Carotid-Femoral Pulse Wave Velocity Is Associated With Cerebral White Matter Lesions in Type 2 Diabetes

OBJECTIVE

Patients with type 2 diabetes have a high incidence of cardiovascular events including stroke. Increased arterial stiffness (AS) predicts cardiovascular events in the general population. Cerebral white matter lesions (WMLs) are associated with an increased risk of stroke. It is unknown whether AS in patients with type 2 diabetes is associated with WMLs.

RESEARCH DESIGN AND METHODS

We examined 89 patients recently diagnosed with type 2 diabetes (<5 years) and 89 sex- and age-matched controls. AS was assessed with carotid-femoral pulse wave velocity (PWV). WMLs were identified using magnetic resonance imaging and graded qualitatively with the Breteler scale (no/slight changes = 0, moderate changes = 1, severe changes = 2) and semiquantitatively.

RESULTS

The diabetic population had excellent glycemic control (HbA_1c, 6.5% [6.2–6.8]; median [interquartile range {IQR}]) and had, compared with the controls, lower office blood pressure (BP) (127 ± 12/79 ± 8 vs. 132 ± 14/84 ± 10 mmHg) and total cholesterol (4.3[3.9–4.7] vs. 5.6 [5.1–6.4]; mmol/L; median [IQR]), (P < 0.01 for all). Despite this, PWV was higher in the patients with diabetes compared with controls (9.3 ± 2.0 vs. 8.0 ± 1.6 m/s; P < 0.0001). PWV was associated with Breteler score (OR 1.36 [95% CI 1.17–1.58]; P < 0.001) and WML volume (OR 1.32 [95% CI 1.16–1.51]; P < 0.001) per 1 m/s increase in PWV. These associations remained significant when adjusted for age, sex, diabetes, 24-h mean arterial BP, BMI, heart rate, and use of antihypertensives and statins (Breteler score: OR 1.28 [95% CI 1.03–1.60]; P < 0.05 and WML volume: OR 1.30 [95% CI 1.06–1.58]; P < 0.05).

CONCLUSIONS

PWV was higher among patients with well-controlled type 2 diabetes compared with controls and was independently associated with WMLs. PWV may represent a clinically relevant parameter in the evaluation of cerebrovascular disease risk in type 2 diabetes.Despite intensified treatment, patients with type 2 diabetes have a significantly higher incidence of cardiovascular events, including stroke, compared with patients without diabetes (1–3). Identifying new risk factors for incident cardiovascular disease, which add prognostic information to established risk factors, is important to improve risk stratification and enable timely initiation of individually tailored preventive measures in this high-risk population (4). Increased arterial stiffness, as indicated by increased pulse wave velocity (PWV), is an independent predictor of cardiovascular morbidity and mortality and total mortality in various nondiabetic populations (5–11). In patients with diabetes, PWV independently predicts cardiovascular and total mortality (12). Several studies have found cerebral white matter lesions (WMLs) to be associated with the risk of stroke (13). Nevertheless, it remains unknown whether PWV in patients with type 2 diabetes is associated with the severity of WMLs. In this study of a sample of patients with recently diagnosed type 2 diabetes and a sex- and age-matched control group, our aims were to 1) compare PWV and established cardiovascular risk factors and 2) study the association between PWV and WMLs.     

New reference intervals for cortisol,cortisol binding globulin and free cortisol index in women using ethinyl estradiol

Abstract

Healthy women using contraceptives containing a low dose of an estrogen may have a higher serum concentration of cortisol (s-cortisol) and cortisol binding globulin (s-CBG) than the commonly used upper reference limits. There are no published reference intervals for s-cortisol, s-CBG, serum free cortisol index (s-FCI) or cortisol in saliva (sa-cortisol) for these women. The aim was to establish the above-mentioned reference intervals and document the differences in s-cortisol and s-CBG in one group of women using and another group not using ethinyl estradiol (EE). In this cross-sectional study, the reference limits presented were given as the 2.5 and 97.5 percentiles of the distribution of reference values in a population of 277 healthy volunteer women, aged 18–45?years. 157 women were not using any type of estrogen, while 120 women were using contraceptives containing a daily dose of 15–35?μg of EE. Serum and salivary cortisol, and serum CBG were measured using standard laboratory methods. S-FCI was calculated as s-cortisol/s-CBG. The reference intervals for s-cortisol in samples collected at 0800–1030 am in women using and not using EE contraception were: 284–994?nmol/L and 159–569?nmol/L respectively, and for s-CBG: 847–3366?nmol/L and 860–1940?nmol/L, respectively. For s-FCI and sa-cortisol, no clinically significant differences were found. Sa-cortisol may be the preferred measurand for evaluation of possible hypercortisolism in women using estrogens, since cortisol in saliva is not influenced by estrogen. If assessing morning s-cortisol and s-CBG in women using EE, we recommend using separate – and not the commonly used – reference intervals.     

Wood dust exposure in the Danish furniture industry using conventional and passive monitors

A study of wood dust exposure at furniture factories in one county in Denmark was performed as a cross sectional study. Dust exposure was measured with personal passive dust monitors and calibrated against active sampling on filters. Measurements of 1685 workers were included in the exposure assessment. The passive dust monitor conversion models for equivalent concentrations of inhalable dust and total dust based on data from the present study were not significantly different from the original models. Therefore models based on all available data were used. The parameters of the distribution of equivalent concentration of inhalable dust were 0.94 mg/m3 (geometric mean) and 2.10 (geometric standard deviation). Compared with a national cross sectional study from 1988 the exposure level (geometric mean) was reduced by a factor 2.0. Inhalable dust exposure was about 50% higher than exposure measured by the Danish 'total' dust method.     

Raman spectroscopy to distinguish grey matter,necrosis, and glioblastoma multiforme in frozen tissue sections

The need exists for a highly accurate, efficient and inexpensive tool to distinguish normal brain tissue from glioblastoma multiforme (GBM) and necrosis boundaries rapidly, in real-time, in the operating room. Raman spectroscopy provides a unique biochemical signature of a tissue type, with the potential to provide intraoperative identification of tumor and necrosis boundaries. We aimed to develop a database of Raman spectra from normal brain, GBM, and necrosis, and a methodology for distinguishing these pathologies. Raman spectroscopy was used to measure 95 regions from 40 frozen tissue sections using 785 nm excitation wavelength. Review of adjacent hematoxylin and eosin sections confirmed histology of each region. Three regions each of normal grey matter, necrosis, and GBM were selected as a training set. Ten regions were selected as a validation set, with a secondary validation set of tissue regions containing freeze artifact. Grey matter contained higher lipid (1061, 1081 cm^?1) content, whereas necrosis revealed increased protein and nucleic acid content (1003, 1206, 1239, 1255–1266, 1552 cm^?1). GBM fell between these two extremes. Discriminant function analysis showed 99.6, 97.8, and 77.5 % accuracy in distinguishing tissue types in the training, validation, and validation with freeze artifact datasets, respectively. Decreased classification in the freeze artifact group was due to tissue preparation damage. This study shows the potential of Raman spectroscopy to accurately identify normal brain, necrosis, and GBM as a tool to augment pathologic diagnosis. Future work will develop mapped images of diffuse glioma and neoplastic margins toward development of an intraoperative surgical tool.     

COMPARISON OF INTRAMEDULLARY FIXATION AND PERCUTANEOUS PINNING OF DISPLACED AND COMMINUTED COLLES' FRACTURES: A PROSPECTIVE AND CONSECUTIVE STUDY

This consecutive study comprised 86 patients who were available for follow up 5-51 months after sustaining a Colles' fracture-Older type IV. A total of 42 patients were treated with Kirschner (K) wires of whom one had bilateral fracture. Forty-four patients (of whom two had bilateral fractures) were treated with Rush nails. A functional assessment of the patients was made using both a questionnaire and a clinical examination. The end-results of residual deformity, subjective and objective findings, and complications were evaluated according to the Lucas' modification of the Sarmiento demerit point-rating system. At follow-up, the ulnar/radial deviation was significantly better in the patients operated on with K-wires (37° compared with 27°, p &lt; 0.02, range in both groups 0-80°), but no differences were found in the other directions of movement. A total of three patients (7%) developed complications. The final result showed that 40 (93%) of the fractures treated with K-wires were excellent or good compared with 38 (86%) of those operated on with a Rush nail. One fracture in each group (2%) had a poor outcome. Comparison of the final results showed no significant difference between the two groups.     

An update on head and neck cancer: new entities and their histopathology,molecular background,treatment, and outcome

The head and neck region harbor numerous specialized tissues of all lineages giving rise to a plethora of different malignancies. In recent years, new types and subtypes of cancer has been described here due to the recognition of their histological and molecular characteristics. Some have been formally accepted in the most recent classifications from the World Health Organization (WHO) and American Joint Committee on Cancer (AJCC) as distinct diseases due to characteristics in clinical presentation, outcome, and treatment. In particular, this applies to malignancies of the salivary gland, sinonasal tract, and oropharynx. In this overview, we present the most recent developments in the classification, histopathological characteristics, and molecular features of head and neck cancer. The clinical and radiological characteristics, outcome, and treatment options including perspectives for targeted therapies, are discussed.     

An extended vascular model for less biased estimation of permeability parameters in DCE‐T1 images

One of the key elements in dynamic contrast enhanced (DCE) image analysis is the arterial input function (AIF). Traditionally, in DCE studies a global AIF sampled from a major artery or vein is used to estimate the vascular permeability parameters; however, not addressing dispersion and delay of the AIF at the tissue level can lead to biased estimates of these parameters. To find less biased estimates of vascular permeability parameters, a vascular model of the cerebral vascular system is proposed that considers effects of dispersion of the AIF in the vessel branches, as well as extravasation of the contrast agent (CA) to the extravascular‐extracellular space. Profiles of the CA concentration were simulated for different branching levels of the vascular structure, combined with the effects of vascular leakage. To estimate the permeability parameters, the extended model was applied to these simulated signals and also to DCE‐T1 (dynamic contrast enhanced T₁) images of patients with glioblastoma multiforme tumors. The simulation study showed that, compared with the case of solving the pharmacokinetic equation with a global AIF, using the local AIF that is corrected by the vascular model can give less biased estimates of the permeability parameters (K^trans, v_p and K_b). Applying the extended model to signals sampled from different areas of the DCE‐T1 image showed that it is able to explain the CA concentration profile in both the normal areas and the tumor area, where effects of vascular leakage exist. Differences in the values of the permeability parameters estimated in these images using the local and global AIFs followed the same trend as the simulation study. These results demonstrate that the vascular model can be a useful tool for obtaining more accurate estimation of parameters in DCE studies.     

Atypical furunculosis vaccines for Atlantic cod (Gadus morhua); vaccine efficacy and antibody responses

Atypical furunculosis caused by atypical Aeromonas salmonicida, is an emerging problem in farming of Atlantic cod (Gadus morhua) in Norway, and vaccines are needed. Atypical A. salmonicida comprises a heterogeneous group of bacteria differing in surface antigens such as the A-layer protein and lipopolysaccharides (LPS). Except for one of the experimental oil-adjuvanted whole cell vaccines based on various isolates they all resulted in moderate protection. No clear correlation between vaccine efficacies and the A-protein group or LPS type of the vaccine isolates was revealed, while a correlation between efficacy and the presence of cross-reacting LPS-specific antibodies is indicated.