Biomedical subjects
M Gordon
Publications and source records attributed to M Gordon.
Interleukin-1 modulation of cytokine receptors on human neutrophils: in vitro and in vivo studies.
Interleukin-1 (IL-1) modulation of cytokine receptors (human IL-1 receptor [hIL-1R], human granulocyte colony-stimulating factor [hG-CSFR], human granulocyte-macrophage CSF receptor [hGM-CSFR], and human tumor necrosis factor receptor [hTNFR]) on human neutrophils was studied both in vitro and in vivo. In vitro, incubation of neutrophils with IL-1 at 37 degrees C for 0.5 or 8 hours caused a reduction of IL-1 binding in a dose-dependent manner, but did not demonstrably affect binding of the other cytokines tested. In vivo, neutrophils from patients with gastrointestinal malignancies who were participating in a clinical trial of recombinant human IL-1 beta (rhIL-1 beta) demonstrated modulation of cytokine receptors in an IL-1 beta dose- and time-dependent manner. At the two highest dose levels of IL-1 beta (0.068 and 0.1 microgram/kg), reduction (> 40%) of G-CSF binding and elevation (twofold to sixfold) of IL-1 binding to neutrophils was observed after 1 hour and 4 to 8 hours, respectively. In addition, IL-1 beta rapidly elevated G-CSF and glucocorticoid levels in plasma. Patients at the lowest dose level (0.002 microgram/kg) had a less dramatic change in these parameters. Further in vitro studies showed that synthetic glucocorticoids and G-CSF synergistically up-modulated IL-1 binding to neutrophils in a dose- and time-dependent manner. Scatchard analysis of binding data showed that this in vitro synergistic modulation was due to an increase in receptor numbers, rather than an increase in binding affinity. In addition, both human umbilical cord blood and bone marrow neutrophils responded to G-CSF and dexamethasone (Dex) with a superadditive increase in IL-1 binding. Therefore, one of mechanisms for IL-1 up-modulation of IL-1R on human neutrophils in vivo was due to the fact that IL-1 rapidly elevates serum levels of G-CSF and glucocorticoids.
[Nursing diagnosis as cornerstone. 5 American researchers on nursing diagnosis. Interview by Leo Regeer].
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Community care for the elderly: is it really better?
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Necrotizing vasculitis--relapse despite cytotoxic therapy.
The pattern of relapses is described in a consecutive series of 150 patients with vasculitis. Relapse occurred in 42 out of 124 patients who survived for more than 3 months.
Cutaneous reactions to vitamin K1 injections.
Cutaneous reactions to vitamin K1 injections are reported infrequently. Most previously reported cases have been associated with liver disease, primarily alcoholic cirrhosis and viral hepatitis. Four new cases are reported. One patient had polycythemia vera and the Budd-Chiari syndrome, the second such report in the literature. The other three patients had no known hepatic disease. The reactions consisted of erythematous plaques at the injection site without progression to sclerodermatous plaques. Histopathologic examination in three cases showed spongiotic changes and mononuclear infiltrates typical of cutaneous reactions to vitamin K1. In one instance a neutrophilic infiltrate was associated with the reaction site. Our findings support the observation that liver disease is not a necessary condition for the occurrence of vitamin K1 hypersensitivity.
Poor outcome of on-site CPR in a multi-level geriatric facility: three and a half years experience at the Baycrest Centre for Geriatric Care.
Our objective was to determine the outcome of onsite CPR in elderly patients receiving institutional care who had access to 24-hour on-site full ACLS capability. We used a retrospective chart and CPR protocol review of all patients who received CPR during the study period; these were patients or residents in a multi-level geriatric long-term care facility that provides various degrees of facility-based and ambulatory care. Immediate, short-term, and long-term survivorship were determined and correlated where possible with the category of patient seen (short-term care versus long-term care) and the relationship between the witnessing of the arrest and survival. Of the 41 patients who underwent CPR, there were only four survivors of 60 days or greater. Of these, three subjects were short-term, not long-term care patients of the Centre; they returned to their previous level of function. One fully dependent bed-ridden patient returned to that level of care for a survival period of 100 days. Of the four long-term survivors, three of the arrests were witnessed, and one was indeterminate. No unwitnessed arrests resulted in long-term survival. Our experience suggests that CPR in the elderly long-term care patient is unlikely to be successful even when it is available on-site. Unwitnessed arrests in this population were universally fatal. This information has helped Baycrest Centre for Geriatric Care develop protocols, guidelines, and policies for CPR that are suitable for our population.
Middle ear air injection after chronic ear surgery.
In the early period after chronic ear surgery, the reasons for conductive hearing loss may be difficult to determine. Patients who cannot autoinflate the middle ear after 3 weeks, or who have a negative Rinne test result with the 512 Hz tuning fork, are treated with a transtympanic injection of 0.5 cc of air with a 27-gauge needle and tuberculin syringe. This represents 20% of patients who had chronic ear surgery. Results show that hearing may be immediately improved, the sensation of pressure in the ear may be reduced, and fluid may be cleared from the middle ear. Other benefits may include the release of adhesions. The surgeon is better able to assess the thickness of the graft, and the status of the ossicular chain reconstruction can be determined. There have been no complications of middle ear infection or failure of the micropuncture site to heal. In our practice, middle ear air injection is a routine procedure in patients with inadequate eustachian tube function after chronic ear surgery. This report describes the results of 100 patients over 14 years who received middle ear air injections after chronic ear surgery compared with a control group of 100 patients who did not meet the criteria for requiring air injection. Hearing was immediately improved in 74% of patients as determined by Rinne testing. Audiograms were performed in 25 of these patients, documenting a mean improvement in pure-tone average of 16 dB. The long-term hearing results in patients undergoing air injection, who by definition had evidence of poor eustachian tube function, are similar to the results in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolic Changes after Roux-en-Y Gastric Bypass: A Preliminary Report.
A body composition analysis is performed as part of pre-operative testing to establish a baseline for the patient. The purpose of this preliminary study is to track weight loss, percent body fat and percent lean tissue in post-operative bariatric patients. As this is accomplished, It is noted that the ratio between body fat and lean tissue changes and the basal metabolic rate decreases. It is Interesting to note that lean tissue decreases along with body fat. Performing a body composition analysis every 3 months also assists in proper nutrition counseling for the patient. The method used to accomplish these readings is a bioelectrical impedance analysis. Using electrodes and a computer, the impedance reading is gathered from current weight, height and age of the subject. As weight is lost, basal metabolic rate slows and the body uses less calories for maintenance. Some depletion in lean tissue is noted with weight loss. If protein is decreased substantially from the diet, a great deal more lean tissue is lost. This preliminary study will track subjects over a 5-year period to document the long-term metabolic changes post-operatively and the effects reduced caloric intake has on the body.
Potential mechanisms of action of interferon-alpha in CML.
Treatment with interferon-alpha (IFN-alpha) adequately controls the leukemic cell mass in the majority of newly diagnosed patients with chronic myeloid leukemia (CML). However, the degree of response ranges from no 'hematologic' response to complete suppression of the leukemic clone. The mechanism(s) by which IFN-alpha elicits these responses is unknown, but in vitro studies have indicated that IFN-alpha might function by (1) selective toxicity against the leukemic clone, (2) enhancement of 'immune' regulation, and (3) modulation of bone marrow microenvironmental regulation of hematopoiesis. Using in vitro clonogenic assays we were unable to demonstrate that IFN-alpha selectively inhibited the proliferation of CML progenitor cells. We also found no difference in the expression of LFA-3 on normal or CML CD34+ cells. However, by panning and co-culturing hematopoietic cells on monolayers of bone marrow stromal cells, grown with and without IFN-alpha, we found that IFN-alpha enhanced the adhesion of CML progenitors to stromal cells, whereas adhesion by normal progenitor cells was essentially unaffected. This enhanced adhesion by CML progenitor cells was associated with a reduction in neuraminic acid levels in the extracellular matrix overlying stromal cells. Therefore, it is possible that one of the mechanisms by which IFN-alpha exerts its regulatory effect on the leukemic clone is through enhancement of hematopoietic cell-microenvironmental cell interactions.
Differential responses of myeloid progenitor cells from patients with myeloid leukemia and myelodysplasia to the costimulating effects of steel factor in vitro.
Steel factor (SLF, c-kit ligand), a potent costimulating cytokine in vitro for myeloid progenitor cells from normal donors, is currently being evaluated in clinical trials for effects on hematopoiesis. Based on a preliminary observation that colony-stimulating factor (CSF)-responsive myeloid progenitor cells (CFU-GM) from a few patients with acute myeloid leukemia (AML) did not respond to the costimulating effects of SLF, we evaluated responsiveness of bone marrow or blood CFU-GM from 26 patients with either AML, chronic myeloid leukemia (CML) or myelodysplastic syndrome (MDS) to the effects in vitro of SLF and/or granulocyte-macrophage CSF (GM-CSF). Cells from all 26 patients responded to the stimulating effects of GM-CSF, but marked heterogeneity was detected in each disease category to the costimulating effects of SLF. Nine of 13 patients with AML, 2 of 6 patients with CML and 4 of 7 patients with MDS had clonogenic cells that did not respond significantly to the costimulating effects of SLF. In a more limited study of cells from patients with MDS, it was noted that if the CFU-GM of that patient did not respond to SLF enhancement of CSF-induced colony formation, neither did the erythropoietin (Epo)-dependent erythroid (BFU-E) or multipotential (CFU-GEMM) cells of that patient (3 cases of refractory anemia [RA] evaluating bone marrow and in 1 case blood progenitors as well). If CFU-GM responded, BFU-E and CFU-GEMM responded (bone marrow from 1 patient with chronic myelomonocytic leukemia [CMMol]). Clinical criteria did not readily distinguish between patients who had SLF-responsive vs. -nonresponsive clonogenic cells. While the mechanistic reason for this heterogeneity in responsiveness is not clear, these differences should be carefully considered for possible clinical trials with SLF in patients with acute and chronic myeloid leukemia and MDS.
Relapses in patients with a systemic vasculitis.
Treatment with cyclophosphamide and steroids has greatly improved survival in patients with systemic necrotizing vasculitis but does not always provide a complete cure. There are as yet few data on the incidence, pattern and outcome of relapses in these diseases. We studied relapses in 150 consecutive patients with an idiopathic necrotizing vasculitis: 12 with classical polyarteritis (CPAN); 95 with microscopic polyarteritis (MPA); 28 with Wegener's granulomatosis (WG); and 15 with limited Wegener's granulomatosis (LWG). The relapse rates and median time to relapse in months were: CPAN, 41.7%/33; MPA, 25.4%/24; WG, 44%/42; LWG, 52%/18. The clinical features of relapse were similar to or more aggressive than those of the original presentation in CPAN and LWG and included renal disease for the first time, but in MPA and WG, relapse involved less renal involvement in the majority of cases. Laboratory tests, although often positive at relapse, were unhelpful in its prediction. The considerable accumulative non-fatal relapse rate contrasts with the very good long-term survival rates, and confirms the importance of long-term follow-up in systemic vasculitis.
Review of platinum anticancer compounds.
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The status of the New York State Journal of Medicine: where are we?
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In vitro expression and secretion of functional mammalian intrinsic factor using recombinant baculovirus.
Intrinsic factor was produced at levels of 1-2 mg per 1 (0.25 micrograms per 10(6) cells) by growth of recombinant baculovirus-infected Sf9 cells in spinner culture. The recombinant IF showed a binding affinity for cobalamin (2.6.10(-10) M) and for the intrinsic factor-cobalamin receptor (3.5.10(-10) M) nearly identical with native IF. Purification of the recombinant intrinsic factor could be accomplished by affinity chromatography, but final purification by gel chromatography (FPLC) was necessary to separate intrinsic factor from a 62 kDa protein secreted from uninfected Sf9 cells. This protein binds selectively to the cobalamin-Sepharose column, but demonstrates no cobalamin binding activity after elution. Microgram quantities of radiolabelled protein could be produced for metabolic and autoradiographic studies. The stability of intrinsic factor to pancreatic proteinases was nearly identical with human gastric intrinsic factor, both native and recombinant as produced in mammalian cells. Glycosylation of the intrinsic factor was demonstrated by lectin binding to the recombinant protein separated on SDS-PAGE, and by a shift in apparent molecular mass from 47 kDa to 43 kDa following treatment of Sf9 cells with tunicamycin. Most of the recombinant IF was produced by Sf9 cells in the first 48 h post infection.
Ontario's proposed consent laws: 2. Advocacy.
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Emergency care and the patient in the long-term care facility.
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Efficacy of 131I ablation following thyroidectomy in patients with invasive follicular thyroid cancer.
The role of thyroid ablation following thyroidectomy for invasive follicular cancer remains controversial. The use of iodine 131 (131I) ablation as adjuvant therapy may facilitate follow-up of patients in whom serum thyroglobulin levels and 131I total body scans are used to detect metastatic disease. It is uncertain if 131I ablation improves survival of patients with follicular thyroid cancer. Thus, the purpose of this study was to determine if survival is enhanced following ablation, with particular reference to those patients with minimally invasive cancer. Between the years 1955 to 1988, 142 patients with invasive thyroid follicular cancer were treated at the British Columbia Cancer Agency, of whom 71 had minimal invasion and no extrathyroidal extension of tumor. In this group of patients, 46 underwent hormone suppression only, 17 had ablation, and 8 had neither. The average follow-up was 9 years and extended beyond 15 years in many patients. Data were entered in a mainframe computer, and Kaplan-Meier survival analysis was used, comparing crude survival, disease-specific survival, and disease-free survival. There was no significant difference between groups. In patients with follicular thyroid cancer and capsular invasion only, 131I ablation does not improve survival compared with patients treated with thyroid hormone suppression only.