British Thoracic Society Winter Meeting 2001.
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Biomedical subjects
Publications and source records attributed to R H Green.
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A prospective study of the CD34+ cell collection efficiency of three cell separators was undertaken comparing the mononuclear cell, CD34+ cell and CFU-GM yield. Twenty patients were entered in the study, all had received mobilising chemotherapy and daily G-CSF (5 microg/kg subcutaneously). The first leucapheresis was performed when the peripheral blood absolute CD34+ cell count was > or = 20 cells/microl. All patients underwent two leucaphereses on consecutive days. The patients were randomised to undergo either the first or second leucapheresis using the COBE Spectra Version 4.7 and then randomised to either the COBE Spectra Version 6 or Haemonetics MCS+ for the other leucapheresis. The target durations of the procedure on the COBE Spectra Version 4.7 and Version 6 were 180 min or two total blood volumes (TBV), and for the Haemonetics MCS+ was 20 cycles with four recirculations. All machines were operated on the 1997 software supplied by the respective manufacturers. The time taken for the procedure was significantly longer with both the Haemonetics MCS+ and the COBE Spectra Version 6 than the COBE Spectra Version 4.7. Both COBE Spectra versions processed significantly larger volumes of blood than the Haemonetics MCS+. The absolute yield of mononuclear cells, CFU-GM and CD34+ cells were all significantly lower with the Haemonetics MCS+ compared with both COBE Spectra Versions, as were the yields per unit volume of blood processed. There was no significant difference in the reduction in the platelet count following leucapheresis with any of the machines.
A new approach to the use of commercial databases for the dereplication of purified natural products has been developed. This is based on searching a text file that links each structure with its molecular weight and an exact count of the number of methyl, methylene, and methine groups it contains. Analysis of such a text file, constructed from a database containing more than 126,000 natural product structures, revealed that these data, readily measured using MS and NMR spectroscopy, are highly discriminating. The identification of an alkaloid and a sesquiterpene using this new approach is described.
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The forced expiratory volume in 1 sec (FEV1) is the most established outcome measure in chronic obstructive pulmonary disease (COPD). However, changes in FEV1 in response to treatment are small in relation to the repeatability of the measurement and there is increasing interest in other measures including markers of lower airway inflammation in induced sputum, assessment of symptoms and health status using visual analogue scores, and questionnaires. Little is known about the repeatability of these measures or the safety of sputum induction in COPD. We have assessed the safety of sputum induction in 61 subjects with moderate and severe COPD who participated in a placebo-controlled cross-over study The within-subject repeatability of sputum markers of airway inflammation, health status using the chronic respiratory disease questionnaire (CRQ) and symptom visual analogue scores (VAS) were estimated from the data obtained from before and after 2 weeks of treatment with placebo. Sputum induction was performed on 122 occasions and was successful resulting in a cytospin adequate to assess a differential cell count in 95% of inductions. The group mean (SEM) FEV1 was 1.09 (0.05)[41.6 (2.9)% predicted] and the mean (SEM) fall in FEV1 after sputum induction was 120 ml (6) and % fall 10.9% (0.55%). Seven inductions were stopped due to a fall in FEV1 >20% and at a further 13 visits the full sputum induction protocol was not completed due to development of symptoms. The reproducibility of measurements, calculated by the intra-class correlation coefficient, was relatively high for all indices measured (0.4-0.95) with the exception ofthe proportion of lymphocytes (0.15) and epithelial cells (0.3). The ICC for symptom scores and the CRQ domains ranged between 0.87 and 0.96. In conclusion, sputum induction is safe and the cell and fluid phase mediators repeatable in the investigation of airway inflammation in patients with COPD. VAS symptom scores and the CRQ are reproducible outcome measures in COPD.
BACKGROUND: Pulmonary rehabilitation programmes have been shown to improve both exercise tolerance and health status in patients with chronic obstructive pulmonary disease (COPD). The optimal duration for a pulmonary rehabilitation programme is, however, unknown. To assess whether the current pulmonary rehabilitation programme could be shortened a randomised controlled trial was conducted in 44 patients with COPD who were allocated to either a seven week or a four week course. METHODS: Patients were randomised to either our standard seven week twice weekly outpatient based programme or a comparable but shortened four week course. They were assessed at baseline and at completion by the Chronic Respiratory Questionnaire (CRQ), the Breathing Problems Questionnaire (BPQ), the incremental shuttle walking test (SWT), and the treadmill endurance test (TET). RESULTS: Twenty one patients (61% men) of mean (SD) age 68 (9.2) years and forced expiratory volume in one second ( FEV(1)) 1.08 (0.4) l completed a conventional seven week course and 23 (67% men) of mean (SD) age 69 (8.8) years and FEV(1) 1.03 (0.3) l completed a shortened four week course. Patients who completed the seven week rehabilitation programme had greater improvements in all outcome measures than those undertaking the four week course. These differences reached clinical and statistical significance for the total CRQ score, which was the primary outcome variable (mean difference (95% confidence intervals (CI) of difference) -0.61(-0.15 to -1.08), p<0.05), and the CRQ domains of dyspnoea (-0.80 (95% CI -0.13 to -1.48), p<0.05), emotion (-0.89 (95% CI -0.33 to -1.45), p<0.005), and mastery (-0.84 (95% CI -0.10 to -1.58), p<0.05). There were also trends towards greater improvements in exercise assessments in the seven week group but the differences did not reach statistical significance (SWT: mean difference -16.9 (95% CI 24.8 to -58.6), p=0.41; TET: geometric mean difference -1.21 (95% CI -0.60 to -2.47), p=0.56). CONCLUSIONS: A seven week course of pulmonary rehabilitation provides greater benefits to patients than a four week course in terms of improvements in health status. Larger prospective studies are required to determine the optimal duration of a pulmonary rehabilitation programme.
A prospective study of three cell separators was undertaken to compare the mononuclear cell, CD34+ cell and CFU-GM yield. Twenty patients were entered in the study; all had received chemotherapy and daily G-CSF (5 microg/kg subcutaneously) up to and including the first day of leucapheresis. The first leucapheresis was performed on the first day the peripheral blood absolute CD34+ cell count was > or =20 cells/microl. All patients underwent two leucaphereses on consecutive days. The patients were randomised to undergo either the first or second leucapheresis using the COBE Spectra Version 4.7 and then randomised to either the COBE Spectra Version 6 or Haemonetics MCS+ for the other leucapheresis. The target durations of the procedure on the COBE Spectra Version 4.7 and Version 6 were 180 minutes or 2 total blood volumes (TBV), and for the Haemonetics MCS+ was 20 cycles with four recirculations. All machines were operated on the 1997 software supplied by the respective manufacturers. The time taken for the procedure was significantly longer with both the Haemonetics MCS+ and the COBE Spectra Version 6 than the COBE Spectra Version 4.7. Both COBE Spectra versions processed significantly larger volumes of blood than the Haemonetics MCS+. The absolute yield of mononuclear cells, CFU-GM and CD34+ cells were all significantly lower with the Haemonetics MCS+ compared with both COBE Spectra versions, as were the yields per unit volume of blood processed. The product volume was significantly higher with the COBE Spectra Version 4.7 compared to the other two machines. There was no significant difference in the reduction in the platelet count following leucapheresis with any of the machines. The COBE Spectra Version 6 is particularly useful for patients with potentially poor peripheral venous access because of its increased interface stability.
Functional human GABA(B(1a,2)) and GABA(B(1b,2)) receptors have been stably expressed in mammalian CHO K1 cells. Detailed characterization of GABA(B) ligand binding at each of the receptors has been compared using [(3)H]-CGP54626A. In cell membranes fractions, [(3)H]-CGP54626A bound to a single site with a K(D) of 1. 51+/-1.12 nM, B(max) of 2.02+/-0.17 pmoles mg protein(-1) and 0. 86+/-0.20 nM, B(max) of 5.19+/-0.57 pmoles mg protein(-1) for GABA(B(1a,2)) and GABA(B(1b,2)) respectively. In competition binding assays the rank order was identical for both GABA(B) receptors. For known GABA(B) agonists the rank order was CGP27492>SKF97541=CGP46381>GABA>Baclofen and for GABA(B) antagonists the rank order was CGP54262A>CGP55845>CGP52432>SCH 50911>CGP51176>CGP36742=CGP35348 > or =2-OH Saclofen > or =ABPA. The allosteric effect of calcium cations was also investigated. The effect of removal of CaCl(2) from the binding assay conditions was ligand dependent to either cause a decrease in ligand affinity or to have no significant effect. However, these effects were similar for both GABA(B) receptors. A whole cell, scintillation proximity binding assay was used to determine agonist affinity at exclusively heterodimeric GABA(B) receptors. In competition assays, the rank order was the same for both GABA(B(1a,2)) and GABA(B(1b,2)) and consistent with that seen with cell membrane fractions. These data suggest that, in terms of ligand binding, the currently identified isoforms of the GABA(B) receptor are pharmacologically indistinguishable.
Rehabilitation after armed conflict is a direct intellectual descendant of thinking about rehabilitation after natural calamity. It is related, generally, to poverty reduction and, operationally, to associated action at the micro level. This history has limited its strategic conceptualisation and, in particular, its links with reconciliation and state re-legitimation and also with macro-economic stabilisation and renewed growth. In post-war--or more generally, a lull in conflict with the potential to become permanent--a country's rapid, focused, prioritised action within a strategic framework is urgent. It is not risk-free for political and natural disasters as well as for those with economic and social bases. Flexibility, learning from initial experience and asking intended household beneficiaries about their needs in advance can reduce risk as can pre-positioning of contingency or standby resources to avert post-war calamities (for example, drought, flood) and catastrophes (renewed violence) from delaying and discrediting rehabilitation efforts.
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Overall, the number of allogeneic transplants performed world-wide has not increased dramatically over the past 5 years. However, the proportion of allogeneic transplants undertaken using peripheral blood progenitor cells (PBPCs) has risen significantly. Currently, as part of an ethically approved trial, potential donors are seen, assessed and consented by physicians not caring directly for the recipients. Thirty-five potential sibling donors were seen and assessed for their willingness and fitness to donate for 28 patients. One donor opted to give bone marrow and the rest selected PBPC donation. Seven of these donors were found to have concurrent medical conditions. Due to poor venous access, one donor was advised to donate bone marrow and two others donated bone marrow due to an underlying condition. Four others were deemed unfit for donation. Donation of stem cells from bone marrow or peripheral blood is not a risk-free procedure; careful preassessment and counselling is mandatory especially when the age of prospective patients and therefore donors is increasing.
BACKGROUND: The contribution and role of emphysema and small airways disease in causing expiratory airflow limitation in COPD is controversial. METHODS: We obtained high-resolution thin-section 2-mm CT scans of the lung for emphysema grading and lung function in 116 consecutively seen COPD outpatients with fixed expiratory airflow limitation. In this group, inflated whole lung(s) were subsequently obtained in 24 patients (23 autopsy, 1 surgery) for morphologic studies and results compared with lung CT. Airway histologic condition was studied in 17 of the 24 patients. RESULTS: There was fair to weak negative correlation between CT emphysema score and either FEV1/FVC percent (r = -0.51, p = 0.001) or FEV1 percent predicted (r = -0.31, p = 0.001). In only 24 of the 81 patients (30%) with FEV1 less than 50% predicted, the CT emphysema score was 60 or more, indicating severe emphysema. In the 24 patients studied, there was a good correlation (r = 0.86, p = 0.001) between CT and pathologic grade of emphysema. While respiratory bronchioles (RBs) and membranous bronchioles (MBs) demonstrated marked morphologic abnormalities, there was a weak correlation with emphysema grade (for RB, r = 0.36, p = 0.16; for MB, r = 0.41, p = 0.10) or with FEV1 percent predicted (for RB, r = -0.21, p = 0.42; for MB, r = -0.28, p = 0.28). There was no correlation between emphysema and FEV1 percent predicted (r = -0.13, p = 0.54). CONCLUSIONS: High-resolution CT lung scans are an in vivo surrogate to quantitate moderate to severe morphologic emphysema. Emphysema does not appear to be primarily responsible for severe expiratory airflow limitation in most patients with severe COPD. There was no correlation between severity of small airway histologic condition and emphysema or FEV1 percent predicted. The causes of the lesions responsible for small airways obstruction need to be identified.
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Health for All by 2000 could become a reality in the Third World countries. On present resource allocation, medical professional and political patterns and trends that is unlikely to happen in more than a few countries. For it to happen requires basic priority shifts to universal access primary health care (including preventative). The main obstacles to such a shift are not absolute resource constraints but medical professional conservatism together with its interaction with elite interests and with political priorities based partly on perceived demand and partly on (largely medical) professional advice. These obstacles are surmountable-as illustrated by divergent performances among countries--but only if education, promotion, efficiency in terms of lives saved and healthy years gained, community participation and political activism for Health for All are more carefully analytically based and pursued more seriously and widely than they have been to date.
A 3 year old girl presented with malignant osteopetrosis, which was treated by allogeneic bone marrow transplantation. Successful engraftment was complicated by prolonged hypercalcaemia, which was controlled by a combination of a bisphosphonate, phosphate infusions, vigorous resalination, and salmon calcitonin. She was alive and well 16 months after the transplant.
Different types of enzyme-catalyzed processes are reviewed, with particular regard to those procedures leading to the generation of chiral compounds of high optical purity. The main body of the review deals with hydrolyses and esterification as well as the reduction and oxidation of organic substrates. Other biotransformations of current and/or future importance in the synthesis of homochiral fine chemicals (such as the formation of carbon-carbon bonds using aldolases) are also discussed in some detail. Attention is drawn to current trends in the area and, to this end, a majority of the references are taken from journals published during the period April 1987 to September 1988.
What sample size n is needed to have 1 - beta chance of detecting a magnitude delta response to pollution impact? A design where the same sites are sampled both before and after impact is more efficient than a design where sites are reallocated for the after-impact sampling. Taylor's Power Law can be used to estimate the n necessary to achieve specified power for a wide range of variance-mean relationships. Solutions can easily be obtained where the error coefficient of variation and the percentage change due to impact are of interest rather than the error standard deviation and absolute change. Estimation of the n necessary to detect a hypothesized multivariate response can easily be done. When p response variables are uncorrelated and all respond equally to impact, the required n is approximately the same as for a univariate test using one of the variables. If only one of the p variables responds, n is approximately p times that number. However, if the variables are correlated and the vector of response differs from the natural variation, then the required sample size is smaller. In this circumstance the multivariate test can be very powerful.