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Biomedical subjects

P Powell

Publications and source records attributed to P Powell.

At least 19 recordsLinked to original sources
PubMed2006

Fatigue Intervention by Nurses Evaluation--the FINE Trial. A randomised controlled trial of nurse led self-help treatment for patients in primary care with chronic fatigue syndrome: study protocol. [ISRCTN74156610].

BACKGROUND: Chronic fatigue syndrome, also known as ME (CFS/ME), is a condition characterised primarily by severe, disabling fatigue, of unknown origin, which has a poor prognosis and serious personal and economic consequences. Evidence for the effectiveness of any treatment for CFS/ME in primary care, where most patients are seen, is sparse. Recently, a brief, pragmatic treatment for CFS/ME, based on a physiological dysregulation model of the condition, was shown to be successful in improving fatigue and physical functioning in patients in secondary care. The treatment involves providing patients with a readily understandable explanation of their symptoms, from which flows the rationale for a graded rehabilitative plan, developed collaboratively with the therapist. The present trial will test the effectiveness and cost-effectiveness of pragmatic rehabilitation when delivered by specially trained general nurses in primary care. We selected a client-centred counselling intervention, called supportive listening, as a comparison treatment. Counselling has been shown to be as effective as cognitive behaviour therapy for treating fatigue in primary care, is more readily available, and controls for supportive therapist contact time. Our control condition is treatment as usual by the general practitioner (GP). METHODS AND DESIGN: This study protocol describes the design of an ongoing, single-blind, pragmatic randomized controlled trial of a brief (18 week) self-help treatment, pragmatic rehabilitation, delivered by specially trained nurse-therapists in patients' homes, compared with nurse-therapist delivered supportive listening and treatment as usual by the GP. An economic evaluation, taking a societal viewpoint, is being carried out alongside the clinical trial. Three adult general nurses were trained over a six month period to deliver the two interventions. Patients aged over 18 and fulfilling the Oxford criteria for CFS are assessed at baseline, after the intervention, and again one year later. Primary outcomes are self-reported physical functioning and fatigue at one year, and will be analysed on an intention-to-treat basis. A qualitative study will examine the interventions' mechanisms of change, and also GPs' drivers and barriers towards referral.

Clinical Protocols↗
PubMed2001

Randomised controlled trial of patient education to encourage graded exercise in chronic fatigue syndrome.

OBJECTIVE: To assess the efficacy of an educational intervention explaining symptoms to encourage graded exercise in patients with chronic fatigue syndrome. DESIGN: Randomised controlled trial. SETTING: Chronic fatigue clinic and infectious diseases outpatient clinic. SUBJECTS: 148 consecutively referred patients fulfilling Oxford criteria for chronic fatigue syndrome. INTERVENTIONS: Patients randomised to the control group received standardised medical care. Patients randomised to intervention received two individual treatment sessions and two telephone follow up calls, supported by a comprehensive educational pack, describing the role of disrupted physiological regulation in fatigue symptoms and encouraging home based graded exercise. The minimum intervention group had no further treatment, but the telephone intervention group received an additional seven follow up calls and the maximum intervention group an additional seven face to face sessions over four months. MAIN OUTCOME MEASURE: A score of >/=25 or an increase of >/=10 on the SF-36 physical functioning subscale (range 10 to 30) 12 months after randomisation. RESULTS: 21 patients dropped out, mainly from the intervention groups. Intention to treat analysis showed 79 (69%) of patients in the intervention groups achieved a satisfactory outcome in physical functioning compared with two (6%) of controls, who received standardised medical care (P<0.0001). Similar improvements were observed in fatigue, sleep, disability, and mood. No significant differences were found between the three intervention groups. CONCLUSIONS: Treatment incorporating evidence based physiological explanations for symptoms was effective in encouraging self managed graded exercise. This resulted in substantial improvement compared with standardised medical care.

Adult↗
PubMed2001

That little nudge.

Explore the source record for details and available documents.

Anecdotes as Topic↗
PubMed2000

A convenient synthesis of novel bifunctional prochelators for coupling to bioactive peptides for radiometal labelling.

New DOTA-based bifunctional prochelators, e.g., 1-(1-carboxy-3-carbotertbutoxypropyl)-4,7,10-(carbotertbutoxyme thyl)-1,4,7,10-tetraazacyclodode-cane (DOTAGA(tBu)4), (6d) for a broad application in the modification of biomolecules with metal ions were prepared. The five-step synthesis of 6d has an overall yield of about 20%. The coupling of 6d to a bioactive peptide on solid-phase was exemplified with use of a CCK-B (cholecystokinin) analogue.

Chelating Agents↗
PubMed2000

Is childhood allergy more common amongst an island population?

A rise in the prevalence of childhood asthma has been reported in both the UK and in several overseas countries during recent years. Wide geographical variations have also been demonstrated in the distribution of hay fever, atopic eczema and other allergic symptoms. It is the impression of many parents and some clinicians that allergic symptoms may be even higher amongst children in an island environment compared with a similar population on the mainland. To test this hypothesis, Guernsey and Jersey in the Channel Islands, and the Isle of Man in the Irish Sea participated as an independent arm in the International Study of Asthma and Allergy in Childhood (ISAAC). This entailed self-completion of a 38-part pretested and validated questionnaire in a classroom setting under standardised conditions. A total of 3,772 secondary students in school years eight and nine living in the three islands were compared with 27,507 students of similar age in 93 British secondary schools enrolled in the larger UK study. There are a number of demonstrable differences in climate, home environment and lifestyle factors between the islands and mainland UK. Although results were generally above the UK mean, they were comparable with the reference region of South West England and invariably below the UK maximum. For instance, the prevalence of 'ever wheezed?', 'wheezed in last twelve months?', 'wheezed with exercise?' and 'diagnosis of asthma' were a mean of 50.5%, 34.5%, 31% and 19.7% in the islands compared with a UK prevalence of 48.8%, 33.3%, 28.5% and 20.7%, whilst the prevalence of 'runny nose ever?' and 'runny nose in last twelve months?' was a mean of 46.6% and 36.7% in the islands, compared with 47.1% and 37.9% in the UK mean. These differences were not statistically significant. This information will be reassuring to parents of island children, and also demonstrates that services for the management of asthma and other allergic conditions should not be a higher public health priority in these locations than on the mainland of Britain.

Adolescent↗
PubMed2000

Preclinical comparison in AR4-2J tumor-bearing mice of four radiolabeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-somatostatin analogs for tumor diagnosis and internal radiotherapy.

Somatostatin analogs labeled with radionuclides are of considerable interest in nuclear oncology as diagnostic or therapeutic tools for somatostatin receptor (SSTR)-expressing tumors. We investigated the suitability of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) as a replacement for the widely used diethylenetriaminepentaacetic acid, to enable stable labeling of somatostatin analogs with both therapeutic (90Y) and diagnostic (111In) radionuclides. The three clinically relevant somatostatin agonists, octreotide, vapreotide, and lanreotide, together with the newly designed Tyr3-octreotide (TyrOc), were conjugated to DOTA and labeled with 90Y or 111In. For all DOTA-somatostatin analogs tested, irrespective of the incorporated radionuclide, we observed favorable biodistribution profiles in AR4-2J tumor-bearing mice: 1) a rapid clearance from all SSTR-negative tissues except kidney; 2) a specific uptake in SSTR-positive tissues, including tumor; and 3) an excellent tumor penetration. The main route of excretion was via the kidneys. Nevertheless, DOTATOC was clearly superior to the other DOTA-somatostatin analogs tested, as well as OctreoScan, as indicated by the highest tumor-to-nontarget-tissue ratio, including the tumor-to-SSTR-positive-tissue ratios. The presence of different SSTR subtypes in the SSTR-positive tissues possibly contributes to these differential uptakes. We assume that the very favorable behavior of DOTATOC in our mouse model makes this radioligand very promising for future applications in nuclear oncology.

Animals↗
PubMed1999

Polytopic anomalies with agenesis of the lower vertebral column.

We describe clinical, pathological and radiological findings in 15 cases of sporadic and familial lower spine agenesis with additional anomalies of the axial skeleton and internal organs and speculate about the cause and pathogenesis of this malformation complex. We show that all of these findings are defects of blastogenesis, originate in the primary developmental field and/or the progenitor fields, thus representing polytopic field defects. This concept appears applicable in our cases and makes such terms such as "caudal regression syndrome" or "axial mesodermal dysplasia spectrum" redundant.

Abnormalities, Multiple↗
PubMed1999

Antibody response to accelerated Hib immunisation in preterm infants receiving dexamethasone for chronic lung disease.

AIM: To study the effect of dexamethasone on the routine immunisation of preterm infants with chronic lung disease. METHODS: Serum samples were obtained before and after immunisation from an unselected cohort of 59 preterm infants. Haemophilus influenzae antibodies were measured using an ELISA method and differences in the geometric mean values between the two groups of babies analysed. RESULTS: Sixteen infants received no dexamethasone. Before and after immunisation antibody titres for those receiving no dexamethasone were 0.16 and 4.63 mcg IgG/ml. Corresponding values for those receiving dexamethasone were 0.10 and 0.51 mcg IgG/ml, respectively. CONCLUSION: Dexamethasone used in the treatment of chronic lung disease seems to significantly affect the antibody response of preterm infants to immunisation against Haemophilus influenzae.

Anti-Inflammatory Agents↗
PubMed1999

Yttrium-90 DOTATOC: first clinical results.

In a pilot study, DOTA-d-Phe(1)-Tyr(3)-octreotide (DOTATOC), which can be labelled with the beta-emitting radioisotope yttrium-90, has recently been used for the treatment of patients with advanced somatostatin receptor-positive tumours who had no other treatment option. The aim of the present study was to elucidate the therapeutic potential of (90)Y-DOTATOC in a larger number of patients employing a standardized treatment protocol. Careful attention was paid to any side-effects (renal and/or haematological toxicity). Of 44 patients with advanced somatostatin receptor-positive tumours of different histology, 29 could be included in the study. The 15 patients who were excluded from the study protocol were assigned to our institution for purely compassionate reasons. The 29 patients who were included received four or more single doses of (90)Y-DOTATOC with ascending activity at intervals of approximately 6 weeks (cumulative dose 6120+/-1347 MBq/m(2)) with the aim of performing an intra-patient dose escalation study. In total, 127 single treatments were given. In eight of these 127 single treatments, total doses of > or = 3700 MBq were administered. In an effort to prevent renal toxicity, two patients received Hartmann-Hepa 8% solution during all therapy cycles, while 13 patients did so during some but not all therapy cycles; in 14 patients no solution was administered during the therapy cycles. The treatment was monitored by computed tomography and indium-111 DOTATOC scintigraphy. Blood parameters were controlled weekly, while tumour markers and liver enzymes were controlled 6-weekly. Of the 29 patients, 24 patients showed no severe renal or haematological toxicity (toxicity < or = grade 2 according to the National Cancer Institute grading criteria). These 24 patients received a cumulative dose of < or = 7400 MBq/m(2). Five patients developed renal and/or haematological toxicity. All of these five patients received a cumulative dose of >7400 MBq/m(2) and had received no Hartmann-Hepa 8% solution during the therapy cycles. Four of the five patients developed renal toxicity; two of these patients showed stable renal insufficiency and two require haemodialysis. Two of the five patients exhibited anaemia (both grade 3) and thrombopenia (grade 2 and 4, respectively). To date, 20 of the 29 patients have shown a disease stabilization, two a partial remission, four a reduction of tumour mass <50% and three a progression of tumour growth. (90)Y-DOTATOC could be a powerful and promising new therapeutic agent for anti-cancer treatment - at least in terms of an adjuvant starting point of the disease. However, problems with toxicity have to be solved. Evaluation of the effect of amino acid infusions (e.g. Hartmann-Hepa 8% solution) during (90)Y-DOTATOC treatments with the aim of reducing renal toxicity is ongoing.

Adult↗
PubMed1997

Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0,d-Phe1,Tyr3]octreotide, a promising somatostatin analogue for radionuclide therapy.

In vitro octreotide receptor binding of [111In-DOTA0,d-Phe1, Tyr3]octreotide (111In-DOTATOC) and the in vivo metabolism of 90Y- or 111In-labelled DOTATOC were investigated in rats in comparison with [111In-DTPA0]octreotide [111In-DTPAOC). 111In-DOTATOC was found to have an affinity similar to octreotide itself for the octreotide receptor in rat cerebral cortex microsomes. Twenty-four hours after injection of 90Y- or 111In-labelled DOTATOC, uptake of radioactivity in the octreotide receptor-expressing tissues pancreas, pituitary, adrenals and tumour was a factor of 2-6 that after injection of 111In-DTPAOC. Uptake of labelled DOTATOC in pituitary, pancreas, adrenals and tumour was almost completely blocked by pretreatment with 0.5 mg unlabelled octreotide, indicating specific binding to the octreotide receptors. These findings strongly indicate that 90Y-DOTATOC is a promising radiopharmaceutical for radiotherapy and that 111In-DOTATOC is of potential value for diagnosis of patients with octreotide receptor-positive lesions, such as most neuroendocrine tumours.

Animals↗
PubMed1995

Surveillance of adverse reactions in patients self-infusing intravenous immunoglobulin at home.

This is the first prospective study of adverse reactions occurring in primary-antibody-deficient patients self-infusing intravenous immunoglobulin at home. One hundred nineteen patients, already self-infusing at home, were entered into the study. They had been fully instructed about all aspects of adverse reactions, including their prevention and treatment. In the event of any adverse reaction, a form was completed detailing the product, the dose, the symptoms that occurred and the time they lasted, the rate of infusion, and other relative information such as predisposing factors and any medication taken. The severity of reactions were classified as mild, moderate, or severe. The total number of reactions documented was 19 in 2031 infusions, and all resolved without medical aid. No serious reactions occurred. Excluding those reactions in which predisposing factors were identified, the overall reaction rate was 0.7%. In conclusion the study showed the reaction rate in patients self-infusing intravenous immunoglobulin at home was low following formal training of selected patients at recognized training centers.

Adolescent↗
PubMed1992

Hurricane Hugo blows down the broccoli: preschoolers' post-disaster play and adjustment.

This article reports highlights from over 200 parents' observations of their preschoolers' play and verbalizations in the year following Hurricane Hugo. Commonly reported activities included reenactment and discussion of the event in multiple mediums, personification of "Hugo", and expression of fears related to storms. Precocious concern for others, insight, and vocabulary were also noted. In these intact, relatively high functioning families, parents seemed able to facilitate their youngsters' adjustment without outside intervention.

Adaptation, Psychological↗
PubMed1992

Guanylnucleotide specificity for muscarinic receptor inhibitory coupling to cardiac adenylate cyclase.

The guanylnucleotide specificity of muscarinic acetylcholine receptor (MR) inhibitory coupling to cardiac adenylate cyclase (AC) was investigated under low MgCl2 (i.e., 0.5 mM) conditions. In purified cardiac sarcolemma, carbachol maximally inhibited AC activity 60% in the presence of GTP. Carbachol-dependent inhibition in the presence of guanosine 5'-O-(3-thiotriphosphate (GTP gamma S) or guanylylimidodiphosphate [Gpp(NH)p] was of lesser magnitude (i.e., 30%) and was evident only during short incubation periods. Of greater interest, carbachol maximally inhibited AC activity in the presence of GDP and guanosine 5'-O-(2-thiodiphosphate (GDP beta S) by 35 and 60%, respectively. Control studies ruled out transphosphorylation of GDP and GDP beta S by nucleoside diphosphate kinase or guanylnucleoside triphosphate contamination as reasons for the inhibitory effects of GDP and GDP beta S. Furthermore, isoproterenol stimulated AC in the presence of GTP, GTP gamma S, and Gpp(NH)p but not in the presence of GDP or GDP beta S. Therefore, GDP and GDP beta S may serve as agonists on MR-activated Gi but not on beta-adrenergic receptor-activated Gs in these membranes. Time course studies revealed that carbachol-dependent inhibition of AC in the presence of either GTP or GDP occurred without a detectable lag period, and this inhibition was rapidly reversed by atropine. In contrast, a 1-2-min lag time was required for carbachol- and GDP beta S-dependent inhibition of AC to occur, and inhibition, once developed, was only partially and slowly reversed by atropine. Preincubation of sarcolemma with carbachol and GDP beta S, in the absence of ATP or under nonphosphorylating conditions, eliminated the lag time for inhibition of AC activity. Although it is unlikely that GDP and GDP beta S have physiological relevance of MR-Gi-AC coupling, these studies provide unique insights into this coupling mechanism in cardiac membranes.

Adenylyl Cyclase Inhibitors↗
PubMed1989

A cytosolic protein activator of cardiac sarcolemmal phosphoinositide phospholipase C.

Ca2+ dependent polyphosphoinositide phospholipase C (PLC) activity in cardiac sarcolemma hydrolyzed both endogenous and exogenous phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) with an associated increase in inositol bisphosphate (IP2). Dialyzed cytosol and certain fractions of cytosol isolated by anion exchange or gel filtration chromatography activated sarcolemmal PLC activity by approx. 100%. The PLC activator eluted with an apparent molecular weight of 160 Kdal on a Sephacryl 300 column and was destroyed by heat or trypsin treatment. Exogenous 3H-PIP2 was not hydrolyzed by cytosolic fractions containing sarcolemmal PLC activator. These studies demonstrate that the polyphosphoinositide PLC in cardiac sarcolemma is regulated by a cytosolic protein.

Animals↗