Biomedical subjects
R A Jones
Publications and source records attributed to R A Jones.
Midwives and money matters. A simple guide to mortgages.
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Midwives and money matters: taxation and rebates.
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Midwives and money matters. Why you should consider making a will.
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Mechanism of synergy of levamisole and fluorouracil: induction of human leukocyte antigen class I in a colorectal cancer cell line.
BACKGROUND: The use of the combination of fluorouracil (5-FU) and levamisole has been shown to improve the survival of patients with resected Dukes' stage C colon carcinoma. 5-FU is incorporated into RNA, which results in aberrant processing and turnover of RNA. Neither the mechanism of synergy between the two drugs nor the precise molecular mechanism of action of levamisole is known. Each drug has previously been shown to alter the expression of class I human leukocyte antigens (HLA class I) in colorectal cancer cell lines. PURPOSE: The purpose of this study was to explore the mechanism of interaction between 5-FU and levamisole by investigating the effect of this combination on HLA class I gene expression in the colorectal cancer cell line WiDr. METHODS: WiDr cells were treated either with 5-FU alone or with 5-FU and levamisole. Expression of HLA class I antigens was analyzed by flow cytometry using the monoclonal antibody W6/32. Specific DNA probes for HLA class I, beta 2-microglobulin, beta-actin, HLA class II, and p53 (also known as TP53) were used in Northern blot analysis of the steady-state level of messenger RNAs (mRNAs) and for "run-on" transcription analysis. RESULTS: 5-FU alone produced more than 50% increases in the expression of the HLA class I antigens, and levamisole caused a further 8%-18% increase. 5-FU caused the steady-state level of HLA class I mRNAs to increase by about 80%, and levamisole enhanced this effect of 5-FU by a further 70%. 5-FU did not increase the other mRNAs. In vitro run-on transcription revealed that 5-FU caused a 20%-57% reduction in RNA synthesis, while levamisole caused a 30%-190% increase in RNA synthesis. Levamisole therefore reversed the inhibition of RNA synthesis caused by 5-FU. Both drugs had a general effect on RNA synthesis that was not restricted to HLA class I transcription. CONCLUSIONS: The apparent synergy between levamisole and 5-FU is a result of the incorporation of 5-FU, which may stabilize HLA class I mRNAs, leading to their accumulation, while levamisole augments the accumulation of these stable mRNAs by increasing the rate of transcription. IMPLICATIONS: Levamisole reduces the toxicity of 5-FU caused by generalized inhibition of RNA synthesis, and at the same time augments the effects of 5-FU, which may be due to selective stabilization of certain mRNAs.
Can an echocardiographic score predict who will benefit clinically from balloon dilation of the mitral valve?
Deciding whether a patient with sub-optimal mitral valve anatomy will benefit from percutaneous mitral valvotomy remains a demanding clinical problem. We assessed the ability of an established echo score applied to transoesophageal images to predict absolute increases in mitral valve area and improvement in exercise capacity. Twenty five consecutive patients undergoing routine percutaneous mitral valvotomy were studied. Changes in exercise tolerance were measured by serial cardiorespiratory treadmill exercise testing. Before the procedure, exercise duration was directly related to mitral valve area (rs = 0.44, P < 0.05). Following percutaneous mitral valvotomy there was an increase in valve area (0.9 +/- 0.2 to 1.4 +/- 0.3 cm2, P < 0.0001) and repeat exercise testing demonstrated increases in exercise duration (470 +/- 220 to 610 +/- 240 s, P < 0.001) and peak VO2 (12.6 +/- 4.2 to 15.1 +/- 4.5 ml/kg/min, P < 0.01). There was an inverse correlation between the echo score and the increase in valve area (rs = -0.52, P < 0.05) but no relationship between the echo score and the increase in exercise duration or peak minute oxygen consumption (VO2). These data demonstrate that a score applied to transoesophageal images echocardiographic images can predict changes in mitral valve area but that the score fails to predict functional improvement for an individual patient. This suggests, therefore, that patients without contraindications to valvotomy whose valves have a high echo score should still be considered for valvotomy as they may benefit considerably from the procedure.
Nasal complications of the direct transnasal approach to the pituitary fossa.
The transnasal trans-sphenoidal approach to the pituitary fossa is direct and fast. This study is aimed at establishing the nasal morbidity arising from this approach. One of the 25 patients developed secondary haemorrhage and another suffered recurrent minor epistaxis. The peak nasal inspiratory flow rates showed no significant difference between the left and right anterior nasal passages. Adhesions were noted in seven patients and no septal perforations were found. Three patients, who had no previous nasal symptoms, developed postoperative unilateral nasal obstruction, two secondary to left septal deviation and the other caused by right-sided anterior nasal space adhesions. The study suggests that the operation has a low nasal morbidity.
Combined perfusion and diffusion-weighted magnetic resonance imaging in a rat model of reversible middle cerebral artery occlusion.
BACKGROUND AND PURPOSE: Diffusion-weighted imaging and dynamic first-pass bolus tracking of susceptibility contrast agents (perfusion imaging) are two new magnetic resonance imaging techniques that offer the possibility of early diagnosis of stroke. The present study was performed to evaluate the diagnostic information derived from these two methods in a rat model of temporary focal ischemia. METHODS: Fifteen male Wistar rats were assigned to 45 (n = 7) or 120 minutes (n = 8) of middle cerebral artery occlusion followed by reperfusion using the intraluminal filament technique. The diffusion-weighted images were collected, and areas of hyperintensity were compared with histologically assessed areas of ischemic injury. The magnetic resonance perfusion image series were postprocessed to produce topographic maps reflecting the maximum reduction in the signal obtained during the first passage of the contrast agent and the time delay between the arrival of the bolus and the point of maximum contrast-agent effect. RESULTS: Hyperintensity in diffusion-weighted images was demonstrated after 30 minutes of middle cerebral artery occlusion and was mainly expressed in the lateral caudoputamen and parts of the lower frontoparietal cortex. Reperfusion after 45 minutes of occlusion reduced the area of hyperintensity from 24.2% to 9.9% of hemispheric area. In the group with 120 minutes of occlusion, the hyperintense area increased from 24.4% to 29.1%. Relative to the nonischemic hemisphere, the changes in the topographic maps of maximum signal reduction occurred in the lateral caudoputamen and adjacent lower neocortical areas. Increased time delay to maximum effect, however, was seen also in the upper frontoparietal cortex. CONCLUSIONS: Hyperintensity in diffusion-weighted images was reversible after 45 minutes but not after 120 minutes of middle cerebral artery occlusion. Analysis of the signal-reduction and time-delay parametric maps demonstrated regions of different perfusion changes in the ischemic hemisphere.
Perfusion and diffusion-weighted MR imaging for in vivo evaluation of treatment with U74389G in a rat stroke model.
BACKGROUND AND PURPOSE: The present study was performed to examine the potential of diffusion-weighted (DW) imaging and dynamic first-passage bolus tracking of susceptibility contrast agents (perfusion imaging) for early in vivo evaluation of the effects of treatment with the free radical scavenger U74389G in a rat model of temporary focal ischemia. METHODS: After 45 minutes of middle cerebral artery occlusion, the treatment group (n = 9) received an infusion of U74389G, and the control group (n = 9) received the identical volume of the vehicle. Reperfusion was instituted in both groups after 120 minutes of middle cerebral artery occlusion. The DW images were collected during middle cerebral artery occlusion and reperfusion and were compared with histologically assessed areas of tissue injury after 2 hours of reperfusion. The dynamic perfusion series were processed on a pixel-to-pixel basis to produce parametric maps reflecting the maximum reduction in the signal obtained during the first passage of the contrast agent and the time delay between the arrival of the bolus and the point of maximum contrast-agent effect. RESULTS: The area of ischemic injury, as assessed from the DW imaging at 60 minutes of reperfusion, was significantly smaller in the treatment group: 9 +/- 8% of ipsilateral hemisphere compared with 19 +/- 8% in the control group. The histological examination after 2 hours of reperfusion demonstrated an area of ischemic injury of 10 +/- 8% for the treatment group compared to 25 +/- 10% in the control group. In the treatment group, the perfusion imaging showed a reduction in time delay to maximum effect of the contrast agent in the ischemic hemisphere compared with the control group. CONCLUSIONS: The DW imaging during early reperfusion showed a protective effect of postocclusion treatment with the free radical scavenger U74389G. The improvement of time delay to maximum effect of the contrast agent observed in the perfusion imaging of the treatment group may reflect an improvement in the collateral flow to the ischemic tissue.
Preconditioning by brief ischaemic episodes in the isolated rat heart assessed by 31P NMR spectroscopy: dissociation between metabolic and functional recovery?
31P NMR spectroscopy was used to investigate whether improved functional recovery in ischaemic preconditioning was due to improved metabolic recovery in isolated rat hearts. The preconditioning stimulus was global ischaemia of 1 or 4 min followed by 12 min of reperfusion (Langendorff mode). The hearts were then subjected to a main ischaemic period of 16 min and 40 min of reperfusion. Functional and metabolic recoveries of hearts were compared to a control group subjected only to the main ischaemia. Preconditioning improved recovery of contractile function during the final reperfusion. Thus left ventricular developed pressure (LVDP) and heart rate (HR) product after 40 min of reperfusion recovered to 56, 67 and 68% in the control group, 1 min group and 4 min group, respectively. However, the metabolic recovery was comparable in all groups. CrP and ATP recovered to levels of 67-78% (CrP) and 35-41% (ATP), and pH to a level of 7.13-7.15 (not different from baseline values) at the end of the final reperfusion. We conclude that the improved functional recovery in preconditioning is not due to a higher level of high energy phosphates or less acidosis during the final reperfusion.
Immunophenotypic and DNA genotypic analysis of T-cell and NK-cell subpopulations in patients with B-cell chronic lymphocytic leukaemia (B-CLL).
Absolute numbers and distributions of peripheral blood T-cells and NK cells were immunophenotypically determined in 21 patients with B-CLL and compared with those obtained from a series of 13 elderly normal controls with an age range of 60-87 years. For absolute CD3+, CD4+ and CD8+ T-cell, and CD16+ NK subpopulation numbers, there were no consistent differences between the normal and B-CLL groups although some individual patient variation was seen. Immunophenotypic analyses did however reveal that CD3+ T-cells in almost half (10/21) of the B-CLL patients were Ia+ (defined as > 20% positive cells), compared to 0/13 of the elderly control group (p < 0.001), and that the proportions of CD4+ and CD8+ cells expressing membrane CD45RO were significantly increased compared to the control group. Subdivision of the B-CLL cases into those with low (< 20%) and high (> 20%) proportions of CD3+ T-cells co-expressing Ia further showed that CD45RO expression by CD4+ fractions was particularly prominent in the Ia+ subgroup, and that the relative increase of CD4+CD45RO+ cells was primarily a consequence of decreased absolute numbers of CD4+CD45RA+ lymphocytes. This study also examined extracted DNA from enriched CD3+ T-cell fractions (obtained by immunomagnetic bead selection in 9 of the B-CLL cases) by PCR analysis with two primers for the T-cell gamma gene locus. With the V gamma C (consensus) primer, 8/9 cases were polyclonal and the remaining case was oligoclonal. For comparison, 7/9 CD3+ fractions were oligoclonal with the V gamma 9 primer with the other two cases being polyclonal. No monoclonal CD3+ components were found. It is suggested that the observed increased Ia expression by CD3+ cells and the predominance of CD4+ cells expressing membrane CD45RO in patients with B-CLL may be of potential relevance to understanding the pathogenesis and patterns of disease progression.
CD45RO+ T-cells immunoregulate spontaneous in vitro immunoglobulin production by normal and chronic lymphocytic leukaemia B-cells.
Immunophenotypic changes in the T-cell compartment in B-CLL are well recognised, although the functional significance is less well established. In this study we examined the immunoregulatory capacity of CD45RO+ T-cells to modulate in vitro IgG and IgM production by B-CLL cells in comparison to normal PB B-cells. Removal of CD45RO+ T-cells from normal PB lymphocyte cultures was associated with a 2.3-fold reduction in IgM production and a 7.9-fold reduction in IgG production. Activation of the T-cell component by alpha CD3 stimulation enhanced IgG and IgM production by factors of 1.85 and 3.4 respectively. Removal of CD45RO+ T-cells from alpha CD3-stimulated cultures reduced IgG production 3.7-fold, whereas no significant change in IgM production occurred. Supplementing T- and NK-depleted B-cell fractions with purified autologous CD45RO+ T-cells produced a positive correlation between Ig concentration and the CD45RO:CD19 ratio for IgG production but not for IgM. Collectively, these results suggest that: 1) 'resting' CD45RO+ ('primed' or memory) T-cells drive mainly the IgG response; 2) activation of these T-cells enhances this response; 3) activated CD45RO+ T-cells derived from the recent transformation of the CD45RA+ ('virgin' or naive) population drives mainly the IgM response. In B-CLL cultures however, the pattern of Ig production in response to alpha CD3 stimulation is more typical of regulation by CD45RO+ T-cells derived from the recent activation of virgin CD45RA+ T-cells. We believe this challenges the view that T-cells in B-CLL are largely memory cells.
Evaluation of a nursing documentation system revision.
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Synthesis of [15N]-labeled DNA fragments.
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Trauma audit--closing the loop.
The philosophy of medical audit and methods of data collection and statistical analysis have been extensively reviewed but less has been written about the effect of audit on medical practice. The measurement of performance is only valuable if it identifies areas of concern and stimulates appropriate change. This paper describes the work of the Salford Trauma Audit Group which has been developed at Hope Hospital, the problems that have been recognized, the strategies that have been introduced to effect change and their influence on management and outcome. Analysis of performance reveals an initial fall in adjusted mortality rate from severe injury after the introduction of resuscitation teams, the adherence to Advanced Trauma Life Support protocols and an integrated multidisciplinary approach to trauma care. Problems remain and there is continuing concern about trauma management in the hospital. This has been reinforced by performance feedback through the Trauma Audit Group which has attracted the interest of senior clinicians in several specialties.
Conceptual development of nurse-physician collaboration.
The concept of nurse-physician collaboration has significance in today's changing health care environment. Two camps' views concerning nurse-physician collaboration are presented. Camp I supports nurse-physician collaboration using four indicators: (1) mutual power-control, (2) separate and combined practice spheres, (3) mutual concerns, and (4) common patient goals. Camp II takes a totally different approach and describes the structure that must be present before collaboration may exist. The literature supports the use of both camps' views in developing measures for the concept of collaboration. Once these aspects of collaboration can be accurately measured then recommendations can be made concerning changes needed in health care delivery systems to effect outcomes.
Nurse-physician collaboration: a descriptive study.
The purpose of this research was to investigate the nature of nurse-physician collaboration using four indicators (power-control, practice spheres, concerns, and goals) in a random mail survey of registered nurses (N = 59) and physicians (N = 67) in a midwestern metropolitan county. Subjects completed a nurse or physician communication scale, an adaptation of the Weiss and Davis Collaborative Practice Scales, a practice spheres, and a goals checklist. Nurses and physicians were homogeneous on the power-control indicator, (chi 2 = .3(3), p = .98) and concern indicator (chi 2 = 7.2(4), p = .13). Nurses and physicians were inconsistent in their perceptions of responsibilities for practice spheres and patient goals. Relationships of demographic variables to collaboration indicators supported profiles of nurses and physicians who may be less collaborative.
Experience with the direct transnasal transsphenoidal approach to the pituitary fossa.
The direct transnasal transsphenoidal approach to the pituitary fossa has been used in our unit since 1987. We describe the procedure and report its use in 48 patients with pituitary lesions. Successful access to the pituitary fossa was made in 46 out of 50 operations (92%). In two cases, repeat transnasal exploration was successfully performed for recurrent tumour 3 and 5 years following an initial trans-nasal exploration. This approach is straightforward, quick and does not require dissection of nasal mucosa or removal of septal cartilage. There was a 5.8% rate of major post-operative complications, and this compares favourably with other routes of access to the pituitary fossa. No long-term nasal, septal or dental complications have occurred, such as may happen with the other routes to the sphenoid sinus and pituitary fossa.