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Biomedical subjects

R Walker

Publications and source records attributed to R Walker.

At least 19 recordsLinked to original sources
PubMed2006

A multicentre longitudinal observational study of changes in self reported health status in people with Parkinson's disease left untreated at diagnosis.

BACKGROUND: The issue of when to start treatment in Parkinson's disease (PD) remains controversial. Some favour treatment at diagnosis while others opt for a "wait and watch" policy. The effect of the latter policy on the self reported health status of people with PD is unknown. AIMS: To record self reported health status through longitudinal use of a validated PD specific questionnaire (PDQ-39) in untreated PD patients in multiple centres in the UK. To compare patients who were left untreated with those who were offered treatment during follow-up. METHODS: A multicentre, prospective, "real life" observational audit based study addressing patient reported outcomes in relation to self reported health status and other sociodemographic details. RESULTS: 198 untreated PD were assessed over a mean period of 18 months. During two follow-up assessments, the self reported health status scores in all eight domains of the PDQ-39 and the overall PDQ-39 summary index worsened significantly (p<0.01) in patients left untreated. In a comparative group in whom treatment was initiated at or soon after diagnosis, there was a trend towards improvement in self reported health status scores after treatment was started. CONCLUSIONS: This study addresses for the first time self reported health status, an indicator of health related quality of life, in untreated PD. The findings may strengthen the call for re-evaluation of the policy to delay treatment in newly diagnosed patients with PD.

Aged↗
PubMed2006

Grading evidence and recommendations for clinical practice guidelines in nephrology. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).

Considerable variation in grading systems used to rate the strength of guideline recommendations and the quality of the supporting evidence in Nephrology highlights the need for a uniform, internationally accepted, rigorous system. In 2004, Kidney Disease: Improving Global Outcomes (KDIGO) commissioned a methods expert group to recommend an approach for grading in future nephrology guidelines. This position statement by KDIGO recommends adopting the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach for the grading of evidence and guidelines on interventions. The GRADE approach appraises systematic reviews of the benefits and harms of an intervention to determine its net health benefit. The system considers the design, quality, and quantity of studies as well as the consistency and directness of findings when grading the quality of evidence. The strength of the recommendation builds on the quality of the evidence and additional considerations including costs. Adaptations of the GRADE approach are presented to address some issues pertinent to the field of nephrology, including (1) the need to extrapolate from studies performed predominantly in patients without kidney disease, and (2) the need to use qualitative summaries of effects when it is not feasible to quantitatively summarize them. Further refinement of the system will be required for grading of evidence on questions other than those related to intervention effects, such as diagnostic accuracy and prognosis.

Global Health↗
PubMed2006

Consensus meeting: monosodium glutamate - an update.

OBJECTIVE: Update of the Hohenheim consensus on monosodium glutamate from 1997: Summary and evaluation of recent knowledge with respect to physiology and safety of monosodium glutamate. DESIGN: Experts from a range of relevant disciplines received and considered a series of questions related to aspects of the topic. SETTING: University of Hohenheim, Stuttgart, Germany. METHOD: The experts met and discussed the questions and arrived at a consensus. CONCLUSION: Total intake of glutamate from food in European countries is generally stable and ranged from 5 to 12 g/day (free: ca. 1 g, protein-bound: ca. 10 g, added as flavor: ca. 0.4 g). L-Glutamate (GLU) from all sources is mainly used as energy fuel in enterocytes. A maximum intake of 6.000 [corrected] mg/kg body weight is regarded as safe. The general use of glutamate salts (monosodium-L-glutamate and others) as food additive can, thus, be regarded as harmless for the whole population. Even in unphysiologically high doses GLU will not trespass into fetal circulation. Further research work should, however, be done concerning the effects of high doses of a bolus supply at presence of an impaired blood brain barrier function. In situations with decreased appetite (e.g., elderly persons) palatability can be improved by low dose use of monosodium-L-glutamate.

Adolescent↗
PubMed2006

FTY720/cyclosporine regimens in de novo renal transplantation: a 1-year dose-finding study.

FTY720 is a novel immunomodulator being investigated for rejection prophylaxis in renal transplantation when combined with full-dose cyclosporine (CsA; FDC). This 1-year phase II study compared FTY720 plus FDC (Neoral) with FTY720 plus reduced-dose CsA (RDC) and mycophenolate mofetil (MMF) plus FDC in de novo renal transplant patients. Patients were randomized 2:2:2:1 to FTY720 5 mg plus RDC (n = 72); FTY720 2.5 mg plus RDC (n = 74); FTY720 2.5 mg plus FDC (n = 76); or MMF plus FDC (n = 39) for 12 months. CsA exposure in the RDC group was reduced on average by 50% as assessed by C(2) monitoring. The primary efficacy endpoint was the composite incidence of biopsy-proven acute rejection (BPAR), graft loss, death or premature study discontinuation. The incidences for this composite endpoint were 24% and 22%, respectively, for FTY720 5 mg plus RDC and FTY720 2.5 mg plus FDC versus 39% for MMF plus FDC. Patients receiving FTY720 2.5 mg plus RDC were discontinued from treatment due to risk of under-immunosuppression. FTY720 2.5 mg plus FDC and FTY720 5 mg plus RDC were safe and effective in de novo renal transplant patients over 12 months.

Adult↗
PubMed2005

18F-fluorodeoxyglucose positron emission tomography contributes to the diagnosis and management of infections in patients with multiple myeloma: a study of 165 infectious episodes.

PURPOSE: Correctly identifying infection in cancer patients can be challenging. Limited data suggest that positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may be useful for diagnosing infection. To determine the role of FDG-PET in the diagnosis of infection in patients with multiple myeloma (MM). PATIENTS AND METHODS: The medical records of 248 patients who had FDG-PET performed for MM staging or infection work-up revealing increased uptake at extramedullary sites and/or bones and joints that would be atypical for MM between October 2001 and May 2004 were reviewed to identify infections and evaluate FDG-PET contribution to patient outcome. RESULTS: One hundred sixty-five infections were identified in 143 adults with MM. Infections involved the respiratory tract [99; pneumonia (93), sinusitis (six)], bone, joint and soft tissues [26; discitis (10), osteomyelitis (nine), septic arthritis (one), cellulitis (six)], vascular system [18; septic thrombophlebitis (nine), infection of implantable catheter (eight), septic emboli (one)], gastrointestinal tract [12; colitis (seven), abdominal abscess (three), and diverticulitis and esophagitis (one each)], and dentition [periodontal abscess (10)]. Infections were caused by bacteria, mycobacteria, fungi, and viruses. FDG-PET detected infection even in patients with severe neutropenia and lymphopenia (30 episodes). The FDG-PET findings identified infections not detectable by other methods (46 episodes), determined extent of infection (32 episodes), and led to modification of work-up and therapy (55 episodes). Twenty silent, but clinically relevant, infections were detected among patients undergoing staging FDG-PET. CONCLUSION: In patients with MM, FDG-PET is a useful tool for diagnosing and managing infections even in the setting of severe immunosuppression.

Adult↗
PubMed2005

A tubeless anaesthetic technique for paediatric laryngeal laser surgery.

Laser surgery on the paediatric larynx requires cooperation between the surgeon and anaesthetist to carry out the procedure in the safest manner possible. Over a period of 3 years, 45 laser procedures have been undertaken on the upper airway of 14 patients at our institution. All procedures were performed with volatile gas anaesthesia supplied via a nasopharyngeal tube in a spontaneously ventilating patient, thus allowing the surgeon an unobstructed view of the larynx. In only one case, was a problem experienced with the technique, that of laryngospasm. The technique provides an unrivalled view of the larynx whilst allowing safe anaesthesia.

Anesthesia, Inhalation↗
PubMed2005

Mechanisms of action of emodepside.

The research of the class of cyclic octadepsipeptides started at the beginning of the 1990s. PF1022A, the starting material of emodepside, is a natural secondary metabolite of the fungus Mycelia sterilia, which belongs to the microflora of the leaves of Camellia japonica. PF1022A consists of four N-methyl-L-leucins, two D-Iactic acids and two D-phenyllactic acids, which build up a cyclic octadepsipeptide with an alternating L-D-L-configuration. Emodepside is a semisynthetic derivative of PF1022A, which contains a morpholine attached in para position at each of both D-phenyllactic acids. Emodepside is efficacious against a variety of gastrointestinal nematodes. Emodepside binds to a presynaptic latrophilin receptor in nematodes. The following presynaptic signal transduction occurs via activation of Gqalpha protein and phospholipase-Cbeta, which leads to mobilization of diacylglycerol (DAG). DAG then activates UNC-13 and synaptobrevin, two proteins which play an important role in presynaptic vesicle-functioning. This finally leads to the release of a currently unidentified transmitter. The transmitter (or modulator) exerts its effects at the postsynaptic membrane and induces a flaccid paralysis of the pharynx and the somatic musculature in nematodes.

Animals↗
PubMed2005

Gastrointestinal-specific patient-reported outcome instruments differentiate between renal transplant patients with or without GI complications.

BACKGROUND: Gastrointestinal (GI) complications are frequently reported postrenal transplant and are often associated with immunosuppressant regimens including mycophenolate mofetil (MMF). This study evaluated the ability of two GI-specific patient-reported outcome (PRO) instruments to differentiate between patients with and without GI complaints. METHODS: Discriminant validity of the Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI), as well as two generic instruments (Psychological General Well-Being Index (PGWB) and EQ-5D, was assessed in a multinational study of renal transplant recipients. Patients received therapy that included a calcineurin inhibitor and MMF. Both t-tests and ANOVAs were used to examine differences between patients with and without GI complaints, among levels of severity, and between patients reporting presence/absence of specific GI side effects. RESULTS: Of 96 patients recruited (56% male), 43% had none, 39% mild, 13% moderate, and 6% severe GI symptoms. All GSRS subscales and the GIQLI total and four of the five subscale scores significantly differentiated between patients with/without GI complications (P < .05). The PGWB total score and three subscales, the EQ-5D significantly differentiated between the two groups (P < .05). Only GI-specific instruments discriminated between some severity levels; for example, the GSRS abdominal pain subscale discriminated between patients at all levels of severity (P < .05). The GIQLI total score and symptoms subscale differentiated between patients with no symptoms and those with mild or moderate or severe symptoms (P < .05). CONCLUSIONS: The GSRS and GIQLI differentiated between patients with/without GI side effects and by symptom severity better than did generic instruments, demonstrating excellent discriminant ability in this population.

Adult↗
PubMed2005

Relapse with transformation of lupus nephritis in a transplant kidney.

Lupus nephritis is a constellation of different renal histologies, characterized by an immune complex mediated glomerular disease. Histological transformation in lupus nephritis usually occurs from a mild mesangial proliferative glomerulonephritis to a more aggressive diffuse proliferative lesion. We present a case of relapsed systemic lupus erythematosus (SLE) in a renal transplant recipient in which there was a histological transformation from the original diffuse proliferative lupus nephritis in the native kidneys to a membranous lupus nephritis in the renal transplant.

Adult↗
PubMed2004

Safety issues of botanicals and botanical preparations in functional foods.

Although botanicals have played a role in the marketing of health products for ages, there is an increased interest today due to their perceived health benefits. Not only do consumers increasingly take charge of their health, but the scientific information and understanding of the beneficial health effects of bioactive substances in food, functional foods and food supplements have improved. Increasing use of these products has also led to concerns about their actual safety. Recorded cases of intoxications have triggered such concerns. The safety assessment of these substances is complicated by, amongst others, the variability of composition. Furthermore, consumption of such functional products is expected to produce physiological effects, which may lead to low margins of safety as the margin between exposure of such products and the safe level of intake are likely to be small. The safety assessment of botanicals and botanical preparations in food and food supplement should at least involve: the characterisation and quality of the material, its quality control; the intended use and consequent exposure; history of use and exposure; product comparison(s); toxicological information gathering; Risk characterisation/safety assessment. As a guidance tool, a decision tree approach is proposed to assist in determining the extent of data requirements based on the nature of the such product. This guidance tool in safety assessment was developed by an expert group of the International Life Sciences Institute (ILSI), European Branch, and is currently in press. In this paper a summarised version of this tool is presented.

Decision Trees↗
PubMed2004

Criteria for risk assessment of botanical food supplements.

The increasing use of botanical food supplements has raised concerns among scientific and regulatory communities. Occasional cases of intoxication have occurred from misuse, misidentification of the botanical species or contamination with extraneous plants. Consequently, risk assessment of botanical products requires adequate specification of identity and composition. Sources vary from staple food plants to herbals used in folk medicine; the supplement may comprise the whole plant, extracts thereof or purified components. This variability poses problems in adopting a generic approach to their risk assessment. The nature and extent of toxicological testing required will depend on: nature of the supplement, prior knowledge of human consumption, likely exposure and nutritional impact, and intended beneficial effects. Generally, for herbs or complex extracts, it is not possible to make a risk assessment on the basis of a single active component as more than one may be of toxicological significance and matrix effects may affect bioavailability. Nevertheless, studies on single components may be useful in elucidating potential interactions. Botanical supplements are intended to produce physiological effects, so there is a need to distinguish a No Observed Effect Level from a No Observed 'Adverse' Effect Level and the margin of exposure between that producing the desired effect and the upper safe level may be smaller than that adopted for food additives and contaminants. Human studies of efficacy and possible side effects may help in determining the acceptable margin of exposure. A decision tree will be presented to assist in determining the extent of data requirements based on the nature of the product.

Animals↗
PubMed2004

The epidemiology, diagnosis and treatment of subarachnoid haemorrhage in Nigeria: what do we know and what do we need to know?

Our goal was to review published literature on the epidemiology, diagnosis and treatment of subarachnoid haemorrhage (SAH) in Nigeria. With an estimated population of 126 million, roughly 6 million persons in Nigeria have or will develop an intracranial aneurysm in their lifetime. This study should highlight the areas requiring research and development, and facilitate future health care planning. A Medline and Embase literature review of reports on the management of SAH in Nigeria was conducted. The search terms were as follows: stroke, subarachnoid haemorrhage, intracerebral haemorrhage, brain, Nigeria, Nsukka, Ibadan, Lagos, Kaduna, Jos, Benin, Port Harcourt, Africa. All identified abstracts were reviewed for inclusion in the study. Only papers dealing with the study objectives were obtained for review of the bibliography and further analysis. Thirty articles have now been published about stroke in Nigerians. Fifteen of these either discussed SAH specifically or, in general, with other stroke subtypes (ischaemic stroke and intracerebral haematoma) or reviewed vascular intracranial anomalies such as aneurysms. The most detailed paper on this issue was published in 1970 and according to that report SAH is more common in males and prevalent in young people below the age of 40 years (68% of the patients reviewed). Worldwide improvements in medical and surgical management have not been reflected in the literature on SAH. Neurologists, stroke physicians and not neurosurgeons, treat patients with SAH in Nigeria. The results presented in this study reflect the current status of the medical and surgical management of SAH in Nigeria. Conclusive data relating to epidemiology, incidence, diagnosis, current treatment modalities and outcome of SAH in Nigeria have not been published. There is, therefore, a pressing need for further study in these areas and improvements in the management of patients with SAH.

Adult↗
PubMed2004

Training with computer-supported motor imagery in post-stroke rehabilitation.

Converging lines of evidence suggest that motor imagery (the mental simulation of a motor act within working memory) is associated with subliminal activation of the motor system. This observation has led to the hypothesis that cortical activation during motor imagery may affect the acquisition of specific motor skills and help the recovery of motor function. In this paper, we describe a clinical protocol in which we use interactive tools to stimulate motor imagery in hemiplegic stroke patients, thereby helping them to recover lost motor function. The protocol consists of an inpatient and an outpatient phase, combining physical and mental practice. In the inpatient phase, patients are trained in a laboratory setting, using a custom-made interactive workbench (VR Mirror). After discharge, patients use a portable device to guide mental and physical practice in a home setting. The proposed strategy is based on the hypotheses that: (a) combined physical and mental practice can make a cost-effective contribution to the rehabilitation of stroke patients, (b) effective mental practice is not possible without some form of support, from a therapist (as in our inpatient phase) or from technology (as in the outpatient phase), (c) the inclusion of an outpatient phase will allow the patient to practice more often than would otherwise be possible, therefore increasing the speed and/or effectiveness of learning, and (d) the use of interactive technology will reduce the patient's need for skilled support, therefore improving the cost-effectiveness of training.

Cerebral Infarction↗
PubMed2004

Comparison of application methods to prolong the survival of potential biocontrol bacteria on stored sugar-beet seed.

AIMS: To develop bacterial inoculation treatments on sugar-beet seed that will maintain a commercially acceptable degree of viability for a minimum of 4 months storage at ambient temperature. METHODS AND RESULTS: Single rifampicin-resistant (Rif(+)) strains of both Gram-positive and negative bacterial isolates (mostly pseudomonads) were applied in turn to sugar-beet seed in a comparative study by seed soaking, encapsulation in alginate, pelleting using an inoculated peat carrier or seed priming. The treated seed was assessed for bacterial survival over a time course by plating out homogenized samples onto a selective medium. Priming inoculation offered a significant improvement over all the other application strategies tested. After pelleting with fungicides and drying at 40 degrees C, Pseudomonas marginalis/putida P1W1 maintained populations of >6.6 log(10) CFU g(-1) seed during 4 months storage at 15 degrees C. Subsequent experiments verified a stabilized population under these storage conditions with commercial pellets at <7% moisture content. CONCLUSION: An inoculation method was established which allowed the survival on seed of a Gram-negative bacterium at ambient temperature with little loss in viability. SIGNIFICANCE AND IMPACT OF THE STUDY: This has promising implications for the delivery of beneficial bacteria, especially Gram-negative strains, on sugar beet.

Bacterial Physiological Phenomena↗
PubMed2004

Efficacy of cyclosporin in the treatment of atopic dermatitis in dogs--combined results from two veterinary dermatology referral centres.

OBJECTIVE: To evaluate the efficacy of cyclosporin in controlling the clinical signs associated with atopic dermatitis in dogs under Australian field conditions. DESIGN: A multicentre prospective clinical investigation of the use of cyclosporin in 41 dogs with atopic dermatitis. PROCEDURE: Dogs were treated with cyclosporin (5 mg/kg orally once daily with food) for 6 weeks. Four clinical parameters of severity of atopic dermatitis were measured on Day 0 and on Day 42 using a 0 to 4 scoring system. Individual variables were then combined to form a Global Score. Both client and clinician observed pruritus scores were combined to form a Pruritus Score. Pre- and post-treatment scores were statistically analysed. The difference in results between the two investigators was also recorded and analysed. RESULTS: All dogs showed a marked reduction in pruritus and erythema during the 6-week treatment period. All dogs showed a significant (P < 0.001) improvement in clinical lesion scores and Global Score (P < 0.001). The mean percentage improvement in Global Score from Day 0 to Day 42 was 83.9%. The mean percentage improvement in Pruritus Score from Day 0 to Day 42 was 83%. The medication was well tolerated. Side effects such as vomiting, diarrhoea and soft stools were observed in four dogs. Another four dogs developed bacterial pyoderma during the trial period. There was no significant difference in results between the two centres. CONCLUSION: Cyclosporin was well tolerated and efficacious in the symptomatic treatment of atopic dermatitis in dogs attending two veterinary dermatology referral centres in Australia, under Australian field conditions, when administered at 5 mg/kg/day for 6 weeks.

Administration, Oral↗