Toxicity evaluation of 4-chloro-2-methylphenoxyacetic acid by Microtox and comparison with FETAX.
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2-Methyl-4-chlorophenoxyacetic Acid↗
Biomedical subjects
C Rossetti
Publications and source records attributed to C Rossetti.
Preoperative radiotherapy for resectable cancer of the middle-distal rectum: its effect on the primary lesion as determined by endorectal ultrasound using flexible echo colonoscope.
20 patients with rectal cancer within 8 cm of the anal verge were studied. Endoscopic endosonography was carried out before and after pre-operative radiotherapy (45 Gy over three weeks). The local extent (tumour stage and diameter) was compared with the results of histopathological examination of the resected specimen after anterior resection or total rectal excision. The Tumour Regression Grade (TRG) and lymph node status were also estimated. Two patients were not evaluated endosonographically. Two (11%) of the remaining 18 patients showed ultrasound evidence of down staging (14/18 uT3/4 pre-radiotherapy: 12/18 uT3/4 after) and tumour diameter was significantly reduced. Tumour Regression Grade estimation showed evidence of response to treatment, showing regression of more than 50% in 13 (65%) of cases. Involved nodes were less than 5 mm in diameter in 45% of cases. Histopathological evidence of nodal metastatic regression was seen in 13 (28%) of all involved nodes found. The ultrasonically determined response to radiotherapy may offer useful information in predicting outcome and possibly in selecting surgery.
Adenocarcinoma↗
Molecular screening of families affected by familial adenomatous polyposis (FAP).
OBJECTIVES: To assess the risk of developing familial adenomatous polyposis (FAP) in presymptomatic individuals using APC gene flanking and intragenic polymorphic markers. SETTING: Twenty families enrolled in the Italian Registry of Polyposis comprising a total of 217 individuals, including 53 (24%) presymptomatic subjects with a 50% a priori risk of FAP, were analysed. Direct analysis techniques had previously failed to identify the FAP mutation in these families. METHODS: DNA isolated from peripheral mononuclear blood cells and tissue sections was analysed by the polymerase chain reaction and a panel of seven highly polymorphic markers--YN5.64, CB83, CB26, LNS, APC1458.5, MBC, 37AB. Amplification products were separated by a modified denaturing gel electrophoresis method. RESULTS: The haplotype associated with the disease was identified in 18 families (90%). The segregation of the FAP haplotype in these kindreds showed that 10 presymptomatic individuals had inherited the FAP mutation and carried a high risk of developing the disease. The remaining two families were not informative because of the lack of a sufficient number of probands or biological specimens. CONCLUSIONS: These data indicate that indirect analysis with linked DNA markers has a high rate of success in defining the risk of FAP of presymptomatic subjects, provided that a sufficient number of probands or samples is available. Uninformative families accounted for 10% of the total, indicating that linkage analysis may still have higher sensitivity than direct mutation analysis techniques. The combined use of both approaches should be implemented, however, to enhance further the application of molecular genetics to the screening of families with FAP.
Adenomatous Polyposis Coli↗
Effects of chlorocresol (4-chloro-2-methyl phenol) administered during the fertilization and cleavage phases of Xenopus laevis.
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Animals↗
Assessment of myocardial perfusion and viability with technetium-99m methoxyisobutylisonitrile and thallium-201 rest redistribution in chronic coronary artery disease.
We compare thallium-201 rest redistribution and fluorine-18 fluorodeoxyglucose ([18F]FDG) for the assessment of myocardial viability within technetium-99m methoxyisobutylisonitrile (MIBI) perfusion defects in 27 patients with chronic stable coronary artery disease. The following studies were performed: (1) stress 99mTc-MIBI, (2) rest 99mTc-MIBI, (3) 201Tl rest-redistribution single-photon emission tomography, (4) [18F]FDG positron emission tomography. The left ventricle was devided into 11 segments on matched tomographic images. The segment with the highest activity at stress was taken as the reference (activity=100%). Perfusion defects at 99mTc-MIBI rest were classified as severe (activity<50%), moderate (activity 50%-60%) or mild (activity 60%-85%). Uptakes of [18F]FDG and rest-redistributed 201Tl were recognized as significant if they exceeded 50% of that in the reference segment. Among the 33 segments with severe 99mTc-MIBI rest perfusion defects, 21 had significant [18F]FDG and 10 significant rest-redistributed 201Tl uptake. As regards the 37 segments with moderate defects, [18F]FDG was present in 29 and 201Tl in 31, while of the 134 segments with mild defects, 128 showed [18F]FDG uptake, and 131, 201Tl uptake. In conclusion, there is an inverse relationship between the severity of 99mTc-MIBI perfusion defects and the uptake of rest-redistributed 201Tl and [18F]FDG. Both tracers are adequate markers of viability in mild and moderate defects; in severe defects 201Tl might underestimate the presence of viability as assessed by [18F]FDG.
Adult↗
Spatial registration of echocardiographic and positron emission tomographic heart studies.
A method has been developed to match corresponding heart regions from functional echocardiographic (Echo) and metabolic fluorine-18-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) studies in individual patients. Echo and PET images are spatially correlated by determining homologous anatomical landmarks (the two papillary muscles and the inferior junction of the right ventricle), identifiable in images obtained by both acquisition modalities. Echo-PET image registration is first performed in the plane identified by the three landmarks, using a rigid rotate-translate scale model. The registration parameters are then used to transform the whole PET volume. This allows a consistent Echo-PET regional analysis, according to a segmental subdivision of the heart. The technique was tested on patients. The overlay of Echo and PET registered images proved the reliability of realignment of the three markers and a good spatial correlation of myocardial walls. This approach to image registration could be applied to other acquisition modalities (such as magnetic resonance imaging and single-photon emission tomography), provided that the three anatomical landmarks are visualized.
Deoxyglucose↗
Mutation in a splice-donor site of the APC gene in a family with polyposis and late age of colonic cancer death.
Adenomatous polyposis coli (APC) is an autosomal dominant disease characterized by the development of hundreds of colorectal adenomatous polyps during the first decades of life. The expression of the disease varies, as the age of onset of colonic cancer and the severity of extracolonic manifestations often differ between affected families. An attenuated form of APC has also been described in which a small number of polyps and a later age of onset of colonic cancer is observed. Cloning of the APC gene has allowed disease-causing mutations in APC families to be identified. Here, we report a novel splice site mutation (a G to T transversion at position +5 of the splice donor site in intron 9) in the APC gene of affected individuals in an Italian family. Characterization of the transcription products from this mutant APC allele revealed that normal splicing was disrupted: a shorter mRNA was expressed in which exon 8 was connected directly to exon 10. This created a shift in the reading frame and the introduction of a stop codon at position 1358. In addition, some normal APC transcript was produced from the mutant allele in lymphoblastoid cells. A comparison of the clinical features of affected members of this family with four unrelated Italian APC kindreds, in which the same AAAAG deletion at position 3926 has been found, showed a significant difference in the onset of disease symptoms and in the age of death attributable to colorectal cancer. Inefficient exon skipping may be, at least in part, responsible for the delay in the development of the disease in the reported family.
Adenomatous Polyposis Coli↗
Identification and revascularization of hibernating myocardium in angina-free patients with left ventricular dysfunction.
We examined 17 angina-free patients with left ventricular dysfunction, referred for surgical decision-making, who presented with no or few signs and symptoms of myocardial ischemia according to treadmill stress test. On cardiac catheterization they were affected by severe multi-vessel coronary artery disease; the mean left end-diastolic pressure of this population was 26.3 +/- 5.5 mm Hg (mean +/- SD) and their mean ejection fraction was 27.6 +/- 4.9% (mean +/- SD). They all were investigated for the presence of viable myocardium by the combined assessment of cardiac perfusion and metabolism using single photon emission tomography with [99mTc] labelled hexakis-2-methoxy-isobutyl-isonitrile [99mTc]MIBI/SPET) and positron emission tomography with [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG/PET), respectively. Patients were considered for coronary surgery when [18F]FDG was detectable in at least two cardiac segments with wall motion abnormalities and perfusion defects. Nine patients were operated on, six were medically treated and two were scheduled for heart transplantation. We recorded no in-hospital mortality. At a mean follow-up of 28.4 +/- 9.8 (mean +/- SD) months all surgical patients were alive and their NYHA functional classes have improved, except in one case. Among the patients refused for bypass surgery, three are in stable conditions, three have worsened clinical statuses and two died while waiting for heart transplantation. In conclusion, for patients with bypassable coronaries, left ventricular dysfunction and lack of angina, successful coronary revascularization may be predicted by the presence of viable myocardium demonstrated with positron emission tomography.
Adult↗
Relation between myocardial 18F-FDG uptake in the fasting state and coronary angiography in patients with coronary artery disease.
The relationship between severity of coronary artery stenosis (CAS) and myocardial 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) uptake in the fasting state, assessed with positron emission tomography (PET), was examined in a series of 48 patients with CAS undergoing both studies for diagnostic purposes. The data analysis was based on the subdivision of the left ventricular myocardium into four segments defined in relation to ventricular vascularization: the anterior and septal segments, perfused by the left anterior descending artery; the lateral segment, perfused by the left circumflex; and the inferior segment, perfused by the right coronary artery. The 192 segments were grouped according to degree of CAS: I 0-50%, II 51-75%; III 76-90%; IV 91-99%; V and VI occluded coronary artery with good or poor collaterals, respectively. An 18F-FDG index was determined as the tissue/blood pool radioactivity ratio in each segment. The statistical analysis was performed by one-way ANOVA, multiple comparison tests and the chi-squared test. The proportion of segments with 18F-FDG uptake was also analysed for a linear trend across the ordered levels of CAS. The 18F-FDG index in groups I to V was significantly higher than in controls, but it was not different among the groups with CAS, except for group V versus I. However, the proportion of segments with enhanced 18F-FDG uptake was correlated to the degree of CAS. In cases of complete occlusion of a major afferent coronary artery, the proportion of segments with 18F-FDG uptake varied in relation to the presence of collaterals.(ABSTRACT TRUNCATED AT 250 WORDS)
Collateral Circulation↗
Comparative analysis of results of guaiac and immunochemical tests for faecal occult blood in colorectal cancer screening in two oncological institutions.
The performances of three faecal occult blood tests, rehydrated Hemoccult (HOR), Hemoccult sensa (HOS) and Hemeselect (HSEL) on 3 days were compared in 1,725 subjects consecutively recruited in two oncological institutions in Milan and Florence. Significant differences between the results were evident as far as HOR positivity rates (7.5% vs 4.0%, respectively) and specificity (94.3% vs 97.5%, respectively) are concerned. Overall positivity rates of HOR, HOS and HSEL were 5.9%, 5.4% and 12%, respectively; significant differences were evident between HSEL and each of the two guaiac tests. Cancer was detected in eight subjects, adenoma/s in 47. Specificity estimates were 95.8%, 90.2% and 90.5% for HOR, HOS and HSEL, respectively; significant differences were evident between HSEL and the other two tests. No significant difference between tests was evident for sensitivity or positive predictive values for cancer or adenomas. In the CSPO (Florence) population (1,223 subjects; five with cancer, 16 with adenoma/s) the performances of 1-day HSEL testing were determined on the basis of the first faecal sample only and compared with 3-day HOR, HOS and HSEL testing. The positivity rates of 1-day HSEL, 3-day HOR, HOS and HSEL testing were 7.0%, 5.0%, 5.5% and 12.9%, respectively. Only 3-day HSEL positivity rate was significantly higher than 1-day HSEL. One-day HSEL specificity (94.9%) was significantly higher than 3-day HSEL (90.0%), whereas no significant difference was seen between 1-day HSEL, HOR (96.5%), and HOS (96.1%) specificity. No significant difference between tests is evident in the CSPO population as far as positive predictive values and sensitivity for cancer and adenomas are concerned.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenoma↗
Age of onset in familial adenomatous polyposis: heterogeneity within families and among APC mutations.
Heterogeneity among and within FAP pedigrees for the age of symptom onset and the age at death from colorectal cancer was studied in a sample of 583 patients of the Italian Polyposis Registry. The among pedigree variation was largely explained by clustering of families in two groups, 'early FAP' (most colorectal cancer deaths below 45 years of age) and 'late FAP' families (most deaths above age 45). The within-family variation was explained by a marked phenomenon of anticipation (15 years per generation, on the average), possibly not due to ascertainment bias. We then considered the pedigrees with identified mutation in the APC gene. Six families shared a common deletion at codon 1309 and showed the early FAP phenotype. Two families shared a mutation at codon 1061 and revealed the late FAP phenotype. Another two families (codons 453 and 302) clustered with the late FAP group, whereas a family with mutation at codon 835 clustered with the early FAP group. We suggest that there are at least two classes of mutations in the APC gene with different consequences at the phenotypic level. It seems that there are several critical points within the APC protein sequence at which truncation causes a more aggressive disease than truncation at other points.
Adenomatous Polyposis Coli↗
Rest distribution of 99mTc-MIBI in patients with coronary artery disease assessed by SPECT: comparison with the distribution of [18F]FDG assessed by PET.
The distribution of 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI), assessed by single photon emission computed tomography (SPECT) was compared to the distribution of 2-[18F]-2-deoxy-D-glucose ([18F]FDG) assessed with positron emission tomography (PET) under fasting conditions, in 21 patients with coronary artery disease (CAD) and severe left ventricular dysfunction in order to evaluate the potential usefulness of SPECT/99mTc-MIBI for the identification of viable myocardium. Stress and rest SPECT/99mTc-MIBI studies were scored based on the percent of 99mTc-MIBI uptake defined by semi-quantitative circumferential-profile analyses. PET metabolic studies with [18F]FDG under fasting conditions, were adopted as a standard of viability. The results of the comparison of 99mTc-MIBI and [18F]FDG distribution showed that among the segments with stress hypoperfusion, [18F]FDG uptake was present in 95% of the segments that had > 40% of the peak tracer uptake at the rest SPECT/99mTc-MIBI study. [18F]FDG uptake was also present, however, in 25% of the segments that had < 40% uptake at the rest SPECT/99mTc-MIBI scintigraphy. We conclude that in patients with CAD the pattern of 99mTc-MIBI distribution appears to underestimate the extent of viable myocardium but only in those regions that are very severely hypoperfused.
Aged↗
Human biodistribution, dosimetry and clinical use of technetium(III)-99m-Q12.
UNLABELLED: Technetium(III)-99m-Q12, trans-(1,2-bis(dihydro-2,2,5,5-tetramethyl- 3(2H)furanone-4-methyleneimino)ethane)bis(tris(3-methoxy-1-propyl) - phosphine)technetium(III)-99m, is a nonreducible complex of Tc(III) which is herein evaluated as a myocardial perfusion imaging agent. METHODS: The biodistribution and dosimetry of 99mTc-Q12 were assessed in 10 normal volunteers, while its potential clinical use was evaluated in 70 patients. RESULTS: Safety parameters measured up to 24 hr postinjection demonstrate no clinically significant drug-related adverse reactions. Technetium(III)-99m-Q12 exhibits good heart uptake (2.2% injected dose at 1 hr postinjection under resting conditions) and no detectable myocardial washout or redistribution up to 5 hr postinjection. The biodistribution is characterized by very rapid hepatobiliary clearance which allows effective myocardial imaging at times as short as 15 min postinjection. Blood and plasma clearances and myocardial uptake are rapid, while lung uptake is minimal. The heart-to-lung and heart-to-liver ratios are higher at stress than at rest, independent of the time elapsed between injection and image acquisition, and independent of whether the patient is fasted or fed after tracer administration. A preliminary correlation shows that 46/47 patients with angiographically demonstrated CAD also have perfusion defects demonstrated by 99mTc-Q12. CONCLUSIONS: On the basis of the studies reported herein, 99mTc-Q12 appears to be a promising myocardial perfusion imaging agent.
Adult↗
Time dependence of residual tissue viability after myocardial infarction assessed by [18F]fluorodeoxyglucose and positron emission tomography.
Areas of myocardial infarction may retain glycolytic activity and this finding is indicative of tissue viability and predictive of functional recovery after revascularization. In order to assess the relation between the time elapsed from the occurrence of acute myocardial infarction and persistence of myocardial metabolic activity in the infarcted tissue, we prospectively studied 65 patients with previous myocardial infarction diagnosed clinically and by electrocardiographic (Q wave) and enzymatic criteria. All patients underwent coronary angiography and contrast left ventriculography, evaluation of regional myocardial glucose metabolism (in the fasting state) by positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), and assessment of myocardial perfusion by single photon emission computed tomography (SPECT) with technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI). Based on the regional metabolic and perfusion findings, patients were divided into 2 groups, depending on the absence (group 1, 26 patients) or presence (group 2, 39 patients) of [18F]FDG uptake in the underperfused regions. Areas of underperfusion at rest, consistent with the clinically identified myocardial infarction site, were observed in all patients. Severity of coronary artery disease, presence of collaterals, number of hypocontractile segments, and wall motion score did not differ significantly in the 2 groups. The time elapsed from the infarction was significantly greater (1,860 +/- 1,333 days) in group 1 than in group 2 (92 +/- 115 days; p < 0.0001). Exercise caused an increase in severity and/or extent of resting perfusion abnormalities in a greater proportion of patients of group 1 (53% vs 23%).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Congenital hypertrophy of retinal pigment epithelium (CHRPE) as a marker for familial adenomatous polyposis (FAP).
Seventy-eight patients from 26 families were examined to evaluate the potentiality of congenital hypertrophy of retinal pigment epithelium (CHRPE) as a phenotypic marker for familial adenomatous polyposis (FAP). The examined subjects were divided into three different groups: Group I, patients with FAP without extra colonic manifestations (ECM); Group II, patients with FAP and ECM (desmoids/osteomas/upper gastrointestinal adenomas); and Group III, individuals at risk without FAP. Of 24 Group I patients (median age 18 years) 16 had CHRPE compared with 14 out of 24 patients (median age 29 years) in Group II and only three out of 30 patients in Group III. The overall sensitivity of CHRPE for FAP was 70% (+/- 13%) without any difference related to ECM; the predictive value was 92%. The specificity calculated from Group III (median age 26 years) was 90%, but the results should not be considered as definitive because a longer follow-up to determine the appearance of adenomas is required. The data suggest that examination for CHRPE is an inexpensive, non-invasive test for FAP, but the absence of retinal lesions does not eliminate the necessity for adequate follow-up of individuals at risk.
Adenomatous Polyposis Coli↗
Correlation between relatives for colorectal cancer mortality in familial adenomatous polyposis.
It has long been realized that age-specific cancer mortality in Familial Adenomatous Polyposis (FAP) was bimodal, and a theory was proposed in which the involved locus was polymorphic in the general population. After the molecular cloning of the region 5q21, it has been suggested that the phenotypic variability in FAP may be due to the interaction of two loci, one of which is polymorphic. We show that these two hypotheses lead to different predictions of the correlation between relatives for a phenotypic trait, and use colorectal cancer mortality data from the Italian Polyposes Registry to verify them. We conclude that the first of the two is more likely and suggest that the same variation that we observe among the affected subjects is present in the general population, thus causing a significant difference between individuals for colon cancer susceptibility.
Adenomatous Polyposis Coli↗
Presurgical identification of hibernating myocardium by combined use of technetium-99m hexakis 2-methoxyisobutylisonitrile single photon emission tomography and fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography in patients with coronary artery disease.
We tested the possibility of identifying areas of hibernating myocardium by the combined assessment of perfusion and metabolism using single photon emission tomography (SPET) with technetium-99m hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI) and positron emission tomography (PET) with fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG). Segmental wall motion, perfusion and 18F-FDG uptake were scored in 5 segments in 14 patients with coronary artery disease (CAD), for a total number of 70 segments. Each subject underwent the following studies prior to and following coronary artery bypass grafting (CABG): first-pass radionuclide angiography, electrocardiography gated planar perfusion scintigraphy and SPET perfusion scintigraphy with 99mTc-MIBI and, after 16 h fasting, 18F-FDG/PET metabolic scintigraphy. Wall motion impairment was either decreased or completely reversed by CABG in 95% of the asynergic segments which exhibited 18F-FDG uptake, whereas it was unmodified in 80% of the asynergic segments with no 18F-FDG uptake. A stepwise multiple logistic analysis was carried out on the asynergic segments to estimate the postoperative probability of wall motion improvement on the basis of the preoperative regional perfusion and metabolic scores. The segments with the highest probability (96%) of functional recovery from preoperative asynergy after revascularization were those with a marked 18F-FDG uptake prior to CABG. High probabilities of functional recovery were also estimated for the segments presenting with moderate and low 18F-FDG uptake (92% and 79%, respectively). A low probability of functional recovery (13%) was estimated in the segments with no 18F-FDG uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Coronary Artery Bypass↗
Confocal microscopical analysis of epithelial cell heterogeneity in mouse Peyer's patches.
Cyanine dye fluorescence and alkaline phosphatase activities have been compared directly by confocal microscopy in a wide variety of cells present in the follicle-associated epithelium of the mouse Peyer's patch to test the hypothesis that antigen-transporting M cells have a low membrane potential. In order to make these comparisons it was first necessary to equilibrate living tissue with the membrane potential sensitive dye DIOC5(3), fix with glutaraldehyde and then incubate the fixed tissue with naphthol AS-BI phosphate, a substrate which is hydrolysed by alkaline phosphatase present in the luminal membrane of these epithelial cells. Naphthol AS-BI produced by this reaction is then coupled to Fast Red TR diazonium salt at the site of hydrolysis. Selecting the 488 nm wavelength of the argon laser source then allows one to measure alkaline phosphatase activities as Fast Red absorbance and membrane potentials by DIOC5(3) fluorescence. Results obtained show a linear correlation between membrane potential and alkaline phosphatase activity. Relative lack of alkaline phosphatase activity, determined in fixed tissue, has been used previously to identify antigen-transporting M cells (Smith et al., 1987). The present work shows that it is now possible to recognize these cells in living tissue by measurement of DIOC5(3) fluorescence. The possible importance of this finding in providing a way to study cell surface-antigen interactions taking place in living tissue is discussed.
Alkaline Phosphatase↗