Discussions on prescriptive authority.
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Biomedical subjects
Publications and source records attributed to C Bailey.
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The OmpU outer membrane protein is a member of the ToxR regulon of Vibrio cholerae and has recently been shown to be a potential adherence factor for this species. Using PCR and degenerate oligonucleotide primers based on internal peptide sequences of purified OmpU, we have cloned and sequenced the gene encoding OmpU. The ompU gene is predicted to encode a 36,646-molecular-weight protein which is present in both cholera toxin-positive and -negative V. cholerae O1 and O139 strains.
Standard treatment for the majority of malignant brain tumours consists of surgery and radiotherapy. This treatment has late morbidity which is accentuated in the very young child. As part of a strategy to improve quality of life and overall survival of young children with brain tumours, members of the United Kingdom Children's Cancer Study Group (UKCCSG) have piloted an intensive chemotherapy regimen which aims to avoid or delay radiotherapy following surgery. Twenty eight children with a variety of malignant brain tumours have received the regimen, which contains carboplatin, vincristine, cyclophosphamide, methotrexate, and cisplatin. The treatment is toxic, resulting in one death from infection. The bulk of the toxicity was associated with the administration of carboplatin. All but three children eventually required adjuvant radiotherapy and this was given between 1.5 and 27 months from diagnosis (median delay to radiotherapy, 12 months). Using this treatment regimen, overall survival at four years is 35% (confidence intervals 10% to 60%). While there is no evidence from this study that radiotherapy can be abandoned in the management of malignant brain tumours, its introduction may be delayed using suitable chemotherapy, thus allowing time for further CNS development. This treatment strategy has been taken forward as an international clinical trial run through the International Society for Paediatric Oncology, but using a smaller dose of carboplatin to reduce toxicity.
OBJECTIVE: To evaluate the effect of non-pharmacological intervention for breathlessness in lung cancer on breathlessness ratings and patient functioning. DESIGN: Randomised controlled pilot study. SETTING: A nurse led clinic in a specialist cancer centre. SUBJECTS: 20 patients with advanced small cell and non-small cell lung cancer. INTERVENTION: Weekly sessions with a nurse research practitioner over 3-6 weeks using counselling, breathing re-training, relaxation and teaching coping and adaptation strategies. MAIN OUTCOME MEASURES: Visual analogue scale ratings of breathlessness, distress caused by breathlessness, functional capacity, ability to perform activities of daily living and the Hospital Anxiety and Depression Scale. RESULTS: Improvements in median scores on all measures were observed in the intervention group with the exception of depression, compared with the control group where median scores were static or worsened. Distress from breathlessness was improved by a median of 53%, breathlessness at worst by 35% and functional capacity by 21%. In contrast, distress in the control group worsened by a median of 10%. Significant improvements compared with the control group were observed in breathlessness at best (p < 0.02), breathlessness at worst (p < 0.05), distress caused by breathlessness (p < 0.01), functional capacity (p < 0.02) and ability to perform activities of daily living (p < 0.03) but were not observed for anxiety or depression. CONCLUSION: Lung cancer patients suffering from breathlessness benefited from this rehabilitative approach to breathlessness management and strategies employed in this pilot study warrant further multicentre research. Macmillan nurses and palliative care teams are recommended to explore the potential of adopting similar approaches.
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The UK Medical Research Council trial MRC UKALL X was designed to investigate the benefit of one or two courses of additional intensification therapy in children with acute lymphoblastic leukaemia receiving standard treatment. From 1985 to 1990 1612 children, comprising more than 90% of eligible cases in the UK, were treated with intensive induction therapy, central nervous system directed therapy with cranial irradiation and intrathecal methotrexate, and continuing treatment for 2 years. 1171 children were randomised to receive additional intensification therapy at 5 weeks, 20 weeks, both, or neither. At follow-up of at least 3 years disease-free survival for all children at 5 years was 62% (95% confidence interval [Cl] 60.0-64.4), a significant improvement over the 56% (53.0-59.6) found in the preceding MRC UKALL trial. The 5-year disease-free survival was 71% (65.5-76.1) for children randomised to two blocks of intensification therapy, this being significantly better than the 62% (56.6-68.0), 61% (55.7-67.1), and 57% (50.9-62.7) rates for the groups randomised to one intensification block at 5 weeks, one at 20 weeks, and no intensification, respectively. The benefits of intensification therapy were seen irrespective of clinical factors known to influence outcome such as age, sex, and initial leucocyte count. We conclude that the addition of two courses of intensification therapy has produced a 14% improvement in disease-free survival and an 11% improvement in overall survival for the randomised patients. This additional treatment is of benefit to all children with acute lymphoblastic leukaemia, even those traditionally deemed at lower risk of relapse.
Between the autumn of 1989 and January 1990, 21 of the 44 children on the paediatric oncology ward of St. James's University Hospital, Leeds, UK were infected or colonised with Enterobacteriaceae producing extended-spectrum beta-lactamases. This represents 48% of the patients on the ward. Only six patients (14%) had microbiologically proven septicaemia caused by such bacteria during this period. Eighty-one isolates of Enterobacteriaceae producing extended-spectrum beta-lactamases derived from blood culture (7 isolates from 6 patients) or faecal samples (74 isolates) were available for examination. These comprised 28 Escherichia coli, 28 Klebsiella oxytoca, 11 Klebsiella pneumoniae, 10 Citrobacter freundii, 3 Enterobacter spp. and 1 Serratia marcescens. Clinical isolates were resistant to penicillins and to ceftazidime. Strains isolated in this study also showed multiple resistance to a range of antimicrobial agents. Transfer to a nalidixic acid resistant laboratory strain of E. coli UB5201 was attempted, but transfer of the ceftazidime resistance determinant was only successful in 25 isolates (31%). Examination of plasmid DNA revealed sequences in each isolate that hybridised with the TEM beta-lactamase gene probe used on a variety of plasmids ranging in size from 2.5- > 150 kb, sometimes found on several replicons in a single isolate. The TEM gene probe also hybridised with chromosomal DNA in a large number of isolates. Nucleotide sequence analysis demonstrated the presence of three extended-spectrum beta-lactamases: TEM-10B produced by two isolates, TEM-12B produced by 37 isolates and TEM-26B produced by 40 isolates. In two cases, isolates produced two beta-lactamases, and it proved impossible to identify these enzymes unequivocally. The genes encoding TEM-10B and TEM-26B both differ from TEM-12B by single nucleotide substitutions. Analysis of the ribotype patterns derived from the clinical isolates provided evidence for cross-colonisation between patients, and this was confirmed by analysis of the plasmid profiles. Four years after discontinuing ceftazidime and other extended-spectrum cephalosporins on this ward, patients were still colonised with bacteria that produced extended-spectrum beta-lactamases.
Breathlessness has been described as an unpleasant sensation, but if it encompasses suffering, as some argue, it is much more than this. Breathlessness is also a major issue for people with cancer. Much of the effort to manage breathlessness has thus far focused on the treatment of underlying causes or on pharmacological strategies. In this paper, broader rehabilitative goals of care and treatment for breathlessness in lung cancer are addressed. Breathing control techniques have been developed to help patients with non-malignant disease to avoid breathlessness at rest or on exertion. A study is described (Corner et al., 1995) which evaluated the effectiveness of breathing retraining and psychosocial support for breathlessness in lung cancer. Breathlessness can be a frightening and powerful experience. It can symbolize a threat to life itself. In these circumstances, the goal of therapy is to alleviate loss of function and to ease the psychological burden that so restricts the individual. An 'integrative' model of breathlessness is discussed, in which the emotional experience of breathlessness is considered inseparable from the sensory experience and the biological mechanisms. Evidence is presented from a small study of the experiences of nurses working in the experimental clinic for breathlessness which suggests that the emotional consequences of breathlessness have a profound influence on how it is managed in practice. Finally, it is argued that symptoms are sometimes generalized too much. Experience is particular, not universal, and an open, accepting and therapeutic approach to managing illness has to be involved with messy and sometimes frightening emotions.
Porcine valve failure after a Bentall procedure presents a particularly challenging situation for cardiothoracic surgeons. We describe a patient who was initially turned down for operative intervention because of the excessive operative risk involved, but who subsequently underwent successful valve replacement without removal of the aortic conduit.
The MAXM is a compact blood count and differential analyzer that appeals to both the space-limited, full-service laboratory and the large outpatient practice. The authors compared the performance of the Coulter MAXM to the larger Coulter STKS. Linearity and precision studies were comparable to the STKS. MAXM leukocyte differentials were closely correlated with STKS and manual readings, being excellent in the neutrophil, lymphocyte, and eosinophil categories but poorer on monocyte counts. Basophil counts did not correlate with STKS or manual counts. Analyzer suspect flagging was similar in both machines, with the MAXM exhibiting slightly reduced sensitivity and greater specificity. MAXM processing of a single sample requires twice the time. The MAXM functions well for a large office practice and as a backup for large medical laboratories but, because of its hands-on requirements and lack of speed, cannot replace the larger, more automated analyzers.
Continuing education for home-care nurses is necessary because of the many different levels of educational preparation among nurses working in this practice setting and the lack of a structured orientation program at many agencies. Unique educational needs include the need to feel confident with physical assessment skills, nursing diagnosis, family dynamics, patient teaching, and counseling. Competence in the use of computers and documentation forms also is a necessity. The development of any educational program should include identification of the target audience, needs assessment, planning and design of the program, strategy for implementation, and an evaluation strategy.
One hundred nineteen individuals from 11 families with X-linked ocular albinism (OA1) were studied with respect to both their clinical phenotypes and their linkage genotypes. In a four-generation Australian family, two affected males and an obligatory carrier lacked cutaneous melanin macroglobules (MMGs); ocular features were identical to those of Nettleship-Falls OA1. Four other families had more unusual phenotypic features in addition to OA1. All OA1 families were genotyped at DXS16, DXS85, DXS143, STS, and DXS452 and for a CA-repeat polymorphism at the Kallmann syndrome locus (KAL). Separate two-point linkage analyses were performed for the following: group A, six families with biopsy-proved MMGs in at least one affected male; group B, four families whose biopsy status was not known; and group C, OA-9 only (16 samples), the family without MMGs. At the set of loci closest to OA1, there is no clear evidence in our data set for locus heterogeneity between groups A and C or among the four other families with complex phenotypes. Combined multipoint analysis (LINKMAP) in the 11 families and analysis of individual recombination events confirms that the major locus for OA1 resides within the DXS85-DXS143 interval. We suggest that more detailed clinical evaluations of OA1 individuals and families should be performed for future correlation with specific mutations in candidate OA1 genes.
Measurements of lead (Pb) in bone reflect cumulative Pb exposure, whereas blood Pb levels are indices of absorption during the previous 21-30 days. This study was undertaken to estimate bone Pb concentrations by L-line x-ray fluorescence (LXRF) in a United States suburban population which was exposed to unusually high levels of Pb in emissions from an adjacent factory during 1963-1981, compared with concentrations similarly estimated in a matched suburban community without unusual Pb exposure. The mean bone Pb value in 269 residents of the highly exposed suburb (15 ppm) was 3-fold greater than that of the reference suburb (5 ppm). LXRF estimates of bone Pb identified those individuals at risk for adverse effects of Pb, whereas blood Pb levels were uninformative. Average LXRF-estimated bone Pb concentrations in residents of the unusually exposed suburb approximated estimated values in workers at Pb-processing factories.
Primary cultures of bovine brain microvessel endothelial cells (BMECs) were used to characterize blood-brain barrier (BBB) uptake and transport of biotin. Both the uptake and the transcellular transport of either radiolabeled or fluorescein-conjugated biotin by confluent monolayers of BMECs were measured. Biotin uptake (Km = 123 microM) and bidirectional transport across BMEC monolayers was a saturable process and could be competed for by unlabeled biotin, biocytin, and biotinmethyl ester. Pantothenic and nonanoic acid were found not to be effective competitors for either biotin uptake or transport. The metabolic inhibitor, 2-deoxyglucose, had only small effects on the saturable apical-to-basolateral transport and apical uptake of biotin by BMECs. In contrast, basolateral-to-apical transport of biotin was substantially attenuated by 2-deoxyglucose pretreatment. Results supported the existence of specific and saturable uptake and efflux carrier systems for biotin in BMEC monolayers. The function of these systems was dependent to some degree on the metabolic status of the BMECs. Our findings confirm the existence of a biotin uptake system at the BBB in vivo and provide the first indication of an efflux system for biotin in BMECs.
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Bone marrow transplantation (BMT) has been recommended for children with high-risk acute lymphoblastic leukaemia (ALL) in first remission. The recent MRC UKALL X trial was designed to facilitate a non-randomised comparison between BMT and chemotherapy in children deemed to be at high risk of treatment failure. 198 children aged 1-15 had a presenting leucocyte count of more than 100 x 10(9)/l. All received induction and early intensification therapy. Children with an HLA-compatible sibling donor were eligible for BMT in first remission. All other children received cranial irradiation at 24Gy, late intensification, and two years of continuous treatment. 183 children achieved a stable remission of whom 111 were HLA typed; these tended to be older and to have T-cell ALL. A donor was identified in 41 cases, of whom 34 proceeded to BMT at a median time of 17 weeks; there was no difference in distribution of age, sex, or leucocyte count between the groups receiving BMT and chemotherapy. Comparison of the 144 children who were in remission at 17 weeks and received chemotherapy with the 34 proceeding to BMT showed no significant difference in event-free survival at five years (69% for BMT and 52% for chemotherapy). There were significantly more treatment-related deaths in the marrow transplant group (6 vs 4) and more relapses in the chemotherapy group (59 vs 4). There was no significant difference in event-free survival between children who were HLA typed and had a donor and those without a donor, although there were fewer relapses among the former. BMT can be evaluated in the context of a multicentre trial for paediatric ALL but the number of children with donors is too small to make a significant impact on overall survival. However, marrow transplantation was associated with a much lower relapse rate than that with the UK ALL protocol, and with better definition of higher risk patients BMT may be of benefit in some children with high-risk ALL in first remission.