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  • 1
    ISSN: 1432-1440
    Keywords: Induction ; p53 ; WAF1/CIP1 ; CLL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The treatment of chronic lymphocytic leukemia includes the use of alkylating agents, steroids, and more recently nucleoside analogues. While prior studies have described potential mechanisms of 2-chlorodeoxyadenosine cytotoxicity including the accumulation of DNA strand breaks and induction of apoptosis or programmed cell death, the expression of p53 and its downstream target WAF1/CIP1 have not been examined. In this report we describe the induction of p53 and WAF1/CIP1 in the apoptotic chronic lymphocytic leukemia cells after exposure to 2-chlorodeoxyadenosine.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Key words Induction ; p53 ; WAF1/CIP1 ; CLL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The treatment of chronic lymphocytic leukemia includes the use of alkylating agents, steroids, and more recently nucleoside analogues. While prior studies have described potential mechanisms of 2-chlorodeoxyadenosine cytotoxicity including the accumulation of DNA strand breaks and induction of apoptosis or programmed cell death, the expression of p53 and its downstream target WAF1/CIP1 have not been examined. In this report we describe the induction of p53 and WAF1/CIP1 in the apoptotic chronic lymphocytic leukemia cells after exposure to 2-chlorodeoxyadenosine.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Keywords Insulin-dependent diabetes mellitus ; HLA class II alleles ; newborn screening ; autoimmunity.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Autoimmunity causing insulin-dependent diabetes mellitus (IDDM) begins in early childhood due to interactions between genes and unknown environmental factors that may be identified through follow-up of a large cohort of genetically susceptible children. Such a cohort has been established using a simple and rapid cord blood screening for HLA alleles. The DRB1 and DQB1 second exon sequences were co-amplified using the polymerase chain reaction and hybridized with single and pooled sequence-specific oligonucleotide probes. Four individual probes were used to detect the susceptibility alleles DRB1*03, DRB1*04, and DQB1*0302 as well as the usually protective DRB1*15/16 (DR2) alleles. In addition, pooled probes allow the distinction of DR3/3 from the DR3/x genotype (where x is neither DR2, 3, nor 4) and DR4/4 from DR4/x. Among 5000 newborns from the general Denver population, we have found the high-risk genotype (DRB1*03/DRB1*04, DQB1*0302) to be present in 2.4 % of non-Hispanic whites, 2.8 % of Hispanics, and 1.6 % of African Americans. The moderate-risk genotypes (DRB1*04, DQB1*0302/DRB1*04, DQB1*0302, DRB1*04, DQB1*0302/x, or DRB1*03/DRB1*03) are present in 17 % of American non-Hispanic whites, 24 % of Hispanics and in 10 % of African Americans. These results demonstrate the feasibility of a large-scale newborn screening for genes associated with IDDM. The ultimate role for such a screening in future routine prediction and prevention of IDDM will depend on the availability of an effective and acceptable form of clinical intervention. [Diabetologia 1996) 39: 807–812]
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: Key words Deep vein thrombosis prophylaxis ; Clinical audit ; Low molecular weight heparin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: This retrospective evaluation aimed to assess the adequacy of prophylaxis against thromboembolism prescribed to surgical patients at the authors' institution, and to compare it with generally accepted published guidelines. Aspects considered were indications for prophylaxis, regimens used and monitoring. Methods: Eleven units (nine surgical and two surgical intensive care) took part in the survey on a voluntary basis. The clinical audit system used involved developing a set of criteria based on existing guidelines, comparing observed practice with those recommendations, analysing the factors underlying any deviation and developing corrective measures. Results: When the medical records of 117 patients hospitalized in October 1995 were examined, prophylaxis against deep vein thrombosis was documented in 86 (low molecular weight heparin in 85, dextran in one). No associated physical preventative measures were recorded. Indications and dosage were appropriately handled in 90.7% and 75.2% of patients, respectively. Ninety-five cases were outside the reference criteria: 74 for excluded surgical indications, 13 which involved laparoscopy, and eight in which spinal or epidural anaesthesia was administered. Platelet count was performed in 73.8% of cases before prophylactic treatment, and in 23.1% during its course. Anti-Xa activity was measured in 0.4% of cases. Analysis of causes showed that guidelines were not complied with either because of lack of organization, or because of disagreement with them. Discussion: In this study, indications for prophylaxis were well established and heparin dosages used were not fundamentally flawed. The weak point in practice was a failure to carry out platelet counts, particularly during the course of treatment. Appropriate corrective action consists of disseminating guidelines and relevant information, and using a preoperative checklist to assess thromboembolic risk. Conclusion: Physicians agree that opportunities to improve preventative practices exist, and that the quality improvement programme should be pursued.
    Type of Medium: Electronic Resource
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