Recurrent Crohn's disease and resection margins: bigger is not better.
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Anastomosis, Surgical↗
Biomedical subjects
F Marchetti
Publications and source records attributed to F Marchetti.
Synergic interactions of macrolides and proton-pump inhibitors against Helicobacter pylori: a comparative in-vitro study.
Thirty-eight clinical strains of Helicobacter pylori were isolated from patients with chronic gastritis and gastroduodenal ulceration, and their susceptibility to macrolide antibiotics (roxithromycin, flurithromycin, azithromycin, erythromycin) in combination with proton-pump inhibitors (lansoprazole and omeprazole) and bismuth subcitrate was assayed. Chequerboard titration was used to analyse the results of antimicrobial interactions and showed that the activity of macrolides was enhanced by combining them with lansoprazole, omeprazole or, to a lesser extent, bismuth subcitrate. While the interactions between erythromycin and the proton-pump inhibitors or bismuth subcitrate were always additive, the combinations of roxithromycin-lansoprazole, flurithromycin-omeprazole and azithromycin-lansoprazole acted synergically on 82%, 60% and 60% of H. pylori strains, respectively. These results may, in part, account for the enhanced clinical efficacy of macrolides administered with proton-pump inhibitors in the treatment of H. pylori-associated diseases.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Comparative in-vitro activity of levofloxacin against Chlamydia spp.
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Anti-Bacterial Agents↗
Induction of chromosomal aberrations in mouse zygotes by acrylamide treatment of male germ cells and their correlation with dominant lethality and heritable translocations.
The objectives of this research were: 1) to investigate the time course of the cytogenetic defects induced by acrylamide (AA) treatment (5 x 50 mg/kg) of male germ cells in first-cleavage zygote metaphases using PAINT/DAPI analysis, and 2) to characterize the correlation between chromosomal aberrations at first cleavage, dominant lethality, and heritable translocations. PAINT/DAPI analysis employs multicolor fluorescence in situ hybridization painting plus DAPI staining to detect both stable and unstable chromosomal aberrations at first-cleavage metaphase of the zygote. High levels of chromosomally defective zygotes were detected after mating at all postmeiotic stages (20-190-fold, P < 0.001). Early spermatozoa (6.5 d post-treatment) were the most sensitive, with 76% of the zygotes carrying cytogenetic defects. A significant 10-fold increase was also detected 27.5 d post-treatment, indicating that AA had a cytogenetic effect on meiotic stages. PAINT/DAPI analysis revealed that: 1) AA-induced chromosomal breaks occurred at random, and 2) the frequencies of symmetrical and asymmetrical exchanges were similar at all mating days, except 9.5 d after AA treatment, where significantly (P < 0.02) more asymmetrical aberrations were found. Furthermore, the proportions of zygotes carrying unstable and stable chromosomal aberrations followed a similar post-treatment time course as the proportions of dominant lethality among embryos and heritable translocations among offspring. These findings indicate that PAINT/DAPI analysis of zygotic metaphases is a promising method for detecting male germ cell mutagens capable of inducing chromosomal aberrations and for evaluating the associated risks for embryonic loss and balanced translocations at birth.
Acrylamide↗
Mechanisms and targets involved in maternal and paternal age effects on numerical aneuploidy.
Trisomy in the human appears to be predominantly associated with maternal age. The maternal-age effect, however, shows considerable variability across affected chromosomes. Chromosome-specific variation has been reported in the shapes of the maternal-age-effect curves, including very small effects for the large chromosomes (groups A and B), linear increases (chromosome 16), and exponential increases (chromosome 21). There is also variation among chromosomes in whether the segregation errors occur predominantly at maternal meiosis I, meiosis II, and/or postfertilization mitotic divisions. There is also limited epidemiological evidence for a paternal-age effect, which was recently supported by the findings of age-related increases in sperm aneuploidy using fluorescence in situ hybridization methods. The paternal-age effect is considerably smaller than the maternal and is more likely to involve meiotic II errors of the sex chromosomes, whereas the maternal-age effect is more likely to arise from meiotic I errors producing autosomal trisomies. These and other differences suggest that constitutional aneuploidy arises by multiple mechanisms that may affect (1) the nature and timing of an initiating lesion affecting the oocyte or sperm; (2) the cellular physiology of the time of the nondisjunction event at meiosis I, II, or postfertilization; and (3) the selection against specific chromosomal aneuploidies during embryonic development. Multidisciplinary research is needed to understand the maternal and paternal-age effects on aneuploidy, to (1) identify and characterize the genes that control meiosis, recombination, and segregation; (2) identify the micro-environmental factors around the oocyte and mole germ cells that are involved in the age effects; (3) develop a laboratory animal model for the age effects; (4) characterize the role of genetics, physiology, and environmental toxicology for the paternal-age effects; and (5) identify cohorts of men and women of differing ages who have been exposed to high doses of candidate aneugens and conduct epidemiological investigations of aneuploidies transmitted to their offspring.
Adult↗
Adenocarcinoma arising from a strictureplasty site in Crohn's disease. Report of a case.
The occurrence of small-bowel cancer in Crohn's disease (CD) is a rare event. The risk seems to be greatest in patients with long-standing disease. Strictureplasty has proved to be a valuable alternative in the management of Crohn's strictures of the small-bowel. Critics and proponents of strictureplasty for selected patients with small-bowel Crohn's disease have voiced their concerns about cancer risk in the strictured or strictureplasty site. To date, there has been no clear or detailed report of such an occurrence. The authors report the first case of small-bowel adenocarcinoma arising at the site of a previous strictureplasty. In this patient, biopsies of the strictures at the original operation confirmed CD and excluded both cancer and dysplasia. Malignancy occurred seven years later at a strictureplasty site. The main clinical sign associated with the adenocarcinoma was severe, persistent anemia. The authors conclude that the risk of adenocarcinoma developing at the site of a previous strictureplasty for CD, although small, is real.
Adenocarcinoma, Mucinous↗
Paternally inherited chromosomal structural aberrations detected in mouse first-cleavage zygote metaphases by multicolour fluorescence in situ hybridization painting.
We describe a fluorescence in situ hybridization (FISH) procedure for assessing zygotic risk of paternal exposure to endogenous or exogenous agents. The procedure employs multicolour FISH with chromosome-specific DNA painting probes plus DAPI staining for detecting both balanced and unbalanced chromosomal aberrations in mouse first-cleavage (1-Cl) zygote metaphases. Four composite probes specific for chromosomes 1, 2, 3 or X, each labelled with biotin, plus a composite probe specific for chromosome Y labelled with digoxigenin, were used. We applied this method to evaluate the effects of paternal exposure to acrylamide, a model germ cell clastogen. First-cleavage zygote metaphases, collected from untreated females mated to males whose sperm or late spermatids were treated with acrylamide, were scored for the induction of structural aberrations using both chromosome painting (PAINT analysis) and DAPI analysis. Structural chromosomal aberrations were observed in the sperm-derived, but not in the egg-derived, pronuclei. While 59.4% of the zygotes had structural aberrations by DAPI analysis, 94.1% of the same zygotes had structural aberrations by PAINT analysis (P < 0.001), illustrating the increased sensitivity for detecting translocations and insertions obtained by adding chromosome painting. These findings show that FISH painting of mouse 1-Cl zygotes when used in conjunction with DAPI analysis is a powerful model for investigating the cytogenetic defects transmitted from father to offspring.
Animals↗
Dose-response study and threshold estimation of griseofulvin-induced aneuploidy during female mouse meiosis I and II.
The relative sensitivity of the two meiotic divisions of mouse oogenesis to griseofulvin (GF)-induced aneuploidy was investigated. The first meiotic division was studied by administering GF 4 h after human chorionic gonadotrophin (HCG) injection and analyzing metaphase II (MII) oocytes, whereas study of the second meiotic division involved treating the females 10 h after HCG and analyzing one-cell (1-Cl) zygotes. Data from previous studies have shown that these treatment times represented the most sensitive times for aneuploidy induction during meioses I and II. The statistical analyses of the data showed that the dose-response curves for aneuploidy induction did not differ quantitatively or qualitatively between the two meiotic divisions. The percentages of hyperploid MII oocytes and 1-Cl zygotes were significantly higher (P < 0.001) than in the controls for all doses except 125 mg/kg GF. The highest percentages of hyperploid cells were found after administering 1500 mg/kg GF. However, these percentages were not different (P > 0.05) from those observed after 500 or 1000 mg/kg GF, suggesting saturation of the GF aneuploid target(s). These results suggest that the relative sensitivity to GF-induced aneuploidy between the two meiotic divisions of oogenesis are similar. They also suggest the presence of a lower (125 mg/kg) and an upper 500 mg/kg) threshold for GF-induced aneuploidy.
Aneuploidy↗
Numerical and structural chromosome aberrations induced by etoposide (VP16) during oocyte maturation of mice: transmission to one-cell zygotes and damage to dictyate oocytes.
The antineoplastic drug etoposide (ET) inhibits topoisomerase II (topo II) activity by forming a ternary complex (DNA-ET-topo II). This complex prevents the DNA-strand-rejoining activity of topo II and may result in structural chromosome aberrations. Inhibition of topo II activity may also predispose cells to aneuploidy because this enzyme is needed for removing regions of DNA catenation prior to chromosome segregation. Our objectives were to study the dose response for ET-induced numerical and structural chromosomal aberrations in mouse one-cell zygotes, to compare these data with those obtained from a contemporary metaphase II (MII) oocyte study and to evaluate the sensitivity of dictyate oocytes to ET-induced aneuploidy. ICR female mice were superovulated and injected i.p. with either 6% dimethylsulphoxide (controls) or 20, 40 or 60 mg/kg ET 2 h after human chorionic gonadotrophin (HCG). ICR males were paired (1:1) with females immediately after treatment. After 17 h the males were removed, and after 24 h the females with a vaginal plug were given colchicine. One-cell zygotes were harvested for cytogenetic analysis 17 h after colchicine. The percentages of hyperploid zygotes were 1.1, 5.7, 13.8 and 20.7 and of zygotes with structural aberrations were 2.5, 16.3, 37.7 and 64.7, for control, 20, 40 and 60 mg/kg ET respectively. The differences between each succeeding dose for both structural and numerical aberrations were statistically significant (P < 0.01). When the ET dose response aneuploidy data from zygotes were compared with similar data from a contemporary study involving metaphase II oocytes, the frequencies of hyperploidy were greater in zygotes than in oocytes. We conclude that when ET is administered during the preovulatory phase of meiosis, it is both an aneugen and a clastogen in mouse one-cell zygotes.
Aneuploidy↗
Effect of resection margins on the recurrence of Crohn's disease in the small bowel. A randomized controlled trial.
OBJECTIVE: The authors assess the effect of surgical margin width on recurrence rates after intestinal resection of Crohn's Disease (CD). BACKGROUND: The optimal width of margins when resecting DC of the small bowel is controversial. Most studies have been retrospective and have had conflicting results. METHODS: Patients undergoing ileocolic resection for CD (N = 152) were randomly assigned to two groups in which the proximal line of resection was 2 cm (limited resection) or 12 cm (extended resection) from the macroscopically involved area. Patients also were classified by whether the margin of resection was microscopically normal (category 1), contained nonspecific changes (category 2), were suggestive but not diagnostic for CD (category 3), or were diagnostic for CD (category 4). Recurrence was defined as reoperation for recurrent preanastomotic disease. RESULTS: Data were collected on 131 patients. Median follow-up time was 55.7 months. Disease recurred in 29 patients: 25% of patients in the limited resection group and 18% of patients in the extended resection group. In the 90 patients in category 1 with normal tissue, recurrence occurred in 16, whereas in the 41 patients with some degree of microscopic involvement, recurrence occurred in 13. Recurrence rates were 36% in category 2, 39% in category 3, and 21% in category 4. No group differences were statistically at the 0.01 level. CONCLUSION: Recurrence of CD is unaffected by the width of the margin of resection from macroscopically involved bowel. Recurrence rates also do not increase when microscopic CD is present at the resection margins. Therefore, extensive resection margins are unnecessary.
Adult↗
Variation of mouse oocyte sensitivity to griseofulvin-induced aneuploidy during the second meiotic division.
The effects of griseofulvin (GF) treatment during the second meiotic division of oogenesis were investigated by cytogenetic analysis of mouse one-cell (1-Cl) zygotes. After determining the duration of fertilization and the second meiotic division, 1500 mg/kg GF were administered to superovulated mice at 10, 12 or 14 h after human chorionic gonadotrophin (HCG) injection. The results showed that GF reduced the frequencies of fertilized oocytes (P < 0.01) and of 1-Cl zygotes that reached the first mitotic metaphase stage (P < 0.001). Aneuploidy was induced regardless of the moment of treatment, but the various treatment times were associated with statistically different (P < 0.05) levels of hyperdiploidy. The maximum frequency of hyperdiploidy (39.6%) occurred when GF was given 10 h after HCG. Polyploid 1-Cl zygotes were significantly induced only at the 10 and 12 h treatment times and their level never exceeded 1.8% of fertilized oocytes. GF also induced abnormalities of chromosome condensation along with centromeric chromosome associations. These results support the conclusion that GF treatment during the second meiotic division induced aneuploidy, polyploidy, and reduced rates of fertilization and zygotic development. Also, the time of chemical treatment influenced the frequencies of these effects.
Aneuploidy↗
Synergism between gonadotrophins and vinblastine relative to the frequencies of metaphase I, diploid and aneuploid mouse oocytes.
Ovulated oocytes are used to obtain estimates of germ cell aneuploidy following in vivo treatment with various chemicals. Such studies commonly use exogenous gonadotrophins to increase the number of ovulated oocytes and to induce ovulation during specific time periods. However, the gonadotrophin dosages have not been evaluated relative to the possibility that synergistic and antagonistic interactions may exist between the hormones and the chemical being studied. We, therefore, studied the interactions of different hormone dosages (5 IU pregnant mare's serum (PMS) and 2.5 IU human chorionic gonadotrophin (HCG), 7.5 IU PMS and 5 IU HCG, and 10 IU PMS and 7.5 IU HCG) alone (controls) and in combination with 0.2 mg/kg of the aneugen vinblastine sulfate (VBS) relative to the number of oocytes ovulated, the frequencies of metaphase I (MI), diploid and aneuploid oocytes. The results indicated that the proportions of oocytes ovulated were not significantly (P > 0.05) different among the various control and VBS groups. VBS, however, resulted in significantly (P < 0.01) higher levels of MI oocytes than in controls. In the VBS-treated females, higher frequencies (P < 0.05) of MI oocytes were found in the 7.5 IU PMS and 5 IU HCG and 10 IU PMS and 7.5 IU HCG groups as compared to the 5 IU PMS and 2.5 IU HCG group. The frequencies of diploid oocytes did not differ significantly (P > 0.05) within the control of VBS groups; whereas, when comparisons were made between each control and VBS group, only the difference between the 5 IU PMS and 2.5 IU HCG groups was significant (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Aneuploidy↗
Parental and primary care physicians' views on the management of chronic diseases: a study in Italy. The Italian Collaborative Group on Paediatric Chronic Diseases.
A survey on the burden and quality of care and the parental and primary care physicians' views on management of eight chronic illnesses and disabilities was conducted from 1990 to 1993. Data were collected on 993 children and adolescents from family interviews and physicians' postal questionnaires. Approximately 70% of patients used two or more services for care management and 149 children were treated outside their region. Only 36% of the physicians were case managers and half of these agreed that better communication with other care providers could facilitate their role. A wide difference in parental satisfaction was found between medical and disabling conditions. Approximately 90% of the parents expressed satisfaction with care for children with coeliac disease (112/120), asthma (80/89) and diabetes (98/111), whereas approximately one-third of parents of children with cerebral palsy and Down's syndrome were dissatisfied (88/242 and 72/189, respectively). Primary care physicians expressed similar satisfaction with case management. Distance from hospital, the need for more information on disease management and financial aid were the sources of greatest dissatisfaction. Children with disabling diseases had more problems integrating at school than children with other chronic disorders. Closer interaction between health services, providers and families is necessary to manage the needs of disabled (Italian) children better.
Absenteeism↗
Partial screening in Ca silicides measured by Ca 2p electron-energy-loss spectroscopy.
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Journal Article↗
Variation of mouse oocyte sensitivity to griseofulvin-induced aneuploidy and meiotic delay during the first meiotic division.
The effects of varying the time of chemical treatment on the induction of aneuploidy and meiotic delay in metaphase II (MII) oocytes were studied by administering 1,500 mg/kg griseofulvin (GF) at 0, 2, 4, 6, or 8 hr after an injection of human chorionic gonadotrophin (HCG). The results show that the oocytes have a different sensitivity to GF-induced aneuploidy and meiotic delay during the course of meiotic maturation. Although not restricted to a particular period of meiotic maturation, the frequency of aneuploidy was highest (P < 0.05) when GF was given at 2, 4, or 6 hr after HCG. The maximum frequency of hyperploidy (42.4%) occurred at the 4-hr treatment time. Also, GF treatment resulted in the induction of meiotic delay as demonstrated by ovulated metaphase I (MI) and polyploid MII oocytes. The meiotic delay data depict a period of relative resistance between two periods of sensitivity in that the percentages of ovulated MI oocytes were 53.3, 21.3, 3.5, 6.7, and 25.7 when GF was given at 0, 2, 4, 6, and 8 hr after HCG, respectively. Also, at these treatment times the percentages of polyploid oocytes were 0.6, 1.7, 7.7, 20.1, and 15.4, respectively. Therefore, the oocytes seem to be more sensitive to GF-induced meiotic delay during the periods preceding and following meiotic spindle assembly. In conclusion, the results demonstrate that the time of chemical treatment influences the frequency of aneuploidy and the degree of meiotic delay. Also, the results emphasize that to thoroughly characterize the aneugenic potential of a specific chemical several treatment times may be needed.
Aneuploidy↗
Preferential pericentric lesions and aneuploidy induced in mouse oocytes by the topoisomerase II inhibitor etoposide.
Etoposide (VP-16) is used as an antineoplastic drug in humans. It inhibits topoisomerase II(topoII) activity by forming a ternary complex (DNA-etoposide-topoII). This complex prevents the DNA-strand rejoining activity of topo II, which results in DNA-strand breaks and the formation of structural chromosome aberrations. Topo II activity is also required for removing regions of DNA catenation prior to chromosome segregation. The possibility exists that patients undergoing etoposide chemotherapy may incur genetic damage and, consequently, may be at a greater risk for developing secondary tumors and having genetically abnormal offspring. We studied the ability of etoposide for inducing both structural chromosome aberrations and aneuploidy in mouse oocytes. Different dosages of etoposide were given to female mice at various times before and after human chronic gonadotrophin injection, and ovulated oocytes were collected 17 h later. The proportions of chromatid acentric fragments and of hyperploid metaphase II oocytes were significantly higher (P < 0.01) in the etoposide groups than in concurrent controls. These results indicate that both structural and numerical aberrations can be induced without direct interaction with DNA or with the various organelles associated with chromosome segregation. Additionally, unlike other compounds (vinblastine, colchicine, benomyl, and griseofulvin) that induce both meiotic delay (ovulated metaphase I oocytes and polyploidy) and aneuploidy, etoposide did not cause meiotic delay in oocyte maturation.
Aneuploidy↗
Comparison of the aneugenic activity of diazepam in mouse oocytes and other mammalian cells.
Previous studies have reported that diazepam (DZ) is capable of inducing mitotic-meiotic arrest and increasing the frequency of aneuploidy in mammalian cells both in vitro and in vivo. We now report that DZ failed to induce either meiotic arrest or aneuploidy in mouse oocytes. In fact, doses of 0, 50, 100, or 150 mg/kg DZ administered at the same time as human chorionic gonadotropin did not induce the ovulation of metaphase I oocytes or of hyperploid metaphase II oocytes. A reduction in the number of ovulated oocytes was observed in the treated groups relative to controls, but this reduction was only significant (p < 0.01) at the highest dose. These findings indicate that different results are found among the assays used for detecting chemically induced aneuploidy. Determining the factors responsible for these differences is an important area for future research.
Aneuploidy↗
Chemically-induced aneuploidy in mammalian oocytes.
The ability of certain chemicals to elevate the frequency of aneuploidy above spontaneous levels in mammalian experimental models prompts the concern that a similar situation might exist in humans. Validation of experimental models for aneuploidy studies is in progress since there is much to be learned about the causes and mechanisms of chemically-induced aneuploidy. Several biological variables have been shown to influence the results from aneuploidy assays. In this review, we examine these variables as they relate to female germ cell aneuploid assays. Also, we have found that the aneuploidy results obtained from different cell types, sexes, and experimental models cannot necessarily be expected to agree due to certain anatomic and physiologic differences and the end points measured.
Aneuploidy↗