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Biomedical subjects

J Dunn

Publications and source records attributed to J Dunn.

At least 73 records · Page 4Linked to original sources
PubMed1998

Cellular alloreactivity of human cord blood cells detected by T-cell frequency analysis and a human skin explant model.

BACKGROUND: Recent clinical data have demonstrated the success of allogeneic stem cell transplantation using HLA-mismatched unrelated human umbilical cord blood (CB). The incidence and severity of acute graft-versus-host disease (GVHD) in these mainly pediatric transplants is low. The immunological mechanisms by which CB transplants may result in reduced GVHD is not completely clear. In this study, the functional cellular alloreactivity of CB cells was investigated, by measuring the frequency of alloreactive helper and cytotoxic T lymphocyte precursors (HTLp and CTLp, respectively) in CB and detecting the ability of CB cells to induce graft-versus-host (GVH) type alloreactivity in vitro. METHODS: A human skin explant model was used to measure GVH type alloreactivity in vitro. A combined limiting dilution assay was carried out in parallel to determine alloreactive HTLp and CTLp frequencies. The cellular alloreactivity was compared between cord and HLA-haploidentical parental blood cells against the same HLA-mismatched unrelated stimulator. RESULTS: The results demonstrated that alloreactive CTLp frequency in CB mononuclear cells (CBMCs) was significantly lower (mean, 1:35,694, range, 1:1,667-<1:500,000) than that in adult peripheral blood mononuclear cells (PBMCs) (mean, 1:5,333, range, 1:544-1:47,619). Alloreactive HTLp frequencies, however, were comparable for CBMCs and PBMCs (mean, 1:7,586, range, 1:1,359-1:200,000; and mean, 1:5,976, range, 1:385-1:50,000, respectively). A significantly decreased ability to induce in vitro GVH type alloreactivity was observed for CBMCs and that was strongly associated with low alloreactive CTLp frequencies (P=0.001). CONCLUSIONS: The present study provides the first clear in vitro evidence to suggest that CBMCs are less able than PBMCs to induce skin GVH type alloreactivity in HLA-mismatched pairs. The severity of in vitro GVH type alloreactivity (graded as I-IV) was strongly associated with the levels of alloreactive CTLp frequencies. The low cellular alloreactivity of CBMCs detected in vitro suggests that in a proportion of cases HLA-mismatched unrelated CB may not give rise to severe GVHD in vivo after transplantation.

Blood Cells↗
PubMed1998

Relation of a common mutation in methylenetetrahydrofolate reductase to plasma homocysteine and early onset coronary artery disease.

OBJECTIVE: In the presence of low serum folate, mutant 5,20-methylenetetrahydrofolate reductase (MTHFR + [A223V/C677T]) in the homozygous state (+/+), may predispose to higher plasma homocysteine (tHct) levels and coronary artery disease (CAD). To determine the impact of this relationship on predisposition to early-onset CAD, we examined the prevalence of the mutation and plasma tHct in patients with early-onset CAD and compared them to patients manifesting CAD later in life. METHODS: Three hundred patients with history of acute myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients consisted of two groups: group 1 (G1 = 150 patients) presenting with these findings under age 50; while group 2 (G2 = 150) presented for the first time over age 65 years. Prevalence of the MTHFR+ mutation was assessed by molecular analysis, and plasma tHct and folate were measured. An association of the +/+ genotype with early onset CAD could lead to its higher prevalence in the younger age group. RESULTS: There was no significant difference in the frequency of the (+/+) genotype between the two groups (G1: 11.3% vs. G2: 11.3%). However, patients with the (+/+) genotype in both groups had higher tHct when plasma folate was below the mean value (G1: p < 0.0001 while G2: p < 0.01). CONCLUSION: The mutant MTHFR genotype was not found to be a determining factor in early-onset CAD. Higher tHct values were obtained in the older age group, which is expected because other studies have shown that tHct levels increase with age. A significant relation was shown between MTHFR genotype and low folate status yielding high tHct levels in those with the (+/+) genotype. As this relation was seen in both groups, although to a lesser extent in the older G2, it does not explain the underlying cause of early-onset CAD.

Age of Onset↗
PubMed1998

Five-year follow-up of a prospective randomised multi-centre trial of weekly chemotherapy (CAPOMEt) versus cyclical chemotherapy (CHOP-Mtx) in the treatment of aggressive non-Hodgkin's lymphoma. Central Lymphoma Group.

BACKGROUND: Weekly alternating regimen known as CAPOMEt is compared to standard cyclical chemotherapy (CHOP-Mtx) in aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Three hundred and eighty-one patients with aggressive NHL were randomised to receive either cyclophosphamide, doxorubicin, vincristine, prednisone and methotrexate (CHOP-Mtx) on a cyclical basis or a weekly regimen incorporating the same drugs with the addition of etoposide (CAPOMEt). RESULTS: After pathological review, 281 patients were deemed eligible. At the census date of 31 March 1994, 158 patients were alive with a median follow up of 5.9 years (minimum 3.0 years). Analysis of all patients and eligible patients showed no significant treatment differences in the rates of complete remission (CR), failure free survival (FFS) or overall survival (OS) between the two arms. The actuarial median OS was 24 months for CAPOMEt compared with 31 months for CHOP-Mtx, with five-year actuarial survival rates of 37% and 43%, respectively. Myelosuppression was significantly more severe with CHOP-Mtx and neurotoxicity was much more common with CAPOMEt. CONCLUSION: Weekly CAPOMEt is equally effective as standard cyclical CHOP-Mtx treatment in aggressive NHL.

Adolescent↗
PubMed1998

Understanding mind and emotion: longitudinal associations with mental-state talk between young friends.

Developmental changes in children's understanding of mind and emotion and their mental-state talk in conversations with friends were examined in a longitudinal study of 50 children (M age at each time point = 3 years 11 months, 4 years 6 months, 5 years 0 months). Significant and related improvements over time were found for both theory-of-mind task performance and affective perspective taking. Associated with these cognitive developments were quantitative and qualitative changes in children's references to mental states in their conversations with friends. Individual differences in theory of mind, emotion understanding, and mental-state talk were strikingly stable over the 13-month period. Although there were no gender differences in children's task performances, girls showed more frequent and more developed mental-state talk than boys.

Child, Preschool↗
PubMed1998

A randomized trial of the effect of clodronate on skeletal morbidity in multiple myeloma. MRC Working Party on Leukaemia in Adults.

In patients with multiple myeloma, despite a major reduction of bone pain achieved with chemotherapy, skeletal disease continues to progress. The effects of clodronate, an inhibitor of osteoclastic bone resorption, are evaluated on the natural history of skeletal disease in patients with newly diagnosed multiple myeloma. Within the framework of the VIth MRC Multiple Myeloma Trial, 536 patients (218 women, 318 men) with recently diagnosed multiple myeloma were randomized to receive either clodronate 1600 mg daily (n=264) or an outwardly identical placebo (n=272) in addition to chemotherapy. Treatment with clodronate was associated with a 50% decrease in the proportion of patients with severe hypercalcaemia (5.1% v 10.1%, P=0.06) and a similar reduction in reported non-vertebral fractures (6.8% v 13.2%, P=0.04). Fewer patients receiving clodronate sustained vertebral fractures after entry to the trial (38% v 55%, P=0.01) and patients also lost less height over 3 years compared to those receiving placebo (2.0 v 3.4 cm, P=0.01). Biochemical indices of bone turnover were significantly lower in patients receiving concomitant clodronate, both at plateau and at disease relapse. The frequencies of back pain and poor performance status were significantly lower at 24 months in clodronate than in placebo-treated patients (10.9% v 19.9%, P=0.05, and 18.3% v 30.5% P=0.03 respectively.) There was no statistically significant difference in survival between the clodronate and placebo treated patients. The study indicates that long-term oral clodronate slows the progression of skeletal disease in multiple myeloma and decreases the associated morbidity. Patients without overt skeletal disease at diagnosis were also found to benefit from clodronate, indicating that this treatment should be initiated as early in the course of the disease as possible.

Aged↗
PubMed1998

Screening for gastric cancer by Helicobacter pylori serology: a retrospective study.

BACKGROUND: Screening by serology for Helicobacter pylori in young dyspeptic patients has been shown to be effective in reducing demand for endoscopy. H. pylori has been implicated in the causation of gastric cancer and the reported seropositivity rate in patients with gastric cancer ranges from 69 to 94 per cent. The aim of this study was to assess the potential value of Helicobacter antibodies as a method of selecting dyspeptic patients over the age of 45 years for endoscopy. METHODS: A retrospective comparison of the antibody status to H. pylori was made between 154 patients with gastric cancer and a sex- and date of birth-matched dyspeptic control group. Results from the former group were correlated with demographic data and tumour characteristics. RESULTS: Significantly more patients with gastric cancer were seropositive than controls (77 versus 66 per cent). H. pylori was not related to the Laurén classification of the tumour. Tumour site was significant: body and antrum tumours were associated with Helicobacter whereas cardial tumours appeared to be unrelated. CONCLUSION: Screening by antibody assays to H. pylori would miss more than 30 per cent of current gastric cancers. The increasing incidence of cardial cancer would cause this percentage to rise in the future.

Adult↗
PubMed1998

The development of dysplasia and adenocarcinoma during endoscopic surveillance of Barrett's esophagus.

OBJECTIVE: Periodic endoscopic surveillance is generally recommended for patients with Barrett's esophagus. The optimal follow-up strategy for uncomplicated Barrett's esophagus is controversial, in part because of limited data on the rate of neoplastic progression (through the sequence of metaplasia-dysplasia-carcinoma) during endoscopic surveillance. This study aims to quantify the development of dysplasia in patients with uncomplicated Barrett's esophagus and to explore clinical risk factors associated with the development of dysplastic lesions. METHODS: We identified 102 patients with endoscopic evidence of Barrett's esophagus and the presence of specialized columnar epithelium who had received endoscopic surveillance for adenocarcinoma at our medical center between 1970 and 1994. We abstracted endoscopic and histologic data from the medical record. All specimens that showed any degree of atypia (per report) were reexamined in blinded fashion by a team of study pathologists who indicated the grade of dysplasia. Time to first diagnosis of dysplasia was plotted using Kaplan-Meier survival curves, and risk factors for development of dysplasia were assessed using Cox regression. RESULTS: During 563 patient-yr of endoscopic follow-up, three patients developed adenocarcinoma at least 4 yr after initial diagnosis (one developed adenocarcinoma of the cardia, which was incidentally detected during surveillance for Barrett's esophagus). At some point during follow-up, 19 patients developed new onset, low grade dysplasia and four developed high grade dysplasia. None of the patients who had received antireflux surgery developed dysplasia. CONCLUSION: If confirmed by larger follow-up studies, our results suggest that surveillance endoscopy can be safely deferred for at least 2 yr following an initial biopsy that is negative or indeterminate for dysplasia. Adoption of this approach would substantially reduce the cost of surveillance for adenocarcinoma. Future trials should explore the role of antireflux surgery in protecting against neoplastic transformation of Barrett's esophagus.

Adenocarcinoma↗
PubMed1998

Predictors of crop diversification: a survey of tobacco farmers in North Carolina (USA).

OBJECTIVE: To assess the attitudes and behaviours of North Carolina tobacco farmers around crop diversification. DESIGN: Cross-sectional telephone survey. PARTICIPANTS: Active tobacco farmers in 14 North Carolina counties (n = 1236), interviewed between January and April 1997 (91% response rate). OUTCOME MEASURES: Interest in, experience with, and perceived barriers to diversification. RESULTS: Most farmers (95%) grew/raised a commodity other than tobacco (mean = 2.8). A total of 60% of farmers expressed interest in trying other on-farm activities to supplement their tobacco and 60% reported taking action in the past year around supplementation. Younger age and college education were positively associated with interest. College education, off-farm income, and larger farm size were associated with the number of actions taken. For perceived external barriers to diversification, use of tobacco, percent income from tobacco, lack of college education, and younger age were most strongly associated with the number of barriers. For internal barriers (personal factors), percent income from tobacco, use of tobacco, and lack of college education were most strongly associated with the number of barriers. CONCLUSIONS: Most farmers were involved in diverse operations and expressed interest in continuing to diversify, although the breadth of diversification was narrow. Farmers noted many barriers to diversifying. If conventional production and marketing techniques are employed for non-tobacco alternatives, these alternatives may not provide the sustainable profitability that tobacco has afforded. Competition from foreign tobacco growers is the primary threat to the future of American growers and tobacco dependent communities.

Adult↗
PubMed1998

Relation of HFE gene mutations, high iron stores and early onset coronary artery disease.

OBJECTIVE: To determine the impact of mutations in the HFE gene (human leukocyte antigen H) on predisposition to coronary artery disease (CAD) in patients not diagnosed with hereditary hemochromatosis. BACKGROUND: Elevated iron stores can predispose to acute myocardial infarction. Two mutations (C282Y and H63D) in the novel major histocompatibility complex (MHC) class 1 gene HFE were found in most patients with hereditary hemochromatosis causing high iron stores. The effect of these mutations on predisposition to CAD has not been investigated previously. METHODS: Three hundred patients with a history of myocardial infarction or angina pectoris and angiographically documented CAD were studied. Patients were divided into two groups: group 1 (150 patients), manifesting early onset CAD and presenting with these findings under age 50 years; and group 2 (150 patients), presenting for the first time over age 65 years. Prevalence of the C282Y and H63D mutations was assessed by molecular analysis, and plasma ferritin was measured immunochemically. RESULTS: There was no difference in the prevalence of homozygous, heterozygous or compound heterozygous (C282Y/H63D) states between the groups. Males in group 1 had higher plasma ferritin than those in group 2 (234 +/- 174 micrograms/L versus 136 +/- 103 micrograms/L, P < 0.0001), but this was not significantly different in females (75 +/- 54 micrograms/L versus 92 +/- 73 micrograms/L, P = 0.26). Ferritin remained higher in group 1 than in group 2 males after exclusion of mutation carriers (195 +/- 121 micrograms/L versus 109 +/- 76 micrograms/L, respectively, P < 0.0001), but did not change in females. CONCLUSIONS: Higher iron stores were found in males with early onset CAD. This association was not related to the C282Y or H63D mutation in HFE. It is suggested that association of the MHC locus with delayed onset CAD is probably unrelated to HFE in these patients, and that HFE mutations are not a major risk factor in the development of high iron stores in early onset CAD.

Coronary Disease↗
PubMed1998

Domains of distress: the experience of breast cancer in Australia.

PURPOSE/OBJECTIVES: To describe difficulties experienced by women after treatment for primary breast cancer. DESIGN: Descriptive and exploratory. SETTING: Queensland, Australia. SAMPLE: 245 women (70% response rate) less than 16 weeks postsurgery for breast cancer completed a survey. The mean age for this sample was 55 years; 71% had undergone mastectomy, and 29% had undergone conservative breast surgery. METHODS: Focus groups were used to generate items for the survey, "Experience of Breast Cancer Questionnaire" (EBCQ). The EBCQ and the psychological subscale of the Rotterdam Symptom Checklist (RSCL) were administered by mail to the sample. MAIN RESEARCH VARIABLES: Psychological distress, fear of recurrence, decisional uncertainty, informational support, self-image and social relationships, sexual morbidity, and physical effects of treatments. FINDINGS: Factor analysis of the EBCQ identified five factors, accounting for 60% of the variance. These included psychological effects, treatment concerns, physical effects, self-image, and chemotherapy effects. Four of the five subscales had reliability coefficients of greater than 0.80. Psychological effects included cognitive and emotional effects. Treatment concerns included decisional uncertainty and poorly perceived informational support. Physical effects reflected the symptom pattern of axillary dissection. Self-image included breast loss and social isolation. CONCLUSIONS: Nurses who assist women in adjusting to breast cancer should consider the effect of fear of recurrence and perceptions of body image on the recovery process. Because participation in treatment decisions may increase the demands on women at diagnosis, informational support appropriate to each woman's needs is essential. How self-esteem can affect self-image and social relationships after breast cancer requires further investigation. IMPLICATIONS FOR NURSING PRACTICE: Understanding the experience of illness from the perspective of the patient assists nurses in validating their nursing practice and provides clinically relevant information to guide intervention. In particular, supportive psychological care should target both emotional and cognitive responses to breast cancer. Informational support is integral to a patient's satisfaction with treatment decisions and is likely to predict adjustment. When assisting women to adjust to self-image changes, nurses may need to target women's perceptions about their body image.

Body Image↗
PubMed1998

Trick or treat?: uneven understanding of mind and emotion and executive dysfunction in "hard-to-manage" preschoolers.

It is widely recognised that impaired social relations are characteristic of school-aged children with behavioural disorders, and predict a poor long-term outcome (Parker & Asher, 1987). However, little is known about the early antecedents of social impairment in behaviourally disturbed children. The aim of the present study was to explore three areas of potential dysfunction in younger children: theory of mind, emotion understanding, and executive function. Forty preschoolers, rated by their parents on the Strengths and Difficulties Questionnaire (Goodman, 1994) as "hard to manage" (H2M) were compared with a control group on a set of: (1) theory of mind tasks (including an emotion prediction task involving either a nice or a nasty surprise); (2) emotion understanding stories (that required affective perspective-taking skills as well as situational understanding); and (3) simple executive function tasks (adapted for preschoolers, and tapping inhibitory control, attentional set-shifting, and working memory). Small but significant group differences were found in all three cognitive domains. In particular, hard-to-manage preschoolers showed poor understanding of emotion and executive control, poor prediction or recall of a false belief, and better understanding of the belief-dependency of emotion in the context of a trick than a treat. Moreover, executive function was associated with performance on the theory of mind tasks for the hard-to-manage group alone, suggesting both direct and indirect links between executive dysfunction and disruptive behaviour.

Affect↗
PubMed1998

Children's adjustment and prosocial behaviour in step-, single-parent, and non-stepfamily settings: findings from a community study. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

The adjustment and prosocial behaviour of 4-year-old children and their older siblings growing up in step-parent or single-parent families, or with two biological parents, was investigated within a longitudinal community study, the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC). Mean differences in mothers' perception of adjustment were found for children in different family settings, with higher levels of problems and lower prosocial scores reported for those in single- and step-parent families than those in non-stepfamilies. Individual differences within each family setting were marked. With the exception of single parenthood, which remained a risk indicator for the 4-year-olds, the contribution of family type to differences in adjustment and prosocial behaviour largely disappeared when account was also taken of negativity in family relationships, maternal age, education level, depressive symptomatology, and history of previous live-in relationships, mothers' support networks, and the family's current financial and housing circumstances. Boys remained more at risk for adjustment difficulties than girls when this range of factors was taken into account. The limitations and implications of these findings on a community sample, a first step in a programme of research into family processes in children's adjustment, are discussed.

Adolescent↗