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Biomedical subjects

S Stewart

Publications and source records attributed to S Stewart.

At least 55 records · Page 3Linked to original sources
PubMed2001

Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma.

PURPOSE: The objective of this phase III study was to determine the efficacy, safety, and pharmacokinetics of denileukin diftitox (DAB389IL-2, Ontak [Ligand Pharmaceuticals Inc, San Diego, CA]) in patients with stage Ib to IVa cutaneous T-cell lymphoma (CTCL) who have previously received other therapeutic interventions. PATIENTS AND METHODS: Patients with biopsy-proven CTCL that expressed CD25 on > or = 20% of lymphocytes were assigned to one of two dose levels (9 or 18 microg/kg/d) of denileukin diftitox administered 5 consecutive days every 3 weeks for up to 8 cycles. Patients were monitored for toxicity and clinical efficacy, the latter assessed by changes in disease burden and quality of life measurements. Antibody levels of antidenileukin diftitox and anti-interleukin-2 and serum concentrations of denileukin diftitox were also measured. RESULTS: Overall, 30% of the 71 patients with CTCL treated with denileukin diftitox had an objective response (20% partial response; 10% complete response). The response rate and duration of response based on the time of the first dose of study drug for all responders (median of 6.9 months with a range of 2.7 to more than 46.1 months) were not statistically different between the two doses. Adverse events consisted of flu-like symptoms (fever/chills, nausea/vomiting, and myalgias/arthralgias), acute infusion-related events (hypotension, dyspnea, chest pain, and back pain), and a vascular leak syndrome (hypotension, hypoalbuminemia, edema). In addition, 61% of the patients experienced transient elevations of hepatic transaminase levels with 17% grade 3 or 4. Hypoalbuminemia occurred in 79%, including 15% with grade 3 or 4 changes. Tolerability at 9 and 18 microg/kg/d was similar, and there was no evidence of cumulative toxicity. CONCLUSION: Denileukin diftitox has been shown to be a useful and important agent in the treatment of patients whose CTCL is persistent or recurrent despite other therapeutic interventions.

Adult↗
PubMed2001

Expression of a reporter gene after microinjection of mammalian artificial chromosomes into pronuclei of bovine zygotes.

The introduction of mammalian artificial chromosomes (ACs) into zygotes represents an alternative, more predictive technology for the production of recombinant proteins in transgenic animals. The aim of these experiments was to examine the effects of artificial chromosome microinjection into bovine pronuclei on embryo development and reporter gene expression. Bovine oocytes aspirated from 2-5 mm size follicles were matured in vitro for 22 hr. Mature oocytes were fertilized in vitro with frozen- thawed bull spermatozoa. Artificial chromosome carrying either beta-galactosidase (Lac-Z) gene or green fluorescence protein (GFP) gene were isolated by flow cytometry. A single chromosome was microinjected into one of the two pronuclei of bovine zygotes. Sham injected zygotes served as controls. Injected zygotes were cultured in G 1.2 medium for 7 days. Hatched blastocysts were cultured on blocked STO cell feeder layer for attachment and outgrowth of ICM and trophectoderm cells. The results showed a high zygote survival rate following LacZ-ACs microinjection (74%). However, the blastocyst development rate after 7 days of culture was significantly lower than that of sham injected zygotes (7.5 vs. 22%). Embryonic cells positive for Lac-Z gene were detected by PCR in three of nine outgrowth colonies. In addition, GFP gene expression was observed in 15 out of 85 (18%) embryos at the arrested 2-cell stage to blastocyst stage. Six blastocysts successfully outgrew, three outgrowths were GFP positive for up to 3 weeks in culture. We conclude that the methodology for artificial chromosome delivery into bovine zygotes could lead to viable blastocyst development, and reporter gene expression could be sustained during pre-implantation development.

Animals↗
PubMed2001

Community-based cancer screening for underserved women: design and baseline findings from the Breast and Cervical Cancer Intervention Study.

BACKGROUND: Underutilization of breast and cervical cancer screening has been observed in many ethnic groups and underserved populations. Effective community-based interventions are needed to eliminate disparities in screening rates and thus to improve prospects for survival. METHODS: The Breast and Cervical Cancer Intervention Study was a controlled trial of three interventions in the San Francisco Bay Area from 1993 to 1996: (1) community-based lay health worker outreach; (2) clinic-based provider training and reminder system; and (3) patient navigator for follow-up of abnormal screening results. Study design and a description of the interventions are reported along with baseline results of a household survey conducted in four languages among 1599 women, aged 40-75. RESULTS: Seventy-six percent of women ages 40 and over had had at least one mammogram, and most had had a clinical breast examination (88%) and Pap smear (89%). Rates were significantly lower for non-English-speaking Latinas and Chinese women (56 and 32%, respectively, for mammography), and maintenance screening (three mammograms in the past 5 years) varied from 7% (non-English-speaking Chinese) to 53% (Blacks). Pap smear screening in the past 3 years was low among non-English-speaking Latinas (72%) and markedly lower among non-English-speaking Chinese women (24%). The strongest predictors of screening behavior were having private health insurance and frequent use of medical services. Having a regular clinic and speaking English were also important. Race/ethnicity, education, household income, and employment status were, overall, not significant predictors of screening behavior. CONCLUSIONS: These baseline results support the importance of cancer screening interventions targeted to persons of foreign origin, particularly those less acculturated.

Adult↗
PubMed2001

Electrical cardioversion for atrial fibrillation: outcomes in "real-life" clinical practice.

BACKGROUND: There is currently considerable debate with regard to the optimal management of atrial fibrillation/flutter (AF), including the long-term success of electrical cardioversion and the duration of anti-coagulation thereafter. The aim of this study was to investigate the current management and outcomes of electrical cardioversion in unselected patients in ordinary clinical practice. METHODS: A prospective, observational study of 111 consecutive patients with AF who had been referred for electrical cardioversion was undertaken in a large teaching hospital. After cardioversion, patients were followed-up for 12 months or until death if this occurred earlier. RESULTS: Sinus rhythm was restored immediately in 96 of 111 (86%) patients. Only 54 of 88 (61%) patients in sinus rhythm at discharge remained in this rhythm at 1 month. Of these 54, a further 21 (39%) had relapsed into AF by 12 months. Independent predictors of sinus rhythm at discharge were younger age (for a difference of 5 years, odds ratio=1.54; 95% confidence interval 1.04 to 1.16; P=0.002) and absence of hypertension (1.73, 1.22-1.91; P=0.015). The presence of sinus rhythm at discharge (6.4, 1.6-25.3; P=0.007) was an independent predictor of sinus rhythm at 1 month, whereas older age was a negative predictor (0.96, 0.92-1.0; P=0.05). Health-related quality of life improved at 1 and 12 months in those patients who remained in sinus rhythm compared to those who remained in AF. CONCLUSIONS: Though electrical cardioversion for AF has a high initial success rate only a minority of patients remained in sinus rhythm 1 year. The common practice of discontinuing anticoagulant treatment in patients in sinus rhythm at 1 month may be unsafe. Long-term maintenance of sinus rhythm is, however, associated with better health-related quality of life.

Aged↗
PubMed2001

Gender and survival: a population-based study of 201,114 men and women following a first acute myocardial infarction.

OBJECTIVES: We tested the hypotheses that the effect of gender on short-term case fatality following a first admission for acute myocardial infarction (AMI) varies with age, and that this effect is offset by differences in the proportion of men and women who survive to reach hospital. BACKGROUND: Evidence is conflicting regarding the effect of gender on prognosis after AMI. METHODS: All 201,114 first AMIs between 1986 and 1995 were studied. Both 30-day and 1-year case fatality were analyzed for the 117,749 patients hospitalized and for all first AMIs, including deaths before hospitalization. The effect of gender and its interaction with age on survival was examined using multivariate modeling. RESULTS: Gender-based differences in survival varied according to age in hospitalized patients, with younger women having higher 30-day case fatality than men (e.g., <55 years, women 6.5% vs. 4.8% men, p < 0.0001). When deaths from first AMI before hospitalization were included in 30-day case fatality, women were less likely to die (adjusted odds ratio 0.9, confidence interval 0.89 to 0.93). Gender was not an independent predictor of one-year survival (p = 0.16). CONCLUSIONS: Female gender increases the probability of surviving to reach hospital, and this outweighs the excess risk of death occurring in younger women following hospitalization. Overall, men have a higher 30-day case fatality than women. Women do not fare worse than men after AMI when age and other factors are taken into account. However, men are more likely to die before hospitalization.

Age Factors↗
PubMed2001

More 'malignant' than cancer? Five-year survival following a first admission for heart failure.

BACKGROUND: The prognostic impact of heart failure relative to that of 'high-profile' disease states such as cancer, within the whole population, is unknown. METHODS: All patients with a first admission to any Scottish hospital in 1991 for heart failure, myocardial infarction or the four most common types of cancer specific to men and women were identified. Five-year survival rates and associated loss of expected life-years were then compared. RESULTS: In 1991, 16224 men had an initial hospitalisation for heart failure (n=3241), myocardial infarction (n=6932) or cancer of the lung, large bowel, prostate or bladder (n=6051). Similarly, 14842 women were admitted for heart failure (n=3606), myocardial infarction (n=4916), or cancer of the breast, lung, large bowel or ovary (n=6320). With the exception of lung cancer, heart failure was associated with the poorest 5-year survival rate (approximately 25% for both sexes). On an adjusted basis, heart failure was associated with worse long-term survival than bowel cancer in men (adjusted odds ratio, 0.89; 95% CI, 0.82-0.97; P<0.01) and breast cancer in women (odds ratio, 0.59; 95% CI, 0.55-0.64; P<0.001). The overall population rate of expected life-years lost due to heart failure in men was 6.7 years/1000 and for women 5.1 years/1000. CONCLUSION: With the notable exception of lung cancer, heart failure is as 'malignant' as many common types of cancer and is associated with a comparable number of expected life-years lost.

Age Factors↗
PubMed2001

Poles apart, but are they the same? A comparative study of Australian and Scottish patients with chronic heart failure.

This paper reports on an international comparison of the characteristics, treatment and health outcomes of chronic heart failure (CHF) patients discharged from acute hospital care in Australia and Scotland. The baseline characteristics and treatment of 200 CHF patients recruited to a randomised study of a non-pharmacological intervention in Australia and 157 CHF patients concurrently recruited to a similar study in Scotland were compared. Subsequent health outcomes (including survival and readmission) within 3 months of discharge in those patients who received usual post-discharge care in Australia (n=100) and Scotland (n=75) were also compared. Individuals in both countries were predominantly old and frail with significant comorbidity likely to complicate treatment. Similar proportions of Australian and Scottish patients were prescribed either a 'high' (20 vs. 18%) or medium (64 vs. 66%) dose of an angiotensin-converting enzyme inhibitor. Proportionately more Australian patients were prescribed a long-acting nitrate, digoxin and/or a beta-blocker. At 3 months post-discharge, 57 of the 100 (57%: 95% CI 47--67%) Australian and 37 of the 75 (49%: 95% CI 38--61%) Scottish patients assigned to 'usual care' remained event-free (NS). Similarly, 15 vs. 12% required > or =2 unplanned readmission (NS) and 16 vs. 19% of Australian and Scottish patients, respectively, died (NS). Australian and Scottish patients accumulated a median of 0.6 vs. 0.9 days, respectively, of hospitalisation/patient/month (NS). On multivariate analysis (including country of origin), unplanned readmission or death was independently correlated with severe renal impairment (adjusted odds ratio 4.4, P<0.05), a previous hospitalisation for CHF (2.3, P<0.05), longer index hospitalisation (2.7 for >10 days, P<0.05) and greater comorbidity (1.3 for each incremental unit of the Charlson Index, P=0.05). Health outcomes among predominantly old and frail CHF patients appear to be independent of the health-care system in which the patient is managed and more likely to be dependent on the syndrome itself.

Aged↗
PubMed2001

Alcoholic liver disease: new insights into mechanisms and preventative strategies.

Alcoholic liver disease has a known aetiology but a complex pathogenesis. It is an extremely common disease with a high mortality, but the reason why only a relatively small proportion of heavy drinkers progress to advanced disease remains elusive. Accumulating evidence points towards an elaborate interplay between metabolism, inflammation and immunity in the development of steatosis, hepatitis and fibrosis. These complex pathways leading to liver injury offer many potential susceptibility loci, as well as sites for potential therapeutic intervention.

Apoptosis↗
PubMed2001

Uniformly (14)C-ring-labeled 2,4-dichlorophenoxyacetic acid: a metabolism study in bluegill sunfish, Lepomis macrochirus.

The fate of 2,4-dichlorophenoxyacetic acid (2,4-D), a mixture of [phenyl(U)-(14)C]-2,4-D and unlabeled 2,4-D, in bluegill sunfish was investigated after exposure to approximately 11 ppm under static conditions for 4 days. Total radioactive residues (TRR) in whole fish increased from 0.41 ppm on day 1 to 0.60 ppm on day 3. TRR levels in fillet (edible) and viscera (nonedible) of treated fish on day 4 were 0.41 and 1.9 ppm, respectively. Most residues in both matrices were acetonitrile soluble; small amounts were hexane soluble or unextractable with solvents. Acid and base hydrolyses with ethyl acetate partitioning were used to release the fillet unextractable residues. The identification of 2,4-D and 2,4-dichlorophenol (2,4-DCP) in the fillet was conclusively confirmed by GC-MS analysis. On the basis of the experimental data from this study, a metabolic pathway for 2,4-D in bluegill sunfish in which the 2,4-D is metabolized to 2,4-DCP and conjugates of 2,4-D and 2,4-DCP is proposed.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2001

T-cell depletion and autologous stem cell transplantation in the management of tumour stage mycosis fungoides with peripheral blood involvement.

Nine patients with tumour stage mycosis fungoides (MF) have been entered into a pilot study of T-cell depletion and autologous stem cell transplantation (SCT). Eight patients had detectable rearrangements of the T-cell receptor (TCR) gamma-gene demonstrated by polymerase chain reaction (PCR)/single-stranded conformation polymorphism (SSCP) in the peripheral blood. The median age was 47 years and the median duration of disease before SCT was 61 months; Peripheral blood progenitor cells were mobilized using high-dose etoposide (1.6 g/m2) and granulocyte colony-stimulating factor (G-CSF). The apheresis products underwent rigorous T-cell depletion with immunomagnetic methods. Double CD34-positive and CD4/CD8-negative selection achieved a median reduction of 3.89 log of T cells. All nine patients have been transplanted. Conditioning included carmustine (BCNU), etoposide and melphalan (BEM) in seven patients and total body irradiation plus etoposide or melphalan in two. Eight patients engrafted promptly and one patient died of septicaemia. All survivors entered complete remission. Seven patients have relapsed at a median of 7 months (2-14) post SCT. However, most patients have relapsed into a less aggressive stage, which has responded to conventional therapy. Four out of seven evaluable patients had detectable TCR rearrangements in the T-cell depleted graft. A T-cell clone was also detected in the peripheral blood before relapse in four cases. Autologous SCT is feasible, safe and can result in complete remission in a significant proportion of patients with tumour stage mycosis fungoides. Despite a short relapse-free survival, most patients achieved good disease control at the time of relapse.

Adult↗
PubMed2001

Trends in hospitalization for heart failure in Scotland, 1990-1996. An epidemic that has reached its peak?

AIMS: Studies in the 1980s and early 1990s showed striking increases in hospitalization rates for heart failure. This report describes contemporary trends in hospitalization for heart failure. METHODS: Scotland (population of 5.1 million) has a well described system for recording details of all hospitalizations. All hospital discharges (and deaths) can be linked to each patient. We examined the period 1990-1996 (158 989 hospitalizations with a principal or secondary diagnosis of heart failure). RESULTS: Compared to 1990, the number of hospitalizations with a principal diagnosis of heart failure increased in men (by 16%) and women (by 12%), although the highest numbers were recorded in 1993 in women (21%) and in 1994 in men (24%). Similar trends were seen for the number of patients hospitalized overall and those having a 'first ever' hospitalization. Hospitalizations with a secondary diagnosis of heart failure increased much more strikingly (by 110% and 60% in men and women, respectively). Re-hospitalization became more common, increasing by 53% and representing 23% of all hospitalizations in 1996. Median length of stay fell (from 9 to 8 days in men and 13 to 10 days in women with a principal diagnosis of heart failure), resulting in 100 877 fewer inpatient days. Heart failure (principal diagnosis) still, however, accounted for 4.2% of all inpatient medicine/geriatric bed-days in 1996. Although inpatient case fatality fell slightly, the total number of deaths due to heart failure (principal diagnosis) increased slightly. CONCLUSIONS: Heart failure continues to be a common cause of hospitalization. The previously reported 'epidemic' of increasing rates of hospitalization for heart failure in Scotland and elsewhere between 1980 and 1990, however, seems to have peaked (in about 1993/4).

Aged↗
PubMed2001

Trends in hospital activity, morbidity and case fatality related to atrial fibrillation in Scotland, 1986--1996.

AIMS: Atrial fibrillation is a common and important cause of cardiovascular morbidity and mortality that may become more prevalent due to an ageing population and more prolonged exposure to predisposing cardiovascular disease states. This study examines recent trends in hospitalizations related to atrial fibrillation in Scotland. METHODS AND RESULTS: Scotland (population 5.1 million) has a well described system for recording hospitalization data. All hospital discharges (and death) can be linked for each individual patient. We examined the period 1986--1996, during which time a total of 103,085 hospitalizations with a principal or secondary diagnosis of atrial fibrillation were recorded. The number of hospitalizations with a principal diagnosis of atrial fibrillation increased threefold from 1869 in 1986 to 5757 in 1996; the number with a secondary diagnosis rose from 3577 to 11,522. Similar increases were seen in the number of patients hospitalized, in those having a 'first-ever' hospitalization and in population hospitalization rates overall. The average age of patients rose, in men from 63.8 (SD 13.2) to 65.0 (13.2) years and in women from 72.2 (12.2) to 73.2 (11.4) years. The proportion of those aged >75 years rose from 33% to 35% in men and from 56% to 60% in women. Average length of stay and case fatality fell during this period, but, because of the overall increase in hospitalizations, atrial fibrillation contributed to a growing proportion of cardiovascular-related bed-days utilized (from 18% to 37% with atrial fibrillation coded in any diagnostic position). CONCLUSION: The number of hospitalizations for atrial fibrillation has increased dramatically (two- to threefold) in recent years. These findings may be due to a real increase in atrial fibrillation prevalence, changing medical practice (e.g. coding or admission thresholds) or both. Consequently, the public health burden of atrial fibrillation is enormous. Moreover, the observed increase in atrial fibrillation-related hospital activity shows no sign of abating.

Age Distribution↗
PubMed2001

Transport risk index of physiologic stability: a practical system for assessing infant transport care.

OBJECTIVES: To develop and validate a practical, physiology-based system for assessment of infant transport care. STUDY DESIGN: Transport teams prospectively collected data, before and after transport, from 1723 infants at 8 neonatal intensive care units (NICUs) from 1996 to 1997. We used logistic regression to derive a prediction model for mortality within 7 days of NICU admission and develop the Transport Risk Index of Physiologic Stability (TRIPS). We validated TRIPS for prediction of 7-day mortality, total NICU mortality (until discharge), and severe (> or =grade 3) intraventricular hemorrhage. RESULTS: TRIPS comprises 4 empirically weighted items (temperature, blood pressure, respiratory status, and response to noxious stimuli). TRIPS discriminated 7-day NICU mortality and total NICU mortality from survival with receiver operating characteristic areas of 0.83 and 0.76, respectively. There was good calibration across the full range of TRIPS scores and gestational age groups. Increase and decrease in TRIPS scores after transport were associated with increased and decreased mortality, respectively. The receiver operating characteristic area for TRIPS prediction of severe intraventricular hemorrhage was 0.74. Addition of TRIPS improved performance of prediction models in which gestational age and baseline population risk variables were used. CONCLUSIONS: TRIPS is validated for infant transport assessment.

APACHE↗