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Biomedical subjects

T A Treves

Publications and source records attributed to T A Treves.

At least 37 records · Page 2Linked to original sources
PubMed1996

M1 agonists for the treatment of Alzheimer's disease. Novel properties and clinical update.

The AF series compounds, AF102B and congeners of AF150(S), are functionally selective agonists for m1 muscarinic receptors (m1AChRs). This is shown in stable transfected CHO and PC12 cells (PC12M1) with m1m5AChRs and m1AChRs, respectively. AF102B and AF150(S) are partial agonists, but AF150, AF151, and AF151 (S) are full agonists in stimulating phosphoinositides hydrolysis or arachidonic acid release in these cells. Yet, all these compounds behave as antagonists when compared with carbachol in elevating cAMP levels. In PC12M1 cells, unlike carbachol, the AF series compounds induce only minimal to moderate neurite outgrowth. Yet, these agonists synergize strongly with NGF, which by itself mediates only a mild response. Stimulation of m1AChRs by AF102B, AF150(S) and AF151(S) in PC12M1 cells enhances secretion of beta/A4 amyloid precursor protein derivatives (APPs). The enhanced APPs secretion induced by AF102B is potentiated by NGF. AF102B also stimulates APPs secretion from rat cortical slices. Stimulation of m1AChR in PC12M1 cells with carbachol or AF102B decreases tau phosphorylation as indicated by specific tau-1 mAb and alkaline phosphatase treatment. Due to the above mentioned properties m1 agonists may be of unique value in delaying the progression of Alzheimer's disease (AD). The AF series compounds show a wide safety margin and improve memory and learning deficits in animal models for AD. There is a dearth of clinical reports on m1 agonists. These include studies on AF102B and xanomeline, another m1 selective agonist. We tested AF102B in escalating doses of 20, 40, 60 mg, tid, po, (each dose for 2 weeks) for a total of 10 weeks. This was a single-blind placebo-controlled, parallel-group study in patients with probable AD. AF102B was significantly effective at 40 and 60 mg, tid in the ADAS, ADAS-cognitive and ADAS-word recognition scales.

Alzheimer Disease↗
PubMed1996

Cognitive effects of scopolamine in dementia.

Cholinergic deficiency was postulated to play an important role in the mental decline observed in Alzheimer's (AD), Parkinson's (PD) and multiinfarct (MID) dementia. In the present study, 11 AD, 8 MID and 7 PD patients (DSM III-R diagnostic criteria for dementia) and 9 healthy age-matched controls (CTRL) were given IV 0.5 mg scopolamine (SCO) or placebo (PLA) in random order (double blind) within one week. The Hebrew Short Mental Test (SMT) and Wechsler Memory Scale (WMS) were administered before and after SCO and PLA in each patient. A comparison of SCO vs. PLA utilizing MANCOVA (the covariate being the basal mental performance [BAS] with SMT or WMS) showed that SCO affected all the groups similarly, except for the Wechsler subtest of logic memory which showed larger deterioration in CTRL compared to demented patients. ANOVA and MANCOVA analyses did not distinguish between the three demented groups. SCO administration does not differentiate between demented patients and CTRL and does not enable discrimination between patients with AD, MID and PD. Moreover, some CTRL with still normal cognitive performance, but lower BAS may be more vulnerable to SCO than others. The integrity of the cholinergic system may be responsible for the different sensitivity to SCO challenge.

Aged↗
PubMed1996

A novel mutation of presenilin 1 in familial Alzheimer's disease in Israel detected by denaturing gradient gel electrophoresis.

Germline mutations in the presenilin 1 (PS1) gene apparently account for the majority of early-onset, familial Alzheimer's disease (AD). Using a mutation-screening strategy (denaturing gradient gel electrophoresis; DGGE), we analyzed a large family with early onset AD and seizures. The patients in this family showed a novel missense mutation in exon 5 of the PS1 gene (A to T change in codon 120, altering glutamine to aspartic acid). This novel mutation is located within the second hydrophilic domain of the molecule, a region not particularly involved in previously described germline mutations, and is of unknown biological significance. These results also demonstrate that DGGE can be used effectively to screen for mutations within this gene.

Alzheimer Disease↗
PubMed1996

Is transcranial Doppler effective in avoiding the hazards of carotid surgery?

The middle cerebral artery flow velocities were measured to test the hypothesis that transcranial Doppler is a useful technique for intraoperative monitoring in 50 consecutive carotid endarterectomies which were performed under local anaesthesia. The patients' neurological status was continuously monitored. The peak middle cerebral artery velocities were measured before clamping, during clamping and after restoration of flow, and again 24 h and 4 weeks later. Clamping produced a decrease in the velocity of the middle cerebral artery, from 97 to 45 cm/s (P < 0.001). Neurological manifestations occurred in eight patients; one patient lost consciousness, and seven experienced transient focal deficits during the procedure. Another three (6%) developed minor strokes postoperatively. The velocity changes were similar in those who developed complications to those who did not. These results do not support the view that transcranial Doppler monitoring is helpful in deciding whether to use a shunt during carotid endarterectomy. Further data are needed to evaluate the importance of transcranial Doppler monitoring during carotid surgery.

Adult↗
PubMed1996

APOE-epsilon 4 in patients with Alzheimer disease and vascular dementia.

The apolipoprotein E (APOE) epsilon 4 allele has been consistently found to be frequent in patients with progressive degenerative dementia of the Alzheimer type (DAT). Vascular dementia (VD) may occur as strokes superimposed on presymptomatic DAT, in which case APOE-epsilon 4 frequency should also be increased in VD. We have examined the distribution of APOE-epsilon 4 in patients with DAT (n = 176) or VD (n = 74) and controls (n = 133), and evaluated the risk of dementia associated with APOE-epsilon 4. APOE-epsilon 4 allele frequency was 27% in DAT patients, 21% in VD patients, and 11% in controls. The difference in the distribution of the epsilon 4 allele between DAT or VD patients and controls was statistically significant (chi(2) test, p < 0.05), with a 3.6- and 2.1-fold risk of dementia in DAT and VD patients carrying an epsilon 4 allele. The result that the APOE-epsilon 4 allele is more frequent in DAT patients than in controls, with VD patients falling in between, is consistent with the assumption that VD is a heterogeneous condition, with some patients having an underlying preclinical brain degeneration, in whom the dementia was precipitated by strokes.

Aged↗
PubMed1996

The Tel Aviv Stroke Registry. 3600 consecutive patients.

BACKGROUND AND PURPOSE: We undertook to estimate the frequency of various risk factors and the type and severity of stroke in different ethnic groups documented in a large hospital-based stroke registry. Tel Aviv is a metropolis with about 400000 inhabitants and about 600000 daily visitors and workers. The Tel Aviv Medical Center (TAMC) is the only tertiary medical care facility to which all patients with acute stroke are referred. Israel is a country with a heterogeneous population, of which a significant proportion was born abroad. The people differ in their genetic background, as well as in their early environmental conditions, lifelong diet, and other habits. This variety has proved to be a fertile ground for the study of different neurological diseases, including stroke. METHODS: A prospective hospital-based registry using systematic computer coding of data of all consecutive stroke patients admitted to the TAMC has been conducted since May 1988. Different aspects of the amassed data were analyzed statistically. RESULTS: From May 1988 until April 1994, 3600 stroke patients were admitted to the TAMC. The mean age was 73.2 years, and 58.2% were males. Cerebral infarctions were diagnosed in 80.9%, primary intracerebral hemorrhages in 8.0%, and transient ischemic attacks in 11.1%. There were 861 patients (24%) who were admitted with recurrent strokes. Past medical history of hypertension was the major risk factor (occurring in 52.2% of the patients), followed by ischemic heart disease (29.7%), diabetes mellitus (25.2%), smoking (17.0%), atrial fibrillation (14.3%), and hyperlipidemia (8.4%). Ischemic heart disease and atrial fibrillation were more frequent in patients from Europe and America (Ashkenazi group), whereas diabetes mellitus and smoking were more prominent in the other groups. The in-hospital mortality rate was 13.8% and was similar in both ethnic groups. CONCLUSIONS: This registry allows the study of the risk factors, natural history, and clinical manifestations of stroke in different ethnic groups.

Africa↗
PubMed1996

Do silent brain infarctions predict the development of dementia after first ischemic stroke?

BACKGROUND AND PURPOSE: Silent brain infarctions (SBI) are common findings in advanced age, but their relationship to dementia is still uncertain. The present study was designed to evaluate whether SBI predict the development of dementia after first clinical ischemic stroke. METHODS: We blindly studied admission CT scans of 175 consecutive nondemented patients presenting with ischemic stroke that clinically was their first stroke episode. SBI were defined as CT evidence of infarcts not compatible with the acute event. The patients were subsequently followed for their mental state for 5 years. Survival analysis, wherein onset of dementia was the end point, was performed on the total sample population and conducted separately on those with and without SBI at admission. RESULTS: Dementia developed in 56 patients (32%), including 22 of the 63 (35%) with SBI and 34 of the 112 (30%) without SBI. Thus, dementia was not related to SBI. CONCLUSIONS: Our data indicate that SBI do not predict the development of dementia after stroke.

Aged↗
PubMed1995

Low-dose clozapine in the treatment of levodopa-induced mental disturbances in Parkinson's disease.

Delusions and other manifestations of psychotic behavior are common side effects in Parkinson's disease (PD) patients chronically treated with dopaminergic drugs. Clozapine, a dibenzodiazepine derivative, is an antipsychotic drug largely devoid of extrapyramidal side effects. We evaluated the effects of low doses of clozapine on the mental and motor functions in PD patients requiring antipsychotic treatment. Twenty-seven PD patients taking dopaminergic drugs and who had psychotic behavior received clozapine at 12.5 to 75 mg/d. Fifteen patients received clozapine for 1 to 11 months (mean, 6.8 months) and seven received it for 12 to 24 months (mean, 18 months). No patient exhibited motor deterioration, and the psychotic features disappeared immediately, allowing discontinuation of clozapine after several months in 10 patients. Fifteen patients are still receiving clozapine and are free of psychiatric symptoms. The clozapine treatment was discontinued after 5 days (25 mg/d) in two patients because of somnolence. No patient developed neutropenia. Clozapine in low doses is effective in the treatment of drug-induced delusions and hallucinations in PD.

Aged↗
PubMed1994

Effects of a single intravenous dose of scopolamine on the quantitative EEG in Alzheimer's disease patients and age-matched controls.

Quantitative EEG (qEEG) was evaluated in Alzheimer's disease (AD) patients and age-matched controls following the administration of a single acute intravenous dose of scopolamine. Eleven AD patients and 8 cognitively intact age-matched controls underwent qEEG in baseline conditions, following double-blind intravenous administration of 0.5 mg scopolamine or placebo. At baseline, AD patients had significantly decreased absolute and relative alpha and increased relative theta amplitudes. In both groups, scopolamine administration was followed by a decrease in absolute and relative alpha amplitude, and increase in the absolute and relative delta activity. The increase in the absolute and relative delta amplitude by scopolamine was significantly more prominent in the controls; the decrease of alpha activity, while larger in controls, was not statistically different from AD. We conclude that scopolamine affects the change in delta amplitude differently in AD patients and controls, probably reflecting the reduced cholinergic tone in AD.

Aged↗
PubMed1994

Transdermal physostigmine in the treatment of Alzheimer's disease.

Physostigmine has been reported to improve the memory function of some patients with Alzheimer's Disease (AD). However, the drug has a short half-life and a narrow therapeutic window. To overcome these impediments, we developed a continuous transdermal delivery system and tested it for 2 weeks in 12 AD inpatients, using a single-blind design. No major adverse effects were recorded in any of the patients. Physostigmine plasma concentrations were relatively stable (0.56 +/- 0.10 ng/ml) and correlated well with blood acetylcholinesterase inhibition. Six of the 12 patients reported improved vigilance and concentration, and also had higher scores in all four neuropsychological tests employed (Mini Mental State examination, Short Mental Test [SMT], Wechsler's Memory Scale [WMS], and Buschke's Selective Reminding Test). The performance of two additional patients improved in only two tests (SMT and WMS). Transdermal delivery of physostigmine appears to be safe and may be useful for the treatment of a subset of AD patients.

Administration, Cutaneous↗
PubMed1994

EEG as predictor of dementia following first ischemic stroke.

INTRODUCTION: Predictive factors for occurrence of vascular dementia may help identify patients at increased risk of developing this condition. Our purpose was to evaluate the prognostic value of early EEG findings in patients after first ischemic cerebral stroke on the development of dementia. MATERIAL AND METHODS: We performed routine EEG recordings in 199 consecutive non-demented patients with first-ever ischemic stroke, within 48 h of the event. The patients were subsequently followed for their mental state for 2 years. Survival analysis, wherein onset of dementia was the end-point, was performed on the total sample population and conducted separately on those who had normal EEG at time of the event and on those who had abnormal EEG findings (focal or diffuse slowing). RESULTS: Patients with abnormal EEG at baseline had 2.6 times the risk of developing dementia than those who had normal EEG; this odds ratio was statistical significant (CL: 1.3-5.1, p = 0.003). Development of dementia was not related to any specific EEG abnormal pattern. CONCLUSIONS: Abnormal EEG performed close to the first ischemic stroke appears to be an indicator of subsequent cognitive decline, probably because it indicates cortical involvement by the stroke or an underlying indolent cerebral degeneration.

Aged↗
PubMed1994

Failure of aspirin treatment after stroke.

BACKGROUND AND PURPOSE: Despite its low efficacy, aspirin is the most widely used drug for secondary stroke prevention. The reasons why stroke recurs while patients are on aspirin are unknown. We have analyzed a series of patients who had recurrent strokes while on aspirin. METHODS: Out of 2231 consecutive patients who were admitted to the Tel Aviv Medical Center from May 1988 through December 1992 with the diagnosis of ischemic stroke, 129 admissions were due to recurrent ischemic strokes while the patients were already on aspirin, and these were defined as aspirin failures. The clinical characteristics of those patients in whom aspirin treatment failed were compared with three control groups, each comprising 129 patients who had had only a single ischemic stroke and were then taking aspirin. One control group was matched for aspirin dose and date of first stroke; another control group was matched for age, sex, and date of first stroke; and a third control group was matched for age, sex, date of first stroke, and aspirin dose. Statistical analysis was carried out by two-tailed Student's t test and chi 2 test. RESULTS: The average period until stroke was longer for patients on higher aspirin doses. Patients matched for aspirin dose and date of first stroke did not differ significantly in age (72.4 years in aspirin failures versus 74.2 years in the first control group) and sex (89 versus 94 men, respectively). Matching for age, sex, and date of first stroke but not for aspirin dose demonstrated a trend toward high frequency of aspirin failure in patients taking lower doses of aspirin (chi 2 test for trend = 3.5; P = .06). Comparison of aspirin-failure patients with a control group matched for age, sex, date of first ischemic stroke, and aspirin dose demonstrated that these patients more commonly had statistically significant hyperlipidemia (odds ratio, 2.6; 95% confidence interval, 1.0 to 6.8; P = .04) and ischemic heart disease (odds ratio, 2.3; 95% confidence interval, 1.3 to 3.9; P = .002). CONCLUSIONS: We conclude that age and sex do not influence the efficacy of aspirin. Lower aspirin dose in patients with stroke recurrence suggests that aspirin doses of 500 mg daily or more should be used in secondary stroke prevention. Hyperlipidemia and ischemic heart disease are risk factors for stroke recurrence despite aspirin treatment, which requires further clinical and laboratory evaluation.

Aged↗
PubMed1994

Interrater agreement in evaluation of stroke patients with the unified neurological stroke scale.

BACKGROUND: We sought to determine interrater agreement in evaluation of stroke patients with the Unified Form for Neurological Stroke Scales (UFNSS). SUMMARY OF REPORT: Fifty inpatients were independently examined by three neurologists. Kendall coefficients of concordance were computed for the different items of the UFNSS. There was a high concordance among the raters. The best agreements were obtained for motor functions and the worst for grading of eye movements. CONCLUSIONS: The UFNSS was shown to be reliable for evaluation of motor functions, verbal communication, orientation, and vigilance in stroke patients.

Arousal↗
PubMed1993

Parkinson's and Alzheimer's diseases: epidemiological comparison. 1. Descriptive aspects.

Parkinson's (PD) and Alzheimer's (AD) diseases are age-related degenerative disorders that share common clinical, pathological and biochemical features. Epidemiological studies show similar age-specific incidence and prevalence curves, although PD tends to occur at earlier ages and, at old age, AD is more frequent. Both diseases are more common in western than in Mediterranean or Asiatic populations. These findings suggest that these diseases may have common determinants.

Age Factors↗
PubMed1993

Parkinson's and Alzheimer's diseases: epidemiological comparison. 2. Persons at risk.

Parkinson's and Alzheimer's diseases are age-related degenerative disorders that share common clinical, pathological and biochemical features. Epidemiological studies demonstrate a similar distribution of the disease in place and time. Causes of death and populations at higher risk are similar. These findings suggest that these diseases must have common determinants.

Age Factors↗
PubMed1992

DSM-III-R criteria for primary degenerative dementia and multi-infarct dementia [corrected].

Primary degenerative dementia (PDD) and multi-infarct dementia (MID) are the two most common categories of cognitive decline in old age. The definitions of these two clinical entities are currently based on clinical evaluation and on the exclusion of other underlying causes, and still lack a consensus. The DSM-III-R criteria are widely used for the diagnosis of dementia. However, their role in the differentiation between PDD and MID has not been thoroughly examined. A consecutive series of 98 demented patients who met the DSM-III-R criteria for dementia were admitted to a clinical study. Upon evaluating their type of dementia according to these criteria, 53 patients could not be diagnosed either as having PDD or MID. The DSM-III-R criteria for these two types of dementia are critically reviewed. Proposed modifications, aimed at refining their differential diagnostic role, are presented, enabling better allocation of demented patients into PDD, MID, or intermediate groups.

Aged↗
PubMed1992

Naproxen sodium versus ergotamine tartrate in the treatment of acute migraine attacks.

A double-blind parallel study compared the efficacy and safety of naproxen sodium (NPX) and ergotamine tartrate (ERG) as abortive therapy for acute headache in 79 patients with classical or common migraine. The design study was of the double-blind design. Forty-two patients completed the study. Discontinuation of treatment was generally due to lack of efficacy or adverse reactions. NPX was significantly better than ERG in the overall efficacy of treatment rated by the patients (p less than 004). NPX was comparable to ERG in reducing the severity and duration of the headache and its associated symptoms. In classical migraine, NPX was better than ERG in alleviating the severity of headache. Patients in the NPX group tended to use less rescue medication. There was no significant difference in the frequency of side-effects reported by the patients under NPX or ERG. This study demonstrates that NPX is as safe as ERG, and somewhat more effective in acute migraine attacks (although the difference is not statistically significant) and that migrainous patients tend to prefer NPX to ERG in treating their acute migraine headaches.

Acute Disease↗