Biomedical subjects

P Tiraboschi

Publications and source records attributed to P Tiraboschi.

9 recordsLinked to original sources

PubMed1994

Multiple-dose pharmacokinetics and safety of a potential memory-enhancing compound, CL 275,838, in healthy male volunteers.

The pharmacokinetics and safety of CL 275,838, a new potential memory-enhancing compound, were examined after 14 daily doses (50 and 100 mg) in 16 healthy male volunteers, age 20 to 59 years, in a randomized, double-blind, placebo-controlled, parallel group study. Trough blood samples (predose) were collected on days 2, 4, 7, 10, and 14, and further samples were drawn after the final dose (day 14) to define the multiple-dose kinetics of the parent compound and its metabolites II and IV. Intercurrent clinical events, vital functions, EEG, ECG, and cognitive tests (attention, verbal memory, and spatial memory) were considered as outcome measures of safety. Performance in cognitive tests was also studied to collect preliminary information on possible therapeutic action. Predose plasma concentrations of the parent compound and its two metabolites increased approximately in proportion to the dose, and accumulation was complete within 7 days, regardless of the dose. At steady state, mean Cmax and AUC of the parent compound and its two metabolites were dose related. Mean wash-out t1/2 was 18 to 20 hours for the parent compound, 22-23 hours for metabolite II, and 28-33 hours for metabolite IV; these elimination t1/2 are comparable for the two doses, and are similar to those observed in single-dose studies. For the 50-mg-dose group, predicted and observed average plasma concentrations (Css) of CL 275,838 and its two metabolites did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Single-dose safety and pharmacokinetics of a potential cognition-enhancing compound, CL 275,838, in healthy volunteers.

The pharmacokinetics and safety of CL 275,838, a potential cognition-enhancing compound, were studied after single escalating oral doses first in young healthy male volunteers and then in old (60-74 years) and very old (over 75 years) volunteers of both sexes. In all age groups absorption of CL 275,838 was rapid as assessed by the mean time to reach maximum plasma concentrations (Cmax) which averaged 1-2 hr, regardless of the dose administered. In young male volunteers both Cmax and area under the curve (AUC) increased proportionally with dose from 10 to 100 mg. Mean elimination half-lives (t1/2) of the parent compound (18-21 hr) and of its circulating metabolites II (20-22 hr) and IV (27-30 hr) were well comparable for the doses tested (50 and 100 mg). Age did not appreciably affect plasma Cmax of CL 275,838 or its two metabolites. Mean AUC and elimination half-life did not appreciably differ between old and very old subjects given 50 mg CL 275,838, with the limitations dictated by the small number of elderly subjects examined. Compared with younger volunteers receiving comparable doses, however, the elderly had higher mean plasma AUC of the unchanged compound and its two metabolites, although the parameter varied widely between subjects. The mean elimination t1/2 (+/- SD) was longer in the elderly (38.8 +/- 19.6, 50.5 +/- 24.5 and 41.7 +/- 12.1 hr, respectively, for the parent compound and its metabolites II and IV) than in the young subjects. The cause(s) of these variations and the possible clinical implications remain to be established.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Rate of progression and prognostic factors in Alzheimer's disease: a prospective study.

OBJECTIVE: To study rate of progression and correlates of cognitive and functional/behavioral deterioration in Alzheimer patients. DESIGN: A 1-year multicenter prospective study. SETTING: Outpatients and inpatients at geriatric institutions. PATIENTS: Fifty-six patients with a clinical diagnosis of Alzheimer's disease according to DSM-III criteria of Primary Degenerative Dementia. MAIN OUTCOME MEASURES: Blessed Dementia Scale (BDS) and Blessed Information-Memory-Concentration test (BIMC) measured at baseline, third, sixth, and twelfth month. RESULTS: The mean annual (+/- SD) rate of progression of our sample was 3.5 (+/- 3.7) points on the BDS and 2.6 (+/- 4.9) on the BIMC, with a wide range of variability. The level of cognitive impairment (BIMC score) at baseline predicted functional and behavioral deterioration: the better the initial BIMC score, the less the rate of negative change of BDS (r = 0.37, P = 0.006). Furthermore, the younger the patients at the disease onset, the faster the progression of cognitive impairment (r = 0.48, P = 0.0003), with men having a slower rate of progression (P = 0.004) than women. CONCLUSIONS: The present study confirms previous findings showing a wide individual variability in rate of progression of cognitive and functional/behavioral impairment as assessed by BIMC and BDS. The cognitive profile may predict the clinical evolution better than the functional and behavioral status, with patients with an earlier onset and women having a faster deterioration.

Age Factors↗

PubMed1991

Long-term acetyl-L-carnitine treatment in Alzheimer's disease.

In a double-blind, placebo-controlled, parallel-group, randomized clinical trial, we studied the efficacy of long-term (1-year) oral treatment with acetyl-L-carnitine in 130 patients with a clinical diagnosis of Alzheimer's disease. We employed 14 outcome measures to assess functional and cognitive impairment. After 1 year, both the treated and placebo groups worsened, but the treated group showed a slower rate of deterioration in 13 of the 14 outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, ideomotor and buccofacial apraxia, and selective attention. Adjusting for initial scores with analysis of covariance, the treated group showed better scores on all outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, verbal critical abilities, long-term verbal memory, and selective attention. The analysis for patients with good treatment compliance showed a greater drug benefit than for the overall sample. Reported adverse events were relatively mild, and there was no significant difference between the treated and placebo groups either in incidence or severity.

Acetylcarnitine↗

PubMed1989

An example of a clinical trial in patients with Alzheimer's disease: some methodological issues.

UNLABELLED: In ten Italian centers--hospitals and geriatric institutions--130 outpatients and inpatients with a diagnosis of Alzheimer's disease were recruited for a randomized, double blind, placebo controlled clinical trial with 1-acetylcarnitine. In planning the trial, we had to deal with some important and largely open issues. DIAGNOSIS: we decided not to use neuropsychological tests (NPT) in the diagnostic process, both for the unknown risk of false positive and false negative rate and to improve the feasibility of the trial. FOLLOW-UP: it must be representative of the disease and consequently we chose to follow the patients for one year (assessment at baseline, 3rd, 6th and 12th month) in spite of a possible high rate of drop-outs. ASSESSMENT: to assess the patients' outcome we used NPT and behavioural scales. However, the validity, reliability and feasibility of these instruments are rarely discussed and their usefulness as indicators of the relevant aspects of the disease needs a careful evaluation. STATISTICAL ANALYSIS: in this type of trial there is both a high risk of alpha-error, in view of the high number of NPT and behavioural scales used to assess the drug efficacy, and a high risk of beta-error connected with the usually small sample size. Thus, the role of small trials in defining the risk/benefit ratio of a treatment needs to be discussed.

Acetylcarnitine↗

PubMed1988

Atypical features and prognosis of Wallenberg syndrome: longitudinal study.

The lessons of a retrospective study of 24 consecutive cases of Wallenberg syndrome observed during a 6-year span are described: the high frequency of signs and symptoms not considered typical, such as headache, diplopia, supranuclear homolateral facial paresis and homolateral brachiocrural hemiparesis; the unfavorable short term course in a high percentage of cases, and the risk of sudden respiratory arrest.

Aged↗

PubMed1986

[Diagnostic problems in spontaneous bacterial peritonitis].

In spontaneous bacterial peritonitis (SBP) the ascitic fluid culture (certain criterion of diagnosis) may be negative despite an evident clinical and biochemical picture. Therefore the diagnosis may be sometimes more "probable" than "certain". The authors performed a comparative analytical study--from a clinical, biochemical and prognostic point of view--between a group of 10 "probable" SBP (10 cirrhotic pts.) and 9 "certain" SBP (9 cirrhotic pts.). 115 "normal ascitic fluids" (negative culture in absence of any SBP-symptoms), collected from 82 cirrhotic pts., were used as control group. The ascitic concentration of white blood cells (WBC)/mmc and polymorphonuclear cells (PMN)/mmc was significantly different between the SBP and control group (p less than 0.001) and between the "certain" and "probable" SBP (p less than 0.02). The latter have a mean WBC and PMN/mmc count that is lower than the "certain" SBP and on the contrary a significantly higher ascitic glucose content (p less than 0.05). Probably that means a lower ascitic bacterial inoculum, which is below the threshold of detectability by current culture techniques. Serum laboratory tests showed no differences between the "probable" and the "certain" SBP groups, although, however they were worse than the control group. The symptoms and the prognosis resulted nearly the same in both groups. In spite of a high rate of recovery (57.9%) the global survival at the follow-up (10 +/- 5.2 months, range 6-19) was only 26.3%. The wide clinical, biochemical and prognostic overlap of the two groups leads us to consider as "certain" all the cases of "probable" SBP. Owing to the fact that only an early recognition and therapy are known to affect the prognosis significantly, the obvious conclusion is that in the SBP the suspicion is more important that the diagnostic certainty. Furthermore--in agreement with previous studies--the cutoff limit of 250 PMN/mmc has shown the best statistical diagnostic value for a rapid diagnosis (sensibility 100%, diagnostic accuracy 92.5%, negative predictive value 100%, likelihood ratio 1.9).

Adult↗

PubMedDate not supplied

[Fluoxetine].

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Depressive Disorder↗

PubMedDate not supplied

[Mianserin].

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Adjustment Disorders↗