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Biomedical subjects

A Zia

Publications and source records attributed to A Zia.

9 recordsLinked to original sources

Why wait for a colonoscopy? An easy cure.

OBJECTIVE: Three thousand five hundred and forty-nine patients are waiting for a colonoscopy in the Kent and Medway cancer network. New guidelines identify those who require surveillance for polyp, cancer, IBD and family history. Our hypothesis was that most of the patients on the waiting list would no longer need a colonoscopy if the new guidelines were applied. PATIENTS AND METHODS: We compared the ACPGBI guidelines for screening/surveillance colonoscopy with the indications in 411 notes of one hospital's waiting list and removed patients as appropriate. In the second part of study we analysed 192 patients attending colonoscopy in seven hospitals in the region and calculated the potential impact of the guidelines on our waiting lists. RESULTS: Of 411 patients on the waiting list in one hospital, only 98 (24%) needed to remain on the list. 142 (34%) were cancelled completely. One hundred and seventy-one (42%) were taken off the 'waiting' list and rebooked for a later date since according to the new guidelines the colonoscopy was not due yet. Of 192 colonoscopies actually performed during the study period in 7 hospitals of Kent and Medway cancer network, 72 (38%) were for surveillance. Two thirds of those were not in line with the guidelines. As a result of implementing the guidelines, waiting times for diagnostic colonoscopy fell from 12 to 4 weeks for urgent, and from 40 to 15 weeks for routine referrals. CONCLUSION: A quarter of the 8000 colonoscopies performed annually in our region are unnecessary when compared to the guidelines. More than three quarters of our waiting list could be removed by reviewing the notes. Implementing the guidelines in one cancer network would save pounds 1 million per year even on conservative estimates of pounds 500 per colonoscopy. It would also reduce the waiting times for diagnostic colonoscopy.

Colonoscopy↗

MHC class I negative phenotype of disseminated tumor cells in bone marrow is associated with poor survival in R0M0 breast cancer patients.

Changing the major histocompatibility complex (MHC) class I phenotype is a pivotal strategy of tumor cells to circumvent an effective immune response and is associated with tumor progression in cancer patients. Epithelial cells in bone marrow have been detected in various tumor types, but the clinical observation that only a portion of the patients with a positive bone marrow status develops solid bone metastasis suggests a certain molecular equipment of the isolated tumor cells as a prerequisite for metastatic formation. In the present study the prognostic impact of the MHC class I phenotype of disseminated epithelial cells in bone marrow was evaluated in a cohort of 30 curatively resected (R0) patients without distant metastases (M0) (designated R0M0) who had minimal residual disease. Immunocytochemical analysis using the alkaline/anti-alkaline immunogold double staining procedure revealed a heterogeneous MHC class I expression profile [monoclonal antibody (mAb) W6/32] of the epithelial cells (mAb CK2). In 16 patients (53.3%) all epithelial cells were human leukocyte antigen (HLA) class I-positive (CK2+//W6/32+ phenotype). Eight patients (26.7%) showed complete loss of the HLA class I molecules (CK2+//W6/32- phenotype) and in 6 patients (20%) partial loss of HLA class I expression was found (CK2+//W6/32+ and - phenotype). CK2+ cells with the HLA class I negative phenotype (CK2+//W6/32- phenotype and CK2+//W6/32+ and - phenotype) were often derived from poorly differentiated (G3) primary breast carcinomas (p = 0.036) and were associated with short survival of the R0M0 patients (follow-up 15-98 months, log rank p = 0.072). These findings support the necessity to develop immmunotherapeutic strategies leading to the restoration of MHC class I positive phenotype.

Antibodies, Monoclonal↗

Peaks of linkage are localized by a BAC/PAC contig of the 6p reading disability locus.

A gene for reading disability has been localized by nonparametric linkage to 6p21.3-p22 in several published reports. However, the lack of an uninterrupted genomic clone contig has made it difficult to determine accurate intermarker distances, precise marker order, and genetic boundaries and hinders direct comparisons of linkage. The search and discovery of the hemochromatosis gene (HFE) led to the creation of a bacterial artificial chromosome (BAC) and P-1 derived artificial chromosome (PAC) contig that extended physical maps 4 Mb from the MHC toward pter and localized new markers in that region [10-12]. Using this contig, we localized 124 sequence tagged sites, expressed sequence tags, and short tandem repeats including most of the markers in linkage with reading disability phenotypes, succinic semialdehyde dehydrogenase, GPLD1, prolactin, and 18 uncharacterized genes. This new contig joins and extends previously published physical maps to span the entire chromosome 6 reading disability genetic locus. Physical mapping data from the complete contig show overlap of the published linkage peaks for reading disability, provide accurate intermarker distances and order, and offer resources for generating additional markers and candidate genes for high resolution genetic studies in this region.

Bacteriophage P1↗

Bio-active cardenolides from the leaves of Nerium oleander.

A bioactivity directed isolation of the methanolic extract of the fresh, uncrushed leaves of Nerium oleander showing a central nervous system (CNS) depressant effect in mice has been undertaken. As a result, four CNS depressant cardenolides including a new cardenolide, neridiginoside and three known constituents, nerizoside, neritaloside and odoroside-H, have been isolated which exhibited CNS depressant activity in mice at a dose of 25 mg/kg. The structure of neridiginoside was elucidated as 3 beta-O-(D-diginosyl)-5 beta, 14 beta-dihydroxy-card-20(22)-enolide, using spectroscopic methods including one-dimensional and two-dimensional NMR (COSY-45, NOESY, J-resolved, HMQC and HMBC). The known compounds have been indentified through spectral studies and comparison of data with those reported in the literature.

Animals↗

Cardenolides from the methanolic extract of Nerium oleander leaves possessing central nervous system depressant activity in mice.

Two new cardenolides, 3 beta-O-(D-2-O-methyldigitalosyl)-14 beta-hydroxy-5 beta-carda-16,20(22)-dienolide (1) and 3 beta-hydroxy-8,14-epoxy-5 beta-carda-16,20(22)-dienolide (2), and two known cardenolides, 3 beta-O-(D-digitalosyl)-14 beta-hydroxy-16 beta-acetoxy-5 beta-card-20(22)-enolide (3) and 3 beta-O-(D-digitalosyl)-14 beta-hydroxy-5 beta-card-20(22)-enolide (4), have been isolated from the leaves of Nerium oleander following a bioactivity-directed isolation of the MeOH extract, which showed central nervous system (CNS) depressant activity in mice at a dosage of 50 mg/kg i.p. Their structures were established on the basis of chemical and spectral data. Compounds 1, 3, and 4 were found to exhibit sedation in mice at a dosage of 25 mg/kg, although 2 had no effect on the CNS of mice at a dosage of up to 50 mg/kg.

Animals↗

Studies on the constituents of the leaves of Nerium oleander on behavior pattern in mice.

Fresh, undried and uncrushed leaves of Nerium oleander were subjected to methanol extraction and bioassay directed fractionation. This led to the isolation of two purified fractions namely, B-1 and B-3. Fractions B-1 and B-3 were studied with respect to their actions on the central nervous system and behavior pattern in mice. Both fractions were found to produce reduction in locomotor activity, rota rod performance and potentiation of hexobarbital sleeping time. These fractions also showed analgesic activity. When tested against picrotoxin induced convulsions fraction B-1 showed 40% protection, while fraction B-3 exhibited 60% protection against bicuculline induced convulsions. These findings suggest that both fractions possess a CNS depressant action.

Animals↗