The effect of bacterial melanin on electrical activity of neurons of the substantia nigra under conditions of GABA generation

The changes in spike activity of single neurons of the compact part of the substantia nigra, evoked by nucleus caudatus stimulation under conditions of long-term registration of the single and multiple, isolated and combined actions of GABA, GABA-amide, glutamine, and ethanolamine-O-sulfate (EOS) were studied in albino rats. Inhibition of poststimulus activity under GABA action was recorded and the inhibitory effect of GABA-amide was revealed. Primary excitatory and subsequent inhibitory effects of glutamine in combination with EOS were shown. The subsequent administration of bacterial melanin, synthesized by a mutant culture of Bacillus thuringiensis (BT-M) evoked a clear-cut and prolonged excitatory reaction during all the combined actions of GABA, GABA-amide, glutamine, and EOS. Preliminary administration of BT-M abolished the inhibitory poststimulus effects of GABA, GABA-amide, and EOS, as well as glutamine-induced excitation.     

Does the establishment of a Vascular Unit reduce the prevalence of ruptured aortic aneurysms?

AIM: The aim of this study was to assess the effect of a specialised Vascular Unit upon the prevalence of ruptured aortic aneurysms in the same population catchments' area and associated mortality rates. METHODS: Setting: prospective computerised data collection from 1997 to today, retrospective from 1990-1996. Subjects: 108 aneurysms were operated upon from 1990-1996, compared to 317 from 1997 to Aug 2002. Main outcome measures: statistical analysis was done using SPSS statistics with Kaplan Meier life table curves and compared by the log rank test while the Mann Whitney test was used for comparison of mortality. RESULTS: The median values for ruptured aneurysms per year were 5 for the early period, compared to 10 for the recent years, while the median values for both urgent and ruptured were 7 and 18.5 cases annually, respectively. The number of scheduled procedures increased by 500% in the second period, with median values of 7 and 36.5, respectively. In-hospital mortality according to category was 21% for scheduled, 31% for urgent and 69% for ruptured aneurysms in the early period, compared to 3.7%, 16% and 29% respectively, following the establishment of the Vascular Unit. CONCLUSION: Despite the five-fold increase in the total number of aortic aneurysm repairs (as expected), the number of ruptured aneurysms operated upon increased as well. There was just a trend for a reduction in the absolute numbers of ruptured aneurysms operated upon in the last 2 years. Mortality, on the other hand, decreased dramatically in all categories, with the overall 30-day mortality decreasing more than four-fold, from 40% to 9.3%, while the respective mortalities according to the category of intervention were 3.7% vs 21% for scheduled, 16% vs 35% for urgent and 29% vs 69% for ruptured aneurysms, with a P value of less than 0.01. However, there was no difference in the numbers of patients with ruptured aneurysm reaching the hospital (operated or not) between the two periods (median values of 11 and 10.5 annually). The presence of a Vascular Unit, although it achieves dramatically better results, is not associated with a reduction in the number of emergency proceduresaeat least in the intermediate termaedespite an expansion in the indications for surgery, increased awareness and prompt referrals (centralisation).     

Densitometry for assessment of effect of lung volume reduction surgery for emphysema.

To explore if change in the extent of emphysema correlated with change in lung function, the effect of resection of emphysematous tissue was studied by computed tomography (CT) densitometry. In addition, the current authors studied how surgery-induced change in emphysema related to lung density in control subjects. In total, 30 patients (14 females; mean+/-sd age 59+/-10 yrs) with severe emphysema before and 3 months after lung volume reduction surgery (LVRS), 48 patients with moderate emphysema and 76 control subjects were investigated. Lung density (15th percentile point) of both lungs and heterogeneity of lung density between 12 isovolumetric partitions in each lung were calculated from chest CT images. The 15th percentile point and its heterogeneity could distinguish controls from subjects with moderate emphysema with a sensitivity and specificity of >95%. LVRS significantly increased lung density by 5.0+/-10.9 g.L(-1) (n=30). Improvement in the diffusing capacity of the lung for carbon monoxide and in residual volume significantly correlated with an increase in lung density (n=20 and 28, respectively). Change in forced expiratory volume in one second did not correlate with change in lung density. In conclusion, lung density 15th percentile point is a valuable surrogate marker for detection of both the extent of and reduction in emphysema.     

Lucian Leape on Patient Safety in U.S. Hospitals

PURPOSE: To describe and discuss the status of patient safety in U.S. hospitals. METHODS: Personal interview. This report is part of a series of discussions with a leading expert on patient safety. FINDINGS AND CONCLUSIONS: Some improvements have been made in the past 10 years. But changes have not been adequate. Continuing barriers include the punitive environment in hospitals, physicians' denial of the scope of the problem, lack of national leadership, and lack of systems thinking.     

Adrenal function under long-term raloxifene administration.

The aim of the present study was to evaluate the effect of long-term (12 months) administration of raloxifene hydrochloride (60 mg/day) on the steroid production of the adrenal cortex and on the hypothalamic-pituitary-adrenal axis in postmenopausal women. We performed a basal evaluation, a corticotropin releasing factor (CRF) (100 microg i.v. bolus) test and a dexamethasone (DXM) (0.25 mg) suppression-adrenocorticotropic hormone (ACTH) (10 microg i.v. bolus) stimulation test in 11 postmenopausal women, before and after 3, 6 and 12 months of raloxifene treatment. Raloxifene administration significantly modified circulating levels of adrenal steroids, decreasing cortisol (-24%), dehydroepiandrosterone (DHEA) (-36%), and its sulfate (DHEAS) (-41%), and androstenedione (-29%), and increasing circulating allopregnanolone (+39%) levels. Progesterone and 17OH-progesterone levels remained unmodified, while estradiol and estrone levels showed a significant decrease (-51% for estradiol and -61% for estrone). We also observed an increase in circulating ACTH (+58%) and beta-endorphin (+120%). No modifications in the hormonal responses to CRF were observed during the treatment. DXM significantly suppressed circulating steroids at any time with a lower suppression of cortisol from the third month and a higher suppression of DHEA at 12 months. ACTH administration was associated with a significantly blunted cortisol response from the sixth month and a significantly increased response of allopregnanolone from the third month. The present data exclude a raloxifene effect on pituitary sensitivity to CRF and demonstrate a reduced adrenal sensitivity to ACTH, sustained by the opposite changes in basal cortisol and Delta5 androgens, which were reduced, and in ACTH and beta-endorphin, which were increased, as well by the reduced response of cortisol to the direct ACTH stimulus. The reduction of circulating cortisol levels and cortisol response to the ACTH challenge suggests that raloxifene protects against the neurotoxic effects of endogenous glucocorticoids. Furthermore, the progressive increase in basal allopregnanolone and its increased response to ACTH indicate that chronic raloxifene administration exerts direct effects on the pattern of adrenal enzymes, leading to specific changes in the circulating levels of this anxiolytic progesterone metabolite. The important reduction in the circulating levels of estradiol and estrone under long-term raloxifene administration may represent a further mechanism by which this molecule may exert a protective effect against breast and endometrial malignancies.     

Characterization of normal and infarcted rat myocardium using a combination of small-animal PET and clinical MRI.

The combination of small-animal PET and MRI data provides quantitative in vivo insights into cardiac pathophysiology, integrating information on biology and morphology. We sought to determine the feasibility of PET and MRI for the quantification of ischemic injury in the rat model. METHODS: Fourteen healthy male Wistar rats were studied with 18F-FDG PET and cine MRI. Myocardial viability was determined in a transmural myocardial infarction model in 12 additional rats, using 18F-FDG PET and delayed-enhancement MRI with gadolinium-diethylenetriaminepentaacetic acid. All PET was acquired with a dedicated small-animal PET system. MRI was performed on a 1.5-T clinical tomograph with a dedicated small-animal electrocardiographic triggering device and a small surface coil. RESULTS: In normal rats, 18F-FDG uptake was homogeneous throughout the left ventricle. The lowest mean uptake of the 18F-FDG was found in the apical regions (79% +/- 6.0% of maximum) and the highest uptake was in the anterior wall (93% +/- 4.3 % of maximum). Myocardial infarct size as determined by histology correlated well with defects of glucose metabolism obtained with 18F-FDG PET (r = 0.89) and also with delayed-enhancement MRI (r = 0.91). Left ventricular ejection fraction in normal rats measured by cine MRI was 57% +/- 5.4% and decreased to 38% +/- 12.9% (P < 0.001) in the myocardial infarction model. CONCLUSION: Integrating information from small-animal PET and clinical MRI instrumentation allows for the quantitative assessment of cardiac function and infarct size in the rat model. The MRI measurements of scar can be complemented by metabolic imaging, addressing the extent and severity of ischemic injury and providing endpoints for therapeutic interventions.     

Familial amyloidotic polyneuropathy: long-term follow-up of abdominal fat tissue aspirate in patients with and without liver transplantation.

To estimate the evolution of amyloid in tissue, we studied abdominal fat aspirates of cases with familial amyloidotic polyneuropathy (FAP) longitudinally at regular intervals between 1994 and 2006. In 22 cases (13 carriers and nine patients) not yet transplanted median follow-up was 3.3 years (range 0.4-11.3). We found a significant increase in the amyloid grade of fat tissue from 2+ to 4+ and from 0 to 4+ in two of three subjects with follow-ups of >7 years, after 7 and 11 years, respectively. All other subjects remained negative or did not show a significant change. In 11 liver transplant patients, follow-up with fat aspirate was available with a median duration of 3.1 years (range 1.0-10.1). A comparison was made with cardiac amyloid as judged by the cardiac septum diameter and the serum NT-ProBNP (N-terminal pro-B-type natriuretic peptide) level. No stable increase of amyloid in fat was seen in any patient. A stable decrease of amyloid grade was seen in one patient 5 years after transplantation. In contrast, the cardiac septum diameter increased >or=4 mm in six of the 11 transplant patients. Our study shows the diagnostic utility of a regularly repeated fat aspirate in carriers at risk for the development of ATTR amyloidosis. Evolution of amyloid deposition in fat tissue is very gradual. After liver transplantation, amyloid deposition in fat tissue seems to stabilize and may even decrease in the long term, whereas amyloid deposition in cardiac tissue appears to be progressive.