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Biomedical subjects

M Edwards

Publications and source records attributed to M Edwards.

At least 19 recordsLinked to original sources

CDIP-58 can measure the impact of botulinum toxin treatment in cervical dystonia.

We compared the responsiveness of the Cervical Dystonia Impact Profile (CDIP-58), Medical Outcome Study Short Form-Health Survey (SF-36), Functional Disability Questionnaire (FDQ), and Pain and Activities of Daily Living subscales of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in participants with cervical dystonia treated with botulinum toxin A. Subscales of CDIP-58 were more sensitive in detecting statistical and clinical change than comparable subscales of the SF-36, FDQ, and TWSTRS.

Adult↗

Parallel declines in pollinators and insect-pollinated plants in Britain and the Netherlands.

Despite widespread concern about declines in pollination services, little is known about the patterns of change in most pollinator assemblages. By studying bee and hoverfly assemblages in Britain and the Netherlands, we found evidence of declines (pre-versus post-1980) in local bee diversity in both countries; however, divergent trends were observed in hoverflies. Depending on the assemblage and location, pollinator declines were most frequent in habitat and flower specialists, in univoltine species, and/or in nonmigrants. In conjunction with this evidence, outcrossing plant species that are reliant on the declining pollinators have themselves declined relative to other plant species. Taken together, these findings strongly suggest a causal connection between local extinctions of functionally linked plant and pollinator species.

Animal Migration↗

The adult phenotype in Costello syndrome.

We report clinical findings in 17 adults with Costello syndrome ranging in age from 16 to 40 years. Two patients in this series have had bladder carcinoma, the only malignancy reported to affect adults with Costello syndrome. Benign tumors included multiple ductal papillomata in two women, and a fourth ventricle mass in one man, thought to be a choroid plexus papilloma. Endocrine problems in this series were osteoporosis, central hypogonadism, and delayed puberty. Other health problems were symptomatic Chiari malformations in three patients. Four patients had adult-onset gastro-esophageal reflux, three of whom had Chiari malformations. Fourteen adults had mild to moderate intellectual disability with three individuals having severe intellectual disability; 15 individuals attained some reading and writing skills and 14 showed ongoing acquisition of new skills into adulthood. On the basis of this data, we recommend that neuro-imaging be considered in adults with Costello syndrome if they develop symptoms suggestive of a Chiari malformation. In the event of pubertal delay, endocrine investigations are indicated and hormone treatment may be required. Bone density assessments should be performed in adults with Costello syndrome, particularly in those with pubertal abnormalities. Screening for microscopic hematuria as a marker for bladder carcinoma may be indicated, although this requires further evaluation.

Abnormalities, Multiple↗

Systemic administration of the chemokine macrophage inflammatory protein 1alpha exacerbates inflammatory bowel disease in a mouse model.

INTRODUCTION: Exacerbations of inflammatory bowel disease are thought to be related to concurrent infections. As infections are associated with elevated local and serum concentrations of chemokines, we have determined whether systemic administration of the CC chemokine macrophage inflammatory protein 1alpha (MIP-1alpha) exacerbates colitis in a mouse model. METHODS: Colitis was induced in Balb/c mice using trinitrobenzene sulfonic acid (TNBS). Starting four days later, animals received daily intraperitoneal injections of recombinant MIP-1alpha. On day 7, mice were killed and pieces of colon taken for immunohistology and polymerase chain reaction analysis. The direct effects of MIP-1alpha on mucosal T cells and fibroblasts in vitro were also investigated. RESULTS: Systemic administration of MIP-1alpha markedly enhanced colitis with mice developing large transmural ulcers filled with granulation tissue. Treatment resulted in increased numbers of CD4 cells infiltrating the colonic lamina propria, increased interferon gamma (IFN-gamma) levels, and increased transcripts for tumour necrosis factor alpha (TNF-alpha) and matrix metalloproteinase 3 (MMP3). Isolated lamina propria lymphocytes from mice with TNBS colitis contained increased numbers of IFN-gamma and TNF-alpha transcripts when stimulated with MIP-1alpha in vitro. Colonic lamina propria fibroblasts also responded to MIP-1alpha with increased proliferation and decreased collagen 1 synthesis but fibroblast proliferation was not seen in vivo. CONCLUSIONS: These experiments show that increasing serum concentrations of a chemokine, MIP-1alpha, exacerbates immune mediated colitis. The effect seems to be due to the ability of MIP-1alpha to boost Th1 responses in the gut wall. Our findings also suggest a potential pathway by which peripheral infections can exacerbate inflammatory bowel disease.

Animals↗

Diagnosis and outcome from suspected mesenteric ischaemia following cardiac surgery.

A three-year retrospective chart review was undertaken of all post-cardiothoracic ICU patients who underwent laparotomy for suspected mesenteric ischaemia, or who had the diagnosis confirmed at post mortem. The aim was to compare the clinical and diagnostic characteristics of cardiothoracic patients with suspected mesenteric ischaemia with patients who had a confirmed diagnosis. There were 3024 admissions to the cardiothoracic ICU over the three-year period. Twenty-six laparotomies were performed for suspected mesenteric ischaemia and 15 were positive for mesenteric ischaemia. The overall incidence of mesenteric ischaemia was 17/3024 (0.6%). Mortality for patients with mesenteric ischaemia was 13/17 (76%). Ischaemia was limited to a single segment of bowel in the four survivors. Mortality in patients who had a negative laparotomy for suspected mesenteric ischaemia was 7/11 (64%), attributable to cardiovascular failure (2/11) and multi-organ dysfunction syndrome (5/11). No clinical, biochemical or haematological test was discriminatory for mesenteric ischaemia. In patients with proven ischaemia, 7/13 plain abdominal radiographs were positive for ischaemia and 7/7 radiographs were negative for ischaemia in patients with no ischaemia (P = 0.05, PPV 1.0, NPV 0.5, sensitivity 54%, specificity 100%). Neither routine clinical investigations nor plain abdominal radiography reliably diagnose mesenteric ischaemia when the diagnosis is suspected clinically. Early laparotomy is recommended in these patients and further investigation may delay this procedure unnecessarily. The presence of mesenteric ischaemia identifies a cohort of patients with high mortality.

Aged↗

ReN-1869 [(R)-1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3-piperidine carboxylic acid], a novel histamine H1 receptor antagonist, produces potent and selective antinociceptive effects on dorsal horn neurons after inflammation and neuropathy.

We characterized the effect of a novel selective histamine H1 receptor antagonist, (R)-1-(3-(10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5-ylidene)-1-propyl)-3-piperidine carboxylic acid (ReN-1869), on the responses of dorsal horn neurons in anesthetized rats after carrageenan induced-inflammation and peripheral neuropathy (L5/6 spinal nerve ligation; SNL). ReN-1869 was administered systemically (0.1-4 mg/kg), and drug effects were assessed using a wide range of peripheral electrical and natural stimuli (brush, von Frey filaments, and heat). Comparisons were made between unoperated naive groups and either carrageenan inflamed or SNL rats. ReN-1869 produced little effect on the electrically evoked responses (wind-up, Abeta-, Adelta-, and C-fiber-evoked responses); however, it significantly attenuated neuronal responses to noxious heat in carrageenan and SNL rats. A robust effect was seen with the low-threshold mechanical punctate (von Frey 9 g) stimuli, which were selectively inhibited by ReN-1869 after tissue and nerve injury. These inhibitory actions were in marked contrast to the naive animal group, where only nonsignificant effects were observed. To investigate whether the actions of ReN-1869 are mediated via the antagonism of histamine H1 receptors, the effects of this novel compound were compared with that of another H1 receptor antagonist, mepyramine (1-20 mg/kg). Systemic mepyramine produced strong inhibitions of the 9-g von Frey-evoked responses in carrageenan and SNL rats. The similar pharmacological profile of these two compounds suggests for a similar mechanism of action. We propose that ReN-1869 may represent a novel agent for the treatment of certain modalities of persistent pain states, in particular for the treatment of mechanical allodynia.

Analgesics↗

Patterns of EMG-EMG coherence in limb dystonia.

Dystonia of the limbs may be due to a wide range of aetiologies and may cause major functional limitation. We investigated whether the previously described pathological 4 to 7 Hz drive to muscles in cervical dystonia is present in patients with aetiologically different types of dystonia of the upper and lower limbs. To this end, we studied 12 symptomatic and 4 asymptomatic carriers of the DYT1 gene, 6 patients with symptomatic dystonia due to focal basal ganglia lesions, and 11 patients with fixed dystonia, a condition assumed to be mostly psychogenic in aetiology. We evaluated EMG-EMG coherence in the tibialis anterior (TA) of these and 15 healthy control subjects. Ten of 12 (83%) of symptomatic DYT1 patients had an excessive 4 to 7 Hz common drive to TA, evident as an inflated coherence in this band. This drive also involved the gastrocnemius, leading to co-contracting electromyographic bursts. In contrast, asymptomatic DYT1 carriers, patients with symptomatic dystonia, patients with fixed dystonia, and healthy subjects showed no evidence of such a drive or any other distinguishing electrophysiological feature. Moreover, the pathological 4 to 7 Hz drive in symptomatic DYT1 patients was much less common in the upper limb, where it was only present in 2 of 6 (33%) patients with clinical involvement of the arms. We conclude that the nature of the abnormal drive to dystonic muscles may vary according to the muscles under consideration and, particularly, with aetiology.

Adult↗

Controlling corrosion in drinking water distribution systems: a grand challenge for the 21st century.

It is argued that the water distribution system will be a key public health battlefield of the 21st century. Corrosion in private plumbing is deserving of special attention, since the health and economic impacts are probably of equal or greater magnitude compared to public systems, and there has not been an advocate working on behalf of the consumer to solve these problems. To better serve society in this endeavour we will need educational programs, aggressive research to minimize the unsustainable costs of corrosion, and to consider our legacy to future generations when making decisions on materials use.

Community Participation↗

Health and aesthetic impacts of copper corrosion on drinking water.

Traditional research has focused on the visible effects of corrosion--failures, leaks, and financial debits--and often overlooked the more hidden health and aesthetic aspects. Clearly, corrosion of copper pipe can lead to levels of copper in the drinking water that exceed health guidelines and cause bitter or metallic tasting water. Because water will continue to be conveyed to consumers worldwide through metal pipes, the water industry has to consider both the effects of water quality on corrosion and the effects of corrosion on water quality. Integrating four key factors--chemical/biological causes, economics, health and aesthetics--is critical for managing the distribution system to produce safe water that consumers will use with confidence. As technological developments improve copper pipes to minimize scaling and corrosion, it is essential to consider the health and aesthetic effects on an equal plane with chemical/biological causes and economics to produce water that is acceptable for public consumption.

Copper↗

Assessing copper pinhole leaks in residential plumbing.

Pinhole leaks in copper tubes are a major problem for homeowners, and an aggressive conscientious effort by utilities is recommended to diagnose the problem and identify potential solutions. In a case study at one utility, pinhole leak frequency data was compiled and a methodology was followed that might prove to be a useful guide for those facing similar problems.

Copper↗

PEHO and PEHO-like syndromes: report of five Australian cases.

PEHO syndrome is a rare progressive infantile encephalopathy with onset within the first few months of life. Few patients fulfilling the diagnostic criteria for PEHO syndrome have been reported outside Finland. Affected infants have facial dysmorphism and suffer from severe hypotonia, profound mental retardation, convulsions (often with a hypsarrhythmic EEG pattern), transient or persistent peripheral oedema, and optic atrophy. Cerebellar and brainstem atrophy are usually present on neuroimaging. A PEHO-like syndrome has been described, in which the affected individuals have neither optic atrophy nor the typical neuroradiological findings. We report five Australian patients, the first with classical features of PEHO syndrome, and four who have a PEHO-like disorder. We compare their features with other published cases. We suggest that PEHO or a PEHO-like syndrome may affect more patients than are currently identified, based on the original diagnostic criteria for this disorder.

Brain Diseases, Metabolic, Inborn↗

CIR sand casting system for trans-tibial socket.

The authors have developed a trans-tibial socket fabrication system based on the "dilatancy" principle, a process that has been commonly used in forming wheelchair Seating. The CIR Sand Casting System replaces plaster of Paris with sand for forming both a negative sand mould and a positive sand model, which can be modified for either thermoplastic socket formation or resin lamination. Initial clinical trials suggest that fabrication times are approximately 90 minutes from patient evaluation and casting to dynamic alignment. Compatibility with all existing prosthetic components is retained. It is believed the CIR socket fabrication system may be a competitive alternative for prosthetic service providers in developing countries.

Amputation, Surgical↗

A simple, reproducible substrate for studying biofilms in aquatic environments.

In this paper we present a simple in expensive substrate for studying biofilms. Bioballs are robust plastic spheres with high surface area to volume ratios (ca 130:1) used in home aquarium filters. Their properties make them ideal substrates for use in studies of aquatic biofilms. As examples, in this paper we describe the growth and enzyme activities of biofilms grown on these substrates and explore the interaction between DOC concentration and biofilm biomass. Biofilm growth and activity on the bioballs was very reproducible. For example maximum biofilm growth following approximately 3 months inundation was estimated to be 40 (+/- 3.6) mg protein and 120 (+/- 11) microg chlorophyll a per bioball.

Biofilms↗

Health visiting at the crossroads: which way to the 21st century?

This article presents a response from a group of lecturers at Florence Nightingale School of Nursing and Midwifery, King's College London and one service user to the perception of a crisis of confidence within health visiting. Changes in registration procedures and shifts in policy have led health visiting to question its place within primary care and the model of preparation for health visiting practice. The group argues that this debate is based on a misunderstanding of the changing health care environment and that health visiting can find a place within the primary care team. Key to this is the continued adherence to a basic nursing training. The authors suggest an incremental model of health visitor training to provide the fullest scope to implement the new health agenda.

Attitude of Health Personnel↗

Physiological studies in carriers of the DYT1 gene mutation.

The DYT1 gene mutation is associated with early onset generalised dystonia. However, only 30-40 per cent of gene carriers develop symptoms. We have used electrophysiological tests to search for subclinical effects of the presence of the mutation in non-manifesting cases and compared these with those seen in clinically affected cases and healthy controls. Clinically affected patients had the same pattern of abnormalities in spinal and motor cortical circuits as described previously in non-genetically characterised patients. Non-manifesting cases had some but not all of these defects, suggesting that additional genetic or environmental factors may be needed to produce the full range of physiological deficiencies needed to give rise to clinical symptoms.

Carrier Proteins↗

Implications of aqueous silica sorption to iron hydroxide: mobilization of iron colloids and interference with sorption of arsenate and humic substances.

This work highlighted practical implications of aqueous silica sorption to iron hydroxide in natural and engineered systems. Two types of surfaces were prepared by exposing 10 mg/L preformed Fe(OH)3 to aqueous silica (0-200 mg/L as SiO2) for periods of 1.5 h or 50 days. After 1.5 h, the concentration of iron passing through a 0.45 microm pore size filter at pH 6.0-9.5 was always negligible, but if zeta potential < or =-15 mV as much as 35% of the iron passed through filters after 50 days of aging. When arsenate was added to 10 mg/L iron hydroxide particles equilibrated with aqueous silica for 1.5 h, percentage arsenate removals were high. In contrast, if silica was preequilibrated with iron for 50 days, arsenate removals decreased markedly at higher pH and aqueous silica concentrations. Similar trends were observed for humic substances, although their removal was nearly completely prevented at pH 8.5 at SiO2 concentrations above 50 and 10 mg/L at 1.5 h and 50 days exposure, respectively. The mechanism of interference was hindered sorption to the iron hydroxide surface.

Arsenates↗

Xenobiotic induction of cytochrome P450 2B1 (CYP2B1) is mediated by the orphan nuclear receptor constitutive androstane receptor (CAR) and requires steroid co-activator 1 (SRC-1) and the transcription factor Sp1.

The constitutive androstane receptor (CAR) activates the expression of a reporter gene attached to the phenobarbital-response element (PBRE) of the cytochrome P450 2B1 (CYP2B1) gene in response to the barbiturate phenobarbital and the plant product picrotoxin. The xenobiotic-mediated increase in transactivation occurs in transfected primary hepatocytes and in liver transfected by biolistic-particle-mediated DNA transfer, but not in the transformed cell lines HepG2, CV-1 and HeLa, which support only constitutive activation of gene expression by CAR. Steroid co-activator 1 (SRC-1) enhances both constitutive and xenobiotic-induced CAR-mediated transactivation via the CYP2B1 PBRE in transfected primary hepatocytes. The nuclear receptor 1 (NR1) site of the PBRE is sufficient for CAR-mediated transactivation, but additional sequences within the PBRE, and hence the proteins that bind to them, are required for the interaction of CAR with SRC-1. The NR2 site of the PBRE binds proteins other than CAR, including an unidentified nuclear receptor heterodimerized with retinoid X receptor alpha. By binding to the proximal promoter of CYP2B1, the transcription factor Sp1 increases both basal transcription and xenobiotic-induced expression via the PBRE. Thus induction of CYP2B1 expression by xenobiotics is mediated by the nuclear receptor CAR and, for optimal expression, requires SRC-1 and Sp1.

Animals↗