Incorporating physiologic principles into neonatal education.
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Curriculum↗
Biomedical subjects
D Johnson
Publications and source records attributed to D Johnson.
Preparing for electronic documentation.
Anticipating JCAHO review within 1 year, the nursing department developed and implemented a staff-developed manual system using Focus charting. Forms were developed that would be easily transferred to computerization.
Forms and Records Control↗
Peripheral blood progenitor cell transplantation: a single centre experience comparing two mobilisation regimens in 67 patients.
Between June 1991 and January 1995 we performed 67 peripheral blood progenitor cell transplants (PBPCT). Ten patients (group 1) were mobilised with 7 gm/m2 of cyclophosphamide followed by daily G-CSF injections (5 micrograms/kg, subcutaneously). When the white cell count reached 1 x 10(9)/1 they were leukapheresed for 5 days. After stem cell infusion they received G-CSF (10 micrograms/kg/day) until the neutrophil count reached 1.5 x 10(9)/1. Fifty-six patients had PBPCs mobilised with 3 gm/m2 of cyclophosphamide followed by daily subcutaneous G-CSF (5 micrograms/kg) and PBPCs were harvested on 2 consecutive days, when the white cell count rose to 4 x 10(9)/1. After stem cell infusion this group did not receive G-CSF. In 47 of the 56 patients (group 2) adequate MNC (> or = 4 x 10(8)/kg) and/or CFU-GM (> or = 10 x 10(4)/kg) were obtained. Insufficient MNC and/or CFU-GM were obtained in 10 patients. They were therefore transplanted using a combination of bone marrow and peripheral blood progenitor cells (group 3). Overall 64 patients successfully engrafted. Median days to neutrophils > or = 0.5 x 10(9)/1 were 9 (range 8-13), 12 (range 8-25) and 11 (range 9-16) and to platelets > or = 50 x 10(9)/1 were 11 (range 9-23), 13 (range 9-90) and 16 (range 13-99) in groups 1, 2 and 3 respectively. Patients in group 1 had a faster neutrophil recovery than patients in group 2 (P = 0.0002). The three patients who failed to engraft all received a combination of autologous peripheral blood and bone marrow cells.
Adolescent↗
A quality assessment scheme for blood glucose monitoring: competition improves performance.
Quality assurance procedures are often ignored or forgotten about by wards involved in the blood glucose monitoring of patients. We have devised a complete quality assurance scheme for checking the ward performance of 38 B-M Reflolux meters and two B-M Accutrend meters. Quality control (QC) material, supplied commercially and distributed by the laboratory, is analysed and recorded daily by the wards (internal QC). In addition, a 'spiked', whole blood sample is prepared by the laboratory and distributed for analysis to all wards at six-monthly intervals (external QC). The laboratory also conducts a monthly survey of meter operation (quality assessment) based on a 'scoring system' that allows easy identification of poor performers. Poor performers are counselled accordingly and, if poor performance is persistent, their meter is removed. In our experience, the publication and distribution of ward quality assessment scores has increased competition between wards in terms of avoiding low scores, dramatically improved performance, and ultimately led to improved patient care.
Blood Glucose↗
High-dose therapy and autologous stem cell rescue for poor risk and refractory lymphoma: a single centre experience of 123 patients.
Over an 8-year period we autografted 123 patient with poor-risk lymphoma. Sixty-three patients had Hodgkin's disease (HD) and 60 non-Hodgkin's lymphoma (NHL). Of the patients with HD, 45 had responsive and 18 resistant disease prior to high-dose therapy. Fifty-three patients with NHL had responsive and seven had resistant disease at the time of transplantation. Seventy-seven patients received autologous bone marrow (BM) rescue, 39 autologous peripheral blood progenitor cell (PBPC) rescue, and seven combined BM and PBPC rescue. High-dose chemotherapy was BEM in 67, BEAM in 39, TBI and cyclophosphamide or etoposide or BCNU in 10, etoposide/mitozantrone in six and etoposide/melphalan in one. There was eight (6.5%) deaths due to treatment-related toxicity, within the first 100 days post-transplantation. Of the patients with HD 41 (65%) are alive at a median follow-up of 39 months (range 2-94). Thirty-three (52%) patients remain in CR. The median DFS of the 63 patients with HD is 34 months (95% CI 7-61). The median DFS for patients transplanted with responsive disease was significantly better than for those transplanted with refractory disease (61 vs 21 months P < 0001). Thirty-five (58%) of the patients with NHL are alive, and 20 (33%) remain in CR. The median DFS for patients transplanted with responsive and refractory disease was 11 months (95% CI 3-19) and 4 months (95% CI 0-9; P = NS) respectively. The median DFS for patients transplanted with HD was significantly better than for patients transplanted with NHL (34 vs 8 months, P < 0.002). In both groups there was no significant difference in DFS in patients receiving one, two, three or more lines of therapy prior to transplantation. In summary, in patients with poor-risk lymphoma who have responsive disease high-dose therapy may result in durable CRs. Conversely, only a small proportion of patients with HD or NHL with resistant disease achieve CR after autologous stem cell rescue.
Adolescent↗
Managing impotence. A general practice approach.
The burgeoning interest in men's health, together with the greater recognition given to the existence of erectile dysfunction, suggests that many more men will in future expect their family doctors to be able to deal with this problem. This article attempts to present options for management in practical terms that translate readily into actual clinical practice.
Erectile Dysfunction↗
Counseling to reduce road injuries and deaths.
OBJECTIVE: To study undergraduate learning of and current clinical practice on counseling to reduce road injuries and deaths. DESIGN: Questionnaire on high-risk clinical scenarios. SETTING: Canadian medical schools, one family medicine program, and a Toronto trauma centre. PARTICIPANTS: Three groups: 338 final-year medical students from 12 Canadian universities, 183 family practice teachers from the Ontario-wide University of Toronto teaching network, and 45 trauma-team members from a Toronto regional trauma centre. MAIN OUTCOME MEASURES: All health promotion items identified by students are relevant to the clinical scenarios presented to them were tabulated to identify general knowledge of health promotion counseling and specific knowledge of road trauma prevention. The trauma-related counseling practices of family practice teachers were tabulated from their responses to one of the student scenarios. The same process tabulated the counseling that trauma-team members would expect family physicians to do in busy practices. RESULTS: Students' knowledge about health promotion counseling was generally good, except for road trauma prevention, where counseling is seldom done unless heavily prompted. Family practice teacher responses indicated that approximately 15% have not accepted road trauma counseling as part of clinical practice. Trauma-team members ranked trauma prevention items similarly to family practice teachers, but had higher expectations for performance. The neck is the most commonly injured site, but no group identified headrest adjustment as important. CONCLUSIONS: Counseling to prevent road trauma is deficient both in practice and teaching.
Accidents, Traffic↗
Measurement of serum acetylsalicylic acid in a porcine model of aspirin overdose.
Although the pharmacokinetics of acetylsalicylic acid (ASA) absorption and metabolism in therapeutic doses are well described, there is little information for overdose. A porcine model was developed to study ASA pharmacokinetics in overdose and to establish the feasibility of using area-under-the-curve (AUC) for serum ASA vs time rather than salicylate vs time as an indirect method of quantifying total drug absorption. Such a model could be useful in comparing the effectiveness of different methods of gastrointestinal decontamination in poisoning. The hydrolysis of ASA to salicylate, known to be a first-order process in therapeutic doses, was confirmed to remain first-order at high serum concentrations using iv aspirin in 2 pigs. Five simulated overdoses were then carried out in 4 pigs using 500 mg ASA/kg administered enterally as intact tablets. Serial determinations of both serum ASA and salicylate concentration were carried out over 72 h. Plots of ASA concentration vs time for each of the trials revealed delayed, multiple and erratic peaks consistent with a bolus effect from sudden dissolution of aspirin concretions, suggesting our model accurately simulates human overdose. Despite the variable peaks, the AUC of ASA concentration vs time for the 5 trials revealed a coefficient of variation of only 13%, compared with 27% for salicylate concentration vs time AUC. This suggests that serial measurements of serum ASA in a porcine ASA overdose model can be used to measure total drug absorption and thereby compare the effectiveness of different methods of gastrointestinal decontamination.
Administration, Oral↗
Determining ejection fraction by Doppler echocardiography.
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Confidence Intervals↗
Evaluation of four alternative methodologies for determination of absolute CD4+ lymphocyte counts. The National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study.
Standard methods for determining absolute CD3+CD4+ T-lymphocyte concentrations using combined results from flow cytometry and hematology analyzers are expensive and require fresh (< 18 h old) blood. We evaluated four new "alternative" methods for determining absolute CD4+ T-lymphocyte counts; (a) the FACSCount System (Becton Dickinson Immunocytometry Systems), (b) VCS Technology/Coulter Cyto-Spheres (Coulter Corporation), (c) Zymmune CD4/CD8 Cell Monitoring Kit (Zynaxis, Inc.), and (d) TRAx CD4 Test Kit (T Cell Diagnostics). EDTA-anticoagulated whole-blood specimens from HIV-seropositive patients and anti-HIV-negative adult blood donors and staff were tested by the standard flow cytometry method on fresh blood (0-6 postphlebotomy) and by the four alternative methods at 0 to 6 h and 24 to 30 h postphlebotomy. Representative specimens (< 6 h old) were tested five times with each system to evaluate reproducibility. Correlation coefficients for absolute CD4+ counts between standard flow cytometry and the alternative methods ranged from 0.84 to 0.92 for both fresh and 24- to 30-h-old specimens. Average coefficient of variation for reproducibility ranged from 4.5 to 7.1%. The four alternative CD4+ T-lymphocyte counting methods performed well relative to standard methods. Each alternative method offers advantages over standard flow cytometry with respect to sample throughout, required technical expertise, and cost per result. These methods should facilitate wider availability of low-cost CD4 counts.
Blood Donors↗
Cloning of a human receptor of the NPY receptor family with high affinity for pancreatic polypeptide and peptide YY.
Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) are structurally related peptides found in all higher vertebrates. NPY is expressed exclusively in neurons, whereas PYY and PP are produced primarily in gut endocrine cells. Several receptor subtypes have been identified pharmacologically, but only the NPY/PYY receptor of subtype Y1 has been cloned. This is a heptahelix receptor that couples to G proteins. We utilized Y1 sequence information from several species to clone a novel human receptor with 43% amino acid sequence identity to human Y1 and 53% identity in the transmembrane regions. The novel receptor displays a pharmacological profile that distinguishes it from all previously described NPY family receptors. It binds PP with an affinity (Ki) of 13.8 pM, PYY with 1.44 nM, and NPY with 9.9 nM. Because these data may identify the receptor as primarily a PP receptor, we have named it PP1. In stably transfected Chinese hamster ovary cells the PP1 receptor inhibits forskolin-stimulated cAMP synthesis. Northern hybridization detected mRNA in colon, small intestine, pancreas, and prostate. As all three peptides are present in the gut through either endocrine release or innervation, all three peptides may be physiological ligands to the novel NPY family receptor PP1.
Amino Acid Sequence↗
Early gene signalling-dependent and -independent induction of apoptosis in Ramos human B cells can be inhibited by over-expression of Bcl-2.
We have previously shown that calcium ionophore-induced apoptosis of Ramos human B cells is preceded by the induced expression of early response genes, implying a requirement for new gene expression in this mode of programmed cell death. We have found in the present studies that inhibitors of macromolecular synthesis, cycloheximide and actinomycin D, are also potent inducers of apoptosis in the same Ramos cell model. These drugs trigger apoptosis through apparently early gene signalling-independent pathways. Although different mechanisms for induction of apoptosis exist in Ramos cells, enforced over-expression of Bcl-2 protects cells from apoptosis induced in response to different agents, demonstrating that Bcl-2 blocks a final common pathway for programmed cell death in the Ramos cell model.
Apoptosis↗
Confined alpha distribution measurements in a deuterium-tritium tokamak plasma.
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Journal Article↗
Herpes simplex virus turns off the TAP to evade host immunity.
Many viruses have evolved mechanisms to avoid detection by the host immune system. Herpes simplex virus (HSV) expresses an immediate early protein, ICP47, which blocks presentation of viral peptides to MHC class I-restricted cells. The properties of the newly synthesized class I molecules in HSV-infected cells resemble those of cell lines deficient in the transporter associated with antigen processing (TAP) in that class I molecules are retained in the endoplasmic reticulum, and the heavy chain and beta 2-microglobulin subunits dissociate in detergent extracts but the complex can be stabilized by peptides. We show here that ICP47 binds to TAP and prevents peptide translocation into the endoplasmic reticulum.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer.
BACKGROUND: Regionally advanced, surgically unresectable non-small-cell lung cancer represents a disease with an extremely poor prognosis. External-beam irradiation to the primary tumor and regional lymphatics is generally accepted as standard therapy. The use of more aggressive radiation regimens and the addition of cytotoxic chemotherapy to radiotherapy have yielded conflicting results. Recently, however, results from clinical trials using innovative irradiation delivery techniques or chemotherapy before irradiation have indicated that patients treated with protocols that incorporate these modifications may have higher survival rates than patients receiving standard radiation therapy. PURPOSE: On the basis of these results, the Radiation Therapy Oncology Group (RTOG)-Eastern Cooperative Oncology Group (ECOG) elected to conduct a phase III trial comparing the following regimens: 1) standard radiation therapy, 2) induction chemotherapy followed by standard radiation therapy, and 3) twice-daily radiation therapy. METHODS: Patients with surgically unresectable stage II, IIIA, or IIIB non-small-cell lung cancer were potential candidates. Staging was nonsurgical. Patients were required to have a Karnofsky performance status of 70 or more and weight loss less than 5% for 3 months prior to entry into the trial, to be older than 18 years of age, and to have no metastatic disease. Of the 490 patients registered in the trial, 452 were eligible. The disease in 95% of the patients was stage IIIA or IIIB. More than two thirds of the patients had a Karnofsky performance status of more than 80. Patients were randomly assigned to receive either 60 Gy of radiation therapy delivered at 2 Gy per fraction, 5 days a week, over a 6-week period (standard radiation therapy); induction chemotherapy consisting of cisplatin (100 mg/m2) on days 1 and 29 and 5 mg/m2 vinblastine per week for 5 consecutive weeks beginning on day 1 with cisplatin, followed by standard radiation therapy starting on day 50; or 69.6 Gy delivered at 1.2 Gy per fraction twice daily (hyperfractionated radiation therapy). RESULTS: Toxicity was acceptable, with four treatment-related deaths. Three patients subsequently died of chronic pulmonary complications. Compliance with protocol treatment was acceptable. One-year survival (%) and median survival (months) were as follows: standard radiation therapy--46%, 11.4 months; chemotherapy plus radiotherapy--60%, 13.8 months; and hyperfractionated radiation therapy--51%, 12.3 months. The chemotherapy plus radiotherapy arm was statistically superior to the other two treatment arms (logrank P = .03). CONCLUSIONS: In "good-risk" patients with surgically unresectable non-small-cell lung cancer, induction chemotherapy followed by irradiation was superior to hyperfractionated radiation therapy or standard radiation therapy alone, yielding a statistically significant short-term survival advantage.
Adult↗
A graphic, three-dimensional teaching model to demonstrate the topography of the human heart.
A three-dimensional graphic model of the human heart and an accompanying description are presented as a teaching aid. Each of the four chambers is represented by a cube of equal size. Drawings of the model from various angles give views of each of the surfaces and show the interatrial, interventricular, and atrioventricular grooves, and superimposed coronary arteries and cardiac veins.
Coronary Vessels↗
Synthetic peptides deduced from the amino acid sequence of Epstein-Barr virus nuclear antigen 6 (EBNA 6): antigenic properties, production of monoreactive reagents, and analysis of antibody responses in man.
Studies on the antibody responses to various Epstein-Barr virus (EBV) antigens have been instrumental in the understanding of the seroepidemiology and diagnosis of this viral infection and the subsequent carrier state. While antibodies to the viral capsid antigen (VCA), early antigen (EA), and nuclear antigens 1 and 2 (EBNA 1 and 2) have been well characterized, the antibody response to the other nuclear antigens is not well understood. EBNA 6 is expressed by lymphoblasts during acute EBV infection and may be an important antigen for diagnosis and evaluation of the immune response. In order to analyze the antibody response to EBNA 6, ten peptides (20-21 amino acids), deduced from the EBNA 6 coding region, were synthesized and evaluated for antigenicity by ELISA. One peptide (p-63; PAPQAPYQGYQEPPAPQAPY) derived from the amino acid repeats showed the highest specific reactivity with human sera. This peptide was evaluated further for detection of human EBNA 6-reactive antibodies. Forty-two of forty-nine (86%) EBV-seropositive healthy donors had p-63-specific IgG reactivity, while none of 50 EBV-seronegative patients reacted with the p-63 peptide. Twenty-two of fifty-one (43%) patients with ongoing primary EBV infection had detectable p-63-specific IgG. Serum samples drawn sequentially from patients during and after primary EBV infection revealed an increase in p-63-reactive IgG over time.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Racemization of ketorolac in aqueous solution.
The racemization of ketorolac was studied in aqueous buffered solution at 25 and 80 degrees C and analyzed in detail with respect to the catalytic species in solution. The reaction has a U shaped pH rate profile at 80 degrees C with the pH of maximum stability occurring in the region of pH 3.0-7.5. A T90 value of 8 months was observed for a 1.5% (R)-ketorolac tromethamine solution at pH 7.4 and 25 degrees C. Additionally, the data shows that alternative salt forms are necessary in order to prepare a stable single isomer formulation. Alternative buffers, in particular phosphate buffer, provide formulations exhibiting a T90 greater than 2 years.
Catalysis↗