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Biomedical subjects

G Gilli

Publications and source records attributed to G Gilli.

At least 19 recordsLinked to original sources

Prognosis of childhood epilepsy: a community-based study in Copparo, Italy.

We performed a community-based study among children and adolescents with idiopathic and cryptogenic epilepsy and onset of the seizures between 0 and 19 years of age on the prognosis of being seizure-free. The study population was recruited during a descriptive investigation in the Local Health Service of Copparo (USL 34), Ferrara, Northern Italy. We included 111 patients (61 males and 50 females). The average length of follow-up was 18.8 years (ranging from 7 to 24 years). The cumulative probability of being in remission was 81.2% at 15 years after onset and the estimated percentage of patients in remission without therapy was 56% for the same time period. At 15 years after the onset of epilepsy, approximately 20% of patients continued to have seizures; nearly 25% continued to take antiepileptic drugs but had been free of seizures for at least 5 years; nearly 56% had been without seizures and free of medication for at least 5 years. Seizure type, gender, age at onset of the illness, epileptic abnormalities on EEG, family history of convulsive disorders, number and frequency of seizures prior to the start of treatment were found not to be helpful as prognostic factors. This community study, carried out on patients without the well known factors that adversely affect prognosis, confirms that the prospect of seizure control and for withdrawal of therapy is (generally) good.

Adolescent

Binding thermodynamics of 5-HT1A receptor ligands.

The thermodynamic parameters delta G degree, delta H degree and delta S degree of the binding equilibrium of 15 ligands (eight agonists and seven antagonists) to the 5-HT1A receptor subtype have been determined by affinity measurements carried out on rat cortex membranes (minus striatum) at six different temperatures (0, 10, 20, 25, 30, 35 degrees C), and by van't Hoff plots. Most of the compounds studied are tryptamine, phenylpiperazine and tetralin derivatives. Affinity constants were measured by saturation experiments for the selective 5-HT1A receptor agonist [3H]8-hydroxy-N,N-dipropyl-2-aminotetralin ([3H]8-OH-DPAT) and by inhibition assays of [3H]8-OH-DPAT binding for the other compounds. Scatchard plots were monophasic in the full range of temperatures, indicating a single class of high affinity binding sites. Van't Hoff plots of all ligands were linear in the temperature range investigated (0-30 degrees C or 0-35 degrees C). 5-Hydroxytryptamine (serotonin) and 5-methoxy-tryptamine (mexamine) displayed a positive slope. Experimental data indicate that for 5-HT1A receptor subtype agonists and antagonists are not thermodynamically discriminated. The results are discussed from a quantitative point of view with the aim of obtaining new details on the nature of the forces driving the 5-HT1A binding at a molecular level.

8-Hydroxy-2-(di-n-propylamino)tetralin

Thermodynamics of 5-HT3 receptor binding discriminates agonistic from antagonistic behaviour.

Thermodynamic parameters delta G degree, delta H degree and delta S degree of the binding equilibrium of eleven ligands (seven agonists and four antagonists) to the serotonin 5-HT3 receptor subtype have been determined by affinity measurements carried out on rat cortex membranes at six different temperatures (0, 10, 20, 25, 30, 35 degrees C) and van't Hoff plots. Affinity constants were obtained from saturation experiments of [3H]endo-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1-methyl-1-H-indazole- 3- carboxamide ([3H]BRL 43694, a selective 5-HT3 ligand) or by its displacement in inhibition assays for the other compounds. Van't Hoff plots were essentially linear in the temperature range investigated, showing that the delta Cp degree of the binding equilibrium is nearly zero. Thermodynamic parameters are in the range 18 < or = delta H degree < or = 53 kJ mol-1 and 202 < or = delta S degree < or = 320 J K-1 mol-1 for agonists and -16 < or = delta H degree < or = 0 kJ mol-1 and 70 < or = delta S degree < or = 179 J K-1 mol-1 for antagonists indicating that agonistic binding is totally entropy-driven while antagonistic binding is relatively less entropy- and more enthalpy-driven in the -T delta S degree versus delta H degree plot the thermodynamic data are clearly arranged in separate clusters for agonists and antagonists, which, therefore, turn out to be thermodynamically discriminated. Experimental results are discussed according to the following main points: (i) the approximate linearity of the delta H degree versus delta S degree plot in terms of enthalpy-entropy compensation and (ii) the fact that delta Cp degree approximately equal to 0 for practically all membrane receptors at variance with most reactions involving biomacromolecules in solution. Finally, the phenomenon of thermodynamical discrimination is reviewed and found to occur in five distinct membrane receptorial systems.

Animals

The combination of cisplatin, doxorubicin, and mitomycin (PAM) compared with the FAM regimen in treating advanced gastric carcinoma. A phase II randomized trial of the Italian Oncology Group for Clinical Research.

BACKGROUND: In a randomized Phase II study, the authors evaluated the activity and toxicity of the new cisplatin, doxorubicin, and mitomycin C (PAM) combination, that includes cisplatin (P) instead of 5-fluorouracil as in the 5-fluorouracil, doxorubicin, and mitomycin C (FAM) combination, in patients with advanced gastric carcinoma. FAM was utilized as a control treatment arm. METHODS: Fifty eligible patients were assigned to the FAM (5-fluorouracil 600 mg/m2 intravenous (i.v.) on Days 1, 8, 29, 36; doxorubicin 30 mg/m2 i.v. on Days 1 and 29; mitomycin C 10 mg/m2 i.v. on Day 1; every 8 weeks) and 52 to the PAM combination (cisplatin 60 mg/m2 i.v. on Days 1 and 29; doxorubicin 30 mg/m2 i.v. on Days 1 and 29; mitomycin C 10 mg/m2 i.v. on Day 1; every 8 weeks). All eligible patients were included in the evaluation of response, toxicity and survival. RESULTS: The PAM combination complete response (CR) rate was 8%, and the CR plus partial response (PR) rate was 21% (95% confidence interval [CI] from 10% to 32%). The median time to progression, duration of response, and duration of survival were 15, 26, and 29 weeks, respectively. The FAM combination CR rate was 2% and the CR plus PR rate was 26% (95% CI from 14% to 38%). The median time to progression, duration of response, and duration of survival were 17, 27, and 23 weeks, respectively. Hematologic and nonhematologic toxicity were mild with both regimens. CONCLUSIONS: This study shows that this new combination, that does not include 5-fluorouracil, is active in patients with advanced gastric carcinoma. Since treatment with 5-fluorouracil alone is still considered the standard according to some authors, the PAM combination may be included among the sequential clinical options before or after treatment with 5-fluorouracil alone.

Adult

Cost analysis of long-term feeding by percutaneous endoscopic gastrostomy in cancer patients in an Italian health district.

The aim of this study was to evaluate prospectively the cost of long-term feeding by percutaneous endoscopic gastrostomy (PEG). Cost analysis was carried out in 34 head and neck cancer patients, followed from the time of PEG placement to the death or the end of the study. Three main items were considered: (a) PEG placement (on an inpatient basis), subdivided into five subitems: the Freka FK-07 gastrostomy kit, materials and anaesthetic drugs used, antibiotics and antisecretory drugs, gastroscope amortization expenses and staff; (b) nutrition, considering the costs of enteral-feeding products, nutrition container and flexible tube connecting the container to the PEG; (c) patient care, dividing the patients into three groups: outpatients, home-care patients and outpatients shifting to home care during the follow-up. All patients had one medical and two nursing visits/month, and, if necessary, immediate additional access to a physician or nurse. The mean daily cost per patient of long-term feeding via PEG was obtained by adding up the mean daily costs per patient of the three items, and was compared with that of feeding via nasogastric tube, calculated in 11 patients using the same criteria. No procedure-related death nor periprocedural major or minor complications were observed. The 60-day mortality was 3/34. Seventeen patients were always seen on an outpatient basis and 8 were followed by our home-care unit: 9 outpatients shifted to home care during the follow-up. The mean duration of PEG use was 180.5 days (range 47-639). Two wound infections, treated with antibiotics, occurred during the follow-up. The mean daily costs of placement, nutrition and patient care were (Italian Iiras) L 2500, 24 510 and 1880 respectively (Deutschemarks: DM 2.08, 20.42 and 1.56), for a total mean daily cost of L 28,890 (DM 24.06), slightly higher than that of feeding via a nasogastric tube (L 27,340; DM 22.78). On the basis of the improved quality of life, as well as from the economic point of view, PEG can be considered the procedure of choice for enteral feeding of cancer patients, provided that a reasonably long survival can be expected.

Aged

Binding thermodynamics at A1 and A2A adenosine receptors.

Only recently the binding equilibrium of a number of ligands at adenosine A1 and A2a receptors has been analyzed from a thermodynamic point of view. This approach presents the advantage, with respect to usual affinity constant measurements, of a greater capability to give information about the molecular mechanisms underlying the binding process. All available data agree in indicating that, for both A1 and A2a receptors, agonist binding of adenosine derivatives was totally entropy-driven, while xanthine antagonist binding was essentially enthalpy-driven. The differences in thermodynamic behaviour of A1 and A2a agonists and antagonists could be interpreted in terms of a simplified general model of drug-receptor interaction, which accounted for the role played by the ribose moiety and N6-substituents of adenosinic drugs in determining both affinity and intrinsic activity properties. In the frame of this model, measurements of thermodynamic parameters of N6-monosubstituted agonists allowed to hypothesize, for the first time, the existence of partial agonists to adenosine A1 receptors, as now confirmed experimentally. All thermodynamic data concerning the interaction of all ligands studied with A1 and A2a receptors are briefly discussed in terms of the enthalpy-entropy compensation phenomenon which appears to be widely determined by the reorganization of solvent molecules in the binding process.

Animals

The assessment of skeletal maturation.

The measurement of skeletal maturity is important for the analysis of growth and growth disorders. Several methods are available for the assessment of skeletal age. They are all based on the recognition of maturity indicators, that is, of changes in the radiographic appearance of hand-wrist bones. The most commonly used methods are the Greulich and Pyle Atlas and the Tanner-Whitehouse (TW2) method. More recently, the FELS method has been described by Roche and coworkers. The assessments made using the Greulich and Pyle Atlas are often very inaccurate, whereas experience with the FELS method is still very limited. At the present time, the TW2 is still the method of choice. It is hoped that the development of a computerized method of assessment will lead to greater accuracy in the determination of skeletal maturity.

Age Determination by Skeleton

Geographical distribution of benzene in air in northwestern Italy and personal exposure.

Benzene is a solvent strictly related to some industrial activities and to automotive emissions. After the reduction in lead content of fuel gasoline, and the consequent decrease in octane number, an increase in benzene and other aromatic hydrocarbons in gasoline occurred. Therefore, an increase in the concentration of these chemicals in the air as primary pollutants and as precursors of photochemical smog could occur in the future. The objectives of this study were to describe the benzene air pollution at three sites in northwestern Italy throughout 1991 and 1994; to examine the relationship between benzene air pollution in indoor, outdoor, and personal air as measured by a group of nonsmoking university students; and to determine the influence of environmental tobacco smoke on the level of benzene exposure in indoor air environments. The results indicate a direct relationship between population density and levels of contamination; an indoor/outdoor ratio of benzene air pollution higher than 1 during day and night; a similar level of personal and indoor air contamination; and a direct relationship between levels of personal exposure to benzene and intensity of exposure to tobacco smoke. Human exposure to airborne benzene has been found to depend principally on indoor air contamination not only in the home but also in many other confined environments.

Air Pollutants

Binding thermodynamics of adenosine A2a receptor ligands.

The thermodynamic parameters delta G degree, delta H degree, and delta S degree of the binding equilibrium of seven adenosine agonists and five xanthine antagonists binding specifically to adenosine A2a receptors were determined by means of affinity measurements at six different temperatures (0, 10, 20, 25, 30 and 35 degrees) and van't Hoff plots. Affinity constants were measured on rat striatum membranes by saturation experiments for the selective A2a agonist 2-[p-(carboxy-ethyl)-phenethylamino-]5'-(N-ethyl)carboxamidoadenos ine ([3H]CGS 21680) and by inhibition assays of [3H]CGS 21680 binding for all other compounds. Scatchard plots were monophasic in the full range of temperatures, indicating a single class of high affinity binding sites whose receptor density, BMAX, is essentially temperature independent. Van't Hoff plots were linear in the temperature range 0-30 degrees for agonists and 0-35 degrees for antagonists; their thermodynamic parameters fall, respectively, in the ranges 7 < or = delta H degree < or = 50 kJ/mol and 177 < or = delta S degree < or = 278 J K-1 mol-1 and -36 < or = delta H degree < or = -7 kJ/mol and -33 < or = delta S degree < or = 94 J K-1 mol-1, showing that agonist binding is entropy-driven while antagonist binding is enthalpy-driven. The results are compared with those already reported for the binding of the same compounds to rat brain minus striatum adenosine A1 receptors obtained by displacing [3H]CHA as A1 selective radioligand (Borea PA et al., Mol Neuropharmacol 2: 273-281, 1992). The comparison suggests that the two receptors are very similar as far as their binding sites are concerned and possibly philogenetically related. The analysis of thermodynamical data makes it possible to propose an analogical model of drug-receptor interaction which may account for both affinity and intrinsic activity properties.

1-Methyl-3-isobutylxanthine

Updating about reductions of air and blood lead concentrations in Turin, Italy, following reductions in the lead content of gasoline.

Considering its well-know toxicity and the chronic human exposure to lead, international law-makers enforced some directives or laws calling for the reduction of lead content of gasoline. All of these legislative acts aimed to reduce health risks for the general population. The aim of this study was to consider the effectiveness of these laws on air lead levels and consequently on blood lead levels in a randomly selected urban Italian population. In particular, these markers were analyzed over the course of several years, corresponding to the periods just before and after enforcements of the reductions of lead in petrol. Data presented point out some considerations: (1) enforcement of legislative measures concerning the reduction of lead in petrol has reduced atmospheric levels of lead. This result demonstrates a major environmental success in primary prevention efforts. (2) This success is clear especially considering that the actual Pb-B levels can be extended to the urbanized populations. Pb-B levels were consistently higher for drinkers, for older adults, and for males. The mean of Pb-B level for the present urbanized population is higher than the U.S. overall population (6.4 vs 3 microgram/dl). This difference can be also explained considering the different historical period of enforcement of the restriction laws.

Adult

Binding thermodynamics of serotonin to rat-brain 5-HT1A, 5HT2A and 5-HT3 receptors.

The thermodynamic parameters delta G degrees, delta H degrees and delta S degrees of the binding equilibrium of serotonin to 5-HT1A, 5-HT2A and 5-HT3 rat-brain membrane receptors have been determined by means of affinity constant measurements at six temperatures in the range 0 -35 degrees C and van't Hoff plots. At variance with 5-HT1A and 5-HT3, the binding at the 5-HT2A receptors is strongly endothermic and entropy-driven. Comparison with the results obtained by other authors on 5-HT2A receptors in rats and humans suggests that the observed differences can be explained by a single amino acid difference in the receptor sequence between these two species.

Animals

Impaired glucose tolerance leads to delayed diagnosis of Alström syndrome.

OBJECTIVE: To emphasis the need for timely diagnosis of Alström syndrome. CASE: We report a case of late-detected Alström syndrome in a boy 15 1/2 years of age who was admitted because of poor wound healing and hyperglycemia. RESULTS: Diagnosis was made and the patient's impaired glucose tolerance improved by diet. CONCLUSIONS: Regular follow-ups are needed to recognize and possibly prevent late-appearing complications.

Adolescent

Benzene, toluene and xylenes in air, geographical distribution in the Piedmont region (Italy) and personal exposure.

The objectives of this study were the determination of: (a) benzene (B), toluene (T) and xylene (X) air pollution in three sites of the Piedmont region (north-western Italy), (b) the relationship between BTX pollution in indoor, outdoor and personal air measured for a group of non-smoking university students, (c) the influence of environmental tobacco smoke on the level of BTX exposure for indoor air environments. Results indicate (i) a direct relationship between human density and level of contamination and higher toluene pollution, (ii) an indoor/outdoor ratio of > 1 for all the three aromatics, (iii) a similar level of personal and indoor air contamination. Human exposure to BTX air pollution has been found to depend principally on indoor air contamination, not only on home pollution, but also, probably on many other confined environments.

Air Pollutants

Prevention of aspiration pneumonia during long-term feeding by percutaneous endoscopic gastrostomy: might cisapride play any role? An open pilot study.

The risk of aspiration during tube feedings has been reduced but not abolished by percutaneous endoscopic gastrostomy (PEG). This open study was planned to evaluate whether cisapride may play some role in preventing aspiration in long-term enteral feeding via PEG. A group of 29 patients, unable to swallow because of head and neck cancer (14 cases) or neurological disorders (15 cases) entered the study; 7 neurological patients, fed via nasogastric tube before PEG placement, had suffered from aspiration pneumonia during nasogastric feeding. All patients underwent PEG, and 10 mg cisapride was routinely given via PEG before each administration of enteral feeding and 6 h after its initiation when the feeding was continued for 12 h or more. Only 1 minor complication was observed during the acute hospital setting (ileus, spontaneously resolving after 36 h). After hospital discharge, the patients were followed for a total of 4935 days of feeding (range 47-508 days, mean time per patient: 170 days) and assessed weekly for the development of complications. No episode of probable/possible aspiration pneumonia was observed during the follow-up. Two neurological patients with involuntary movements had rupture of the feeding tube, which was replaced without complications. These results support the hypothesis that cisapride might play some role in the prevention of aspiration in patients fed via PEG, and justify the planning of some controlled, double-blind trials to verify such a hypothesis.

Adolescent

Growth and skeletal maturation in children with phenylketonuria.

Growth and skeletal maturation was evaluated in 82 children participating in the German Collaborative Study of Children Treated for Phenylketonuria (PKU). Height, weight, head circumference and bone age were recorded at regular intervals for the first 6 years of life. The mean SD score (SDS) for height was not significantly different from zero at study entry, but decreased mainly during the second year of life to a nadir of -0.78 in boys and -0.54 in girls at 2.5 years. During the subsequent years, a significant trend towards a regain of height SDS was noted in both sexes. Weight-for-height SDS was close to zero in both sexes, with a significant continuous increasing trend throughout the observation period. Head circumference SDS decreased in boys during the first year of life from -0.28 to -0.68, whereas girls showed only a minor change. During the further follow-up period, head circumference SDS remained at approximately -0.3 in boys and 0.0 in girls. While the mean verbal and performance IQ of the total study population at 5 and 6 years of age did not differ from a group of 212 healthy non-PKU children, patients with a head circumference SDS less than the population median at 2 years of age exhibited poorer cognitive abilities at school age than those patients with a relative head size greater than the population median. The children with a head circumference less than the median at 2 years had smaller head sizes already at birth; in addition, the change in relative head size during the first 2 years was correlated significantly with cognitive abilities at school age in boys. Mean bone age was identical to chronological age at each time point of observation. The rate of maturation was one year of bone age per year of chronological age. No correlation between phenylalanine intake or phenylalanine concentrations and the rates of body or head growth or skeletal maturation could be established. We conclude that despite adequate weight gain, moderate growth retardation occurred during the first 2 years of life in this group of children treated for PKU. Growth was more compromised in boys than in girls and tended to be compensated during later follow-up. Early infantile head circumference and growth appear to be predictors of cognitive development.

Age Determination by Skeleton

[Primary lymphoma of the breast. Clinico-pathologic description of a case].

Primary malignant lymphomas of the breast are extremely rare, accounting for only 0.04% to 0.53% of all breast malignancies. Recently a connection between some primary breast lymphomas and mucosa-associated lymphoid tissue (MALT) has been reported identifying an extranodal lymphoma as MALT-type bears some biologic relevance, especially in terms of its spread to other mucosal sites, which sometimes occurs before disseminating into peripheral lymphoid tissue. The Authors report a case of primary breast lymphoma associated with a possible connective disease. Nevertheless the case reported cannot confirm a precise time relationship between malignant lymphomas and autoimmunity, we think that it can be possible.

Aged

Influence of spontaneous and surgical menopause on atherogenic metabolic risk.

We evaluated serum total-, LDL-, HDL-, cholesterol and triglycerides in 858 women. Sixty-seven were in premenopause, 307 in perimenopause, 326 in spontaneous menopause, and 158 women underwent hysterectomy. Of these, 101 had bilateral ovariectomy, 24 with unilateral ovariectomy and 33 with retention of both ovaries. After correcting for chronological age and body mass index by variance analysis, it was found that total-, LDL- and HDL-cholesterol significantly increased during menopause without changes in the total cholesterol/HDL-cholesterol, LDL-cholesterol/HDL-cholesterol and triglycerides/HDL-cholesterol ratio. The changes gradually occurred during the months preceding spontaneous cessation of menses. Atherogenic metabolic risk (as relative risk of high total and LDL-cholesterol, estimated by logistic regression analysis) significantly increased in all groups of women in reference to premenopause. The risk observed in surgical menopause with bilateral ovariectomy was higher than in spontaneous menopause, and conservation of ovaries in hysterectomized women seems to protect only partially against such an increase.

Adult

Geographical and temporal patterns of air-borne and personal 1,1,1-trichloroethane exposure in Piedmont region (Italy).

During the summer of 1989 and the winter 1989-1990, we initiated measurements of 1,1,1-trichloroethane concentrations in indoor, outdoor, and 'personal' air, in urban and rural sites. In the Piedmont region (North-Western Italy) we have carried out an atmospheric monitoring study: in the centre of Turin city (urban site), in Cuorgnè (rural site), and in Banchetta (remote site). First results confirm a higher winter contamination (11.67 vs. 2.79 micrograms/m3) and a higher contamination at the urban site, compared to rural and remote sites. Excluding Cuorgnè in the summer, all indoor/outdoor ratios are greater than 1 and, in all cases, the 'personal' air shows higher 1,1,1-trichloroethane levels than indoor and outdoor air. In Turin the relationships between winter and summer all show a higher winter contamination, while, in Cuorgnè no differences are proven.

Air Pollutants