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Biomedical subjects
Publications and source records attributed to M Kennedy.
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Forty cases of gastric lymphoma presenting in Grampian Region (1974-91) were reviewed to examine the effects of changing ideas in the fields of chemotherapy, gastric surgery and diagnostic techniques, as well as the impact of Helicobacter pylori. Presentation was non-specific, and the diagnosis was made pre-operatively in only 12 cases. Survival was related to tumour size, staging (Ann Arbor), and grade, with a crude 5-year survival of 49%. Helicobacter pylori was found in all specimens reviewed. Patients who underwent "potentially curative' surgery followed by adjuvant therapy had the best survival (85% at 5 years). There remains a need for larger studies to define the best treatment for this uncommon condition.
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AIMS: To establish a DNA-based test for the diagnosis and carrier detection of fragile X syndrome, and to investigate the nature of the mutation and patterns of inheritance in New Zealand families. METHODS: A probe for the FRAXA region was generated by polymerase chain reaction, cloned in a plasmid vector, and its structure was confirmed by DNA sequencing. This probe was used in a Southern blot assay to detect full mutations or premutations associated with fragile X syndrome in DNA from peripheral blood samples submitted to our laboratory for routine testing. RESULTS: We tested 379 individuals from throughout New Zealand. Full mutations were found in 29 males, leading to a fragile X diagnosis, or confirmation of an earlier cytogenetic diagnosis. Premutations were detected in 45 females and 11 males, all of whom are asymptomatic carriers of the disease. CONCLUSIONS: The DNA test is rapid and accurate, in contrast to the cytogenetic test. It allows unequivocal detection of carriers, enabling effective counselling, prenatal testing, and more generalised screening of at-risk populations. Our discovery of one large pedigree with many carriers and no prior history of X-linked mental retardation demonstrates that the DNA test is appropriate even in apparently sporadic cases of mental retardation.
Calcineurin (CaN) is a calcium- and calmodulin-dependent serine/threonine phosphatase whose inhibition by the immunosuppressant-immunophilin complexes (cyclosporin-cyclophilin and FK506-FKBP) is considered key to the mechanism of immunosuppression. CaN is a heterodimer, consisting of a 59 kDa catalytic subunit (A) and a 19 kDa calcium-binding regulatory subunit (B). The latter is postulated to harbor four calcium binding domains of the EF hand type. The titration of the CaN B apoprotein with the isomorphic Cd2+ was followed by 113Cd NMR and these data support one high-affinity metal binding site and three lower-affinity ones. Flow dialysis data with Ca2+ indicate one high affinity calcium binding site with Kd approximately 2.4 x 10(-8) M and three other sites with Kd approximately 1.5 x 10(-5) M. The chemical shifts of all four 113Cd resonances (-75, -93, -106 and -119 ppm) are in the same range as found in other 113Cd substituted calcium-binding proteins, and are indicative of all-oxygen coordination of pentagonal bipyramidal geometry.
The response to an inactivated hepatitis A vaccine was assessed in 307 persons: 163 Alaska Native children, ages 3-6 years, and 144 Native (84) and non-Native (60) adults. All adults received the same vaccine schedule (0, 1, and 12 months), whereas children were randomized to receive three different schedules (0, 1, and 6; 0, 1, and 2; or 0, 1, and 12 months). After one dose, 141 (96%) of 147 children and 129 (90%) of 143 adults responded with levels of antibody to hepatitis A virus > 20 mIU/mL. After three doses, all participants responded. The geometric mean titer (GMT) 1 month after the third dose was significantly higher in children who received the third dose 12 months after the first dose rather than 2 months after the first dose. While there were differences in the GMT of some blood samples by age, sex, and ethnicity, all participants responded to the vaccine.
The Catastrophic Anti-phospholipid Syndrome (CAPS) is a rare acute clinical syndrome associated with serum anti-phospholipid antibodies (aPL). It is rarely preceded by a precipitating event. It may occur as a primary event or be associated with auto-immune diseases. We report a fatal case occurring post-endoscopic retrograde cholangio-pancreatography (ERCP) in a patient with Systemic Lupus Erythematosus (SLE), positive lupus anticoagulant and negative IgG with positive IgM anti-cardiolipin titres. The diagnostic and therapeutic difficulties of such cases is addressed.
An analytical procedure for describing agrammatic spoken language based on government and binding theory is used to characterise the spoken grammar of an aphasic adult (JR) with severe agrammatism. Analysis of JR's spoken language revealed that he produced a greater number of single-word utterances (single lexical items) in comparison with lexical and/or functional projections. both morphological and syntactic evidence suggested that JR retained a differentiated set of lexical categories. No violations of word order were found. Target determiners and target inflection phrases were not always correctly realised. No 'complementiser' phrases or complex sentences were produced by JR. Analysis of the data collected suggests that JR's morphosyntactic abilities were not 'lost', but rather specific morphosyntactic representations were inaccessible. We hypothesise that his deficit is best characterised (rather loosely, in the absence of a clear and full account of language-processing impairments, and other theoretical evidence) as a deficit in performance rather than in competence. Implications of the results of the analysis for intervention are discussed as are future plans for adaptation of the profile into a clinically useful procedure.
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