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Biomedical subjects

D Jones

Publications and source records attributed to D Jones.

At least 37 records · Page 2Linked to original sources

Two-year results from the asthma self-management program: long-term impact on health care services, costs, functional status, and productivity.

Participants in a variety of health plans, clinics and employer groups were invited to participate in the Asthma Self-Management Program (ASMP), an education program designed to improve self-management skills and daily functioning in individuals with asthma. The ASMP is an 8-week classroom program that provides information on the respiratory system, trigger avoidance, use of monitoring techniques and asthma medications. After program completion, graduates were contacted at scheduled intervals to reinforce performance of behaviors that are important to asthma self-management and to collect outcomes data. This paper reports the results of 2 years of follow-up with these individuals.

Absenteeism↗

Bisphenol a binds to the low-affinity estrogen binding site.

Environmental estrogens are suspected of being involved in the current increase in the incidence of human reproductive malfunctions, such as a decrease in male reproductive capacity and an increased incidence of breast cancer in women. The influences of these compounds have been proposed to be mediated through binding to macromolecules, such as estrogen receptor alpha or beta. In this study we examined whether the low-affinity Type II estrogen binding site (Type II EBS), originally identified in the rat uterus, is a possible mediator of environmental estrogens such as bisphenol A (BPA). Analysis of BPA's binding to an enriched fraction of Type II EBS, using a competition assay, indicated that BPA was able to compete with estradiol in binding to this site. At a concentration of 10-15 microM (comparable to that required to induce uterine proliferation), BPA inhibited the binding of estradiol to Type II EBS by greater than 50%. The binding affinity of BPA for the Type II EBS was only 8-10-fold lower than that of the synthetic estrogen diethylstilbestrol. The binding of BPA to Type II EBS appeared specific to BPA, in that endosulfan, another environmental estrogen, failed to displace estradiol from the site. A comparison of the relative binding affinities of BPA for rat uterine estrogen receptor alpha to that of the Type II EBS implies that BPA preferentially binds to the Type II EBS.

Animals↗

Health status assessments using the Veterans SF-12 and SF-36: methods for evaluating otucomes in the Veterans Health Administration.

This article describes a study in which the administration of two health surveys, the Veterans SF-36 and SF-12, by telephone and mail-out was used to assess the differences in the health surveys' costs and scores by mode of administration and determine which mode was cost-efficient. The study employed a crossover design: after 12 unsuccessful attempts to contact patients by telephone, the patients were administered the survey by mail, and after 2 unsuccessful mail-outs, up to three attempts were made to interview the patients by telephone. The analysis of the data showed that mail administration, with or without crossover to telephone, was more cost-efficient than telephone administration, having both lower average total and variable costs per completed questionnaire. Overall, telephone administration was about 30% more expensive that mail administration, primarily due to the cost of labor. The marginal cost of an additional completed Veterans SF-12 or Veterans SF-36 was also substantially lower for mail administration. Mail administration without crossover to telephone administration was the most cost-efficient strategy for administering both the Veterans SF-12 and SF-36. The results of this study strongly suggest the need to consider the mode of administration if questionnaires like the Veterans SF-12 or SF-36 are to be used to assess health outcomes within and across large health care systems.

Costs and Cost Analysis↗

The relationship between dental overbite and eustachian tube dysfunction.

OBJECTIVE: The purpose of this study was to investigate the association between deep dental overbite and eustachian tube dysfunction (ETD). DESIGN: Case-control study. SETTING: Tertiary care pediatric otolaryngology outpatient clinic at the Children's Hospital, Boston, Massachusetts. PATIENTS: 105 patients between the ages of 2 and 6 years. STUDY MEASUREMENTS: Dental overbite, overjet, and occlusal relationships were measured by an observer who was unaware of ETD status. ETD was defined as having ventilation tubes in place or having the recommendation for ventilation tube placement by an attending pediatric otolaryngologist. In addition, demographic information and medical and social histories were prospectively recorded. RESULTS: In a multivariate logistic regression model, children with deep bites were 2.8 times more likely to have ETD than those without deep bites (P = .03). Other independent risk factors for ETD identified in this model were family history of otitis media (OM) and age less than 3 years. CONCLUSIONS: Children with deep dental overbites are at a significantly increased risk for developing ETD.

Child↗

A response to California's mandated nursing ratios.

PURPOSE: To explore the need for evidence-based health policy, as illustrated by the mandatory staffing bill passed by the California state legislature in 1999. DESIGN: Prospective data were collected from a voluntary sample of California acute care hospital representatives to describe selected patient safety and clinical outcomes and nurse staffing variables at the patient-care unit level. METHODS: Data for descriptive analysis were collected on hospital nurse staffing, patient falls, and pressure ulcers from 257 medical, surgical, medical-surgical combined, step-down, 24-hour observation units, and critical care patient care units in 38 California acute care hospitals from June 1998 to June 1999. FINDINGS: Nursing staffing ratios varied among the 257 units. RNs provided 91% of the nursing care in critical care units. Patients in medical-surgical units received 59% of their care from RNs, 11% from licensed vocational nurses, and 30% from other caregivers. Preliminary data showed no relationships between reported staffing ratios in these hospitals and the incidence of patient falls or hospital-acquired pressure ulcers. CONCLUSIONS: California Nursing Outcomes Coalition (CalNOC) data showed wide variations in staffing ratios, patient falls, and hospital-acquired pressure ulcers among nursing units and hospitals. These early findings indicate the need for additional research before determining minimal RN staffing requirements. Analysis of multiple sources of data may be necessary to determine safe staffing ratios and to provide evidence-based data for public policy.

Accidental Falls↗

HLA and interleukin 1 gene polymorphisms in primary biliary cirrhosis: associations with disease progression and disease susceptibility.

BACKGROUND AND AIMS: Twin and family studies suggest that there is a genetic component to primary biliary cirrhosis (PBC) but the genetic associations which have been described are weak with marked variations between centres. PBC is heterogeneous and genetic associations with disease progression may be obscured when the PBC population is analysed only as a whole and not subdivided. METHODS: We have investigated two candidate gene loci in 164 well characterised patients, 88 (54%) of whom had advanced disease. RESULTS: There was an increased frequency of the HLA DRB1*0801-DQA1*0401-DQB1*0402 haplotype in patients who had progressed to late stage disease (23% v 2% of controls; p=0000044; odds ratio (OR) 15.5, 95% confidence interval (CI) 3.52-68.4) but not in those with early stage disease (4% v 2%). Patients had a higher frequency of the IL-1B*1,1 genotype and lower frequencies of the IL-1B*1,2 and *2,2 genotypes (p=0.00078; OR 2.37, 95% CI 1.38-4.06), and higher frequency of the IL-1RN*1,1 genotype and lower frequency of the IL-1RN*1,2 genotype (p=0.0011; OR 2.28, 95% CI 1.34-3.89). The difference in the IL-1B*1,1 genotype distribution was most marked in patients with early stage disease (77% v 43% of controls; p=0.000003; OR 4.8, 95% CI 2.31-10) but the IL-1RN genotype distribution was similar in patients with early and late stage disease. CONCLUSIONS: These data indicate a complex relationship between immunoregulatory genes and PBC. While the IL-1 genes are markers of both disease susceptibility and progression, HLA genes appear to be principally associated with disease progression.

Case-Control Studies↗

Osteoporosis in primary biliary cirrhosis revisited.

BACKGROUND: Primary biliary cirrhosis (PBC) is increasingly being diagnosed in the earlier non-cholestatic stages of disease. Accepted wisdom has been that PBC is frequently complicated by osteoporosis. Whether this association holds true for the broader spectrum of PBC patients now recognised has not as yet been studied. AIMS: To examine the extent to which osteoporosis occurs more commonly in PBC patients than in normal individuals of the same age and sex. DESIGN: Retrospective review of a large cohort of well characterised PBC patients. PATIENTS: A total of 272 PBC patients with definite or probable PBC followed up for a mean of 10.1 years (total follow up 2726 patient years) who had at least one bone mineral density measurement (BMD). RESULTS: In this unselected group of PBC patients, mean Z scores (number of SDs from age and sex matched normal mean values) at the neck of femur (NOF) and lumbar spine (LS) at first BMD measurement (7 (6) years after PBC diagnosis) were -0.1 (1.4) and 0.1 (1.4), respectively. At first BMD measurement, 18 PBC patients had Z scores less than -2.0 and 85 had T scores less than -2.5. No factors predictive of osteoporosis were found in affected patients. A total of 957 BMD measurements were performed (0.35 per patient year of follow up); 220 patients had two or more measurements. No patient went on to develop de novo osteoporosis during follow up. In the 51 patients (who were clinically representative of the whole group) who received no PBC or bone related treatment during follow up, %BMD changes per year at the NOF and LS were -1.6 (3.2) and 0.1 (2.2), respectively. No variance in this "natural" rate of BMD measurement was seen in patients receiving PBC modulating agents (including prednisolone and UDCA) or osteoporosis prophylaxis/therapy. Significant improvement at the LS was seen in patients undergoing liver transplantation. CONCLUSIONS: Osteoporosis is not a specific complication of PBC.

Absorptiometry, Photon↗

Alterations in development, behavior, and physiology in Drosophila larva that have reduced ecdysone production.

We investigated behavior, physiology, sensitivity to exogenous application of ecdysone, and nerve terminal structure for differences between the reduced ecdysone genotype, ecd(1)/ecd(1), and wild-type control ecd(1)/TM6B animals during the early and late third instars when raised at 25 degrees C. The ecd(1) mutants were able to survive through larval development and form pupae. However, the results demonstrate that the time to pupation is lengthened by about 50 h for the ecd(1)/ecd(1) as compared with the wild-type control siblings. In addition to the lengthened larval cycle in the mutant, ecd(1)/ecd(1) animals, they also display behavioral differences as compared with controls. The rate of body wall contraction and mouth hook movements are reduced in the early third instar of ecd(1)/ecd(1) as compared with controls. The physiological measure of excitatory junction potential amplitude for the combined Is and Ib terminals did not reveal any differences among the two genotypes during the early third instar but the synaptic strength is reduced in the late third instars for controls. Application of exogenous ecdysone is still effective during the late third instar for the ecd(1)/ecd(1) but not the controls. This suggests that endogenous production of ecdysone have already taken place in the wild-type but not the ecd(1)/ecd(1) larvae, thus the rapid nongenomic responses could still be observed in the late third ecd(1)/ecd(1) larvae. Structurally the number of varicosities and the terminal length showed significant differences between ecd(1)/ecd(1) and the wild-type ecd(1)/TM6B genotype in the late third instars.

Animals↗

Mapping Pavlovian conditioning effects on the brain: blocking, contiguity, and excitatory effects.

Pavlovian conditioning effects on the brain were investigated by mapping rat brain activity with fluorodeoxyglucose (FDG) autoradiography. The goal was to map the effects of the same tone after blocking or eliciting a conditioned emotional response (CER). In the tone-blocked group, previous learning about a light blocked a CER to the tone. In the tone-excitor group, the same pairings of tone with shock US resulted in a CER to the tone in the absence of previous learning about the light. A third group showed no CER after pseudorandom presentations of these stimuli. Brain systems involved in the various associative effects of Pavlovian conditioning were identified, and their functional significance was interpreted in light of previous FDG studies. Three conditioning effects were mapped: 1) blocking effects: FDG uptake was lower in medial prefrontal cortex and higher in spinal trigeminal and cuneate nuclei in the tone-blocked group relative to the tone-excitor group. 2) Contiguity effects: relative to pseudorandom controls, similar FDG uptake increases in the tone-blocked and -excitor groups were found in auditory regions (inferior colliculus and cortex), hippocampus (CA1), cerebellum, caudate putamen, and solitary nucleus. Contiguity effects may be due to tone-shock pairings common to the tone-blocked and -excitor groups rather than their different CER. And 3) excitatory effects: FDG uptake increases limited to the tone-excitor group occurred in a circuit linked to the CER, including insular and anterior cingulate cortex, vertical diagonal band nucleus, anterior hypothalamus, and caudoventral caudate putamen. This study provided the first large-scale map of brain regions underlying the Kamin blocking effect on conditioning. In particular, the results suggest that suppression of prefrontal activity and activation of unconditioned stimulus pathways are important neural substrates of the Kamin blocking effect.

Acoustic Stimulation↗

An exploration of the effects of weighted garments on balance and gait of stroke patients with residual disability.

OBJECTIVE: To explore the effects of weighted garments on the balance and gait of stroke patients. DESIGN: A pilot randomized controlled study with blinded measurement. SETTING: Weighted garments were worn by patients living in the community and measurement was made in a hospital-based gait laboratory. SUBJECTS: Twenty-four adults who were at least six months post stroke and were able to walk 10 metres with or without assistance or a walking aid. INTERVENTION: The six-week treatment-phase subjects were given a set of weighted garments which they were shown how to apply and instructed to wear on their paretic side. Subjects randomly allocated to the six-week control phase were not given any weighted garments. MAIN OUTCOME MEASURES: Balance was measured with the Berg Balance Scale. Gait was measured using GaitMat II, an instrumented walkway. Gait parameters of interest were velocity and symmetry of: step length; single support time; double support time; and support base width. Measures were made at baseline before randomization (baseline) and at the end of the six weeks of intervention (outcome). RESULTS: No statistically significant differences were found between the treatment and control groups at outcome for balance (Mann-Whitney U-test; p = 0.74), gait velocity (p = 0.68) or symmetry of gait parameters (p = 0.33 to p = 0.75). CONCLUSIONS: We found no evidence to support the clinical use of these weighted garments for stroke survivors.

Activities of Daily Living↗

Discitis in young children.

Discitis is uncommon in children and presents in different ways at different ages. It is most difficult to diagnose in the uncommunicative toddler of one to three years of age. We present 11 consecutive cases. The non-specific clinical features included refusal to walk (63%), back pain (27%), inability to flex the lower back (50%) and a loss of lumbar lordosis (40%). Laboratory tests were unhelpful and cultures of blood and disc tissue were negative. MRI reduces the diagnostic delay and may help to avoid the requirement for a biopsy. In 75% of cases it demonstrated a paravertebral inflammatory mass, which helped to determine the duration of the oral therapy given after initial intravenous antibiotics. At a mean follow-up of 21 months (10 to 40), all the spines were mobile and the patients free from pain. Radiological fusion occurred in 20% and was predictable after two years. At follow-up, MRI showed variable appearances: changes in the vertebral body usually resolved at 24 months and recovery of the disc was seen after 34 months.

Anti-Bacterial Agents↗

The T-cell chemokine receptor CXCR3 is expressed highly in low-grade mycosis fungoides.

Three chemokines, Mig, IP-10, and I-TAC, are expressed highly in the epidermis. We examined the expression of the receptor for these chemokines, CXCR3, in cutaneous T-cell lymphoma. We compared CXCR3 expression with that of cutaneous lymphocyte antigen (CLA) and the activation marker CD30. CXCR3 was expressed by at least a subset of tumor lymphocytes in all 25 cases of low-grade mycosis fungoides (MF), with most cells positive in 20 cases. In progressed or transformed MF, CXCR3 expression was noted in 5 of 22 cases. In 4 of 5 MF cases with sequential biopsy specimens, large cell transformation was accompanied by loss of CXCR3 expression. In contrast, CLA was expressed in 35 of 42 MF cases with no significant differences in expression level between low-grade and transformed cases. In other lymphomas, CXCR3 was expressed in 4 of 4 cases of lymphomatoid papulosis, 3 of 4 cases of CD8+ cutaneous T-cell lymphoma, and 3 of 6 cases of systemic T-cell lymphoma in skin, but not in 10 cases of cutaneous anaplastic large cell lymphoma. CXCR3 expression was associated with epidermotropic T-cell tumors but was largely absent in dermal-based tumors. This phenotypic change likely influences the loss of epidermal localization.

Adolescent↗

A novel four-color PCR assay to assess T-cell receptor gamma gene rearrangements in lymphoproliferative lesions.

We describe a novel 4-color polymerase chain reaction (PCR) assay combined with GeneScan analysis to assess for T-cell receptor gamma chain gene (TCRgamma) rearrangements and evaluate its usefulness in 86 lymphoproliferative lesions. In this assay, each variable region (Vgamma) family primer is 5' end-labeled with a different fluorescent dye, allowing determination of the Vgamma family involved in each TCRgamma rearrangement. PCR products were analyzed by capillary electrophoresis. We detected clonal TCRgamma rearrangements in 60 (98%) of 61 T-cell lymphomas, 2 (15%) of 13 B-cell lymphomas, and 3 (25%) of 12 reactive lesions. These results compared favorably with conventional PCR methods using denaturing gradient gel electrophoresis, which revealed clonal TCRgamma rearrangements in 37 (90%) of 41 T-cell lymphomas, 1 (25%) of 4 B-cell lymphomas, and 2 (25%) of 8 reactive lesions. This 4-color PCR assay is at least equivalent to conventional PCR methods and is convenient, allows accurate size determination of TCRgamma rearrangements, and identifies the specific Vgamma family involved, providing more specific information about TCRgamma rearrangement.

Gene Rearrangement↗

Cytogenetic findings in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Chromosomal abnormalities are associated with the polymorphous subtype and an aggressive clinical course.

We correlated bone marrow cytogenetic findings with morphologic and immunophenotypic data in 37 patients with lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM). Each LPL/WM case was classified as lymphoplasmacytoid (n = 18), lymphoplasmacytic (n = 10), or polymorphous (n = 9) using the Kiel criteria. Of 12 cases with chromosomal abnormalities, a single numeric abnormality was present in 4 and a complex karyotype in 8. The most common numeric abnormalities were and -8 in 3 cases each; the most common structural abnormality was del(6q) in 6 cases. Cytogenetic abnormalities were significantly less common in the lymphoplasmacytic and lymphoplasmacytoid groups (5/28 [18%]) compared with the polymorphous group (7/9 [78%]). Clinical follow-up was available for 28 patients for a median of 36 months. Six (67%) of 9 patients with aneuploid tumors, including 4 with polymorphous subtype, subsequently had clinical progression or developed high-grade lymphoma. In contrast, 4 (21%) of 19 patients with diploid tumors, including 1 of polymorphous type, developed clinical progression or high-grade lymphoma. We conclude that abnormal cytogenetic findings in LPL/WM correlate with the polymorphous subtype and poor prognosis.

Adult↗

Hepatosplenic gamma/delta T-cell lymphoma in bone marrow. A sinusoidal neoplasm with blastic cytologic features.

We report 8 cases of hepatosplenic T-cell lymphoma (HSTCL) involving bone marrow and correlate histologic findings with disease progression. Immunophenotypic analysis demonstrated mature, aberrant gamma/delta T-cell immunophenotypes. Isochromosome 7q was identified in 4 cases; 1 case showed the t(7;14)(q34;q13). Seven of 7 cases tested had monoclonal TCR gamma gene rearrangements. The initial diagnostic bone marrow biopsy specimens were hypercellular with a frequently subtle, predominantly sinusoidal infiltrate of atypical small to medium-sized lymphoid cells. In all cases, aspirate smears at diagnosis and in subsequent specimens contained malignant cells that resembled blasts, some with fine cytoplasmic granules. With progression, the pattern of HSTCL in bone marrow biopsy specimens became increasingly interstitial, and the neoplastic cells became larger. In aspirate smears, the proportion of blasts increased. Seven patients died; 1 was lost to follow-up. Autopsy performed on 1 patient demonstrated malignant cells within vascular channels in all organs sampled, with relatively little tumor formation, resembling intravascular lymphoma at these sites. HSTCL often can be recognized in bone marrow by its unique combination of a sinusoidal pattern in core biopsy specimens and blastic cytology in aspirate smears.

Adolescent↗

Absence of CD26 expression is a useful marker for diagnosis of T-cell lymphoma in peripheral blood.

We report flow cytometric characterization of surface CD26 expression in 271 peripheral blood samples from 154 patients evaluated for the presence of a T-cell lymphoproliferative disorder, primarily mycosis fungoides/Sézary syndrome (MF/SS). The presence of morphologically identifiable tumor cells on peripheral blood smears was the criterion for lymphomatous involvement. In 66 of 69 samples from 28 patients, we identified an abnormal CD26-/dim T-cell population that was distinct from the variable CD26 expression seen in normal peripheral blood T cells. This population was CD26- in 23 patients and weakly CD26+ in 5 patients. CD7 was more variably expressed in MF/SS tumor cells, allowing recognition of a distinct, quantifiable abnormal T-cell population in only 34 of 69 involved samples. An increased CD4/CD8 ratio and lower surface expression of CD4 in tumor cells also helped separate the CD26-/dim atypical population for quantification. In 35 blood samples from other types of T-cell tumors, tumor cells in 10 of 11 morphologically involved cases showed absent/dim CD26. Although capable of detecting abnormalities in most cases of MF/SS, CD7 expression does not provide as clear a separation of the neoplastic population and can be replaced by CD26 staining in routine peripheral blood flow cytometric screening of MF/SS patients.

Antigens, CD7↗

Phenotypic characterization of subsets of T cell lymphoma: towards a functional classification of T cell lymphoma.

T cell non-Hodgkin's lymphomas (T-NHL) have traditionally been classified according to a variety of criteria including histological and clinical features, sites of involvement and etiologic agents. Except in select T-NHL types (e.g. CD30-positive anaplastic large cell lymphoma (ALCL)), immunophenotypic criteria are not used for routine subclassification of T-NHL. In this article. we outline the current models for classification and diagnosis of T cell tumors. We also briefly review the current understanding of non-neoplastic T cell subsets with regards to expression of activation markers belonging to the tumor necrosis factor receptor (TNFR) gene family. We summarize the currently available information on expression of these subset markers in T cell tumors, focusing on TNFR family members CD30 and CD134/OX40. CD134/OX40 expression is characteristic of certain entities (angioimmunoblastic lymphoma, angiocentric T-NHL) and a subset of T-NHLs of unspecified type, whereas CD30 expression is characteristic of ALCL and a largely non-overlapping subset of T-NHLs of unspecified type. Immunophenotypic stratification of T-NHL, using TNFR family members and other T cell subset-specific gene products, may provide a functional model for T-NHL classification as is currently the case for B cell tumors.

Humans↗