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Electrooxidation potential as a tool in the early screening for new safer clozapine-like analogues.

The chemical modification of clozapine (1) has permitted the finding of new analogues, e.g., olanzapine (2), quetiapine (3), 5-(4-methylpiperazin-1-yl)-8-chloropyrido[2,3-b][1,5]benzoxazepine fumarate (9), with a clinical or psychopharmacological profile similar to that of clozapine. However, when developing new derivatives, the designers are discouraged by the development of clozapine-induced agranulocytosis. Different researchers have raised the role played by the oxidizability of the molecule in such a deleterious effect. In the present paper, we examined the oxidation profile (direct scavenging abilities, efficacy in inhibiting lipid peroxidation, and electrooxidation potential) of newly developed methoxy and trifluoromethylsulfonyloxy analogues related to clozapine, some of them being described as putative antipsychotic. The oxazepine derivative 7, unlike the other diazepine derivatives (6, 10--12), was not readily oxidized. Using a statistical predictive model for hematotoxicity previously described, 7 was found in the cluster of potentially nontoxic compounds while diazepine derivatives 6 and 10-12 were classified as potentially toxic compounds. Among these original compounds, 7, which presents a preclinical clozapine-like profile and a low sensitivity to oxidation, could be a promising antipsychotic candidate with low side effects. Considering the tricyclic derivatives examined so far, some elements of structure-oxidation relationship (SOR) might be pointed out. Regarding the nature of the tricyclic ring substituent, from the most to the least sensitive to oxidation, the sequence was as follows: HO > Cl > CH(3)O > CF(3)SO(2)O. The nature of the tricyclic ring influenced also the sensitivity to oxidation; the diazepine moiety appeared to be the most reactive ring compared to oxa- and thiazepine congeners. These parameters could be advantageously integrated in the early design of new safer clozapine-like analogues.

Antioxidants↗

Single nucleotide polymorphic marker enabling rapid and early screening for the homoeolocus of beta-amylase-R1: a gene linked to copper efficiency on 5RL.

This study describes the development of a PCR marker to detect the beta-amylase-R1 gene of rye. It provides an easy and rapid means for the identification of plants containing the beta-amylase-R1. Because rye chromosome segments do not normally recombine with wheat chromosomes, this marker provides a means for tracking all linked genes on that alien 5RL chromosome segment. Reaction conditions were optimised for an annealing temperature of 60 degrees C for a high stringency. The reaction was also optimised for low reaction volumes reducing the cost of the reagents required for the reaction. This PCR test can be used in breeding or mapping programs for the rapid screening of progeny containing translocations of 5RL and hence select for the copper efficiency trait of rye.

Base Sequence↗

Importance of early screening and prophylactic thyroidectomy in asymptomatic nonindex RET germline carriers.

Genetic testing for RET germline mutations affords rapid identification of germline carriers, offering the prospect of cure before C-cell hyperplasia (CCH) has progressed to medullary thyroid carcinoma (MTC). Although nonindex RET mutation carriers have a better prognosis than do the index patients, it remains to be ascertained whether age represents a risk factor for MTC when screening patients. The current institutional study (October 1994 through June 1999) was set up to compare asymptomatic nonindex patients who were grouped by age: < 20 years and > or = 20 years. Inclusion criteria were confirmed RET mutations in the germline, with no MTC being more advanced than pT1pN1M0. Adult patients (> or = 20 years) had MTC significantly more often (84% vs. 43%), significantly larger tumors (5 mm vs. 3 mm), and significantly higher basal calcitonin levels preoperatively (78.0 vs. 9.7 pg/ml) than their pediatric/adolescent counterparts (< 20 years). There was a close correlation between pT1 MTC and an elevated basal serum calcitonin level (r = 0.67; Spearman's rho). All three patients with lymph node metastases from MTC had elevated basal calcitonin levels. The two groups did not differ in terms of multifocality of MTC (pT1b), lymph node involvement (pN1) or bilateral lymph node metastasis (pN1b), or preoperative stimulated and postoperative basal and stimulated serum calcitonin. Prophylactic thyroidectomy should not be postponed beyond the age of 20, and it should be performed before basal serum calcitonin has turned positive. Pathologic conversion of stimulated serum calcitonin obviously marks the time in carriers of RET germline mutations when surgery should be scheduled at the latest to be prophylactic.

Adolescent↗

Early screening for anti-plum pox virus monoclonal antibodies with different epitope specificities by means of gold-labelled immunosorbent electron microscopy.

The technique of gold-labelled immunosorbent electron microscopy for the initial screening of monoclonal antibodies 10 days after cell fusion from 96-well culture plates is described. The technique is used to identify clones that secrete antibodies binding on the surface of the virion or to viral subunits, and compared to ELISA and Western blotting. High sensitivity was demonstrated.

Antibodies, Monoclonal↗

Early screening of pain to prevent it from becoming intractable.

The pain of primary care patients remained, in a large number of instances, unexplained after careful physical examination. In the analysis of these instances a correlation was observed between anger and pain in the neck, between fear and abdominal pain and between sorrow and despair and low back pain. A simple test was developed in which the patients assess their own emotional situation. Good correlation makes subsequent manifestation of an organic cause very unlikely. This helps to avoid unnecessary referrals.

Abdomen↗

Machine learning techniques in early screening for gastric and oesophageal cancer.

A database on 2692 dyspeptic patients over the age of 40 was established, consisting of 73 epidemiological and clinical variables. A tree-based machine learning algorithm (PREDICTOR) was applied to this database, in order to attempt to find rules which would classify patients into 2 groups, i.e., those suffering from gastric or oesophageal cancer, and the remainder. The results were encouraging. The cross-validated classification performance figure showed that by classifying 61.3% of the patients as high risk, a sensitivity of 94.9% and a specificity of 39.8% could be achieved. It is planned to construct an expert system based on the rules produced by the machine learning algorithm, in order to provide preliminary screening for cancer in dyspeptic patients.

Algorithms↗

[Differential traits of prostatic cancer detected through an early screening program versus the one detected during urologic consultation].

OBJECTIVE: To compare some features of prostate cancers (PCa) detected in a screening program, versus cancers diagnosed in an outpatient clinic. MATERIAL AND METHODS: Retrospective study of 393 patients with biopsy evidence of PCa: 93 (23.7%) from a screening campaign, and 300 (76.3%) detected in an outpatient Urology clinic. Features studied at the moment of diagnosis were age, PSA, digital rectal examination (DRE), transrectal ultrasound (TRUS) characteristics and volume stimation, PSA density (PSAD), clinical stage and Gleason score. A comparison was established between the two groups of patients taking into account the mentioned parameters. RESULTS: A higher age, PSA and DPSA values were found among cancers detected out of the screening program. A greater probability of abnormal DRE and a more advanced clinical stage was also noted. In the screening group, 78.5% of the cancers were localized and 8.6% metastatic. In the outpatient clinic group, the proportions were 50.7% and 26%, respectively. No differences were found with respect to TRUS findings, prostate volume, or Gleason score. CONCLUSIONS: Cancers detected in screening programs are found in earlier stages. Nevertheless, results from long term randomized studies are necessary to verify if these data really mean that a disease-specific mortality reduction can be achieved.

Aged↗

Immunohistochemical techniques in the early screening of monoclonal antibodies to human colonic epithelium.

Selected monoclonal antibodies (McAbs) isolated after immunization of rats with a human colonic carcinoma membrane preparation, have been screened on frozen and paraffin sections of colonic tissue, using immunohistochemical techniques, in order to provide additional information with regard to specificity and crossreactivity with normal tissues.Of 10 McAbs previously shown to bind to a colonic carcinoma membrane preparation in a radioimmunoassay, 7 show specific staining when tested by indirect immunofluorescence on crysotat sections of colonic tissue. Three of these 7 show activity on both normal and malignant colonic epithelium, and the remaining 4 stain normal epithelium, with little or no activity on malignant tissue. In the indirect immunofluorescent and immunoperoxidase techniques on paraffin sections of the same material, only 2 McAbs retain activity; one detects an antigen in colonic mucus, and the other recognises an antigen which is sparse on normal colonic epithelium and abundant on colonic tumours.We conclude that screening of McAbs on frozen tissue sections, using indirect immunofluorescence, is a useful adjunct to conventional screening methods, e.g. binding to membrane preparations and/or cell lines in a radioimmunoassay. These techniques distinguish McAbs with similar binding values in conventional assays, identify their activity on a wide range of normal and malignant tissues, demonstrate antigens that are lost or gained in malignant transformation and finally assist in the selection of McAbs for further extensive study before possible clinical use.

Animals↗

Surgeon-performed focused assessment with sonography for trauma as an early screening tool for pregnancy after trauma.

BACKGROUND: Incidental pregnancy in trauma patients is associated with a high fetal mortality. Because of quality assurance reasons, many trauma centers have eliminated the rapid urine pregnancy screen. We sought to determine the utility and impact of the initial ultrasound examination in the diagnosis of pregnancy in female trauma patients. METHODS: Data were analyzed for all female trauma patients in whom pregnancy was diagnosed during a 5-year period. RESULTS: One hundred one (70%) of 144 pregnant women had an initial ultrasound examination. Eighteen patents had newly diagnosed pregnancies, of whom 8 of 9 patients (89%) at > or = 8 weeks' gestation were diagnosed by the initial ultrasound. This directly contributed to a significant decrease in the amount of radiation exposure (p < 0.001) compared with patients diagnosed by serum beta-human chorionic gonadotropin. CONCLUSION: An initial ultrasound examination should be considered in all female trauma patients of reproductive age. This may help to promote a reduction in fetal radiation exposure.

Adolescent↗

The effect of alcohol consumption on recency discrimination ability: an early screening test for alcohol-induced cognitive impairment.

In this short study the relationship between recency discrimination ability and a measure of alcohol intake was examined using a series of regression analyses. Semi-partial correlations were extracted in order to evaluate which variables (level of alcohol consumption, age and IQ) best predicted recency discrimination performance on both verbal and non-verbal tasks. Results showed that while IQ best predicted performance on the verbal task both IQ and alcohol intake were significant predictors on the non-verbal task. The results are discussed in relation to current findings and the continuity hypothesis.

Adult↗