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Biomedical subjects

K M Taylor

Publications and source records attributed to K M Taylor.

At least 73 records · Page 4Linked to original sources
PubMed2000

Incomplete and inaccurate death certification--the impact on research.

BACKGROUND: The objectives of this study were (1) to investigate the extent of erroneous and/or omitted information on death certificates of patients-implanted with Bjork-Shiley Convexo-Concave (BSCC) heart valves; (2) to determine whether this information could be associated with a possible under-reporting of acute mechanical failure of this valve. METHODS: A review was carried out of death certificates and clinical notes for patients implanted in the United Kingdom with BSCC valves. This was a multicentre study (38 hospitals) based at the Cardiothoracic Department, NHLI, Imperial College School of Medicine at Hammersmith Hospital, London. The subjects were 478 patients implanted with a BSCC valve between 1979 and 1986 who died in the following years: 1984, 1987, 1990, 1993 and 1996. The main outcome measures were: (1) percentage of death certificates that record the presence of a valve prosthesis; (2) percentage of death certificates that record the presence of a valve prosthesis for patients who had a post mortem; (3) percentage of death certificates that record inaccurate or incomplete information related to the surgery; (4) percentage of death certificates that do not record a post mortem where one is known to have been performed. RESULTS: Twenty-one per cent (101/478) of the total number of death certificates record the presence of the valve prosthesis. Thirty-five per cent (43/123) of the death certificates for patients who had a post mortem record the presence of a valve prosthesis. Six per cent (30/478) of death certificates report inaccurate information related to the valve surgery. Twenty-five per cent (118/478) of the total number of death certificates recorded a single cause of death. Twenty-three per cent (110/478) of all death certificates reviewed recorded only the mode of dying. Eight per cent (10/123) of the total number of death certificates for patients who had a post mortem did not record a post mortem. CONCLUSIONS: The relatively high number of death certificates that do not record the presence of a valve prosthesis and the observed under-reporting of post mortems may lead to inaccurate reporting of the number of BSCC valves that fail. Previous recommendations to improve accuracy in death certification appear to have gone unheeded, and changes in the way certificates are completed for patients with implanted cardiac devices should be considered.

Aged↗
PubMed2000

Ovine uterine gland knock-out model: effects of gland ablation on the estrous cycle.

Ovine endometrial gland development is a postnatal event that can be inhibited epigenetically by chronic exposure of ewe lambs to a synthetic progestin from birth to puberty. As adults, these neonatally progestin-treated ewes lack endometrial glands and display a uterine gland knockout (UGKO) phenotype that is useful as a model for study of endometrial function. Here, objectives were to determine: 1) length of progestin exposure necessary from birth to produce the UGKO phenotype in ewes; 2) if UGKO ewes display normal estrous cycles; and 3) if UGKO ewes could establish and/or maintain pregnancy. Ewe lambs (n = 22) received a Norgestomet (Nor) implant at birth and every two weeks thereafter for 8 (Group I), 16 (Group II), or 32 (Groups III and IV) weeks. Control ewe lambs (n = 13) received no Nor treatment (Groups V and VI). Ewes in Groups I, II, III, and VI were hemihysterectomized (Hhx) at 16 weeks of age. After puberty, the remaining uterine horn in Hhx ewes was removed on either Day 9 or 15 of the estrous cycle (Day 0 = estrus). Histological analyses of uteri indicated that progestin exposure for 8, 16, or 32 weeks prevented endometrial adenogenesis and produced the UGKO phenotype in adult ewes. Three endometrial phenotypes were consistently observed in Nor-treated ewes: 1) no glands, 2) slight glandular invaginations into the stroma, and 3) limited numbers of cyst- or gland-like structures in the stroma. Overall patterns of uterine progesterone, estrogen, and oxytocin receptor expression were not different in uteri from adult cyclic control and UGKO ewes. However, receptor expression was variegated in the ruffled luminal epithelium of uteri from UGKO ewes. Intact UGKO ewes displayed altered estrous cycles with interestrous intervals of 17 to 43 days, and they responded to exogenous prostaglandin F(2 approximately ) (PGF) with luteolysis and behavioral estrus. During the estrous cycle, plasma concentrations of progesterone in intact control and UGKO ewes were not different during metestrus and diestrus, but levels did not decline in many UGKO ewes during late diestrus. Peak peripheral plasma concentrations of PGF metabolite, in response to an oxytocin challenge on Day 15, were threefold lower in UGKO compared to control ewes. Intact UGKO ewes bred repeatedly to intact rams did not display evidence of pregnancy based on results of ultrasound. Collectively, results indicate that 1) transient, progestin-induced disruption of ovine uterine development from birth alters both structural and functional integrity of the adult endometrium; 2) normal adult endometrial integrity, including uterine glands, is required to insure a luteolytic pattern of PGF production; and 3) the UGKO phenotype, characterized by the absence of endometrial glands and a compact, disorganized endometrial stroma, limits or inhibits the capacity of uterine tissues to support the establishment and/or maintenance of pregnancy.

Animals↗
PubMed2000

Progesterone modulation of osteopontin gene expression in the ovine uterus.

Osteopontin (OPN) is an acidic phosphorylated glycoprotein component of the extracellular matrix that binds to integrins at the cell surface to promote cell-cell attachment and cell spreading. This matrix constituent is a ligand that could potentially bind integrins on trophectoderm and endometrium to facilitate superficial implantation and placentation. OPN mRNA increases in the endometrial glandular epithelium (GE) of early-pregnant ewes, and OPN protein is secreted into the uterine lumen. Therefore, progesterone and/or interferon-tau (IFNtau) may regulate OPN expression in the uterine GE. Cyclic ewes were ovariectomized and fitted with intrauterine (i. u.) catheters on Day 5 and treated daily with steroids (i.m.) and protein (i.u.) as follows: 1) progesterone (P, Days 5-24) and control serum proteins (CX, Days 11-24); 2) P and ZK 136.317 (ZK; progesterone receptor [PR] antagonist, Days 11-24) and CX proteins; 3) P and recombinant ovine IFNtau (roIFNtau, Days 11-24); or 4) P and ZK and roIFNtau. All ewes were hysterectomized on Day 25. Progesterone induced the expression of endometrial OPN mRNA in the GE and increased secretion of a 45-kDa OPN protein from endometrial explants maintained in culture for 24 h. Administration of ZK ablated progesterone effects. Intrauterine infusion of roIFNtau did not affect OPN gene expression or secretion in any of the steroid treatments. Interestingly, OPN mRNA-positive GE cells lacked detectable PR expression, although PR were detected in the stroma. Results indicate that progesterone regulates OPN expression in GE through a complex mechanism that includes PR down-regulation, and we suggest the possible involvement of a progesterone-induced stromal cell-derived growth factor(s) that acts as a progestamedin.

Animals↗
PubMed2000

Neonatal ovine uterine development involves alterations in expression of receptors for estrogen, progesterone, and prolactin.

Effects of age on uterine histoarchitecture, cell proliferation, and hormone receptor expression were determined for neonatal ewe lambs from birth (Postnatal Day [PND] 0) to PND 56. Uteri were histologically evaluated and proliferating cell nuclear antigen (PCNA), estrogen receptor alpha (ER-alpha), progesterone receptor (PR), and prolactin receptor (PRL-R) expression were characterized by in situ hybridization (ISH), immunohistochemistry, or both. The most striking feature of neonatal uterine development was the genesis and development of glands in the intercaruncular areas of endometrium. After birth, endometrial glandular epithelium (GE) budded and differentiated into the underlying stroma from the luminal epithelium (LE) between PNDs 1 and 7. Between PNDs 14 and 56, extensive coiling and branching morphogenesis of nascent endometrial glands occurred. By PND 56, the uterine wall appeared to be histoarchitecturally mature. At birth, nuclear PCNA protein was strongly detected in LE. Between PNDs 7 and 56, high levels of PCNA, ER-alpha, and PR gene expression were detected in both nascent and developing GE. Higher levels of PCNA and ER-alpha expression were detected in GE at the tips of developing glands as well as in the surrounding stroma. Progesterone was below detectable limits in serum. Serum estradiol-17beta levels were high on PND 1, increased from PNDs 14 to 28, and declined from PND 42 to PND 56. Serum PRL levels increased from PNDs 1 to 14 and declined thereafter. Using ISH and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, expression of mRNAs for short and long forms of the ovine PRL-R were first detected in nascent GE on PND 7 and increased between PNDs 7 and 56 in proliferating and differentiating GE. These results indicate that 1) uterine gland genesis is initiated between PNDs 1 and 7 after birth and is essentially completed by PND 56; 2) neonatal uterine morphogenesis involves temporal and spatial alterations in cell proliferation and ER-alpha, PR, and PRL-R gene expression; 3) PRL-R expression is a unique marker of GE differentiation and proliferation; and 4) serum estradiol-17beta and PRL levels increase during the onset of GE tubular branching morphogenesis. Results support the hypothesis that neonatal ovine uterine development involves epithelial PRL-R and ER-alpha activation to stimulate and maintain endometrial gland genesis and branching morphogenesis.

Animals↗
PubMed2000

Inhibition of neutrophil L-selectin shedding: a potential anti-inflammatory effect of aprotinin.

The cardiopulmonary bypass (CPB)-related inflammatory response involves leucocyte activation and increased leucocyte-endothelial cell interaction. L-selectin is an adhesion molecule expressed on the surface of leucocytes which participates in the initial rolling step of the leucocyte-endothelial cell adhesion cascade. L-selectin is proteolytically cleaved off the surface of leucocytes when they become activated, an event that is regarded as a marker of leucocyte activation. Aprotinin is a protease inhibitor that has been used in cardiac surgery as a haemostatic agent and also exhibits certain anti-inflammatory properties. In this study, peripheral venous blood from volunteers was pre-incubated with aprotinin at 200, 800 and 1600 kallikrein inhibiting units (kiu)/ml and stimulated with the chemoattractants N-formyl-methyl-leucyl-phenylalanine (fMLP) or platelet activating factor (PAF). Surface expression of L-selectin on neutrophils was measured using a monoclonal antibody and flow cytometry. The results demonstrate that aprotinin inhibits shedding of L-selectin in a dose-dependent fashion (p=0.0278 and 0.0005, respectively, at 800 and 1600 kiu/ml for fMLP-stimulated shedding; p=0.0017 and 0.0010, respectively, at 200 and 800 kiu/ml for PAF-stimulated shedding). This effect may be of significance with respect to the anti-inflammatory action of aprotinin in patients undergoing CPB.

Aprotinin↗
PubMed2000

Role of aprotinin in the management of patients during and after cardiac surgery.

Management of patients undergoing cardiac surgery has evolved in recent years as more is understood about the physiological changes and responses that occur during and after cardiopulmonary bypass (CPB). In particular, our understanding of the mechanisms involved in haemostasis and in the inflammatory response to bypass surgery, has allowed significant refinements in patient management. Improvements in the pharmacological conservation of blood loss have been striking, particularly with the development of the serine protease inhibitor, aprotinin (Trasylol, Bayer). Aprotinin represents a significant improvement, especially for patients at high risk, since it reduces the need for allogeneic and (sometimes scarce) blood products. However, in view of its cost, making an appropriate selection of patients most at risk of serious blood loss is a major consideration in the use of aprotinin. While its mechanisms of action are not well understood, the use of aprotinin also appears to reduce inflammatory response to CPB.

Aprotinin↗
PubMed1999

C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction.

Myocardial infarction in humans provokes an acute phase response, and C-reactive protein (CRP), the classical acute phase plasma protein, is deposited together with complement within the infarct. The peak plasma CRP value is strongly associated with postinfarct morbidity and mortality. Human CRP binds to damaged cells and activates complement, but rat CRP does not activate complement. Here we show that injection of human CRP into rats after ligation of the coronary artery reproducibly enhanced infarct size by approximately 40%. In vivo complement depletion, produced by cobra venom factor, completely abrogated this effect. Complement depletion also markedly reduced infarct size, even when initiated up to 2 h after coronary ligation. These observations demonstrate that human CRP and complement activation are major mediators of ischemic myocardial injury and identify them as therapeutic targets in coronary heart disease.

Acute Disease↗
PubMed1999

Factors affecting the size distribution of liposomes produced by freeze-thaw extrusion.

This paper describes the development of a protocol for the production of liposomes using a freeze-thaw extrusion methodology. Laser diffraction particle size analysis showed that the median diameter of freeze-thawed egg phosphatidylcholine multilamellar vesicles (eggPC MLVs) was increased when cholesterol was included in the bilayers. Using a freeze-thaw cycle of 3 min freezing in liquid nitrogen at -196 degrees C followed by 3 min thawing at 50 degrees C resulted in an anomalously large particle size for eggPC/cholesterol formulations. When liposomes were repeatedly freeze-thawed a maximum size was achieved after five freeze-thaw cycles. Dispersion of liposomes in sodium chloride solutions promoted size increases following freeze-thawing, suggesting that vesicles had aggregated or fused. Poloxamers P338 and P407 inhibited the size increases observed during freeze-thawing for eggPC MLVs dispersed in 1.0 M NaCl, probably through steric prevention of aggregation and fusion.

Chemistry, Pharmaceutical↗
PubMed1999

Essential thrombocythaemia.

Essential thrombocythaemia (ET) is a clonal stem cell disorder that frequently presents as an incidental finding of elevated platelet counts. Diagnosis depends on exclusion of other myeloproliferative disorders and reactive thrombocytosis. Patients with platelet counts above 1000 x 10(9)/L should receive platelet-lowering therapy, even if asymptomatic. Definitive recommendations cannot yet be made for asymptomatic patients with lower platelet counts. ET can be treated with alkylating agents, radioactive phosphorus or hydroxyurea, but there is evidence that these agents increase transformation to acute leukaemia. Interferon alfa-2a and anagrelide are useful treatment agents, particularly in younger patients.

Diagnosis, Differential↗
PubMed1999

A high sensitivity differential scanning calorimetry study of the interaction between poloxamers and dimyristoylphosphatidylcholine and dipalmitoylphosphatidylcholine liposomes.

High sensitivity differential scanning calorimetry (HSDSC) has been used to measure the thermal behaviour of dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) liposomes to which poloxamer surfactants P338 or P407 had been added during or after preparation. The phospholipid pre-transition was more sensitive than the main transition to the association of poloxamers with liposomal bilayers. Poloxamers reduced the enthalpy of the pre-transition of liquid-crystalline state DMPC and DPPC MLVs but not that of gel state DPPC MLVs. Freezing and thawing DMPC and DPPC liposomes in the presence of poloxamers was shown to increase their interaction with the liposomal bilayers.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1999

The cleavable carboxyl-terminus of the small coat protein of cowpea mosaic virus is involved in RNA encapsidation.

The site of cleavage of the small coat protein of cowpea mosaic virus has been precisely mapped and the proteolysis has been shown to result in the loss of 24 amino acids from the carboxyl-terminus of the protein. A series of premature termination and deletion mutants was constructed to investigate the role or roles of these carboxyl-terminal amino acids in the viral replication cycle. Mutants containing premature termination codons at or downstream of the cleavage site were viable but reverted to wild-type after a single passage through cowpea plants, indicating that the carboxyl-terminal amino acids are important. Mutants with the equivalent deletions were genetically stable and shown to be debilitated with respect to virus accumulation. The specific infectivity of preparations of a deletion mutant (DM4) lacking all 24 amino acids was 6-fold less than that of a wild-type preparation. This was shown to be a result of DM4 preparations containing a much increased percentage (73%) of empty (RNA-free) particles, a finding that implicates the cleavable carboxyl-terminal residues in the packaging of the virion RNAs.

Binding Sites↗
PubMed1999

First redo heart valve replacement: a 10-year analysis.

BACKGROUND: The United Kingdom Heart Valve Registry (UKHVR) has recently completed collecting information on 52 659 heart valve replacements (in 47 718 patients) performed during the period 1986 to 1995 in the whole of the United Kingdom. Information stored in the UKHVR's computer database was used for this study. Factors affecting the time from first prosthesis to first redo prosthesis were analyzed and provided useful predictive information. The association between prosthesis-induced local pathological processes and redo valve size was investigated. METHODS AND RESULTS: This is a retrospective study of 43 301 patients (from among 47 718 in the database) undergoing single-site replacement of a diseased native mitral or aortic valve over a 10-year period from January 1986 to December 1995 in the United Kingdom. Of these patients, 1051 (2.43%) went on to have a first redo heart valve replacement. Valve survival analysis (Cox regression and Kaplan-Meier curves) was used to study the natural progression to the first redo heart valve replacement. Female sex and having a replacement at the aortic rather than the mitral position were both associated with a longer interval to the first redo operation. Regression analysis showed the size of the redo valve to be influenced by the interoperative time. This effect was more pronounced at the mitral position. CONCLUSIONS: Females and patients having an aortic valve replacement exhibit a longer interval to the first redo operation than do males and patients having mitral valve replacements, respectively. The time from the first replacement to the first redo operation significantly affects the size of the first redo valve.

Aged↗
PubMed1999

Outcome of coronary endarterectomy: a case-control study.

BACKGROUND: Despite early reports showing a high incidence of postoperative morbidity and mortality, coronary endarterectomy continues to be used as an adjunct to coronary artery bypass grafting, particularly in diffusely diseased coronary arteries. The changing nature of patients and improvements in modern cardiac surgery call for a reevaluation of the role of coronary endarterectomy. METHODS: Data from the 56 patients, who underwent coronary endarterectomy in our institution between January 1993 and August 1996, were reviewed retrospectively and compared with a control group of 56 patients matched for age, sex, LV function, and angina class. In the endarterectomy group, there were 47 men and nine women, with a mean age of 59.6 years. The mean follow-up time was 21 months. Indications for operation were angina in 45 (80.3%), angina with signs or symptoms of cardiac failure in 3 (5.4%), and prognosis in 8 (14.3%) asymptomatic patients. RESULTS: Fifty (89%) patients had one, four (7.2%) had two, and 2 (3.6%) patients had three coronary arteries endarterectomized. Of these 64 endarterectomies, 33 (51.5%) involved the right coronary artery, 20 (31.3%) the left anterior descending artery, and 11 (17.2%) branches of the circumflex artery. There were three (5.4%) nonfatal myocardial infarctions in the endarterectomy group, but none in the control group (p>0.05). Two patients (3.6%) in the endarterectomy group, but none in the control group, died within the first 30 days (p>0.05). Actuarial survival and incidence of recurrent angina were similar in the two groups. CONCLUSIONS: In current cardiac surgical practice, coronary endarterectomy displays satisfactory rates of postoperative morbidity and medium term results in selected groups of patients.

Angina Pectoris↗
PubMed1999

Lung injury and acute respiratory distress syndrome after cardiopulmonary bypass.

Cardiopulmonary bypass is often followed by pulmonary dysfunction as assessed by measuring the alveolar-arterial oxygenation gradient, intrapulmonary shunt, degree of pulmonary edema, pulmonary compliance, and pulmonary vascular resistance. It is also regarded as a risk factor for development of acute respiratory distress syndrome. On the other hand, cardiopulmonary bypass is associated with a whole body inflammatory response, which involves activation of complement, leukocytes, and endothelial cells with secretion of cytokines, proteases, arachidonic acid metabolites, and oxygen free radicals. Leukocyte adhesion to microvascular endothelium, leukocyte extravasation, and tissue damage are the final steps. Although the inflammatory response to cardiopulmonary bypass often remains at subclinical levels, it can also lead to major organ dysfunction and multiple organ failure. This review article summarizes the recent literature on the molecular and cellular mechanisms involved in the phenomenon of pulmonary dysfunction after cardiopulmonary bypass. It also summarizes reports on the prevalence and mortality of acute respiratory distress syndrome after cardiac surgery.

Cardiopulmonary Bypass↗
PubMed1999

The development of an international surgical registry: the ECSUR project. The European Cardiac Surgical Registry.

OBJECTIVES: Cardiac surgery is the first of any therapeutic discipline to attempt to establish a major international registry on a patient-by-patient basis. Being the first necessarily imposes a challenge since no rules or guidelines exist. Possibilities and boundaries must be identified. METHODS: The EACTS database committee established ECSUR (The European Cardiac SUrgical Registry) with the aim of collecting patient-by-patient information from centres across Europe. It was decided to collect patient data in three areas; adult cardiac surgery, paediatric cardiac surgery and thoracic surgery. Currently, these three areas are in different stages of development, with multinational data collection now having already commenced in adult cardiac surgery. RESULTS: After just over a year of data collection ECSUR has now received data from 98 centres in 30 countries, encompassing approximately 100,000 patients. Three national cardiac surgical registries currently send their data to ECSUR, and agreement has been reached with three other countries for prospective data sharing during 1999. CONCLUSION: This paper describes how ECSUR was established, the on-going status of the project, and how the project has now developed a global perspective through a joint European and US initiative to undertake international dataset unification for surgeons worldwide, by the definition of core adult cardiac, paediatric cardiac and thoracic surgical datasets.

Data Collection↗
PubMed1999

A hyperstable collagen mimic.

BACKGROUND: Collagen is the most abundant protein in animals. Each polypeptide chain of collagen is composed of repeats of the sequence: Gly-X-Y, where X and Y are often L-proline (Pro) and 4(R)-hydroxy-L-proline (Hyp) residues, respectively. These chains are wound into tight triple helices of great stability. The hydroxyl group of Hyp residues contributes much to this conformational stability. The existing paradigm is that this stability arises from interstrand hydrogen bonds mediated by bridging water molecules. This model was tested using chemical synthesis to replace Hyp residues with 4(R)-fluoro-L-proline (Flp) residues. The fluorine atom in Flp residues does not form hydrogen bonds but does elicit strong inductive effects. RESULTS: Replacing the Hyp residues in collagen with Flp residues greatly increases triple-helical stability. The free energy contributed by the fluorine atom in Flp residues is twice that of the hydroxyl group in Hyp residues. The stability of the Flp-containing triple helix far exceeds that of any untemplated collagen mimic of similar size. CONCLUSIONS: Bridging water molecules contribute little to collagen stability. Rather, collagen stability relies on previously unappreciated inductive effects. Collagen mimics containing fluorine or other appropriate electron-withdrawing substituents could be the basis of new biomaterials for restorative therapies.

Collagen↗