ABSTRACT
BACKGROUND: Many UK communities experience food insecurity, and consume diets high in energy-dense, nutrient poor, processed foods and low in fruit and vegetables (FV). We explored a novel area-based approach to promote FV consumption and healthy eating in one such community. METHODS: We developed a weekly subsidy scheme for fresh FV with key local stakeholders in an area of socioeconomic deprivation in Northern England. The scheme (Fresh Street) offered five £1 vouchers to every household, regardless of income or household type. Vouchers were redeemable with local suppliers of fresh FV (not supermarkets). The feasibility of the scheme was assessed in four streets using rapid ethnographic assessment and voucher redemption information. RESULTS: Local councillors and public health teams were supportive of the scheme. Most eligible households joined the scheme (n = 80/97, 83%), and 89.3% (17 849/19 982) of vouchers issued were redeemed. Householders reported that the scheme made them think about what they were eating, and prompted them to buy and eat more FV. CONCLUSIONS: This feasibility study reported high levels of acceptance for a place-based, household-level weekly FV subsidy scheme. Further research is required to evaluate the effectiveness of this approach to creating healthy diets, eating behaviours and food systems.
Subject(s)
Fruit , Vegetables , Diet , Feasibility Studies , Humans , PovertyABSTRACT
BACKGROUND: Body mass index (BMI) can be used to group individuals in terms of their height and weight as obese. However, such a distinction fails to account for the variation within this group across other factors such as health, demographic and behavioural characteristics. The study aims to examine the existence of subgroups of obese individuals. METHODS: Data were taken from the Yorkshire Health Study (2010-12) including information on demographic, health and behavioural characteristics. Individuals with a BMI of ≥30 were included. A two-step cluster analysis was used to define groups of individuals who shared common characteristics. RESULTS: The cluster analysis found six distinct groups of individuals whose BMI was ≥30. These subgroups were heavy drinking males, young healthy females; the affluent and healthy elderly; the physically sick but happy elderly; the unhappy and anxious middle aged and a cluster with the poorest health. CONCLUSIONS: It is important to account for the important heterogeneity within individuals who are obese. Interventions introduced by clinicians and policymakers should not target obese individuals as a whole but tailor strategies depending upon the subgroups that individuals belong to.
Subject(s)
Health Status , Obesity/epidemiology , Obesity/psychology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Alcohol Drinking/epidemiology , Body Mass Index , Chronic Disease/epidemiology , Chronic Disease/psychology , Cluster Analysis , England/epidemiology , Female , Happiness , Health Behavior , Humans , Longitudinal Studies , Male , Middle Aged , Risk Factors , Sex Distribution , Socioeconomic Factors , Surveys and Questionnaires , Young AdultABSTRACT
INTRODUCTION: Various techniques are used for spinal cord untethering. The purpose of this study was to compare patient characteristics, postoperative course, and early complications after laminotomy vs. laminoplasty for transection of the filum terminale for tethered cord release. METHODS: Retrospective analysis of clinical and magnetic resonance imaging data was undertaken for all patients (<18 years) who underwent tethered cord release by transection of the filum terminale at Oregon Health & Science University, Doernbecher Children's Hospital, from 2000 to 2011. RESULTS: Data from two hundred and forty-eight patients were analyzed. Mean age was 5.2 years (range 0.3 to 16.8 years). Access to the thecal space during surgery was achieved using laminotomy or laminoplasty in 82 (33.1 %) and 166 (66.9 %) patients, respectively. Laminoplasty patients were significantly younger than laminotomy patients (3.2 vs. 9.3 years, p<0.0001); other clinical and radiographic characteristics were similar between the groups. Nine patients (3.6 %) experienced early complications, including cerebrospinal fluid leak (n=2), suprafascial infection requiring surgical management and intravenous (IV) antibiotics (n=3) or IV antibiotics alone (n=1), a small area of peri-incisional cutaneous necrosis (n=1), perioperative seizures (n=1), and mild, transient malignant hyperthermia (n=1). There was no difference in the number of early complications between the two groups. Univariate and multivariate analyses revealed no significant risk factor for postoperative complication associated with technique. As judged by caregivers, independent of surgical technique, 97 % of patients improved after surgery. CONCLUSION: There was no difference in complication risk when performing transection of the filum terminale for tethered cord release using laminotomy or laminoplasty.
Subject(s)
Cauda Equina/surgery , Laminectomy/methods , Laminoplasty/methods , Peripheral Nervous System Diseases/surgery , Postoperative Complications/physiopathology , Adolescent , Child , Child, Preschool , Databases, Factual/statistics & numerical data , Female , Humans , Infant , Magnetic Resonance Imaging , Male , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: To analyse whether an individual's neighbourhood influences the uptake of weight management strategies and whether there is an interaction between individual socio-economic status and neighbourhood deprivation. METHODOLOGY: Data were collected from the Yorkshire Health Study (2010-2012) for 27 806 individuals on the use of the following weight management strategies: 'slimming clubs', 'healthy eating', 'increasing exercise' and 'controlling portion size'. A multi-level logistic regression was fit to analyse the use of these strategies, controlling for age, sex, body mass index, education, neighbourhood deprivation and neighbourhood population turnover (a proxy for neighbourhood social capital). A cross-level interaction term was included for education and neighbourhood deprivation. Lower Super Output Area was used as the geographical scale for the areal unit of analysis. RESULTS: Significant neighbourhood effects were observed for use of 'slimming clubs', 'healthy eating' and 'increasing exercise' as weight management strategies, independent of individual- and area-level covariates. A significant interaction between education and neighbourhood deprivation was observed across all strategies, suggesting that as an area becomes more deprived, individuals of the lowest education are more likely not to use any strategy compared with those of the highest education. CONCLUSIONS: Neighbourhoods modify/amplify individual disadvantage and social inequalities, with individuals of low education disproportionally affected by deprivation. It is important to include neighbourhood-based explanations in the development of community-based policy interventions to help tackle obesity.
Subject(s)
Diet, Reducing , Exercise , Obesity/epidemiology , Residence Characteristics , Social Environment , Adolescent , Adult , Body Mass Index , Cross-Sectional Studies , Diet, Reducing/psychology , Educational Status , England/epidemiology , Exercise/psychology , Female , Health Behavior , Humans , Male , Middle Aged , Obesity/prevention & control , Obesity/psychology , Prevalence , Socioeconomic FactorsABSTRACT
BACKGROUND AND PURPOSE: Previous studies have suggested that elevated progesterone levels are associated with a slower disease course in amyotrophic lateral sclerosis (ALS). Given that the effects of progesterone are mediated in part by the classical progesterone receptor (PR), the expression and cellular localization of the A and B isoforms (PR-A and PR-B, respectively) of the PR in control (neuropathologically normal) and ALS-affected spinal cord (SC) were examined. METHODS: Semi-quantitative RT-PCR, immunohistochemistry and immunofluorescence analyses of the cervical and lumbar SC of post-mortem ALS patients (n = 19) and control subjects (n = 10) were performed. Primers and antibodies used allowed the detection of both PR-A and PR-B isoforms together (PR-A+B) or PR-B isoform alone. RESULTS: Lumbar PR-A+B and cervical PR-B mRNA expression were significantly higher in ALS than controls. In both ALS and controls, PR-A+B immunoreactivity (IR) was occasionally detected in motor neurons. In contrast, PR-A+B IR was prominent in axonal processes and vessels. This was more evident in nerve roots and large arteries in ALS compared with controls. Colocalization of PR-A+B with markers of neurons, axonal processes and vascular endothelium was also observed. CONCLUSIONS: Evidence that both PR-A and PR-B isoforms are expressed in the human SC is provided, with some regional variation in isoform expression between ALS and controls. The IR was more prominent in nerve roots and large arteries in ALS, suggesting a potential role in the degenerative process.
Subject(s)
Amyotrophic Lateral Sclerosis/metabolism , Motor Neurons/metabolism , Receptors, Progesterone/metabolism , Spinal Cord/metabolism , Adult , Aged , Aged, 80 and over , Amyotrophic Lateral Sclerosis/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Motor Neurons/pathology , Spinal Cord/pathology , Spinal Nerve Roots/metabolism , Spinal Nerve Roots/pathologyABSTRACT
In recent years, magnesium based materials have been proposed as a potential biodegradable metallic implant material for orthopedic applications. Magnesium alloys are an excellent material for this purpose because they have mechanical properties that are similar to bone, have been shown to dissolve in biological fluids and are non-toxic. However, there is still relatively little information on the surface chemistry of these materials in physiological solutions. The interaction of phosphates with magnesium alloys is of particular interest because the deposition of calcium phosphate at implant surfaces is critical to the healing process in orthopedic applications. In the present work, the chemistry at the magnesium hydroxide/solution interface for model solutions containing physiologically relevant ions and protein was investigated using in situ ATR-FTIR. These studies are complemented by ex situ analysis of magnesium alloy coupons exposed to similar solutions. Our results demonstrate that precipitation of phosphate minerals at the solid/liquid interface dominates the observed changes in surface chemistry. The mineralization process was further observed to be strongly affected by the presence of chloride salts and protein in solution.
Subject(s)
Calcium/chemistry , Chlorides/chemistry , Magnesium Hydroxide/chemistry , Phosphates/chemistry , Proteins/chemistry , Particle Size , Solutions , Surface Properties , Water/chemistryABSTRACT
N-acetyl-glutamate synthase (NAGS) deficiency is a rare autosomal recessive urea cycle disorder (UCD) that uncommonly presents in adulthood. Adult presentations of UCDs include; confusional episodes, neuropsychiatric symptoms and encephalopathy. To date, there have been no detailed neurological descriptions of an adult onset presentation of NAGS deficiency. In this review we examine the clinical presentation and management of UCDs with an emphasis on NAGS deficiency. An illustrative case is provided. Plasma ammonia levels should be measured in all adult patients with unexplained encephalopathy, as treatment can be potentially life-saving. Availability of N-carbamylglutamate (NCG; carglumic acid) has made protein restriction largely unnecessary in treatment regimens currently employed. Genetic counselling remains an essential component of management of NAGS.
Subject(s)
Brain Diseases/etiology , Urea Cycle Disorders, Inborn/complications , Adult , Amino-Acid N-Acetyltransferase , Ammonia/blood , Brain Diseases/mortality , Brain Diseases/therapy , Female , Humans , Male , Metabolic Networks and Pathways/physiology , Urea Cycle Disorders, Inborn/mortality , Urea Cycle Disorders, Inborn/therapyABSTRACT
BACKGROUND AND PURPOSE: Sporadic amyotrophic lateral sclerosis (sALS) is a disease with a focal clinical onset and contiguous spread. We examined patterns of disease spread following symptoms onset in sALS and whether the pattern of spread predicted survival. METHODS: Review of medical records (2003-2009) at London Ontario and Buenos Aires clinic cohorts retrieved 318 patients with sporadic sALS. According to patient self-report, we determined eight spread patterns: rostro-caudal, caudo-rostral, crossed, circular, superior interposed, middle interposed, inferior interposed and isolated. The variables studied were as follows: age, gender, sALS phenotypes, time from onset to diagnosis and time and direction of the spreading to the first region. Survival from symptoms onset was analysed by Kaplan-Meier, Tarone-Ware and Cox proportional hazards methods. RESULTS: The direction of first spread was horizontal in 33%, rostral to caudal in 32% and caudal to rostral in 21%, whereas spread to remote regions was observed in 14% of patients. Survival curves and 3- and 5-year survival rates favoured patients with an isolated and caudo-rostral pattern of spread compared to patients progressing to distant regions without involvement in the intervening region, or 'superior and inferior interposed patterns' (Tarone-Ware P = 0.001, χ(2) = 0.002 and χ(2) = 0.006, respectively). Factors affecting survival were gender, time to diagnosis, flail arm phenotype and age at diagnosis. CONCLUSIONS: We have provided evidence that not all spread in ALS is contiguous and that the nature of symptom progression influences survival. Patients with sALS with 'interposed patterns' had a worse prognosis, whereas patients with caudo-rostral pattern fared better than the rest.
Subject(s)
Amyotrophic Lateral Sclerosis/mortality , Amyotrophic Lateral Sclerosis/pathology , Brain/pathology , Adult , Age of Onset , Aged , Aged, 80 and over , Cohort Studies , Disease Progression , Female , Functional Laterality , Humans , Male , Middle Aged , Phenotype , Proportional Hazards Models , Retrospective Studies , Self Report , Survival Rate , Young AdultABSTRACT
The hydrogen and oxygen isotope ratios of water vapor can be measured with commercially available laser spectroscopy analyzers in real time. Operation of the laser systems in relatively dry air is difficult because measurements are non-linear as a function of humidity at low water concentrations. Here we use field-based sampling coupled with traditional mass spectrometry techniques for assessing linearity and calibrating laser spectroscopy systems at low water vapor concentrations. Air samples are collected in an evacuated 2 L glass flask and the water is separated from the non-condensable gases cryogenically. Approximately 2 µL of water are reduced to H(2) gas and measured on an isotope ratio mass spectrometer. In a field experiment at the Mauna Loa Observatory (MLO), we ran Picarro and Los Gatos Research (LGR) laser analyzers for a period of 25 days in addition to periodic sample collection in evacuated flasks. When the two laser systems are corrected to the flask data, they are strongly coincident over the entire 25 days. The δ(2)H values were found to change by over 200 over 2.5 min as the boundary layer elevation changed relative to MLO. The δ(2)H values ranged from -106 to -332, and the δ(18)O values (uncorrected) ranged from -12 to -50. Raw data from laser analyzers in environments with low water vapor concentrations can be normalized to the international V-SMOW scale by calibration to the flask data measured conventionally. Bias correction is especially critical for the accurate determination of deuterium excess in dry air.
ABSTRACT
During the containment phase of the 2009 influenza A(H1N1) pandemic, mass treatment and prophylaxis with oseltamivir was used to control an outbreak of pandemic influenza in a primary school in Sheffield, United Kingdom, where ten cases of pandemic influenza had been laboratory confirmed over a three day period in June 2009. A subsequent cross-sectional survey showed that 51 of 297 (17%) pupils and 10 of 58 (17%) reported an influenza-like illness. The most common symptoms were headache, cough, fever, tiredness, sore throat and nausea. Fifty-three staff and 273 pupils took oseltamivir for treatment or prophylaxis. Of this group, 41% (113/273) of pupils and 47% (25/53) of staff reported adverse effects. Overall, 14% (37/273) of pupils and 20% (11/53) of staff did not complete the course of oseltamivir, primarily due to adverse effects. Nausea, vomiting and rash were statistically significantly associated with failing to complete the course of oseltamivir. Given the potential for side effects from oseltamivir, particularly among those without influenza who receive the drug for prophylaxis, our findings have two important implications. Firstly, the benefits of mass treatment in an outbreak setting must clearly be greater than the benefits of targeted treatment. Secondly, any large scale regional or state level system for distribution of antiviral drugs for treatment should ideally include a robust quantification of an individual s probability of infection with influenza virus in order to avoid unnecessary treatment.
Subject(s)
Disease Outbreaks/prevention & control , Disease Outbreaks/statistics & numerical data , Drug-Related Side Effects and Adverse Reactions/epidemiology , Influenza A Virus, H1N1 Subtype , Mass Vaccination/statistics & numerical data , Oseltamivir/administration & dosage , Students/statistics & numerical data , Antiviral Agents/administration & dosage , Child , Comorbidity , Humans , Incidence , Risk Assessment/methods , Risk Factors , Schools/statistics & numerical data , United Kingdom/epidemiologyABSTRACT
The neurosteroid allopregnanolone (ALLO) is a progesterone metabolite that is one of a family of neuroactive steroids (NAS) that are potent positive allosteric modulators of gamma-aminobutyric acid(A) (GABA(A)) receptors. These GABAergic NAS are produced peripherally (in the adrenals and gonads) and centrally in the brain. Peripherally produced NAS modulate some effects of ethanol intoxication (e.g., anxiolytic, antidepressant, and anticonvulsant effects) in rodents. We have found that NAS also may be involved in the rebound neural hyperexcitability following a high ethanol dose. Removal of the adrenals and gonads (ADX/GDX) increased withdrawal severity following 4 g/kg ethanol, as measured by handling-induced convulsions (HICs) in male and female DBA/2J mice. NAS are produced through the metabolism of progesterone (PROG), deoxycorticosterone (DOC), or testosterone, which can be blocked with the administration of finasteride (FIN), a 5alpha-reductase enzyme inhibitor. The current investigation was undertaken to clarify the step(s) in the biosynthetic NAS pathway that were sufficient to restore the acute ethanol withdrawal profile in ADX/GDX mice to that seen in intact animals. Male and female DBA/2J mice underwent ADX/GDX or SHAM surgery. After recovery, separate groups of animals were administered PROG, DOC, PROG+FIN, DOC+FIN, FIN, ALLO, ganaxalone (a synthetic ALLO derivative), corticosterone, or vehicle. Animals were then administered a 4 g/kg ethanol dose and allowed to undergo withdrawal. HICs were measured for 12 h and again at 24 h. The results indicate that replacement with PROG and DOC restored the withdrawal profile in ADX/GDX animals to SHAM levels, and that this effect was blocked with co-administration of FIN. Administration of FIN alone increased the withdrawal profile in both SHAM and ADX/GDX males. These findings indicate that the increase in acute withdrawal severity after ADX/GDX may be due to the loss of GABAergic NAS, providing insight into the contribution of endogenous GABAergic NAS to ethanol withdrawal severity.
Subject(s)
Alcohol-Induced Disorders, Nervous System/metabolism , Neurotransmitter Agents/metabolism , Receptors, GABA-A/metabolism , Substance Withdrawal Syndrome/metabolism , gamma-Aminobutyric Acid/metabolism , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism , 5-alpha Reductase Inhibitors , Acute Disease/therapy , Alcohol-Induced Disorders, Nervous System/drug therapy , Alcohol-Induced Disorders, Nervous System/physiopathology , Animals , Castration , Central Nervous System Depressants/toxicity , Desoxycorticosterone/metabolism , Desoxycorticosterone/pharmacology , Disease Models, Animal , Enzyme Inhibitors/pharmacology , Ethanol/toxicity , Female , Finasteride/pharmacology , Male , Mice , Neural Inhibition/drug effects , Neural Inhibition/physiology , Neurotransmitter Agents/pharmacology , Neurotransmitter Agents/therapeutic use , Pregnanolone/metabolism , Progesterone/metabolism , Progesterone/pharmacology , Receptors, GABA-A/drug effects , Substance Withdrawal Syndrome/drug therapy , Substance Withdrawal Syndrome/physiopathologyABSTRACT
OBJECTIVE: To systematically review evidence bearing on the management of patients with amyotrophic lateral sclerosis (ALS). METHODS: The authors analyzed studies from 1998 to 2007 to update the 1999 practice parameter. Topics covered in this section include slowing disease progression, nutrition, and respiratory management for patients with ALS. RESULTS: The authors identified 8 Class I studies, 5 Class II studies, and 43 Class III studies in ALS. Important treatments are available for patients with ALS that are underutilized. Noninvasive ventilation (NIV), percutaneous endoscopic gastrostomy (PEG), and riluzole are particularly important and have the best evidence. More studies are needed to examine the best tests of respiratory function in ALS, as well as the optimal time for starting PEG, the impact of PEG on quality of life and survival, and the effect of vitamins and supplements on ALS. RECOMMENDATIONS: Riluzole should be offered to slow disease progression (Level A). PEG should be considered to stabilize weight and to prolong survival in patients with ALS (Level B). NIV should be considered to treat respiratory insufficiency in order to lengthen survival (Level B) and to slow the decline of forced vital capacity (Level B). NIV may be considered to improve quality of life (Level C) [corrected].Early initiation of NIV may increase compliance (Level C), and insufflation/exsufflation may be considered to help clear secretions (Level C).
Subject(s)
Amyotrophic Lateral Sclerosis/therapy , Respiratory Therapy/methods , Amyotrophic Lateral Sclerosis/diet therapy , Amyotrophic Lateral Sclerosis/drug therapy , Enteral Nutrition/methods , Evidence-Based Medicine , Humans , Lithium Carbonate/therapeutic use , Quality of Life , Riluzole/therapeutic useABSTRACT
OBJECTIVE: To systematically review evidence bearing on the management of patients with amyotrophic lateral sclerosis (ALS). METHODS: The authors analyzed studies from 1998 to 2007 to update the 1999 practice parameter. Topics covered in this section include breaking the news, multidisciplinary clinics, symptom management, cognitive and behavioral impairment, communication, and palliative care for patients with ALS. RESULTS: The authors identified 2 Class I studies, 8 Class II studies, and 30 Class III studies in ALS, but many important areas have been little studied. More high-quality, controlled studies of symptomatic therapies and palliative care are needed to guide management and assess outcomes in patients with ALS. RECOMMENDATIONS: Multidisciplinary clinic referral should be considered for managing patients with ALS to optimize health care delivery and prolong survival (Level B) and may be considered to enhance quality of life (Level C). For the treatment of refractory sialorrhea, botulinum toxin B should be considered (Level B) and low-dose radiation therapy to the salivary glands may be considered (Level C). For treatment of pseudobulbar affect, dextromethorphan and quinidine should be considered if approved by the US Food and Drug Administration (Level B). For patients who develop fatigue while taking riluzole, withholding the drug may be considered (Level C). Because many patients with ALS demonstrate cognitive impairment, which in some cases meets criteria for dementia, screening for cognitive and behavioral impairment should be considered in patients with ALS (Level B). Other management strategies all lack strong evidence.
Subject(s)
Amyotrophic Lateral Sclerosis/therapy , Cognition Disorders/diagnosis , Patient Care Team , Amyotrophic Lateral Sclerosis/diagnosis , Dementia/diagnosis , Evidence-Based Medicine , Fatigue/drug therapy , Humans , Muscle Cramp/drug therapy , Palliative Care/methods , Pseudobulbar Palsy/drug therapy , Sialorrhea/drug therapy , Sialorrhea/radiotherapy , Terminal Care/methods , Truth DisclosureABSTRACT
BACKGROUND: Primary lateral sclerosis (PLS) is an idiopathic upper motor neuron degenerative disorder. The aim of this study was to compare brain volumes in patients with PLS and controls and determine whether differences were due to loss of gray matter (GM), white matter (WM), or both. METHODS: T1-weighted images were acquired in patients with PLS and controls. Freesurfer was used for volumetric segmentation of whole brain, cortical GM, precentral and postcentral cortex, WM, corpus callosum, basal ganglia, thalamus, cerebellum, and CSF. Relationships were sought between disease severity, disease duration, age and brain volumes. RESULTS: Eleven patients with PLS and 10 age-matched healthy controls were included in this study. Compared to control subjects, patients with PLS had significantly smaller whole brain (p = 0.043), frontal lobe (p = 0.036), precentral cortex (p = 0.016), and corpus callosum (p = 0.036) volumes. There was a trend toward a smaller thalamus (p = 0.051). Disease severity correlated with ventricular CSF volume (rho = -0.604, p = 0.025) and precentral cortex volume loss (rho = 0.599, p = 0.026). Disease duration tended to correlate with a loss of WM (rho = -0.636, p = 0.063). CONCLUSIONS: Our results suggest that there is focal atrophy in patients with primary lateral sclerosis compared with controls especially in the precentral cortex and the corpus callosum, specifically where there is transfer of motor fibers.
Subject(s)
Brain/pathology , Motor Neuron Disease/pathology , Aged , Atrophy , Cerebral Cortex/pathology , Corpus Callosum/pathology , Disease Progression , Electromyography , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Motor Neurons/pathologyABSTRACT
Additional hand contact of external objects has been shown to reduce postural instability caused by a deficiency of one or more senses. Little is known, however, if additional contact can help in an environment where the senses are available but conflicting. This question was investigated by analyzing the effect of different types of hand contact on postural stability perturbed by the moving visual scene. While standing for 1min on a rocker board in front of a screen, eight healthy young subjects observed a projection of a virtual ship rocking on water to simulate standing on the ship's deck. In randomly assigned trials subjects were asked (a) to stand with arms at sides (with no contact); (b) to hold a standard cane parallel to the ground; (c) to lightly touch a rocker cane handle with their index finger; or (d) touch a standard quad cane handle with their index finger. Based on the kinematic data collected, the displacement of the center of mass (COM) and angular displacements in the hip and ankle joints were computed. Results showed that the moving visual scene perturbed body stability. However, additional contact with support of varying stability reduced the destabilizing effect. The results can be potentially used for practical purposes; when in an environment with visual perturbations simply holding an object in hand may help stabilize the body when at risk for a fall.
Subject(s)
Hand/physiology , Motion Perception/physiology , Posture/physiology , Touch/physiology , Biomechanical Phenomena , Humans , Random AllocationABSTRACT
In recent years, magnesium alloys have been proposed as a new class of metallic bioabsorbable implant material. Unfortunately, hydrogen gas evolution and an increase in alkalinity are both byproducts of the degradation process. This necessitates the development of magnesium alloys with controlled degradation rates. The development of biocompatible coatings that can delay the onset of corrosion is essential for improving the lifetime and performance of these materials in vivo. Calcium phosphate coatings have been shown to improve the biocompatibility of metallic implants for orthopedic applications. In this article, we report a solution chemistry technique for depositing calcium phosphate coatings on magnesium alloy surfaces. Our kinetic studies indicate that the deposition of the coating is related to the anodic dissolution of the substrate. Characterization of the coating by XPS, SEM/EDS, and XRD reveal that the coating produced is a poorly crystalline calcium magnesium hydroxyapatite material.
Subject(s)
Alloys/chemistry , Calcium Phosphates/chemistry , Durapatite/chemistry , Magnesium/chemistry , Biocompatible Materials , Calcium/chemistry , Chromatography, High Pressure Liquid , Coated Materials, Biocompatible/chemistry , Crystallization , Humans , Ions , Models, Chemical , Polymers/chemistry , Spectrophotometry, Atomic/methods , Surface PropertiesABSTRACT
BACKGROUND: TCH346 exerts antiapoptotic effects by binding to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and blocking the apoptotic pathway in which GAPDH is involved. Apoptosis is considered to be a key pathogenic mechanism in neurodegenerative diseases including ALS. METHODS: Patients were randomly assigned in a double-blind fashion to receive either placebo or one of four doses of TCH346 (1.0, 2.5, 7.5, or 15 mg/day) administered orally once daily for at least 24 weeks. The primary outcome measure was the rate of change in the revised ALS functional rating scale (ALSFRS-R). The trial design included a 16-week lead-in phase to determine each patient's rate of disease progression. The between treatment comparison was adjusted for the individual pretreatment rates of progression. The study was powered to detect a 25% reduction in the rate of decline of the ALSFRS-R as compared with placebo. Secondary outcome measures included survival, pulmonary function, and manual muscle testing (MMT). RESULTS: Five hundred ninety-one patients were enrolled at 42 sites in Europe and North America. There were no differences in baseline variables. There were no significant differences between placebo and active treatment groups in the mean rate of decline of the ALSFRS-R or in the secondary outcome measures (survival, pulmonary function, and MMT). CONCLUSION: The trial revealed no evidence of a beneficial effect of TCH346 on disease progression in patients with ALS.
Subject(s)
Amyotrophic Lateral Sclerosis/drug therapy , Apoptosis/drug effects , Nerve Degeneration/drug therapy , Oxepins/administration & dosage , Administration, Oral , Adult , Aged , Aged, 80 and over , Apoptosis/physiology , Central Nervous System/drug effects , Central Nervous System/enzymology , Central Nervous System/physiopathology , Dose-Response Relationship, Drug , Double-Blind Method , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/adverse effects , Female , Glyceraldehyde-3-Phosphate Dehydrogenases/antagonists & inhibitors , Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism , Humans , Male , Middle Aged , Nerve Degeneration/enzymology , Nerve Degeneration/prevention & control , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/adverse effects , Oxepins/adverse effects , Placebo Effect , Treatment FailureABSTRACT
BACKGROUND: Scabies is an intensely itchy parasitic infection of the skin caused by the Sarcoptes scabiei mite. It is a common public health problem with an estimated global prevalence of 300 million cases. Serious adverse effects have been reported for some drugs used to treat scabies. OBJECTIVES: To evaluate topical and systemic drugs for treating scabies. SEARCH STRATEGY: In February 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE, EMBASE, LILACS, and INDMED. In March 2007, we also searched the grey literature and sources for registered trials. We also checked the reference lists of retrieved studies. SELECTION CRITERIA: Randomized controlled trials of drug treatments for scabies. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Results were presented as relative risks with 95% confidence intervals and data combined where appropriate. MAIN RESULTS: Twenty small trials involving 2392 people were included. One trial was placebo controlled, 16 compared two or more drug treatments, two compared treatment regimens, and one compared different drug vehicles.Fewer treatment failures occurred by day seven with oral ivermectin in one small trial (55 participants). Topical permethrin appeared more effective than oral ivermectin (85 participants, 1 trial), topical crotamiton (194 participants, 2 trials), and topical lindane (753 participants, 5 trials). Permethrin also appeared more effective in reducing itch persistence than either crotamiton (94 participants, 1 trial) or lindane (490 participants, 2 trials). One small trial did not detect a difference between permethrin (a synthetic pyrethroid) and a natural pyrethrin-based topical treatment (40 participants). No significant difference was detected in the number of treatment failures between crotamiton and lindane (100 participants, 1 trial), lindane and sulfur (68 participants, 1 trial), benzyl benzoate and sulfur (158 participants, 1 trial), and benzyl benzoate and natural synergized pyrethrins (240 participants, 1 trial); all were topical treatments. No trials of malathion were identified. No serious adverse events were reported. A number of trials reported skin reactions in participants randomized to topical treatments. There were occasional reports of headache, abdominal pain, diarrhoea, vomiting, and hypotension. AUTHORS' CONCLUSIONS: Topical permethrin appears to be the most effective treatment for scabies. Ivermectin appears to be an effective oral treatment. More research is needed on the effectiveness of malathion, particularly when compared to permethrin, and on the management of scabies in an institutional setting and at a community level.