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Biomedical subjects

A Knight

Publications and source records attributed to A Knight.

At least 19 recordsLinked to original sources
PubMed2006

Ionic Contra-Viral Therapy (ICVT); a new approach to the treatment of DNA virus infections.

The sequestration of cellular K(+) has been shown elsewhere to elicit a broad spectrum of antiviral activity. The obligatory, coupled cotransports of Na(+), K(+) and Cl(-) (NKCC1) and of Na(+) and K(+) (NKATPase) effect net cellular K(+) influx. We examined the effects of specific inhibitors of these transports; a cardiac glycoside (Digoxin) and a loop diuretic (Furosemide) on virus replication in vitro. The replication of the DNA viruses, herpes simplex virus, varicella zoster virus, human cytomegalovirus and adenovirus was inhibited. There was normal replication of the RNA virus encephalomyocarditis virus. Antiviral activities of both drugs were influenced by extracellular K(+). Antiviral effects were most potent when Digoxin and Furosemide were used in combination. Targeting the host cell in this way is fundamentally different to other antiviral drug developments to date and we propose the descriptive term Ionic Contra Viral Therapy (ICVT) for the purpose of definition. We believe that specific inhibitors of coupled K(+) transports merit controlled clinical trial for a broad spectrum of DNA virus infections by local application.

Antiviral Agents↗
PubMed2006

Comparative efficacy of once-daily ciclesonide and budesonide in the treatment of persistent asthma.

BACKGROUND: The aim of this study was to compare the efficacy and safety of once-daily ciclesonide, a new-generation, on-site-activated, inhaled corticosteroid, with once-daily budesonide in persistent asthma. METHODS: Eligible patients requiring budesonide or equivalent 320-640 microg (ex-mouthpiece, equivalent to 400-800 microg; Turbohalertrade mark) daily entered a 2-week baseline, and then a 2- to 4-week pretreatment period (budesonide 1280 microg/day; ex-mouthpiece, equivalent to 1600 microg/day). Patients with an increase in forced expiratory volume in 1s (FEV1) of 7% or 0.15 L were randomised to ciclesonide 320 microg (ex-actuator, equivalent to 400 microg ex-valve) via a hydrofluoroalkane-metered dose inhaler (HFA-MDI) without a spacer or budesonide 320 microg once daily in the morning for 12 weeks. Change in FEV1 was the primary endpoint. RESULTS: In all, 359 patients were randomised. The FEV1 and forced vital capacity (FVC) decreased by 0.18 and 0.12L, respectively, in the ciclesonide group, and by 0.23 and 0.21L in the budesonide group. For FEV1, ciclesonide was noninferior and numerically superior to budesonide. For FVC, ciclesonide was statistically superior to budesonide (P=0.010). Asthma symptom scores were comparable; the median percentage of symptom-free days was significantly higher for ciclesonide (43.6%) versus budesonide (25.8%) (P=0.017). Rescue medication use decreased significantly only for ciclesonide patients (P=0.009). Frequency of adverse events was low in both groups. CONCLUSION: Ciclesonide 320 microg once daily by HFA-MDI without a spacer was at least as effective as budesonide 320 microg once daily in persistent asthma.

Administration, Inhalation↗
PubMed2006

A single common urgent pathway for all colorectal referrals reduces time to diagnosis and treatment.

OBJECTIVE: Guidelines for the urgent referral of patients with suspected colorectal cancer were introduced in 2000. They aimed to facilitate the prompt diagnosis and treatment of patients with symptoms suggestive of malignant disease. Recent assessment of these guidelines has suggested that although they identify 9-14% of patients with colorectal cancer, they may be used inappropriately and may lead to delays in treatment for those patients with cancers whose symptoms do not fit the guidelines. We aimed to assess the effect of introducing a single pathway for all referrals irrespective of indicated urgency. METHOD: All referral letters to a single consultant colorectal surgeon over a 6-month period were coded 'urgent' irrespective of the indicated urgency on the original referral letter. Data was collected prospectively on 47 patients diagnosed with colorectal cancer identified over the trial period. Patient demographics, the mode of presentation, urgency of referral and waiting times were documented. RESULTS: Following the introduction of the common urgent referral pathway, no patient waited longer than 62 days from referral to treatment or 31 days from the decision to treat to first treatment, thus meeting government targets introduced in 2005. CONCLUSION: The introduction of the urgent referral guidelines has accelerated the referral pathway for patients with symptoms suggestive of colorectal cancer, although this is at the expense of the majority of patients who present via conventional pathways. The introduction of a common urgent pathway allows prompt diagnosis and treatment and is of particular benefit for the majority of patients not referred via the 2-week standard. Until a more accurate method of identifying the highest risk patients is implemented, we suggest that all patients are seen on an urgent basis.

Colorectal Neoplasms↗
PubMed2006

Use of icodextrin 4% solution in the prevention of adhesion formation following general surgery: from the multicentre ARIEL Registry.

INTRODUCTION: Intra-abdominal adhesions occur in many patients following major abdominal surgery and represent a serious burden to patients and healthcare providers. The multicentre ARIEL (Adept Registry for Clinical Evaluation) Registry was established to gather clinical experiences in the use of icodextrin 4% solution, an approved adhesion-reduction agent, during routine general surgery. PATIENTS AND METHODS: General surgeons from five European countries completed anonymised data collection forms for patients undergoing laparotomy or laparoscopy. Surgeons recorded patient demographics, use of icodextrin 4% solution and adverse events, and made subjective assessments of ease of use and patient acceptability with the agent. RESULTS: The general surgery registry included 1738 patients (1469 laparotomies, 269 laparoscopies). Leakage of fluid from the surgical site did not appear to be affected by icodextrin 4% solution and was classified as 'normal' or 'less than normal' in most patients (laparotomies 86%, laparoscopies 88%). Overall, satisfaction with ease of use was rated as 'good' or 'excellent' by the majority of surgeons (laparotomies 77%, laparoscopies 86%). Patient acceptability was also good, with ratings of 'as expected' or 'less than expected' in most cases for both abdominal distension (laparotomies 90%, laparoscopies 91%) and abdominal discomfort (laparotomies 91%, laparoscopies 93%). Adverse events occurred in 30.6% of laparotomy patients and 16.7% of laparoscopy patients; the most common events were septic/infective events (4.2% and 3.4% in the laparotomy and laparoscopy groups, respectively). Anastomotic wound-healing problems were reported in 7.6% of patients in the subset of laparoscopy patients undergoing anastomotic procedures (n = 66). DISCUSSION: Volumes of icodextrin 4% solution used as an irrigant and instillate were in line with recommendations. Surgeons considered the agent to be easy to use and acceptable to patients. The reported frequencies of adverse events were in line with those published in the literature for surgical procedures, supporting the good safety profile of this agent. CONCLUSIONS: Icodextrin 4% solution can be used in a wide range of surgical procedures. In combination with good surgical technique, it may play an important role in adhesion reduction.

Glucans↗
PubMed2005

Surrogate markers and survival in women receiving first-line combination anthracycline chemotherapy for advanced breast cancer.

Surrogate markers may help predict the effects of first-line treatment on survival. This metaregression analysis examines the relationship between several surrogate markers and survival in women with advanced breast cancer after receiving first-line combination anthracycline chemotherapy 5-fluorouracil, adriamycin and cyclophosphamide (FAC) or 5-fluorouracil, epirubicin and cyclophosphamide (FEC). From a systematic literature review, we identified 42 randomised trials. The surrogate markers were complete or partial tumour response, progressive disease and time to progression. The treatment effect on survival was quantified by the hazard ratio. The treatment effect on each surrogate marker was quantified by the odds ratio (or ratio of median time to progression). The relationship between survival and each surrogate marker was assessed by a weighted linear regression of the hazard ratio against the odds ratio. There was a significant linear association between survival and complete or partial tumour response (P<0.001, R(2)=34%), complete tumour response (P=0.02, R(2)=12%), progressive disease (P<0.001, R(2)=38%) and time to progression (P<0.0001, R(2)=56%); R(2) is the proportion of the variability in the treatment effect on survival that is explained by the treatment effect on the surrogate marker. Time to progression may be a useful surrogate marker for predicting survival in women receiving first-line anthracycline chemotherapy and could be used to estimate the survival benefit in future trials of first-line chemotherapy compared to FAC or FEC. The other markers, tumour response and progressive disease, were less good.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Urinary bladder cancer in Wegener's granulomatosis: risks and relation to cyclophosphamide.

OBJECTIVE: To assess and characterise the risk of bladder cancer, and its relation to cyclophosphamide, in patients with Wegener's granulomatosis. METHODS: In the population based, nationwide Swedish Inpatient Register a cohort of 1065 patients with Wegener's granulomatosis, 1969-95, was identified. Through linkage with the Swedish Cancer Register, all subjects in this cohort diagnosed with bladder cancer were identified. Nested within the cohort, a matched case-control study was performed to estimate the association between cyclophosphamide and bladder cancer using odds ratios (ORs) as relative risk. In the cohort the cumulative risk of bladder cancer after Wegener's granulomatosis, and the relative prevalence of a history of bladder cancer at the time of diagnosis of Wegener's granulomatosis, were also estimated. RESULTS: The median cumulative doses of cyclophosphamide among cases (n = 11) and controls (n = 25) were 113 g and 25 g, respectively. The risk of bladder cancer doubled for every 10 g increment in cyclophosphamide (OR = 2.0, 95% confidence interval (CI) 0.8 to 4.9). Treatment duration longer than 1 year was associated with an eightfold increased risk (OR = 7.7, 95% CI 0.9 to 69). The absolute risk for bladder cancer in the cohort reached 10% 16 years after diagnosis of Wegener's granulomatosis, and a history of bladder cancer was (non-significantly) twice as common as expected at the time of diagnosis of Wegener's granulomatosis. CONCLUSION: The results indicate a dose-response relationship between cyclophosphamide and the risk of bladder cancer, high cumulative risks in the entire cohort, and also the possibility of risk factors operating even before Wegener's granulomatosis.

Adult↗
PubMed2004

Are prophylactic haematopoietic growth factors of value in the management of patients with aggressive non-Hodgkin's lymphoma?

Combination chemotherapy used to treat patients with aggressive non-Hodgkin's lymphoma is associated with neutropenia and subsequent infection, hospital admission and treatment delays. Haematopoietic growth factors (HGF) can prevent neutropenia and improve quality of life. We undertook a meta-analysis of six randomised and one nonrandomised trials to quantify the effect in previously untreated patients, and a simple cost-effectiveness analysis. The trials compared HGF plus chemotherapy with chemotherapy alone. In total, there were 779 patients aged between 15 and 82 years. Haematopoietic growth factors was associated with a statistically significant 44% reduction in the incidence of severe neutropenia (neutrophil count <0.5 x 10(9) l(-1)), a 60% reduction in the number of hospital admissions due to infection, an 80% reduction in the number of patients who had a treatment delay due to neutropenia and a 50% reduction in hospital stay. These data together with UK G-CSF drug costs were combined to develop a simple cost-effectiveness model, based on direct costs. Given the current cost of G-CSF, it would only be cost-effective among patients in which high rates of hospital stay due to neutropenia or infection are expected. Alternatively, if the cost could be reduced then all patients may be able to obtain the benefits. However, the evidence that prophylactic HGFs are clinically worthwhile is clear.

Adolescent↗
PubMed2004

Delivering cognitive therapy to people with psychosis in a community mental health setting: an effectiveness study.

OBJECTIVE: Cognitive therapy (CT) has been shown to be an efficacious treatment for persistent psychotic symptoms. However, there is some debate regarding whether this is transportable to real life clinical settings. This study aimed to evaluate the effectiveness of CT for psychosis in a community mental health team (CMHT) setting. METHOD: Patients referred for CT for psychosis were naturalistically allocated (determined by the availability of a therapist) to CT or waiting-list (WL)/treatment-as-usual (TAU). Outcome assessments were performed at WL, pre-CT, post-CT and 1-year follow-up. Data from 59 patients were analysed. RESULTS: Random effects regression analyses showed there was a significant improvement, attributable to CT, on most outcome measures, and that many of the symptomatic improvements were maintained at follow-up. Wilcoxon signed ranks tests indicated that there was a significant reduction in psychiatric hospital use following CT. CONCLUSION: These results confirm that CT is an effective treatment for psychosis that is generalizable to a community setting.

Adolescent↗
PubMed2002

Randomised controlled trial of early detection and cognitive therapy for preventing transition to psychosis in high-risk individuals. Study design and interim analysis of transition rate and psychological risk factors.

BACKGROUND: There is interest in the possibility of indicated prevention of psychosis. There is a strong case for using psychological approaches to prevent transition to psychosis in high-risk patients. AIMS: To identify individuals at high risk of transition to psychosis, and psychological characteristics relevant to the development of psychosis in this group. METHOD: The design of a randomised controlled trial of cognitive therapy for the prevention of psychosis in people at high risk (meeting operational criteria of brief or attenuated psychotic symptoms, or first-degree family history with functional decline) is outlined. The first patients recruited are compared with non-patient samples on cognitive and personality factors; an interim analysis of transition rate is reported. RESULTS: Cases (n = 31) were recruited mainly from primary care. Of the 23 high-risk patients monitored for 6-12 months, 5 (22%) made the transition to psychosis. The high-risk group scored significantly higher than non-patients on measures of schizotypy, metacognitive beliefs and dysfunctional self-schemas (sociotropy). CONCLUSIONS: The findings validate the methods of identifying individuals at high risk of experiencing a psychotic episode. Compared with non-patient controls, the cases showed dysfunctional metacognitive beliefs and self-schemas.

Adult↗
PubMed2001

A novel peptide, THALWHT, for the targeting of human airway epithelia.

Targeting gene vectors to human airway epithelial cells may help to overcome the current inefficiency of gene transfer as the major problem confronting cystic fibrosis gene therapy. To elucidate novel ligands targeting abundant, apically located receptors on airway epithelial cells, a phage display library was screened for peptides binding with high affinity to such cells. This screening yielded a selectively enriched amino acid sequence, Thr-His-Ala-Leu-Trp-His-Thr (THALWHT). Subsequent binding studies confirmed that THALWHT-displaying phages bound much stronger than phages displaying control peptides to human airway epithelial cells. In contrast, no significant binding differences were observed on a variety of non-airway-derived human cell lines suggesting selective binding of the THALWHT motif to airway epithelia. Confocal microscopy of such cells after exposure to labelled synthetic THALWHT peptide indicated that its binding is followed by specific internalisation via endocytosis. A synthetic peptide comprising a cyclic CTHALWHTC domain and a DNA binding moiety enabled efficient targeted gene delivery into human airway epithelial cells. Competition assays with free THALWHT peptide confirmed the specificity of gene delivery. Thus, the THALWHT motif may prove a useful targeting moiety for both non-viral and viral gene therapy vectors.

Amino Acid Sequence↗
PubMed2001

The value of community mental health nurses based in primary care teams: 'switching the light on in a cellar'.

This paper explores the impact of placing Community Mental Health Nurses (CMHNs) at two primary care practices in South Staffordshire. Data were collected by means of a questionnaire which was sent to primary care personnel at these practices, to ascertain their opinions with respect to the contribution of practice-based CMHNs. Overall, primary care personnel were satisfied with the quality of the service received from the CMHNs, especially in terms of improved communication. They felt that the new arrangements enabled a quicker and more efficient access to the services of the CMHN. The results are discussed in terms of the value of having CMHNs within the primary care setting, and in terms of service planning and future recommendations for mental health services within primary care.

Attitude of Health Personnel↗
PubMed2001

Small bowel obstruction due to postoperative adhesions: treatment patterns and associated costs in 110 hospital admissions.

The workload and costs of the emergency admissions and treatment of adhesive small bowel obstruction (ASBO) are unclear. This review details and costs the admission workload of ASBO. All admissions over a 2-year period for ASBO at two district general hospitals were identified through ICD10 diagnostic codes. Diagnostic investigations, treatment patterns, ward stay and outcome information for admissions were detailed from clinical records to develop mean cost estimates and assess the associated workload. Of the 298 admissions identified, 188 were not due to ASBO and were excluded from analysis. Of the 110 admissions detailed, 41 (37%) were treated surgically and 69 (63%) conservatively. Most admissions occurred through general practitioner referral (86.4%) to accident and emergency (90.0%). Mean (SD) length of stay was 16.3 days (11.0 days) for surgical treatment and 7.0 days (4.6 days) for conservative treatment. In-patient mortality was 9.8% for the surgical group and 7.2% for the conservative group. Costs were based on the mean values from both centres for surgical and conservative admissions and detailed according to the cost of referral and follow-up (100.98 Pounds surgical versus 102.61 Pounds conservative), hospital ward and ICU stay (3,327.48 Pounds versus 1,267.92 Pounds), theatre time (832.32 Pounds surgical only), investigations (282.73 Pounds versus 207.33 Pounds) and drug costs (133.90 Pounds versus 28.29 Pounds). Total treatment cost per admission for ASBO was 4,677.41 Pounds for surgically treated admissions and 1,606.15 Pounds for conservatively treated admissions. The impact of admissions for ASBO is considerable in terms of both costs and workload. Bed stay for these admissions represents the equivalent of almost one surgical bed per year and at least 2 days theatre time, impacting on surgical capacity and waiting lists. Adhesion prevention strategies may reduce the workload associated with ASBO. The review provides useful information for planning resource allocation.

Adolescent↗
PubMed2001

Contemporary trends and practice strategies in pediatric occupational and physical therapy.

This paper identifies and reflects on recent trends in pediatric occupational therapy and physical therapy practice. These trends were initially identified by the student authors for a Maternal and Child Health (MCH) leadership seminar, which was conducted as part of the postprofessional graduate program in physical therapy at the University of Washington. Trends were then reviewed and discussed among the student and faculty authors. Consensus was reached on the most important trends, which were subsequently summarized in this paper. The first part of the paper reviews the impact of these trends on current and future clinical practices in health, educational, and community-based settings. The second part of the paper offers proposed directions to meet the challenges presented by the trends in four key areas; (1) research, (2) professional education, (3) enhancing family-centered care, and (4) advocacy.

Female↗
PubMed2000

Exploiting viral cell-targeting abilities in a single polypeptide, non-infectious, recombinant vehicle for integrin-mediated DNA delivery and gene expression.

A recombinant, multifunctional protein has been designed for optimized, cell-targeted DNA delivery and gene expression in mammalian cells. This hybrid construct comprises a viral peptide ligand for integrin alpha(V)beta(3) binding, a DNA-condensing poly-L-lysine domain, and a complete, functional beta-galactosidase protein that serves simultaneously as purification tag and DNA-shielding agent. This recombinant protein is stable; it has been produced successfully in Escherichia coli and can be purified in a single step by affinity chromatography. At optimal molar ratios, mixtures of this vector and a luciferase-reporter plasmid form stable complexes that transfect cultured cells. After exposure to these cell-targeted complexes, steady levels of gene expression are observed for more than 3 days after transfection, representing between 20 and 40% of those achieved with untargeted, lipid-based DNA-condensing agents. The principle to include viral motifs for cell infection in single polypeptide recombinant proteins represents a promising approach towards the design of non-viral modular DNA transfer vectors that conserve the cell-target- ing specificity of native viruses and that do not need further processing after bioproduction in a recombinant host.

Amino Acid Sequence↗
PubMed2000

Stimulation of dichlorofluorescin oxidation by capsaicin and analogues in RAW 264 monocyte/macrophages: lack of involvement of the vanilloid receptor.

In studies into the oxidative burst in RAW 264 monocyte/macrophages, it was observed that capsaicin, a vanilloid receptor agonist, stimulated dichlorofluorescin (DCFH) oxidation in a concentration-dependent manner, which could be blocked by capsazepine, a vanilloid receptor antagonist. However, by use of a number of vanilloid agonists (including N-octyl-3-chloro-4-hydroxyphenylacetamide, 4m), we demonstrated that there was no relationship between vanilloid agonist potency and the capacity to stimulate DCFH oxidation. The oxidative burst stimulators Tween 20 and phorbol myristyl acetate (PMA) also stimulated reactive oxygen species generation, which again was inhibited by capsazepine. Use of the selective inhibitor diphenyliodonium iodide ruled out a role for plasma membrane NAD(P)H oxidase as the site of capsaicin- and 4m-stimulated DCFH oxidation. However, this DCFH oxidation was modulated by a number of inhibitors of mitochondrial respiration. Rotenone enhanced DCFH oxidation induced by capsaicin and 4m, whilst malonic acid and potassium cyanide inhibited this response. 2,4-Dinitrophenol, an inhibitor of oxidative phosphorylation, was without effect. The antioxidant trolox c inhibited DCFH oxidation stimulated by capsaicin, 4m, and PMA, whereas N-acetylcysteine, a precursor of glutathione, was without effect. Capsazepine inhibited DCFH oxidation in unstimulated cells and in cells treated with menadione, a redox-cycling quinone. Capsazepine was also a potent antioxidant when measured in a Fe3+ reduction assay. We concluded that DCFH oxidation stimulated by vanilloid analogues was not mediated via a vanilloid receptor, but rather by impairment of mitochondrial electron transport.

Acetylcysteine↗
PubMed2000

Comparison of efficacy and safety between flunisolide/AeroChamber and budesonide/turbuhaler in patients with moderate asthma. AER-MD-04 Study Group.

BACKGROUND: There is a limited body of evidence comparing the clinical effects of different inhaled corticosteroids in the treatment of asthma. This study compared the safety and efficacy of inhaled flunisolide and budesonide, both with unique delivery systems that may affect clinical response. OBJECTIVE: This multicenter study was carried out to compare the efficacy and safety of flunisolide, administered via AeroChamber, with budesonide, administered via Turbuhaler, in the treatment of moderate asthma. METHODS: Patients with moderate asthma, defined as an FEV1 of 40% to 85% of predicted, underwent a 2-week run-in period during which beclomethasone, 750 microg twice daily by MDI, was administered, along with salbutamol prn. Patients (n = 176) were then randomized into two groups. One group received flunisolide administered via AeroChamber, 750 microg (3 puffs), twice daily. The second group received budesonide administered via Turbuhaler, 600 microg (3 puffs), twice daily. All patients took salbutamol prn. RESULTS: At the end of the 6-week treatment period, there were no significant differences (P > .05 for all comparisons) in efficacy between the groups as evaluated by any efficacy parameter. The treatment groups also did not differ significantly in the number of adverse events or in the incidence of oropharyngeal Candida infection. CONCLUSION: Flunisolide administered by AeroChamber and budesonide administered via Turbuhaler demonstrate similar efficacy and safety in the treatment of moderate asthma.

Administration, Inhalation↗