Cord blood as an alternative source of haemopoietic stem cells.
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Adult↗
Biomedical subjects
C Donaldson
Publications and source records attributed to C Donaldson.
Programme budgeting and marginal analysis: a case study of maternity services.
BACKGROUND: This paper reports on a study which applied the framework of programme budgeting and marginal analysis (PBMA) to assist in developing a strategy for purchasing maternity services within the Grampian region of Scotland. METHODS: PBMA as a process involves assessing how health care resources are currently distributed within services or programmes and making recommendations, in a resource neutral environment, about possible future changes. Data on activity and the extent of service provision within maternity care were used alongside information from national policy documents to decide on the main proposals for change in service delivery. Candidates for more resources were compared with each other and with candidates for service reduction to determine whether and what changes should go ahead. This involved 'marginal analysis' of the costs and benefits of the proposed changes. RESULTS: The results demonstrate that modest changes in maternity services in line with government policy are achievable. Estimates of the cost of larger changes in line with policy appear to be feasible 'on paper'. However, it may not be possible to achieve the resource shifts required. CONCLUSIONS: This paper introduces the theoretical concept of PBMA and, in describing the study of maternity services, illustrates not only its usefulness but also practical problems in its implementation.
Budgets↗
Assessing the costs of assisted reproductive techniques.
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Cost-Benefit Analysis↗
Bone mineral density measurements: are they worth while?
Bone mineral density measurements have been criticized on the grounds that they are not a worth-while screening tool. In this paper we argue that bone mineral measurements can be an efficient diagnostic tool even if they are not of proven value for screening. There is complex relationship between the costs of a measurement, the intervention and the predictive value of the test all of which must be accounted for when assessing the value of a bone density measurement. For bone density measurements to be used for screening, a wider evaluation needs to be undertaken compared with that for their use as a diagnostic tool. We address some common objections, for example, that low compliance with screening would undermine efficiency, and show that these are not relevant. Evaluations of screening need to address issues that are likely to affect efficiency.
Aged↗
Optimal cryopreservation of human umbilical cord blood.
Cryopreservation techniques for umbilical cord blood (UCB) have been based on methods established for marrow (BM) and peripheral blood progenitor cells (PBPC) with varying degrees of success. The aim of this study was to optimise cryopreservation of UCB haemopoietic cells based on sound cryopreservation principles. UCB samples were cryopreserved with different combinations of DMSO and hydroxyethyl starch (HES) by a variety of freezing protocols. After cooling at 1 degree C/min in solutions containing 4% HES and various concentrations of DMSO there was a dramatic fall in CD34+ recovery from 85.4% (s.d. 28.4) to 12.2% (s.d. 10.0) as DMSO concentration was reduced from 5 to 2.5%. Varying HES concentration in solutions containing 5% DMSO did not have a significant effect on CD34+ cell recovery. Increasing cooling rate from 1 to 10 degrees C/min significantly reduced CD34+ recovery (P < 0.0001) while increasing DMSO concentration up to 10% had little effect (P = 0.8, two-way ANOVA). Good recovery of UCB CD34+ cells can be achieved with 5-10% DMSO at a controlled cooling rate of 1 degrees C/min. There was a significant difference (P < 0.0001) in the apparent recovery of CD34+ cells between paired aliquots thawed in the presence (recovery = 76.8%, s.d. 26.0) and absence (32.5%, s.d. 18.7) of DNase. In conclusion, conditions for cryopreserving UCB for clinical banking that yield optimal recovery of CD34+ cells have been established.
Antigens, CD34↗
Optimal processing of human umbilical cord blood for clinical banking.
Human umbilical cord blood (UCB) has been successfully used as an alternative source of allogeneic hematopoietic stem cells for pediatric transplantation. Clinical banking of UCB requires volume reduction and red cell depletion for cost-effective storage. We have compared processing UCB by Ficoll, Percoll, methylcellulose, gelatin, starch, and red cell lysis. As individual UCB collections vary widely in colony forming cell (CFC) and CD34+ cell content, each UCB (n = 26) was processed by three or more techniques in parallel with Ficoll as the "standard" method. Gelatin gave a consistently high recovery of CFC (92%) and CD34+ cells (86%). Between 0.10-2.50% of the leukocytes in gelatin-treated UCB were CD34+ with an intra-assay variation of 2.1%. Combining data from individual experiments, the correlation between CD34+ and CFC content was excellent (r = 0.77). Lysis rated second in terms of CD34+ and CFC recoveries but is not as practical because of the large volumes involved. Ficoll and Percoll came third but are more expensive and more involved techniques. Starch sedimentation proved to be slow, while methylcellulose processing lost over 60% of CFC and CD34+ cells. After gelatin processing, we calculated 70-mL donations of UCB would contain a mean +/- SD of 9 +/- 2 x 10(8) nucleated cells, 32 +/- 18 x 10(5) CD34+ cells, and 20 +/- 12 x 10(5) CFC with greater than 95% red cell depletion. Recent published computer studies suggest that as few as 2 x 10(5) CD34+ cells may be needed for sustained engraftment of allogeneic marrow in adult transplant recipients. We conclude that average 70-mL UCB donations contain sufficient marrow repopulating cells for adult recipients.
Antigens, CD34↗
Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor.
Corticotropin-releasing factor (CRF), a peptide first isolated from mammalian brain, is critical in the regulation of the pituitary-adrenal axis, and in complementary stress-related endocrine, autonomic and behavioural responses. Fish urotensin I and amphibian sauvagine were considered to be homologues of CRF until peptides even more closely related to CRF were identified in these same vertebrate classes. We have characterized another mammalian member of the CRF family and have localized its urotensin-like immunoreactivity to, and cloned related complementary DNAs from, a discrete rat midbrain region. The deduced protein encodes a peptide that we name urocortin, which is related to urotensin (63% sequence identity) and CRF (45% sequence identity). Synthetic urocortin evokes secretion of adrenocorticotropic hormone (ACTH) both in vitro and in vivo and binds and activates transfected type-1 CRF receptors, the subtype expressed by pituitary corticotropes. The coincidence of urotensin-like immunoreactivity with type-2 CRF receptors in brain, and our observation that urocortin is more potent than CRF at binding and activating type-2 CRF receptors, as well as at inducing c-Fos (an index of cellular activation) in regions enriched in type-2 CRF receptors, indicate that this new peptide could be an endogenous ligand for type-2 CRF receptors.
Adrenocorticotropic Hormone↗
Identification of a second corticotropin-releasing factor receptor gene and characterization of a cDNA expressed in heart.
Corticotropin-releasing factor (CRF; corticoliberin) regulates the secretion of corticotropin (ACTH) and beta-endorphin and has a broad range of effects on the nervous, endocrine, reproductive, cardiovascular, gastrointestinal, and immune systems. Recently, human, rat, and mouse CRF receptors (CRF-R) have been cloned and functionally and anatomically characterized. We report here the cloning of a second CRF-R cDNA (CRF-RB), which encodes a protein of 431 amino acids, which is 16 amino acids longer and 68% similar to the previously cloned CRF-R, CRF-RA. When transiently expressed in COS-M6 cells, CRF-RB binds CRF with high affinity [Kd = 1.2 (0.57-2.5)nM] and transduces the CRF-stimulated signal of the accumulation of intracellular cAMP, which is inhibited by a CRF antagonist. Comparison of the amino acid sequences of CRF-RB and the previously cloned receptor reveals major differences in the N-terminal domain and in the extracellular loops, whereas the sequences of the intracellular loops are nearly identical. CRF-RB and related transcripts are expressed in the heart, as well as in other tissues, including the gastrointestinal tract, epididymis, and brain.
Amino Acid Sequence↗
Human S100b protein: formation of a tetramer from synthetic calcium-binding site peptides.
Human brain S100b protein is a unique calcium-binding protein comprised of two identical 91-amino acid polypeptide chains that each contain two proposed helix-loop-helix (EF-hand) calcium-binding sites. In order to probe the assembly of the four calcium-binding sites in S100b, a peptide comprised of the N-terminal 46 residues of S100b protein was synthesized and studied by CD and 1H NMR spectroscopies as a function of concentration and temperature. At relatively high peptide concentrations and in the absence of calcium, the peptide exhibited a significant proportion of alpha-helix (45%). Decreasing the peptide concentration led to a loss of alpha-helix as monitored by CD spectroscopy and coincident changes in the 1H NMR spectrum. These changes were also observed by 1H NMR spectroscopy as a function of temperature where it was observed that the Tm of the peptide was lowered approximately 14 degrees C with a 17-fold decrease in peptide concentration. Sedimentation equilibrium studies were used to determine that the peptide formed a tetramer in solution in the absence of calcium. It is proposed that this tetrameric fold also occurs in S100b and is a result of the interaction of portions of all four calcium-binding sites.
Amino Acid Sequence↗
Hormone replacement therapy: compliance and cost after screening for osteoporosis.
OBJECTIVE: To assess HRT compliance and cost 1 year after population screening for low bone density. DESIGN: Postal questionnaire sent out to women 1 year after having a bone density scan. MAIN OUTCOME MEASURES: Compliance with HRT, type of HRT and cost. RESULTS: Compliance with HRT after screening for women with low bone density was 48% for postmenopausal women and 59% for women with a simple hysterectomy. The most often used form of HRT was Estraderm (49%) for women with a hysterectomy, whilst for women with an intact uterus Prempak-C (54%) was the most popular. The average annual cost of treating women who had had a hysterectomy was 67 pounds whilst for women with an intact uterus it was 61 pounds, a non-significant difference. CONCLUSIONS: Approximately 50% of women with low bone density had started HRT within 1 year of having a densitometry examination. Previous reports of the cost advantage of treating women who had had a hysterectomy relative to those who had not has been overstated.
Bone Density↗
Differential effects of CGS 12066B and CP-94,253 on murine social and agonistic behaviour.
Although it has been previously proposed that 5-HT1B agonism specifically attenuates rodent agonistic behaviour, more recent investigations have indicated that such influences may be ancillary to an anxiogenic effect. The present study examined the influences of two 5-HT1B agonists, CGS 12066B and CP-94,253, on murine agonistic behaviour. In a resident-intruder paradigm, CGS 12066B (0.5-5.0 mg/kg) decreased resident offensive aggression, social interest, and exploration while dose-dependently enhancing defensive behaviours across the dose range tested. CP-94,253 (2.5-10.0 mg/kg) also reduced elements of resident offensive behaviour whereas defensive behaviours were largely unchanged. Some elements of resident nonsocial and social behaviour were enhanced at 2.5 and 5.0 mg/kg but decreased at 10.0 mg/kg. The behavioural profile of CP-94,253, but not CGS 12066B, supports the proposal that 5-HT1B receptors inhibit agonistic behaviour without concomitant sedative or anxiogenic effects. Findings are discussed in relation to 5-HT1A/1B/2C receptors involved in agonistic behaviour and anxiety.
Agonistic Behavior↗
Costs of intrapartum care in a midwife-managed delivery unit and a consultant-led labour ward.
OBJECTIVE: to investigate whether there are differences between the cost of intrapartum care for women at low obstetric risk in a midwife-managed labour and delivery unit and that in a consultant-led labour and delivery ward. DESIGN: cost analysis based on the findings of a randomised controlled trial comparing two alternative types of intrapartum care. SETTING: Aberdeen Maternity Hospital, Grampian. SUBJECTS: the number of women 'booked' for care in the Midwives' Unit in a standard year and a comparable group of women cared for in the consultant-led labour ward. PRIMARY OUTCOME MEASURE: the cost 'outcome' is the extra (or reduced) cost per woman resulting from the introduction of a midwife-managed delivery unit. FINDINGS: the baseline extra cost of the introduction of the Midwives' Unit was found to be 40.71 pounds per woman. Depending on the scenario used, this ranged from a cost saving of 9.74 pounds per woman to an additional cost of 44.23 pounds per woman. CONCLUSIONS: this study has shown that, in terms of costs incurred during the intrapartum period, the marginal cost of caring for women at low obstetric risk alongside women at high obstetric risk in a standard labour ward is small. However, the impact of establishing a separate midwife-managed delivery unit, requiring an increase in midwifery staffing levels, can be significant.
Cost-Benefit Analysis↗
Stepwise or couple antenatal carrier screening for cystic fibrosis?: women's preferences and willingness to pay.
Several antenatal cystic fibrosis carrier screening trials have offered women testing by either the stepwise or the couple method. In this study, both approaches were described to women attending an antenatal clinic, who were then asked which method they preferred. An estimate of the value to women of each type of test was also ascertained using a "willingness to pay" (WTP) method. Of 450 women, 279 (62%) preferred stepwise screening, 117 (26%) preferred couple screening, and 54 (12%) had no preference. Mean WTP for stepwise screening was 19 pounds (95% CI 17.50 pounds-20.50 pounds), and that for couple screening was 18 pounds (95% CI 16.50 pounds-19.50 pounds). The majority of women preferred stepwise screening although the average WTP for each method was similar.
Anxiety↗
Analysis of cord blood CD34+ cells purified after cryopreservation.
Many practical issues regarding processing blood samples for cord blood banking remain. After cryopreservation, a reduction in clonogenicity has been reported, although it is unknown whether this is associated with lower potential for long-term engraftment. CD34+ cell purification of cryopreserved cord blood (CB) may be important for the clinical application of in vitro expansion. We compared purity, yield, clonogenicity, and growth in long-term stromal-based culture of fresh and cryopreserved CD34+ purified cells (n = 12) using the miniMACS separation system. Mean purity of CD34+ cells was 93% when processed before and 73% when processed after cryopreservation. Fresh CD34+ cells had higher clonogenic potential than cryopreserved cells (45 vs 20%, p < 0.05) in CFU-Mix assays, indicating that progenitor cell loss during cryopreservation is due in part to reduced cloning efficiency of viable CD34+ cells. In long-term culture (LTC) on irradiated normal human bone marrow stroma (n = 7), CFU-GM production in the two groups was the same over 12 weeks, suggesting identical long-term culture-initiating cell (LTC-IC) numbers. We conclude that apparent clonogenic cell loss during cryopreservation is associated with relative sparing of the more primitive LTC-ICs. CFU-Mix assays may therefore underestimate the transplant potential of cryopreserved CB. Purification of CD34+ cells following cryopreservation gives sufficient purity for detailed evaluation of CD34+ cells and for stem cell expansion.
Antigens, CD34↗
Midwife managed delivery unit: a randomised controlled comparison with consultant led care.
OBJECTIVE: To examine whether intrapartum care and delivery of low risk women in a midwife managed delivery unit differs from that in a consultant led labour ward. DESIGN: Pragmatic randomised controlled trial. Subjects were randomised in a 2:1 ratio between the midwives unit and the labour ward. SETTING: Aberdeen Maternity Hospital, Grampian. SUBJECTS: 2844 low risk women, as defined by existing booking criteria for general practitioner units in Grampian. 1900 women were randomised to the midwives unit and 944 to the labour ward. MAIN OUTCOME MEASURES: Maternal and perinatal morbidity. RESULTS: Of the women randomised to the midwives unit, 647 (34%) were transferred to the labour ward antepartum, 303 (16%) were transferred intrapartum, and 80 (4%) were lost to follow up. 870 women (46%) were delivered in the midwives unit. Primigravid women (255/596, 43%) were significantly more likely to be transferred intrapartum than multi-gravid women (48/577, 8%). Significant differences between the midwives unit and labour ward were found in monitoring, fetal distress, analgesia, mobility, and use of episiotomy. There were no significant differences in mode of delivery or fetal outcome. CONCLUSIONS: Midwife managed intrapartum care for low risk women results in more mobility and less intervention with no increase in neonatal morbidity. However, the high rate of transfer shows that antenatal criteria are unable to determine who will remain at low risk throughout pregnancy and labour.
Consultants↗
Commentary: possible road to efficiency in the health service.
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Efficiency, Organizational↗
Distribution of corticotropin-releasing factor receptor mRNA expression in the rat brain and pituitary.
Corticotropin-releasing factor (CRF) is a major hypophysiotropic peptide regulating pituitary-adrenal response to stress, and it is also widely expressed in the central nervous system. The recent cloning of cDNAs encoding the human and rat CRF receptors has enabled us to map the distribution of cells expressing CRF receptor mRNA in rat brain and pituitary by in situ hybridization. Receptor expression in the forebrain is dominated by widespread signal throughout all areas of the neo-, olfactory, and hippocampal cortices. Other prominent sites of CRF receptor mRNA expression include subcortical limbic structures in the septal region and amygdala. In the diencephalon, low levels of expression are seen in a few discrete ventral thalamic and medial hypothalamic nuclei. CRF receptor expression in hypothalamic neurosecretory structures, including the paraventricular nucleus and median eminence, is generally low. In the brainstem, certain relay nuclei associated with the somatic (including trigeminal), auditory, vestibular, and visceral sensory systems, constituted prominent sites of CRF receptor mRNA expression. In addition, high levels of this transcript are present in the cerebellar cortex and deep nuclei, along with many precerebellar nuclei. In the pituitary, moderate levels of CRF receptor mRNA expression were detected throughout the intermediate lobe and in a subset of cells in the anterior lobe identified as corticotropes by concurrent immunolabeling. Overall, the central distribution of CRF receptor mRNA expression is similar to, though more expansive than, that of regions reported to bind CRF, and it shows limited overlap with loci expressing CRF-binding protein. Interestingly, CRF receptor mRNA is low or undetectable in several cell groups implicated as central sites of CRF action.
Adrenocorticotropic Hormone↗
Compliance in screening programmes.
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Female↗