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M Comelli

Publications and source records attributed to M Comelli.

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

Different methods to analyze clinical experiments with multiple endpoints: a comparison of real data.

In many clinical experiments multiple measurements are required for evaluation of the results. Several methods have been illustrated in the literature to deal with this problem. Some of these solve the problem of multiple testing bias just by looking at the significance of the most pronounced difference. On the other hand, some other methods are designed to take into account all the information available from an experiment. The purpose of this paper is to review these methods and compare the results they gave when applied to a clinical trial in which drug efficacy was assessed by 14 outcome measures.

Analysis of Variance↗
PubMed1996

Proteinuria and blood pressure as causal components of progression to end-stage renal failure. Northern Italian Cooperative Study Group.

AIMS: To identify the prognostic factors possibly related to end-stage renal failure development. SUBJECTS AND METHODS: The prognostic factors affecting chronic renal failure progression were analysed in 456 patients who had participated in a formal, multicentre, prospective randomized trial aimed at verifying the role of protein restriction in slowing down or halting the progression of chronic renal failure. The 24-month follow-up foreseen by the protocol was completed by 311 patients and 69 reached an end-point. An inductive analysis on patient survival was made by using the Cox proportional hazard regression model, using a stepwise procedure in order to select only those factors which are significantly associated with survival. For each individual risk factor, a univariate descriptive analysis of survival was performed using the Kaplan-Meier technique. RESULTS: Underlying nephropathy, baseline plasma creatinine, proteinuria, and plasma calcium were all shown to be related to end-stage renal failure onset. Hypertensive patients (mean blood pressure > 107 mmHg) had a worst cumulative renal survival but the degree of proteinuria was even more important as a prognostic factor of renal death than hypertension. The cumulative renal survival of patients whose proteinuria decreased during the trial follow-up was better than those of patients without changes. However, the interaction between baseline lying mean blood pressure and proteinuria was not significant. CONCLUSIONS: Only primary renal disease and proteinuria were related to renal survival, being baseline plasma creatinine confounding factor. By blocking the possible causal role of proteinuria and hypertension, end-stage renal failure could be prevented in a significant percentage of patients.

Adolescent↗
PubMed1994

Differentiation potentiates oxidant injury to mitochondria by hydrogen peroxide in Friend's erythroleukemia cells.

Oxidative damage to mitochondrial functions was investigated upon non-lethal treatment with H2O2 of Friend's erythroleukemia cells induced to differentiate, in comparison with the parental cell line. Both respiration and maximal ATP synthase capacity were more severely diminished by H2O2 in induced cells. The effects were mediated by intracellular redox-active iron and OH. radicals. Specifically, the mechanisms of the selective oxidant injury to F0F1 ATP synthase observed in differentiating cells likely involved impairment of F0-F1 coupling sensitive to oligomycin. We suggest a Fenton-like reaction of H2O2 with iron ions, more available in the differentiating cells, as occurring at the surface and/or in the lipid bulk phase of the inner mitochondrial membrane, thus injuring subunits responsible for the coupling of F0F1 ATP synthase through generation in situ of the actual damaging species. Besides, we propose heme iron as the most likely candidate for such reaction in induced cells actively synthesizing heme. In accordance, pretreatment of uninduced cells with hemin made H2O2-damage qualitatively identical.

Acetamides↗
PubMed1993

Factors that predict spontaneous remission of ectopic atrial tachycardia.

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)

Adolescent↗
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↗
PubMed1993

[The behavior of late potentials in myocardial infarct patients undergoing myocardial revascularization].

Ventricular late potentials recorded on the body surface in patients with old myocardial infarction (MI) are considered to reflect slow conduction, due to the presence in the infarct border zone of viable myocardium within scarred tissue. To assess the prevalence of late potentials in a population with old MI and no malignant arrhythmias and to verify whether myocardial revascularization may influence the substrate responsible for the occurrence of late potentials, 80 patients with old MI (75 males, 5 females), aged 55 +/- 9 years, undergoing coronary surgery, were studied. A Marquette MAC15 HiRes electrocardiogram recorder was used to identify late potentials before and after surgery. Late potentials were defined following the most accepted criteria reported in the literature. Statistical analysis was performed using logistic regression to determine the association of several clinical, hemodynamic and surgical variables with the presence of late potentials. Late potentials were present in 28 patients (35%) before surgery and disappeared in 11 (39%) after surgery. Inferior MI and female sex were the only independent predictors of the presence of preoperative late potentials. On the other hand, persistence of late potentials after surgery was related to the presence of inferior MI and left ventricle aneurysm. These data suggest that revascularization is capable of abolishing late potentials, probably due to functional recovery of perinecrotic hibernated myocardium. With particular anatomic conditions (inferior MI, aneurysm), this functional recovery seems not to be sufficient for the disappearance of late potentials.

Adult↗
PubMed1993

[Gaucher's disease: study of a family from Friuli].

Gaucher's disease is the most frequent of lysosomal storage diseases. In a family study two affected sisters of a type I patient were identified. Two of them underwent splenectomy, so reaching hematological normalization.

Female↗
PubMed1992

Treatment of sphingomyelinase deficiency by repeated implantations of amniotic epithelial cells.

Five young patients with Niemann-Pick disease type B were treated with repeated implantations of amniotic epithelial cells, as a source of exogenous sphingomyelinase. This treatment abolished the recurrent infections, mainly of the respiratory tract, and led to other improvements of the general conditions of the patients. In particular, we noticed a disappearance of vomiting, a recovery from muscular hypotrophy, and significantly reduced pulmonary distress. In four subjects, who were in a prepuberal state, there was a puberal spurt with a concomitant burst of growth. In two cases, characterized by a greater than normal content of sphingomyelin in urinary sediments, a single implantation caused a sustained normalization of sphingomyelin and total phospholipids in the urine. Finally, sphingomyelinase activity of peripheral leukocytes, when assayed 0.5 to 4 months after some of the implantations, showed a rise to heterozygous values in 30-40% of the assays.

Adolescent↗
PubMed1991

The inactivation of mitochondrial F1 ATPase by H2O2 is mediated by iron ions not tightly bound in the protein.

Exposure to purified mitochondrial F1 ATPase to continuous flux of H2O2 resulted in significant loss (up to 60%) of the ATP hydrolytic activity. The presence of chelating agents including desferrioxamine or previous selective removal of the iron ions not tightly bound in the protein completely prevented the inactivation, whereas re-loading of the enzyme with F3+ restored the sensitivity to H2O2. A marked protective effect was provided as well by mannitol or by Cu,Zn superoxide dismutase. The results indicated the decomposition of H2O2 by redox-active iron-protein adducts as responsible for the enzyme inactivation, probably through site-directed generation of more highly reactive oxygen species. A possible role for iron associated to F1 component in the oxidation, aging and turnover of ATP synthase complex in vivo may be suggested on the basis on these results.

Adenosine Triphosphate↗
PubMed1991

Secretion of lysosomal hydrolases by cultured human amnion epithelial cells.

Primary microcultures of human amnion epithelial cells were established, starting from sterile term placentae. Over a period of 1 week in culture, the epithelial cells release into the extracellular medium substantial amounts of some lysosomal hydrolases, such as sphingomyelinase, N-acetyl-beta-glucosaminidase, alpha-fucosidase, beta-glucuronidase, alpha-mannosidase, and arylsulfatase. Judging from experiments conducted with the protein synthesis inhibitor, cycloheximide, the enzymes released are not newly synthesized forms, but very likely derive from lysosomes. The constitutive secretion of lysosomal enzymes, coupled with lack of immunogenicity, makes amnion epithelial cells a convenient source of enzymes for implantation in attempts of enzyme replacement therapies.

Acetylglucosaminidase↗
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↗
PubMed1990

Statistical analysis of the clinical trial of a therapy for Alzheimer's disease. Univariate tests and logistic regression.

A placebo controlled, randomized, double blind, multicentric clinical trial was carried out in Italy to test the effectiveness of a drug in the therapy of Alzheimer's disease. Informed consensus was gained for the inclusion of 130 patients, whose mental performance was assessed before allocation and after 3, 6, 12 months of continuing assumption of treatment. 14 different outcome variables were used. The main analysis was performed on measures adjusted for baseline, using both univariate and multivariate techniques for each of the three assessing times. The former is mainly descriptive in its scope and allows an analytical view of the results; the latter protects from a too high type I error probability, without implying the loss of power produced by the Bonferroni correction. The techniques are respectively Mann-Whitney test, and analysis of deviance of logistic models, which was suggested by Cupples et al. (1984). In the latter we used the allocation of the patients as response variable, and compared the predictor containing all outcome measures with that having just a constant term. It is shown that a significant difference of fit implies that treatment significantly affects outcome. For the 3 and 6 month follow-up assessment, univariate tests do not show clearcut trends (only 1 outcome measure is significantly better for the drug, none is for the placebo). After 12 months, a trend shows: 13 out of 14 variables are in favour of the drug and 4 of them are significant. Of the three multivariate test carried out, that relative to the 12-month follow-up is significant at the 0.05 level, which is consistent with the univariate results.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗
PubMed1989

Drug compliance and unreported drugs in the elderly.

A random sample of 46 general practitioners of the Unitá Sanitaria Locale in Torino recruited 802 elderly outpatients and collected information about complaints and current drug treatment. Within a week each patient received a home interview and details were collected on drug compliance and use of drugs other than those reported by the general practitioners. On average, each patient was taking 3.6 drugs, of which 2.9 were correctly reported by the general practitioners and 0.7 were unreported. Among the most prescribed therapeutic groups there were drugs with a narrow therapeutic index (cardiovascular drugs, diuretics, psychotropic agents) and substances whose efficacy has never been fully documented ("cerebroactive-vasoactive" agents). Age and number of complaints were positively and significantly correlated with number of prescribed drugs. Nearly half of the sample (44.4%)--more frequently women and people with higher education--were taking one or more drugs not detected by the general practitioners, often benzodiazepines taken over a long period for anxiety or insomnia. Full compliance occurred for 81.5% of the prescriptions and 59.9% of patients were correctly taking all prescribed drugs. Compliance was lower for prescriptions of the general practitioners compared with other doctors' prescriptions (eg, hospital doctor, private doctor) and probability of taking correctly all the prescribed drugs decreased with the number of medicines concurrently taken. The most common reason for noncompliance was fear of side effects.

Aged↗
PubMed1989

[The elderly and drugs: the possible role of a home visit in improving a "difficult relationship". I. The results of an epidemiological study of drug prescription and use by the elderly conducted in the area of local health unit No. 1-23 in Turin].

A random sample of 46 general practitioners of the Unità Sanitaria Locale in Torino recruited 802 elderly outpatients and collected information about complaints and current drug treatment. Within a week each patient received a home interview and details were collected on drug compliance and use of drugs other than those reported by the GP. On average, each patient was taking 3.6 drugs of which 2.9 were correctly reported by the GP and 0.7 were un reported. Among the most prescribed therapeutic groups there were drugs with a narrow therapeutic index (cardiovascular drugs, diuretics, psychotropic agents) and substances whose efficacy has never been fully documented ("cerebroactive/vasoactive"). Age and number of compliants were positively and significantly correlated with number of prescribed drugs. The most common reason for non-compliance was fear of side-effects.

Aged↗
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↗