PCA: patient-controlled analgesia or politically correct analgesia?
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Analgesia, Patient-Controlled↗
Biomedical subjects
P Salmon
Publications and source records attributed to P Salmon.
High-level transgene expression in human hematopoietic progenitors and differentiated blood lineages after transduction with improved lentiviral vectors.
Recent experiments point to the great value of lentiviral vectors for the transduction of human hematopoietic stem cells (hHSCs). Vectors used so far, however, have been poorly satisfying in terms of either biosafety or efficiency of transgene expression. Herein is described the results obtained with human immunodeficiency virus-based vectors optimized in both of these aspects. It is thus shown that vectors containing the EF1alpha and, to a lesser extent, the phosphoglycerate kinase (PGK) promoter, govern high-level gene expression in human hematopoietic progenitors as well as derived hematopoietic lineages of therapeutic relevance, such as erythrocytes, granulocytes, monocytes, dendritic cells, and megakaryocytes. EF1alpha promoter-containing lentiviral vectors can also induce strong transgene expression in primary T lymphocytes isolated from peripheral blood. A self-inactivating design did not affect the performance of EF1alpha promoter-based vectors but significantly reduced expression from the PGK promoter. This negative effect could nevertheless be largely rescued by inserting the post-transcriptional regulatory element of woodchuck hepatitis virus upstream of the vector 3' long terminal repeat. These results have important practical implications for the genetic treatment of lymphohematologic disorders as well as for the study of hematopoiesis via the lentivector-mediated modification of hHSCs.
Antigens, CD34↗
Reversible immortalization of human primary cells by lentivector-mediated transfer of specific genes.
We exploited the ability of lentiviral vectors to govern the stable transduction of cells irrespective of their cycling status to induce the reversible immortalization of human primary cells. First, bicistronic HIV-derived lentiviral vectors expressing GFP- and the HSV1 thymidine kinase and containing the LoxP sequence in their LTR (HLox) were used to transduce HeLa cells. Cre expression led to efficient proviral deletion, and unexcised cells could be eliminated by ganciclovir treatment. A human liver biopsy was then exposed to a combination of HLox vectors that harbored either the SV40 large T (TAg) or the human telomerase (hTERT) DNAs in place of GFP. This led to the isolation of liver sinusoidal endothelial cell (LSEC) clones that exhibited an immortalized phenotype while retaining most of the features of primary hLSEC. Complete growth arrest of these cells was observed in 2 days of Cre expression, and the resulting stationary culture could be kept for at least 2 weeks. Transduction of human adult pancreatic islets with HLox vectors coding for Tag and Bmi-1 also induced the proliferation of insulin-positive cells. These results indicate that lentivectors can be used to mediate the reversible immortalization of primary nondividing cells and should allow for the production of large supplies of a wide variety of human cells for both therapeutic and research purposes.
Animals↗
Residual fructose and osmolality affect the levels of pneumocandins B0 and C0 produced by Glarea lozoyensis.
A high total pneumocandin titer (B0 + C0) with a low percentage of the structural isomer pneumocandin C0 was achieved by carrying out fermentations of Glarea lozoyensis at a high residual fructose concentration (125 g/l initial). When the fermentation was carried out at a low residual fructose concentration (40 g/l initial), pneumocandin production increased by 34%. However, a disproportionate increase in the level of pneumocandin C0 synthesized (250% increase vs 30% increase for pneumocandin B0) was observed. Midcycle addition of 150 mM NaCl or 116 mM Na2SO4 to low residual fructose fermentations returned the titer and isomer levels to those seen for the high residual fructose fermentation. The increase in pneumocandin C0 synthesis under low residual fructose conditions appears to be linked to the increase in the synthesis of trans-4 hydroxyproline, with the synthesis of trans-3 hydroxyproline remaining unaffected. This suggests that the formation of pneumocandin C0 is the result of a misincorporation of trans-4 hydroxyproline instead of trans-3 hydroxyproline by the pneumocandin peptide synthetase, and that the amount of trans-4 hydroxyproline formed dictates the frequency of this misincorporation.
Anti-Bacterial Agents↗
Surgery in the absence of pathology the relationship of patients' presentation to gynecologists' decisions for hysterectomy.
OBJECTIVE: To test predictions from a theory about patients' influence over doctors' treatment decisions when physical symptoms are presented in the absence of physical pathology. METHOD: We audiotaped 88 gynecological consultations of consecutive patients who presented menstrual symptoms without pathology. Each consultation was coded according to a scheme, developed from previous qualitative research, which identified specific strategies of patients and gynecologists. The occurrence of each strategy was compared between consultations in which hysterectomy was decided upon (N=15) and those leading to conservative treatment. RESULTS: Consultations were more likely to lead to hysterectomy if patients deployed specific strategies, including reporting social effects of symptoms, catastrophization, requesting surgery and citing clinical or lay authority in support. Each strategy could account statistically for gynecologists' perceptions that decisions for hysterectomy reflected patients', rather than gynecologists', influence. CONCLUSION: The findings are consistent with the theory that, in the absence of physical pathology, patients deploy specific strategies that influence gynecologists to offer surgery.
Adult↗
Patients who present physical symptoms in the absence of physical pathology: a challenge to existing models of doctor-patient interaction.
Many patients seek physical treatment for physical symptoms in the absence of physical pathology and incur symptomatic interventions that are ineffective, costly and iatrogenic. It is therefore important to understand how decisions to provide physical intervention can arise in consultations in the absence of physical pathology. Existing models of doctor-patient communication are ill-suited to understanding these consultations. A series of studies has provided the components of an alternative approach that is based on understanding consultation from the patients' perspective. Specifically, these studies have delineated: sources of patients' perception of their authority over doctors; what patients seek by consulting their doctors; and ways that patients use their authority to influence doctors to provide what they seek. Patients' authority reflects primarily their own sensory and infallible knowledge of symptoms. Their influence derives from descriptions of subjective symptoms and from additional strategies including descriptions of the psychosocial effects of symptoms, catastrophising and requesting treatment. This analysis suggests directions for future research and medical training.
Attitude of Health Personnel↗
Hip and knee arthroplasty: a comparison and the endocrine, metabolic and inflammatory responses.
Changes in circulating levels of catecholamines, cortisol, glucose, interleukin-6 and C-reactive protein and in the leucocyte count were investigated for 7 days after surgery in 158 patients undergoing hip or knee arthroplasty. We compared the responses to the two operations, and also examined the effects of pathology (osteoarthritis and rheumatoid arthritis) on the changes associated with knee arthroplasty. Exploratory factor analysis was applied to the data to identify the variables and sampling times that could be used in future to provide a concise description of the response. Patients undergoing knee arthroplasty showed significantly greater changes in noradrenaline, adrenaline and glucose levels, but not in cortisol levels, compared with those undergoing hip arthroplasty. Interleukin-6 and C-reactive protein concentrations were also significantly greater in knee patients than hip patients; however, when corrected for pathology, many of these differences were not significant. Minimal effects of pathology (chronic inflammation with rheumatoid arthritis) were found on the hormonal changes in knee patients. In particular, there was little evidence to support the inference from animal data that the hypothalamic-pituitary-adrenal axis is impaired. The expected increases in interleukin-6 and C-reactive protein concentrations were found in the rheumatoid arthritis patients. Exploratory factor analysis showed that the response could be separated into six components, accounting for 60% of the total variance, and identified the variables and sampling times indicative of each. In conclusion, there are differences in the hormonal, but not inflammatory, responses to hip and knee arthroplasty. Little evidence was found for an important effect of pathology on the changes associated with knee surgery. Factor analysis provided a useful summary of the data.
Aged↗
The role of CD8 alpha' in the CD4 versus CD8 lineage choice.
During thymic development the recognition of MHC proteins by developing thymocytes influences their lineage commitment, such that recognition of class I MHC leads to CD8 T cell development, whereas recognition of class II MHC leads to CD4 T cell development. The coreceptors CD8 and CD4 may contribute to these different outcomes through interactions with class I and class II MHC, respectively, and through interactions with the tyrosine kinase p56lck (Lck) via their cytoplasmic domains. In this paper we provide evidence that an alternatively spliced form of CD8 that cannot interact with Lck (CD8 alpha') can influence the CD4 vs CD8 lineage decision. Constitutive expression of a CD8 minigene transgene that encodes both CD8 alpha and CD8 alpha' restores CD8 T cell development in CD8 alpha mutant mice, but fails to permit the development of mismatched CD4 T cells bearing class I-specific TCRs. These results indicate that CD8 alpha' favors the development of CD8-lineage T cells, perhaps by reducing Lck activity upon class I MHC recognition in the thymus.
Animals↗
Patients' perceptions of medical explanations for somatisation disorders: qualitative analysis.
OBJECTIVES: To describe, from the perspective of patients, distinguishing features of doctors' attempts to explain the symptoms of somatisation disorders. DESIGN: Qualitative analysis of verbatim records of interviews in which patients recounted doctors' explanations of their symptoms. SETTING: Patients with persistent somatising symptoms referred from general practices in Liverpool and St Helens and Knowsley were interviewed before entry into a treatment programme. SUBJECTS: 228 of 324 patients referred were interviewed. Initial interviews were used to develop the process and technique, and the final analysis was based on a subsample of 68 records, randomly chosen from the transcripts of 188 subjects who were interviewed subsequently. RESULTS: Doctors' explanations were often at odds with the patients' own thinking. Analysis showed that medical explanations could be grouped into one of three categories, defined by the patients' perceptions. Most explanations were experienced as rejecting the reality of the symptoms. An intermediate category comprised explanations that were viewed as colluding, in which the doctor acquiesced with the patients' own biomedical theories. However, a few explanations were perceived by patients as tangible, exculpating, and involving. These explanations were experienced by patients as satisfying and empowering. CONCLUSIONS: Patients with somatisation disorders feel satisfied and empowered by medical explanations that are tangible, exculpating, and involving. Empowering explanations could improve these patients' wellbeing and help to reduce the high demands they make on health services.
Adult↗
The association of sexual and physical abuse with somatization: characteristics of patients presenting with irritable bowel syndrome and non-epileptic attack disorder.
BACKGROUND: Physical symptoms are commonly presented for treatment in the absence of physical pathology. This study tests predictions arising from the theory that childhood sexual abuse leads to emotional distress, illness orientation and social dysfunction as adults and that one or more of these effects, in turn, leads to presentation of functional (i.e. unexplained) symptoms. METHODS: Two groups of patients with physical symptoms in the absence of organic disease (non-epileptic attack disorder or irritable bowel syndrome) were contrasted with organically diseased groups with comparable symptoms (epilepsy and Crohn's disease, respectively). RESULTS: Despite their contrasting clinical presentation, irritable bowel and non-epileptic attack groups were similar in recalling more sexual and physical abuse, as both children and adults, than their comparison groups. They were also similar in being more emotionally and socially disturbed and illness-orientated, but these putative mediating variables could not account for the relationship of abuse with presentation of functional symptoms. CONCLUSIONS: Adults presenting functional neurological and abdominal symptoms are characterized by history of abuse. The current focus on childhood sexual abuse should be broadened to include sexual, and particularly physical, abuse in adulthood as well as childhood. The intervening processes that link abuse to somatization remain to be identified but are unlikely to include adult emotional and social disturbance or general illness-orientation.
Adult↗
Why do patients feel positive about patient-controlled analgesia?
We studied 200 patients to identify the aspects of their experience of patient-controlled analgesia (PCA) that made them feel 'extremely positive' about this technique. After PCA had been withdrawn, patients completed a questionnaire which included the following topics: pre-operative information, pain relief, the degree of control that PCA afforded the patient, side-effects and safety. Multiple regression analysis identified three factors of their experience which were associated uniquely with feeling 'extremely positive' about PCA: having better pain relief, not worrying about 'giving oneself too much drug' and not experiencing feeling 'peculiar in the head'. Control over pain relief, although highly correlated with feeling 'extremely positive' about PCA, was unimportant when these variables were controlled. Because of the well-recognised difficulties in measuring satisfaction with analgesic regimens, we suggest that a satisfaction score based on these variables would be a significant advance on existing methods.
Analgesia, Patient-Controlled↗
The systematic assessment of short-term functional recovery after major joint arthroplasty.
Despite extensive information about long-term recovery from major joint arthroplasty, little attention has been given to the measurement of functional recovery in the immediate postoperative period. Therefore assumptions about the importance of physical therapy during this period remain untested. We devised a way of recording functional recovery before discharge, based primarily on the achievement of objective milestones. This was incorporated into routine physiotherapy practice and applied to sequential patients undergoing elective hip (n = 163) or knee (n = 66) replacement. Six months later, we followed up 160 patients, of whom 145 completed questionnaires to assess subjective physical and emotional state and functional recovery. The method was sensitive to known influences on pace of recovery, including type of arthroplasty (hip vs knee) and surgeons' differing requirements for mobilization. In addition, we were able to confirm and quantify sources of variation in functional recovery which previously were suspected but unconfirmed: in particular, the timing of early mobilization. Outcome at 6 months was unrelated to objective functional recovery in hospital, although fatigue and wellbeing at this time were predicted by physiotherapists' subjective assessment of patients' motivation before discharge. The findings can be used to inform patients and as a source of comparison data for the assessment of functional recovery in other centres. More importantly, the procedure reported may be applied to quantify functional recovery in routine practice and thereby expose variability in recovery to scientific scrutiny.
Aged↗
Plasma catecholamines, pharmacotherapy and mood of subjects with cardiovascular disorder.
This study investigated whether drug therapy explains why the concentration of arterial plasma catecholamines in patients who have received an orthotopic heart transplant (OHT) or coronary bypass and graft (CABG) is greater than in those with heart failure (HF). The results suggest that the differences in plasma catecholamine concentrations in these groups of patients could not be attributed to administration of any of the drugs studied here. An additional finding is that the use of aspirin is associated with a higher concentration of plasma noradrenaline, but not adrenaline. Patients who were taking aspirin also had a more positive mood, as rated by the Profile of Mood States; this was mainly because they had a lower fatigue score than did patients who were not taking this drug. In contrast, several agents (warfarin, Ca2+-channel blockers and 'mixed cardiac' drugs), which had no effects on catecholamine overspill, were linked with negative mood; this was expressed consistently as a higher tension score. These findings suggest that drugs which are administered for their effects in the periphery could also influence patients' psychological status. With the possible exception of aspirin, this does not involve changes in spillover of catecholamines in the periphery.
Adult↗
Psychological adjustment after cardiac transplantation.
Psychosocial function improves after cardiac transplantation but the extent of improvement is not established. Neither are the factors established that account for variability in function between patients following successful transplantation. We therefore compared illness-related dysfunction in patients following orthotopic cardiac transplantation (OCT) with that in angina-free patients following coronary artery bypass graft (CABG) and stable patients in heart failure awaiting transplantation (HF). We also measured two factors that might contribute to variation in function: emotional distress and concern with physical symptoms. Psychosocial function was as good in OCT as in CABG patients and, in both, was better than in HF patients. Differences in emotional distress and in physical symptoms showed a similar pattern and contributed to, but did not completely account for, differences in function. Concern with physical symptoms contributed to variability in functional impairment in HF but not CABG patients; transplantation strengthened this relationship. The results show that successful cardiac transplantation enhances psychosocial function to a level comparable with that after CABG, and suggest targets for psychological or educational intervention to improve quality of life after transplantation in patients whose recovery is inhibited by concern about physical symptoms.
Adaptation, Psychological↗
Patients' reactions to attempts to increase passive or active coping with surgery.
It is generally regarded as valuable for patients to exercise control over aspects of their medical treatment. Although psychological and other interventions are commonly used with the aim of increasing patients' ability or willingness to control events, it is not known whether patients experience these procedures in the way assumed. The present study compared responses to (i) a psychological intervention designed to increase patients' readiness to exercise control and cope actively and (ii) a comparable intervention intended to induce acceptance and passive coping. Hip or knee arthroplasty patients were visited preoperatively by a researcher who administered the active (N = 15) or passive (N = 15) intervention in a dialogue with the patient. Patients' verbal responses to the interventions were analyzed qualitatively to identify the range of reactions to each type of intervention. Patients readily accepted the passive message on the grounds of doctors' and nurses' authority and the value of the patients' emotional detachment from their surgery. Few responses to the active message indicated acceptance that patients have control over their care and its outcomes; instead, recipients typically interpreted it in terms of the need for obedience to medical and nursing authority. In conclusion, patients do not automatically accept messages intended to change ways of coping. In particular, the attempt to increase patients' readiness to take control over aspects of care can be perceived by patients in an opposite way to that intended. This and previous studies suggest that patient control over aspects of treatment is a professional and theoretical construction that often means little to patients.
Adaptation, Psychological↗
Maternal satisfaction.
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Journal Article↗
Patients' expectations of outcome of hysterectomy and alternative treatments for menstrual problems.
Patients can influence treatment to the extent of securing surgery in the absence of medical need, but their expectations of effects of surgery are poorly understood. Interviews with 26 patients presenting menstrual problems without confirmed pathology were used to construct a questionnaire to measure expectations of effects of treatment. Principal-components analysis of responses of 200 similar patients identified six discrete areas in which improvement was expected, including general well-being, menstrual function, and physical symptoms. Expectations of harm were nonspecific and unidimensional. Component-based scale scores showed that patients who anticipated hysterectomy expected more benefit, but also more harm, than those anticipating conservative procedures. In study 2, these different expectations were largely replicated in patients who were randomly allocated to provide their expectations of specific procedures. Patients' uniquely positive expectations of hysterectomy may help to explain its frequent use in the absence of pathology.
Adolescent↗
Patient-controlled analgesia: an assessment by 200 patients.
Two hundred patients completed a questionnaire about their experiences of patient-controlled analgesia. The questionnaire covered the following topics: pre-operative information, reasons for pressing and not pressing the button, pain relief, side-effects, safety, advantages and disadvantages of patient-controlled analgesia, worries associated with its use and control over pain. A high level of satisfaction with the device, together with a view that it afforded control over pain, emerged from replies to simple, general questions. However, more detailed questions revealed side-effects and fears that constrained its use and hence patients' ability to control pain. Control is predominantly a feature of the professional's view of patient-controlled analgesia, rather than the patient's experience of this analgesic technique.
Adolescent↗