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Biomedical subjects

P H Kay

Publications and source records attributed to P H Kay.

At least 55 records · Page 3Linked to original sources
PubMed1994

A ten-year study of the Ionescu-Shiley low-profile bioprosthetic heart valve.

Seven hundred and eight adults (age > or = 16 years) with isolated aortic (n = 433) or mitral (n = 275) Ionescu-Shiley Low-Profile (ISLP) pericardial valves were followed at 14 implanting centres in Canada, the United Kingdom, and the United States for a mean of 6.7 years, providing 4,729 patient-years of clinical data. The operative mortality rate was 3.0% for aortic valve replacement (AVR) and 5.5% for mitral valve replacement (MVR) (p = ns). Actuarial patient survival following AVR at 5 years was 81.6%, and 62.9% at 10 years; for MVR patients it was 78.1% at 5 years and 59.6% at 10 years. The ISLP valve appears to have durability comparable to other contemporary bioprosthetic valves. For aortic prostheses, the freedom from structural deterioration was 96.5% at 5 years and 73.7% at 10 years, and 89.7% at 5 years and 62.4% at 10 years for mitral prostheses. Structural deterioration was significantly more frequent following MVR than after AVR (p < 0.05). Structural deterioration was the principal cause for reoperation, but sudden deterioration precluding safe reoperation was not a dominant feature of this series. The ISLP valve appeared to engender more thrombo-embolic events than would be anticipated from earlier studies of pericardial bioprostheses, but was indistinguishable from other tissue valves in its incidence of other valve-related complications. We conclude that ISLP valves now implanted for 7 years or more are entering a phase of increasing structural deterioration, indicating the need for regular clinical and echocardiographic surveillance, and that long-term anticoagulation should be instituted for relatively minimal indications in these patients.

Adolescent↗
PubMed1994

Southern blot analysis of lymphoproliferative disorders: use and limitations in routine surgical pathology.

Antigen receptor gene rearrangement studies are a sensitive means of determining lineage and clonality in lymphoproliferative disorders (LPDs) which remain difficult to classify after assessment of morphology and immunohistochemistry (IHC). This study investigates the utility of genotyping LPDs in a surgical pathology laboratory servicing a large teaching hospital. Ninety-eight specimens with detailed frozen (FS) and/or paraffin section IHC were studied, including 65 B-cell lymphomas, 14 T-cell lymphomas, 2 biopsies of T-zone dysplasia, one unclassifiable lymphoma, 8 Hodgkin's disease (HD) and 8 reactive nodes. Southern blotting (SB) was performed on tumor and control DNA cleaved with restriction enzymes EcoR1, Hind III and BamH1, using radiolabelled probes for the immunoglobulin heavy chain joining region, constant regions of kappa and lambda light chains, and the constant region of the T-cell receptor beta chain. All reactive nodes and those harbouring HD and DNA in the germline configuration, apart from JH rearrangement in one case each of HD and florid reactive hyperplasia. Of the non-Hodgkin's lymphomas (NHL), 17% did not reveal clonal rearrangements (11% B-NHL; 44% T-NHL). Most of the negative results could be explained by sampling error in partially involved nodes, highly polymorphous infiltrates where the neoplastic population may have been below the 1% threshold detectable by SB, and instances of anaplastic large cell lymphoma. After accounting for these cases, a 5% negative rate of genoclonality remained (3% B-NHL; 13% T-NHL). In the majority of NHL (95%), the diagnosis could be established on the basis of morphology and/or IHC alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Southern↗
PubMed1993

Studies on the evolution and function of different forms of the mouse myogenic gene Myo-D1 and upstream flanking region.

The product of the murine Myo-D1 gene is able to initiate the complete sequence of genetic events required for formation of skeletal muscle. Because efficiency of regeneration of skeletal muscle is more pronounced in SJL/J mice, as compared to other strains, differences in the structure of Myo-D1 and the upstream regulatory region were sought to determine whether efficiency of tissue repair was influenced by the structure of the gene itself. Analysis of the restriction-fragment length polymorphism (RFLP) of genomic DNA from SJL/J and different sub-strains of mouse indicated that there are at least three different structural forms of Myo-D1, one of which is unique to SJL/J mice and may have been derived from a double recombinational event involving founder forms of Myo-D1. The unique form of Myo-D1 in SJL/J mice also exhibits a PvuII RFLP upstream from the gene, which may reflect some form of rearrangement or variation in methylation of a potential Myo-D1-binding region. Reference to the size of fragments hybridising with the Myo-D1 probe, following digestion of genomic DNA with TaqI, suggests that in most tissues, adenine residues within Myo-D1 may be extensively methylated. Segregation of Myo-D1 allotypes with response to mechanical injury to skeletal muscle in F2 offspring derived from SJL/J and BALB/c parental strains reveals that increased efficiency of tissue repair is associated with the SJL/J type of Myo-D1 gene. These observations provide new approaches to investigation of genetic control of tissue regeneration and cellular differentiation and proliferation in general.

Adenine↗
PubMed1993

Studies on the structure of complement C3 and the stability of C3 derived phagocytic ligands C3b/iC3b in SJL/J and BALB/c mice.

Female SJL/J mice are more susceptible to development of experimental autoimmune myositis than most other mouse strains. Since complement has been implicated in the pathogenesis of inflammatory muscle disease in humans, quantitative and qualitative studies of complement C3 were undertaken in SJL/J and BALB/c mice to determine whether complement may influence disease susceptibility in SJL/J mice. In accordance with previous studies, mature male and female BALB/c mice were shown to have similar serum C3 concentrations. However, differences were found between mature male and female SJL/J mice. Male SJL/J mice have significantly higher serum C3 concentrations than SJL/J females and both sexes of BALB/c mice suggesting that serum C3 concentration may be variably influenced by sex in some mouse strains. Qualitatively, SJL/J mice were shown to have a different allotypic form of C3 (C3F) compared to the common electrophoretically slow form (C3S) found in BALB/c mice and most other mouse strains. Furthermore, studies on the decay rate of C3 revealed that C3b/iC3b fragments are converted to C3c/d at a faster rate in sera from female SJL/J mice compared to female BALB/c mice. Because removal and solubility of immune complexes is influenced by complement C3, it is possible that the more rapid decay of the phagocytic ligands C3b/iC3b may account for the increased susceptibility to development of autoimmune disease in female SJL/J mice.

Animals↗
PubMed1993

Genetic, structural, and functional studies of a C3-like protein in the marsupial Setonix brachyurus.

A monospecific goat antiserum was prepared against a putative C3 protein (QuC3) from serum of the Western Australian macropod Setonix brachyurus (quokka) using the classical method previously used to produce antiserum against C3 from other mammalian species. Sodium dodecyl sulphate-polyacrylamide gel electrophoretic analysis of reduced immunoprecipitated QuC3 revealed two polypeptide chains with an estimated M(r) of 128,000 and 82,000, respectively--presumably reflecting subunit molecules similar to the C3 alpha and beta subunits found in other mammalian species. No variation in the size of either of the QuC3 alpha or beta subunits was found in different quokka serum samples. Furthermore, no variation in the electrophoretic mobility of QuC3 was detected amongst the same samples using a standard immunofixation electrophoretic technique. The addition of zymosan or immune complexes to fresh quokka serum resulted in activation of QuC3. Immune complex mediated activation of QuC3 was inhibited by the addition of EDTA and Mg(2+)-EGTA. By contrast, EDTA only inhibited activation of QuC3 following incubation of fresh quokka serum with zymosan, suggesting that the quokka has a classical and an alternative C3 activation pathway, similar to those found in eutherian mammals. This study has shown for the first time that one of the macropod marsupials (S. brachyurus) has a C3-like protein with similar structural and functional characteristics to C3 found in eutherian mammals. However, unlike C3 in other mammalian species, genetic variability of the structure of the quokka C3-like protein may be restricted.

Animals↗
PubMed1992

Giant epicardial lipoma.

A patient undergoing coronary artery bypass was found to have a giant epicardial lipoma weighing 1.36 kg which was excised uneventfully. The radiological and pathophysiological features are considered, and the options for management discussed.

Cardiac Tamponade↗
PubMed1992

Problems associated with mechanical heart valve sounds.

A cross-sectional study of 50 randomly selected patients 12-36 months following mechanical heart valve replacement with Bjork-Shiley tilting disc valves was undertaken to investigate the factors which affect perception of, and reaction to, sounds generated by mechanical heart valves implanted in patients. Numerous problems were generated by the valves, including annoyance (68%), sleep disturbance (52% in patients; and 46% in patients' partners), interference with concentration (36%) and social embarrassment (28%). These findings are not affected by the measured level of sound or any variation in the number or anatomical position of the valve(s), though age and sex do seem to matter, more problems being reported by younger patients and those of the female sex. Aspects of the patient's personality did not seem to alter the difficulties experienced, though a high level of psychological morbidity was identified in the group as a whole. Most patients experience problems due directly to the noise generated by their valve and should be adequately warned of this before operation. This should also be taken into consideration in designing and evaluating new valve prostheses.

Adaptation, Psychological↗
PubMed1992

Distinguishing between monoclonal rearrangements and allelic forms of the immunoglobulin lambda light chain constant region genes. Significance in the diagnosis of non-Hodgkin's lymphoma.

Four allelic forms of the immunoglobulin lambda light chain constant region (C lambda) genes are found in the caucasoid population and are recognised by the presence of Eco RI restriction fragments of sizes 8, 13, 18, and 23 kb hybridising with a C lambda probe. The less common allelic forms of the C lambda genes are marked by the 13, 18, and 23 kb fragments, and these may be misinterpreted as rearranged fragments derived from a monoclonal population of B-cells. The 13, 18, and 23 kb alleles result from the insertion of one, two, and three copies, respectively, of a 5.2 kb repeat unit that can be demonstrated by hybridising genomic DNA digested with Hind III with a C lambda probe. Using selected histologically and immunophenotypically well-defined cases, we assessed the usefulness of the 5.2 kb Hind III/C lambda fragment in distinguishing between rearrangements indicative of a B-cell lymphoma and germline configurations representing uncommon allelic forms of the C lambda genes. From these studies, we conclude that Hind III digestion should routinely be performed when using the C lambda probe to assess B-cell monoclonality. Identification of the 5.2 kb Hind III fragment obviates the need to examine DNA from normal peripheral blood granulocytes to exclude allelism of the C lambda genes in cases exhibiting the uncommon restriction fragments after Eco RI digestion.

Adult↗
PubMed1991

Genetic polymorphism of the murine myogenic gene Myo-D1.

Polymorphism of the myogenic gene, Myo-D1, has been sought to examine genetic mechanisms which control skeletal muscle development. By Southern analysis, three restriction-fragment length polymorphisms (RFLPs) have been found in various mouse strains using the TaqI, SacI and BglII restriction endonucleases and a full-length cDNA Myo-D1 probe. Reference to the distribution of RFLPs in different mouse strains derived from Mus mus (M.m.) domesticus and M.m. musculus subspecies suggests that Myo-D1 rearrangements are subject to nonrandom association. The biological significance of RFLP of the Myo-D1 gene is yet to be determined.

Alleles↗
PubMed1991

Long-term results of Ionescu-Shiley valve in the tricuspid position.

A retrospective analysis of the long-term results of using the Ionescu-Shiley pericardial bioprosthesis in the tricuspid position was carried out on 73 patients (8 men, 65 women). Of these procedures, ten were tricuspid valve replacement alone and the remainder were in combination with other valve procedures. The mean follow-up was 9.6 years (range, 4 to 18 years). The mean age of the patients was 53 years (range, 27 to 78 years). Seventy-one of the patients suffered tricuspid valve dysfunction from rheumatic heart disease. There were 13 postoperative deaths (within 30 days), giving a mortality rate of 17.8%. The actuarial survival at 10 years was 71% +/- 4.2%. Of the survivors, 49 (79.6%) were in functional class I or II. Primary tissue valve failure in the tricuspid position occurred in 1 patient 12 years after implantation and required reoperation. In another patient bioprosthetic tricuspid valve endocarditis developed. There was no incidence of thromboembolic complications. We conclude that the Ionescu-Shiley pericardial bioprosthesis was a satisfactory prosthesis in the tricuspid position in patients with acquired valvar dysfunction.

Adult↗
PubMed1991

Murine candidiasis: sex differences in the severity of tissue lesions are not associated with levels of serum C3 and C5.

Mice deficient in the fifth component of complement are known to be extremely susceptible to lethal challenge with Candida albicans. However, male mice, that have significantly higher concentrations of serum C5 than females, were markedly more susceptible to infection. This difference was observed in both susceptible (CBA/H) and resistant (BALB/c) mice. Levels of serum C3 likewise showed no correlation with susceptibility.

Animals↗
PubMed1990

Postoperative autologous transfusion in cardiac surgery. A prospective, randomised study.

To investigate the safety and efficacy of postoperative autologous blood transfusion (AT) using the Shiley hardshell venous reservoir, a prospective, randomised, controlled study was carried out in two matched groups of twenty patients undergoing elective coronary artery bypass surgery. The mean volume of shed mediastinal blood reinfused in the first 6 h postoperatively was 371.7 +/- 63.23 ml. Use of homologous blood was reduced from 760.5 +/- 108.37 ml in the control patients to 466.25 +/- 87.44 ml in the AT patients, a reduction of 38.7% (p less than 0.05). There was no statistically significant difference in the clinical outcome, overall blood loss, use of platelets, fresh frozen plasma and colloids, haematological indices, renal and hepatic functions, or clotting mechanism, although there was a reduction in the fibrinogen level in the patients who received AT (p less than 0.05). Mediastinal blood did not clot and was defibrinogenated. It contained significant levels of haemoglobin (8.175 +/- 0.506 g/dl), platelets (96.55 +/- 10.39 per mm3 10(3)), protein (42.5 +/- 1.13 g/l), calcium (2.385 +/- 0.054 mmol/l) and was well oxygenated (PO2 = 20.46 +/- 0.81 kPa). No patients developed bacteraemia or had any AT-related infections. We conclude that postoperative autologous transfusion using the Shiley hardshell venous reservoir is a safe and efficient method for reducing postoperative homologous blood requirement after coronary artery bypass surgery.

Adult↗
PubMed1990

What's new in the role of complement in diseases?

The importance of complement in the potentiation of the immune response is now firmly established. More recently, however, evidence has accumulated which suggests that complement may influence biological events following non-immunologically mediated tissue damage. Several of the many different genetically controlled structural forms of complement components, which are now recognised, have been shown to influence immunoregulation and disease susceptibility. Furthermore, molecular and genetic analyses have revealed that some of the regulatory elements such as S-protein may have multiple biological functions. As a consequence, it is likely that reference to detailed functional and molecular properties of various complement components, with special reference to regulatory elements will provide new insights into mechanisms of pathogenesis of disease.

Complement System Proteins↗
PubMed1990

Supratypes and ancestral haplotypes in IDDM: potential importance of central non-HLA MHC genes.

Juvenile insulin-dependent diabetes mellitus develops in susceptible children exposed to unknown environmental factors. If the genes responsible for susceptibility could be identified, it should be possible to understand the method of injury to beta cells as well as identify the infectious or other agents involved. For a decade it has been known that one or more of the susceptibility genes must be within the major histocompatibility complex (MHC). Unfortunately, there are at least 20 different genes in the complex and it has not been possible to determine which are actually responsible. Therefore, we undertook to apply a new concept and new technology to the problem. Over several years we have shown that the diabetogenic gene(s) are contained within conserved ancestral haplotypes which can then be used as markers of the DNA which must contain the gene(s), whether present in a patient or an asymptomatic carrier such as a parent. This approach avoids the confusion which has resulted from using DR3 or DR4 which are only sometimes associated with the relevant genes. The new technology involves pulsed field gel electrophoresis which allows examination of large fragments of DNA containing all of the MHC, and makes it possible to identify deletions and duplications which were otherwise undetectable. In the first instance we compared two ancestral haplotypes [1,8,3 (8.1) and 18,F1,3 (18.2)] known to contain the relevant genes, and contrasted the DNA with that of another ancestral haplotype [3,7,2(7.1)] which is known to lack these genes. We have shown that there are three major deletions common to the two carrier haplotypes but absent in the protective haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 1↗
PubMed1989

Reoperation after pericardial closure with bovine pericardium.

To reduce the risk of damage to the anterior surface of the right ventricle after resternotomy, it has been recommended that the pericardium be closed with a patch after open heart operations. We have examined 4 patients undergoing resternotomy for the third time 3 to 8 years after bovine pericardium valve replacement. On each occasion the pericardium was closed with a patch of bovine pericardium. In all cases, the patch was frozen to the inner aspect of the sternum, increasing the difficulty of resternotomy. Histological examinations of the patches confirmed dense fibrous connective tissue, patchy calcification, and foreign body giant cell reaction. Bovine pericardium appears to increase the difficulty of repeat cardiac operations. We recommend its use be discontinued.

Adult↗
PubMed1989

Some disease-associated ancestral haplotypes carry a polymorphism of TNF.

We describe here an Nco I restriction fragment length polymorphism of tumor necrosis factor carried by the 8.1 (HLA-A1,B8,BfS,C4AQ0,C4B1,DR3) and the 44.1 (HLA-B44,BfS,C4A3,C4BQ0,DR4) ancestral haplotypes associated with complications of rheumatoid arthritis. By examining multiple examples of these and other ancestral haplotypes it was seen that 8.1 and 44.1 ancestral haplotypes yield fragments of approximately 5.5 kb while many other ancestral haplotypes carry fragments of approximately 10.5 kb. The polymorphism is associated with the ancestral haplotype rather than the HLA-B or -DR allele defined by conventional serology.

Cell Line, Transformed↗
PubMed1989

Comparative mapping of the human major histocompatibility complex in different racial groups by pulsed field gel electrophoresis.

The molecular map of the human major histocompatibility complex was examined in multiple examples of various Caucasoid and Japanese major histocompatibility complex supratypes using pulsed field gel electrophoresis. Extensive differences in restriction fragment lengths were observed. However, each supratype showed specific genomic characteristics including deletions, duplications, or insertions supporting the hypothesis that these supratypes are markers of conserved ancestral haplotypes. Some of the gene arrangements are consistent with the deletions or duplications previously described or suggested by conventional DNA techniques and protein typing, while others have not been recognized previously. Characterization of the gene organization within disease-associated ancestral haplotypes will provide new insights into the functional role and evolution of the major histocompatibility complex.

Asian People↗