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Biomedical subjects

Peter Heywood

Publications and source records attributed to Peter Heywood.

16 recordsLinked to original sources
PubMed2006

Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease.

OBJECTIVE: Glial cell line-derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open-label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin). METHODS: Thirty-four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15 microg/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and (18)F-dopa uptake. RESULTS: At 6 months, mean percentage changes in "off" UPDRS motor score were -10.0% and -4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, -23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean (18)F-dopa influx constant (p = 0.019) was observed. Serious, device-related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on-study and two in the open-label extension). INTERPRETATION: Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased (18)F-dopa uptake. It is uncertain whether technical differences between this trial and positive open-label studies contributed in any way this negative outcome.

Adult↗
PubMed2006

Antiretroviral therapy and HIV prevention in India: modeling costs and consequences of policy options.

OBJECTIVES: The objective of this study is to assess the costs, cost-effectiveness, and HIV epidemic impact of 3 antiretroviral therapy (ART) policy options. STUDY DESIGN: We constructed an epidemiologic model to predict the course of the HIV epidemic in the absence of expanded ART availability. Based on background studies of the willingness to pay for ART among patients with AIDS, of the costs to the government of the alternative treatment interventions, and of ART's likely effects on HIV transmission, we simulated the consequences of 3 possible alternative government ART policies. RESULTS: A program to reduce the negative consequences of the currently unstructured private-sector provision of ART is the most cost-effective of the 3 options at a 10% discount rate and least cost-effective at a 3% rate. The costs and cost-effectiveness of all options are highly sensitive to the effect of ART on condom use. CONCLUSION: The design of ART policy should capitalize on the potential of ART to decrease HIV transmission through institutional arrangements that reward effective prevention programs, thereby raising the likelihood that treatment has beneficial rather than negative external effects.

Antiviral Agents↗
PubMed2005

Year-round daylight saving and serious or fatal road traffic injuries in children in the north-east of England.

BACKGROUND: It has been suggested that year-round daylight saving would reduce road traffic injuries. METHODS: and results Using 15 years of police data from north-east England, we estimate that 6.9 (95 per cent CI 1.5-12.6) fewer serious or fatal road traffic injuries to child pedestrians would have occurred in this area over this period had year-round daylight saving operated (equivalent to 0.5 per year). CONCLUSION: The results suggest that operating daylight saving year-round would have a small but tangible effect on the number of serious and fatal road traffic injuries in children in this area. Further work is required to assess the community wide impact of year round daylight saving.

Accidents, Traffic↗
PubMed2005

Intraputamenal infusion of glial cell line-derived neurotrophic factor in PD: a two-year outcome study.

We have shown previously that intraparenchymal infusion of glial cell line-derived neurotrophic factor (GDNF) continuously into the posterior putamen in five Parkinson's disease patients is safe and may represent a new treatment option. Here, we report a continuation of this phase I study. After 2 years of continual GDNF infusion, there were no serious clinical side effects and no significant detrimental effects on cognition. Patients showed a 57% and 63% improvement in their off-medication motor and activities of daily living subscores of the Unified Parkinson's Disease Rating Scale, respectively, and health-related quality-of-life measures (Parkinson's Disease Questionnaire-39 and Short Form-36) showed general improvement over time.

Activities of Daily Living↗
PubMed2004

Weight-for-age malnutrition in Indonesian children, 1992-1999.

BACKGROUND: This article measures changes over time in Indonesia in the prevalence of moderate and severe child malnutrition, and examines the factors associated with these changes. A child with a weight-for-age Z-score below -2.0 is classified as underweight and either moderately or severely malnourished. METHODS: A pooled cross-sectional dataset of 163 986 children <5 years of age from the 1992, 1995, 1998, and 1999 Indonesia Socioeconomic Household Surveys was analysed using multivariate logistic regression, and by running separate pooled regressions to calculate the effect of the each of the principal independent variables separately for each year. Robust regression techniques corrected for non-constant variance resulting from multilevel modelling. RESULTS: The overall percentage of children <5 years that are underweight decreased from 37.7% in 1992 to 28.5% in 1999. Nearly all of the gains occurred in children over one year of age. Child nutritional status improved for all major social groups in Indonesia. There was no measurable general effect of the 1997-1999 East Asian economic crisis on levels of underweight children. CONCLUSIONS: Disparities among social and economic groups have narrowed over time in Indonesia; the relatively high risk of male children compared with females has also decreased. Maternal education and economic status-as measured by quintile of adjusted per-capita household expenditures-have continued to be very strong predictors of children's nutritional outcomes.

Age Distribution↗
PubMed2004

Dopamine agonist switching in Parkinson's disease.

There are a number of situations for patients with Parkinson's disease in which a safe and efficacious switch from treatment with one dopamine agonist to another may be required. This article explores reasons for making such a switch, and provides practical guidance on performing it.

Communication↗
PubMed2003

Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease.

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor with restorative effects in a wide variety of rodent and primate models of Parkinson disease, but penetration into brain tissue from either the blood or the cerebro-spinal fluid is limited. Here we delivered GDNF directly into the putamen of five Parkinson patients in a phase 1 safety trial. One catheter needed to be repositioned and there were changes in the magnetic resonance images that disappeared after lowering the concentration of GDNF. After one year, there were no serious clinical side effects, a 39% improvement in the off-medication motor sub-score of the Unified Parkinson's Disease Rating Scale (UPDRS) and a 61% improvement in the activities of daily living sub-score. Medication-induced dyskinesias were reduced by 64% and were not observed off medication during chronic GDNF delivery. Positron emission tomography (PET) scans of [(18)F]dopamine uptake showed a significant 28% increase in putamen dopamine storage after 18 months, suggesting a direct effect of GDNF on dopamine function. This study warrants careful examination of GDNF as a treatment for Parkinson disease.

Dihydroxyphenylalanine↗
PubMed2003

Unilateral subthalamotomy in the treatment of Parkinson's disease.

Hyperactivity in the subthalamic nucleus (STN) is seen in animal models of Parkinson's disease, and lesioning of the STN dramatically relieves the animal's parkinsonism. Deep brain stimulation (DBS) of the STN is an effective treatment for patients with advanced Parkinson's disease. We have studied the effects of a unilateral lesion placed in the STN in predominantly hemi-parkinsonian patients. Twenty-one patients with advanced idiopathic Parkinson's disease were studied. Seventeen had asymmetrical tremor-dominant Parkinson's disease and four had bilateral disease. All patients underwent radiofrequency lesioning of the dorsolateral part of the STN under stereotactic guidance. The four patients with bilateral disease had, in addition, an electrode implanted contralaterally in the STN. Twenty-one patients have been followed for a minimum of 12 months. Clinical evaluation included the use of the Unified Parkinson's Disease Rating Scale (UPDRS) before and after surgery. Post-operative high-resolution MRI was performed in each patient to confirm lesion location, and this was correlated with clinical outcome. There was improvement in contralateral tremor, rigidity and bradykinesia in all patients followed for 6, 12 and 24 months, with the effect on tremor being greatest. L-dopa equivalent daily intake was approximately halved, and this resulted in a significant reduction in dyskinesia. Psychometric test scores were mostly unchanged or improved. All lesions were successfully located in the dorsolateral STN. Nineteen of the 21 lesions extended beyond the STN to involve pallidofugal fibres (H2 field of Forel) and the zona incerta (ZI). Lesion-induced dyskinesias were not a management problem except in one patient, whose lesion was confined to the STN. This patient was successfully treated with deep brain stimulator placement in the region of H2/ZI. Unilateral STN lesions can be made safely and are an effective alternative to thalamotomy, pallidotomy and unilateral STN DBS for the treatment of asymmetrical tremor-dominant advanced Parkinson's disease. Com bined lesioning of the dorsolateral STN and H2/ZI is particularly effective.

Antiparkinson Agents↗
PubMed2002

MRI-directed subthalamic nucleus surgery for Parkinson's disease.

The subthalamic nucleus (STN) is now regarded as the optimal surgical target for the treatment of medically refractory idiopathic Parkinson's disease. In our center, a predominantly MRI-directed method has been developed for targeting the STN. The STN is localized on T2-weighted images from a 1.5-T MRI scanner. Long acquisition, high-resolution images are acquired in both the axial and coronal planes under strict stereotactic conditions with the patient under general anesthesia. The boundary of STN is co-registered in both planes to give optimal 3-dimensional target definition. Stereotactic coordinates of the dorsolateral STN are recorded and the trajectory is planned down the axis of the nucleus in the coronal plane. Initially, per-operative macrostimulation was used for adjustment at the target prior to unilateral subthalamotomy in 26 patients. Five patients were lost to follow-up. Assessments of the lesions in post-operative images confirmed successful localisation of the lesions within the dorsolateral STN in all of the remaining 21 cases. In a subsequent series of 19 patients treated by deep brain stimulation (DBS), unilateral in 1 patient and bilateral in 18, the STN was targeted using the same MRI-directed method, guide tubes and radio-opaque stylettes were implanted, and target verification was entirely MRI-based. Following implantation of the guide tubes and stylettes, assessments of the per-operative MRI images for the 37 STN targetings confirmed a mean target error, between the stylette and the desired target in the axial plane, of 0.3 mm mediolaterally (SD = 0.4) and 0.4 mm anteroposteriorly (SD = 0.4), with median errors of 0.5 mm. This study demonstrates that MRI-directed targeting of the STN through guide tubes is accurate, and allows direct verification and corrections as necessary. Cumulative frequencies predict that the majority of DBS electrodes placed in this manner will be within 0.5 mm of the planned target. Because physiological methods are not required, the whole procedure can be performed under general anesthesia. We feel that planning with reference to a standard atlas is unreliable and not significantly helped by the addition of microelectrode recording, the accuracy of which in the axial plane is dependent upon the distance between the recording trajectories, which is typically 2 mm.

Electric Stimulation Therapy↗
PubMedDate not supplied

Factors affecting breastfeeding practices: applying a conceptual framework.

Knowledge about factors affecting breastfeeding can be developed by further research on underlying factors and by drawing out the implications and lessons from intervention research. The use of a conceptual framework to guide this research and the interpretation of results can help us to understand the relative importance of different factors, and how they interact, in turn, helping us to design effective interventions.

Breast Feeding↗