Challenges in family practice related to informed and shared decision-making: a survey of preceptors of medical students.
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Attitude of Health Personnel↗
Biomedical subjects
R McKendry
Publications and source records attributed to R McKendry.
Chemical force microscopy with active enzymes.
The adhesion forces have been measured between an atomic force microscope tip derivatized with an active enzyme, shikimate kinase, and an ATP mimic immobilized on a gold surface. Experiments with competitive binding of other ligands in solution show that the observed adhesion forces arise predominantly from specific interactions between the immobilized enzyme and surface-bound adenine derivative. These experiments represent a step in the development of a screening methodology based upon chemical force microscopy.
Binding, Competitive↗
Legalized, regulated, but unfunded: midwifery's laborious professionalization in Alberta, Canada, 1975-99.
In 1992, Alberta became the second Canadian province to legalize midwifery. This happened even though there were only approximately 20 midwives in practice at the time, and despite strong opposition from the medical and nursing professions. Between 1992 and 1999. Alberta established a regulatory framework for midwifery as a profession but. unlike Ontario and British Columbia, failed to pay midwives out of the provincial health care budget. This sent midwifery in Alberta into a crisis as many midwives closed their practices. This article first considers why midwifery was legalized and then professionalized in Alberta. Our answer emphasizes the leading role of state health bureaucrats in promoting midwifery as part of the state's challenge to medical dominance. Second. the article addresses why midwifery received so little governmental support at the same time that it attained professional status. This analysis includes a comparison with how midwifery developed in Ontario and British Columbia. Our conclusion is that midwifery in Alberta became a victim in the post-1993 period when a new Right government set aside bureaucratic initiatives in health care and committed itself to major cuts in government spending.
Alberta↗
Evaluation of the quality of patient information to support informed shared decision-making.
OBJECTIVES: (a) To find out how much patient information material on display in family physicians' offices refers to management choices, and hence may be useful to support informed and shared decision-making (ISDM) by patients and (b) to evaluate the quality of print information materials exchanged during the consultation, i.e. brought in by patients or given out by family physicians. DESIGN: All print information available for patients and exchanged between physicians and patients was collected in a single complete day of the office practices of 21 family physicians. A published and validated instrument (DISCERN) was used to assess quality. SETTING AND PARTICIPANTS: Community office practices in the greater Vancouver area, British Columbia, Canada. The physicians were purposefully recruited by their association with the medical school Department of Family Practice, their interest in providing patients with print information and their representation of a range of practice types and location. MAIN VARIABLES STUDIED: The source of the pamphlets and these categories: available in the physicians' offices; exchanged between physician and patient; and produced with the explicit or apparent intent to support evidence-based patient choice. MAIN OUTCOME MEASURES: The quality of the print information to support ISDM, as measured by DISCERN and the ease of use and reliability of the DISCERN tool. RESULTS AND CONCLUSIONS: Fewer than 50% of pamphlets available in these offices fulfilled our minimum criteria for ISDM (mentioned more than one management option). Offices varied widely in the proportion of pamphlets on display that supported ISDM and how particular the physician was in selecting materials. The DISCERN tool is quick, valid and reliable for the evaluation of patient information. The quality of patient information materials used in the consultation and available in these offices was below midpoint on the DISCERN score. Major deficiencies were with respect to the mention of choices, risks, effect of no treatment or uncertainty and reliability (source, evidence-base). Good quality information can be produced; some is available locally.
British Columbia↗
Synovial cyst of the proximal tibiofibular joint.
We describe a case of an unusual synovial cyst originating from the proximal tibiofibular joint. This cyst presented as a painless, soft tissue swelling just distal to the fibular head. We review the literature on this topic regarding clinical presentation, imaging, and management.
Female↗
Activin-induced factors maintain goosecoid transcription through a paired homeodomain binding site.
Previous studies in both Xenopus and zebrafish have shown that goosecoid is one of the first genes to be transcribed at the onset of gastrulation. Goosecoid transcription still initiates when embryos are treated with protein synthesis inhibitors, indicating that it is mediated by preexisting factors and suggesting that goosecoid transcription is immediately downstream of the maternal mesoderm-inducing signal. However, goosecoid transcription continues long after this maternal signal has ceased to be active, indicating that there are mechanisms to maintain activin-induced transcription. Our study has focused on understanding the factors required to maintain this transcription. We have defined an element within the zebrafish goosecoid promoter that is sufficient for activin inducibility in both Xenopus and zebrafish embryos. This element, the goosecoid activin element, interacts with two developmentally regulated proteins from Xenopus embryos. A maternal protein interacts through cleavage stages until the midblastula transition, and a second protein binds from the onset of gastrulation. The second protein is zygotically expressed, and its binding is required for activin inducibility in our assay system. We suggest that the zygotic protein we have identified is a good candidate to be involved in the maintenance of goosecoid transcription. Furthermore, this zygotic protein is likely to contain a paired class homeodomain since a consensus binding site for such proteins is present within the goosecoid activin element and is essential for its function.
Activins↗
LEF-1/TCF proteins mediate wnt-inducible transcription from the Xenopus nodal-related 3 promoter.
The Xenopus nodal-related 3 gene (Xnr3) is expressed in the Spemann organizer of the embryo and encodes a member of the transforming growth factor beta family that mediates some activities of the organizer. Xnr3 is transcriptionally activated by wnt signaling during gastrulation in the Xenopus embryo. Here we show that a small region of the Xnr3 promoter is sufficient to confer wnt-inducible transcription. By mutational analysis of the promoter, we have identified two distinct sequence elements required for the response to wnt signals. One regulatory sequence interacts with a factor which accumulates in Xenopus gastrulae independent of wnt signaling. The other functionally important site can bind mammalian LEF-1 protein, a member of the LEF-1/TCF family of transcription factors. In addition, misexpression of LEF-1 in embryo explants induces transcription of the endogenous Xnr3 gene. Taken together, these data provide further evidence for a role of LEF-1/TCF proteins in wnt signaling and identify the Spemann organizer-specific gene Xnr3 as a direct target of these transcription factors in vertebrates.
Animals↗
Combination treatment of severe rheumatoid arthritis with cyclosporine and methotrexate for forty-eight weeks: an open-label extension study. The Methotrexate-Cyclosporine Combination Study Group.
OBJECTIVE: To determine whether the clinical benefit and favorable safety profile previously noted with the combination of cyclosporine (CSA) and methotrexate (MTX) given for 24 weeks in patients with rheumatoid arthritis (RA) would be maintained for a further 24 weeks, and whether the addition of CSA in patients who had previously been randomized to receive placebo + MTX would result in clinical benefit. METHODS: Eligible subjects from the initial study (weeks 0-24), in which the addition of placebo or CSA to MTX therapy was compared in patients with RA that was partially responsive to MTX, were enrolled. Patients who had received CSA + MTX continued this regimen for a further 24 weeks (weeks 24-48) (group 1; n = 48), and patients who had initially received placebo + MTX now received CSA + MTX for 24 weeks (weeks 24-48) (group 2; n = 44), in an open-label extension study. The primary outcome measures were the number of tender joints, number of swollen joints, physician and patient global assessments, pain, functional disability as measured by the modified Health Assessment Questionnaire, and erythrocyte sedimentation rate. RESULTS: Of the 92 patients enrolled, 80 (87%) completed the extension study. In patients in group 1, the clinically and statistically significant improvement in response outcomes previously noted at week 24, ranging from 25% to 50%, was maintained through week 48. In patients in group 2, the addition of CSA resulted in significant clinical improvement. By week 48, most outcome measures in group 2 patients were similar to those in group 1 patients. CSA treatment resulted in a small increase in serum creatinine levels, but only 1 patient was withdrawn from the study for this reason. CONCLUSION: The clinical improvement previously observed in patients treated with the CSA + MTX combination for 24 weeks was maintained for 24 subsequent weeks, without serious adverse effects, and was also observed in the patients whose treatment was switched from placebo + MTX to CSA + MTX.
Adult↗
Interferon-alpha-dependent activation of Tyk2 requires phosphorylation of positive regulatory tyrosines by another kinase.
Tyk2 and JAK1, members of the Janus kinase (JAK) family of protein tyrosine kinases, are required for interferon-alpha/beta binding and signaling. Both enzymes are associated with the interferon-alpha/beta receptor, and upon ligand binding, they undergo tyrosine phosphorylation and catalytic activation in an interdependent manner. To identify residues involved in Tyk2 regulation and to understand the basis of the interdependence of Tyk2 and JAK1, six mutated versions of Tyk2 bearing single or multiple point mutations in the tyrosine kinase domain were studied in a cell line lacking endogenous Tyk2. The Y1054F/Y1055F substitutions in the putative activation loop prevented ligand-dependent activation of Tyk2, without abolishing its catalytic potential. The K930R mutation in the ATP binding site generated a kinase-negative protein, which however, still became phosphorylated upon interferon-alpha treatment. The Y1054F/Y1055F substitutions in this kinase-negative Tyk2 abolished the induced phosphorylation. These results indicate that Tyk2 is activated by phosphorylation on Tyr-1054 and/or Tyr-1055 and that this phosphorylation requires another kinase, most likely JAK1. While the Tyk2 forms mutated on Tyr-1054 and Tyr-1055 or on Lys-930 allowed some inducible gene expression, the combination of the three point mutations totally abolished signaling.
Amino Acid Sequence↗
Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. The Methotrexate-Cyclosporine Combination Study Group.
BACKGROUND: Patients with severe rheumatoid arthritis who are treated with methotrexate frequently have only partial improvement. METHODS: In a six-month randomized, double-blind trial, we compared combination therapy with cyclosporine (2.5 to 5 mg per kilogram of body weight per day in two divided doses at 12-hour intervals) and methotrexate (at the maximal tolerated dose) with methotrexate and placebo in 148 patients with rheumatoid arthritis who had residual inflammation and disability despite partial but substantial responses to prior methotrexate treatment. The primary outcome measure was the change in the number of tender joints. RESULTS: The mean (+/- SD) dose of cyclosporine at the final treatment was 2.97 +/- 1.02 mg per kilogram per day. As compared with the placebo group, the patients in the treatment group had a net improvement in the tender-joint count of 25 percent, or 4.8 joints (95 percent confidence interval, 0.7 to 8.9; P = 0.02), and in the swollen-joint count of 25 percent, or 3.8 joints (95 percent confidence interval, 1.3 to 6.3; P = 0.005); improvement in overall disease activity as assessed by the physician (19 percent, P < 0.001) and the patient (21 percent, P < 0.001); and improvement in joint pain (23 percent, P = 0.04) and in the degree of disability (26 percent, P < 0.001). The mean erythrocyte sedimentation rate increased by 4.2 mm per hour in the cyclosporine group and decreased by 4.8 mm per hour in the placebo group (P = 0.006). Thirty-six patients (48 percent) in the cyclosporine group and 12 patients (16 percent) in the placebo group (P < 0.001) met the 1993 criteria for improvement of the American College of Rheumatology (more than 20 percent improvement in the numbers of both swollen and tender joints and improvement in three of five other variables). Seventeen patients in the cyclosporine group and 12 patients in the placebo group were withdrawn from the study; 2 patients in the cyclosporine group died, 1 from viral pneumonia and the other in a motor vehicle accident. Serum creatinine concentrations increased by a mean of 0.14 +/- 0.27 mg per deciliter (12 +/- 24 mmol per liter) in the cyclosporine group and by 0.05 +/- 0.19 mg per deciliter (4 +/- 17 mmol per liter) in the placebo group (P = 0.02). CONCLUSIONS: In a six-month study, patients with severe rheumatoid arthritis and only partial responses to methotrexate had clinically important improvement after combination therapy with cyclosporine and methotrexate. Side effects were not substantially increased. Long-term follow-up of patients treated with this combination is needed.
Arthritis, Rheumatoid↗
A nodal-related gene defines a physical and functional domain within the Spemann organizer.
A functional screen for gene products that rescue dorsal development in ventralized Xenopus embryos has yielded Xenopus nodal-related 3 (Xnr3), a diverged member of the TGF beta superfamily. Xnr3 is specifically expressed in the Spemann organizer and is only expressed in the epithelial layer of the organizer immediately preceding and extending through gastrulation. Like noggin, Xnr3 can induce muscle in ventral mesoderm explants, consistent with a role in patterning the gastrula. In other ways, the activity of Xnr3 is different from noggin. Embryos receiving injections of Xnr3, particularly in the animal pole, send out tube-like extensions of tissue from the site of injection. These protrusions usually contain no axial mesoderm and only occasionally are positive for neural markers. It has previously been proposed that the epithelial layer of the organizer initiates and coordinates the morphogenetic movements at gastrulation. The protrusions observed may reflect an activity of Xnr3 in promoting morphogenesis.
Actins↗
Constitutive production of alpha and beta interferons in mutant human cell lines.
Alpha and beta interferons control expression of a selectable marker in the human hypoxanthine phosphoribosyltransferase-negative cell line 2fTGH, in which transcription of gpt is regulated by the upstream region of an interferon-responsive human gene. Selection of mutagenized 2fTGH cells in hypoxanthine-aminopterin-thymidine medium yielded mutants in one recessive (C1) and two dominant (C2 and C3) complementation groups. The mutants constitutively expressed low levels of beta interferon (C1), alpha interferon (C2), or both (C3).
Base Sequence↗
Orbital panniculitis as the initial manifestation of systemic lupus erythematosus.
Inflammation of the fat in lupus erythematosus also known as lupus erythematosus profundus (panniculitis) is a rare clinical entity. As the presenting feature of lupus, it is even more unusual. In this report, we describe an elderly woman who presented with an orbital mass infiltrate as the initial manifestation of lupus that had the classical histological features of lupus panniculitis.
Aged↗
High-frequency mutagenesis of human cells and characterization of a mutant unresponsive to both alpha and gamma interferons.
2fTGH is a human cell line containing the selectable marker guanine phosphoribosyltransferase regulated by alpha interferon (IFN-alpha). Two IFN-alpha-unresponsive mutants were isolated previously at a low frequency (ca. 10(-8)) by selecting mutagenized 2fTGH cells in selective medium containing 6-thioguanine and IFN-alpha. By using five rounds of mutagenesis, mutants can be isolated at an appreciably higher frequency, greater than 3 x 10(-7). Five new mutants have been isolated, and all are recessive, as are the two mutants we described previously. The seven mutants are in four complementation groups (U1-U4). Since several different types of mutants unresponsive to IFN-alpha have been isolated with high frequency, related approaches may succeed with other cytokines or growth factors. Mutants in the two new complementation groups U3 and U4 are unresponsive to IFN-alpha and, surprisingly, also unresponsive to IFN-gamma. They are also partially defective in response to double-stranded RNA. These results indicate that the signaling pathways for the two types of IFN and double-stranded RNA share common components or that their function depends on common enzymes or transcription factors. IFN receptors are unaffected in mutants U3A and U4A. A major defect appears to be in the synthesis or activation of E, the transcription factor mediating the primary response to type I (alpha/beta) IFNs. Band-shift complementation assays show that U3A contains the E gamma subunit but does not contain an active E alpha subunit after treatment with IFN-alpha.
Aminacrine↗
Isolation and characterization of a new mutant human cell line unresponsive to alpha and beta interferons.
Previously we described human cell line 2fTGH, in which expression of guanine phosphoribosyltransferase is tightly controlled by the upstream region of interferon (IFN)-stimulated human gene 6-16. After mutagenesis of 2fTGH and selection with 6-thioguanine and IFN-alpha, we isolated 11.1, a recessive mutant that does not respond to IFN-alpha. We now describe U2, a second recessive mutant, selected similarly, that complements 11.1. U2 had no response to IFN-alpha or IFN-beta, and its response to IFN-gamma was partially defective. Although many genes did respond to IFN-gamma in U2, the 9-27 gene did not and the antiviral response of U2 cells to IFN-gamma was greatly reduced. Band shift assays showed that none of the transcription factors normally induced in 2fTGH cells by IFN-alpha (E and M) or IFN-gamma (G) were induced in U2. However, extracts of untreated U2 cells gave rise to a novel band that was increased by treatment with IFN-gamma but not IFN-alpha. Band shift complementation assays revealed that untreated and IFN-gamma-treated U2 cells lack the functional E gamma subunit of transcription factor E and that IFN-alpha-treated U2 cells do contain the functional E alpha subunit.
Aminacrine↗
Rheumatology. Cellular suicide: critical concept or fleeting fad?
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Apoptosis↗
Labour dispute: Alberta midwives and nurses battle over birth attendance.
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Canada↗