Biomedical subjects
B Smith
Publications and source records attributed to B Smith.
EEG results are rarely the same if repeated within six months in childhood epilepsy.
OBJECTIVE: To assess the reliability of interictal spike discharge in routine electroencephalography (EEG) testing in children. METHOD: EEG results of all children diagnosed in Nova Scotia with epilepsy onset between 1977-85 (excluding myoclonic, akinetic-atonic and absence) were reviewed. The results of the EEG at time of diagnosis (EEG1) were compared with those of a second EEG (EEG2) within 6 months. RESULTS: Of 504 children with epilepsy, 159 had both EEG1 and EEG2. EEG2 was more likely ordered if EEG1 was normal or showed focal slowing but less likely if EEG1 contained sleep (p < 0.05). EEG1 and EEG2 were both normal in 23%. If EEG1 was abnormal, there was a 40-70% discordance for the type of abnormality on EEG2. Abnormalities were present on both EEG1 and EEG2 in 67 cases. Of the 42/67 with major focal abnormalities on EEG1, 7 had only generalized spike wave on EEG2. Of the 17/67 with only generalized spike wave on EEG1, 7 showed only major focal abnormalities on EEG2. Statistical testing showed low Kappa scores indicating low reliability. CONCLUSIONS: The interictal EEG in childhood epilepsy appears to be an unstable test. A repeat EEG within 6 months of a first EEG may yield different and sometimes conflicting information.
Loss of cyclin-dependent kinase inhibitor genes and chromosome 9 karyotypic abnormalities in human bladder cancer cell lines.
Loss of cell cycle control through the structural or functional aberration of checkpoint genes and their products is a potentially important process in carcinogenesis. In this study, a panel of well-characterised established human bladder cancer cell lines was screened by the polymerase chain reaction for homozygous loss of the cyclin-dependent kinase inhibitor genes p15, p16 and p27. The results demonstrate that, whereas there was no genetic loss of p27, homozygous deletion of both p15 and p16 genes occurred in seven of 13 (54%) independent bladder cell lines tested. Differential loss of either the p15 or p16 gene was not seen. The p15 and p16 genes are known to be juxtaposed on chromosome 9p21 at the locus of a putative tumour-suppressor gene involved in the initiation of bladder cancer. Cytogenetic analysis of the cell lines revealed karyotypes ranging from near diploid to near pentaploid with complex rearrangements of some chromosomes and a high prevalence of chromosome 9p rearrangements, although all cell lines contained at least one cytogenetically normal 9p21 region. These observations support a role for p15/p16 gene inactivation in bladder carcinogenesis and/or the promotion of cell growth in vitro and lend support to the hypothesis that homozygous deletion centred on 9p21 is a mechanism by which both p15 and p16 genes are co-inactivated.
Detection of epithelial cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction.
Circulating cancer cells in the blood play a central role in the metastatic process. Their number can be very small and techniques for their detection need to be both sensitive and specific. Polymerase chain reaction (PCR) has been successfully used to detect small numbers of tumour cells in haematological cancer in which abnormalities in DNA are sufficiently consistent to make this possible. For most solid tumours this not yet feasible. However, we have found that reverse transcriptase (RT)-PRC for tissue-specific gene expression is a useful technique for identifying small numbers of circulating cells in melanoma and neuroblastoma patients. In this report we describe detection of colon carcinoma cells by RT-PCR using CK 20 mRNA as a marker. Unlike other cytokeratin genes examined (CK 8 and CK 19), CK 20 was not transcribed in normal haematopoietic cells. This suggests a role for RT-PCR in the detection of colon carcinoma metastasis in blood and bone marrow, using CK 20 as the target gene. Future analysis of clinical material will determine the clinical significance of this technique.
Further studies of the binding specificity of the leukocyte adhesion molecule, L-selectin, towards sulphated oligosaccharides--suggestion of a link between the selectin- and the integrin-mediated lymphocyte adhesion systems.
This communication is concerned with the binding specificity of the leukocyte-adhesion molecule L-selectin (leukocyte homing receptor) towards structurally defined sulphated oligosaccharides of the blood group Le(a) and Le(x) series, and of the glycosaminoglycan series heparin, chondroitin sulphate and keratan sulphate. The recombinant soluble form of the rat L-selectin (L-selectin-IgG Fc chimera) investigated here was shown previously to bind to lipid-linked oligosaccharides 3-O, 4-O and 6-O sulphated at galactose, such as sulphatides and a mixture of 3-sulphated Le(a)/Le(x) type tetrasaccharides isolated from ovarian cystadenoma, as well as to the HNK-1 glycolipid with 3-O sulphated glucuronic acid. In the present study, the L-selectin investigated in both chromatogram binding and plastic microwell binding experiments using neoglycolipids was found to bind to the individual 3-sulphated Le(a) and Le(x) sequences (penta-, tetra- and trisaccharides), and with somewhat lower intensities to their non-fucosylated analogues. Glycosaminoglycan disaccharides of keratan sulphate, heparin and chondroitin sulphate types were also bound by L-selectin in one or both assay systems, leading to the conclusion that clustered glycosaminoglycan oligosaccharides with 6-O sulphation of N-acetylgalactosamine, N-acetylglucosamine or glucosamine, 4-O sulphation of N-acetylgalactosamine, 2-O sulphation of uronic acid, N-sulphation of glucosamine and, to a lesser extent, the non-sulphated uronic acid-containing disaccharides, can support L-selectin adhesion. As inflammatory chemokines (short-range stimulators of lymphocyte migration which trigger integrin activation) are known to bind to endothelial glycosaminoglycans, we propose that the binding of the lymphocyte membrane L-selectin to endothelial glycosaminoglycans may provide a link between the selectin-mediated and integrin-mediated adhesion systems in leukocyte extravasation cascades. The possibility is also raised that lymphocyte L-selectin interactions with glycosaminoglycans may contribute to pathologies of glycosaminoglycan-rich tissues, e.g. cartilage loss in rheumatoid arthritis and inflammatory lesions of the cornea.
Inducible transposition in Streptomyces lividans of insertion sequence IS6100 from Mycobacterium fortuitum.
Transposition of IS6100, originally isolated as part of the compound transposon Tn610 from Mycobacterium fortuitum, was tested in the related actinomycete Streptomyces lividans. Cointegrate formation was observed, as expected for this IS6-related element, and involved apparent random integration of the temperature-sensitive vector carrying IS6100 and concomitant duplication of the insertion sequence. This establishes that a single copy of the insertion sequence can promote transposition and is a precedent for the functioning of a heterologous transposable element in Streptomyces. Transposition could be induced 100-fold by external transcription emanating from a copy of the thiostrepton-inducible promoter ptipA located outwith the insertion sequence and resulting in overexpression of the transposase gene. Thus, in contrast to other prokaryotic transposable elements, IS6100 appears to have no effective means of protecting itself from external activation.
Acute regional myocardial ischemia and recovery after cardiopulmonary bypass: effects of intensity of antecedent ischemia.
Aortic cross-clamping with inadequate myocardial preservation has been shown to cause postoperative decreases in myocardial performance following coronary artery bypass graft surgery. We have demonstrated a mild decrement in myocardial beta-receptor function associated with cold cardioplegia in a normal animal model; in normal human hearts, however, response to beta-adrenergic inotropic stimulation was diminished significantly. Beta-receptor dysfunction also is associated with chronic myocardial ischemia that is associated with severe ischemic heart disease. Although the change in beta-receptor function with acute regional myocardial ischemia associated with severe ischemic heart disease is not understood fully, we found that the intensity of regional ischemia significantly affects functional recovery after cardiopulmonary bypass (CPB). Myocardial stunning does not appear to be significant in this dysfunction; however, alterations in beta-receptor density and function may play a critical role in post-CPB ventricular function.
The prenatal exclusion test for Huntington's disease: experience in the west of Scotland, 1986-1993.
Information about the prenatal exclusion test for Huntington's disease (HD) has been given to an unselected series of couples who attended the genetic counselling clinic from 1986 onwards. Ten couples underwent 13 prenatal tests during this period with expressed intention of stopping a pregnancy if the result indicated a high risk (almost 50%) that the fetus carried the HD gene. Nine fetuses at nearly 50% risk of carrying the HD gene were identified but only six such pregnancies were terminated. In each of three high risk pregnancies which continued, the mother made a "final hour" decision not to undergo the scheduled, first trimester termination. In our experience, late reversal of a previous decision to undergo first trimester pregnancy termination for a genetic indication is uniquely frequent among couples who have undergone the prenatal exclusion test for HD.
Studies of the effect of Pall leucocyte filters LG6 and AV6 in an in vitro simulated extracorporeal circulatory system.
Neutrophil activation is thought to play a major role in the inflammatory response seen in reperfusion injury and similar clinical situations, i.e. extracorporeal circulation. Impairment of neutrophil function or reduction of total numbers of neutrophils using a leucocyte filter may be beneficial in reducing the adverse clinical effects. In this study we have investigated the effect of the Pall LG6 and control AV6 filters during simulated in vitro cardiopulmonary bypass (CPB). Various parameters were evaluated including neutrophils, total leucocytes, monocytes, lymphocytes and platelets, expression of antigens on neutrophils using a panel of leucocyte-associated monoclonal antibodies CD13, 14, 15, 45Ro, 67, 11a, 11b and L selectin. The effects of leucocyte stimulation with phorbol myristate acetate (PMA) and a leucocyte bolus from a patient with chronic myeloid leukaemia (CML) were also investigated. We have demonstrated that the LG6 significantly reduces leucocytes, in particular neutrophils, with a modest reduction of lymphocytes, platelets and haematocrit, whereas the AV6 had no effect on leukocytes or neutrophils in the test system. In addition the LG6 was associated with a reduction in expression of all leucocyte antigens by approximately 20%; however there was no appreciable alteration of any of the antigens with AV6. Leucocyte stimulation with PMA resulted in a dramatic decrease of all cellular elements and an extra leucocyte load (using CML leucocytes) was not effectively filtered by the LG6 filter. These studies identify the capacity of the LG6 as compared with the AV6 to deplete activated neutrophils in an in vitro simulated cardiopulmonary bypass circuit.
Merger mania: surviving the on-going shake-outs.
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Expert systems for third-party reimbursement: planting seeds for accuracy.
Predictably, the genesis of most business expert systems development is not related to one particular issue, but to a series of business issues that converge to form the basis for system design as either enhancements or overhauls. Rarely, if ever, is there a conclusion to the system's enhancement process, but rather, an ongoing evolution of the system as dictated by a multitude of both internal and external forces. The focal point of these processes must be to benefit our customers and the markets we serve.
The mobilization of nurses: experiences of a lifetime. Interview by Jane Harris.
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Understanding rostering. Part 6. Changing rosters--managing roster change.
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Understanding rostering. Part 2. The rights & wrongs of rostering.
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Understanding rostering. Part 3. How a roster is developed.
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Understanding rostering. Part 4. Products & consequences.
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Bronchial hygiene therapy.
Bronchial hygiene therapy is useful and effective in the presence of careful patient evaluation, clear definition of therapeutic goals, and application of appropriate modalities. This article defines the variable bronchial hygiene modalities and discusses their indications, contraindications, and applications. Prophylactic and therapeutic bronchial hygiene modalities, diagnostic methods associated with bronchial hygiene therapy, inhaled antibiotic therapy, and therapist driven protocols are also addressed.
Understanding rostering. Part 1. The rights & wrongs of rostering.
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