Real time endoscopic imaging of oxyradical generation in pig stomach during ischemia–reperfusion

BACKGROUND: Oxygen-free radicals generation is considered to be a major cause of gastric injury during reperfusion. Chemiluminescence has been used to assess real-time free radical release on the surface of isolated organs. AIMS: To evaluate the combined use of chemiluminescence and gastroendoscopy techniques and to assess the real-time production of free radicals during ischemic damage of the gastric wall in an animal model. PATIENTS AND METHODS: For the experiment, an optical junction was set up between a fibroendoscope and a luminograph apparatus. Three pigs were submitted to gastrofibroendoscopy before, during and after 30 min of clamping of the coeliac artery. Under basal conditions, at the end of the ischemic phase and at the beginning of reperfusion, 1 mM of lucigenin, a specific superoxide enhancer, was injected in the left gastric artery of the animal. The endoscopic live images and chemiluminescence emission were recorded and successively superimposed to measure rate and spatial distribution of photon emission (photons/s). RESULTS: Free radical production was not observed under basal conditions or during the ischemic phase, but significantly increased during reperfusion reaching a maximum peak after 15 min (0.6+/-0.2 photons x 10(5)/s) and decreased progressively thereafter. The superimposition of live and chemiluminescence images allowed the determination of the regional production rate and distribution of photons. CONCLUSIONS: Preliminary observations, in an animal model, on an innovative imaging system which allows the visualization of rate and spatial distribution of reactive oxygen species formation are presented. This new endoscopic technique could be useful for the assessment of oxidative gastric mucosal injury in several gastric diseases; however, further studies remain necessary to determine the applicability of this technique in humans.     

Down-regulation of 3H-lofentanil binding to opiate receptors in different cultured neuronal cells

Summary There was stereospecific binding of ³H-lofentanil (K _D value = 1.53 nM) to membranes of neuroblastoma-glioma NG 108-15 cells which are known to bear high affinity binding sites for enkephalin derivatives (-opiate receptor subtype). There was no high affinity specific binding of the -opiate specific ligand ³H-sufentanil. The specific binding of ³H-lofentanil to -opiate receptor subtype was down-regulated (decrease in B _max value without change in the K _D value) after prolonged incubation of the cells in the presence of leu- and met- enkephalin (0.1 M). There was no down-regulation of the opiate receptors (³H-lofentanil and ³H-d-ala-d-leu-enkephalin specific binding) after incubation of NG 108-15 cells with drugs from the fentanyl series (alfentanil or sufentanil).In cultured neurones from rat forebrain (15 day old embryos), the ³H-lofentanil binding was specific with high affinity (K _D: 0.048 nM) and a slow dissociation rate similar to that in adult rat cortex. Drugs of the fentanyl series (4-anilino-piperidines) were potent displacers whereas agonists of the - (enkephalin derivatives), (phencyclidine, haloperidol, 3-hydroxyphenyl-propylpiperidine) or K- (U 50488) opiate sites had a low affinity (K _i > 0.5 M) for ³H-lofentanil specific binding sites. Since there was also specific binding of ³H-sufentanil, the opiate receptors in cultured neurones seem to be mainly of the -subtype and this is consistent with the ontogeny of opiate receptors subtypes. These receptors were down-regulated after incubation in the presence of etorphine, sufentanil and alfentanil but not enkephalin derivatives.These results strongly suggest specific binding of ³H-sufentanil and ³H-lofentanil mainly to the so-called -opiate receptors in cultured neurones and a specific binding of ³H-lofentanil to lower affinity -opiate receptors in neuroblastoma-glioma cells. The down-regulation of the -opiate binding sites in cultured neurones and that of the -site in neuroblastoma × glioma hybrid cells were dose-and temperature-dependent, induced by the corresponding high affinity agonists and prevented by naloxone. Morphine did not induce down-regulation of or receptor sites, possibly because of a partial antagonist effect on both receptor subtypes. Send offprint requests to J. M. Maloteaux at the above address     

Behavioral and psychological symptoms in Alzheimer's disease. Relation between apathy and regional cerebral perfusion

Fundamental and therapeutic research in Alzheimer's disease (AD) focused for a long time exclusively on cognitive aspects. However, AD also frequently involves complex disorders of affect and behavior, which are currently grouped under the heading 'behavioral and psychological signs and symptoms of dementia' (BPSSD). Several rating tools have been developed over the years on the basis of a variety of source data. Some are derived from psychiatric practise or have specifically been developed for dementia, such as the Neuropsychiatric Inventory (NPI). In this study we prospectively used the NPI to examine BPSSD. Sixty-three French patients (mean age 74.7 years, SD 7.9) with a Mini-Mental State Examination (MMSE) score higher than 10 were examined. BPPSD were detected by NPI in 95. 2% of the patients. Anxiety was the most common abnormality (65.1%), followed by apathy and dysphoria (58.7%). The highest frequency x severity NPI score was observed for apathy. In order to identify the relationship between regional cerebral perfusion and apathy, 20 of these AD patients underwent a technetium-99m-bicisate SPECT protocol within the same week as the NPI evaluation. The mean age of this population was 74.4 years (SD 5.3) and the mean MMSE score was 21 (SD 4.1). The apathy NPI score was correlated with right cingulate deficit whereas the highest correlation for the MMSE was with the left temporoparietal area. This stresses the interest to focus on SPECT imaging of AD patients not only in the posterior areas. CopyrightCopyright 1999S.KargerAG,Basel     

Ventricular patch endocarditis caused by Propionibacterium acnes: advantages of gallium scanning

Propionibacterium acnes is a weakly pathogenic commensal of the skin. When isolated from blood cultures it is often considered a contaminant. However, P. acnes may be responsible for severe infections and its role in certain cases of infectious endocarditis has now been definitely established.(1) We report a case of endocarditis due to P. acnes stemming from a ventricular patch and revealed by a gallium 67 scan.     

Early (99m)Tc-ethylcysteinate dimer brain SPECT patterns in the acute phase of stroke as predictors of neurological recovery

OBJECTIVES: Accurate prediction of outcome in acute stroke would help in identifying subgroups of patients for therapeutic trials and intravenous thrombolysis. The purpose of this study was to prospectively test the hypothesis that brain SPECT, with (99m)Tc-L, L-ethylcysteinate dimer (ECD), a tracer sensitive to cell function, performed in the first hours after stroke onset, adds predictive power to concomitant neurological evaluation. METHODS: Twenty-four patients with a first-ever middle cerebral artery stroke were prospectively studied with ECD-SPECT within 12 h after stroke onset. Neurological evaluation was performed using Orgogozo's scale at admission and 3 months later in order to calculate the percent Martinez-Vila evolution indices (EI%). Semiquantitative visual analysis of SPECT images was performed in 6 cortical regions relevant for carotid artery territory. Both the extent and the intensity of cortical reduced ECD uptake were calculated, leading to an 'ischemia' score, corresponding to the sum of regions of interest (ROI) where ECD uptake was between 40 and 80% of the contralateral healthy hemisphere, and an 'irreversibly damaged tissue' (IDT) score, corresponding to an uptake below 40%, and a total score (ischemia + IDT). Each patient was assigned to one of three patterns: (1) pattern I with severe ECD cortical uptake reduction defined by at least one ROI with uptake under 40%, (2) pattern II with moderate ECD cortical uptake reduction (40-80%) only and (3) pattern III with normal ECD uptake. RESULTS: There were 11 patients (46%) with pattern I ECD-SPECT. This group had almost invariably (10/11 patients) a poor outcome. The 12 patients (50%) classified in pattern II had a variable clinical outcome, ranging from improvement to deterioration. The single patient with a normal SPECT (pattern III) had a full clinical recovery. Both total score and IDT score were strongly significantly correlated with neurological recovery EI% (respectively p = 0.006 and 0.004). Their predictive value was significantly higher than, and independent of, day 0 neurological evaluation. No patient had an increased ECD uptake. CONCLUSION: Our results show that the degree of ECD cortical uptake reduction, measured on early brain SPECT, is a strong predictor of neurological recovery. ECD-SPECT data have a higher predictive value than day 0 neurological evaluation. The apparently better predictive value of ECD over hexamethylpropyleneamine oxime may reflect this tracer's brain retention mechanisms which are weighted more towards cell function than towards perfusion. ECD-SPECT is easily obtainable and may help in selecting out from therapy those patients who are likely to have either very good or very poor spontaneous outcome, and thus improve the assessment of acute stroke and the choice of therapeutic strategy.     

Diet and chronic corticosteroid therapy

Corticosteroid therapy is widely used in the acute and chronic treatment of different diseases, with consequent possible onset of typical side effects on multiple systems of the organism, including also energy metabolism and metabolism of water and minerals (sodium, potassium, calcium and phosphorus). Clinical signs, related to the type and dosage of the steroidal drug, may lead to secondary illnesses with variable degrees of severity, depending on proneness of the individual patient and on the underlying disease that motivated the treatment. The role of dietetic intervention in the management of a patient chronically receiving corticosteroid therapy is not ancillary, although often underestimated, its aim being the reduction of some long-term therapy related side effects, and the correction of major metabolic derangements. In particular, the diet shall be moderately rich in protein (1.5 g/Kg/day of proteins) and low in fat (< 30% of calories, obtained mostly from unsaturated fatty acids), based mainly on complex carbohydrates (80%), providing 50% of the caloric intake. Diet has to be specifically characterized by food containing little sodium and yielding high amounts of water, calcium, magnesium and potassium. Minor directions concern the reduced intake of ethanol and purines. The efficacy of supplementation with antioxidant vitamins (vitamin C and E) and selenium is currently under investigation.     

Hypertensive crises: diagnosis and management in the emergency room

Hypertensive crises are commonly observed in an emergency room. Regardless blood pressure values, hypertensive crises are classified in emergencies, characterized by life-threatening acute organ damage, and urgencies, with no evidence of acute or progressive organ injury. In an hypertensive emergency an appropriate and immediate management with parenteral drugs is mandatory, while in an hypertensive urgency blood pressure should be decreased within 24-48 h with orally active agents. This article reviews the spectrum of clinical syndromes that comprise hypertensive emergencies, focusing on specific drugs and therapeutic strategies available in the emergency department, based on current literature. Since no randomized prospective trials are available, an evidence-based approach recommending an optimal therapeutical management is not possible. Much of the therapy is therefore entirely empirical and based on the underlying pathophysiologic and clinical findings. Further studies are needed to clarify pathophysiologic mechanisms in order to optimize therapeutic approach.     

AGT and AT1R gene polymorphism in hypertensive heart disease

Left ventricular hypertrophy in patients with hypertension is a main clinical prognostic entity The aim of this study was to evaluate the association between mutations at genes of the renin-angiotensin system (RAS) and the development of left ventricular hypertrophy. Genetic polymorphism in angiotensinogen (AGT) and angiotensin Il-type 1 receptor (AT1R) genes was examined in a group of well-selected essential hypertensive caucasians with left ventricular involvement (n = 40) and a group of healthy unrelated caucasians (n = 150). Cardiac morphology and function were assessed by M-mode echocardiography. Molecular variants were analysed by amplified fragment length polymorphism. We observed a statistically significant difference both for AGT and AT1R genotype distribution in patients with left ventricular hypertrophy compared with controls (p<0.05). A 0.49 and 0.225 frequency was detected among cases for T and C mutant alleles at AGT and AT1R genes. Mutations in RAS genes are involved in the pathophysiology of target-organ damage in essential hypertension. Evaluation of molecular factors conferring a risk of developing heart involvement may lead to better identification of patient subgroups and more effective control of the clinical course.