Brain amyloid and vascular risk are related to distinct white matter hyperintensity patterns

White matter hyperintensities (WMHs) are associated with vascular risk and Alzheimer’s disease. In this study, we examined relations between WMH load and distribution, amyloid pathology and vascular risk in 339 controls and cases with either subjective (SCD) or mild cognitive impairment (MCI). Regional deep (DWMH) and periventricular (PWMH) WMH loads were determined using an automated algorithm. We stratified on Aβ1-42 pathology (Aβ+/−) and analyzed group differences, as well as associations with Framingham Risk Score for cardiovascular disease (FRS-CVD) and age. Occipital PWMH (p = 0.001) and occipital DWMH (p = 0.003) loads were increased in SCD-Aβ+ compared with Aβ− controls. In MCI-Aβ+ compared with Aβ− controls, there were differences in global WMH (p = 0.003), as well as occipital DWMH (p = 0.001) and temporal DWMH (p = 0.002) loads. FRS-CVD was associated with frontal PWMHs (p = 0.003) and frontal DWMHs (p = 0.005), after adjusting for age. There were associations between global and all regional WMH loads and age. In summary, posterior WMH loads were increased in SCD-Aβ+ and MCI-Aβ+ cases, whereas frontal WMHs were associated with vascular risk. The differences in WMH topography support the use of regional WMH load as an early-stage marker of etiology.     

Alcohol consumption and its relation to risk factors for cardiovascular disease in the north-west of Russia: the Arkhangelsk study

BACKGROUND: To explore indicators and levels of alcohol consumption in a Russian population, and to elaborate these in relation to risk factors for cardiovascular disease. METHODS: A total of 1963 men and 1734 women, aged 18-75 years, consecutively recruited at their compulsory annual medical check-up at the Semashko outpatient clinic, Arkhangelsk, participated in a cross-sectional health survey. The survey comprised a physical examination, a six-page questionnaire on health and lifestyle, and blood tests. RESULTS: Gamma-glutamyltransferase (GGT) levels in both sexes were more than twice as high as found in comparable studies. Elevated GGT-levels were 4-5 times more frequent than found in Norwegian studies. Alcohol Use Disorder Identification Test (AUDIT) identified up to 75% of male workers and 47% of female workers as hazardous or harmful alcohol drinkers. The traditional risk factors for cardiovascular disease were significantly higher in subjects with a high level of GGT. CONCLUSION: The findings indicate an extremely high level of alcohol consumption in this population. Elevation in GGT was significantly associated with increased risk for cardiovascular disease.     

Single-chip mechatronic microsystem for surface imaging and force response studies

We report on a stand-alone single-chip (7 x 10 mm) atomic force microscopy unit including a fully integrated array of cantilevers, each of which has an individual actuation, detection, and control unit so that standard atomic force microscopy operations can be performed by means of the chip only without any external controller. The system offers drastically reduced overall size and costs as well as increased scanning speed and can be fabricated with standard complementary metal oxide semiconductor technology with some subsequent micromachining steps to form the cantilevers. Full integration of microelectronic and micromechanical components on the same chip allows for the controlling and monitoring of all system functions. The on-chip circuitry, which includes analog signal amplification and filtering stages with offset compensation, analog-to-digital converters, a powerful digital signal processor, and an on-chip digital interface for data transmission, notably improves the overall system performance. The microsystem characterization evidenced a vertical resolution of < 1 nm and a force resolution of < 1 nN as shown in the measurement results. The monolithic system represents a paradigm of a mechatronic microsystem that allows for precise and fully controlled mechanical manipulation in the nanoworld.     

Urgent carotid endarterectomy is safe in patients with few comorbid medical conditions

Recent reports from single institutions have confirmed the efficacy of carotid endarterectomy (CEA) performed in the urgent or emergent setting, although with higher perioperative mortality and morbidity. We determined the results of urgently performed CEA in academic and community hospitals and whether patient or hospital factors affected outcome. The records of patients undergoing CEA in all nonfederal hospitals in the state of Connecticut between 1992 and 2002 were reviewed, and symptomatic patients who presented in an urgent or emergent fashion were compared to patients treated electively. Multivariable logistic regression was used to determine the effect of patient risk factors on perioperative mortality, stroke, and cardiac complications. Patients undergoing urgent CEA (n = 764, 6.3%) had higher perioperative mortality (2.0% vs. 0.3%, p < 0.0001) and stroke (2.9% vs. 1.1%, p < 0.0001) but not cardiac complications (3.0% vs. 2.2%, p = 0.14) compared to patients undergoing elective CEA (n = 11,312). Patients undergoing urgent CEA and with high rates of associated comorbidity had a higher risk of perioperative mortality (7.8% vs. 0.4, p = 0.001), stroke (10.9% vs. 0.8%, p = 0.0002), and cardiac complications (14.1% vs. 0.8%, p < 0.0001) compared to patients presenting urgently but with little comorbidity. Perioperative mortality was associated with performance of the procedure in hospitals with low bed capacity (odds ratio [OR] = 4.6, p = 0.01). Perioperative stroke was associated with renal insufficiency (OR = 5.3, p = 0.04). Perioperative cardiac complications were associated with diabetes (OR = 2.6, p = 0.03) and performance in hospitals with low bed capacity (OR = 5.0, p < 0.01). Urgent admission was associated with age >/=80 (OR = 1.2, p = 0.04), renal disease (OR = 1.8, p = 0.05), and cardiac disease (OR = 1.3, p < 0.01). Urgently performed CEA has higher perioperative mortality and stroke compared with electively performed cases. However, the subset of patients with low rates of associated comorbid medical conditions but urgently needing CEA is associated with low rates of perioperative complications. Patients with severe associated comorbid medical conditions who present urgently for CEA may form a high-risk group of patients to be considered for referral to large treatment centers or possibly alternative therapy.     

Dynamic contrast‐enhanced‐MRI of tumor hypoxia

Patients with highly hypoxic primary tumors show increased frequency of locoregional treatment failure and poor survival rates and may benefit from particularly aggressive treatment. The potential of gadolinium diethylene‐triamine penta‐acetic acid‐based dynamic contrast‐enhanced‐MRI in assessing tumor hypoxia was investigated in this preclinical study. Xenografted tumors of eight human melanoma lines were subjected to dynamic contrast‐enhanced‐MRI and measurement of the fraction of radiobiologically hypoxic cells and the fraction of pimonidazole‐positive hypoxic cells. Tumor images of K^trans (the volume transfer constant of gadolinium diethylene‐triamine penta‐acetic acid) and v_e (the fractional distribution volume of gadolinium diethylene‐triamine penta‐acetic acid) were produced by pharmacokinetic analysis of the dynamic contrast‐enhanced‐MRI data, and K^trans and v_e frequency distributions of the non‐necrotic tumor tissue were established and related to the extent of hypoxia. Tumors showing high K^trans values and high v_e values had low fractions of hypoxic cells, whereas tumors showing both low K^trans values and low v_e values had high hypoxic fractions. K^trans differentiated better between tumors with low and high hypoxic fractions than did v_e. This study supports the current attempts to establish dynamic contrast‐enhanced‐MRI as a method for assessing the extent of hypoxia in human tumors, and it provides guidelines for the clinical development of valid assays. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Long-term outcome of surgically and medically treated patients with gastroesophageal reflux disease: a matched-pair follow-up study

OBJECTIVE: A recent randomized study has shown that the long-term effects of continuous medical treatment of gastroesophageal reflux disease (GERD) with a proton-pump inhibitor are comparable to those of open fundoplication. We compared the long-term effects of anti-reflux surgery with those of medical care according to clinical practice. MATERIAL AND METHODS: This is a questionnaire-based 3-10 years follow-up study of 373 patients with GERD operated on in two hospitals with either open or laparoscopic fundoplication, and pair-matched non-operated controls treated medically according to clinical practice. The controls were matched for hospital, age, sex, follow-up time, degree of esophagitis, presence of hiatus hernia and Barrett's esophagus. The questionnaires used for symptoms and health-related quality of life (QoL) were the Gastrointestinal Symptoms Rating Scale and the Psychological General Well-Being Index, respectively. RESULTS: Response rates were about 80%, and 179 pairs of operated patients and controls remained for analysis (102 based on laparoscopic and 77 on open fundoplication). Independently of the surgical technique, the operated patients suffered at the follow-up from significantly (p <0.001) fewer reflux symptoms than the non-operated controls, the mean scores being 1.34 and 2.51, respectively. The operated patients suffered from slightly more symptoms of indigestion (p <0.05). No consistent significant differences between the groups were found for QoL. Significant differences in QoL in favor of the operated patients were found when dealing only with the 43 pairs with no concurrent disease. CONCLUSION: The study shows that in our area anti-reflux surgery is more effective in relieving reflux symptoms than medical care according to clinical practice.     

New Alcohol Markers—How Useful Are They in Population Studies: The Svalbard Study 1988–89

Regular high consumption of alcohol in selected populations have, with high precision, been identified by two new alcohol markers; carbohydrate-deficient transferrin and mitochondrial aspartate aminotransferase. To test these markers in an unselected population, gamma-glutamyltransferase (GGT), carbohydrate-deficient transferrin (CDT), and mitochondrial aspartate aminotransferase (mAST) were measured in the Norwegian population, 310 males and 171 females, aged 18 to 60 years, living at Svalbard. Using self-reported alcohol intake as gold standard, sensitivity, specificity, positive predictive value, and likelihood-ratio were estimated according to different cutoff-points for alcohol intake and for the tests. In contrast to earlier studies, the sensitivity was in general low. With a specificity of 90% or higher, the sensitivity did not exceed 26% for any of the tests. Whereas CDT showed its best discriminatory power at lower intake of alcohol, GGT discriminated best at higher levels. Parallel and serial analysis of CDT and GGT indicated a conditional independence between the tests, as well as at higher and at lower levels of alcohol consumption. mAST was judged as not suitable in population studies.