Variation is the rule.
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Attitude of Health Personnel↗
Biomedical subjects
E Davis
Publications and source records attributed to E Davis.
Structural instability of mutant beta-cell glucokinase: implications for the molecular pathogenesis of maturity-onset diabetes of the young (type-2).
The catalytic function and thermal stability of wild-type and mutant recombinant human pancreatic beta-cell glucokinase was investigated. The mutants E70K and E300K, which are thought to be the cause of impaired insulin production by the pancreatic beta-cell and decreased glucose uptake by the liver of patients with maturity-onset diabetes of the young, were found to be functionally indistinguishable from the wild-type, i.e. their kcat.S0.5, inflection point and h were normal. However, these two mutants showed markedly reduced stability under a variety of test conditions. Glucokinase instability, not low enzyme catalytic activity, may be the cause of diabetes mellitus with E70K and E300K mutants.
Diabetes Mellitus, Type 2↗
Lymphocyte and monocyte subset changes during cardiopulmonary bypass: effects of aging and gender.
Complications of cardiopulmonary bypass (CPB) may be associated with either immune suppression or immune activation, but the specific effects of CPB on many lymphocyte and monocyte subsets are unclear. In addition, the increasing age of patients undergoing cardiac surgery raises the possibility of even greater effects on the immune system in elderly patients. We measured immunophenotypic alterations of circulating lymphocytes and monocytes after CPB in male and female cardiac surgery patients who were either younger than 60 or older than 75 years of age. The total lymphocyte counts in all patients decreased postoperatively; older patients had significantly lower counts at all time points. The absolute decline was greatest among T cells and particularly CD4+ T cells, which reached an average nadir of 251 cells/microl on postoperative day 1 in the older patients. The percentages of CD8+, CD4+CD45RA+, and CD4+CD45RO+ T cells did not change significantly, whereas the percentages of B cells and natural killer cells increased. Both T and B lymphocytes and monocytes showed evidence of activation, with increased percentages of CD3+HLADr+, CD3+IL2R+, and CD19+CD23+ lymphocytes and increased expression of CD11b on monocytes. By contrast, expression of class II major histocompatibility antigen (HLADr) monocytes decreased significantly. We conclude that CPB produces a profound alteration in the pool of circulating lymphocytes and monocytes, evidenced by decreased numbers of lymphocyte subsets including CD4+ cells and decreased expression of monocyte surface membrane proteins important for antigen presentation; CPB also activates a variety of specific circulating mononuclear cell subsets. Older patients showed patterns of lymphocyte and monocyte activation comparable to those of younger patients; however, they had consistently lower lymphocyte numbers and a trend toward decreased monocyte HLADr expression, potentially placing them at greater risk for infectious complications. Gender had no effect.
Age Factors↗
The leadership role of health services managers.
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Canada↗
Start with the small circle: an interview with Elizabeth Davis. Interview by Cher Mikkola.
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Female↗
Transesophageal echocardiography and the perioperative management of valvular heart disease.
Transesophageal echocardiography (TEE) is an integral part of decision-making and monitoring in the perioperative period for patients undergoing valvular heart surgery. Multiplanar probes with improved pre- and intraoperative evaluation, eg, improved accuracy of estimation of mitral regurgitation jet size, have led to a more precise surgical approach. In the intensive care unit, TEE is proving invaluable in diagnosing occult causes of clinical instability that are usually surgically correctable. Advances in imaging technology with three- and four-dimensional TEE will facilitate preoperative decision-making, determine intraoperative approaches to valvular surgery, and provide earlier recognition of complications in the intensive care unit.
Aortic Valve↗
Autonomy at work: woman-centered birth and midwifery.
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Humans↗
Intuition as authoritative knowledge in midwifery and homebirth.
As defined by Jordan (1992, 1993[1978]), authoritative knowledge motivates decision and action. Based on interviews with 22 white middle-class midwives in the United States conducted between 1992 and 1993, this article explores the inner knowing that constitutes a primary source of authoritative knowledge for homebirthers but is granted no authority in the realm of technomedicine. The purpose of this article is to call attention to these midwives' utilization of and reliance on intuition as a guide to action and decision making during homebirths. The midwife-interviewees are highly literate and competent in technological skills and biomedical diagnosis, and are keenly aware of the cultural and legal risks they run when they cannot justify their actions during a birth in logical, rational terms. Nevertheless, the deep value they place on connection, in the context of their holistic model of birth and health care, leads them to listen to and follow their "inner voice" during birth, rather than operating only according to protocols and standard parameters for "normal birth". The nature of intuition and the reasons for and consequences of the general devaluation of intuitive thinking by the wider society are also considered.
Authoritarianism↗
Shaping a preferred future: Catholic healthcare beyond the year 2000.
The Catholic Health Association of Canada recognizes that the Canadian healthcare system is changing. In a special supplement to the summer edition of the Review, we explored the forces at play within our healthcare environment and identified significant emerging trends. In Part II of this review, we look at the role for Catholic healthcare in Canada beyond the year 2000 by presenting the perspectives of four key spokespersons. These spokespersons outline the valuable contribution Catholic healthcare make within the Canadian healthcare system.
Canada↗
Purchaser and payers: who's driving the market II?
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Cost Control↗
A mutant form of p135tyk2, an interferon-alpha inducible tyrosine kinase, suppresses the transformed phenotype of Daudi cells.
The type I interferons induce an anti-viral state and suppress cell growth. The p135tyk2 non-receptor tyrosine kinase appears to initiate, at least in part, the type I interferon signal transduction pathway, and thereby activates type I interferon-dependent gene expression. To determine if p135tyk2 can suppress growth and/or tumorigenesis, derivatives of the tyk2 gene were introduced into the tumorigenic cell line Daudi. Transfectants expressing a tyk2 construct missing the carboxy-terminal 22 amino acids cloned with a greatly reduced efficiency in soft agar and displayed a partial decrease in the ability to form tumors in athymic mice. In addition, transfectants producing a kinase deficient version of tyk2 show an increase in both growth rate and agar cloning efficiency, suggesting that the inactive kinase can act in a dominant-negative manner. Surprisingly, the carboxyl-terminal deleted protein lacks both auto-kinase activity, and activity towards a putative substrate, even though it induces a phenotype which is precisely the opposite of that produced by another kinase-deficient tyk2 mutant containing an altered ATP binding site. Thus, while these results add tyk2 to a growing list of interferon-alpha regulated proteins that might be able to suppress tumor formation, the biochemical basis of this activity remains unknown.
Animals↗
Acadesine inhibits neutrophil CD11b up-regulation in vitro and during in vivo cardiopulmonary bypass.
Granulocyte adhesion to ischemic tissue, mediated in large part by beta 2 integrin receptors, is important in the pathophysiology of reperfusion injury. Acadesine, a drug that modulates adenosine levels in ischemic tissue, has been shown to reduce reperfusion injury in animal models of ischemia. The purpose of this study was to measure changes in granulocyte CD11b/CD18 in an in vitro assay and in an in vivo trial of acadesine administered during cardiopulmonary bypass to determine whether this agent might modulate up-regulation of this adhesion receptor. In vitro, whole blood was incubated with acadesine or control diluent, stimulated with N-formyl-methionyl-leucyl-phenylalanine, and granulocyte CD11b measured. Acadesine significantly (p < 0.01) inhibited N-formyl-methionyl-leucyl-phenylalanine-induced granulocyte CD11b up-regulation by a mean of 61%. In similar experiments, adenosine also inhibited N-formyl-methionyl-leucyl-phenylalanine-induced granulocyte CD11b up-regulation (p < 0.01). In vivo, 34 patients at our institution participating in a multicenter trial of acadesine during cardiopulmonary bypass were randomized to placebo, low-dose, or high-dose acadesine infusion perioperatively. Combining low- and high-dose treatment groups, there was significant (p = 0.05) inhibition of granulocyte CD11b up-regulation in patients receiving acadesine; granulocyte CD11b expression in the acadesine group peaked at 2.8 times baseline versus 4.3 for placebo. By contrast, monocyte CD11b up-regulation (peaking after cardiopulmonary bypass at 3 times baseline) was not affected by acadesine. Acadesine and adenosine inhibit up-regulation of granulocyte CD11b in vitro, and acadesine is capable of a similar inhibition during in vivo cardiopulmonary bypass. This inhibition may contribute to the ability of these agents to decrease in vivo reperfusion injury.
Adenosine↗
A maturing benefit: eldercare after a decade.
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Aged↗
cDNA and protein sequence of polymorphic macaque albumins that differ in bilirubin binding.
The rhesus monkey, Macaca mulatta, exhibits a geographically restricted polymorphism of serum albumins Mac A and Mac B that is recognized by electrophoresis and is associated with a difference in bilirubin-binding parameters. To identify the basis of the polymorphism, the cDNA and protein sequences of serum albumin from M. mulatta were determined. Screening of a lambda gt11 rhesus liver cDNA library yielded a 1988-bp cDNA sequence that encodes the complete amino acid sequence of mature albumin, the entire propeptide, and part of the prepropeptide. Isoelectric focusing and amino-terminal protein sequencing of CNBr fragments of albumin from A/A and B/B homozygotes were performed, and the structural difference was localized to a CNBr fragment (MCB3) spanning residues 124-264. Sequence analysis of lysyl endopeptidase peptides of MCB3 established that Mac A albumin has a glutamine residue at position 188 while the Mac B albumin has a glutamic residue at the same position. PCR amplification, subcloning, and DNA sequence analysis of clones from A/A and B/B homozygotes confirmed the protein sequence data and the codon difference of CAA versus GAA, respectively. Comparison of macaque and human serum albumin shows a 93.5% identity at the amino acid level. In human serum albumin, Glu188 is located close to the IIA binding pocket for ligands, probably including bilirubin. Derivatives of coumarin compete more efficiently with bilirubin for binding sites on the Mac A albumin than on the Mac B albumin. In regions where coumarin-containing plants are important food resources, Mac B albumin may confer a selective advantage because bilirubin is less readily displaced from it.
Amino Acid Sequence↗
Stabilization of aspartame by polyethylene glycol 400.
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Aspartame↗
A clinical computer database entry form for an intraoperative anesthesiology-based transesophageal echocardiography monitoring service.
Transesophageal echocardiography (TEE) has been increasingly applied to supplement and, in instances, to supplant conventional intraoperative cardiac monitoring. Our body of experience (> 1600 intraoperative TEE procedures), combined with insights gleaned from an intramural quality assurance study, and clinical implications of certain recent advances in the field, led us to develop the following TEE computer database entry form. The form, completed intraoperatively, consists of a patient and surgical procedure demographics section, followed by fields based on the TEE examination. The scans encompass transverse plane basal short axis, long axis, and transgastric views of the heart and great vessels. The two-dimensional echocardiographic, saline-contrast, color flow and pulsed Doppler data represent both right and left ventricular performance, valvular function and specific lesions. This database entry form is intended to serve as a guide for performance of a nominally complete intraoperative study and facilitate maintenance of a TEE archive consistent with current advances.
Anesthesia Department, Hospital↗
The diagnostic puzzle and management challenge of Raynaud's syndrome.
Raynaud's syndrome manifests as a progressive color change of the fingers in response to cold, vibration or stress; the digits first turn white, then blue and finally red. The condition is called Raynaud's disease when it is a benign, primary condition. When it is secondary to another disease, such as lupus, scleroderma or atherosclerosis, it is termed Raynaud's phenomenon. Laboratory tests, i.e., complete blood count, chemistry screen, antinuclear antibody, lupus erythematous test and rheumatoid factor, should be used to seek underlying diseases before the symptoms are manifest. Other tests should be selected as indicated by the history and physical. There are many adjustments in lifestyle and working conditions that the patient can use to minimize the symptoms of Raynaud's syndrome. The primary care provider has an important role in teaching patients to protect their hands from the effects of cold, stress, nicotine and vibration. Adaptive devices and protective clothing minimize the symptoms of Raynaud's syndrome.
Humans↗