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Background: It is well known that excessive alcohol consumption correlates with increased infectious disease. However, the molecular microbiological and immunological bases for ethanol-induced alterations in host defense are largely unknown., Methods: To study the effect of alcohol consumption on the pathogenesis of intracellular bacteria, we examined the relative susceptibility of alcohol-fed mice to a virulent strain of Listeria monocytogenes., Results: Based on lethal dose 50% determinations, survival curve analysis, and bacterial burden, alcohol consumption did not increase the susceptibility of C57BL/6, BALB/c, or A/J mice to systemic infection by strain EGD. Mice fed an ethanol-containing liquid diet showed slightly reduced susceptibility to Listeria. Alcohol consumption modestly decreased bacterial numbers in the spleen but not the liver. We also found that mice fed a typical solid diet were more sensitive to EGD infection than were animals fed a control liquid-containing diet., Conclusions: This study indicates that alcohol consumption may not always increase infectious disease progression.

Given the commitment of the Veterans Health Administration (VA) to excellent, compassionate end-of-life and palliative care and the VA's extensive system of academic affiliations with the nation's medical schools, there may exist an opportunity to accelerate acceptance of state-of-the-art training for improved care for dying patients. Accordingly, the VA has initiated a project to develop strategies for implementation of benchmark curricula for end-of-life and palliative care. With the support of the Robert Wood Johnson Foundation, this initiative has been implemented in 30 internal medicine residency training programs affiliated with the VA nationally.

Background and Purpose: Advanced age and hypertension have each been associated with changes in brain morphology and cognitive function. To investigate the interaction of age and hypertension with structural brain changes and neuropsychological performance in otherwise healthy patients with essential hypertension, we compared young-old (ages 56 to 69 years) and old-old (ages 70 to 84 years) hypertensive patients (n = 27) with 20 age-matched normotensive healthy control subjects, using quantitative volumetric MRI and a battery of neuropsychological tests., Methods: Quantitative regions of interest and segmentation analyses were applied to MRI scans of brain to measure volumes of different brain structures and of cerebrospinal fluid (CSF). Severity of white matter hyperintensities (WMHs) was qualitatively rated in the MRI scans. A battery of neuropsychological tests was administered to each subject., Results: The combined hypertensive group (young-old and old-old) had smaller volumes of thalamic nuclei and larger volumes of CSF in the cerebellum and temporal lobes and showed poorer performance in memory and language tests than did the control subjects. Main effects for age were significant in multiple brain regions of interest. The old-old hypertensive patients and age-matched control subjects demonstrated volume reductions in brain structures and increases in ventricular and peripheral CSF volumes compared with the younger subjects. There was a significant group x age-group interaction in temporal and occipital CSF, not related to WMH, with the old-old hypertensive patients having significantly larger CSF volumes in these regions than the young-old hypertensives and both healthy control groups., Conclusions: Hypertension exacerbates the morphological changes accompanying advanced age. Temporal and occipital regions appear most vulnerable to brain atrophy due to the interactive effects of age and hypertension.

Objectives: To examine cerebral metabolism, cognitive performance, and brain volumes in healthy controls and two groups of patients with probable Alzheimer's disease, one group with severe abnormalities of white matter (DAT+) and the other group with none, or minimal abnormalities (DAT-)., Methods: Neuropsychological tests, CT, MRI, quantitative MRI, and PET studies were carried out to allow comparison between the DAT+ and DAT- groups and the healthy controls., Results: Compared with the healthy controls, both demented groups had significantly reduced global and regional cerebral metabolism, significant brain atrophy, and significantly lower scores on neuropsychological testing. The DAT- patient group showed a pattern of parietal-temporal cerebral metabolic reductions and neuropsychological performance deficits typical of Alzheimer's disease. In addition, metabolism in the association neocortex (AD ratio) and measures of neuropsychological task performance were significantly correlated in the DAT- patient group. Comparison of DAT+ with DAT- patients showed a significantly higher ratio of parietal to whole brain glucose utilisation for the DAT+ group. Moreover, when comparing group z score differences from the healthy controls, the DAT+ group had, on average, smaller differences from controls in the frontal, parietal, and temporal regions than did the DAT- group. Discriminant analysis using metabolic ratios of the frontal, parietal, and temporal regions showed cerebral metabolic patterns to be significantly different among the DAT+, the DAT-, and the healthy controls. These differences were due primarily to relatively higher frontal, parietal, and temporal metabolic ratios in the DAT+ group which resulted in discriminant scores for the DAT+ group between the healthy controls and the DAT- group. Group mean scores on tests of neuropsychological performance were not significantly different between the DAT- and DAT+ patients. By contrast with the DAT- group, however, no significant correlations between the AD ratio and any neuropsychological task were seen in the DAT+ group. Multiple regression analysis showed significant between group differences in the relation between the AD ratio and neuropsychological scores on three tasks. The slopes of the relations between the AD ratio and memory scores (memory and freedom from distractability deviation quotient of the Wechsler adult intelligence scale (WMDQ)) also were significantly different for the two groups., Conclusions: Although multiple causes for abnormalities of white matter exist in patients with Alzheimer's disease, these data suggest that the presence of severe abnormalities of white matter indicate a second pathological process in the DAT+ patients. The DAT- patients showed the parietal-temporal metabolic deficits and correlations between association neocortical metabolism and neuropsychological task performance typical of patients with Alzheimer's disease. By contrast, the DAT+ group had a pattern of cerebral metabolism significantly different from healthy controls and DAT+ patients, as well as no significant correlations between metabolism in the association neocortex and neuropsychological performance. These differences probably reflect the superimposed pathology of the abnormalities of white matter which may exert their affect through disruption of long corticocortical pathways.

Using path analysis to determine the systems-level neural networks mediating specific tasks from regional cerebral blood flow (rCBF) data obtained by positron emission tomography (PET), we recently found in young subjects strong functional linkages during a face matching task along a right hemisphere ventral network including occipital, temporal, and frontal regions. In this study, PET data obtained during a face matching task from mildly affected patients with dementia of the Alzheimer type (DAT) and healthy matched controls showed that (1) the neural model obtained in young subjects provides a good fit to data from old subjects; (2) although the DAT patients could perform this task with the same accuracy as controls, they did not use the same functional network.

Objective: To assess the association of MRI white matter hyperintensities (WMHI) with cognitive performance, cerebral structure, and cerebral metabolism in 51 healthy individuals aged 19 to 91 years without cerebrovascular risk factors., Background: Abnormal white matter signals have been associated with brain atrophy, reduced cerebral blood flow, focal neurologic signs, gait disorder, and poorer neuropsychological test performance. Most studies of WMHI, however, include subjects with hypertension or other identifiable causes of cerebrovascular disease that may have an independent effect on brain structure and function. To assess brain changes associated with WMHI independent of cerebrovascular risk factors, we determined WMHI volume, brain volume, cerebral metabolism, and cognitive performance for a group of subjects free of medical illness. Regional cerebral metabolism and cognitive domains were also assessed to evaluate the possible role of frontal lobe dysfunction in subjects with WMHI., Design: Cross-sectional study of 51 very healthy subjects aged 19 to 91 years., Methods: WMHI, brain, and CSF volumes were determined by MRI segmentation. Neuropsychological tests were employed to assess multiple cognitive domains. Brain metabolism was determined from 18-fluoro-2-deoxy-D-glucose PET. Multivariate relations were tested with stepwise linear regression. Models included the potential confounders of age and education where appropriate., Results: The distribution of WMHI volume was bimodal, with five subjects having WMHI volumes beyond three SDs from the normally distributed population. A WMHI volume of greater than 0.5% of intracranial volume was considered abnormal. Within the multivariate models, WMHI volumes were significantly predictive of increased ventricular volume, reduced brain volume, and reduced cognitive scores. Subjects with greater than 0.5% WMHI volume also had significantly lower frontal lobe metabolism, significantly higher systolic blood pressure, significantly larger ventricular volume, and significantly lower scores on frontal lobe-mediated neuropsychological tests than age-matched controls., Conclusion: WMHI volume is associated with structural and functional brain changes even within a group of very healthy individuals. WMHI is associated with poorer frontal lobe cognitive function and, when severe, is accompanied by significantly reduced frontal lobe metabolism. Subjects with large WMHI volumes have significantly higher systolic blood pressure, brain atrophy, reduced cerebral metabolism, and lower scores on tests of frontal lobe function than age-matched controls. Large amounts of WMHI are, therefore, pathologic and may be related to elevated systolic blood pressure even when it is within the normal age-related range.

BACKGROUND AND METHODS. To determine the effects of hypertension on brain function, positron emission tomography (PET) studies using (18F)-2-fluoro-2-deoxy-D-glucose (FDG) were performed on a group of 17 otherwise healthy older hypertensive men (mean age +/- SD = 69 +/- 8 yr) and 25 age- and gender-matched controls. Subjects had medically treated essential hypertension for a minimum of 10 years (range = 10 to 24 yr) with no evidence of end-organ impairment from hypertension by routine clinical screening and by history. All hypertensive and control subjects were determined to be cognitively normal by extensive neuropsychological testing. The hypertensive subjects previously had been reported to have lateral ventricle enlargement and left hemisphere brain atrophy by quantitative MRI. PET data were analyzed using t-tests to look at group differences.

Ectopic atrial tachycardia (EAT) is usually considered as benign and easy to treat. The natural history of the disease, however, has not yet been clarified. The purpose of the study was to analyse its spontaneous evolution in a cohort of EAT patients and to define a predictive model of remission based on several factors. Between 1973 to 1989, 46 patients (25 male, 21 female), aged 38 +/- 18 years, entered the study. Clinically EAT was paroxysmal in 23 patients, permanent in 12 and repetitive in 11; six patients were asymptomatic. Thirty-five complained of palpitations; dyspnoea, dizziness and syncope were also reported less frequently. All patients underwent an electrophysiological study to clarify the mechanism of the arrhythmia and to localize its site of origin. In 15 patients no heart disease was documented. Five patients underwent surgery and were excluded from subsequent analysis. Seven patients were discharged without antiarrhythmic treatment. We defined remission as the absence of recurrence of EAT within 6 months from withdrawal of therapy. Logistic regression was applied to identify potential predictors of remission. Seven clinical and electrophysiological covariates were entered in the model; univariate and multivariate tests were performed, using the GLIM3 statistical package. During a follow-up period of 5.1 +/- 4.5 years, 14 instances of remission (34%) were observed in 5/22 patients with paroxysmal EAT, 4/8 patients with permanent EAT and 5/11 patients with repetitive EAT. Mean age of patients with remission was 25 +/- 14 years vs 45 +/- 15 years in the group without remission. No covariate had an independent predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: To study phosphorus and glucose metabolism in whole-brain slices of otherwise healthy patients with dementia of the Alzheimer type (DAT) and healthy controls., Design: We used proton nuclear magnetic resonance imaging phosphorus spectroscopy and positron emission tomography to study in vivo brain phosphorus and glucose metabolism., Patients: Whole-brain slice phosphorus metabolism was studied in nine drug free patients with mild to moderately severe dementia of the Alzheimer type (DAT) and in eight age- and sex-matched healthy controls. Mean ages (+/- SD) of the patients and controls were 60 +/- 10 years and 64 +/- 16 years, respectively. Positron emission tomography was used to study cerebral glucose metabolism in seven of the patients with DAT and seven of the healthy controls., Results: Patients with DAT had significant brain glucose hypometabolism compared with controls, but there was no significant group difference in any phosphorus metabolite concentration or ratio in the same volume of brain tissue. Also, within patients with DAT there was no correlation between any phosphorus metabolite concentration or ratio and either severity of dementia or glucose metabolism., Conclusions: We suggest glucose metabolism is reduced early in DAT (reflecting decreased basal synaptic functioning) and is unrelated to a rate limitation in glucose delivery, abnormal glucose metabolism, or abnormal coupling between oxidation and phosphorylation. Normal or near-normal levels of phosphorus metabolites are maintained in mild, moderate, and severe DAT. Therefore, altered high-energy phosphate levels are not a consequence of reduced glucose metabolism in DAT, and do not play a major role in the pathophysiology of the disorder, at least in whole-brain sections.

Correlational analysis of regional cerebral glucose metabolism (rCMRglc) obtained by high-resolution positron emission tomography (PET) has demonstrated reduced neocortical rCMRglc interactions in mildly/moderately demented patients with probable Alzheimer's disease (AD). Thus, identification of individual differences in patterns of rCMRglc interactions may be important for the early detection of AD, particularly among individuals at greater risk for developing AD (e.g., those with a family history of AD). Recently, a statistical procedure, using multiple regression and discriminant analysis, was developed to assess individual differences in patterns of rCMRglc interdependencies. We applied this new statistical procedure to resting rCMRglc PET data from mildly/moderately demented patients with probable AD and age/sex-matched controls. The aims of the study were to identify a discriminant function that would (a) distinguish patients from controls and (b) identify an AD pattern in an individual at risk for AD with isolated memory impairment whose initial PET scan showed minor abnormalities, but whose second scan showed parietal hypometabolism, coincident with further cognitive decline. Two discriminant functions, reflecting interactions involving regions most involved in reduced correlations in probable AD, correctly classified 87% of the patients and controls, and successfully identified the first scan of the at-risk individual as AD (probability > 0.70). The results suggest that this statistical approach may be useful for the early detection of AD.

A pattern of reduced cerebral metabolic rate for glucose (rCMRglc) has been shown by positron emission tomography (PET) in patients with dementia of the Alzheimer type. To verify if a similar rCMRglc pattern is present in subjects 'at risk' for Alzheimer's disease (AD), we used high-resolution PET to longitudinally study a subject with isolated memory impairment and a family history for autosomal dominant AD. Initial rCMRglc data did not reveal any consistent abnormality as compared to a group of sex- and age-matched healthy controls. However, 1 year later, a follow-up evaluation did reveal reduced parietal rCMRglc values coinciding with a worsening of cognitive impairment, which suggested that standard analyses of resting rCMRglc data may not be useful in the early diagnosis of AD. In contrast, when a previously determined discriminant function for distinguishing controls from AD patients was applied, the subject was correctly identified as an AD patient on both PET scans.

Menkes disease is a neurodegenerative disorder of copper metabolism. Because the enzyme dopamine-beta-hydroxylase requires copper to catalyze the conversion of dopamine to norepinephrine, we reasoned that patients with Menkes disease would have a neurochemical pattern similar to that seen in patients with congenital absence of dopamine-beta-hydroxylase, i.e., high levels of dopamine, the dopamine metabolite dihydroxyphenylacetic acid (DOPAC), and the catecholamine precursor dihydroxyphenylalanine (DOPA), and low levels of norepinephrine and its neuronal metabolite dihydroxyphenylglycol (DHPG). We measured plasma and cerebrospinal fluid (CSF) levels of catechols in 10 patients ranging in age from 9 days to 27 months. In contrast to patients with congenital absence of dopamine-beta-hydroxylase, norepinephrine levels were normal in plasma of 4 Menkes patients and in CSF of all 10 patients. However, the ratios of DOPA:DHPG and DOPAC:DHPG in plasma and CSF of Menkes patients were invariably increased beyond the ranges of control values. These neurochemical findings indicate partial deficiency of dopamine-beta-hydroxylase in Menkes patients, with compensatory increases in catecholamine biosynthesis in sympathetic nerves and in the brain. Increased tyrosine hydroxylation and increased exocytotic release of norepinephrine may be responsible for preservation of plasma and CSF norepinephrine levels in Menkes patients. The abnormal neurochemical pattern, including high ratios of DOPA:DHPG and DOPAC:DHPG, may serve as a biochemical marker for Menkes disease and provide a baseline against which the influence of proposed therapies can be judged.

Changes in regional cerebral blood flow (rCBF) associated with a face-matching task were examined using positron emission tomography (PET) and H2(15)O in 7 patients with mild-moderate dementia of the Alzheimer type (DAT) and in 8 healthy age-matched controls. rCBF was normalized to whole brain flow and pixel-by-pixel difference images were computed by contrasting flow during a control task to flow during face matching. Both patients and controls showed bilateral rCBF increases in occipitotemporal extrastriate cortex during face matching. The magnitude of these increases was not significantly different between the groups. In addition, the patients showed greater rCBF activation in regions of occipital and frontal cortex. These results show that early in the course of DAT, patients utilize extrastriate cortex to perform a visuoperceptual task, as do control subjects but also show rCBF increases in additional cortical areas. Activation of these additional areas of cortex in the patients may reflect an increased attentional load during face matching due to their reduced cognitive capacity.

Background and Methods: In this study we used two different approaches in radiofrequency catheter ablation (RFCA) of the left free wall atrioventricular accessory pathway (AP): the retrograde transaortic (TAo) approach and the transseptal (TSA) one. Our aim was to evaluate the success rate and the duration of the two procedures. From May 1, 1991 to April 30, 1992, 33 pts (23 M, 10 F; mean age 38 +/- 16 years, range 14-66) with left free wall atrioventricular AP were selected among a 57 patient population, in which RFCA was performed for arrhythmias related to the AP. In 20/33 pts (61%) stable ventricular pre-excitation was present, while in 4/33 (12%) it was intermittent; in the remaining 9/33 pts (27%) only retrograde conduction through the AP was documented. In the majority of the pts (26/33) a diagnostic electrophysiologic study was performed immediately before the ablation procedure, during the same EP test. A 7 F steerable large tip catheter was used for energy delivery. In 8/33 pts, RFCA was performed by using only the TAo approach; other 7/33 pts underwent RFCA with a TSA technique after one completely unsuccessful retrograde TAo ablation and, in the remaining 18/33 pts, the TSA approach was used electively and continuously from January 1992. Overall, the TAo procedure has been carried out in 15 cases, while the TSA one in 25 cases. In the latter group, the ablation catheter was positioned against the left atrioventricular groove through a patent foramen ovale in 5/25 cases (20%), while a TSA puncture was needed in the remaining 20 cases. After successful ablation, the observation period was prolonged up to 60 min., Results: Complete AP ablation was achieved in 31/33 pts (94%), while the remaining 2 pts underwent surgical cryo-ablation after unsuccessful TAo procedure. Among the three different subsets of pts, the success rate was as follows: 40% (6/15 cases) by using TAo technique, 100% (7/7 cases) by TSA after one unsuccessful attempt with the TAo technique, and 94% (17/18 cases) after single elective TSA; in the only case where the first elective TSA procedure failed, a second attempt was successful. The duration of the whole electrophysiologic test was 4.0 +/- 1.3 hours for the TAo approach vs 3.3 +/- 0.9 hours for the TSA one (p < 0.05). The mean fluoroscopy time was significantly (p < 0.05) shorter in pts who underwent elective TSA (43 +/- 27 min), than in pts who underwent only TAo approach (68 +/- 42 min) or both TAo and TSA approach (157 +/- 54 min). No complication during or after the procedure was observed in any case., Conclusions: In RFCA of left free wall atrioventricular APs, the TSA approach seems to be as safe as the TAo approach. In this preliminary experience, the success rate and the short duration of single elective TSA procedure suggest that this can be used as a first-choice approach in these pts.

A correlational analysis of normalized (regional to whole-brain) regional cerebral metabolic rates for glucose obtained in the 'resting' state (eyes covered, ears plugged) using [18F]fluorodeoxyglucose, demonstrated differences between old and young women in patterns of functional associations. Fifteen healthy young (age less than 40 years) and 17 healthy old women (age greater than 64 years) were scanned with a Scanditronix PC1024-7B tomograph. The brain was divided into 65 regions of interest. The old women had fewer and less positive correlations between pairs of metabolic ratios in the frontal and parietal cortices. The results suggest an age-related reduction in frontal and parietal functional interactions in the 'resting' state that is consistent with a prior correlation analysis using a low resolution ECAT II scanner on young and old men. Reduced functional interactions may reflect age-related cognitive changes.

To determine whether hypertension, the predominant risk factor for stroke and vascular dementia, is associated with brain atrophy, magnetic resonance imaging (MRI) scans were performed to quantify brain volumes and cerebrospinal fluid spaces. Eighteen otherwise healthy, cognitively normal older hypertensive men (mean +/- SD age, 69 +/- 8 years, duration of hypertension 10-35 years) and 17 age-matched healthy, normotensive male control subjects were studied in a cross-sectional design. Axial proton-density image slices were analyzed using region-of-interest and segmentation analyses. The hypertensive subjects had significantly larger mean volumes of the right and left lateral ventricles (p less than 0.05, both absolute volume and volume normalized to intracranial volume) and a significantly smaller normalized mean left hemisphere brain volume (p less than 0.05) with a trend toward significance for a smaller normalized mean right hemisphere volume (p less than 0.09). Four hypertensive subjects and one healthy control subject were found to have severe periventricular hyperintensities on T2-weighted MRI images. When data for these subjects were removed from the analyses, the normalized lateral ventricle volumes remained significantly larger in the hypertensive group. Lateral ventricle enlargement was not related to age or use of diuretics in the hypertensive group nor to duration of hypertension between 10 and 24 years. Our findings suggest that long-standing hypertension results in structural changes in the brain. Longitudinal studies will determine whether MRI-associated changes are progressive and if such changes identify hypertensive subjects at increased risk for clinically apparent brain dysfunction.

In order to evaluate the effects of increases of sympathetic tone in ventricular response during atrial fibrillation and in the relationship between the accessory pathway effective refractory period (ERP) and ventricular rate during atrial fibrillation, 20 male subjects, aged 19 +/- 6 years, were studied electrophysiologically in basal conditions, after isoproterenol infusion (2-4 micrograms/min) and during submaximal bicycle exercise test, at a constant workload equal to that which increases the sinus rate to the same extent (140 beats/min) induced by isoproterenol infusion. Accessory pathway ERP was evaluated at the same driven rate (150 beats/min) in both instances. In the control study as during both tests atrial fibrillation paroxysms were induced by burst stimulation. In control conditions the rate increase from 100 to 150 beats/min induced a reduction of accessory pathway ERP from 266 +/- 27 msec to 244 +/- 22 msec (P less than 0.005). At the same driven rate of 150 beats/min, isoproterenol infusion and exercise test induced a more marked shortening of accessory pathway ERP to 211 +/- 28 msec (P less than 0.005) and to 214 +/- 29 msec (P less than 0.005), respectively. Atrial fibrillation paroxysms lasting more than 10 seconds were induced in 20/20 cases in the control study, in 15/20 during isoproterenol infusion and in 13/19 cases during exercise test. The shortest cycle length during atrial fibrillation was reduced from a basal value of 253 +/- 72 msec to 204 +/- 27 msec (P less than 0.05) during isoproterenol infusion and to 236 +/- 32 msec (NS) during exercise test.(ABSTRACT TRUNCATED AT 250 WORDS)

In patients with supraventricular tachyarrhythmias refractory to medical therapy, transcatheter ablation (TA) is necessary. From January 1990, in 27 patients with nodal tachycardia and 6 with atrial fibrillation or flutter, referred to our institution for electrophysiologic evaluation, TA by radiofrequency (RF) was performed, respectively for atrioventricular (AV) junction modulation and total AV junction ablation. In all these cases, a total refractoriness to several antiarrhythmic drugs alone or in combination had been observed. The RF current, generated by the Osypka HAT 100 device, was administered through a tripolar USCI 7 F catheter. The ideal site for energy delivery was defined on the basis of a mapping, performed in the AV junction area to find out the most premature retrograde atrial activation. Local atrial activation time was evaluated during nodal tachycardia by delivering a premature ventricular extrastimulus to discover the atrial deflection from the ventricular one. In the selected area, 5 applications (range 1-12) of 20-25 W power RF energy for 5-30 s were delivered on average. A complete prevention of nodal tachycardia was achieved in 26/27 patients (96.2%). Only in 2 patients (7.4%) a total AV block was induced. The pre- and post-procedure values are as follows: AH = pre 71 +/- 18, post 113.2 +/- 53; HV = pre 46.4 +/- 8, post 48 +/- 7; anterograde Wenckebach point = pre 352 +/- 56, post 389 +/- 91; retrograde Wenckebach point = pre 338 +/- 75, post 419 +/- 61. In 13/27 cases the AH interval was normal after RF application. The retrograde conduction was worsened in all patients and totally abolished in 12/27.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgery can provide treatment for supraventricular tachyarrhythmias without operative risk and with a definite improvement of patients' quality of life. Ectopic atrial tachycardia is a rare but invalidating arrhythmia that may lead to cardiomyopathy: intraoperative mapping is necessary for the location of the location of the ectopic focus; in our experience, surgical, cryothermal or isolation ablation of the area were effective in 9 patients out of 9, with regression of the cardiomyopathy. Atrioventricular node reentry tachycardia is a reentry tachycardia which is often associated with Wolff-Parkinson-White syndrome and is amenable to surgical treatment. Discrete cryolesions around the Koch triangle are effective in interrupting the atrial inputs to the atrioventricular node and therefore the reentry mechanism: in our experience, 7 patients were successfully treated without operative mortality: 3 patients underwent surgical ablation of Kent bundles as well. Atrial fibrillation is not based on a well-defined mechanism, and therefore does not permit an electrically-guided surgical treatment. However, in case of atrial septal defect it is possible to isolate the enlarged right atrium in order to allow sinus rhythm to activate the left atrium and ventricles.(ABSTRACT TRUNCATED AT 250 WORDS)

The article deals with the modern approaches to the treatment of supraventricular tachycardia . The authors analyse the results of operations in ectopic atrial tachycardias, the Wolff-Parkinson-White syndrome, modal re-entry tachycardias, and atrial fibrillation . The last-named is of most interest because the authors possess experience in a new operation for isolation of the internodal tracts. In all conditions the authors obtained convincing evidence on the efficacy of modern surgical treatment in supraventricular tachycardias.

In patients with nodal tachycardia refractory to medical therapy, transcatheter or surgical ablation is necessary. From January 1989 to December 1990, in 26/42 patients with nodal tachycardia, referred to our institution for electrophysiologic evaluation, transcatheter ablation by radiofrequency (20 patients) or surgical ablation by perinodal cryo (6 patients) was performed. In all these cases, a total refractoriness to several antiarrhythmic drugs alone or in association had been observed. The radiofrequency current, generated by the Osypka HAT 100 device, was administered through a tripolar USCI 7 F catheter. The ideal site for energy delivery was defined on the basis of a mapping, performed in the A-V junction area. In order to find out the most premature retrograde atrial activation, the following areas were explored: right bundle, atrial His bundle, peri-nodal region, proximal His bundle and coronary sinus ostium. Local atrial activation time was evaluated during nodal tachycardia by delivering a premature ventricular extrastimulus to discover the atrial deflection from the ventricular one. In the selected area, 5 applications (range 1-12) of 20-25 W power radiofrequency energy for 5-30 s were delivered on average. A complete prevention of nodal tachycardia was achieved in 18/20 patients (90%). Only in 2 patients a total A-V block was induced. The pre- and post-procedure values are as follows: AH: pre 71 +/- 19, post 113.6 +/- 50; HV: pre 45.5 +/- 8, post 47 +/- 6; aWP: pre 353 +/- 57, post 391 +/- 87; rWP: pre 322 +/- 58, post 411 +/- 58. In 10/18 cases the AH interval was normal after radiofrequency application.(ABSTRACT TRUNCATED AT 250 WORDS)

Forty-seven patients with probable dementia of the Alzheimer type (DAT) and 30 healthy age-matched controls were scanned using [18F]-2-fluoro-2-deoxy-D-glucose on a Scanditronix PC 1024-7B tomograph (inplane resolution = 6 mm, axial resolution = 10 mm). Patients and controls were scanned in the resting state with their eyes patched and ears occluded. The regional cerebral metabolic rates for glucose (rCMRglc) in most major neocortical and subcortical gray matter regions, and certain metabolic ratios (rCMRglc/ calcarine rCMRglc), quantitatively discriminated even the mildly demented patients from healthy controls. The association neocortices showed metabolic abnormalities that were more severe than those in the sensorimotor and calcarine regions. All demented groups showed significant neuropsychological disturbances when compared to healthy controls. These data demonstrated widespread metabolic disturbances, particularly in the association areas, relatively early in Alzheimer's disease, and more profound involvement with disease progression.

Positron emission tomography (PET) was used with 18fluorodeoxyglucose to see if gender differences in resting cerebral glucose utilization could be detected. Thirty-two healthy subjects (15 women and 17 men; age range: 21-38 yr) were examined using a high-resolution PET scanner to determine the regional cerebral metabolic rate for glucose (CMRglc) in 65 gray matter regions of interest. Whole brain CMRglc did not differ significantly between the two genders, nor did any of the regional CMRglc values. Only 1 of 65 ratios of regional-to-whole brain CMRglc differed significantly between men and women, which is consistent with chance. These results indicate that there are no differences in resting regional cerebral glucose utilization between young men and women.

Acute cardiac rejection, syndrome X, and arterial hypertension can induce small vessel damage and, therefore, restriction of coronary reserve in the presence of normal epicardial coronary arteries. A characteristic response pattern to dipyridamole (DIP) infusion has been previously described in syndrome X and arterial hypertension: ST segment depression without any measurable systolic dysfunction. The aim of this study was to establish whether acute cardiac rejection might induce electrocardiographic alterations during DIP infusion. Changes in the 12-lead electrocardiogram and two-dimensional echocardiogram during high-dose DIP infusion (up to 0.84 mg/kg in 10 minutes) were evaluated within 24 hours of endomyocardial biopsy in 14 transplanted patients. A total of 47 biopsy-controlled DIP studies were performed within 5 weeks after cardiac transplantation. For each patient, at least 7 days elapsed between two consecutive studies. Electrocardiographic and echocardiographic tracings were analyzed without prior knowledge of endomyocardial biopsy findings. No remarkable side effects occurred in any case, so that the DIP study could be completed in all patients. A diagnostic (greater than 0.1 mV) ST segment depression was found in 11 studies. The sensitivity and specificity of DIP-induced ST segment depression for the detection of biopsy-proven acute rejection were 72% and 94%, respectively. These data show that DIP stress is feasible and safe in transplanted patients and that acute cardiac rejection can be accompanied by DIP-induced ST segment depression without detectable impairment in systolic function. These changes might provide noninvasive markers for surveillance of rejection.

Fifty-six patients with active Prinzmetal's variant angina were studied to determine the incidence and clinical significance of ventricular tachyarrhythmias and the correlation between arrhythmias and degree and time course of S-T segment changes during the ischemic attacks. Twenty-nine patients (Group I) had no ventricular arrhythmias in any of the 1,083 recorded episodes, while 27 patients (Group II) developed arrhythmias in 18% of the attacks. No significant differences in clinical, electrocardiographic, angiographic, or hemodynamic findings could be found between the 2 groups. In 23 of the 27 Group II patients, ventricular arrhythmias developed during maximal S-T segment elevation (occlusion arrhythmias), while in 10 they occurred during resolution of S-T segment changes (reperfusion arrhythmias); 6 of the latter patients also had occlusion arrhythmias. Eight of the 23 patients with occlusion arrhythmias and 6 of the 10 with reperfusion arrhythmias had ventricular fibrillation or ventricular tachycardia. Maximal S-T segment elevation was significantly greater (p less than 0.001) in patients with occlusion arrhythmias than in those without arrhythmias. The episodes with reperfusion arrhythmias were significantly longer (p less than 0.001) and showed a significantly greater S-T segment elevation (p less than 0.001) than those without arrhythmias in Group I patients. This study shows that significant ventricular tachyarrhythmias develop during ischemic attacks in about 50% of patients with active variant angina; clinical and angiographic features are not useful in distinguishing patients with arrhythmias from the others. Our findings suggest that in variant angina ventricular arrhythmias may be due to the effects of both coronary artery occlusion and reperfusion; both types of arrhythmias are correlated with the severity of ischemia, as measured by the degree of S-T segment elevation. Reperfusion arrhythmias also appear to be correlated with the duration of ischemia.

The duration of effect of single oral doses of 10 and 20 mg of nifedipine was studied in 10 patients with angiographically proven coronary artery disease and with stable exercise-induced angina pectoris. In a randomized double-blind manner exercise tests were carried out 1 hour before and 1, 2, 4 and 6 h after the administration of placebo, nifedipine 10 mg(N10) and nifedipine 20 mg(N20). Compared with the placebo both N10 and N20 produced a statistically significant increase in exercise tolerance at 1(P less than 0.05), 2(P less than 0.01), 4(P less than 0.01) and 6(P less than 0.05) hours after N10 and at 1(P less than 0.01), 2(P less than 0.01), 4(P less than 0.01) and 6(P less than 0.05) hours after N20. At peak exercise the product of heart rate X systolic blood pressure (RPP) was significantly increased compared with placebo at 2, 4 and 6 h after N10 and at 2, 4 and 6 h after N20 with maximal ST-segment depression unchanged. At the same duration of exercise at which angina had occurred during control studies the RPP was unaffected by nifedipine while a statistically significant reduction of ST-segment depression was seen at 1, 2 and 4 h after N10 and at 1, 2 and 4 h after N20. Direct measurements of great cardiac vein flow during exercise in two patients showed that nifedipine is effective in preventing the abnormal increase of exercise-induced coronary tone in the area supplied by stenotic vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

A patient with intermittent tachycardia-dependent left posterior hemiblock is reported. Electrocardiographic patterns of complete and incomplete block were documented. Identification of the electrocardiographic characteristics of intraventricular conduction defects is aided when they are intermittent. The difficulty in diagnosing incomplete left posterior hemiblock, and the possible masking of the signs of previous inferior infarction by left posterior hemiblock are emphasised.

Presence of rate-dependent (RD) intraventricular conduction defects (IVCD) was documented by inducing variations in heart rate in 30 acute myocardial infarction (AMI) patients (10 right bundle branch block, six left bundle branch block, 13 left anterior hemiblocks, and two left posterior hemiblocks). Five IVCDs were tachycardia-dependent (TD), 20 were bradycardia-dependent (BD), and six were both TD and BD. In TD blocks shortest cycles showing normal intraventricular conduction ranged from 410 to 1330 msec (697 +/- 84 SE); in BD blocks longest cycles with normal intraventricular conduction ranged from 450 to 1450 msec (962 +/- 52). In 60% of cases intermittent incomplete RD blocks were also present. In one patients RD-IVCD intermittency remained until discharge; in the others it lasted from 4 minutes to 10 days. Afterwards 19 RD-IVCDs disappeared and four became stable; six patients died during RD-IVCD intermittency period. Disappearance of RD block was preceded by gradual reduction in cycle length showing TD block and lengthening of cycles stopped beats with BD block. Serial observation of RD-IVCDs provides information about sequence of electrophysiologic effects on the intraventricular conduction system in clinical AMI.

Myocardial ischemia, particularly when transmural as in variant angina pectoris, may be associated with ventricular tachycardia, ventricular fibrillation and paroxysmal atrioventricular block (15%). Syncope (7%) and sudden death (3%) due to these malignant arrhythmias are sometimes a unique marker of myocardial ischemia. Two-hundred fifty-four patients (220 males and 34 females), aged 5 +/- 9 years with transmural myocardial ischemia related to coronary artery spasm, were studied. Particular attention was paid to the role of syncopal attacks as unique clinical manifestation of silent ischemia. Patients examined were divided into 3 Groups. Group 1 includes 5/254 (2%) patients with atrial fibrillation during acute ischemia. Group 2 was divided into four subgroups: subgroup A includes 17/254 (7%) patients with syncopal attacks due to malignant arrhythmias (ventricular tachycardia and advanced A-V block); subgroup B, 15/254 (6%) patients with documented malignant arrhythmias, without syncopal attacks; subgroup C, 7/254 (3%) with ventricular fibrillation during acute ischemia and subgroup D, 18/254 (7%) patients with history of syncopal attacks without documented arrhythmias during hospital observation. Group 3 includes 17/254 (7%) patients with left anterior hemiblock in basal condition, 7/254 (3%) patients with left anterior hemiblock and one left posterior hemiblock during acute ischemia and one patient with right bundle branch block during acute ischemia. Syncopal symptoms are present in many of these cases of angina pectoris; paroxysmal A-V block is documented in nearly half of the cases with syncope (65%); ventricular tachycardia is frequently demonstrated during ischemia but leads to syncope in only a few cases; patients with syncope do not present specific clinical features.(ABSTRACT TRUNCATED AT 250 WORDS)

The value of the dipyridamole test (0.75 mg/kg i.v.) in the diagnosis of angina pectoris was studied in 54 patients with angina pectoris (35 with angina on effort associated or not associated with rest angina and 19 with angina only at rest) and in 12 control subjects. The test induced electrocardiographic signs of ischemia (positive test) in 74% of patients with angina on effort, while it was negative in all cases with angina only at rest and in control subjects. All anginal patients with normal coronary arteries or less than 50% stenosis had a negative test; a positive response was observed in 36, 79 and 60% of cases with one-, two-or three-vessel disease, respectively. Hemodynamic changes with a marked arteriolar vasodilatation were observed both in the negative and in the positive tests. In the positive tests no significant change of double product, blood pressure and left ventricular end-diastolic pressure occurred before ischemia appeared. The results of the study show that dipyridamole as a diagnostic test in angina pectoris has a high specificity but a lower sensitivity than exercise test. The hemodynamic and eletrocardiographic findings in the positive tests suggest that dipyridamole-induced ischemia is due to a flow maldistribution with selective subendocardial ischemia secondary to the coronary arteriolar dilatation caused by the drug.

Since the introduction and development of mapping methods in clinical practice, some arrhythmias can now be treated surgically. We studied an automatized method of epicardial mapping necessitating only a single ventricular complex for the definition of epicardial activation; the signal was acquired from 35 monopolar electrodes spread out over the whole of the ventricular epicardium or concentrated in the zone of epicardial break through to localise its site more accurately. The acquisition, elaboration and tracing of these maps were performed with a computer; the activation can be presented as isochrones or isopotentials. The main value of this method of automatic mapping is the possibility of studying irregular arrhythmias whose potentials are difficult to obtain beat manually. This method has already been applied to 21 patients with ventricular tachycardia unresponsive to medical treatment and referred for surgery.

Hyperventilation and ergonovine tests were carried out in a group of 30 patients with variant angina to assess the sensitivity of the 2 tests and to correlate the response with spontaneous disease activity. Hyperventilation produced a positive response in 83% (25 of 30) and ergonovine in 93% (28 of 30) of the patients. After hyperventilation 22 of 25 showed ST-segment elevation, 2 ST depression and 1 T-wave pseudonormalization; after ergonovine ST-segment elevation developed in 23 patients, ST depression in 4 and T-wave pseudonormalization in 1. In all cases the electrocardiographic changes occurred in the same leads as during the spontaneous attacks. The incidence of chest pain and ventricular arrhythmias was similar during both tests; spontaneous remission of ischemia, however, was more frequent (48 vs 14%) after hyperventilation than after ergonovine. Acute ischemia developed at a mean of 218 +/- 112 seconds after the end of hyperventilation in 19 of 25 positive tests; at that time double product was not significantly different from basal values. The sensitivity of hyperventilation was similar (95 vs 100%) to ergonovine in the patients with greater than or equal to 1 daily attack, while in those with less than 1 daily attack the sensitivity of hyperventilation decreased to 55% compared to 77% with ergonovine. Thus, in variant angina the sensitivity of both tests correlates with disease activity. Hyperventilation is a safe provocative test with a sensitivity similar to ergonovine in patients with active disease; however, in patients with sporadic attacks hyperventilation has a lower sensitivity than ergonovine and therefore a limited diagnostic value.

Malignant ventricular arrhythmias appearing during acute myocardial ischaemia, are the most frequent mechanism of sudden death. ST-T alternans is the result of an intraischaemic conduction delay and is frequently associated with those potentially lethal arrhythmias. In fact, such a phenomenon was seen in 35% of 46/86 patients with Prinzmetal's variant angina who showed ventricular arrhythmias during ischaemia, while it was never observed in the remaining 40 patients without arrhythmias during ischaemia. Therefore ST-segment alternans should be considered a reliable marker of the possible occurrence of ventricular arrhythmias during myocardial ischaemia. ST-T-segment alternans is associated with R alternans, as clearly demonstrated by thoracic maps, and this phenomenon is due to a 2:1 intraischaemic block. The patients with Prinzmetal's variant angina who present ventricular arrhythmias during ischaemia, show a more prominent increase of the positive area of the QRS (411.75 +/- 102.5 vs 294.05 +/- 80.3 mu volts ms), that is, a more relevant intraischaemic conduction delay. The effects of different pretreatments (lidocaine, propranolol and diltiazem) on arrhythmias related to vasospastic myocardial ischaemia induced by ergonovine maleate, were evaluated in four patients with Prinzmetal's variant angina. As in experimental observations, neither a 'pure' antiarrhythmic agent like lidocaine, nor a betablocking agent like propranolol, prevented acute ischaemic ventricular arrhythmias. Only the calcium antagonist, diltiazem, seemed to prevent such arrhythmias. However, these findings necessitate further confirmation.

Eighteen patients with variant angina, a positive ergonovine test, and a favorable response to calcium antagonists were studied by serial ergonovine tests and Holter monitoring to assess the long-term changes in response to ergonovine and the relationship with the spontaneous activity of the disease. The number of patients with a positive test decreased from 18 of 18 in the acute phase to 12 of 18 (66%) at 3 months, 10 of 17 (59%) at 6 months, and five of 17 (29%) at 12 months. The mean dose level of ergonovine associated with a positive response and the percentage of positive tests with ST segment depression increased progressively during follow-up. The results of the ergonovine test were well correlated with the spontaneous activity of the disease in 94%, 83%, 76%, and 71% of the patients at initial observation and at 3, 6 and 12 months, respectively. Thus in patients with variant angina and a favorable response to calcium antagonists, a time-related decrease in sensitivity to ergonovine develops during follow-up. In most patients the response to ergonovine is well correlated with the spontaneous activity of the disease; thus the ergonovine test may be a useful tool in the assessment of the natural evolution of vasospastic angina.