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Biomedical subjects

M King

Publications and source records attributed to M King.

At least 19 recordsLinked to original sources
PubMed2006

Improved survival after concurrent weekly cisplatin and radiotherapy for cervical carcinoma with assessment of acute and late side-effects.

AIMS: A recent meta-analysis has shown a survival advantage for the addition of concurrent chemotherapy to radiotherapy in the treatment of cervical carcinoma. Controversy persists about the most appropriate chemotherapy schedule and whether similar results for tumour control and toxicity may be achieved with optimally delivered radiotherapy. A single-centre experience of a concurrent chemotherapy regimen is presented. MATERIALS AND METHODS: All women treated with concurrent chemoradiotherapy at a university hospital from 1 January 1999 to 1 May 2002 were identified. Acute and late complications were scored using the National Cancer Institute Common Toxicity Criteria and RTOG/ EORTC system, respectively. Univariate and multivariate analyses were carried out to examine the relationship between demographics, stage, overall treatment time, radiotherapy dose, selectron insertion, number of chemotherapy cycles and occurrence of acute and late toxicity. RESULTS: Seventy-nine women received concurrent weekly cisplatin (40 mg/m2) with radiotherapy. Thirty-eight per cent had early tumours (FIGO IIA or less) and 62% had locally advanced tumours. Twenty-eight per cent of women had surgery as part of primary treatment. Radiation technique included external-beam pelvic radiotherapy (EBRT) (45-50.4 Gy in 25-28 fractions) and medium-dose rate brachytherapy single insertion (25-27 Gy to point A) or EBRT alone. Median overall treatment time was 49 days (range 23-91 days). Three-year survival rate was 87% (95% confidence interval [CI] 79-95%). Three-year, progression-free survival rate was 75% (95% CI 65-85%). At a median follow-up of 35 months: 27 (34%) women experienced 45 episodes of acute grade 3 or 4, and eight women (10%) experienced 12 late grade 3 or 4 complications. CONCLUSIONS: Weekly cisplatin 40 mg/m2 concurrent with radiotherapy is well tolerated when given to an unselected population of patients. Survival rates seem to be excellent, with both local control and overall survival being at least as good as those in published randomised trials.

Adenocarcinoma↗
PubMed2006

Effects of an individually ventilated cage system on the airway integrity of rats (Rattus norvegicus) in a laboratory in Brazil.

The ventilation method used in the management of laboratory rats is important in maintaining their health. Rats kept under general diluting ventilation (GDV) are exposed to high levels of pollutants present in the environment (dust, airborne bacteria, etc.) or those pollutants produced by animal metabolism and excretion inside the boxes (e.g. ammonia and carbon dioxide). These pollutants may contribute to respiratory pathologies. An alternative experimental ventilation system for laboratory animal housing using intracage ventilation technology (individually ventilated cage system, IVC) was developed. In this system, ammonia levels decreased and rats exhibited better reproductive performance and a lower incidence of pneumonia than rats maintained under GDV. Using two different levels of air speed (0.03-0.26 m/s: IVC(1); 0.27-0.80 m/s: IVC(2)), the effects of IVC were compared with GDV (control) in Wistar rats in terms of respiratory mucus properties, on the nasal epithelium (as measured by quantitative morphometry) and on the lungs (as determined by the cellular composition obtained by bronchoalveolar lavage). Mucus of the respiratory system was evaluated using the following techniques: rheology (viscoelasticity) by microrheometer, in vitro mucociliary transportability (frog palate) and contact angle (an indicator of adhesivity). Also, membrane transepithelial potential difference was measured as a biomarker of airway integrity. After bedding was changed, ammonia concentrations inside the cages on day 3 were significantly higher for GDV than for IVC(1) and IVC(2). The potential-difference values for IVC(1), IVC(2) and GDV in the epiglottis and in the trachea also showed differences. Although some significant differences were observed across the three groups in counts of some cell types, the intragroup results were highly variable among individuals and inconsistent between sexes. No significant differences in the other parameters were found across groups. These results establish that rats maintained under GDV in relatively unregulated conditions are exposed to factors that can lead to deleterious effects on the ciliated epithelium of the airways, and that these effects can be prevented by the use of IVC.

Air Pressure↗
PubMed2005

D-D neutron generator development at LBNL.

The plasma and ion source technology group in Lawrence Berkeley National Laboratory is developing advanced, next generation D-D neutron generators. There are three distinctive developments, which are discussed in this presentation, namely, multi-stage, accelerator-based axial neutron generator, high-output co-axial neutron generator and point source neutron generator. These generators employ RF-induction discharge to produce deuterium ions. The distinctive feature of RF-discharge is its capability to generate high atomic hydrogen species, high current densities and stable and long-life operation. The axial neutron generator is designed for applications that require fast pulsing together with medium to high D-D neutron output. The co-axial neutron generator is aimed for high neutron output with cw or pulsed operation, using either the D-D or D-T fusion reaction. The point source neutron generator is a new concept, utilizing a toroidal-shaped plasma generator. The beam is extracted from multiple apertures and focus to the target tube, which is located at the middle of the generator. This will generate a point source of D-D, T-T or D-T neutrons with high output flux. The latest development together with measured data will be discussed in this article.

Journal Article↗
PubMed2005

Conceptual framework and systematic review of the effects of participants' and professionals' preferences in randomised controlled trials.

OBJECTIVES: To develop a conceptual framework of preferences for interventions in the context of randomised controlled trials (RCTs), as well as to examine the extent to which preferences affect recruitment to RCTs and modify the measured outcome in RCTs through a systematic review of RCTs that incorporated participants' and professionals' preferences. Also to make recommendations on the role of participants' and professionals' preferences in the evaluation of health technologies. DATA SOURCES: Electronic databases. REVIEW METHODS: The conceptual review was carried out on published papers in the psychology and economics literature concerning concepts of relevance to patient decision-making and preferences, and their measurement. For the systematic review, studies across all medical specialities meeting strict criteria were selected. Data were then extracted, synthesised and analysed. RESULTS: Key elements for a conceptual framework were found to be that preferences are evaluations of an intervention in terms of its desirability and these preferences relate to expectancies and perceived value of the process and outcome of interventions. RCTs differed in the information provided to patients, the complexity of techniques used to provide that information and the degree to which preference elicitation may simply produce pre-existing preferences or actively construct them. Most current RCTs used written information alone. Preference can be measured in many different ways and most RCTs did not provide quantitative measures of preferences, and those that did tended to use very simple measures. The second part of the study, the systematic review included 34 RCTs. The findings gave support to the hypothesis that preferences affect trial recruitment. However, there was less evidence that external validity was seriously compromised. There was some evidence that preferences influenced outcome in a proportion of trials. However, evidence for preference effects was weaker in large trials and after accounting for baseline differences. Preference effects were also inconsistent in direction. There was no evidence that preferences influenced attrition. Therefore, the available evidence does not support the operation of a consistent and important 'preference effect'. Interventions cannot be categorised consistently on degree of participation. Examining differential preference effects based on unreliable categories ran the risk of drawing incorrect conclusions, so this was not carried out. CONCLUSIONS: Although patients and physicians often have intervention preferences, our review gives less support to the hypothesis that preferences significantly compromise the internal and external validity of trials. This review adds to the growing evidence that when preferences based on informed expectations or strong ethical objections to an RCT exist, observational methods are a valuable alternative. All RCTs in which participants and/or professionals cannot be masked to treatment arms should attempt to estimate participants' preferences. In this way, the amount of evidence available to answer questions about the effect of treatment preferences within and outwith RCTs could be increased. Furthermore, RCTs should routinely attempt to report the proportion of eligible patients who refused to take part because of their preferences for treatment. The findings also indicate a number of approaches to the design, conduct and analysis of RCTs that take account of participants' and/or professionals' preferences. This is referred to as a methodological tool kit for undertaking RCTs that incorporate some consideration of patients' or professionals' preferences. Future research into the amount and source of information available to patients about interventions in RCTs could be considered, with special emphasis on the relationship between sources inside and outside the RCT context. Qualitative research undertaken as part of ongoing RCTs might be especially useful. The processes by which this information leads to preferences in order to develop or extend the proposed expectancy--value framework could also be examined. Other areas for consideration include: how information about interventions changes participants' preferences; a comparison of the feasibility and effectiveness of different informed consent procedures; how strength of preference varies for different interventions within the same RCT and how these differences can be taken account of in the analysis; the differential effects of patients' and professionals' preferences on evidence arising from RCTs; and whether the standardised measurement of preferences within all RCTs (and analysis of the effect on outcome) would allow the rapid development of a significant evidence base concerning patient preferences, albeit in relation to a single preference design.

Attitude of Health Personnel↗
PubMed2004

Partitioning of model toxins to hydrophobically terminated DAB dendrimers.

Dendrimers are attractive in biological and biomedical applications due to the similarity in their molecular size to biologically relevant molecules and the large number of chain ends available functionalization. In the current work, we examined the potential of diamino butane (DAB) dendrimers functionalized with long alkyl chains as partitioning agents for hydrophobic toxins for use as a prefiltering stage in a bioartiticial liver. DAB dendrimers of various generations that had been previously fully modified with palmitoyl chloride were obtained. A study of the kinetics of partitioning of acetylsalicylic acid (ASA) suggested that while significant toxin removal occurred in 30 s, although a slight time dependent increase in removal was noted up to 60 minutes. The partitioning of 6 hydrophobic toxins from aqueous solution to the modified dendrimers in 30 minutes was examined. The results demonstrated that a number of factors, including the pKa of the toxin, its octanol water partitioning coefficient and molecular size contributed to the level of toxin removal. Toxin removal on a molar basis increased with increasing dendrimer generation for all toxins, with the modified G5 dendrimers partitioning 50-100 toxin molecules in most cases. Dendrimer modification with C4 alkyl chains rather than Cl5 chains significantly decreased toxin removal, although chains longer than C10 seemed to partition equal amounts of toxins. The results of the study demonstrate that water-soluble dendrimers modified with hydrophobic end groups may be useful for the removal of toxins from the blood in a prereaction step for a bioartificial liver, but that a better understanding of the molecular mechanisms of removal may be necessary before it is possible to predict the levels of toxin removal.

Butanes↗
PubMed2004

Ophiopogon root (Radix Ophiopogonis) prevents ultra-structural damage by SO2 in an epithelial injury model for studies of mucociliary transport.

We studied the action of the herb, Ophiopogon root (OR) in a epithelial injury model, hypothesizing that it may have beneficial effects on mucociliary transport following injury to the palate induced by sodium metabisulphite (MB) which releases SO(2) on contact with water. OR (extract from 1g of root/ml)-incubated palates and non-incubated palates were compared to assess the effect of MB on mucociliary clearance on the bull frog palate. MB 10(-1) M, acutely increased mucociliary clearance time (MCT) by 254.5 +/- 57.3% in untreated and 243.3 +/- 98.5% in OR-incubated palates, (over all significance assessed by one-way ANOVA, F = 12.82, p < 0.001, df = 8,54 for MB and F = 10.56, p < 0.001, df = 8,54 for OR). MCT returned to normal during recovery in OR-treated palates following MB. In untreated palates, MCT did not return to control values during a similar recovery period. ANOVA comparing MCTs in the recovery period in untreated vs OR-treated palates was significantly different (F = 2.92, p < 0.03, df = 5,36). SEM images of epithelial tissue, analyzed by morphometry, showed a 25 +/- 12% loss of ciliated cells in untreated palates and little or no damage to cilia in OR-treated palates. Intact groups of ciliated cells were found in SEM micrographs of mucus from MB-treated palates. We conclude that the loss of cilia or ciliated cells prevented full recovery of MCT after MB in untreated palates. In OR-incubated palates, mucociliary transport was completely restored within 20 min after topical application of MB, possibly through a protective action on the extra-cellular matrix.

Animals↗
PubMed2004

Hepatitis C virus among childbearing women in Scotland: prevalence, deprivation, and diagnosis.

OBJECTIVES: (A) To examine the prevalence and demographic characteristics of hepatitis C virus (HCV) infection among childbearing women in Scotland; and (B) to determine the extent of maternal HCV infection diagnosed prior to birth. METHODS: (A) Residual dried blood spot samples from routine neonatal screening, collected throughout Scotland during March-October 2000, were unlinked from identifiers and tested anonymously for HCV antibodies; and (B) electronic record linkage of Scotland's databases of births and diagnosed HCV infections was performed. RESULTS: (A) Of 30,259 samples, 121 were enzyme linked immunosorbent assay repeat reactive and 88 of these were confirmed as anti-HCV positive in the recombinant immunoblot assay, representing a seroprevalence of 0.29-0.40%. HCV seroprevalence was high among 25-29 year olds (0.4-0.57%), in high deprivation areas (0.92-1.07%), and in Greater Glasgow (0.83-0.96%) and Grampian (0.38-0.62%). Adjusted relative risk for HCV infection was highest among residents in high deprivation areas of Glasgow (7.2 (95% confidence interval 2.0-25.5)). (B) Of 121 HCV infections found among women at delivery, 24% and 46% were estimated to have been diagnosed prior to pregnancy and birth, respectively. CONCLUSIONS: HCV prevalence among Scottish childbearing women is consistent with that expected from injecting drug use. Based on reported rates of mother to child transmission, 8-11 paediatric infections are expected per annum. Diagnosis in only 24% of infected women prior to pregnancy indicates the extent to which HCV goes unrecognised in the injecting community. The current HCV screening approach-to test only those with a history of injecting drug use (or other risk factors for infection)-identifies approximately a quarter of previously undetected infections among pregnant women.

Adult↗
PubMed2004

Effects of acute hypovolaemia by furosemide on tracheal transepithelial potential difference and mucus in dogs.

Furosemide is a potent diuretic that affects water transfer across the respiratory epithelium, which is closely related to the transepithelial potential difference (PD). Water is a critical factor that determines mucus transport; an important lung defence mechanism that removes particles and microorganisms from the respiratory system. The aim of the present study was to investigate the acute effects of furosemide and hypovolaemia on tracheal PD and mucus properties. A total of 36 male mixed-breed dogs were submitted to anaesthesia, mechanical ventilation and haemodynamic monitoring. They were randomly assigned to three groups consisting of: a control group, a furosemide (40 mg i.v.) + hypovolaemia group, and a furosemide (40 mg i.v.) + volume replacement group. Tracheal PD and mucus samples were collected at time 0, 1 and 2 h after intervention. Mucus properties were analysed by means of a magnetic microrheometer and in vitro mucociliary transportability on the frog palate. Compared to controls, furosemide decreased PD to intermediate values, and only significantly when associated with hypovolaemia (-13+/-5 and -8+/-2 mV, time 0 and 2 h, respectively). In addition to the direct effect of furosemide, these results indicate that hypovolaemia also affects ion transport in the tracheal membrane. Furosemide and hypovolemia have no acute effects on respiratory mucus properties.

Acute Disease↗
PubMed2004

Endoscopic scoring of mucus quantity and quality: observer and horse variance and relationship to inflammation, mucus viscoelasticity and volume.

REASONS FOR PERFORMING STUDY: Endoscopic scoring of airway mucus quantity and quality has not been critically assessed. OBJECTIVES: To evaluate mucus scores for 1) observer- and horse-related variance and 2) association with inflammation, mucus viscoelasticity and measured volume. METHODS: Variance of scoring within and between observers and over time within horses were determined for airway mucus accumulation, apparent viscosity, localisation and colour, and correlations of mucus accumulation scores with neutrophil ratios in secretions. The relationship of accumulation score to measured volumes of 'artificial mucus' was investigated. Correlations of mucus accumulation, apparent viscosity and colour scores with measured viscoelasticity were tested. Viscoelasticity was compared between tracheal secretion samples collected ventrally and dorsally. RESULTS: Mucus accumulation scoring showed excellent interobserver agreement and moderate horse-related variance, was related to measured volumes of 'artificial mucus', and correlated well with neutrophilic airway inflammation. Scores of mucus viscosity, colour and localisation showed high observer-related variance. Mucus accumulation, apparent viscosity and colour scores did not correlate with measured tracheal mucus viscoelasticity, but dorsally-localised mucus showed 2-fold higher measured viscoelasticity than ventrally-localised samples. CONCLUSIONS: Mucus accumulation scores are a reproducible measure of mucus volumes in the trachea. POTENTIAL RELEVANCE: Endoscopic scoring of mucus accumulation is a reliable clinical and research tool. In contrast, apparent viscosity, localisation and colour scores should be interpreted with caution.

Animals↗
PubMed2004

Severe proximal myopathy in advanced renal failure. Diagnosis and management.

Myopathies encountered in uremic patients may have different pathogenetic mechanisms and treatment. Secondary hyperparathyroidism may cause uremic myopathy responding to specific treatment. This study aimed at presenting a case illustrative of the clinical features, diagnosis and management of uremic parathyroid myopathy. A 66-year old man with renal failure from membranous nephropathy developed sensory signs of uremic neuropathy and progressive painless weakness of the pelvic girdle muscles bilaterally. Motor nerve conduction velocity was normal, electromyogram was consistent with a myopathic pattern, while muscle biopsy showed a pattern of atrophy more consistent with a neuropathic pattern. Serological tests for collagen vascular diseases and hyperthyroidism were negative, while serum muscle enzymes were not elevated and serum phosphate levels were not low. Serum parathyroid hormone level was grossly elevated, while serum calcium was mildly elevated in a small fraction of the measurements, serum alkaline phosphatase showed a progressive rise and skeletal bone survey did not disclose osteopenia or signs of parathyroid bone disease. A course of calcitriol failed to improve the myopathy, which responded promptly and dramatically to parathyroidectomy. Uremic parathyroid myopathy, which has a characteristic clinical picture, must be differentiated from other neuropathic or myopathic conditions that require specific treatments. Progressive parathyroid myopathy is, by itself, an indication for parathyroidectomy, which is curative in this case.

Aged↗
PubMed2003

High glucose and endothelial cell growth: novel effects independent of autocrine TGF-beta 1 and hyperosmolarity.

Human endothelial cells were exposed to 5 mM glucose (control), 25 mM (high) glucose, or osmotic control for 72 h. TGF-beta1 production, cell growth, death, and cell cycle progression, and the effects of TGF-beta1 and TGF-beta neutralization on these parameters were studied. High glucose and hyperosmolarity increased endothelial TGF-beta1 secretion (P < 0.0001) and bioactivity (P < 0.0001). However, high glucose had a greater effect on reducing endothelial cell number (P < 0.001) and increasing cellular protein content (P < 0.001) than the osmotic control. TGF-beta antibody only reversed the antiproliferative and hypertrophic effects of high glucose. High glucose altered cell cycle progression and cyclin-dependent kinase inhibitor expression independently of hyperosmolarity. High glucose increased endothelial cell apoptosis (P < 0.01), whereas hyperosmolarity induced endothelial cell necrosis (P < 0.001). TGF-beta antibody did not reverse the apoptotic effects observed with high glucose. Exogenous TGF-beta1 mimicked the increased S phase delay but not endoreduplication observed with high glucose. High glucose altered endothelial cell growth, apoptosis, and cell cycle progression. These growth effects occurred principally via a TGF-beta1 autocrine pathway. In contrast, apoptosis and endoreduplication occurred independently of this cytokine and hyperosmolarity.

Antibodies↗
PubMed2003

Late toxicity after short course preoperative radiotherapy and total mesorectal excision for resectable rectal cancer.

AIMS: The late toxicity of short-course preoperative radiotherapy (SCPRT) after total mesorectal excision (TME) in resectable rectal cancer has not been adequately documented. The acute toxicity in a series of 176 consecutive patients has been previously reported. In this study, the late toxicity in the same cohort is presented. MATERIALS AND METHODS: Side-effects occurring more than 3 months after the start of SCPRT were graded using the EORTC/RTOG late radiation toxicity system. We performed multivariate analysis to identify associated factors. RESULTS: Of 176 patients, 15 died within 3 months of SCPRT and five patients were lost to follow-up. One hundred and fifty-six patients were assessable at a median follow-up interval of 41 months: severe (grade 3-4) toxicity was seen in 20 patients (13%), of which 13 were gastrointestinal (8%); three urological (2%); three thromboembolic (2%), and one musculoskeletal (1%). On multivariate analysis, abdomino-perineal (AP) resection (P < 0.02) was associated with a lower risk of grade 3-4 toxicity. CONCLUSIONS: In this retrospective study, the rate of late grade 3-4 toxicity after SCPRT and TME was 13%. Although AP resection seems to be associated with a lower incidence of late toxicity, this could be counterbalanced by the impact of a stoma on quality of life. These factors should be considered when determining the optimal management of resectable rectal cancers.

Aged↗
PubMed2003

Patient-practitioner agreement: does it matter?

BACKGROUND: Good communication is a crucial clinical skill. Previous research demonstrated better clinical outcomes when practitioners and patients agree about the nature of patients' core presenting complaints. We investigated the nature of this agreement and its impact on outcome among depressed primary care patients. METHOD: We compared presenting problem formulations completed by patients, GPs and therapists in a primary care randomized controlled trial of cognitive-behavioural therapy and non-directive counselling for depression. Participants compiled formulations from a list of 13 potential problems of self-completed questionnaires. Subjects scored at least 14 on the Beck Depression Inventory (BDI) at baseline. Outcome measure for this study included BDI at 4 and 12 months, failure to attend for therapy when referred, dropout from therapy and patient satisfaction. RESULTS: Among 464 trial patients, 395 received therapy. Patient baseline problem formulations included significantly more items than GPs, who identified significantly more items than therapists. Agreement levels varied according to a range of patient and professional variables. While patients in complete agreement with their therapists about their main problem after assessment had lower average BDI scores at 12 months (9.7 v. 12.8, P=0.03); we found no other significant associations between the extent of agreement and clinical outcome. There were significant (but relatively weak) associations between agreement and aspects of patient satisfaction. CONCLUSION: Our results suggest that detailed mutual understanding of the presenting complaints may be less important than agreement that the core problem is psychological, and that referral for psychological therapy is appropriate.

Adolescent↗
PubMed2003

Predictors of outcome in a fatigued population in primary care following a randomized controlled trial.

BACKGROUND: The objective of this study was to examine factors that predicted outcome in a chronically fatigued group of patients who were randomized to cognitive behaviour therapy or counselling in primary care. METHOD: Illness perceptions, attributions, fatigue, disability and demographic variables were recorded at assessment and levels of fatigue and disability were measured at 6 months post randomization. Logistic regression was used to examine associations. RESULTS: Factors that predicted a poor outcome (four or more on the fatigue questionnaire) were: poor social adjustment at assessment; the patients self-report that they had never seen the GP for an emotional reason; a physical illness attribution; and, a long perceived future illness duration. CONCLUSIONS: Patients who are more psychologically minded are more likely to improve with psychological treatments in primary care. General practitioners need to assess this before referring to an appropriate therapist.

Adolescent↗