Tackling organisational change in the new NHS.
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Community Health Services↗
Biomedical subjects
K Smith
Publications and source records attributed to K Smith.
Indazolylamino quinazolines and pyridopyrimidines as inhibitors of the EGFr and C-erbB-2.
Described herein is the design and synthesis of indazolylaminopyridopyrimidines and quinazolines as inhibitors of the class 1 tyrosine kinase receptor family. Data is presented for N(4)-(1-benzyl-1H-indazol-5-yl)-N(6),N(6)-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine 3B. This compound inhibited EGFr and c-erbB-2 enzymes selectively over other kinases. It inhibited the proliferation of a range of tumour cell lines in vitro and the growth of BT474 xenografts in SCID mice.
Animals↗
Growth, feeding frequency, protein turnover, and amino acid metabolism in European lobster Homarus gammarus L.
The effect of feeding frequency on growth and protein metabolism in the European lobster, Homarus gammarus, was investigated. Fourth (IV) stage lobsters H. gammarus were fed individually a marine animal meal (herring/mussels meal) for 56 days. Feeding a daily ration equivalent to 10% of their body weight gave better growth than feeding daily rations of 5% and 20%. Protein synthesis rates were similar for the three food rations but protein growth rates were significantly lower and protein degradation rates highest in the 5% body weight per day ration group. The efficiency with which synthesised protein was retained as growth was found to be 38% in the in the 10% ratio group. Protein synthesis rates of lobsters were found to be lower than those for shrimps (Penaeus vannamei). The amino acid flux also suggests a lower protein conversion efficiency than shrimps P. vannamei. The results suggests that lobsters are slow, periodic feeders and that growth can be readily increased by manipulation of particular environmental factors such as feeding frequency.
Amino Acids↗
Mutant epidermal growth factor receptor enhances induction of vascular endothelial growth factor by hypoxia and insulin-like growth factor-1 via a PI3 kinase dependent pathway.
Over-expression of truncated epidermal growth factor receptor (EGFR) occurs in a variety of malignancies including glioblastoma multiforme, breast and lung cancer. The truncation deletes an extracellular domain and results in constitutive activation of the receptor. NIH3T3 cells were transfected with full length or truncated human EGFR and differences in growth rates in vivo and in vitro analysed. A growth advantage was seen for cells expressing mutant receptor compared to full length EGFR in vivo only. Administration of an anti-mutant EGFR antibody to mice transiently reduced the growth rates of mutant tumours, confirming that the mutant receptor itself was important in this enhanced tumorigenicity. This showed that stimuli present in vivo and not in vitro may be contributing to growth. We therefore analysed the regulation of the angiogenic factor vascular endothelial growth factor (VEGF). Although levels of secreted VEGF did not differ significantly between wild-type and mutant EGFR cell lines when grown in vitro under normoxic conditions, following exposure to 0.1% hypoxia levels of VEGF produced by mutant cells increased 3.5-6.6 fold compared to 2 or less for full length EGFR cells. The fold induction was influenced by experimental conditions, including cell confluence and percentage of fetal bovine serum, but was consistently higher for mutant cell lines. The increase in VEGF under hypoxic conditions was blocked by the addition of PI3 kinase inhibitors, indicating that the latter pathway is important in the hypoxic stress response. Basal levels were not affected. Addition of insulin-like growth factor-1 also increased levels of VEGF under normoxic conditions in the mutant cells and no further increase was seen when added to cells exposed to 0.1% oxygen, indicating that levels of VEGF were already maximally stimulated. These results show that the mutant EGFR interacts with other growth factors and hypoxia to regulate VEGF via a PI3 kinase pathway, and suggests a specific role for anti-mutant EGFR antibodies and PI3 kinase inhibitors as therapy of this specific tumour target.
3T3 Cells↗
Self-obtained vaginal swabs for diagnosis of treatable sexually transmitted diseases in adolescent girls.
OBJECTIVE: To ascertain the acceptability of testing and prevalence of 3 readily treatable sexually transmitted diseases (STDs) (infections with Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis) with the use of patient-obtained vaginal swabs. STUDY DESIGN: Study participants at each initial session were asked to provide self-obtained vaginal swabs for ligase chain reaction testing to detect N gonorrhoeae and C trachomatis, and for culture of T vaginalis. SETTING: Behavioral intervention sessions with African American adolescent girls in a nonclinical program to reduce risk of STDs, human immunodeficiency virus infection, and pregnancy. RESULTS: All study participants were offered their choice of STD screening in the context of a traditional pelvic examination or using self-obtained vaginal swabs. All eligible participants chose self-administered vaginal swabs. Of the 512 participants examined at their initial study visit, 28.7% were found to be infected with 1 or more treatable STDs (5.3% with N gonorrhoeae, 17.8% with C trachomatis, and 12.9% with T vaginalis). CONCLUSIONS: With the use of newer detection systems, STDs can be readily detected in nonclinical settings with the use of self-obtained vaginal swabs, providing new opportunities for efforts to control STDs.
Adolescent↗
Environmental temperature during pregnancy and eating attitudes during teenage years: a replication and extension study.
OBJECTIVE: Among nonclinical adolescents, restrictive eating attitudes are more likely to occur among females born during warmer months. The present study aimed to replicate this finding and to extend it, considering whether such an effect is found in males and across the teenage years. In addition, the influence of temperature across the intrauterine period was considered. METHOD: The participants consisted of younger and older teenagers, all born in England. Each completed the relevant scales of the Eating Disorders Inventory and provided demographic information. Temperature across fetal development was determined using national meteorological records. RESULTS: There was a positive link between restrictive attitudes and temperature at birth among the older female group, although this replication effect did not reach significance. The same association among the older males was highly significant. The range of temperatures during fetal development also predicted later restrictive attitudes. In contrast, these effects were not replicated among the younger group, where a different pattern of effect was found (among the females only). CONCLUSION: Environmental temperature seems to have an important influence on later eating attitudes, but the pattern of influence appears to vary across development. Therefore, studies of the mechanisms behind this effect need to consider the role of gender and development, as well as the role of temperature across the period of intrauterine development.
Adolescent↗
Manual hyperinflation: consistency and modification of the technique by physiotherapists.
BACKGROUND AND PURPOSE: The present study aimed to evaluate the consistency with which physiotherapists apply manual hyperinflation to a test lung using the Air-Viva-2 or Mapleson-B resuscitation circuit, and their ability to modify the technique as pulmonary characteristics change. METHOD: A quasi-experimental, randomized, repeated-measures design was used to study 16 volunteer physiotherapists performing manual hyperinflation to a test lung simulating three clinical situations. Each subject applied manual hyperinflation to the test lung for each simulation three times in one day using the resuscitation circuit that they would normally use in their clinical practice. Eight subjects used the Air-Viva-2 circuit and eight used the Mapleson-B circuit. Measurements of tidal volume (Vp), peak airway pressure (Paw) and fraction of delivered oxygen (FDO2) were recorded during each testing period. Inflation rate and minute volume were calculated. RESULTS: As compliance decreased and airway resistance increased, VT decreased and Paw increased. Of the eight subjects using the Air-Viva-2 circuit, only three subjects delivered greater than 0.80 FDO2. All subjects using the Mapleson-B circuit delivered greater than 0.85 FDO2. CONCLUSIONS: Subjects demonstrated good consistency in the application of manual hyperinflation for all three simulations and modified their technique appropriately as simulated pulmonary characteristics changed.
Female↗
Acceptance of a medical first-responder role by fire fighters.
STUDY OBJECTIVE: In July 1998, a pilot trial which used fire fighters as medical first-responders for the first time in Australia, was implemented in Melbourne. We aimed to assess the impact of the introduction of a medical first-responder role to the fire service, on the fire fighters both professionally and personally. METHODS: Focus groups were conducted at the fire stations located in the study area. Data from the focus groups was collated and examined for themes. The issues identified as important through the focus groups were then incorporated into a questionnaire. RESULTS: The fire fighters located at the pilot stations involved in the first-responder programme appear to view their new role as first-responders as a positive addition to their emergency profession. Some areas of the programme were identified by this study as in need of improvement. Some aspects of the communication strategies utilised by the Fire Brigade were highly criticised. Some aspects of the support system offered by the Fire Brigade also appear to be regarded as unfavourable. CONCLUSION: Results from this study provide useful information on professional fire fighter first-responder programmes and their impact on participating personnel. These results can be used to improve training modules, communication strategies and support services.
Adaptation, Psychological↗
Symbolic description of intracerebral vessels segmented from magnetic resonance angiograms and evaluation by comparison with X-ray angiograms.
We describe and evaluate methods that create detailed vessel trees by linking vessels that have been segmented from magnetic resonance angiograms (MRA). The tree-definition process can automatically exclude erroneous vessel segmentations. The parent-child connectivity information provided by our vessel trees is important to both surgical planning and to guidance of endovascular procedures. We evaluated the branch connection accuracy of our 3D vessel trees by asking two neuroradiologists to evaluate 140 parent-child connections comprising seven vascular trees against 17 digital subtraction angiography (DSA) views. Each reviewer rated each connection as (1) Correct, (2) Incorrect, (3) Partially correct (a minor error without clinical significance), or (4) Indeterminate. Analysis was summarized for each evaluator by calculating 95% confidence intervals for both the proportion completely correct and the proportion clinically acceptable (completely or partially correct). In order to protect the overall Type I error rate, alpha-splitting was done using a top down strategy. We additionally evaluated segmentation completeness by examining each slice in 11 MRA datasets in order to determine unlabeled vessels identifiable in cross-section following segmentation. Results indicate that only one vascular parent-child connection was judged incorrect by both reviewers. MRA segmentations appeared complete within MRA resolution limits. We conclude that our methods permit creation of detailed vascular trees from segmented 3D image data. We review the literature and compare other approaches to our own. We provide examples of clinically useful visualizations enabled by our methodology and taken from a visualization program now in clinical use.
Angiography, Digital Subtraction↗
The effects of leucocyte depletion on the generation and removal of microvesicles and prion related protein in blood components.
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Blood Component Transfusion↗
CD34-positive cellular blue nevi.
BACKGROUND: Although cellular blue nevi (CBN) are well known and characterized, the histopathologic and clinical spectrum of these tumors continues to evolve. We report four CBN with a distinctive histologic and immunohistochemical pattern. METHODS: The histologic features and immunohistochemical staining for S-100 protein, HMB-45, Bcl-2 and CD34 of four CBN with distinctive features were evaluated using routine methods and compared to common CBN. RESULTS: All four of these distinctive CBN where known to be congenital, and all showed aggregates of plump spindled cells with round to oval nuclei in aggregates and more slender spindled cells with thin wavy nuclei. The slender, spindled cells showed an infiltrative pattern laterally into the dermis and deep into the subcutaneous fat. All four tumors showed diffuse expression of an immunohistochemical stain for CD34, as well as for S-100 protein, Bcl-2, and HMB-45. CONCLUSION: Positive immunohistochemical staining with the progenitor marker CD34 defines a subset of CBN. These tumors appear to fit within the spectrum of neurocristic cutaneous hamartomas and may arise from more primitive neurocristically derived cells. Further follow-up of these tumors will be necessary to determine whether this subset of CBN defines a subset with a characteristic biologic behavior.
Adolescent↗
Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy.
Indoleamine 2,3 dioxygenase (IDO) activity during pregnancy protects developing fetuses from maternal immune responses in CBA mice. We show here that fetal allografts were rejected only in mating combinations where paternally inherited tissue antigens elicited potent maternal T cell responses after exposure to IDO inhibitor. IDO inhibitor treatment triggered extensive inflammation at the maternal-fetal interface in susceptible mating combinations, which was characterized by complement deposition and hemorrhagic necrosis. Identical inflammatory responses occurred in B cell-deficient (RAG-I-/-) mothers that carried a monoclonal cohort of CD8+ T cells specific for a single paternally inherited fetal major histocompatibility complex antigen. Thus, fetal allograft rejection was accompanied by a unique form of inflammation that was characterized by T cell-dependent, antibody-independent activation of complement. In contrast, no inflammation, complement deposition or T cell infiltration was elicited when mice carrying syngeneic fetuses were exposed to IDO inhibitor. These data show that IDO activity protects the fetus by suppressing T cell-driven local inflammatory responses to fetal alloantigens.
Animals↗
Priority setting with Health Inequality Impact Assessment.
The imperative to reduce health inequalities whilst keeping within budget means that Health Authorities must prioritise to gain maximum benefit from available resources. Health Inequality Impact Assessment (HIIA) rapid appraisal has been developed by Bro Taf Health Authority to ensure that planning produces positive effects for disadvantaged people. HIIA rapid appraisal consists of assessing the effect of deprivation on the planning topic, examining the relevant evidence, defining opportunities for action and rating these relative to their likely impact on health inequalities. The process is best carried out by a multidisciplinary team including health authority, local authority, voluntary sector and community representatives. This paper describes a HIIA rapid appraisal process, that resulted in a Trust that serves a highly disadvantaged locality agreeing to try a new method of working and to collaborate in research on breaking the cycle of deprivation.
Health Planning↗
Nurse endoscopists in United Kingdom health care: a survey of prevalence, skills and attitudes.
OBJECTIVES: To assess the prevalence and potential benefits of attitudes towards nurse endoscopy in the United Kingdom (UK). DESIGN: Postal questionnaire. SUBJECTS: All hospitals in the UK with accident and emergency, general medical and general surgical services in October 2000. MAIN OUTCOME MEASURES: Number of teaching or district general hospitals employing nurse endoscopists, range of diagnostic and therapeutic endoscopic skills and potential benefits to the endoscopy unit and patients. RESULTS: Seventy-six hospitals employed 102 nurse endoscopists. Forty-four nurse endoscopists performed both oesophago-gastroduodenoscopy (OGD) and flexible sigmoidoscopy with solitary OGD and flexible sigmoidoscopy performed by 17 and 31, respectively. Three performed full colonoscopy while seven could perform all three procedures. Nurse endoscopists were found to provide good patient care in the majority of endoscopy units with no compromise in safety. Lead clinicians were keen to restrict nurse endoscopy to diagnostic OGD and flexible sigmoidoscopy only in the majority of units. CONCLUSIONS: Nurse endoscopy is widely practised in the UK and is not limited to one procedure or solely for diagnostic purposes. Benefits include good patient acceptability, improved care and safety. Most clinicians predict an important but restricted role for nurse endoscopy in contributing to endoscopic services.
Attitude to Health↗
Histologic features seen in changing nevi after therapy with an 810 nm pulsed diode laser for hair removal in patients with dysplastic nevi.
BACKGROUND: The majority of lasers used for hair removal target melanin as the chromophore. In contrast with other cutaneous applications of lasers, lasers used for hair removal must generate a limited, controlled degree of thermal damage to permanently remove hairs. AIM: To remove excess back hair from two male patients, one with a history of multiple nevi, and prior biopsies showing features of dysplastic nevi, and the other with large nevi greater than 6 mm in diameter and a family history of malignant melanoma. METHODS: Both patients received monthly treatments with an 810 nm, pulsed, high-power diode laser using a fluence of 20 J/cm2 and 25-30 J/cm2, respectively, and a pulse duration of 30 ms. RESULTS: Both patients presented 1 month after their last treatment with changing nevi within the treatment areas. Neither patient had clinical inflammation or other alterations suggestive of change in the nevi related to treatment. Thus, the nevi were excised with no mention of the previous laser treatment. The histologic features in all nevi were similar. There was subepidermal blister formation with elongation and disruption of nevus cells. There was homogenization of the collagen within the papillary dermis in all lesions. Only small foci of nevus cells could be identified in the dermis in some of the biopsy specimens. In these biopsy specimens, the dermal stromal matrix homogenization extended into the reticular dermis. CONCLUSIONS: Laser targeting of nevus cells and surrounding structures may produce clinically atypical nevi in areas previously treated for hair removal. This should be kept in mind, especially in patients with a history of dysplastic nevi or with a personal or family history of malignant melanoma.
Adult↗
A 'Third Way' for lay involvement: what evidence so far?
AIMS AND OBJECTIVES: This article considers evidence regarding lay involvement in the NHS, following the White Paper's commitment to rebuild public confidence in an NHS 'accountable to patients and open to the public and shaped by their views'. It looks at two aspects of lay involvement: the lay board member's involvement in primary care group (PCG) decision-making and the engagement of the PCG with the wider public. METHODS: The paper analyses data from the first sweep of the annual Tracker Survey of a sample of PCGs in England, led by the National Primary Care Research and Development Centre in collaboration with the King's Fund between September and December 1999. It draws specifically from the postal questionnaires sent to lay members. Firstly, however, it contextualizes this data by reviewing the history of lay involvement before 1997 in the NHS and particularly in primary care. CONCLUSIONS: The paper concludes that, during the first 6 months of their operation, the lay voice was faintly heard in PCGs. The lay member's role in decision-making at board-level was peripheral. The majority rated their involvement in key aspects of decision-making as low and their influence on decision-making below that of other board members including the Chief Officer, the chair and the GP board members. Beyond the arena of the board, what little contact there was with the lay voice has taken the shape of informing rather than consulting. Mitigating factors include the early stage at which the survey was completed and the lack of precedents for lay involvement in primary care in a broad sense on which PCGs can draw.
Community Participation↗
Stepwise regression analysis to study male and female factors impacting on pregnancy rate in an intrauterine insemination programme.
The aim of this study was to evaluate the impact of male and female factors on the pregnancy rate in an intrauterine insemination (IUI) programme. Data on 522 cycles were retrospectively studied. All patients 39 years or younger were included in the study where data were available on male and female diagnosis, as well as on ovulation induction methodology. Regression analysis was possible on 495 cycles to study different factors affecting the pregnancy rate per treatment cycle. Logistic regression identified variables which were related to outcome and were subsequently incorporated into a statistical model. The number of follicles was found to have a linear association with the risk ratio (chance) of pregnancy. The age of the woman was also found to have a linear (negative) association with pregnancy. The percentage motility and percentage normal morphology (by strict criteria) of spermatozoa in the fresh ejaculate were the male factors that significantly and independently predicted the outcome. Percentage motility > or = 50 was associated with a risk ratio of pregnancy of 2.95 compared to percentage motility < 50. Percentage normal sperm morphology > 14% was associated with a risk ratio of pregnancy of 1.8 compared to percentage normal morphology < or = 14%. Female patients with idiopathic infertility were divided into three groups according to normal sperm morphology. The pregnancy rate per cycle was 2.63% (1/38) for the P (poor) pattern group (0-4% normal forms), 11.4% (17/149) for the G (good) pattern group (5-14%), and 24% (18/75) for the N (normal) pattern group (> 14% normal forms). A female diagnosis of endometriosis or tubal factor impacted negatively on the probability of pregnancy (risk ratio of 0.17), compared with other female diagnoses. Male and female factors contribute to pregnancy outcome, but the clinician can influence prognosis by increasing the number of follicles, especially in severe male factor cases.
Adult↗
Predicted impact on Victoria's ambulance services of a new major trauma system.
BACKGROUND: In 1999, a new major trauma system was proposed for the state of Victoria, Australia. The guidelines for the new system were aimed at delivering major trauma cases to definitive trauma care in the least time possible. The aim of the present study was to analyse the potential effect of this system on Victoria's ambulance services. METHODS: The present study modelled the workload of major trauma cases in Victoria's ambulance service for one year pre- and post-introduction of the guidelines. Cases were analysed regarding whether their first hospital destination would change under the proposed guidelines, and, subsequently, whether they would require interhospital transport to a higher level trauma service. The impact on the ambulance services was modelled as annual changes in distances travelled due to predicted changes in hospital destinations. RESULTS: Analysis of the predicted changes indicated that, in general, Victoria's metropolitan and rural road ambulance crews would not be greatly affected. However, some metropolitan road crews may have to travel extra distances for up to 110 cases per year. The major impact was on air retrieval crews, where the annual number of interhospital transfers is predicted to increase from approximately 150 to 330. CONCLUSIONS: The present study demonstrated that most of the impact of a new trauma system on Victoria's ambulance services could be readily absorbed into the current workload. However, it also highlighted areas affected disproportionately within the ambulance services; in particular, air retrieval. Such studies are important to enable the effective implementation of new trauma systems.
Aged↗