Taking the PACS power to the people.
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Biomedical subjects
Publications and source records attributed to M Shaw.
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BACKGROUND: The absence of valid and reliable health status measures for functional gastrointestinal illness has limited research and patient care for this common group of disorders. A self-report survey has been developed. METHODS: Initial development focused on extensive pre-testing of patients, primary care physicians and gastroenterologists. The disease-specific portion included the Rome criteria for dyspepsia subgroups and the Manning and Rome criteria for irritable bowel syndrome. The Short Form-36 was added. Psychometric analyses included techniques of multitrait scaling, scale internal consistency and criterion validation. RESULTS: Six hundred and ninety patients presenting to their primary care physician for treatment of heartburn, abdominal pain or discomfort completed the 98 question survey. The disease-specific portion revealed five components including reflux, dysmotility, a two-domain bowel dysfunction complex, and a pain index. Internal consistency measures demonstrated good to excellent reliability. Scaling successes were observed on multitrait scaling. The disease-specific portion was reduced to 34 questions. Criterion validity was demonstrated with the correlation of the disease-specific questions to the SF-36. CONCLUSIONS: The psychometric analyses lend credence to the concept of stomach and bowel symptom subgrouping as proposed by expert consensus. The psychometric properties of the five summated disease-specific scales compare favourably with standardized health status measures.
The performance of the Intersurgical disposable soda lime canister was compared to British Pharmacopoeia standards for carbon dioxide absorption and to other carbon dioxide absorber systems. This canister system more than adequately fulfilled the equivalent of the British Pharmacopoeia standard for CO2 absorption. It performed efficiently for over 3 h of continuous use, absorbing 200 ml.min-1 at varying combinations of tidal volume and ventilation rate. Efficiency was not dependent on close matching of tidal volume with canister volume and there was no channelling of gases. Heat was generated by the reaction between soda lime and CO2 and the maximum temperature recorded in the system was 42.1 degrees C. Under clinical conditions this should pose no threat of thermal injury to the patient.
BACKGROUND: Pituitary-adrenal secretion during induced hypotension for middle-ear surgery has received little attention. Previous work failed to differentiate the effects of induced hypotension from surgical stimulation. We have undertaken a preliminary study examining the effects of hypotension, achieved with labetalol or isoflurane, on pituitary-adrenal secretion before, during and after middle-ear surgery. METHODS: Twenty-four patients were allocated randomly to 3 groups. The control group were anaesthetised with isoflurane, and normotension maintained for 30 min before hypotension was induced with isoflurane and surgery started. In the labetalol group, this drug was given i.v. to obtain a mean arterial pressure (MAP) of 60 mm Hg for 30 min before surgery and hypotension maintained with labetalol during the operation. In the isoflurane group, hypotension was induced to a MAP of 60 mm Hg for 30 min before surgery and continued throughout the procedure. All 3 groups received metoprolol i.v. before hypotension was established. Blood samples were collected before induction of anaesthesia, during anaesthesia alone (normotensive or hypotensive), surgery with hypotension, and recovery. They were analysed for adrenocorticotropic hormone (ACTH), arginine vasopressin (AVP), cortisol and aldosterone. RESULTS: Induced hypotension before surgery failed to stimulate release of ACTH, AVP and cortisol. No significant increase in these hormones occurred until the postoperative period. Aldosterone concentrations increased significantly during anaesthesia and hypotension in the labetalol and isoflurane groups (P<0.05) and continued to rise significantly in all 3 groups during surgery. However, there was no significant difference in aldosterone concentration before surgery between the control and the 2 hypotensive groups. CONCLUSION: ACTH, AVP and cortisol secretion were not stimulated by induced hypotension to MAP of 60 mm Hg before surgery. Increased aldosterone secretion occurred and a further study with a larger sample size is needed.
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Paclitaxel, bropirimine and linomide therapy was evaluated in a murine prostate cancer model. All drugs were effective in impeding tumor growth but the mechanisms of action varied. Paclitaxel inhibited bcl-2 expression suggesting an apoptotic mechanism. Bropirimine, while inhibiting bcl-2 expression also significantly depressed tumor necrosis factor-alpha (TNF-alpha) expression. In the bropirimine treated group there was also a correlation between angiogenesis and cyclin D expression. Finally, linomide significantly decreased angiogenesis. Since the mechanism of action of these drugs differ, combining them at lower doses might maintain therapeutic efficacy while reducing toxicity.
The cell surface protein tyrosine phosphatase CD45 is a major target of IgM anti-T cell autoantibodies in systemic lupus erythematosus (SLE). The autoreactive determinants on CD45 are O-linked glycans expressed on activated T cells and certain T cell lines, rather than linear or conformational polypeptide epitopes or N-linked glycans. To identify oligosaccharide structures that may play a role in the functional interactions of CD45 or are candidate target epitopes of SLE anti-CD45 autoantibodies, autoreactive CD45 purified from Jurkat T cells and non-autoreactive CD45 purified from CLL B cells were tested by ELISA for expression of mucin-type O-glycan structures. Monoclonal antibodies (mAbs) directed against blood group A, type 1 H chains, type 2 H chains, T, Le(a), sialylated-Le(a), Le(b), sialylated-Le(c), Le(x), sialylated-Le(x), multi-fucosylated Le(x), Le(y), and sialylated-extended Le(v) failed to react with CD45 from either B cells or T cells. However, mAbs directed against Tn (galNAcalpha1-->O-ser/thr) or sialosyl-Tn (neuNAcalpha2-6gaINAcalpha1-->O-ser/thr) structures reacted with CD45 derived from Jurkat T cells, but not from CLL B cells. Anti-Tn mAbs also reacted in western blotting procedures with CD45 isolated from Jurkat T cells, but did not react with CD45 isolated from CEM, MOLT-3, or PEER T cells; Daudi, Raji, or CLL B cells; or resting or Con A-activated PBL. However, anti-sialosyl-Tn mAbs stained blots of CD45 isolated from Jurkat and CEM T cells and Con A-activated PBL, a pattern of reactivity similar to that of the anti-CD45 autoantibodies. Flow cytometric analyses demonstrated that the sialosyl-Tn epitopes are expressed on a subpopulation of CD4 +/CD8- T cells.
LNCaP tumors were treated by either administration of paclitaxel, thalidomide or by orchiectomy in order to determine their relationship with markers pertaining to the process of tumor growth, apoptosis or angiogenesis. Forty rats bearing LNCaP tumors were divided into 4 groups of 10 and treated by either paclitaxel (20 mg/kg x 5 days); thalidomide (200 mg/kg x 5 days/week x 5 weeks); or orchiectomy. After 6 weeks serum samples were removed for PSA determination and the animals sacrificed for evaluation of: A) tumor volume; B) tissue bcl-2, cyclin D, PSA and factor VIII immunohistochemically graded (0-5 scale) for marker expression; and C) serum PSA. Comparisons were made to untreated LNCaP tumors. Statistically significant differences were determined using the nonparametric Mann-Whitney test. Paclitaxel produced significant differences in volume (p < 0.001), expression of bcl-2 (p < 0.043), cyclin D (p < 0.023), tissue PSA (p < 0.001) and serum PSA (p < 0.019) levels. Thalidomide altered expression of bcl-2 (p < 0.011) and tissue PSA (p < 0.002). Orchiectomy altered volume (p < 0.002) and bcl-2 expression (p < 0.001). All three therapies have been suggested for prostate cancer and each produced alterations in accepted markers for treatment response (either reduced volume or serum PSA). Paclitaxel significantly influenced the most markers. Of interest was that all treatments, especially thalidomide, a known antiangiogenesis agent, reduced factor VIII, although not significantly. Evidently each treatment evokes different pathways of activity.
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A fundamental principle of palliative care is the provision of patient-centred care, an approach explicitly based on the patient's perspective. Although much attention has been given to determining patients' preferences for involvement in medical decisions, choices related to personal and nursing care routines have been largely ignored in the literature. Data from participant observations of nurse-patient interactions involving 16 palliative care patients and their nurses as well as 10 in-depth open-ended interviews with patients were analyzed using grounded theory methods. Although the choices made by patients appeared uncomplicated on the surface, the context of unfamiliarity, uncertainty, and unpredictability in palliative care increased the underlying complexity of decision making. Through a process of deliberation and trade-offs, patients attempted to regain or maintain some balance in their lives. This process of striving for balance consisted of three overlapping phases: weighing things up, communicating choice, and living with one's choices.
DNA transfer techniques allow genetic manipulation of commercial fish. However, marine species have received little attention because of their difficult zootechnical requirements. The seabream (Sparus aurata) has become one of the most important species in the aquaculture of Mediterranean countries, and the development of suitable DNA transfer procedures represents a main step in its genetic improvement. To assess the response of the seabream to exogenous DNA, naturally fertilized eggs were injected with the plasmids pCMV-CAT, pCMVTklacZ, and pEGFP-N1, in supercoiled and linearized forms. Embryo and larval survival, DNA fate, and reporter gene expression were analyzed during early development. The survival results indicate that microinjection is an effective transfer method in spite of the unfavorable conditions. Linearized plasmids were more efficiently polymerized than supercoiled ones; however, no significant differences were detected either in their persistence or in their expression levels. Reporter gene expression was initiated after mid-blastula transition. The duration of transient expression varied between the promoter-gene combinations, and no integration of transgenes into fish chromosomes was detected. Results suggest that the main factor affecting the persistence and expression of DNA seems to be related to developmental processes. Among the markers used, CAT proved to be the most sensitive, but GFP had obvious methodologic advantages over the spatial marker lacZ. The usefulness of GFP for diagnosis of transgenesis is enhanced by the transparency of embryos and larvae in S. aurata.
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293 cells were transfected with wild-type GSK3beta (WT-GSK3beta) or a mutant in which the PKB phosphorylation site (Ser-9) was altered to Ala (A9-GSK3beta). Upon stimulation with IGF-1 or insulin, WT-GSK3beta was inhibited 75% or 60%, respectively, whereas the activity of the A9-GSK3beta mutant was unaffected. Incubation of WT-GSK3beta with PP2A1 (a Ser/Thr-specific phosphatase) completely reversed the IGF-1- or insulin-induced inhibition. IGF-1 stimulation did not induce any tyrosine dephosphorylation of WT-GSK3beta or A9-GSK3beta. Coexpression of WT-GSK3beta in 293 cells with either PKB alpha (also known as AKT) or PDK1 (the 'upstream' activator of PKB) mimicked the IGF-1- or insulin-induced phosphorylation of Ser-9 and inactivation of GSK3beta.
In a search for candidate tumor suppressor genes within a 30-kb common region of deletion previously identified in bladder cancer cell lines, we isolated a 2.4-kb cDNA clone comprising 13 exons that spanned approximately 16 kb of genomic DNA. Mutation analysis was carried out by single-strand conformation polymorphism analysis on DNA from 12 bladder carcinoma cell lines and 26 bladder tumors with LOH on chromosome 4p. Direct sequencing of the transcript in 4 bladder carcinoma cell lines with deletions in this region was also carried out. Two polymorphisms in exons 2 and 5 were identified, but no tumor-specific mutations were found. Sequence analysis identified a high degree of homology with the mouse sh3bp2 gene, which is abl-binding, suggesting that this gene is the human homologue. The predicted amino acid sequence of the putative gene product contains a Src homology 2 domain, a Src homology 3 binding domain, and a pleckstrin homology domain, suggesting a possible role in signal transduction. No evidence was found to indicate that SH3BP2 is the tumor suppressor gene at 4p16.3 involved in bladder cancer. However, this study has identified an interesting human gene that is a potential negative regulator of the abl oncogene.
Insulin stimulated protein kinase B alpha (PKB alpha) more than 10-fold and decreased glycogen synthase kinase-3 (GSK3) activity by 50 +/- 10% in skeletal muscle and adipocytes. Rapamycin did not prevent the activation of PKB, inhibition of GSK3 or stimulation of glycogen synthase up to 5 min. Thus rapamycin-insensitive pathways mediate the acute effect of insulin on glycogen synthase in the major insulin-responsive tissues. The small and very transient effects of EGF on phosphatidylinositol (3,4,5)P3 PKB alpha and GSK3 in adipocytes, compared to the strong and sustained effects of insulin, explains why EGF does not stimulate glucose uptake or glycogen synthesis in adipocytes.
A boy of 3 years 8 months with short stature due to chronic renal insufficiency was treated with recombinant human growth hormone (rhGH) for 20 months. Catch-up growth was achieved and the improvement of the height standard deviation score was sustained throughout an additional 4 years of follow-up without further rhGH therapy.
As latex proteins, which cause latex hypersensitivity, can be found on starch particles and inhalation may be a route for sensitization, the presence of starch particles in hospital air was examined. The starch particles were demonstrated by immobilization onto cellulose acetate filters and staining with iodine. Rooms in which powdered latex gloves were used gave counts of up to > 3,667 particles per cubic meter of air. Starch particles were not found in the air in rooms where latex gloves were not used, and were highest in rooms with a high glove usage but no ventilation. A change to powder-free gloves significantly reduced the count of starch particles in the unventilated Accident/Emergency Department air. Use of powder-free gloves should be considered especially in unventilated areas in healthcare premises.