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Biomedical subjects

G Ronco

Publications and source records attributed to G Ronco.

At least 37 records · Page 2Linked to original sources
PubMed1997

Interaction of spontaneous and organised screening for cervical cancer in Turin, Italy.

In a screening programme for cervical cancer, coverage of the target population is a major determinant of effectiveness and cost-effectiveness and is one of the parameters for programme monitoring recommended by the "European Guidelines for Quality Assurance". An organised screening programme was started in Turin, Italy, in 1992. Spontaneous screening was already largely present, but coverage (proportion of women who had at least a test within 3 years) was low (< 50%) and distribution of smears uneven. No comprehensive registration of spontaneous smears was available. All women were invited for the first round, independently of their previous test history. Coverage was estimated by integrating routine data from the organised programme with data on spontaneous screening obtained by interviews of a random sample of 268 non-compliers to invitation and 167 compliers. Overall (spontaneous + organised) coverage was estimated to be 74% (95% CI, 71-78%). The proportion of the target population covered as an effect of invitation was estimated to be 17% (95% CI, 15-20%). Invitations were successful in increasing coverage in previously poorly screened groups. Although 20-25% of compliers was estimated to have had further tests before the end of the round, we estimated that switching to a 3-year interval saved approximately 0.26 tests per complier. This suggests that invitations to an organised programme even to previously covered women, can be a cost-effective policy. Our method of estimating overall coverage can be useful in many other European areas where a comprehensive registration of smears is not available.

Adult↗
PubMed1996

Estimating the sensitivity of cervical cytology: errors of interpretation and test limitations.

The objective of this study was to estimate: (i) the sensitivity of cytologists in recognizing abnormal smears; (ii) the sensitivity of cervical cytology as a method of detecting abnormal smears among those obtained in the presence of cervical intraepithelial neoplasia (CIN). Study subjects were 61 women with a histologically confirmed CIN identified through colpohistological and cytologic screening. For objective (i) new smears were taken from study subjects just before treatment, mixed with routine preparations, interpreted by unaware cytologists and then blindly reviewed by a group of three expert supervisors, who reached a consensus diagnosis. Cytologists classified as positive for squamous intraepithelial lesion (SIL) 30 of the 34 smears judged as positive by supervisors (100% of smears classified as high-grade and 67% of smears classified as low-grade SIL by the supervisors). Our approach, based on creating a set of smears with a high a priori probability of being positive, proved to be an efficient way of estimating errors of interpretation. For objective (ii), smears taken at the moment of diagnosis, just before biopsy, were also reviewed by the same supervisors. These CIN cases were identified among asymptomatic women independently of cytological findings and results are therefore not subject to verification bias. Among the 33 histological CINII/III, four (12%) smears had no atypical cells (three negatives and one unsatisfactory) at review. The same proportion was 26% (four negatives and one unsatisfactory) among the 19 histological CINI. No significant differences in smear content were found between the seven 'false negatives' and a sample of 'true positive' and 'true negatives' for a number of formal adequacy criteria (including presence of endocervical cells). Strong differences were found between positive smears taken just before biopsy and those taken just before treatment (in 11 women the first smear only was positive, while the opposite was never observed), suggesting an effect of punch biopsy in removing lesions.

Diagnostic Errors↗
PubMed1996

[Effect of the nature of the heteroatom of a monosaccharide derivative on its inhibitory action in relation to P-type calcium channels expressed in the Xenopus oocyte].

Our results demonstrate that saccharidic derivatives obtained by adding a C8 alkyl group through various heteroatomes (O, N or S) to a monoacetonide residue possess an inhibitory effect towards putative P-type calcium channels expressed in Xenopus oocytes. These derivatives partially and reversibly inhibit the activity these channels without changing their electrophysiological properties. Nevertheless, the derivative containing the heteroatome N also affects the fast and tetrodotoxin-sensitive sodium channel activity. Thus, only ether and thioether compounds (heteroatome O or S) can be selected for their inhibitory effect on P-type apparented calcium channels.

Animals↗
PubMed1996

Accuracy of the umbilical arteries Doppler flow velocity waveforms in detecting adverse perinatal outcomes in a high-risk population.

OBJECTIVE: To define the accuracy of the umbilical artery Doppler flow velocity waveforms, according to different cut-off values, in predicting adverse perinatal outcomes among fetuses at high risk of hypoxic complications. SUBJECTS: Two hundred and sixty-five pregnant women with diagnosis of small for gestational age fetus and/or pregnancy induced hypertension studied in four Italian ultrasound units. METHODS: Prospective study. Serial Doppler ultrasound measurements of the umbilical artery were performed. Results were not available for clinical management. Cut-off curves, corresponding to different age-specific centiles of the pulsatility index distribution among pregnancies resulting in healthy newborns, regardless of birthweight, were computed by regression methods. Sensitivity, specificity, positive predictive value and negative predictive value of such cut-off curves, and of absent/reverse end-diastolic flow, in predicting different adverse outcomes were estimated. The adverse outcomes were: perinatal or neonatal death (OUTCOME 1). Death or Apgar<7 at 5' or need for admission to intensive care unit or other hypoxic related abnormalities (OUTCOME 2). Either OUTCOME 2 or birthweight<l0th centile (OUTCOME 3). Both OUTCOME 2 and birthweight<10th centile (OUTCOME 4). RESULTS: The best accuracy was in predicting OUTCOMES 1 and 4. Positive predictive value increased strongly with higher cut-off curves while negative predictive value only decreased slightly. For absent/reverse end-diastolic flow, negative predictive value and positive predictive value were respectively 94% and 39% for death, and 81% and 72% respectively for OUTCOME 2. For the 95th centile curve the corresponding figures were 96%, 33% and 84%, 67%. The 60th centile curve had a 85% and 74% sensitivity value for death and OUTCOME 2 respectively, but the corresponding positive predictive values were 18% and 40% only. CONCLUSIONS: The findings of an absent end diastolic flow or of pulsatility index values above the 95th centile curve strongly suggest it is time to deliver the fetus. The 60th centile curve is the most suitable to recognize fetuses at risk for abnormal outcome, but early delivery should be avoided because of its low positive predictive value.

Apgar Score↗
PubMed1996

Novel monoacetoneglucose derivatives with calcium antagonist activity.

Ethers and thioethers of monosaccharides have been synthesised which show potent toxicity to mouse (LD50 > or = 4 g.kg-1 O.W. and 0.2 to 1.5 g.kg-1 I.P.W.). A study of calcium antagonist activity for the full series of compounds indicated that the activity was similar for both O- and S- ethers and maximum activities were observed for monoacetoneglucose ethers possessing carbon chain close to 8 carbons.

Animals↗
PubMed1995

Effects of various valproic acid derivatives on low-calcium spontaneous epileptiform activity in hippocampal slices.

Lowering of extracellular calcium induces the development of spontaneous epileptiform activities in rat hippocampal slices. The antiepileptogenic effect of four new sugar-ester derivatives of valproic acid--dimethylenexylitol valproate, monoacetoneglucose valproate, diacetoneglucose valproate and glucose valproate--were investigated on such activity through 20-min bath applications and their effect compared to that of valproate, valpromide and phenytoin. Sodium valproate, 5 mM, did not completely suppress the spontaneous epileptiform activity. Valpromide, 2.5 mM, and phenytoin, 0.25 mM, produced complete cessation of seizure activity. Dimethylenexylitol valproate, 0.1 mM, completely suppressed spontaneous epileptiform activities. The other derivatives were less potent: concentrations of 0.25 mM of monoacetoneglucose valproate and 1 mM of diacetoneglucose valproate and glucose valproate were required for complete cessation of activity. The sugar carriers alone were devoid of effect. The data show that these molecules have a direct action on the nervous tissue and their antiepileptogenic efficacy in the low-calcium model is far larger than that of valproic acid itself. Such derivatives, especially dimethylenexylitol valproate, appear to be promising for development of new antiepileptic molecules.

Animals↗
PubMed1994

Selective induction of apoptosis in myeloid leukemic cell lines by monoacetone glucose-3 butyrate.

Butyric acid is a potent cell growth inhibitor and differentiation inducer. Our previous studies have shown that MAG=3but, a monosaccharide ester of butyric acid, used at 1 mM, induces apoptosis in the HL-60 cell line. We report here that this drug can also induce apoptosis in the U-937 leukemic cell lines whereas the myeloblastic KG1 and the NB4 promyelocytic leukemic cell lines were refractory to induction of apoptosis. In order to determine what can trigger cells to undergo apoptosis, cell cycle analysis, induction of differentiation and p53, c-myc and Bcl-2 expression was studied. Apoptosis was correlated to an arrest of cell growth in the G1 phase of the cell cycle and to an induction of differentiation through the monocytic pathway in HL-60 and U-937 cells. Time course studies demonstrated DNA fragmentation after few hours incubation with the drug, while morphological signs appeared later (days 2 or 3). Northern blot analysis and flow cytometric studies have shown that cell death induced by MAG=3but was not associated to an overexpression of c-myc and p53. However, in the HL-60 cells, BCL-2 protein expression was decreased after MAG=3but treatment, corroborating the apoptosis observed.

Apoptosis↗
PubMed1994

Home injuries in children: a population-based intervention trial.

We conducted a population-based intervention trial to evaluate the effectiveness of a program to prevent home injuries in children. We recruited a population of 1,015 young parent couples. Among those couples, we measured attitudes toward prevention of home injuries to children before and after the intervention. The intervention had limited effectiveness, which was somewhat greater among white-collar families and families with a higher paternal educational level. We found an association between the occurrence of injuries and educational level of the fathers (odds ratio = 1.7 and 1.9 for 6-12 years and < 6 years of school completed, respectively, vs > or = 13 years).

Accidents, Home↗
PubMed1994

Who does Pap-test? The effect of one call program on coverage and determinants of compliance.

A pilot phase of a population-based organized screening programme for cervical cancer was run in Turin, Italy, in May-June 1991. Based on the city population lists, 1181 women 25 to 64 years old were invited in two family clinics. Overall compliance to invitation was 41.7%. In order to study the determinants of compliance, a random sample of 372 compliers and 398 non-compliers was interviewed. Interval since last Pap-test was strongly associated with compliance (ORs of complying were 2.52, 1.53, 1.41, 0.50 and 0.16 for intervals longer than 3 years, 1-3 years, 6 months-1 year, 3-6 months and less than 3 months respectively vs. never having had a Pap-test, p < 0.001). Estimated compliance was 39% among never screened women and 65% among those tested since more than 3 years, leading to an over 70% overall estimated coverage (women who complied or had a spontaneous test within 3 years). On the other hand, the effect of a number of sociodemographic variables (age, education, place of birth, marital status) was very weak or opposite (lower compliance among younger and more educated women) to what we found in a previous study on spontaneous Pap-testing. The clinic allocated to pre-fixed appointments had a higher compliance than the clinic with appointments to be arranged (OR = 2.36 95% c.i. 1.66-3.36). Anxiety caused by periodic controls for early diagnosis of cancer was an important negative determinant of compliance (ORs of complying were 0.85, 0.49, and 0.16 for those with mild, moderate and severe levels of anxiety vs. those reassured by the test). We concluded that personal invitations were actually able to reach those women who have a poor level of spontaneous practice and could reduce the selection in access to this preventive practice.

Adult↗
PubMed1993

Butyric acid and its monosaccharide ester induce apoptosis in the HL-60 cell line.

Butyric acid is a potent cell growth inhibitor and differentiation inducer (1-4). However, the short plasma half-life of this fatty acid limits its potential therapeutic use (5,6). The recent synthesis of several monosaccharide esters of butyric sodium salt (BuONa) with a prolonged plasma half-life and similar biological properties as the sodium salt opens new perspectives (7-12). We report here that the human myeloid HL-60 cell line can be induced to apoptosis when cultured with one of these esters, monoacetone glucose 3-butyrate (MAG = 3but) or BuONa. Cytospin slide preparations and flow cytometric studies showed that HL-60 cells treated with 1 mM MAG = 3but or BuONa exhibited a reduction in cell volume and condensation of nuclear structure characteristic of apoptosis, associated with monocytic differentiation. Time course studies demonstrated that DNA fragmentation, as determined by agarose gel electrophoresis, was detected 4 hours after incubation with the drugs, while morphologic signs appeared at day 3. Apoptotic cells increased with culture time and reached a maximum at day 6 of 20 +/- 5% with BuONa, 25 +/- 5% with MAG = 3but, and only 5 +/- 2% in controls. These findings suggest that these drugs may exert their actions, at least in part, through induction of apoptosis.

Antineoplastic Agents↗
PubMed1993

Prevention of exposure of young children to parental tobacco smoke: effectiveness of an educational program.

AIMS AND BACKGROUND: We conducted a population-based trial to evaluate the efficacy of an intervention aimed at preventing exposure of young children to parental tobacco smoke. METHODS: Of the 1142 eligible couples (parents of newborn babies), 1015 were recruited; the intervention was offered to 402 and not to 613 families. RESULTS: A strong association was found between social class and smoking behavior, in particular smoking during meals at home. The intervention itself had limited effectiveness in decreasing the number of smokers. The effect was stronger in mothers and in higher social groups. Among the "white-collar" families belonging to the intervention group, the proportion of mothers who stopped smoking was 3 times higher than in the control group (not statistically significant). CONCLUSIONS: Educational interventions against smoking should be planned taking into account the difference in efficacy according to social class.

Adult↗
PubMed1993

The value of the 1981 WHO histological classification in inter-observer reproducibility and changing pattern of lung cancer.

A series of 722 lung carcinomas, surgically resected and typed some years ago according to the 1967 WHO classification, was independently reviewed by 2 observers in order to test the reproducibility of histopathological typing when using the criteria of the 1981 WHO classification. Typing was fully agreed upon in 87% of cases. Agreement was very high for squamous-cell, small-cell and adeno-carcinomas (kappa = 0.87, 0.89 and 0.85, respectively) while adenosquamous (kappa = 0.56) and large-cell (kappa = 0.71) carcinomas were more controversial categories. A consensus diagnosis was formulated for lesions with discrepant diagnoses. When comparing the final typing to the previous typing based on the 1967 WHO classification, squamous- and large-cell carcinomas were reduced respectively by 22% and 33% and adenocarcinomas increased by 94% of the original number. The 1981 "adenosquamous carcinoma" category included 2.8% of the tumours, while the corresponding 1967 category "combined epidermoid and adenocarcinoma" was empty. These changes must be taken into account when considering epidemiological studies, especially those aiming at evaluation of the secular trends of lung cancer by cell type.

Adenocarcinoma↗
PubMed1993

Differential elimination of synthetic butyric triglycerides in vivo: a pharmacokinetic study.

New butyrate derivatives were synthesized to investigate the residence time of potent butyric acid in vivo. These derivatives were triglycerides in which one, two, or three butyric acid molecules were bound to glycerol or to mono- and dipalmitic esters of glycerol. Pharmacokinetic studies showed that a constant plasma level of each compound was maintained for a long time; all molecules had identical volumes of distribution, but differed about their mean residence time. Triesters in which palmitic acid was present displayed no toxicity and seemed to be even more stable in the organism; this may be due to their adsorption on the tissue. Other triglycerides constituted by butyric acid and various long fatty acids may be synthesized and useful in long-term clinical treatment.

Animals↗
PubMed1993

Histologic parameters of vulvar invasive carcinoma and lymph node metastases.

We evaluated seven histologic parameters (tumor diameter, histologic grading, depth of stromal invasion, vascular invasion, pattern of invasion, lymphoplasmocytic infiltration and amount of necrosis) of 50 cases of vulvar invasive carcinoma to assess their correlation with groin lymph node metastases. Of 50 patients, 25 had groin lymph node metastases. No lymph node metastasis was found in four cases with depth of invasion < or = 2.0 mm. Among the 31 patients with vascular invasion, 23 (74%) had positive nodes, whereas lymph nodes were metastatic only in two of the 19 patients (10%) without vascular invasion. At univariate analysis, performed with Fisher's exact method, all the parameters considered, except pattern of invasion and amount of necrosis, were significantly associated (P < .05) with lymph node metastases. However, after adjustment by multiple logistic regression for the variables statistically significant at univariate level, only the presence of vascular invasion was significantly associated with nodal involvement and tumor diameter was borderline, whereas the effect of the other variables was almost completely explained by confounding.

Aged↗
PubMed1992

Enhancement by stable butyrate derivatives of antitumor and antiviral actions of interferon.

The use of n-butyric acid has been associated with induction of cell differentiation and bypassing of genetic defects in the suppression of malignancy. This biological response modifier satisfies the requirements for specificity and low toxicity, and its use can be considered as an alternative approach to conventional cancer chemotherapy. However, a lack of clinical efficacy has been observed with butyrate and attributed mainly to the rapid metabolism of the compound. Butyric acid pro-drugs derived from monosaccharides such as 3-O-butanoyl-1,2-O-isopropylidene-alpha-D-glucofuranose (MAG = 3but) have consequently been devised. Pharmacokinetic and biological advantages of MAG = 3but have been previously described. In the present report, we have studied the effect of MAG = 3but on murine interferon-alpha, beta (IFN) anticellular, antitumor and antiviral activities. In vitro, it appears that MAG = 3but predisposes malignant MSV cells to a later, complete establishment of the antiproliferative and the cell-differentiating effects of IFN, and the antiviral action of the latter in the same line of cells infected with encephalomyocarditis (EMC) virus. In vivo, combined treatment with MAG = 3but and IFN protects mice effectively against the fatal development of ascitic sarcoma 180 TG and the lethal effect of EMC virus infection.

Animals↗