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Biomedical subjects

M King

Publications and source records attributed to M King.

At least 55 records · Page 3Linked to original sources
PubMed2001

Chronic fatigue in general practice: economic evaluation of counselling versus cognitive behaviour therapy.

BACKGROUND: There is a paucity of evidence relating to the cost-effectiveness of alternative treatment responses to chronic fatigue. AIM: To compare the relative costs and outcomes of counselling versus cognitive behaviour therapy (CBT) provided in primary care settings for the treatment of fatigue. DESIGN OF STUDY: A randomised controlled trial incorporating a cost-consequences analysis. SETTING: One hundred and twenty-nine patients from 10 general practices across London and the South Thames region who had experienced symptoms of fatigue for at least three months. METHOD: An economic analysis was performed to measure costs of therapy, other use of health services, informal care-giving, and lost employment. The principal outcome measure was the Fatigue Questionnaire; secondary measures were the Hospital Anxiety and Depression Scale and a social adjustment scale. RESULTS: Although the mean cost of treatment was higher for the CBT group (164 Pounds, standard deviation = 67) than the counselling group (109 Pounds, SD = 49; 95% confidence interval = 35 to 76, P < 0.001), a comparison of change scores between baseline and six-month assessment revealed no statistically significant differences between the two groups in terms of aggregate health care costs, patient and family costs or incremental cost-effectiveness (cost per unit of improvement on the fatigue score). CONCLUSIONS: Counselling and CBT both led to improvements in fatigue and related symptoms, while slightly reducing informal care and lost productivity costs. Counselling represents a less costly (and more widely available) intervention but no overall cost-effectiveness advantage was found for either form of therapy.

Adolescent↗
PubMed2001

Chronic fatigue in general practice: is counselling as good as cognitive behaviour therapy? A UK randomised trial.

BACKGROUND: Fatigue is a common symptom for which patients consult their doctors in primary care. With usual medical management the majority of patients report that their symptoms persist and become chronic. There is little evidence for the effectiveness of any fatigue management in primary care. AIM: To compare the effectiveness of cognitive behaviour therapy (CBT) with counselling for patients with chronic fatigue and to describe satisfaction with care. DESIGN OF STUDY: Randomised trial with parallel group design. SETTING: Ten general practices located in London and the South Thames region of the United Kingdom recruited patients to the trial between 1996 and 1998. Patients came from a wide range of socioeconomic backgrounds and lived in urban, suburban, and rural areas. METHOD: Data were collected before randomisation, after treatment, and six months later. Patients were offered six sessions of up to one hour each of either CBT or counselling. Outcomes include: self-report of fatigue symptoms six months later, anxiety and depression, symptom attributions, social adjustment and patients' satisfaction with care. RESULTS: One hundred and sixty patients with chronic fatigue entered the trial, 45 (28%) met research criteria for chronic fatigue syndrome; 129 completed follow-up. All patients met Chalder et al's standard criteria for fatigue. Mean fatigue scores were 23 on entry (at baseline) and 15 at six months' follow-up. Sixty-one (47%) patients no longer met standard criteria for fatigue after six months. There was no significant difference in effect between the two therapies on fatigue (1.04 [95% CI = -1.7 to 3.7]), anxiety and depression or social adjustment outcomes for all patients and for the subgroup with chronic fatigue syndrome. Use of antidepressants and consultations with the doctor decreased after therapy but there were no differences between groups. CONCLUSION: Counselling and CBT were equivalent in effect for patients with chronic fatigue in primary care. The choice between therapies can therefore depend on other considerations, such as cost and accessibility.

Adolescent↗
PubMed2001

Psychotherapists' approaches to gay and lesbian patients/clients: a qualitative study.

We used qualitative research methods to examine the core issues relating to the approaches of psychodynamic and psychoanalytic psychotherapists to gay and lesbian patients and clients. The paper begins with a review of the psychoanalytic approaches to gay and lesbian sexuality and continues with material of a clinical nature, providing information about the experience of lesbians and gay men in psychotherapy. It also explores the attitudes of therapists towards gay and lesbian sexuality by discussing a range of psychoanalytic theories and their application to clinical work with patients and clients.

Attitude of Health Personnel↗
PubMed2000

Randomised controlled trial of non-directive counselling, cognitive-behaviour therapy, and usual general practitioner care for patients with depression. I: clinical effectiveness.

OBJECTIVE: To compare the clinical effectiveness of general practitioner care and two general practice based psychological therapies for depressed patients. DESIGN: Prospective, controlled trial with randomised and patient preference allocation arms. SETTING: General practices in London and greater Manchester. PARTICIPANTS: 464 of 627 patients presenting with depression or mixed anxiety and depression were suitable for inclusion. INTERVENTIONS: Usual general practitioner care or up to 12 sessions of non-directive counselling or cognitive-behaviour therapy provided by therapists. MAIN OUTCOME MEASURES: Beck depression inventory scores, other psychiatric symptoms, social functioning, and satisfaction with treatment measured at baseline and at 4 and 12 months. RESULTS: 197 patients were randomly assigned to treatment, 137 chose their treatment, and 130 were randomised only between the two psychological therapies. All groups improved significantly over time. At four months, patients randomised to non-directive counselling or cognitive-behaviour therapy improved more in terms of the Beck depression inventory (mean (SD) scores 12.9 (9.3) and 14.3 (10.8) respectively) than those randomised to usual general practitioner care (18.3 (12.4)). However, there was no significant difference between the two therapies. There were no significant differences between the three treatment groups at 12 months (Beck depression scores 11.8 (9.6), 11.4 (10.8), and 12.1 (10.3) for non-directive counselling, cognitive-behaviour therapy, and general practitioner care). CONCLUSIONS: Psychological therapy was a more effective treatment for depression than usual general practitioner care in the short term, but after one year there was no difference in outcome.

Adult↗
PubMed2000

Randomised controlled trial of non-directive counselling, cognitive-behaviour therapy, and usual general practitioner care for patients with depression. II: cost effectiveness.

OBJECTIVE: To compare the cost effectiveness of general practitioner care and two general practice based psychological therapies for depressed patients. DESIGN: Prospective, controlled trial with randomised and patient preference allocation arms. SETTING: General practices in London and greater Manchester. PARTICIPANTS: 464 of 627 patients presenting with depression or mixed anxiety and depression were suitable for inclusion. INTERVENTIONS: Usual general practitioner care or up to 12 sessions of non-directive counselling or cognitive-behaviour therapy provided by therapists. MAIN OUTCOME MEASURES: Beck depression inventory scores, EuroQol measure of health related quality of life, direct treatment and non-treatment costs, and cost of lost production. RESULTS: 197 patients were randomly assigned to treatment, 137 chose their treatment, and 130 were randomised only between the two psychological therapies. At four months, both non-directive counselling and cognitive-behaviour therapy reduced depressive symptoms to a significantly greater extent than usual general practitioner care. There was no significant difference in outcome between treatments at 12 months. There were no significant differences in direct costs, production losses, or societal costs between the three treatments at either four or 12 months. Sensitivity analyses did not suggest that the results depended on particular assumptions in the statistical analysis. CONCLUSIONS: Within the constraints of available power, the data suggest that both brief psychological therapies may be significantly more cost effective than usual care in the short term, as benefit was gained with no significant difference in cost. There are no significant differences between treatments in either outcomes or costs at 12 months.

Adult↗
PubMed2000

Aicardi-Goutières syndrome displays genetic heterogeneity with one locus (AGS1) on chromosome 3p21.

We have studied 23 children from 13 families with a clinical diagnosis of Aicardi-Goutières syndrome. Affected individuals had developed an early-onset progressive encephalopathy that was characterized by a normal head circumference at birth, basal ganglia calcification, negative viral studies, and abnormalities of cerebrospinal fluid comprising either raised white cell counts and/or raised levels of interferon-alpha. By means of genomewide linkage analysis, a maximum-heterogeneity LOD score of 5.28 was reached at marker D3S3563, with alpha=.48, where alpha is the proportion of families showing linkage. Our data suggest the existence of locus heterogeneity in Aicardi-Goutières syndrome and highlight potential difficulties in the differentiation of this condition from pseudo-TORCH (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus types 1 and 2) syndrome.

Abnormalities, Multiple↗
PubMed2000

Drug target validation: lethal infection blocked by inducible peptide.

Genome projects are generating large numbers of potential new targets for drug discovery. One challenge is target validation, proving the usefulness of a specific target in an animal model. In this paper, we demonstrate a new approach to validation and assay development. We selected in vitro specific peptide binders to a potential pathogen target. By inducing the expression of a selected peptide in pathogen cells causing a lethal infection in mice, the animals were rescued. Thus, by combining in vitro selection methods for peptide binders with inducible expression in animals, the target's validity was rigorously tested and demonstrated. This approach to validation can be generalized and has the potential to become a valuable tool in the drug discovery process.

Amino Acid Sequence↗
PubMed2000

Characterization of plasma proteins adsorbed onto biomaterials. By MALDI-TOFMS.

The analysis of plasma proteins adsorbed onto a polyurethane (PU) biomaterial was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). This article marks the first study on MALDI-TOFMS analysis of multiple proteins adsorbed from plasma, in vitro, onto the surface of a biomaterial to easily enable their characterization. Plasma standards from three different hosts were placed in contact with non-porous PU, a model biomaterial. Following the use of washing protocols developed in our laboratory, the biomaterial was analyzed, directly, with MALDI-TOFMS. Proteins with molecular weights (Mr) ranging from ca. 6.5 to 150 kDa were observed in the mass spectra and characterized upon comparison with proteins of known Mr. The proteins observed were tentatively identified as those known to adsorb onto PU, both in vitro and in vivo. In an attempt to model in vivo sorption, the PU biomaterial was exposed to freshly collected canine plasma, in vitro, for different lengths of time. Corresponding MALDI-TOFMS spectra displayed increasing protein signal for a number of different proteins with increasing times of exposure to plasma. This method provided qualitative and semi-quantitative analysis of the proteins adsorbed onto the biomaterial surface.

Adsorption↗
PubMed2000

Effects of dextran sulfate on tracheal mucociliary velocity in dogs.

We have shown that low molecular weight dextran, as a potential mucolytic agent, reduced the viscoelasticity and spinnability of cystic fibrosis (CF) sputum and improved its ciliary transportability in vitro; it also reduced viscoelasticity of healthy dog mucus in in vitro testing. In anesthetized dogs, dextran administered by aerosol at 65 mg/mL increased tracheal mucus velocity, but this increase was not sustained for higher concentrations. The purpose of the present study is to evaluate whether low mol. wt. dextran sulfate, a charged oligosaccharide, exhibits similar effects to previously tested neutral dextran when administered by aerosol to anesthetized dogs in terms of mucus rheology and mucociliary clearance rate. Healthy mongrel dogs were anesthetized with pentobarbital and intubated. Aerosols of Ringer's solution or dextran sulfate (m.w. 5000) dissolved in Ringer's were generated by Pari LC STAR nebulizer, and delivered during 30-min periods of spontaneous breathing. Tracheal transepithelial potential difference (PD, using agar filled electrodes) and tracheal mucociliary velocity (TMV, by charcoal marker particle transport) were measured under bronchoscopic control, and mucus for viscoelasticity analysis by magnetic rheometry was collected by the endotracheal tube method. We performed experiments in seven dogs, involving 30-min administrations of aerosol, separated by 30-min periods of no aerosol. All dogs received inhalations of 6.5 mg/mL, 20 mg/mL, and 65 mg/mL dextran sulfate. Tracheal mucus viscoelasticity (average log G* over 1-100 rad/s) decreased progressively with increasing dose of dextran sulfate; for the highest concentration (65 mg/mL), log G* decreased by a factor of 2.61 (p = 0.021). A modest increase in the TMV was observed for the first dose of dextran sulfate (128% of baseline at 6.5 mg/mL, p = 0.066); thereafter TMV was stable. PD increased significantly at each concentration of dextran sulfate compared with Ringer control; however, there was no additional change between the three groups. The solids content of collected airway fluid (%SC) was gradually increased during successive 30-min dextran sulfate aerosols, indicating a significant residence time for the dextran in the mucus, and correlating with the decrease in viscoelasticity. These results suggest that dextran sulfate may be potentially of therapeutic value as a mucolytic agent, assisting mucus clearance by cough and physiotherapy, although whether it stimulates mucociliary clearance remains to be proven.

Aerosols↗
PubMed2000

Mitogenic effect of lithium in FRTL-5 cells can be reversed by blocking de novo cholesterol synthesis and subsequent signal transduction.

Lithium therapy is the therapeutic mainstay for bipolar disorder and has been associated in the thyroid with euthymic goiter, hyper and hypothyroidism as well as thyroid autoimmune disease. The FRTL-5 cell line is a well known model of thyroid cell physiology, where lithium has been shown to increase 3H-thymidine uptake at concentrations of 2 mM. This mitogenic effect was not associated with adenylate cyclase as measured by cyclic adenosine monophosphate (cAMP) production. The de novo synthesis of cholesterol is an important signal transduction pathway in FRTL-5 cells, where newly synthesized Rho GTPase is geranylgeranylated, enabling membrane localization of the G-protein and subsequent G1 to S-phase transition, resulting from extracellular stimulation. Here we confirm lithium mitogenicity at therapeutically relevant concentrations (1 mM) and demonstrate a lithium-associated accumulation of FRTL-5 cells in S-phase of the cell cycle. These effects could be abolished by Pravastatin, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), the rate-limiting enzyme in the formation of intermediates (de novo cholesterol synthesis) required for G-protein prenylation. Pravastatin, similar to lithium, showed no effect on cAMP production either under basal or thyroid stimulating hormone (TSH)-stimulated conditions indicating that de novo cholesterol synthesis is not involved with adenylate cyclase. The inhibitory effect of pravastatin could be overcome by reinitiating de novo cholesterol synthesis. This was achieved by the addition of the cell permeable, first metabolite (mevalonate) after HMG-CoA, which allowed the cycle to continue, leading eventually to protein prenylation, despite the presence of Pravastatin. These novel findings demonstrate lithium involvement in de novo cholesterol synthesis and G-protein prenylation, an important signal transduction pathway in FRTL-5 cells.

Animals↗
PubMed2000

Requirements for muscle relaxants during radical retropubic prostatectomy.

BACKGROUND: The need for the routine use of muscle relaxants to provide an adequate surgical field for intraabdominal surgery has not been established. This study tested the hypothesis that vecuronium decreases the frequency of unacceptable operating conditions for patients undergoing radical retropubic prostatectomy who are anesthetized with isoflurane and fentanyl. METHODS: After obtaining informed consent, patients in this blinded, placebo-controlled study were randomized to receive either an infusion of vecuronium or saline (placebo) beginning 5 min after fascial incision during the maintenance of anesthesia with at least 1 minimum alveolar concentration end-tidal isoflurane and fentanyl infusion. The surgical field was graded from 1 (excellent) to 4 (unacceptable) by the surgeons at 15-min intervals. If a grade 4 rating occurred (defined as a treatment failure), the patient received rescue vecuronium. RESULTS: A total of 120 patients are included in this report (59 in the vecuronium group and 61 in the placebo group). The frequency of treatment failure in the placebo group was 17 of 61 (27.9%) versus 1 of 59 (1.7%) in the control group who received vecuronium (P < 0.001). Thirty-eight patients (62.3%) in the placebo group and 52 patients (88.1%) in the vecuronium group had surgical field ratings of < or = 2 (good to excellent) at each time assessed throughout the procedure. CONCLUSION: The study hypothesis was confirmed. However, an isoflurane-fentanyl anesthetic alone produced a good to excellent surgical field in approximately two thirds of patients undergoing radical retropubic prostatectomy without the use of muscle relaxants. Thus, the routine use of muscle relaxants in adequately anesthetized patients undergoing this procedure may not be indicated.

Aged↗
PubMed2000

Effects of a heat and moisture exchanger and a heated humidifier on respiratory mucus in patients undergoing mechanical ventilation.

OBJECTIVE: To evaluate the effects of a heat and moisture exchanger and a heated humidifier on respiratory mucus and transportability by cilia and cough in patients undergoing invasive mechanical ventilation (up to 72 hrs). DESIGN: Prospective, randomized, clinical study. SETTING: General intensive care unit and university research laboratory. PATIENTS: A total of 32 consecutive patients with acute respiratory failure, who were intubated and mechanically ventilated in the intensive care unit setting, were enrolled in the study. INTERVENTIONS: Patients were randomly assigned to receive as a humidifying system a heat and moisture exchanger (HME) or heated humidified water (HHW) at the onset of mechanical ventilation (time 0). Respiratory mucus samples were collected by suction using a sterile technique at time 0, 24, 48, and 72 hrs of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Eleven patients were excluded from this study because of either extubation or death before 72 hrs of mechanical ventilation, leaving 12 patients in the HME group and nine patients in the HHW group. Ventilatory variables including minute volume, mean airway pressure, positive end-expiratory pressure, Fio2, as well as Pao2/Fio2 ratio, fluid balance (last 6 hrs), furosemide, and inotrope administration (last 4 hrs) were recorded. In vitro mucus transportability by cilia was evaluated on the mucus-depleted frog palate model, and the results were expressed as the mucus transport rate. Cough clearance (an estimation of the interaction between the flow of air and the mucus lining the bronchial walls) was measured using a simulated cough machine, the results being expressed in millimeters. Mucus wettability was measured by the contact angle between a mucus sample drop and a flat glass surface. Mucus rheologic properties (mechanical impedance [log G*] and the ratio between viscosity and elasticity [tan delta]) were measured using a magnetic microrheometer at 1 and 100 cGy/sec deformation frequency. The two humidification groups were comparable in terms of the Acute Physiology and Chronic Health Evaluation II score, age, gender, ventilatory variables, fluid balance, use of inotropes, and furosemide. CONCLUSION: Ours results indicate that air humidification with either HME or HHW at 32 degrees C (89.6 degrees F) has similar effects on mucus rheologic properties, contact angle, and transportability by cilia in patients undergoing mechanical ventilation, except for transportability by cough, which diminished after 72 hrs of mechanical ventilation in the HME group (p = .0441).

APACHE↗
PubMed2000

Estimating the responsiveness of an instrument using more than two repeated measures.

The responsiveness of a measuring instrument is its ability to detect change over time. A commonly used index of responsiveness is the effect size for paired differences. This paper generalizes the effect size for paired differences to more than two repeated observations per subject. The sampling distribution of the generalized responsiveness statistic, Rt, is simulated for a range of plausible parameter values and for a range of sample sizes varying both the number of subjects (n) and the number of observations per subject (t). The coverage properties of confidence intervals constructed by four methods are compared. Confidence intervals based on jackknife estimates of the standard error and bias of Rt have good coverage properties even when n and t are small. The methods are used to determine which of two standard quality-of-life measures is more responsive to improvements in quality of life following surgery for early-stage breast cancer.

Bias↗
PubMed2000

Lung delivery of aerosolized dextran.

The ability of nebulizers to deliver dextran (nominal molecular mass, 4,000 g/mol) to the lung as an inhaled aerosol is evaluated by in vitro experimental methods and mathematical models. Dextran in isotonic saline was aerosolized by four nebulizer types (Pari LC STAR, Hudson T-Updraft II, Acorn II, and Sonix 2000) at dextran concentrations </= 400 mg/ml and with 2.5- and 4-ml volume fills. Aerosols inhaled during breath simulation were characterized by in-line phase Doppler anemometry, filter collection, osmometry, and gravimetry. Mathematical models were used to estimate amounts of the characterized aerosols depositing in the different regions of lung models, and mathematical models of mucous thickness were then developed to estimate initial concentrations of the depositing dextran in the mucus of each conducting airway generation. Models of three subjects (4 yr old, 8 yr old, and adult) were used. The high viscosity of the dextran solutions tested (up to seven times that of water) negatively impacts nebulization, and results in poor performance with most delivery systems tested. Our results suggest that airway mucosal dextran concentrations associated with efficacy in previous animal and in vitro models are achievable with reasonable delivery times (</= 12 min) with only one of the delivery systems/formulations tested: the Pari LC STAR nebulizer, using a 2. 5-ml volume fill and a dextran concentration of 200 mg/ml.

Administration, Inhalation↗