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Biomedical subjects

G Jackson

Publications and source records attributed to G Jackson.

At least 55 records · Page 3Linked to original sources

Pregnancy outcomes after peripheral blood or bone marrow transplantation: a retrospective survey.

BACKGROUND: Some patients treated by transplantation of haemopoietic stem cells (peripheral blood or bone marrow) become permanently infertile, but others retain or recover fertility. We assessed the outcome of conception in women, and partners of men previously treated by autologous or allogeneic stem cell transplantation (SCT). METHODS: We sent questionnaires to 229 centres of the European Group for Blood and Marrow Transplantation. We sought details about the original disease, transplant procedure, and outcome of conception for both male and female patients. FINDINGS: 199 centres gave information relating to 19412 allogeneic and 17950 autologous transplant patients. 232 (0.6%) patients conceived after SCT. Crude annual birth rate for 4-month survivors of SCT was lower than the national average for England and Wales at 1.7 per 1000 patients. 312 conceptions were reported in 113 patients (74 allograft) and partners of 119 patients (93 allograft). Most pregnancies were uncomplicated and resulted in 271 livebirths. 28 (42%) of 67 allograft recipients had caesarean section compared with 16% in the normal population (difference =26% [95% CI 15-38]), 12 (20%) of 59 had preterm delivery compared with a normal rate of 6% (14% [4-24]), and 12 (23%) of 52 had low birthweight singleton offspring compared with a normal rate of 6% (17% [6-29]). INTERPRETATION: Pregnancy after SCT is likely to have a successful outcome. Pregnancies in allograft patients who have received total body irradiation should be treated as high risk for maternal and fetal complications.

Adolescent↗

The phytoestrogen genistein produces acute nitric oxide-dependent dilation of human forearm vasculature with similar potency to 17beta-estradiol.

BACKGROUND: Genistein, a phytoestrogen, may have estrogenic cardioprotective actions. We investigated whether genistein influences endothelium-dependent vasodilation in forearm vasculature of healthy human subjects and compared the effects of genistein with those of 17beta-estradiol. METHODS AND RESULTS: The brachial arterial was cannulated with a 27-gauge needle for drug infusion. Forearm blood flow responses were measured with strain-gauge plethysmography. Genistein (10 to 300 nmol/min, each dose for 6 minutes) produced a dose-dependent increase in forearm blood flow from 3.4+/-0.3 to 9.6+/-1.3 mL x min(-1) x 100 mL forearm(-1) (mean+/-SEM) in men (n=9, P:<0.0001 by ANOVA). The mean forearm venous concentration of genistein during infusion of the highest dose was 1.8+/-0.3 micromol/L in 6 additional men. Genistein produced a similar increase in blood flow in premenopausal women. Daidzein, another phytoestrogen, was ineffective, but equimolar concentrations of 17beta-estradiol caused similar vasodilation to genistein. Responses to genistein and 17beta-estradiol were inhibited to the same degree by the NO synthase inhibitor N:(G)-monomethyl-L-arginine. A threshold dose of genistein potentiated the endothelium-dependent vasodilator acetylcholine but not the endothelium-independent vasodilator nitroprusside. CONCLUSIONS: Genistein causes L-arginine/NO-dependent vasodilation in forearm vasculature of human subjects with similar potency to 17beta-estradiol and potentiates endothelium-dependent vasodilation to acetylcholine.

Acetylcholine↗

Digital processing of radiographic images from PACS to publishing.

Several studies have addressed the implications of filmless radiologic imaging on telemedicine, diagnostic ability, and electronic teaching files. However, many publishers still require authors to submit hard-copy images for publication of articles and textbooks. This study compares the quality digital images directly exported from picture archive and communications systems (PACS) to images digitized from radiographic film. The authors evaluated the quality of publication-grade glossy photographs produced from digital radiographic images using 3 different methods: (1) film images digitized using a desktop scanner and then printed, (2) digital images obtained directly from PACS then printed, and (3) digital images obtained from PACS and processed to improve sharpness prior to printing. Twenty images were printed using each of the 3 different methods and rated for quality by 7 radiologists. The results were analyzed for statistically significant differences among the image sets. Subjective evaluations of the filmless images found them to be of equal or better quality than the digitized images. Direct electronic transfer of PACS images reduces the number of steps involved in creating publication-quality images as well as providing the means to produce high-quality radiographic images in a digital environment.

Analysis of Variance↗

The influence of plasma lipoprotein (a) on angiographic restenosis and coronary events in patients undergoing planned coronary balloon angioplasty. Ancillary analysis of the Fluvastatin Angioplasty Restenosis (FLARE) trial.

Elevated Lipoprotein (a) [Lp (a)] has been reported frequently, but not consistently, to be associated with restenosis following percutaneous transluminal coronary angioplasty (PTCA). The purpose of this study was to examine the association between Lp (a) and restenosis and clinical events in the context of a multi-centre randomised restenosis [Fluvastatin Angioplasty Restenosis (FLARE)] study of patients undergoing elective PTCA with full angiographic follow up. In the FLARE trial 40 mg fluvastatin twice daily did not influence restenosis, compared with placebo, after successful balloon angioplasty, measured as late loss in 834 patients, but did reduce the risk of death or myocardial infarction. Lp (a) was not effected by fluvastatin. Lp (a) and other biochemical details were established prior to planned PTCA. Among those undergoing successful PTCA, follow up angiography was performed at 26+/-2 weeks. Clinical follow up was complete to week 40. Included in this analysis are the 823 patients who underwent successful angioplasty and had a baseline Lp (a) performed yielding 891 lesions for quantitative coronary angiography (QCA). No association was observed between Lp (a) and either quantitative markers of restenosis or binary restenosis rates. Late loss was 0.27 (SD 0.51) in the lowest quintile (Lp (a) 0-4 g/dl) compared with 0.23 (SD 0.49) (P>0.05). Elevated Lp (a) was not associated with an increased risk of individual or combined major coronary events over 40 weeks. A major adverse cardiac event (MACE) occurred in 41 (24%) of the lowest quintile and 42 (26%) of the highest (P>0.05). In conclusion, elevated Lp (a) was not associated with restenosis or clinical events following elective coronary balloon angioplasty in this randomised clinical trial and should not be considered a risk factor for post angioplasty restenosis.

Angioplasty, Balloon, Coronary↗

Growing reproducible biofilms with respect to structure and viable cell counts.

We have developed a new method of growing 4-day-old biofilms that are reproducible, with respect to viable cell number and biofilm structure. To demonstrate the utility of the method, we grew biofilms composed of Pseudomonas aeruginosa (ATCC#700829), P. fluorescens (ATCC#700830) and Klebsiella pneumoniae (ATCC#700831), 18 times in flat-plate reactors under well-defined conditions of: flow rate, nutrient concentration, temperature, inoculum and growth rate. The resulting 4-day-old biofilms were approximately 200-300 microm thick and exhibited a high degree of reproducibility. The number of viable cells that accumulated per unit surface area and the biofilm areal porosity were reproduced within 10% error. We have also quantified other parameters characterizing biofilm structure using biofilm-imaging techniques: fractal dimension, textural entropy and diffusion distance as auxiliary parameters characterizing the reproducibility of biofilm accumulation. As a result of analysis, we have introduced a new parameter to better quantify and characterize the number of viable cells in biofilms, "specific number of viable cells" (SNVC). This parameter is the viable cell number normalized with respect to the surface area covered by the biofilm and with respect to the biomass of the biofilm. This new descriptor represents the dynamics of biofilm accumulation better than the traditionally used colony-forming unit (CFU) per surface area covered by the biofilm because it accounts not only for the surface coverage but also for the biofilm thickness.

Bacteriological Techniques↗

Histological correlation between different centers using the skin explant model to predict graft-versus-host disease following bone marrow transplantation.

Acute graft-versus-host disease (GVHD) remains the major complication of allogeneic stem cell transplantation (SCT) with an incidence of 40-60% and a mortality of up to 50%. Several assays have been developed to try to predict the development of GVHD including the mixed lymphocyte culture reaction, cytotoxic and helper T lymphocyte precursor frequency assays. In the Northern region of England we have used an in vitro skin explant model for predicting GVHD in MHC compatible bone marrow transplant recipients since 1988. The aims of the present study was to test the reproducibility of the model in two other bone marrow transplant centers in Europe. The assay consists of incubating patient skin explants with effector cells from mixed donor versus recipient lymphocyte cultures and the subsequent detection of graft-versus-host reactions by histopathological grading (0-IV) of the skin explants. 503 slides from 134 patients were evaluated. All were graded for negative GVHR grade 0-I or positive grade II-IV. Results from control and test slides significantly correlated between centers to the p value of 0.0001 by Fisher's exact probability test. These results show that the skin explant assay is reproducible between centers and supports the continued use of the assay to predict GVHD in allogeneic stem cell transplant recipients.

Biopsy↗

Endothelium-dependent vasodilation is independent of the plasma L-arginine/ADMA ratio in men with stable angina: lack of effect of oral L-arginine on endothelial function, oxidative stress and exercise performance.

OBJECTIVES: This study was designed to determine the effect of two weeks' treatment with L-arginine on the ratio of plasma L-arginine to asymmetric dimethylarginine (ADMA), oxidative stress, endothelium-dependent vasodilatation to acetylcholine, exercise performance and heart rate variability in men with stable angina. BACKGROUND: The ratio of plasma L-arginine:ADMA has been proposed as a determinant of endothelium-dependent dilation; dietary supplementation with L-arginine has been shown to improve endothelium-dependent vasodilation and symptoms in some conditions. METHODS: Men (n = 40) with stable angina, at least one epicardial coronary artery with a stenosis >50% and a positive exercise test were randomized to receive L-arginine (15 g daily) or placebo for two weeks according to a double-blind parallel-group design. Plasma L-arginine, ADMA, 8-epi-prostaglandin F2alpha (a marker of oxidative stress) and forearm vasodilator responses to brachial artery infusion of nitroprusside and acetylcholine (+/-L-arginine) were measured. A standard Bruce protocol exercise test was performed before and at the end of the treatment period. RESULTS: Plasma L-arginine increased after oral L-arginine, whereas ADMA remained unchanged, leading to an increase in the L-arginine/ADMA ratio of 62 +/- 11% (mean +/- SE, p < 0.01). Despite a significant enhancement in acetylcholine response by intra-arterial L-arginine at baseline, this response remained unchanged after oral L-arginine. Measures of oxidative stress and exercise performance after L-arginine/placebo were similar in placebo and active groups. CONCLUSIONS: In men with stable angina, an increase in plasma L-arginine/ADMA ratio after two weeks' oral supplementation with L-arginine is not associated with an improvement in endothelium-dependent vasodilatation, oxidative stress or exercise performance.

Administration, Oral↗

Accelerated telomere shortening following allogeneic transplantation is independent of the cell source and occurs within the first year post transplant.

Telomere shortening has been documented in the blood cells of recipients of allogeneic bone marrow transplants compared with their donors. Allogeneic peripheral blood progenitor cells (PBPCs) have been increasingly used as an alternative to bone marrow. Their advantages include earlier engraftment and immune reconstitution following transplantation. We have measured telomere length of neutrophils and T cells in fully engrafted recipients of allogeneic bone marrow (n = 19) and allogeneic PBPC (n = 17) and also measured sequential telomere length in four patients after transplantation. Overall, significant telomere shortening occurred in recipients in neutrophils (0.3 kb, P < 0.001) and T cells (0.2 kb, P = 0.045). The data demonstrate that first, the degree of shortening was the same for BM and PBPC transplants and was not related to the time taken to engraft neutrophils and platelets and second, telomere shortening occurs in the first year post transplant without further shortening during the period of observation. These data suggest that the superiority of engraftment seen in PBPC transplants is independent of telomere shortening and other mechanisms such as homing or seeding may be more important.

Adolescent↗

Assessment of forearm vasodilator responses to acetylcholine and albuterol by strain gauge plethysmography: reproducibility and influence of strain gauge placement.

AIMS: To determine the within-subject reproducibility of the forearm blood flow response to acetylcholine and the beta2-adrenoceptor agonist albuterol as measured by strain gauge plethysmography. To examine the influence of strain gauge placement on these responses. METHODS: Vasodilator response to brachial artery infusion of drugs was assessed by strain gauge plethysmography in six healthy men on each of three occasions separated by 1 week. Strain gauges were placed on both arms at the point of maximum diameter. On the infused arm two further gauges were positioned approximately 4 cm proximal and distal to the middle gauge. RESULTS: Within-subject coefficients of variation (WCV) of absolute blood flow responses for each dose of acetylcholine (7.5, 15, 30 micrograms min(-1)) ranged from 24% to 27%, as compared with WCV values of 41% to 62% for the percentage changes in blood flow ratio (infused : noninfused arm). For albuterol (0.3, 1, 3 micrograms min(-1)) the corresponding WCV values were 16% to 19% and 30% to 55% for absolute blood flow and percentage change in blood flow ratio, respectively. WCV for the area under dose-response curve (AUC) for absolute blood flow was 18% and 13% for acetylcholine and albuterol, respectively. Vasodilator responses were similar whether recorded proximal to or at the point of maximal forearm circumference. Distal strain gauge misplacement underestimated responses and the difference was greater for acetylcholine than for albuterol. CONCLUSIONS: In healthy men, the WCV for responses expressed as absolute blood flow, to acetylcholine and albuterol ranges from 16% to 27%.

Acetylcholine↗

A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation.

The primary objective of this study was to determine the complete remission (CR) rate achieved with the FLAG (fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor) regimen in patients with relapsed or refractory acute myeloid leukaemia (AML) or de novo refractory anaemia with excess of blasts in transformation (RAEB-t). Secondary objectives were to evaluate survival and toxicity. Induction treatment consisted of between one and two courses of FLAG. Patients achieving CR received between one and two courses of consolidation treatment. Eighty-three of the 89 patients entering the study were eligible for assessment. CR rates were: 17 out of 21 (81%) in late relapse AML (Group 1), 13 out of 44 (30%) in early relapse/refractory AML (Group 2), and 10 out of 18 (56%) in de novo RAEB-t (Group 3). Thirty-four of the 40 responders (85%) achieved CR after one induction course. Median survival times were 1.4 years, 3 months and 1.6 years in Groups 1, 2 and 3 respectively. Other than myelosuppression, the FLAG regimen was not generally associated with clinically significant toxicity and was well tolerated by most patients including the elderly. The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB-t. FLAG delivers high-dose treatment without increasing overall toxicity, an approach which is of particular value in older patients, who constitute the majority in these diseases. It is therefore an important advance in developing new treatment options for these patients.

Acute Disease↗

Hospital utilisation expectancies in New Zealand, 1980-98.

The need to synthesise mortality and morbidity information to achieve a more global and relevant measure of population health status is well recognised, with health expectancy indices being the most common approach used to date. Using New Zealand hospital discharge and mortality data over the 1980-98 period, we introduce readers to a newly developed health index, the Hospital Utilisation Expectancy (HUE). We describe how HUE changes with age and over time. New Zealand national and regional trends are described. The methodological strengths of the measure and its applications in the health sector are discussed.

Adolescent↗

Avoidable mortality in New Zealand, 1981-97.

OBJECTIVE: To describe avoidable mortality in New Zealand, including trends and variations between groups by age, gender, ethnicity and degree of deprivation. METHOD: New Zealand Health Information Service mortality unit records, 1981 to 1997, were classified as 'avoidable' or 'unavoidable' based on a reassessment of ICD9 codes and an upper age limit of 75 years. 'Avoidable' causes of death were further subcategorised according to the level of intervention involved (primary, secondary or tertiary). Deaths were assigned a deprivation score using a Census-based small area deprivation index, the NZDep96. Mortality rates were age standardised by the direct method, with Segi's world population as the reference. RESULTS: Avoidable mortality declined 38% from 1981 to 1997; unavoidable mortality declined only 9%. In 1996-97 almost 70% of deaths in the 0-74 age range were still considered to be potentially avoidable. Almost 80% of avoidable deaths occur in the 45-74 age group. These deaths are dominated by the emergence of chronic diseases such as ischaemic heart disease, diabetes and smoking-related cancers. In younger age groups, injury (including suicide) dominates avoidable mortality. Males experience a greater burden of avoidable mortality than females--a relative excess of 54% (approximately 2,000) in 1996-97. The gender difference is largely attributable to diseases and injuries amenable to primary prevention, with the largest single contribution coming from ischaemic heart disease. The ethnic gap in avoidable mortality remains wide: rates for Mäori and Pacific people were 2-2 1/2 times higher than European rates in 1996-97. Similar gradients are seen with deprivation. CONCLUSION AND IMPLICATIONS: Avoidable mortality analysis provides a useful tool for evidence-based health needs assessment and health policy development.

Acute Disease↗

Potentially avoidable hospitalisations in New Zealand, 1989-98.

OBJECTIVE: To describe potentially avoidable hospitalisation in New Zealand, including recent trends and variations between groups differentiated by age, gender, ethnicity and degree of deprivation. METHOD: Hospital discharges among people aged 0-74 years for the years 1989-98 were classified as 'potentially avoidable' or 'unavoidable' based on the ICD9-CMA code of the principal diagnosis. Potentially avoidable hospitalisations (PAH) were further subcategorised according to the intervention involved--primary prevention, ambulatory care or injury prevention. RESULTS: By 1998, one in three of these hospitalisations was theoretically avoidable--two-thirds of these through more effective primary health care services. Although in practice only a proportion of these could realistically have been avoided, these estimates reveal considerable scope for further reduction in the incidence of serious disease and injury. Maori and Pacific people had age-standardised PAH rates approximately 60% higher than European and other New Zealanders. Similar discrepancies exist by socio-economic deprivation. Had all New Zealanders enjoyed the PAH rates of the most advantaged 40% of the population, 28% fewer potentially avoidable hospitalisations would have occurred in 1998, some 26,000 hospital admissions. CONCLUSION: This analysis has revealed significant scope for the health sector to contribute to population health gain and, in particular, to improvement in equity of outcomes across ethnic and socio-economic groups. Potentially avoidable hospitalisations provide a useful tool for evidence-based population health needs analysis and health policy development.

Adolescent↗

Haemodynamic and metabolic agents in the treatment of stable angina: publication review.

Many patients with stable angina pectoris are over-treated with haemodynamic agents. Understanding the different mode of action of the metabolic agent trimetazidine offers us the opportunity to implement effective combination therapy. Patients who fail to respond to optimal haemodynamic and metabolic therapy should be considered for a revascularisation procedure, not random additional drug therapy.

Angina Pectoris↗