A double-blind crossover study of the effect of a chromone carboxylic acid, FPL 52694, on overnight fasting gastric acid secretion

The chromone FPL 52694 is a preparation thought to act by stabilizing mast cell membranes, thus reducing free histamine in the gastric mucosa. The effect of FPL 52694 on overnight gastric secretion was tested in 15 dyspeptic individuals in a double-blind crossover study. Each individual received the chromone preparation or placebo for 1 week. After each of the treatment periods gastric secretion was collected after 6 h of fasting by continuous suction for 8 h during the night. A significant reduction of the total acid secretion was observed after active drug compared with placebo administration, mean reduction being 17% (median, 23%). No difference was observed between 30-min and 60-min periods. FPL 52694 had no significant effect on pepsin, intrinsic factor (IF) or volume secretion. The difference in the effect on pepsin and acid secretion, reflected in a significant increase in the pepsin to acid ratio, indicates that intrinsic histamine, similarly to extrinsic histamine, has a specific effect on parietal cells. The difference in effect on acid and IF secretion indicates that intrinsic histamine not only has a specific effect on parietal cells but also has different effects on the secretory substances contained in this cell. Since IF was not reduced by the use of FPL 52694, it may be that this substance will not influence vitamin B12 metabolism.     

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.     

Neurotensin-induced mast cell degranulation in human jejunal mucosa. Additive effects of IgE or compound 48/80 and inhibition by sodium cromoglycate

The effect of sodium cromoglycate (SCG) on neurotensin- and compound 48/80-induced mast cell degranulation and the effect of combining these secretagogues with each other and with an immunological mast cell degranulation system was studied. Neurotensin reduced the number of intact mast cells from 119 (60-190)/mm2 to 50 (20-101)/mm2. This figure was 76 (34-164)/mm2 when SCG was added to neurotensin, a change that was statistically significant. No such inhibitory effect on mast cell degranulation was seen when SCG was added to compound 48/80, which was active only in high doses. When neurotensin or compound 48/80 was followed by antigen in sensitized tissue specimens, mast cell degranulation was enhanced compared with that taking place with only one of the secretagogues. Neurotensin and compound 48/80 did not cause further mast cell degranulation when applied after IgE followed by antigen or when applied after one another. It is concluded that neurotensin may act through a selective release mechanism, whereas compound 48/80 acts by a cytotoxic mechanism, but that they act on the same group of cells.     

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.     

Endoscopy guided by an intraoperative 3D ultrasound-based neuronavigation system.

OBJECTIVE: We have investigated the feasibility of using 3D ultrasound-based neuronavigation for guiding neuroendoscopy. METHODS: A neuronavigation system with an integrated ultrasound scanner was used for acquiring the 3D ultrasound image data. The endoscope with a tracking frame attached was calibrated to the navigation system. The endoscope was guided based on intraoperative 3D ultrasound data in 9 operations. In 5 of the operations, ultrasound angiography data were also obtained. Updated image data (e. g., more than one 3D ultrasound dataset) were obtained in 6 of the operations. RESULTS: We found that the image quality of 3D ultrasound was sufficient for image guidance of the endoscope. Planning of the entry point and trajectory as well as finding optimal sites for fenestration were successfully performed. Blood vessels were visualized by 3D ultrasound angiography. In one procedure of third ventriculostomy, the basilar artery was visualized. Updated image data were quickly obtained, and in two of the cases, a reduction of the size of cysts was demonstrated. CONCLUSIONS: 3D ultrasound gives accurate images of sufficiently high quality for image guidance of neuroendoscopy. Updated 3D ultrasound datasets can easily be acquired and may adjust for brain shift. Ultrasound angiography image data are also available with this technology and can visualize vessels of importance.     

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.