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J Johnston

Publications and source records attributed to J Johnston.

At least 19 recordsLinked to original sources
PubMed1995

Health care report cards. Validity of case definitions.

Administrative databases are increasingly being used to construct health care report cards. We analyzed information from one of the original report cards, the Medicare Hospital Information Project. Assessment of mortality statistics for three clinical entities--coronary artery bypass surgery, hip reconstruction, and treatment of sepsis--demonstrated widespread outcome variances that reflected imperfect definitions rather than performance issues in clinical care. The use of administrative data sets to design report cards requires clinical expertise to ensure validity of the data. Designers of report card measures should share preliminary data with providers to enable feedback in methods and uncover definitional and validity concerns before widespread dissemination.

Bias↗
PubMed1995

Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors: binding and signaling of MCP3 through shared as well as unique receptors on monocytes and neutrophils.

The diversity of monocyte chemotactic protein (MCP)3 target cell types, as well as the capacity of MCP3 to desensitize leukocyte responses to other CC chemokines, suggested that MCP3 may interact with multiple CC chemokine receptors. The purpose of this study is to establish how MCP3 binds and activates monocytes and neutrophils. We show that human monocytes exhibit high-affinity binding for 125I-MCP3 with an estimated Kd of 1-3 nM and about 10,000 binding sites/cell. The binding of 125I-MCP3 to monocytes was progressively less well competed by CC chemokines macrophage inflammatory protein (MIP)1 alpha (Kd = 5-10 nM), RANTES (Kd = 5-10 nM), MCP1 (monocyte chemoattractant and activating factor, or MCAF) (Kd = 60 nM) and MIP1 beta (Kd > 100 nM). On the other hand, unlabeled MCP3 displaced the binding of radiolabeled MIP1 alpha, RANTES, MCP1 and MIP1 beta as effectively as the isologous CC chemokines. In agreement with the binding data, pretreatment of monocytes with MCP3 completely desensitized the calcium flux in response to MIP1 alpha and RANTES. However, MIP1 alpha and RANTES failed to desensitize the response of monocytes to MCP3. MCP3 and MCP1 partially desensitized each other's effects on monocytes. These binding and cross-desensitization results suggest that MCP3 binds and signals through other binding sites in addition to those shared with MIP1 alpha, RANTES and MCP1. The unidirectional competition for MIP1 beta binding and signaling by MCP3 suggests the existence of an as-yet unidentified site for MCP3 shared with MIP1 beta. The existence of another unique binding site(s) for MCP3 was further shown by the failure of any of the other CC chemokines to compete effectively for MCP3 binding on neutrophils. MCP3 in our study was also the only human CC chemokine that consistently chemoattracted neutrophils. These results suggest that MCP3 is a ligand that can bind and activate a broad range of target cells through receptors shared by other CC chemokines as well as its own receptor.

Calcium↗
PubMed1995

Issues in private practice: midwife care--the future.

The future for private practitioner midwives depends on an understanding of why such care is not only safe for the mother and her baby, but the ideal. Continuity of caregiver has been shown to reduce the mother's need for obstetric intervention. Skilled medical attention is appropriate when and if it becomes necessary. The inappropriate use of obstetric technology carries a cost to the mother, the child, and society. Many constraints exist in Victoria to autonomous midwife practice. The challenge before us is to support one another in our vision for life.

Female↗
PubMed1995

Bridging the professions: an integrated and interdisciplinary approach to teaching health care ethics.

In 1993, the authors introduced an interdisciplinary course in health care ethics at the University of British Columbia. They were motivated by two convictions: (1) an interdisciplinary approach to health care decision making is best; and (2) every significant health care decision has an ethical component. They wanted to encourage students from the various health care disciplines to participate in interdisciplinary decision making in their future practices by giving them an opportunity to study health care ethics together during their training. The authors give detailed descriptions of the objectives, format, curriculum, and evaluation of this innovative course in the hope that other educators who may want to develop similar courses can learn from their experience.

British Columbia↗
PubMed1995

Children with vesical rhabdomyosarcoma (RMS) treated by partial cystectomy with neoadjuvant or adjuvant chemotherapy, with or without radiotherapy. A report from the Intergroup Rhabdomyosarcoma Study (IRS) Committee.

PURPOSE: Children with bladder rhabdomyosarcoma (RMS) are currently treated with primary chemotherapy and usually with local irradiation. More than 30% of this group ultimately require total cystectomy. The purpose of this study was to review the results of the use of partial as opposed to total cystectomy in 40 patients with bladder RMS during Intergroup Rhabdomyosarcoma Study (IRS)-I, -II, and -III (1972-1989). PATIENTS AND METHODS: A total of 171 children with primary RMS of the bladder were enrolled in the IRS during this interval. Partial cystectomy was performed in 40, in 33 before any other therapy and in seven after 10-57 weeks of chemotherapy (primarily vincristine, actinomycin-D, and cyclophosphamide, i.e., VAC) +/- radiotherapy. Surviving patients have been observed for 4-22 years. RESULTS: Thirty-one of 40 patients (78.5%) have been disease free for 2-16 years. Survival among all other IRS cases with bladder RMS during the same interval was 79.5%. Of the 31 surviving patients, one required secondary total cystectomy and two required bladder augmentation procedures for benign bladder contracture. Three quarters of the total group of living patients who have undergone partial cystectomy are without bladder-related symptoms or demonstrable lower urinary tract disease. The remaining patients have a history of functional bladder problems related to contracture or incontinence. CONCLUSIONS: Partial cystectomy is an alternative to total cystectomy for bladder RMS when the tumor site makes it anatomically feasible. In such patients, it should be considered before total cystectomy and in patients with persistent areas of questionable residual tumor after otherwise apparently successful regimens of primary chemotherapy +/- radiotherapy.

Adolescent↗
PubMed1995

Pitfalls in the interpretation of spectral analysis of the heart rate variability during exercise in humans.

The recent use of spectral analysis of the R-R interval variability to assess the autonomic drive during exercise has produced inconsistent results. The purpose of this study was to assess whether the spectral components of the R-R interval variability reflect different mechanisms at rest and during exercise. Autoregressive spectral analysis of the electrocardiographic and breathing signals was performed in 11 healthy young men at rest and during incremental cycle ergometry. The amplitude of respiratory sinus arrhythmia, i.e. the absolute power of the high frequency spectral component, fell at the onset of exercise, consistent with a reduction in cardiac vagal activity. Conversely, the normalized power of the high frequency component, (i.e. the percentage of R-R interval variance due to the respiratory sinus arrhythmia) increased with increasing work rates. The low frequency spectral component of the R-R interval variability, which when expressed in normalized units is believed to reflect cardiac sympathetic activity, was no longer detectable in severe exercise when the adrenergic drive is known to be elevated. In conclusion, autoregressive spectral analysis of the R-R interval variability does not adequately reflect the autonomic changes that occur during incremental exercise. In particular, the evidence indicates that as the cardiac vagal tone falls with increasing levels of exercise, a greater percentage of the residual power of the high frequency component may be due to non-neural mechanisms.

Adult↗
PubMed1995

Case studies in work redesign: cost considerations in a work redesign project.

Regardless of the limitations and comprehensiveness of plans for redesign, at least one common consideration prevails. Decisions to redesign should be well planned with specific attention to the details of the costs involved. As the unique needs of the institution are incorporated into the plan, a thorough cost-benefit analysis should be used to determine final decisions. Without specific attention to a number of factors, including those noted above, the restructuring project may fall short of the intended goals of reducing costs and may actually increase costs.

Cost-Benefit Analysis↗
PubMed1994

Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation.

The 39- to 43-amino acid amyloid beta-protein (A beta), which is progressively deposited in cerebral plaques and blood vessels in Alzheimer disease (AD), is secreted by cultured human cells during normal metabolism. In studies of cell lines transfected with beta-amyloid precursor protein (beta APP) cDNAs, the beta APP mutation K670N/M671L found in a Swedish familial AD (FAD) pedigree has previously been shown to cause a marked augmentation of A beta secretion. Here, we have conducted blinded analyses of beta APP metabolism in primary skin fibroblasts from affected members of the Swedish FAD pedigree and their unaffected siblings or spouses. These fibroblasts continuously secrete a homogenous population of A beta molecules starting at Asp-1 (D672 of beta APP). We found a consistent and significant approximately 3-fold elevation of A beta release from all biopsied skin fibroblasts bearing the FAD mutation. No significant alterations of other metabolic derivatives of beta APP were detected. The elevated A beta levels were found in cells from both patients with clinical AD and presymptomatic subjects. Thus, A beta overproduction in this FAD pedigree is not a secondary event but is consistent with a causal role in the development of the disease. Increased A beta secretion can begin many years prior to onset of symptoms, even in peripheral tissues, indicating that it does not require preexisting neural abnormalities.

Alzheimer Disease↗
PubMed1994

Tumor immunogenicity determines the effect of B7 costimulation on T cell-mediated tumor immunity.

A costimulatory signal through B7 to its counter-receptor CD28 on T cells enhances T cell activation. We have generated recombinant retroviruses containing cDNA for murine B7 and transduced a panel of murine tumor lines with varying immunogenicity to study the effect of B7 costimulation on antitumor immunity. In contrast to the progressive outgrowth of all wild-type (B7-) tumors in unimmunized syngeneic mice, four immunogenic tumors, lymphoma RMA, EL4, mastocytoma P815, and melanoma E6B2, regressed completely when transduced with the B7 gene. In contrast, four nonimmunogenic tumors, sarcomas MCA101, MCA102, and Ag104, and melanoma B16, remained tumorigenic after transduction of the B7 gene. Immunization with B7-transduced immunogenic tumors enhanced protective immunity and increased specific cytotoxic T lymphocyte (CTL) activity against the respective wild-type tumors as compared to immunization with nontransduced or mock-transduced tumors. Moreover, cocultivation of CTL with B7-transduced EL4 cells augmented the specificity of tumor-reactive CTL in long-term cultures. Treatment by injection of B7-transduced tumor cells cured 60% of mice with established wild-type EL4 lymphoma. In contrast, immunization with nonimmunogenic tumors transduced with B7 did not provide protective immunity and did not increase specific CTL activity. Our results show that tumor immunogenicity is critical to the outcome of costimulation of T cell-mediated tumor immunity by B7.

Animals↗
PubMed1994

Neonatal rhabdomyosarcoma: the IRS experience.

Neonatal rhabdomyosarcoma is rare, and the characteristics and optimal therapy for patients with this condition have not been well described. Of 3,217 eligible patients entered in the Intergroup Rhabdomyosarcoma Study (IRS), 14 were less than 30 days old at the time of diagnosis. Among these patients, male gender, Caucasian race, caudal tumors, and embryonal/botryoid and undifferentiated histology predominate. Although half the neonates survived, neither histology, tumor size, nor type of surgery were predictive of outcome. The presence of necrosis and small round cell configuration coincides with a poor prognosis, regardless of histological diagnosis. Neonatal rhabdomyosarcoma of caudal origin has a favorable prognosis.

Age Factors↗
PubMed1994

The significance of the Swedish APP670/671 mutation for the development of Alzheimer's disease amyloidosis.

Alzheimer's disease is characterized histopathologically by the detection of amyloid plaques and tangles in the brains of its victims. A major component of the amyloid plaques, the beta-amyloid peptide, is a metabolite of a larger transmembrane protein termed the amyloid precursor protein (APP). Several pathogenic mutations causing Alzheimer's disease have been identified in the APP gene, situated on chromosome 21. One of these is a double missense mutation in exon 16 of the APP gene which occurs in a large Swedish pedigree. Studies with transfected cell cultures have shown that cells expressing this double mutation release approximately 7 times more beta-amyloid than their wild type counterparts. Possible mechanisms whereby the APP mutations cause Alzheimer's disease are considered here against the background of current understanding of the physiological role and processing of APP.

Alzheimer Disease↗
PubMed1994

Method for assessment of laboratory turnaround times: comparison before, during, and after analysis.

AIMS: To establish a mechanism to examine the components of turnaround time in a representative cross-section of laboratory users; and to identify potential areas for improvement. METHODS: Information was collected manually from result reports received by eight laboratory users: three wards in the main hospital, four GP practices, and one local psychiatric hospital. This was combined with data from the departmental computer files to create a spreadsheet detailing different time points in the processing of a specimen, from venepuncture to receipt of result report. RESULTS: At the main hospital, 80% of samples arrived within two hours of venesection and 95% by four hours; 75% of samples were analysed within two hours; 85% of results arrived in the wards within six hours of printing, although 12% took more than 18 hours to arrive; median overall time six hours. At the satellite (psychiatric) hospital, all samples arrived within seven hours of venesection; 45% were analysed within two hours--the rest the following morning; there were highly variable post-analytical times, minimum 18 hours, maximum 122 hours; the median overall time was 69 hours. Twenty five per cent of samples from GPs took more than 20 hours to arrive; 75% were analysed within two hours, the rest took over 18 hours--waiting overnight; the post-analytical times were highly variable, minimum 22 hours, maximum 122 hours; the median overall time was 50 hours. CONCLUSIONS: The method is easily repeatable and demonstrates the need for local improvement in the post-analytical period. Although specific to the individual data handling system for one laboratory, this method may be used as a basis for other laboratories in pathology disciplines to undertake a representative assessment of turnaround times for different groups of laboratory users.

Cross-Sectional Studies↗
PubMed1994

Stability of functional outcomes following transitional living programme participation: 3-year follow-up.

The functional status and perceived problems of 21 persons with severe brain injury were reported at admission, and at 1 and 3 years post-discharge from a community-based post-acute rehabilitation programme. Functional status was measured by participation in productive activity, financial support, place of residence and level of supervision required. Improvements observed at 1-year follow-up remained stable or had improved at 3-year follow-up. Loneliness and depression, while not reported at admission, increased over time to become the two problems reported most frequently at 3-year follow-up.

Activities of Daily Living↗
PubMed1993

Expression of HERV-K proviruses in human leukocytes.

HERV-K is a 50-copy, human endogenous, class 1 retroviral element that contains some polycistrons with gag, pol, and env open reading frames. Although expression of HERV-K proviruses has been shown in cultured human cell lines, expression of these elements has not been shown in human blood leukocytes. Using both reverse transcriptase-polymerase chain reaction and ribonuclease protection techniques, we show HERV-K pol gene expression in human blood leukocytes. Expression in blood leukocytes from 7 normal individuals was from a variety of different HERV-K proviruses, while restricted expression was observed in blood cells of 5 leukemia patients and 3 polycythemia vera patients. Evidence is presented suggesting that the restricted expression in leukemia blood cells is a result of gene regulation, not gene amplification.

Adult↗