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Biomedical subjects

A Lippi

Publications and source records attributed to A Lippi.

At least 73 records · Page 4Linked to original sources
PubMed1988

Correlation between cranial computed tomographic scans at diagnosis in children with acute lymphoblastic leukaemia and central nervous system relapse.

145 children with acute lymphoblastic leukaemia (ALL) were evaluated over a period of 3 years in a multicentre study in which serial cranial computed tomographic (CT) scans of the brain were done. All patients were symptom-free. CT scans were graded as normal, borderline (slight or moderate cerebral atrophy), or pathological (severe cerebral atrophy). 62% (90/145) of children had CT scan abnormalities at diagnosis. After a median follow-up of 24 months (range 6-36) 12 of 108 evaluable patients had central nervous system (CNS) relapses (6 isolated relapses and 6 combined with relapse at another site). All patients with CNS relapse had an abnormal CT scan at diagnosis (8 pathological and 4 borderline). No relapses were observed among the 42 patients with a normal cranial CT scan at diagnosis. A significantly higher proportion of severe cerebral atrophy, both following CNS prophylaxis and after the discontinuation of treatment, was found among patients with a borderline CT scan at diagnosis than among patients with a normal CT scan at diagnosis. Thus an abnormal cranial CT scan at diagnosis in children with ALL seems to have prognostic significance.

Adolescent↗
PubMed1988

Risk factors and genetic background for Alzheimer's disease.

Analytic epidemiology has contributed significantly to the generation and testing of hypotheses of the causes of AD. Several case-control studies have indicated risk factors related to the genetic hypothesis, such as: the presence of cases of either AD or Down's syndrome in other family members and the advanced age of the mother at subject's birth. In this respect recent molecular biology studies on DNA from patients affected by the familial form of AD, have demonstrated a genetic polymorphism localized on chromosome 21. On the same chromosome, the gene coding for beta-amyloid has been also recently localized. Immune, viral and toxic factors, thought to cause AD, have been also investigated in case-control studies, none of them has been found consistently associated with the disease, with the only exception of the head trauma. On the other hand most case-control studies have been carried out in younger cases and no large studies are yet available for late onset patients.

Aluminum↗
PubMed1987

The metabolism of carbamazepine in humans: steric course of the enzymatic hydrolysis of the 10,11-epoxide.

Carbamazepine 10,11-oxide (1a,10b-dihydro-6H-dibenzo[b,f]oxireno[d]azepine-6-carboxamide), a key intermediate in carbamazepine metabolism, was found to be unusually resistant to enzymatic hydrolysis when incubated with microsomal and cytosolic fractions from rabbit, rat, and guinea pig livers. However, its hydrolysis product, trans-10,11-dihydro-10,11-dihydroxy-5H-dibenzo[b,f]azepine-5-carboxamide , was excreted, as previously reported, both in the free and in conjugated forms, as the main metabolite in the urine of humans under carbamazepine treatment. The free diol and that obtained after treatment with beta-glucuronidase/arylsulfatase were both found by Mosher's method to be formed in an enantiomeric excess of 80%, the prevalent enantiomer having the (-)-10S,11S absolute configuration, as determined by applying the CD exciton coupling method to its bis[p-(dimethylamino)benzoyl] ester. This finding confirms the pronounced enantioselectivity of the microsomal epoxide hydrolase toward meso and racemic substrates, but is in contrast with the prevalent formation of (R,R)-diols in most other known cases of enzymatic hydrolysis of epoxides. Preparatively useful syntheses of the racemic trans-10,11-dihydro-10,11-diol and of 9-(hydroxymethyl)-10-carbamoylacridan, another carbamazepine metabolite, are reported for the first time.

Adult↗
PubMed1986

A simple conductimetric method as an alternative to the colorimetric p-nitrobenzylpyridine test for the measurement of the reactivity of potentially mutagenic alkylating compounds.

A simple method for the measurement of the kinetics of reaction of potentially mutagenic alkyl halides with amines, based on the direct conductimetric monitoring of the quaternary ammonium salt produced in these reactions, is proposed and applied to the alkylation of p-nitrobenzylpyridine (NBP) and triethylamine (TEA) in different solvents. With respect to the classical colorimetric NBP-test, this method has the advantage that the rates can be measured continuously over the entire course of the reactions and the kinetic order and constants can be easily obtained. It is also shown that the previously proposed, NBP modified test', using simultaneously NBP and TEA, gives actually the sum of the rate constants for the reactions of the alkylating reagent with the two amines.

Alkylation↗
PubMed1986

Risk factors for clinically diagnosed Alzheimer's disease: a case-control study of an Italian population.

We conducted a case-control study of 116 patients with the clinical diagnosis of Alzheimer's disease (AD) in seven Italian centers. One hundred sixteen hospital controls and 97 population controls were matched by age, sex, and region of residence to the cases. A structured questionnaire was administered to the next-of-kin of cases and controls by trained interviewers to identify possible risk factors. Genetic, viral, toxic, immunologic, medical, surgical, and personality factors were investigated. Dementia among first- or second-degree relatives and advanced age of the mother at subject's birth (age over 40) were associated with AD. Head trauma was more frequent in cases than in either hospital or population controls, but the differences were not significant. Our data did not confirm the previously reported association with antecedent thyroid disease or family history of Down's syndrome.

Adult↗
PubMed1984

Structure activity relationship of epoxides: different mutagenicity of the two diastereoisomeric 3-bromo-1,2-epoxycyclohexanes.

The mutagenic activities in V79 Chinese hamster cells and the alkylating abilities towards nicotinamide of the two diastereisomeric cis and trans-3-bromo-1,2-epoxycyclohexanes were measured and compared with those of unsubstituted 1,2-epoxycyclohexane and bromocyclohexane. trans-3-Bromo-1,2-epoxycyclohexane exhibited a mutagenic activity 2.5 times higher than that of its cis diastereoisomer, but very similar to that of the parent unbrominated epoxide, whereas the electrophilic reactivities towards nicotinamide were very similar for the three epoxides tested. Bromocyclohexane showed the highest toxicity, but no alkylating ability. The presence of an epoxide hydrolase activity in the V79 Chinese hamster cells used in the mutagenesis tests has been demonstrated using safrole oxide as the substrate, cis-3-Bromo-1,2-epoxycyclohexane, but not its trans diastereoisomer, is hydrolyzed by the enzyme present in microsomal preparations from the V79 cells. The results indicate that for the cycloaliphatic compounds examined: (1) the introduction of a bromide substituent at the carbon adjacent to the oxirane ring does not cause an increase in mutagenicity, (2) the relative stereochemical configuration at the above carbon does affect the biological activity and (3) the significantly different mutagenicity of the two diastereoisomeric 3-bromo-1,2-epoxycyclohexanes is not attributable to a different electrophilic reactivity, but could be related to some specific interaction with detoxifying enzymes present in the V79 Chinese hamster cells used in the biological experiments.

Alkylation↗
PubMed1983

Mutagenicity of 3 structurally related epoxides, with defined stereochemical configuration, in Saccharomyces cerevisiae and in V79 Chinese hamster cells.

3 structurally related epoxides, 3,4-epoxycyclohexene, trans-1,2,3,4-diepoxycyclohexane and trans-3,4-epoxycyclohexane-r-1,trans-2-diol (anti isomer) were tested for their ability to induce both point mutation, mitotic gene conversion and recombination in a diploid strain (D7) of the yeast Saccharomyces cerevisiae, with and without a mammalian microsomal activation system, and the formation of 6-thioguanine-resistant mutants in V79 hamster cells. Genetic effects were related to the alkylating properties of the epoxides, as measured by alkylation of 4-(p-nitrobenzyl)pyridine (NBP). Of the 3 epoxides, only 3,4-epoxycyclohexene, characterized by the highest reactivity towards NBP, induced all genetic effects in both test systems. A marginal activity was shown by trans-1,2,3,4-diepoxycyclohexane only in the yeast. The lack of genetic activity of the anti isomer of 3,4-epoxycyclohexane-1,2-diol, in spite of the formal similarity of its functional groups with those present in mutagenic polycyclic arene epoxydiols, was attributed to the dramatic reduction of lipophilicity of the molecule.

Animals↗
PubMed1983

Metabolism of 1,3-cyclohexadiene by isolated rat liver cells.

The metabolism of 1,3-cyclohexadiene by hepatocytes from phenobarbital induced rat has been investigated. Parenchymal cells were obtained by liver perfusion with a hyaluronidase-collagenase mixture. The addition of the diene to a suspension of hepatocytes gave rise to a type I difference spectrum indicating the formation of an enzyme-substrate complex with cytochrome P-450. The subsequent metabolic pathway of 1,3-cyclohexadiene has been shown to involve, as the first step, the formation of 1,2-epoxy-3-cyclohexene, which is rapidly hydrolyzed to trans-3-cyclohexene-1,2-diol and trans-2-cyclohexene-1,4-diol by a non-enzymatic process. The monoepoxide could not be detected in the incubation medium because of its high reactivity. Therefore, kinetic parameters of the epoxidation reaction were determined by following the rate of production of the diols. When incubated with hepatocytes, trans-3-cyclohexene-1,2-diol, the main product of 1,3-cyclohexadiene metabolism, elicited a reverse type I spectrum, indicating that this compound is not a good substrate for the monooxygenase system.

Animals↗
PubMed1982

[Determination of metabolizing activities of xenobiotic tissue in rat embryo fibroblasts].

Rat embryo fibroblast suspensions were prepared from 19-day-old wistar rat fetuses by trypsin digestion of the minced fetal tissue. Drug-metabolizing capability of isolated viable rat embryo cells on 7-ethoxycoumarin and 1,3-cyclohexadiene has been investigated. The biotransformation of 7-ethoxycoumarin represents a suitable experimental tool to measure the level and significance of the Phase I and Phase II metabolism systems. We estimated the mixed-function oxidation by the fluorimetric measurement of "unconjugated" 7-hydroxycoumarin in the incubation medium while the conjugates formation was determined by subsequent hydrolysis with beta-glucuronidase and aryl sulphatase. 1,3-Cyclohexadiene was selected as a substrate for mixed-function oxidation for a useful comparison of drug-metabolizing capability in isolated viable rat embryo cells with rat hepatocytes. When 1,3-cyclohexadiene was incubated with rat embryo fibroblasts for different times, cyclohexene-1,2-diol resulted to be the main metabolite. Cyclohexene-1,4-diol was detected only in traces. Therefore the metabolic pathway of 1,3-cyclohexadiene with rat embryo cells, as well as isolated hepatocytes, involves the intermediate formation of the 3,4-epoxycyclohexene, that is rapidly hydrolyzed to diols by a non enzymatic process.

Animals↗
PubMed1982

[Preliminary results on the metabolism of 1,3-cyclohexadiene in isolates rat hepatocytes].

Hepatocytes of adult male rats were isolated by hepatic perfusion with a mixture of collagenase and hyaluronidase. This procedure gave a high yield of viable cells, as determined by trypan blue exclusion. The addition of 1,3-cyclohexadiene to a suspension of isolated liver cells gave rise to a type-I spectral change indicative of the formation of the cytochrome P-450-substrate complex. 1,3-cyclohexadiene was then incubated with hepatocytes for different times, to determine its biotransformation. Cyclohexadiene-1,2-diol resulted to be the main metabolite. It is proposed that the metabolic pathway of 1,3-cyclohexadiene involves the intermediate formation of an epoxide which is rapidly transformed to the correspondent diol.

Animals↗
PubMedDate not supplied

Immune recovery following antineoplastic chemotherapy and highly active antiretroviral therapy (HAART) in a child with HIV-1 infection previously unresponsive to HAART.

We report the case of a perinatally HIV-1-infected child, previously immunologically unresponsive to antiretroviral treatments (including the highly active antiretroviral therapy), who instead developed a vigorous and long-lasting immune response after the highly active antiretroviral therapy was associated with antineoplastic chemotherapy undertaken for a B-cell non-Hodgkin bone lymphoma.

Adolescent↗
PubMedDate not supplied

[Census 2004 of the Italian Renal and Dialysis Units. Emilia-Romagna, Toscana].

The 2004 SIN census of the Italian nephrology and dialysis centres showed many interesting data about the epidemiology and the organization in the Regions of Emilia-Romagna (ER) and Tuscany (T). A) Epidemiology: incidence of dialysis patients 169 pmp (patients per million population) in ER, 147 ppm in T; prevalence of dialysis patients 639 pmp and 665 pmp, respectively; prevalence of transplanted patients 325 ppm in ER and 233 pmp in T; gross mortality of dialysis patients 16.3% and 13.4%, respectively; B) Type of vascular access in prevalently dialysis patients: arteriovenous fistula 83% and 78%; central venous catheter 13% and 12%; vascular graft 5% and 9%. C) Structural resources: nephrology beds 44 mp (per million population) and 50 mp; dialysis places 157 and 146 mp. D) Personnel resources : renal physicians 29 and 41 mp; renal nurses 171 and 202 mp ; each renal physician cares for 22 and 16 dialysis patients, and each renal nurse takes care of 3.7 and 3.3 dialysis patients. E) Activity: hospital admissions 1572, 1769 pmp; renal biopsies 115 and 166 pmp.

Ambulatory Care Facilities↗
PubMedDate not supplied

[Loss of psychic autoactivation syndrome: bilateral lacunae of the neostriatum. Clinico-radiological study of 2 cases].

In two patients with lack of spontaneous activity and emotionality, without dementia or depression and in absence of other neurologic signs, the "athymormia syndrome" has been diagnosed. CT scan and MRI showed bilateral symmetrical lesions in basal ganglia. We discuss the possible pathophysiological basis of the syndrome and the recent data about the functional connections among basal ganglia, frontal cortex and limbic system.

Adult↗
PubMedDate not supplied

[The dementias].

Statistics indicate that in Europe people over 65 years of age will be 23.5% at the beginning of the next century and prevalence of severe dementias is estimated to be 5% in this population group. Clinically, dementia is a syndrome characterized by memory loss, other cognitive dysfunctions and loss of ability for self-care. This organic syndrome, that can have many different causes, must be differentiated from other similar psychiatric disorders of the elderly such as the pseudo-dementias. The most important of these causes are Alzheimer's disease (AD) and vascular dementias. Other causes are infections, toxic and metabolic disorders, normal pressure hydrocephalus and head trauma. Many efforts are required in order to reach an accurate differential diagnosis, as 10-15% of the dementia syndromes are reversible if an appropriate therapy is applied. Because of its high frequency, AD is one of the most actively studied areas in dementia research. The specific causes of AD are still unknown, but recent case-control studies suggest the importance of risk factors such as familiarity and previous head trauma. Other hypotheses concern prion infections, aluminium toxicity and immunologic disorders. The most important findings of the last years however, concern biochemical alterations in Alzheimer's brains. After the first observations of Davies and Maloney (1976), who observed a reduction of choline acetyltransferase in cerebral cortex, many reports successively indicated the importance of deficiencies of the cholinergic systems in AD. Other neurotransmitter systems, such as the noradrenergic and the serotoninergic systems, were also found to be involved in AD. From these findings a rational therapeutic approach to the disease was proposed. Initially, the clinical trials employed physostigmin with uncertain results. Later, therapeutic attempts with choline, lecitine, acetylcarnitine and phosphatidilserine resulted more promising, at least in the initial phase. However, consistent data are not yet completely available. Finally, the management of AD also concerns problems of familiar education to the behavioural management of AD patients and the eventual possibilities of social assistance. Vascular dementia and Creutzfeldt-Jakob disease will also be discussed.

Aged↗