a skewed morphology (as judged by
their axial ratios in the light microscope and by their ultrastructure in the SEM). Similarly, the polymerization of
fibrinogen, as induced in vitro by added thrombin, leads not to the common ‘spaghetti-like’ structures but to dense
matted deposits. Type 2 diabetes is a known inflammatory disease. In the present work, we found that the axial
ratio of the erythrocytes of poorly controlled (as suggested by increased HbA1c levels) type 2 diabetics was
significantly increased, and that their fibrin morphologies were again highly aberrant. As judged by scanning
electron microscopy and in the atomic force microscope, these could be reversed, to some degree, by the addition
of the iron chelators deferoxamine (DFO) or deferasirox (DFX). As well as their demonstrated diagnostic significance,
these morphological indicators may have prognostic value.Biotechnology and Biological Sciences Research Council (grant
BB/L025752/1) as well as the National Research Foundation (NRF) of South
Africa.http://www.cardiab.com/hb201
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
Hyper-IgG4 disease: report and characterisation of a new disease
BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis. METHODS: We report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment. CONCLUSION: We believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good
Interplay between ultrastructural findings and atherothrombotic complications in type 2 diabetes mellitus
Accelerated atherosclerosis is the main underlying factor contributing to the high risk of atherothrombotic events in
patients with diabetes mellitus and atherothrombotic complications are the main cause of mortality. Like with many
bodily systems, pathology is observed when the normal processes are exaggerated or uncontrolled. This applies to
the processes of coagulation and thrombosis as well. In diabetes, in fact, the balance between prothrombotic and
fibrinolytic factors is impaired and thus the scale is tipped towards a prothrombotic and hypofibrinolytic milieu, which
in association with the vascular changes accompanying plaque formation and ruptures, increases the prevalence of
ischaemic events such as angina and myocardial infarction. Apart from traditional, modifiable risk factors for cardiovascular
disease like hypertension, smoking, elevated cholesterol; rheological properties, endogenous fibrinolysis and
impaired platelet activity are rapidly gaining significance in the pathogenesis of atherosclerosis especially in diabetic
subjects. Blood clot formation represents the last step in the athero-thrombotic process, and the structure of the fibrin
network has a role in determining predisposition to cardiovascular disease. It is no surprise that just like platelets and
fibrin networks, erythrocytes have been shown to play a role in coagulation as well. This is in striking contrast to their
traditional physiological role of oxygen transport. In fact, emerging evidence suggests that erythrocytes enhance
functional coagulation properties and platelet aggregation. Among the spectrum of haematological abnormalities in
diabetes, erythrocyte aggregation and decreased deformability of erythrocytes predominate. More importantly, they
are implicated in the pathogenesis of microvascular complications of diabetes. The morphology of platelets, fibrin
networks and erythrocytes are thus essential role players in unravelling the pathogenesis of cardiovascular complications
in diabetic subjects.National Research Foundation of South Africa (UNIQUE GRANT NO: 92709) and the MRC: E Pretorius (fund number A0X331).http://www.cardiab.comhb201
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