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Biomedical subjects

M Lloyd

Publications and source records attributed to M Lloyd.

At least 19 recordsLinked to original sources
PubMed2005

[99mTc]TRODAT-1 SPECT imaging correlates with odor identification in early Parkinson disease.

BACKGROUND: In vivo imaging of the dopamine transporter with [99mTc]TRODAT-1 (TRODAT) and olfactory testing have both been proposed as potential biomarkers in Parkinson disease (PD). OBJECTIVE: To evaluate the relationship between TRODAT SPECT imaging, odor identification skills, and motor function in patients with early PD. METHODS: Twenty-four patients with a clinical diagnosis of early-stage PD (mean Hoehn & Yahr stage = 1.4) underwent TRODAT imaging, Unified PD Rating Scale (UPDRS) ratings of motor function, and administration of the University of Pennsylvania Smell Identification Test (UPSIT). Brain images were obtained using a standardized processing protocol and specific uptake ratios for striatal regions of interest were calculated. Partial correlations between the imaging indices, disease duration, UPSIT scores, and UPDRS motor scores were then calculated. RESULTS: UPSIT scores were correlated with TRODAT uptake in the striatum as a whole (r = 0.66, p = 0.001). The putamen showed the strongest correlation with the UPSIT (r = 0.74; p < 0.001). The correlation between dopamine transporter density in the caudate and UPSIT was moderate (r = 0.36, p = 0.11), but was not significant. CONCLUSIONS: Olfactory function is highly correlated with dopamine transporter imaging abnormalities in early Parkinson disease (PD). Further studies are warranted to determine whether changes over time in these two measures are also correlated in early PD.

Agnosia↗
PubMed2005

"It isn't just consultants that need a BSc": student experiences of an Intercalated BSc in primary health care.

More medical schools are moving towards a compulsory intercalated BSc. These courses have not traditionally been aimed at those students interested in general practice and have tended to have limited clinical relevance. This paper explores the perceptions of students who undertook a BSc in primary health care using qualitative methodology comprising semi-structured interviews with students just before completion of their course. Interviews were undertaken with 24 of the 26 students who started the course over a 4-year period. All the students have finished the course and have graduated with good honours degrees. Students refine existing skills and develop new, relevant skills for medicine. The students discussed the prestige (or lack) of a BSc in this field and how the course has impacted on their career decisions. A Primary Health Care BSc such as this appears to give students an in depth and to some, a positive view of general practice and primary care. The course allowed students to develop a more critical approach to medicine and enabled them to develop skills in addition to those acquired from their undergraduate medicine course. They perceived that these skills will serve them throughout their career in whatever branch of medicine they choose.

Attitude of Health Personnel↗
PubMed2005

Culture shift: carer empowerment and cooperative inquiry.

Government policy has directed local services to address the needs of carers as a way of maintaining care in the community. This study was initiated to enable carers to develop an information pack based upon their identified needs. Cooperative inquiry was the method used to ensure full participation of the carers. Group meetings were already in existence through a charity organization who provides a carers support network. The first author participated in a number of carers group meetings. Cooperative inquiry was used to clarify a number of themes identified and reflective cycles ensured that those themes remained relevant. It was found that carers did want to be involved in their relative's care, not as passive recipients but as collaborative care providers. To do this they need to be fully informed of the processes of care provision. Carers need information that is relevant, easily accessible and obtainable in varying degrees of comprehension. This study suggests that a culture shift within mental health nursing is necessary if professionals are to recognize that a perceived lack of support may lead to a breakdown in relationships between the carer, the person being cared for and the professionals.

Attitude to Health↗
PubMed2001

Dietary advice with or without pravastatin for the management of hypercholesterolaemia associated with protease inhibitor therapy.

BACKGROUND: Therapy with a HIV protease inhibitor is associated with elevations in cholesterol and triglycerides. HMG-CoA reductase inhibitors ('statins') are the established therapy for persons with primary hypercholesterolaemia. Because of drug interactions, pravastatin may represent the preferred choice in those taking HIV protease inhibitors. DESIGN: A randomized, open-label comparative 24 week trial of dietary advice alone or with pravastatin in 31 male patients established on protease inhibitor-based regimens for greater than 12 weeks with viral load < 500 copies/ml and cholesterol > 6.5 mmol/l. RESULTS: There were no significant clinical or laboratory events and no patient discontinuation secondary to adverse effects. Viral rebound did not occur. Relative to baseline, total cholesterol at week 24 fell significantly in the pravastatin (1.2 mmol/l; 17.3%) (P < 0.05) but not in the dietary advice (0.3 mmol/l; 4%) group. The difference between the two groups approached significance at week 24 (P = 0.051). This fall was accounted for entirely by a reduction in low density lipoprotein [calculated change 1.24 mmol/l (19%) and 0.07 mmol (5.5%) in pravastatin and dietary advice groups, respectively] as high density lipoprotein rose non-significantly by 0.6 mmol/l in both groups. Weight, basal metabolic rate, fasting glucose and triglycerides did not change significantly in either group. CONCLUSIONS: Dietary advice plus pravastatin significantly reduced total cholesterol in HIV-positive individuals taking protease inhibitors, without significant adverse effects. The inclusion of pravastatin substantially increases the magnitude of the change, which is comparable with changes achieved in endogenous hyperlipidaemia.

Anticholesteremic Agents↗
PubMed2001

A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease.

BACKGROUND: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. RESULTS: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. CONCLUSION: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.

Acetamides↗
PubMed2001

Cyclic GMP-dependent protein kinase activation and induction by exisulind and CP461 in colon tumor cells.

These studies report on the activation and induction of cGMP-dependent protein kinase (PKG) by exisulind and analogs and test the hypothesis that PKG is involved in the induction of apoptosis in colon tumor cells. Exisulind and analogs are proapoptotic drugs developed as inhibitors of cGMP phosphodiesterase gene families 5 and 2 that have been shown to sustain increased cGMP in SW480 and HT29 cells. At concentrations that induced apoptosis, both exisulind and CP461 increased PKG activity in SW480 cell supernatants. PKG activation was dose-dependent and sustained. Activation of PKG by exisulind and analogs was also seen in the colon tumor cell lines HT29, T84, and HCT116. The guanylyl cyclase activators YC-1 and guanylin increased PKG activity secondary to increased cellular cGMP and induced apoptosis in colon tumor cells. Exisulind and CP461 had no direct effect on purified PKG activity or on basal and stimulated PKG activity from cell supernatants. An additional effect of exisulind after 8 h of drug treatment was a dose-dependent increase of PKG Ibeta protein expression. beta-Catenin, a potential new substrate for PKG, whose regulation influences apoptosis, was phosphorylated by PKG in vitro. 32P-labeled cells treated with exisulind showed increased phosphorylation of beta-catenin. These data indicate that exisulind and analogs activate and induce PKG, resulting in increased phosphorylation of beta-catenin and enhanced apoptosis to promote colon tumor cell death.

3',5'-Cyclic-GMP Phosphodiesterases↗
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

Analysis on the move: deconstructing troublesome health questions and troubling epidemiology.

Qualitative research gets close to experiences of pain, illness, and disease; consequently, qualitative researchers often find themselves asked troublesome questions (i.e., laypeople ask for practical, helpful answers to their everyday illness concerns). This is not surprising, but of interest is the fact that academics ask each other such troublesome questions as part of academic discourse. When academics ask such questions, they may sometimes be after practical information, but they may also be using the questioning as an attack on the supposed excessive relativism of social constructionism. Three key analytical moves that offer a useful deconstruction of troublesome health questions are outlined, showing that they are another useful topic of constructionist inquiry. To lessen abstraction, these moves are brought to bear on a case study of a possible connection between pesticide use and birth defects, thus showing how social science and epidemiology can be connected, troubled, and extended in the process.

Benomyl↗
PubMed2000

Prospective controlled study of psychiatric out-patient non-attendance. Characteristics and outcome.

BACKGROUND: Psychiatric clinics have high non-attendance rates and failure to attend may be a sign of deteriorating mental health. AIMS: To investigate why psychiatric out-patients fail to attend, and the outcome of attenders and non-attenders. METHOD: Prospective cohort study of randomly selected attenders and non-attenders at general adult psychiatric out-patient clinics. Subjects were interviewed at recruitment and severity of mental disorder and degree of social adjustment were measured. Six and 12 months later their engagement with the clinic and any psychiatric admissions were ascertained. RESULTS: Of the 365 patients included in the study, 30 were untraceable and 224 consented to participate. Follow-up patients were more psychiatrically unwell than new patients. For follow-up patients, non-attenders had lower social functioning and more severe mental disorder than those who attended. At 12-month follow-up patients who missed their appointment were more likely to have been admitted than those who attended. CONCLUSIONS: Those who miss psychiatric follow-up out-patient appointments are more unwell and more poorly socially functioning than those who attend. They have a greater chance of drop-out from clinic contact and subsequent admission.

Adolescent↗
PubMed2000

The economics of employing a counsellor in general practice: analysis of data from a randomised controlled trial.

BACKGROUND: Counselling is currently adopted in many general practices, despite limited evidence of clinical and cost effectiveness. AIM: To compare direct and indirect costs of counsellors and general practitioners (GPs) in providing care to people with emotional problems. METHOD: We carried out a prospective, randomized controlled trial of non-directive counselling and routine general practice care in 14 general practices in north London. Counsellors adhered to a Rogerian model of counselling. The counselling sessions ranged from one to 12 sessions over 12 weeks. As reported elsewhere, there were no differences in clinical outcomes between the two groups. Therefore, we conducted a cost minimisation analysis. We present only the economic outcomes in this paper. Main outcome measures were cost data (service utilisation, travel, and work absence) at baseline, three months, and nine months. RESULTS: One hundred and thirty-six patients with emotional problems, mainly depression, took part. Seventy patients were randomised to the counsellors and 66 to the GPs. The average direct and indirect costs for the counsellor was 162.09 Pounds more per patient after three months compared with costs for the GP group; however, over the following six months the counsellor group was 87.00 Pounds less per patient than the GP group. Over the total nine-month period, the counsellor group remained more expensive per patient. CONCLUSIONS: Referral to counselling is no more clinically effective or expensive than GP care over a nine-month period in terms of direct plus indirect costs. However, further research is needed to establish indirect costs of introducing a counsellor into general practice.

Costs and Cost Analysis↗
PubMed2000

Randomised controlled trial of non-directive counselling, cognitive-behaviour therapy and usual general practitioner care in the management of depression as well as mixed anxiety and depression in primary care.

OBJECTIVES: The aim of this study was to determine both the clinical and cost-effectiveness of usual general practitioner (GP) care compared with two types of brief psychological therapy (non-directive counselling and cognitive-behaviour therapy) in the management of depression as well as mixed anxiety and depression in the primary care setting. DESIGN: The design was principally a pragmatic randomised controlled trial, but was accompanied by two additional allocation methods allowing patient preference: the option of a specific choice of treatment (preference allocation) and the option to be randomised between the psychological therapies only. Of the 464 patients allocated to the three treatments, 197 were randomised between the three treatments, 137 chose a specific treatment, and 130 were randomised between the psychological therapies only. The patients underwent follow-up assessments at 4 and 12 months. SETTING: The study was conducted in 24 general practices in Greater Manchester and London. SUBJECTS: A total of 464 eligible patients, aged 18 years and over, were referred by 73 GPs and allocated to one of the psychological therapies or usual GP care for depressive symptoms. INTERVENTIONS: The interventions consisted of brief psychological therapy (12 sessions maximum) or usual GP care. Non-directive counselling was provided by counsellors who were qualified for accreditation by the British Association for Counselling. Cognitive-behaviour therapy was provided by clinical psychologists who were qualified for accreditation by the British Association for Behavioural and Cognitive Psychotherapies. Usual GP care included discussions with patients and the prescription of medication, but GPs were asked to refrain from referring patients for psychological intervention for at least 4 months. Most therapy sessions took place on a weekly basis in the general practices. By the 12-month follow-up, GP care in some cases did include referral to mental healthcare specialists. MAIN OUTCOME MEASURES: The clinical outcomes included depressive symptoms, general psychiatric symptoms, social function and patient satisfaction. The economic outcomes included direct and indirect costs and quality of life. Assessments were carried out at baseline during face-to-face interviews as well as at 4 and 12 months in person or by post. RESULTS: At 4 months, both psychological therapies had reduced depressive symptoms to a significantly greater extent than usual GP care. Patients in the psychological therapy groups exhibited mean scores on the Beck Depression Inventory that were 4-5 points lower than the mean score of patients in the usual GP care group, a difference that was also clinically significant. These differences did not generalize to other measures of outcome. There was no significant difference in outcome between the two psychological therapies when they were compared directly using all 260 patients randomised to a psychological therapy by either randomised allocation method. At 12 months, the patients in all three groups had improved to the same extent. The lack of a significant difference between the treatment groups at this point resulted from greater improvement of the patients in the GP care group between the 4- and 12-month follow-ups. At 4 months, patients in both psychological therapy groups were more satisfied with their treatment than those in the usual GP care group. However, by 12 months, patients who had received non-directive counselling were more satisfied than those in either of the other two groups. There were few differences in the baseline characteristics of patients who were randomised or expressed a treatment preference, and no differences in outcome between these patients. Similar outcomes were found for patients who chose either psychological therapy. Again, there were no significant differences between the two groups at 4 or 12 months. Patients who chose counselling were more satisfied with treatment than those who chose c

Adult↗
PubMed1999

Apoptosis induced by overexpression of hMSH2 or hMLH1.

Mutations of the mismatch repair genes hMSH2 and hMLH1 have been found in a high proportion of individuals with hereditary nonpolyposis colon cancer (HNPCC), establishing the link between mismatch repair and cancer. Tumor cell lines that are deficient in mismatch repair develop a mutator phenotype that appears to drive the accumulation of mutations required for tumor development. However, mutations of other mismatch repair genes such as hPMS2 can lead to a mutator phenotype, although inherited mutations of these genes are rare in HNPCC families. Here, we show that overexpression of hMSH2 or hMLH1 but not of hMSH3, hMSH6, or hPMS2 induces apoptosis in either repair-proficient or -deficient cells. Furthermore, primary mouse embryo fibroblasts derived from Msh2-deficient mice lose their ability to undergo apoptosis after treatment with N-methyl-N'-nitro-N-nitrosoguanidine. These results suggest that the mismatch repair proteins hMSH2 and hMLH1 may be components of a pathway that influences apoptosis. We consider the possibility that loss of apoptosis as a result of hMSH2 or hMLH1 deficiency may be an additional factor in cancer predisposition in HNPCC.

Adaptor Proteins, Signal Transducing↗