Search

Early diagnosis of Alzheimer's disease (AD) is becoming an increasingly important healthcare concern. Prior approaches analyzing event-related potentials (ERPs) had varying degrees of success, primarily due to smaller study cohorts, and the inherent difficulty of the problem. A new effort using multiresolution analysis of ERPs is described. Distinctions of this study include analyzing a larger cohort, comparing different wavelets and different frequency bands, using ensemble-based decisions and, most importantly, aiming the earliest possible diagnosis of the disease. Surprising yet promising outcomes indicate that ERPs in response to novel sounds of oddball paradigm may be more reliable as a biomarker than the more commonly used responses to target sounds.

The diagnosis of Alzheimer's disease (AD) at an early stage is a major concern due to growing number of elderly population affected by the disease, as well as the lack of a standard diagnosis procedure available to community clinics. Recent studies have used wavelets and other signal processing methods to analyze EEG signals in an attempt to find a non-invasive biomarker for AD. These studies had varying degrees of success, in part due to small cohort size. In this study, multiresolution wavelet analysis is performed on event related potentials of the EEGs of a relatively larger cohort of 44 patients. Particular emphasis was on diagnosis at the earliest stage and feasibility of implementation in a community health clinic setting. Extracted features were then used to train an ensemble of classifiers based stacked generalization approach. We describe the approach, and present our promising preliminary results.

With the number of the elderly population affected by Alzheimer's disease (AD) rising, the need to find an accurate, inexpensive and non-intrusive procedure that can be made available to community healthcare providers for early diagnosis of Alzheimer's disease is becoming more and more urgent as a major health concern. Several recent studies have looked at analyzing electroencephalogram signals through the use of wavelets and neural networks. In this study, multiresolution wavelet analysis, coupled with the ensemble of classifiers based boosting algorithm is used on the P300 component of the event related potentials (ERP) to determine the feasibility of the approach as a diagnostic tool for early diagnosis of AD. The technique and its promising initial results are presented.

We describe an ensemble of classifiers based data fusion approach to combine information from two sources, believed to contain complimentary information, for early diagnosis of Alzheimer's disease. Specifically, we use the event related potentials recorded from the Pz and Cz electrodes of the EEG, which are further analyzed using multiresolution wavelet analysis. The proposed data fusion approach includes generating multiple classifiers trained with strategically selected subsets of the training data from each source, which are then combined through a weighted majority voting. Several factors set this study apart from similar prior efforts: we use a larger cohort, specifically target early diagnosis of the disease, use an ensemble based approach rather then a single classifier, and most importantly, we combine information from multiple sources, rather then using a single modality. We present promising results obtained from the first 35 (of 80) patients whose data are analyzed thus far.

Purpose: Since the management of atrial fibrillation may be difficult in the individual patient, our purpose was to develop simple clinical recommendations to help the general internist manage this common clinical problem., Data Sources: Systematic review of the literature with evaluation of data-related evidence and framing of graded recommendations., Data Synthesis: Atrial fibrillation affects some 1% of the population in Western countries and is linked to a significant increase in morbidity and mortality. The management of atrial fibrillation requires individualised evaluation of the risks and benefits of therapeutic modalities, relying whenever possible on simple and validated tools. The two main points requiring a decision in clinical management are 1) whether or not to implement thromboembolic prevention therapy, and 2) whether preference should be given to a "rate control" or "rhythm control" strategy. Thromboembolic prophylaxis should be prescribed after individualised risk assessment: for patients at risk, oral anticoagulation with warfarin decreases the rate of embolic complications by 60% and aspirin by 20%, at the expense of an increased incidence of haemorrhagic complications. "Rate control" and "rhythm control" strategies are probably equivalent, and the choice should also be made on an individualised basis. To assist the physician in making his choices for the care of an atrial fibrillation patient we propose specific tables and algorithms, with graded recommendations., Conclusions: On the evidence of data from the literature we propose simple algorithms and tables for the clinical management of atrial fibrillation in the individual patient.

Early diagnosis of Alzheimer's disease is a major concern due to large portions of the elderly population it affects and the lack of a standard and effective diagnosis procedure that is available to community healthcare providers. Several studies have been performed using wavelets or other signal processing methods to analyze EEG signals in an attempt to find a biomarker for Alzheimer's disease, which showed varying degrees of success. To date, in part due to lack of a large study cohort, the results of these studies remain largely inconclusive. In this paper, we describe a new effort using multiresolution wavelet analysis on event related potentials of the EEG to investigate whether such a link can be established. Several factors sets this study apart from similar prior efforts: We use a larger cohort, compare different mother wavelets, rather then using one generic wavelet, and most importantly, we specifically target early diagnosis of the disease. Our multi-year effort will include a total of 80 patients, whose ERPs will be analyzed with several different wavelets and automated classifiers. We present some preliminary, yet very promising, results on analysis of EEGs of the first 28 patients analyzed thus far using two types of wavelets.

Cx37 is a member of the connexin family of gap junction proteins, whose distribution in heart remains controversial. We have generated novel antibodies against Cx37 to investigate this distribution during normal and pathological development in mouse. Using these affinity-purified antibodies, we have detected Cx37 in hearts and aortas of mouse embryos from day 11 ed. onwards. Immunostaining revealed that during prenatal development Cx37 predominated in endothelial and endocardial cells but was also detectable in small amounts in the trabeculated and compact layers of ventricular myocardium, as well as in the mesenchyme of conotruncal ridges and atrioventricular cushions. Cx37 was also differentially expressed in the ascending and descending portions of the embryonic aorta, according to a pattern which differed in the three layers of the vessel wall. Cx37 distribution was altered in both heart and aorta of mice that had been exposed to all-trans retinoic acid at the beginning of foetal development, whether or not these animals subsequently developed a transposition of great arteries. The data indicate that Cx37 is widely distributed in multiple compartments of cardiovascular system, in patterns which are modulated during development, by retinoic acid., (Copyright 2000 Wiley-Liss, Inc.)

Lengthening of repolarization and refractoriness occurs in hypothyroidism; it is associated with a reduced probability of arrhythmias, with the converse occurring in hyperthyroidism. Because the QT interval and its circadian rhythmicity relative to heart rate is poorly defined in man, we used our new computer-assisted technique to measure QT interval in our analysis of 24-hour Holter tapes before and after (8 to 12 weeks) thyroxine (T4) replacement in 10 patients with hypothyroidism; the findings were compared to those in 6 normal control subjects. QTc interval was prolonged (p less than 0.02) and heart rate decreased (p less than 0.005) during the hypothyroid state. Data were analyzed for circadian rhythmicity by repeated-measures analysis. Circadian variation in QTc and heart rate was statistically significant during hypothyroid and euthyroid states (p less than 0.001) as well as in control subjects, but the circadian rhythmicity of QTc interval and heart rate were out of phase; the maximum prolongation of QTc occurred between midnight and 6 A.M., at a time when heart was at its lowest. QTc interval remained significantly prolonged after 8 to 12 weeks of T4 replacement, when biochemical indexes of hypothyroidism had returned to normal values. The computer-assisted QTc interval determination technique that we used, and our data on the circadian rhythmicity of QTc and heart rate, have significant implications for the development of new class III antiarrhythmic agents.

Nine hypothyroid patients had blood pressure and pulse rate responses to the alpha-adrenergic agonist phenylephrine measured before [T4 index, 45.045 +/- 9.009 nmol/L (mean +/- SEM); TSH, 57.1 +/- 23.6 mU/L] and after 4 +/- 0.5 months of thyroid replacement therapy (T4 index, 141.570 +/- 29.601 nmol/L; TSH, 2.6 +/- 1.0 mU/L). Hypothyroid patients had a smaller blood pressure increment and heart rate decrement at both 66.7 and 100 micrograms/min infusion rates of phenylephrine. Furthermore, the slope of the dose-response curves for systolic (2.06 +/- 0.22 vs. 1.32 +/- 0.19; P less than 0.01) and diastolic (1.04 +/- 0.18 vs. 0.62 +/- 0.08; P less than 0.01) blood pressures were significantly greater after thyroid replacement therapy. Pulse rate changes remained proportional to blood pressure changes in hypothyroid patients, so there was no change in baroreflex sensitivity. Plasma norepinephrine levels were higher before than after thyroid replacement (2.41 +/- 0.28 vs. 1.82 +/- 0.29 nmol/L, respectively; P less than 0.01). Thus, hypothyroid patients have diminished pressor sensitivity to an alpha-adrenergic agonist and increased plasma levels of the alpha-adrenergic neutrotransmitter norepinephrine.

Whether the increased plasma norepinephrine level reported in hypothyroidism is the result of impaired norepinephrine (NE) clearance or increased NE release by nerve terminals is unknown. We, therefore, measured plasma NE levels and clearance in 11 hypothyroid patients before [T4 index, 41.2 +/- 7.7 nmol/L (mean +/- SEM); TSH, 71.4 +/- 23.0 mU/L] and 4 +/- 0.5 months after thyroid replacement (T4 index, 136.4 +/- 24.4 nmol/L; TSH, 3.2 +/- 1.2 mU/L) and in 8 healthy volunteers. Plasma dopamine-beta-hydroxylase and chromogranin-A, which are coreleased with NE by sympathetic nerve endings, were also measured. Plasma NE was higher in the hypothyroid (2.37 +/- 0.24 nmol/L) than in the euthyroid state (1.86 +/- 0.24 nmol/L; P less than 0.02) or in the controls (1.87 +/- 0.27 nmol/L). Plasma clearance of NE, however, was not affected after thyroid replacement (hypothyroid, 2.08 +/- 0.31 L/min; euthyroid, 1.94 +/- 0.21 L/min; controls, 1.86 +/- 0.15 L/min). There was no significant change in plasma dopamine-beta-hydroxylase (hypothyroid, 720 +/- 139 nmol/mL.h; euthyroid, 553 +/- 97 nmol/mL.h) or plasma chromogranin-A (hypothyroid, 48.9 +/- 7.1 ng/mL; euthyroid, 42.9 +/- 5.3 ng/mL) after thyroid replacement. We conclude that the increased plasma NE in hypothyroid patients is not due to a change in plasma clearance, but is more likely secondary to increased NE release.

Cardiovascular sensitivity to catecholamines was assessed in 15 patients with hypothyroidism (mean [+/- SEM] thyroxine [T4] index 2.7 +/- 0.5 micrograms/100 ml, thyroid stimulating hormone [TSH] 136.9 +/- 48.3 microU/ml), aged 45 +/- 4 years and in 8 healthy control subjects. The study was repeated in 10 patients with hypothyroidism 4.0 +/- 0.5 months after thyroid replacement therapy (T4 index 9.9 +/- 2.1 micrograms/100 ml, TSH 3.5 +/- 1.3 microU/ml). In addition, basal, average and maximal heart rates were measured using 24 h ambulatory electrocardiographic (ECG) monitoring, and plasma levels of epinephrine and norepinephrine were determined before and after thyroid replacement. Heart rate increased less after bolus injection of 0.8, 1.6 and 3.2 micrograms of isoproterenol in the hypothyroid (10 +/- 2, 15 +/- 2 and 21 +/- 4 beats/min, respectively) than in the euthyroid (16 +/- 3, 22 +/- 3 and 30 +/- 4 beats/min, respectively) state (p less than 0.05). Control subjects reacted similarly to patients receiving thyroid replacement. Basal heart rate (64 +/- 3 versus 68 +/- 3 beats/min, p less than 0.05) and maximal heart rate (116 +/- 5 versus 133 +/- 5 beats/min, p less than 0.05) were lower on 24 h ambulatory ECG monitoring in the hypothyroid than euthyroid state despite higher basal plasma norepinephrine levels (394 +/- 45 versus 315 +/- 45 pg/ml, p less than 0.05). Thus, patients with hypothyroidism display a decreased cardiac chronotropic response to beta-adrenergic stimulation. This may contribute in part to the decreased basal and maximal daily heart rates seen in patients with hypothyroidism, which occurs despite elevated plasma norepinephrine levels.

A family is described in which nine members over two generations had an aortic dissecting aneurysm or aortic or arterial dilation at a young age. The family has been followed up since 1977 after the death of a second teenager from a kindred of 11. None of the patients had the Marfan syndrome or a history of systemic hypertension. Three members died of ruptured aortic dissecting aneurysm and acute hemopericardium at 14, 18 and 24 years of age, respectively; a fourth member died suddenly at age 48 years, a few years after aortic repair for aneurysmal dilation. One member underwent surgical repair of an ascending aortic dissecting aneurysm at age 18 years and is still alive. Four members are currently under close medical observation for aortic or arterial dilation. Histologic examination of the aortic wall at autopsy or surgery in three patients revealed a loss of elastic fibers, deposition of mucopolysaccharide-like material in the media and cystic medial changes. Types I and III collagen from cultured fibroblasts appeared normal on gel electrophoresis. Results of indirect immunofluorescent studies of the elastin-associated microfibrillar fiber array in skin and fibroblast culture from multiple family members were also normal. This dramatic familial cluster of aortic dissecting aneurysm and aortic or arterial dilation suggests a genetically determined disease of autosomal dominant inheritance although the basic defect remains unknown.

Twenty-six patients with idiopathic hematuria, i.e. with normal intravenous pyelography, without arterial hypertension, renal failure or significant proteinuria, underwent renal biopsy in our institution between 1973 and 1981. Segmental proliferative endocapillary glomerulonephritis was diagnosed in 13 cases; in the other 13 patients the renal tissue was either normal (6) or presented only minor lesions of the mesangium (5) or interstitial tissue (2). Twenty-two patients underwent a follow-up examination after a mean of 51 months (range 12-120). The hematuria had disappeared in half of them and no patients had developed hypertension or renal failure. These results suggest that in cases of idiopathic hematuria renal biopsy is not indicated for prognostic or therapeutic reasons, though in some cases it may avoid repeated and potentially dangerous investigations.

Whether there is a link between the antiarrhythmic efficacy of amiodarone and its blocking effect on the peripheral conversion of tetraiodothyronine (T4) to triiodothyronine (T3) is uncertain. If such a link exists, oral intake of T3 during amiodarone treatment could reverse, at least partially, the antiarrhythmic efficacy of amiodarone. To assess the safety of oral intake of T3 during amiodarone treatment and gain further insight into the relation between the antiarrhythmic action of amiodarone and its metabolic effect on T4, 7 patients (aged 32 to 62 years) with multiple ventricular premature complexes (VPCs) but no underlying heart disease were studied. Antiarrhythmic treatment was indicated for symptomatic relief only. Each patient underwent a 48-hour ambulatory electrocardiographic recording, electrocardiography and thyroid function tests, including plasma T4, T3, reverse T3 (rT3), free T4, free T3 and thyroid-stimulating hormone without treatment (baseline) after 1 month of amiodarone therapy and after a second month of amiodarone therapy with increasing doses of oral T3 (up to 75 micrograms/day). Treatment with amiodarone resulted in a decrease in plasma T3 and free T3, an increase in plasma rT3, a marked diminution in the frequency of VPCs and a prolongation of the corrected QT interval (QTc). During treatment with amiodarone and T3, plasma T3 and free T3 increased and plasma T4, free T4 and rT3 levels decreased; the frequency of VPCs remained low despite shortening of the QTc to values not different from baseline. Thus, in patients with frequent VPCs and no underlying heart disease, oral intake of T3 during amiodarone treatment is safe and does not abolish the antiarrhythmic efficacy of amiodarone, despite a shortening of the QTc.(ABSTRACT TRUNCATED AT 250 WORDS)

Whether thyroid replacement therapy can trigger cardiac arrhythmias in patients with hypothyroidism is not known. In this prospective study, 24 h ambulatory electrocardiographic (ECG) monitoring was used to assess the frequency of atrial and ventricular premature beats in 25 patients with hypothyroidism (5 men and 20 women, aged 56 +/- 3 years) before and 3.5 +/- 0.5 months (mean +/- SEM) after thyroid replacement therapy. Plasma thyroid-stimulating hormone was 73.6 +/- 12.3 and 3.1 +/- 0.6 microU/ml and free thyroxine index was 2.4 +/- 0.4 and 9.8 +/- 0.9 micrograms/100 ml at baseline and after thyroid replacement therapy, respectively. The frequency of ventricular premature beats was not affected by thyroid replacement therapy (from 273 +/- 221 at baseline to 352 +/- 235 beats/24 h after therapy), even in patients with frequent baseline arrhythmias. In contrast, the frequency of atrial premature beats was slightly increased after thyroid replacement therapy (from 47 +/- 17 to 279 +/- 197 beats/24 h), largely as a result of changes seen in three patients. No patient developed new onset of sustained ventricular or supraventricular arrhythmias. Average, basal and maximal heart rates during ECG monitoring increased significantly after thyroid replacement therapy (average 72 +/- 2 to 80 +/- 2; basal 64 +/- 2 to 70 +/- 2; maximal 114 +/- 3 to 130 +/- 3 beats/min, respectively, p less than 0.001). In conclusion, thyroid replacement therapy is safe in patients with common benign cardiac arrhythmias, and does not trigger an increase in arrhythmia frequency except in rare patients with baseline atrial premature beats. It is, however, associated with an increase in basal, average and maximal heart rates.

Some studies have reported increased short-term mortality and higher incidence of multivessel coronary artery disease in patients with inferior myocardial infarction and complete heart block, but information is lacking on clinical outcome after hospital discharge. Therefore, data were obtained and analyzed in 749 patients who were admitted with inferior myocardial infarction to four different centers and followed up for 1 year. Six hundred fifty-four patients (Group 1) did not have complete heart block and 95 (Group 2) had complete heart block during their hospital stay (incidence rate 12.8%). Compared with Group 1, Group 2 patients were older (66 versus 61 years, p less than 0.01), more often had signs of left ventricular failure (p less than 0.001) and had higher peak creatine kinase values (1,840 versus 1,322 IU/liter, p less than 0.001). The in-hospital mortality rate was higher in Group 2 than in Group 1 (24.2 versus 6.3%, p less than 0.001). However, at discharge there was no difference between Group 1 and Group 2 in clinical characteristics, left ventricular ejection fraction (0.52 +/- 0.12 versus 0.52 +/- 0.11) or incidence of complex ventricular arrhythmias on ambulatory electrocardiographic monitoring. Furthermore, during the year after hospital discharge, patients in Groups 1 and 2 did not have significantly different mortality rates (6.4 versus 10.1%, p = NS). The incidence rate of reinfarction (4%) was the same in Groups 1 and 2. The incidence of coronary artery bypass surgery was slightly but not significantly higher in Group 1 compared with Group 2 (11 versus 4%).(ABSTRACT TRUNCATED AT 250 WORDS)