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Biomedical subjects

D Reid

Publications and source records attributed to D Reid.

At least 37 records · Page 2Linked to original sources

Evidence that ceramide mediates the ability of tumor necrosis factor to modulate primitive human hematopoietic cell fates.

In this study, it is shown that short-term exposure of normal human marrow CD34(+)CD38(-) cells to low concentrations of tumor necrosis factor (TNF) in the presence of 100 ng/mL Flt3 ligand and Steel factor and 20 ng/mL interleukin-3 (IL-3), IL-6, and granulocyte colony-stimulating factor, in either bulk or single-cell serum-free cultures, markedly reduces their ability subsequently to generate colony-forming cells (CFCs) in 6-week stromal cell-containing long-term cultures without affecting their viability, mitogenic response, or short-term ability to produce CFCs. A similar differential effect on the functional attributes of CD34(+)CD38(-) cells was seen when C2- or C6-ceramide, but not dihydro-C2-ceramide (an inactive analog of ceramide), was substituted for TNF. The addition of D-erythro-MAPP (a specific inhibitor of intracellular ceramide degradation) enhanced the ability of TNF to selectively eliminate long-term culture-initiating cell (LTC-IC) activity. These findings indicate that TNF can directly modulate the ability of CD34(+)CD38(-) cells to maintain their LTC-IC function at doses below those required to initiate apoptosis, cell cycle arrest, or both, and they suggest that this may be mediated by the TNF-induced generation of intracellular ceramide. Identification of a signaling intermediate that can influence primitive hematopoietic cell fate decisions offers a new approach to the investigation of signaling mechanisms in normal stem cell populations and to how these may be altered in leukemic cells.

Cells, Cultured↗

Corticosteroids for acute severe asthma in hospitalised patients.

BACKGROUND: Corticosteroids are currently used routinely in the management of acute severe asthma. The optimal dose and route of administration continues to be debated. Some investigators have reported a greater benefit of higher doses of corticosteroids in the management of severe asthma, while others have not. OBJECTIVES: To determine whether higher doses of systemic corticosteroids (oral, intravenous or intramuscular) are more effective than lower doses in the management of patients with acute severe asthma requiring hospital admission. SEARCH STRATEGY: Randomised controlled trials were identified from the Cochrane Airways Group Asthma Register. In addition, primary authors and content experts were contacted to identify eligible studies. Bibliographies from included studies, known reviews and texts were also searched. SELECTION CRITERIA: Studies were selected for inclusion in the review if they met the following broad inclusion criteria: described as randomised controlled trials, included patients with acute severe asthma, compared different doses of corticosteroids (any route) in 2 or more treatment arms, and had a minimum period of follow up of 24 hours. Two reviewers independently assessed the studies for inclusion and disagreement was resolved by third party adjudication. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers if the authors were unable to verify the validity of information. Missing data were obtained from authors or calculated from other data presented in the paper. The data were analysed as weighted mean differences (WMD) for primary pulmonary function outcomes using a fixed effects model. For the purposes of the review, three broad categories of corticosteroid dose (equivalent dose of methylprednisolone in 24 hours) were defined in advance: low dose (< or = 80 mg), medium dose (> 80 mg and < or = 360 mg) and high dose (> 360 mg). There were thus 3 main comparison groups: low versus medium dose, medium versus high dose and low versus high dose. MAIN RESULTS: Nine trials were included; a total of 344 adult patients have been studied (96 with low dose, 85 with medium dose and 163 with high dose corticosteroids). Only 6 trials provided sufficient data for the meta-analysis. There were no clinically or statistically significant differences detected in % predicted FEV1 among comparison groups after 24, 48 or 72 hours. At 48 hours, the weighted mean difference was -3.3% predicted (95% confidence interval -12.4 to + 5.8) for the low vs medium dose comparison, -1. 9% predicted (95% CI -8.1 to + 4.3) for the medium vs high dose comparison and + 0.5% predicted (95% CI - 7.8 to + 8.8) for the low vs high dose comparison. There appeared to be no significant differences in side effects or rates of respiratory failure among the varying doses of corticosteroids. REVIEWER'S CONCLUSIONS: No differences were identified among the different doses of corticosteroids in acute asthma requiring hospital admission. Low dose corticosteroids (< or = 80 mg/day of methylprednisolone or < or = 400 mg/day of hydrocortisone) appear to be adequate in the initial management of these adult patients. Higher doses do not appear to offer a therapeutic advantage.

Acute Disease↗

Management and treatment perceptions among young adults with asthma in Melbourne: the Australian experience from the European Community Respiratory Health Survey.

OBJECTIVES: As part of the European Community Respiratory Health Survey (ECRHS) in 1992-1993 we assessed management practices and treatment perceptions among young asthmatic adults in Melbourne, Australia. METHODOLOGY: We conducted a postal questionnaire survey of 4500 randomly selected adults (aged 20-44 years), drawn from three electoral districts, of whom 3200 (71%) subjects responded. A randomly selected sample of 1642 respondents, 'enriched' by a further 433 symptomatic subjects, was invited to complete a second phase respiratory questionnaire. RESULTS: The questionnaire was completed by 757 subjects who underwent laboratory testing. A further 119 subjects who were unable to attend the laboratory completed an identical questionnaire by telephone interview (42% response rate). In the second phase, 16% of subjects reported 'current asthma' (group I) as defined by physician confirmation and a recent attack (within 1 year), 10% had confirmed asthma but reported no recent attack (group II) and 74% did not have asthma (group III). Inhaled corticosteroid use was significantly higher in group I than in group II subjects (45% vs 24%, P<0.01), but only 11% of asthmatic subjects overall reported daily prophylactic use. Regular treatment in any form was considered to be 'bad' by 65% of asthmatic subjects and only 43% took medication as prescribed all of the time. CONCLUSION: Despite national education campaigns, the majority of young asthmatic adults in Melbourne did not adhere to prescribed treatment, but continued to rely upon beta2-agonists alone with neglect of regular inhaled corticosteroid which has probably contributed to Australia's continued high asthma morbidity and mortality rates.

Adrenal Cortex Hormones↗

Prevalence of HIV among pregnant women in Dundee 1988-1997: evidence to gauge the effectiveness of HIV prevention measures.

OBJECTIVES: During November 1988-July 1990, an HIV prevalence survey of pregnant women in Dundee, which used a combined voluntary diagnostic testing and voluntary unlinked anonymous approach, revealed a rate of 0.3%, the highest recorded prevalence among such a population in the U.K. at the time. To determine if, and why, any changes in HIV prevalence had occurred during the early to mid 1990s, further studies were conducted. METHODS: During January 1993-December 1997, antenatal patients of, and women undergoing therapeutic termination of pregnancy at, Ninewells Hospital, Dundee, were offered a diagnostic HIV antibody test. For those declining, residual sera from rubella specimens were tested for HIV antibodies using an unlinked anonymous approach which did not necessitate the securement of informed consent. Information about injecting drug use was obtained from all women and linked to their HIV test results. RESULTS: For all pregnant women, a significant decline in HIV prevalence (P<0.05) from 0.3% (19/6228) during 1988-1990 to 0.12% (22/17899) during 1993-1997 was observed. For those who injected drugs, prevalence decreased significantly (P<0.05) from 27.5% (11/40) to 7% (6/85), while among women who had never injected drugs prevalence decreased slightly, but not significantly (P>0.05), from 0.13% (8/6188) to 0.09% (16/17814).Prevalence in the non-injectors who reported no sexual intercourse with an injector was low at 0.04% (8/17682) during 1993-1997. No significant trends in HIV prevalence were seen over the 5 years up to 1997. CONCLUSION: The decline in HIV prevalence among pregnant women in Dundee during the early to mid-1990s can be explained predominantly by the control of HIV transmission among the city's injectors, and from them to the wider heterosexual population. It is likely that interventions designed to reduce needle/syringe sharing among injectors have been successful. It is imperative that the preventive effort is not allowed to be weakened.

Abortion, Induced↗

Depression among victims of south Mississippi's methyl parathion disaster.

Human-induced disasters have long been considered responsible for a wide array of physiological, psychological, and economic distress. This study examined depressive symptoms among victims of south Mississippi's methyl parathion disaster. Results indicated that irrespective of the level of methyl parathion contamination in respondents' dwellings, more than half the victims interviewed reported depressive symptoms at levels suggesting probable clinical depression. Those at greatest risk of depressive symptoms were people who had been exposed to the neurotoxin for the longest period of time, among whom there was an overrepresentation of women and African Americans. Despite high statistical levels of depression, few victims used mental health services. Implications for social work's response to human-induced disasters are provided.

Adult↗

Canadian anesthesia physician resources: 1996 and beyond.

PURPOSE: To report physician resource information from the 1996 national anesthesia physician and residency programme surveys in Canada. The findings are used to discuss the potential effects on availability of future specialist anesthesia services in Canada. METHODS: Twenty-six hundred and ninety-three physicians (2,206 specialists, 487 family physicians) providing anesthesia services were surveyed. Information on demographics and patterns of clinical practice were sought. Anesthesia programme directors provided trainee information. Projections of the potential number of practicing anesthesiologists to 2026 were made based on the number of available training positions and age distribution of anesthesiologists. RESULTS: There was a 58.3% response rate to the national survey. Since 1986 there has been a 10% increase in the number of specialist anesthesiologists. Marked regional variations in age distribution and changes in the number of specialist anesthesiologists were noted. Most specialists remain in the region or province of postgraduate training. Sixty percent of specialists were either re-entry trainees or international medical graduates. Changes in anesthesia practice patterns have resulted in 40% of the anesthesiologist's work now occurring outside of the operating room. Anesthesia training positions have decreased by at least 15%. The population of Canada is projected to increase by 33.8% between 1996 and 2026. If current government and position allocation policies continue, it is projected there will be 0% increase in the number of specialist anesthesiologists over the same time period. CONCLUSIONS: Changes in anesthesia practices have exacerbated the current shortages of anesthesiologists. These shortages will worsen if the number of, and restrictions to, available residency positions is unchanged.

Anesthesiology↗

Optimization of retroviral-mediated gene transfer to human NOD/SCID mouse repopulating cord blood cells through a systematic analysis of protocol variables.

Retroviral transduction of human hematopoietic stem cells is still limited by lack of information about conditions that will maximize stem cell self-renewal divisions in vitro. To address this, we first compared the kinetics of entry into division of single human CD34+CD38- cord blood (CB) cells exposed in vitro to three different flt3-ligand (FL)-containing cytokine combinations. Of the three combinations tested, FL + hyperinterleukin 6 (HIL-6) yielded the least clones and these developed at a slow rate. With either FL + Steel factor (SF) + HIL-6 + thrombopoietin (TPO) or FL + SF + interleukin 3 (IL-3) + IL-6 + granulocyte-colony-stimulating factor (G-CSF), >90% of the cells that formed clones within 6 days undertook their first division within 4 days, although not until after 24 hours. These latter two, more stimulatory, cytokine combinations then were used to assess the effect of duration of cytokine exposure on the efficiency of transducing primitive CB cells with a gibbon ape leukemia virus-pseudotyped murine retroviral vector containing the enhanced green fluorescent protein (GFP) cDNA and the neomycin resistance gene. Fresh lin- CB cells exposed once to medium containing this virus plus cytokines on fibronectin-coated dishes yielded 23% GFP+ CD34+ cells and 52-57% G418-resistant CFC when assessed after 2 days. Prestimulation of the target cells (before exposing them to virus) with either the four or five cytokine combination increased their susceptibility. In both cases, the effect of prestimulation assessed using the same infection protocol was maximal with 2 days of prestimulation and resulted in 47-54% GFP+ CD34+ cells and 67-69% G418-resistant CFC. Repeated daily addition of new virus (up to three times), with assessment of the cells 2 days after the last addition of fresh virus, gave only a marginal improvement in the proportion of transduced CD34+ cells and CFC, but greatly increased the proportion of transduced LTC-IC (from 40% to >99%). Transplantation of lin- CB cells transduced using this latter 6-day protocol into NOD/SCID mice yielded readily detectable GFP+ cells in 10 of 11 mice that were engrafted with human cells. The proportion of the regenerated human cells that were GFP+ ranged from 0.2-72% in individual mice and included both human lymphoid and myeloid cells in all cases. High-level reconstitution with transduced human cells was confirmed by Southern blot analysis. These findings demonstrate that transplantable hematopoietic stem cells in human CB can be reproducibly transduced at high efficiency using a 6-day period of culture in a retrovirus-containing medium with either FL + SF + HIL-6 + TPO or FL + SF + IL-3 + IL-6 + G-CSF in which virus is added on the third, fourth, and fifth day.

ADP-ribosyl Cyclase↗

Speech and language therapy caseloads in seven districts in the UK.

This paper provides managers and clinicians with an analysis of routine data collected by seven speech and language therapy services in the UK. Managers in seven districts in the UK of varying size and location were asked to provide information on referrals, waiting times and attendances during the six month period, and to give a breakdown of the types of intervention offered and type of clients seen. These data were aggregated and comparisons were made with existing data on speech and language therapy services. The results revealed considerable variations in prevalence, staffing ratios and client management practices. The implications for service planning are discussed.

Adult↗

Comparison of epidural anaesthesia with ropivacaine 0.5% and bupivacaine 0.5% for caesarean section.

PURPOSE: To compare ropivacaine 0.5% with bupivacaine 0.5% for epidural anaesthesia for Caesarean section. METHODS: Healthy pregnant women, scheduled for elective Caesarean section were enrolled into this randomized, double-blind, parallel-group study. Epidural block was obtained with 20-30 ml of ropivacaine (group R) or bupivacaine (group B) and surgery started when anaesthesia was reached T6. Maternal heart rate and blood pressure and fetal heart rate were assessed before the test dose and at five minute intervals until the end of surgery. At the same intervals, sensory and motor block characteristics were determined. Apgar scores and Neurologic and Adaptive Capacity Scores (NACS) were determined after delivery. Adverse events were recorded. RESULTS: Sixty-five patients were enrolled and data from 61 were available for analysis; 30 ropivacaine and 31 bupivacaine. Time from the end of the last injection to the start of surgery was 46 +/- 13 min (mean +/- SD) in gp R and 53 +/- 25 min in gp B (P:NS). The median duration of analgesia varied between 1.7 and 4.2 hr in gp R and between 1.8 and 4.4 hr in gp B (P:NS). In patients who developed Bromage 4 block, it persisted longer in those in gp B (2.5 hr) than in gp R (0.9 hr) (P < 0.05). The quality of analgesia was satisfactory in 27/29 patients (93%) in gp R and 27/31 patients (87%) in gp B (P:NS), although supplemental i.v. opioid was required in ten and seven patients, respectively. The most common adverse events in the mother were hypotension (63% gp R and 61% in gp B) (NS) and nausea (30% and 58%, in group R and B, respectively) (P = 0.05). Apgar scores were 7 after five minutes in all neonates. CONCLUSION: Ropivacaine 0.5% and bupivacaine 0.5% provided effective epidural anaesthesia for Caesarean section although supplementation with i.v. opioid was commonly required.

Adolescent↗

A comparison of the long-term effectiveness of distraction and focusing in the treatment of auditory hallucinations.

Cognitive-behavioural interventions for patients experiencing neuroleptic resistant auditory hallucinations have fallen into two main categories: those which encourage distraction as a coping strategy, and those which encourage patients to focus on or expose themselves to their hallucinations. A 20-session distraction treatment was compared with an equal length focusing treatment for 19 patients who were experiencing chronic auditory hallucinations. Patients were followed-up for approximately 2 years. No differences were observed between the groups for outcome on symptom severity overall, although the focusers showed a greater belief that their voices were their own thoughts at the final follow-up point. When the two groups were combined, there was a significant reduction in the frequency of hallucinations and the disruption to life caused by them during treatment, although this was not maintained at follow-up. During treatment, there was a significant increase in self-esteem for focusers but a significant decrease for distracters. At 2-year follow-up, both focusers and distracters showed a reduction in self-esteem in comparison to the end of therapy. The results show no overwhelming advantage of one treatment over the other and confirm previous observations of the difficulty of treating hallucinations with cognitive-behaviour therapy (CBT). However, there was some indication that CBT influenced some important clinical variables and further investigation is warranted.

Adaptation, Psychological↗

An audit tool for health visitors and SLTs working with the pre-school population.

This paper will present the preliminary findings of a national Royal College of Speech and Language Therapists audit of speech and language therapy and health visiting services to the pre-school population. The audit was carried out in six districts of the United Kingdom, representing a broad range of locations and models of service delivery. The purpose of the audit was to evaluate specific aspects of the management of children with speech and language difficulties. Audit tools were applied to referral and selection procedures, inservice training and parent programmes. Preliminary findings and their implications are discussed.

Child, Preschool↗

Rapid screening of platelet donors for PlA1 (HPA-1a) alloantigen using a solid-phase microplate immunoassay.

PlA1 and PlA2 are alternative platelet-specific alloantigens in the PlA1 system. Sensitization to PlA1 underlies most cases of neonatal alloimmune thrombocytopenia (NAIT) and posttransfusion purpura (PTP) in white populations. A rapid and simple method for large-scale platelet phenotyping is desirable for identifying expectant mothers at risk of allosensitization and for identifying PlA1-negative donors when transfusions are indicated for treatment of NAIT or PTP. We investigated the effectiveness of a solid-phase microplate immunoassay for this purpose. Platelet-rich donor plasmas were tested using the Capture-P(R) kit (Immucor, Norcross, GA). Platelet monolayers in microtiter wells were incubated with anti-PlA1, washed, and exposed to red blood cells (RBCs) precoated with anti-human IgG. Adherence of RBCs in a diffuse pattern across the well surface indicated the attachment of anti-PlA1 to PlA1-positive platelets whereas sedimentation of unattached RBCs into a central pellet indicated the platelets were PlA1-negative. Of 520 donors, 15 (2.88%) tested PlA1-negative, which correlates well with the reported PlA2,2 frequency in whites of 2.25 percent. Results were confirmed by DNA genotyping and/or immunoblotting. This screening technique permits phenotyping donors for PlA1 alloantigen with minimal specialized equipment. Confirmatory testing for PlA2 alloantigen can be reserved for donors that test negative for PlA1.

Journal Article↗

Esophageal strictures. A radiologic approach to diagnosis and management.

Strictures of the esophagus represent persistent luminal narrowing following an inflammatory insult to mural tissues or a manifestation of malignant disease. Barium studies remain the cornerstone of evaluation of patients with a suspected stricture. The diagnostic features of the various causes of strictures are discussed. Balloon dilatation and stent placement, as well as other radiologic interventions, often have an important role in the treatment of patients with advanced disease. This article discusses the indications and general application of these procedures as well as the nature and evaluation of the associated complications.

Barium Sulfate↗