Emergency care in general practice. Irish general practitioners learn immediate cardiac care.
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Cardiology↗
Biomedical subjects
A Murphy
Publications and source records attributed to A Murphy.
Leukocyte function-associated antigen 1 (LFA-1) and CD44 are signalling molecules for cytoskeleton-dependent morphological changes in activated T cells.
Signaling through the leukocyte function-associated antigen 1 (LFA-1) molecule has previously been shown to induce homotypic aggregation in T cells and to induce cytoskeletal changes in T lymphoma cells. In this study we describe the induction of a dendritic phenotype associated with cytoskeletal rearrangement in activated human peripheral blood T cells stimulated with monoclonal antibody SPV-L7 to LFA-1 alpha. Maximal expression of this phenotype required 72 h preactivation with phorbol myristate acetate and expression was abolished using the protein kinase C inhibitor staurosporine. Monoclonal antibody to CD18, the beta-chain of LFA-1, did not induce this phenotype. Monoclonal antibody MEM 83 to presumably a discrete epitope on LFA-1 alpha did not induce this phenotype but induced homotypic aggregation. However, a monoclonal antibody to CD44 induced a similar phenotype in activated lymphocytes. Induction of both homotypic in activated lymphocytes. Induction of both homotypic aggregation and the dendritic phenotype was abolished by preincubation with soluble intracellular adhesion molecule 1 (ICAM-1). Cytoskeletal inhibitors prevented the morphological changes in SPV-L7-activated lymphocytes. Preincubation with tyrosine kinase inhibitor, protein kinase C inhibitors, and inhibitors of new protein synthesis also prevented these morphological changes. These data suggest that discrete epitopes on LFA-1 alpha may be capable of inducing discrete signals either for homotypic aggregation or for a dendritic phenotype. As both LFA-1 and CD44 are involved in the migration of lymphocytes through high endothelial venules, these data could suggest that these molecules transduce signals resulting in cytoskeletal modification necessary for lymphocyte transmigration.
Alkaloids↗
Soft-tissue sarcomas of the shoulder girdle: factors influencing local recurrence distant metastases, and survival.
BACKGROUND: Prognostic factors and the role of radiotherapy have not been well characterized for soft-tissue sarcomas (STS) of the shoulder girdle. METHODS: The cases of 70 patients with primary shoulder STS were reviewed for the following information: size, grade and histology of tumors, extent of resection, and use of adjuvant radiotherapy. The influence of these factors on local disease-free survival (LDFS), distant disease-free survival (DDFS), and overall survival (OS) rates was analyzed using univariate analysis. RESULTS: With a median follow-up of 108 months, the overall 5- and 10-year survival rates for patients with shoulder girdle STS were 82% and 80%, respectively, whereas the 5-year disease-free survival rate was 63%. There were 25 (35%) tumor recurrences: 12 (17%) distant and 13 (18%) local regional. Tumors > 5 cm in size were associated with a significantly decreased 5-year OS rate compared with lesions < 5 cm, and high-grade tumors were associated with significantly decreased DDFS and OS rates. Because most of the patients who underwent amputation had large, high-grade tumors, they had significantly decreased 5-year DDFS and OS rates compared with wide local excision. Radiotherapy produced a significant improvement in LDFS rates, particularly in patients with tumors > 5 cm in size. CONCLUSIONS: The results indicate that both tumor size and grade are important prognostic factors in shoulder girdle STS. Adjuvant radiotherapy should be considered in large tumors to improve the LDFS and to decrease the need for radical ablative surgery.
Adolescent↗
In vivo assessment of catheter-tip PO2 sensor: sampling lumen fabrication.
Fabrication of the sampling lumen of an intra-arterial PO2 sensor is performed in standard catheters mechanically or by laser. Clinical evaluation is performed with respect to catheter insertion, complications, accuracy of oxygen sensor data and fibrin deposition on the catheter surface. The success rate for catheter insertion is 57% for 138 standard and 50% for 74 laser-cut catheters studied. The proportion of catheter failures (blocked or non-reading) is 14% in laser-cut compared with 30% in standard. These differences are not statistically significant at the 5% level. There is no clinically significant difference in sensor accuracy, with 37.5% of results within +/- 0.05 kPa and 80% within +/- 2.0 kPa of simultaneous blood gas values. Drift is within +/- 0.3 kPa h-1 for 78% of monitoring time. Significant errors of recalibration occur in 6% of calibrations. Scanning electron micrographs demonstrate a much smaller sampling lumen in the laser-cut group, but no reduction in fibrin deposition at the site of the sampling hole. The low success rate for catheter insertion is a problem because of cost implications. The accuracy of the system is usually sufficient for clinical purposes, provided the calibration is checked every 4 h.
Catheterization, Peripheral↗
A prospective randomized trial to evaluate different oral dose regimens of medroxyprogesterone acetate in women with advanced breast cancer.
A prospective randomized study was conducted to try to answer two questions: is a loading dose of medroxyprogesterone acetate (1000 mg p.o. q.d.s. for 48 h) superior to conventional dosing; and does an oral maintenance dose of 1000 mg daily offer any advantage over 500 mg daily in women with advanced breast cancer who have failed to respond to, or have relapsed after, tamoxifen? Of 211 patients randomized, 207 were evaluable. There was no improvement in response rates, time to response, response duration or overall survival as a result of the loading dose. When comparing high and low maintenance doses, there was a significant difference in response rates (48% versus 32%; chi 2 = 10.09, df = 2, P = 0.006) and survival (66% versus 41% alive at 12 months; chi 2 = 9.06, df = 1, P = 0.003) in favour of the higher dose regimen, although there was no significant difference in the duration of response. There was no additional toxicity attributable to the loading dose regimen, but side effects were more frequent with the high dose maintenance schedule (141 of 201 adverse effects occurring in these two groups) although the incidence of severe toxicity was similar with both high dose and low dose treatments.
Administration, Oral↗
Laparoscopic implant of Gore-Tex surgical membrane.
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Endometriosis↗
Comparison of metallothionein gene expression and nonprotein thiols in ten Arabidopsis ecotypes. Correlation with copper tolerance.
Seedlings of 10 Arabidopsis ecotypes were compared with respect to copper tolerance, expression of two metallothionein genes (MT1 and MT2), and nonprotein thiol levels. MT1 was uniformly expressed in all treatments, and MT2 was copper inducible in all 10 ecotypes. MT1 and MT2 mRNA levels were compared with various growth parameters for the 10 ecotypes in the presence of 40 microM Cu2+. The best correlation (R = 0.99) was obtained between MT2 mRNA and the rate of root extension. MT2 mRNA levels also paralleled the recovery phase following inhibition by copper. Induction of MT2 mRNA was initiated at copper concentrations below the threshold for growth inhibition. In cross-induction experiments, Ag+, Cd2+, Zn2+, Ni2+, and heat shock all induced significant levels of MT2 gene expression, whereas Al3+ and salicylic acid did not. The correlation between copper tolerance and nonprotein thiol levels in the 10 ecotypes was not statistically significant. However, 2 ecotypes, Ws and Enkheim, previously shown to exhibit an acclimation response, had the highest levels of nonprotein thiols. We conclude that MT2 gene expression may be the primary determinant of ecotypic differences in the copper tolerance of nonpretreated Arabidopsis seedlings.
Arabidopsis↗
Expression of CD44 on rheumatoid synovial fluid lymphocytes.
OBJECTIVES: To investigate the involvement of the adhesion molecule CD44 in the homing of lymphocytes to synovial tissue, by examining the density of expression and molecular mass of CD44 on rheumatoid synovial fluid lymphocytes. METHODS: Twenty patients with rheumatoid arthritis were studied. Peripheral blood and synovial fluid lymphocytes were isolated by Ficoll-Hypaque sedimentation. CD44 expression was analysed by two colour flow cytometry of CD3 positive T lymphocytes with calculation of mean fluorescence intensity. Expression of activation markers M21C5, M2B3, interleukin (IL)-2 receptor and transferrin receptor was quantitated. In addition, CD44 molecular mass was examined by Western blot in six patients. RESULTS: CD44 expression was markedly increased on synovial fluid T lymphocytes of rheumatoid patients relative to peripheral blood lymphocytes from the same individuals. CD44 molecular mass on peripheral blood mononuclear cells was 88 kDa, but that on synovial fluid lymphocytes was only 83 kDa. CD44 expression correlated significantly with expression of activation markers M21C5, M2B3, and the IL-2 receptor. CONCLUSIONS: Alterations in density of expression or of the molecular mass of CD44 could contribute to local tissue injury, either directly by facilitating adhesion, or indirectly through effects on other adhesion molecules.
Arthritis, Rheumatoid↗
Tyrosine phosphorylation in the human duodenum.
Many growth factor receptors including the epidermal growth factor receptor function through tyrosine kinase activity. The aim of this study was to examine the constitutive level of tyrosine phosphorylation in the normal duodenum and in the hyperproliferative coeliac duodenum. A flow cytometric assay was devised using monoclonal antibody to phosphorylated (but not native) tyrosine residues to determine the levels of tyrosine phosphorylation in both CD3 positive intraepithelial lymphocytes and CD3 negative epithelial cells obtained by EDTA treatment of endoscopically obtained duodenal biopsy specimens. In addition, immunohistochemistry was performed on 18 formalin fixed coeliac duodenal biopsy specimens and eight control specimens. Tyrosine phosphorylation could be detected by flow cytometry on duodenal enterocytes and this expression was up regulated by pretreatment with epidermal growth factor. Tyrosine phosphorylation decreased with progression from the villus to the crypt, however, and was virtually undetectable on crypt enterocytes. Immunohistochemistry of the coeliac duodenum showed virtually absent tyrosine phosphorylation in the crypt. Increased tyrosine phosphorylation was detected in the infiltrating T cells. In conclusion, tyrosine phosphorylation in the duodenum is confined to the non-proliferative villous epithelium and is virtually undetectable in the proliferative crypt compartment. These findings suggest that tyrosine kinase activity is not a significant factor in the regulation of crypt cell proliferation in the human duodenum either in normal subjects or in coeliac disease patients.
CD3 Complex↗
Adult-onset congenital erythropoietic porphyria (Günther's disease) presenting with thrombocytopenia.
Cutaneous signs of Günther's disease (congenital erythropoietic porphyria) developing 5 years after the onset of symptomatic thrombocytopenia are described in a 65-year-old man. Persistent thrombocytopenia unresponsive to corticosteroids and immunoglobulin necessitated a splenectomy.
Aged↗
The efficacy of isokinetic, isometric and vertical jump tests in exercise science.
This research examined the efficacy of several tests of muscular strength and power in their capacity to be related to performance, their ability to effectively discriminate between individuals of different performance levels and their sensitivity in detecting training induced changes to performance. Thirty healthy active subjects performed the following maximal tests of muscular function: (1) Vertical jump; (2) Isokinetic knee extension at 1.05, 3.14 and 5.24 rads s-1; and (3) Isometric rate of force development. Performance was assessed by the peak power output achieved on a cycle test. In addition, subjects participated in a 10 week resistance training program. The isokinetic and vertical jump tests were significantly related to performance (r = 0.5-0.73) and could be used to discriminate between subjects of differing performance levels. However, the isometric rate of force development test was an ineffective assessment modality. None of the tests were able to effectively monitor training induced changes in performance, as evidenced by non-significant correlations between the pre- to post-percentage changes in cycling performance and the test variables. Consequently, alterations to training programs for athletes should be based on changes in actual performance, as opposed to muscular function tests.
Adult↗
The minimal fragments of c-Raf-1 and NF1 that can suppress v-Ha-Ras-induced malignant phenotype.
v-Ha-Ras, an oncogenic Ras mutant, causes malignant transformation of mammalian cells by recruiting c-Raf-1, a cytosolic Ser/Thr kinase, to the plasma membranes/cytoskeleton. The kinase activity of c-Raf-1 resides in the C-terminal half, which activates mitogen-activated protein (MAP) kinase kinase, while it is the N-terminal half of c-Raf-1 (Raf257, residues 1-257) that binds the Ras-GTP complex and can compete Ras GTPase-activating proteins such as NF1 for binding to Ras. However, it still remains to be clarified whether overexpression of Raf257 or its minimal Ras-binding fragment alone is sufficient to suppress Ras-induced malignancy. In this paper we demonstrate for the first time that the 81-amino acid fragment (Raf81, residues 51-131), the minimal Ras-binding fragment of Raf, indeed can suppress v-Ha-Ras-induced malignant phenotype. A further deletion of the first 6 amino acids causes 65% reduction in the Ras binding of Raf81. The resultant 75 amino acid fragment (Raf75, residues 57-131) consists of a single alpha-helix, five anti-paralleled beta-sheets and five loops. We have found that a further deletion of either the first beta-sheet/loop or the last two beta-sheets/loops completely abolishes Ras binding. In addition we have found that the removal of the C-terminal 35 amino acids from a Ras-binding 91-amino acid fragment of NF1 (NF91, residues 1441-1531) does not abolish its ability to suppress the Ras-induced malignancy.
3T3 Cells↗
Screening for pediatric lead poisoning. Comparability of simultaneously drawn capillary and venous blood samples.
OBJECTIVE: To determine the ability of capillary blood lead levels to accurately reflect true blood lead levels in children at risk for lead poisoning. DESIGN: A correlation study in which lead levels of capillary blood specimens obtained by four different methods were compared with lead levels of simultaneously drawn venous blood specimens. SETTING: A central-city pediatric primary care clinic and door-to-door home visits in one central-city neighborhood. PATIENTS: Two hundred ninety-five children at high risk for lead poisoning aged 6 months to 6 years. MAIN OUTCOME MEASURES: Blood lead levels of simultaneously drawn capillary and venous blood specimens. RESULTS: Lead levels of all four capillary sampling methods were highly correlated (correlation coefficient > or = 0.96) with matched venous blood lead levels, with mean capillary-venous differences less than 0.05 mumol/L (1 microgram/dL). CONCLUSIONS: Capillary sampling is an acceptable alternative to venipuncture for lead-poisoning screening in young children.
Blood Specimen Collection↗
Influence of surgical margins on outcome in patients with preoperatively irradiated extremity soft tissue sarcomas.
BACKGROUND: Limb-sparing surgery for soft tissue sarcomas of the extremities may result in microscopically positive surgical margins. The consequences of these microscopically positive margins are unknown. We have analyzed the influence of surgical margins on local disease control and overall survival in patients with extremity soft tissue sarcomas who received preoperative radiation therapy followed by limb-sparing surgery. METHODS: Ninety-five consecutive patients with intermediate and high grade extremity sarcomas who received preoperative radiation therapy and limb-sparing surgery were identified from a soft tissue sarcoma data-base. The clinical outcome of 24 patients who had microscopically positive surgical margins was compared with that of 71 patients who had clear surgical margins. RESULTS: Multivariate statistical analysis revealed that patients with microscopically positive surgical margins or intraoperative tumor violation had an increased risk for local failure. High grade, large size, and intraoperative violation of the tumors were associated with decreased overall survival. However, neither the presence of a positive surgical margin nor the occurrence of a local failure adversely affected overall survival. CONCLUSIONS: Achieving negative surgical margins in patients with intermediate and high grade extremity sarcomas enhances local disease control but does not measurably improve overall survival. These data should be factored into patient management decisions in cases where the goal of achieving clear surgical margins requires amputation or the significant functional compromise of the extremity.
Actuarial Analysis↗
Feasibility and effectiveness of screening for childhood lead poisoning in private medical practice.
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Child↗
Adhesion molecules utilized in binding of intraepithelial lymphocytes to human enterocytes.
The expression of adhesion molecules by human duodenal intraepithelial lymphocytes (IEL) was examined by two-color flow cytometry. Resting IEL expressed LFA-1, HML-1, CD44. Stimulation with phytohemagglutinin (PHA) resulted in down-regulation of expression of these molecules with induction of expression of ICAM-1 and VLA-4. VLA-4 expression was also found on non-activated IEL from patients with celiac disease. In addition, IEL expressed an antigen recognized by a novel monoclonal antibody D2.1. The molecular mass of D2.1 is heterogeneous: 82 kDa in peripheral blood lymphocytes and 44 kDa in an IEL line. Expression of this antigen was also up-regulated by PHA. To determine the involvement of these antigens in binding of IEL to human enterocytes, we developed a system based on adherence of an IEL cell line to the I407 fetal intestinal cell line. Monoclonal antibodies VLA-4, D2.1 and to a lesser extent ICAM-1 blocked adherence of IEL to I407 cells. These data suggest that VLA-4 and D2.1 may be involved in adherence of IEL to human enterocytes or secreted matrix molecules in vivo.
Antibodies, Monoclonal↗
An evaluation of school entry immunisation certificates in Victoria.
We evaluated legislation introduced into Victoria in 1991 requiring that all children enrolling in primary school certify their immunisation status. Information was requested from all local councils. All primary schools in two local government areas were followed up, providing an indication of the validity of the analysis obtained from data collected during the mid-year census. From 166 of 210 local councils in Victoria, 48,422 documents relating to school entry immunisation certificates were issued for children entering their preparatory year. At least 522 children were enrolled in school on an undertaking to complete immunisation, and were likely to have had their immunisation completed as a result of the legislation. Only 170 statutory declarations of conscientious objection to immunisation were made, indicating that few parents are willing to express firm anti-vaccine sentiments. Compliance with the immunisation certificate legislation is overestimated by the mid-year census because many schools have accepted nonstatutory evidence of immunisation. Mobile and immigrant families find it particularly difficult to achieve certification. Local councils are inconsistent in the way in which they issue certificates. Further follow-up and feedback is essential to better inform schools and parents about the legislation. Such follow-up can improve the certification rates of children then and in subsequent years. The legislation has imposed a considerable workload on councils, but without efforts to improve compliance with the legislation and to develop practical guidelines for documentation of immunisation and appropriate guidelines regarding transfer, many inadequately immunised children may remain at risk from vaccine-preventable diseases.
Child↗
ChlVPP/PABlOE and radiotherapy in advanced Hodgkin's disease. The Central Lymphoma Group.
PURPOSE: The United Kingdom Central Lymphoma Group (CLG) has modified mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) by substituting mechlorethamine with chlorambucil and dacarbazine with etoposide in the treatment of patients with advanced Hodgkin's disease (HD). Prednisolone is included in the bleomycin-containing combination, and the vinca alkaloids have been switched to balance the myelotoxicity of the two component regimens. PATIENTS AND METHODS: The resulting ChlVPP/PABlOE regimen is as follows: on days 1 to 14, chlorambucil 6 mg/m2 orally, procarbazine 100 mg/m2 orally, and prednisolone 30 mg/m2 orally; on days 1 and 8, vinblastine 6 mg/m2 intravenously (i.v.); on day 29, doxorubicin 40 mg/m2 i.v.; on days 29 and 36, vincristine 1.4 mg/m2 (maximum, 2 mg) i.v., and bleomycin 10 mg/m2 i.v.; on days 30, 31, and 32, etoposide 200 mg/m2/d orally; on days 29 to 43, inclusive, prednisolone, 30 mg/m2 orally. The second full cycle restarts on day 50. Treatment continues to maximum response plus two full cycles, but with a minimum of three full cycles. Radiotherapy is administered, after chemotherapy, to sites of previously bulky disease. Since 1983, 216 patients with previously untreated, advanced Hodgkin's disease (HD) have entered this study. RESULTS: The complete remission (CR) rate after chemotherapy was 73% (95% confidence interval [CI], 67% to 79%), and after additional radiotherapy was 85% (95% CI, 80% to 90%). The failure-free survival (FFS) rate at 5 years was 68% (95% CI, 61% to 74%), and the overall actuarial survival at 5 years was 78% (95% CI, 72% to 84%). The CR rate in patients in the poorer prognostic categories was high: 81% in patients with albumin levels less than 37 g/L, 79% in patients older than 40 years of age, 84% in stages IIIB plus i.v. disease, and 79% in patients presenting with B symptoms. As expected, nausea and vomiting were not major problems, although infection, often in the context of myelosuppression, complicated almost half the cases, and 29% of patients required admission at some stage for treatment of infection. CONCLUSION: In this multicenter study, ChlVPP/PABlOE produced results comparable to those reported for MOPP/ABVD, but with less nausea and vomiting. Treatment duration was shorter than in the original MOPP/ABVD regimen, and than that used in the Cancer and Leukemia Group B (CALGB) trial. It will now be compared with PABlOE alone.
Adult↗