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Biomedical subjects

A Spagnoli

Publications and source records attributed to A Spagnoli.

At least 55 records · Page 3Linked to original sources
PubMed1994

Expression and down-regulation by retinoic acid of IGF binding protein-2 and -4 in medium from human neuroblastoma cells.

Insulin-like growth factors (IGFs) regulate the autocrine/paracrine growth of neuroblastomas. The IGFs bind to specific binding proteins (IGFBPs) which modulate their biological activity. We investigated, by Western ligand blotting (WLB), the presence of IGFBPs and their possible modulation by retinoic acid (RA), IGF-I, IGF-II and truncated Des(1-3)IGF-I in conditioned medium (CM) of the human neuroblastoma SK-N-BE(2) cell line. We demonstrated the presence of two IGFBPs, with MW 37 kDa and 25 kDa. Following immunoprecipitation, they turned out to be IGFBP-2 and -4, respectively. The RA-induced differentiation in SK-N-BE(2) cells was accompanied by a marked reduction of the intensity of both IGFBP bands after 48 h (32% and 24% of control, respectively) and 72 h (2% and 0% of control, respectively) incubation. The addition of exogenous IGFs, which did not induce cell differentiation, did not change the IGFBP pattern significantly, except for the truncated form of IGF-I, which induced a marked decrease in both the 37 kDa and 25 kDa bands after 72 h incubation (45% and 18% of control, respectively). These findings suggest that IGFBPs have a role in RA-induced differentiation in human neuroblastoma cells.

Blotting, Western↗
PubMed1994

Reduced growth hormone secretion in Turner syndrome: is body weight a key factor?

The age-related decline in spontaneous growth hormone (GH) secretion has been suggested to cause growth failure in girls with Turner syndrome (TS). We studied 23 girls (mean age +/- SD: 11.1 +/- 2.7 years) diagnosed to have TS by karyotype analysis. The control group consisted of 18 prepubertal age-matched subjects (10.7 +/- 2.5 years) with growth retardation due to familial short stature and/or constitutional growth delay. In addition, 18 children (10.9 +/- 3.3 years) diagnosed to have GH deficiency by two different provocative tests were chosen as a further comparison group. Spontaneous 12-hour nocturnal GH secretion was assessed by RIA at 30-min intervals. Plasma insulin-like growth factor 1 (IGF-1) levels were determined by RIA after acid-ethanol extraction. Girls with TS had a percentage of ideal body weight significantly higher than controls (p < 0.0001) and showed spontaneous GH secretion significantly lower than controls (mean +/- SD: 3.2 +/- 1.6 in TS vs. 5.5 +/- 1.3 microgram/l in controls; p < 0.0001) but higher than GH-deficient patients (1.3 +/- 0.8 microgram/l; p < 0.0001). No significant difference was found in IGF-1 levels between TS patients and controls, whereas GH-deficient children showed IGF-1 levels significantly lower than those of TS patients (p < 0.0005). As expected, GH concentrations correlated with bone age in controls (r = 0.51, p < 0.05), whereas no relationship was seen in TS. interestingly, in TS, GH levels were negatively related to the percentage of ideal body weight (r = -0.43, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
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↗
PubMed1993

[Administration of 5% +EMLA cream for local anesthesia in ambulatory pediatric surgery].

The use of local anaesthesia has been advocated by most pediatric surgeons in order to cut down hospitalization costs as well as to avoid general anaesthesia. In 1992, 26 patients aged 4 to 14 years (avg. 8 years) underwent small surgical procedures with local anesthesia, obtained by the application of EMLA cream 60 to 120 minutes prior to the procedure. EMLA cream is aneutectic mixture of lidocaine and prilocaine with a meeting point at a lesser temperature than the two compounds separately. In this way, concentration of anaesthetics increases up to 80% in the emulsion droplets. This preparation enables small operations to be performed under local anesthesia even in small children who can be safely treated as outpatients. Disadvantages due to the long time necessary for optimal action can be overcome by application of the cream at home by the parents themselves.

Administration, Topical↗
PubMed1991

Interleukin-1 beta modulates the acute release of growth hormone-releasing hormone and somatostatin from rat hypothalamus in vitro, whereas tumor necrosis factor and interleukin-6 have no effect.

There is clear evidence for communication between the immune and neuroendocrine systems. However, the effect of cytokines as major immune mediators on the hypothalamic growth peptides, GHRH and somatostatin (SRIH), is not well established. To investigate a possible hypothalamic action of the cytokines interleukin-1 beta (IL-1), interleukin-6, and tumor necrosis factor-alpha, on the release of GHRH and SRIH, we used a previously validated acute rat hypothalamic explant system. IL-1 caused a pronounced dose-dependent stimulation of SRIH in the dose-range 1-100 U/ml (P less than 0.01). GHRH showed a slight, but significant, increase in response to IL-1 tested in the dose-range 10-100 U/ml. Similar studies with mediobasal hypothalamic (GHRH and SRIH) or median eminence (SRIH) fragments produced no change in either GHRH or SRIH release. The effects of IL-1 were antagonized by the cyclo-oxygenase inhibitor, indomethacin (10 micrograms/ml). Stimulation of GHRH and SRIH could not be blocked by the CRH-antagonist alpha-helical CRH (9-41) at 10(-6) M. Interleukin-6, in the dose range 10-100 U/ml, and tumor necrosis factor-alpha, in the dose range 10-10,000 U/ml, had no effect on the acute hypothalamic release of either GHRH or SRIH. It is concluded that IL-1 stimulates the acute hypothalamic release of GHRH and SRIH, and that this effect is mediated by cyclo-oxygenase products. The marked IL-1 stimulation of hypothalamic SRIH release may override the minor increase of GHRH increase, and may thus contribute to disturbances in growth seen in the presence of chronic inflammation.

Animals↗
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↗
PubMed1991

Enhancement by growth hormone of phorbol diester-stimulated respiratory burst in human polymorphonuclear leukocytes.

The oxidative metabolic burst of mononuclear and polymorphonuclear phagocytes can be stimulated to produce free oxygen radicals. Several substances can enhance this respiratory burst activity by a priming action: recently growth hormone (rat and porcine) was demonstrated to act as a priming agent on rat peritoneal and on porcine alveolar macrophages. In our study we wanted to verify whether also human GH had a similar priming action on homologous cells, in particular on polymorphonuclear leukocytes. To determine the oxidative activity of polymorphonuclear leukocytes, after stimulation with phorbol myristate acetate, a flow-cytometric assay was employed which registered the intracellular formation of highly fluorescent products as indicators for the intracellular formation of hydrogen peroxide. The incubation of phorbol myristate acetate-stimulated polymorphonuclear leukocytes with GH resulted in a time-dependent and dose-dependent increase in fluorescence, thus demonstrating that human GH enhances in vitro the oxidative metabolic burst of these cells. The action of GH appeared to be significant after 30 min of incubation, was maximal at 60 min, and decreased after 90 min. After one hour of incubation, the first significant variation of fluorescence appeared with GH at a concentration of 50 micrograms/l. The maximum effect was seen at 100 micrograms/l with no further increase. Specificity of GH action was demonstrated by the inhibition of its effect by the addition of monoclonal antibodies to GH.

Adult↗
PubMed1990

[Evaluation of the effectiveness of sodium piperacillin in the treatment of surgical infections in children].

A clinical trial has been carried out in 40 children (age ranging from 2 to 12 years) with postsurgical infections caused by aerobic, anaerobic and facultative bacteria. All have been treated by monotherapy with sodium piperacillin, with doses of 150-200 mg/kg daily in 3 administrations. The drug was administered for a mean period of 7 days, by intravenous infusion or intramuscular route. The causative organism was eradicated in all but 4 cases (90%). Side effects observed were all of mild intensity, and in no case it was necessary to discontinue the treatment with the drug. Both bacterial and clinical results indicate a high tolerability and a very rapid effectiveness of this antibiotic.

Bacterial Infections↗
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↗
PubMed1987

Feasibility of a large prospective study in general practice: an Italian experience. Gruppo di Studio sulla Pressione Arteriosa nell'Anziano.

A study of blood pressure control in elderly outpatients was carried out with the participation of 444 Italian general practitioners. Of 4096 patients aged 65 years or over who were considered for recruitment, 3959 (96.7%) fulfilled all the criteria of admission and were followed up for 12 months. The findings regarding one of the aims of the study--that is, to assess the feasibility of a large scale trial in general practice--are reported. Most (87%) of the doctors completed the study. Their adherence to the protocol was highly satisfactory, leading to an acceptable quality of work. Patients' compliance was also good; 98.6% (3898) of the patients who had fulfilled the admission criteria agreed to participate in the study, and only 4% (158) dropped out. Both of these observations support the feasibility of carrying out prospective studies in general practice. The creation of networks of general practitioners who are prepared to carry out research in their practices would allow treatment and preventive measures to be studied simply and at low cost in the appropriate setting.

Aged↗
PubMed1987

Italian version of the organic brain syndrome and the depression scales from the CARE: evaluation of their performance in geriatric institutions.

The Organic Brain Syndrome (OBS) and the Depression (D) scales derived from the Comprehensive Assessment and Referral Evaluation (CARE) were translated into Italian and used in a survey of geriatric institutions in Milan. During the survey validity and reliability tests of the scales were conducted. Inter-rater reliability (total score weighted kappa) was highly satisfactory for both scales (0.96 for OBS and 0.83 for D scale). Reliability was assessed three times during the survey and showed good stability for both scales, with a slight but significant trend towards reduction over time for the D scale. Reliability of the D scale was significantly lower when the subjects interviewed scored highly on the OBS scale (severe cognitive impairment). Criterion validity was highly satisfactory both for the OBS scale (cut-off point 4/5: sensitivity 77%, specificity 96%, positive predictive value 91%) and the D scale (cut-off point 10/11: sensitivity 95%, specificity 92%, positive predictive value 84%). Results are discussed with special reference to longitudinal assessment of reliability, the choice of the cut-off point, and the context-dependent properties of questionnaires.

Aged↗
PubMed1986

Peritoneovenous shunt and neoplastic ascites: a 5-year experience report.

The cases of 42 patients with malignant ascites treated with a peritoneal venous shunt over a 5-year period are reviewed to establish the incidence of surgical and postsurgical complications. Although the yield of malignant cells found in the peripheral blood was increased after shunting, no new hematogenous metastases were observed after the operation. No evidence of disseminated intravascular coagulation was observed after shunt placement. While the shunt effectively relieved the discomfort due to abdominal distention and respiratory impairment, no restoration of cutaneous hypersensitivity was observed in the nine patients who were anergic prior to surgery. The median survival of patients with breast and gynecological cancer, after surgery, was significantly longer than the survival of patients with primary gastrointestinal neoplasma. In conclusion, peritoneal venous shunt appears to be an effective and safe method to improve the quality of life of patients with malignant ascites.

Ascites↗
PubMed1986

Homes for the elderly in Liguria.

A survey of 55 old people's homes in Liguria, a region in northern Italy, was carried out to investigate some social and demographic characteristics of the residents, their level of dependence and management. A total of 1666 residents was randomly selected and information was obtained from the records and from an interview with the care staff. Homes admitting only independent people were smaller than those admitting both dependent and independent people. Private homes tended to admit only independent people. The resident population showed relatively high geographical stability and a fair amount of outside support. Nearly half the residents were fully independent and 75% were prescribed at least one drug. 'Cerebroactive' drugs, psychotropic drugs, diuretics, and cardiac glycosides were extensively prescribed. Drug treatment was almost the only therapeutic intervention.

Activities of Daily Living↗