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Biomedical subjects

D Reid

Publications and source records attributed to D Reid.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

An abilities assessment instrument for elderly persons with cognitive impairment: psychometric properties and clinical utility.

In this article the psychometric properties of an Abilities Assessment Instrument (AAI), developed to assess the self-care, social, interactional and interpretive abilities of older people with cognitive impairment (CI) related to dementia, are described. The sample consisted of 112 institutionalized older men with CI and 60 institutionalized older men without CI. The psychometric evaluation of the AAI indicated that: (a) it is reliable in terms of test-retest (Pearson's r range .93-.99), interrater (Pearson's r range .95- .99), and internal consistency evaluations (Cronbach's alpha .90-.98), as well as through confirmatory factor analysis; and (b) that it is valid with respect to content validity (CVI 87.3%), concurrent validity (Pearson's r correlations ranging from -.67-.80 on the London Psychogeriatric Rating Scale [LPRS], and from -.76-.85 on the Functional Assessment Stages Scale [FAST]), and construct validity with significant differences between subjects with and without CI (t values ranging from 5.13-9.30). The AAI is a reliable and valid instrument that can be used to provide assessment data.

Activities of Daily Living↗
PubMed1997

Population-based geographic variations in DXA bone density in Europe: the EVOS Study. European Vertebral Osteoporosis.

The purpose of this study was to investigate variations in bone density between 16 European populations, 13 of which were participants in the European Vertebral Osteoporosis Study (EVOS). Men and women aged 50-80 years were recruited randomly from local population registers, stratified in 5-year age bands. The other three centres recruited similarly. Random samples of 20-100% of EVOS subjects were invited for dual-energy X-ray absorptiometry (DXA) densitometry of the lumbar spine and/or proximal femur using Hologic, Lunar or Norland pencil beam machines or, in one centre, a Sopha fan-beam machine. Cross-calibration of the different machines was undertaken using the European Spine Phantom prototype (ESPp). Highly significant differences in mean bone density were demonstrated between centres, giving rise to between centre SDs in bone density that were about a quarter of a population SD. These differences persisted when centres using Hologic machines and centres using Lunar machines were considered separately. The centres were ranked differently according to whether male or female subjects were being considered and according to site of measurement (L2-4, femoral neck or femoral trochanter). As expected, bone mineral density (BMD) had a curvilinear relationship with age, and apparent rates of decrease slowed as age advanced past 50 years in both sexes. In the spine, not only did male BMD usually appear to increase with age, but there was a highly significant difference between centres in the age effect in both sexes, suggesting a variability in the impact of osteoarthritis between centres. Weight was consistently positively associated with BMD, but the effects of height and armspan were less consistent. Logarithmic transformation was needed to normalize the regressions of BMD on the independent variates, and after transformation, all sites except the femoral neck in females showed significant increases in SD with age. Interestingly, the effect of increasing weight was to decrease dispersion in proximal femur measurements in both sexes, further accentuating the tendency in women for low body mass index to be associated with osteoporosis as defined by densitometry. It is concluded that there are major differences between BMD values in European population samples which, with variations in anthropometric variables, have the potential to contribute substantially to variations in rates of osteoporotic fracture risk in Europe.

Absorptiometry, Photon↗
PubMed1997

Perimenopausal bone density screening--will it help prevent osteoporosis?

OBJECTIVE: To estimate the potential efficacy and cost-effectiveness of hormone replacement therapy (HRT) in the prevention of osteoporotic fractures, with and without the assistance of perimenopausal bone mineral density (BMD) screening. METHOD: Residual lifetime fracture experience of a hypothetical cohort of 100,000. British women aged 45 years at baseline, modelled using prevailing UK mortality and fracture rates. Appropriate fracture risk gradients were used to estimate the distribution of future fragility fractures (distal forearm, proximal femur and clinically diagnosed vertebral fractures) according to quarters of baseline bone density measured at fracture specific sites. We assumed that 72% of the population could be contacted and would attend for HRT counselling, with or without bone densitometry, that 10 years of continuous HRT use would reduce fracture rates by 50%, and that compliance with HRT might vary between 10% and 50%. Universal recommendation of HRT was compared to selective treatment protocols offering HRT to those women whose BMD fell below the 25th, 50th or 75th percentile of BMD at the lumbar spine, femoral neck or distal forearm, measured either singly or in combination. RESULTS: The proportion of future fractures averted was closely related to compliance with therapy, but for any given level of compliance, universal treatment always achieved the greatest reduction in fractures. If compliance was 10% universal HRT was also the most cost-effective strategy, but if compliance was higher or if the unit cost of HRT increased, selective strategies were often more cost-effective. The sensitivity of BMD screening in identifying women at risk of future fracture could be increased by relaxing the BMD decision threshold, or expanding the number of skeletal sites measured, or both. However increments in test sensitivity were always accompanied by reductions in specificity. CONCLUSIONS: If BMD measurement does not influence compliance, then universal treatment with HRT is likely to prevent more fractures, at a similar or lower average cost per fracture averted, than selective therapy. However, if BMD screening leads to increased compliance, or if more expensive forms of treatment were used, then our model suggests a favourable impact of screening on the numbers and/or net cost of fractures prevented.

Aged↗
PubMed1996

Enhanced detection, maintenance, and differentiation of primitive human hematopoietic cells in cultures containing murine fibroblasts engineered to produce human steel factor, interleukin-3, and granulocyte colony-stimulating factor.

To determine whether the sensitivity of the human long-term culture-initiating cell (LTC-IC) assay could be increased, we have evaluated a spectrum of different fibroblast cell lines for their abilities to influence the number of cells detectable as LTC-IC, to influence LTC-IC maintenance, and/or to influence LTC-IC differentiation into colony-forming cells (CFC) in cocultures containing various sources of LTC-IC. In a series of initial experiments with highly purified subpopulations of CD34+ cells from normal human marrow, no significant difference could be found between any of 3 different murine stromal fibroblast cells in terms of their support of either LTC-IC detection (CFC production) or maintenance (over a 6-week period), and all were equivalent to primary human marrow feeders (HMF). On the other hand, murine M2-10B4 fibroblasts engineered to produce high levels of both human granulocyte colony-stimulating factor (G-CSF) and interleukin-3 (IL-3; 190 and 4 ng/mL, respectively), either alone or mixed 1:1 with SI/SI fibroblasts engineered to produce high levels of soluble Steel factor (SF), with or without production of the transmembrane form of SF (60 and 4 ng/ mL, respectively), stimulated the production of up to 20-fold more CFC in LTC of cells from normal human marrow, G-CSF-mobilized blood or cord blood when compared with parallel cocultures containing HMF. Limiting dilution analysis of the CFC output from all three sources of LTC-IC showed that most of this increase was due to an ability of the engineered feeders to increase the plating efficiency of the LTC-IC assay (approximately 14-fold for marrow LTC-IC and approximately 4-fold for cord blood or mobilized blood LTC-IC). Analysis of the phenotype of these additionally recruited LTC-IC from marrow showed they had the same primitive CD34+CD45RA-CD71- phenotype as conventionally defined LTC-IC. The limiting dilution studies also showed that the average number of CFC produced per LTC-IC was additionally and independently increased to yield values of 18 CFC per LTC-IC in marrow, 28 for LTC-IC in cord blood, and 25 for LTC-IC in G-CSF-mobilized blood. Replating of cells from primary LTC with different feeders into secondary LTC-IC assays containing the best combination of engineered feeders showed that LTC-IC maintenance could be significantly enhanced (up to 7-fold as compared with primary cocultures containing HMF). However, this enhancement was still not sufficient to amplify the number of LTC-IC present after 6 weeks above the input value. Thus, engineering murine fibroblasts to produce sufficient SF, G-CSF, and IL-3 can markedly enhance the detection as well as the maintenance in vitro of a very primitive population of human progenitor cells present in normal adult marrow, mobilized blood, and cord blood by providing the most sensitive assay conditions thus far described. The present findings also provide new evidence of biologic heterogeneity between different cell populations that can be operationally identified as LTC-IC, thus re-emphasizing the importance of limiting dilution analyses to distinguish between quantitative and qualitative effects on these cells.

Animals↗
PubMed1996

Teenage drug use.

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Adolescent↗
PubMed1996

Continuous epidural infusion of ropivacaine for the prevention of postoperative pain after major orthopaedic surgery: a dose-finding study.

PURPOSE: A dose-finding study to investigate the use of epidural infusions of ropivacaine for postoperative analgesia following orthopaedic surgery. METHODS: This was a randomized, double-blind study. Surgery was performed using a combination of a lumbar epidural block utilizing ropivacaine 0.5% and a standardized general anaesthetic. Postoperatively, an epidural infusion of the study solution (saline, ropivacaine 0.1%, 0.2% or 0.3%) was started at the rate of 10 ml.hr-1 and continued for 21 hr after arrival in the PACU. Analgesia was supplemented with PCA morphine (dose = 1.0 mg, lock-out = 5 min). RESULTS: Forty-four patients completed the study. The ropivacaine 0.1%, 0.2%, 0.3% groups required less morphine over the 21 hr than the saline group (P < 0.01). The VAS pain scores were also lower in the three ropivacaine groups (P < 0.001). The ropivacaine groups maintained sensory anaesthesia to pinprick when compared with saline (P < 0.05). The motor block in the 0.3% group was significantly higher than the saline group at all times (P < 0.05), and higher than the 0.1% group at eight hours (P < 0.01), while the 0.2% group had higher Bromage scores than saline at 4 and 21 hr (P < 0.05). CONCLUSIONS: The use of continuous epidural infusions of ropivacaine 0.1%, 0.2% and 0.3% at 10 ml.hr-1 improved postoperative pain relief and decreased PCA morphine requirements in patients undergoing major orthopaedic surgery. The 0.1% and 0.2% concentrations produced similar sensory anaesthesia with less motor blockade than the 0.3% concentration.

Adult↗
PubMed1996

A double-blind comparison of ropivacaine 0.5%, 0.75%, 1.0% and bupivacaine 0.5%, injected epidurally, in patients undergoing abdominal hysterectomy.

PURPOSE: Ropivacaine is a new long-acting, injectable local anaesthetic currently undergoing clinical investigation world wide. It is structurally very similar to bupivacaine, but with less potential for central nervous system or cardiac toxicity. The purpose of this double-blind study was: to investigate the dose-response relationship of increasing doses of ropivacaine on the quality of anaesthesia and the duration of both motor and sensory blockade, and to compare these results with an established local anaesthetic, bupivacaine. METHODS: One hundred and twenty five patients were randomly assigned to one of four treatment groups and 116 completed the study. Epidural anaesthesia was established using 25 ml test solution, injected over three minutes following a satisfactory test dose. Sensory onset, spread and duration, using the pin prick method, and motor scores using a modified Bromage scoring system were compared. RESULTS: A dose/response relationship was observed with increasing doses of ropivacaine for all variables tested except analgesia and muscle relaxation (P < 0.01). There were differences in: (i) motor onset (Levels 1 and 2), when ropivacaine 1.0% was compared with ropivacaine 0.75% and 0.5% (P < 0.05); (ii) in sensory duration at all levels except T6 when ropivacaine was compared with ropivacaine 0.5% (P < 0.05); (iii) differences in sensory duration at T12 and S1 when ropivacaine 1.0% was compared with bupivacaine 0.5% (P < 0.05); (iv) differences in motor duration at all levels when ropivacaine 1.0% was compared with ropivacaine 0.5% (P < 0.05). No serious adverse events were reported in this study. CONCLUSION: Increasing doses of ropivacaine were associated with an increased clinical effect. The most consistent differences occurred when ropivacaine 1.0% was compared with 0.5% and the least consistent between ropivacaine 0.5%, 0.75% and bupivacaine 0.5%. The main difference between ropivacaine 1.0% and bupivacaine was in sensory duration. No serious adverse events were reported.

Adolescent↗