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Biomedical subjects

J Price

Publications and source records attributed to J Price.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacological MRI of stem cell transplants in the 3-nitropropionic acid-damaged striatum.

Blood oxygen level dependent (BOLD) pharmacological magnetic resonance imaging (phMRI) affords the non-invasive visualization of brain activity resulting from the administration of pharmacological compounds. Once the compound-responsive cells are lost, no change in activity is expected to occur. This principle therefore allows the assessment of neuronal loss or lack of signal transmission. These investigations can provide evidence of pathology in the absence of significant tissue loss and can be highly specific to determine which type of cell has been lost. Conversely, transplantation of cells replacing the lost neurons should restore normal signal transmission. We here demonstrate the application of phMRI to differentiate between rats with 3-nitroproprionic acid (3-NPA)-induced striatal lesions and 3-NPA-lesioned animals with neural stem cell transplants or controls. 3-NPA-induced lesions mainly involve striatal projection neurons that are responsive to dopamine agonists. The D2-agonist bromocriptine acts on these projection cells and loss of these through 3-NPA administration resulted in a significant decrease of locomotor activity and a substantial attenuation of the BOLD-response in the striatum. In contrast, lesioned animals that were grafted with neural stem cells exhibited an activity pattern akin to controls. Hence, grafting of neural stem cells exerts a functionally significant effect on striatal signal transmission that could underpin behavioral recovery.

Animals↗
PubMed2006

Preservation of striatal tissue and behavioral function after neural stem cell transplantation in a rat model of Huntington's disease.

Cell replacement has the potential to become a frontline therapy to remedy behavioral impairments in Huntington's disease. To determine the efficacy of stem cell transplantation, behavioral assessment and in vivo monitoring of the lesion environment are paramount. We here demonstrate that neural stem cells from the MHP36 cell line prevented the development of a deficit on the beam walk test while providing partial recovery of learning in the water maze. However, no beneficial effect on rats' impairment in the staircase test was observed. By quantification of the lesion from serial magnetic resonance images, no effect of neural stem cells on lesion volume was observed. Instead, a preservation of striatal volume over time and its correlation with performance on the beam walk test suggested that sparing of behavioral function was associated with a stagnation of ongoing tissue loss rather than a reduction in lesion size. Serial imaging therefore warrants further implementation in clinical trials of neural grafts to monitor in vivo changes in the damaged brain due to transplantation.

Analysis of Variance↗
PubMed2006

Attitudes of women with chronic pelvic pain to the gynaecological consultation: a qualitative study.

OBJECTIVE: To describe the attitudes that women with chronic pelvic pain (CPP) attending gynaecology clinics have to their consultations and to determine the ways in which their health care can be improved. DESIGN: Qualitative study using semistructured individual interviews. SETTING: UK gynaecology outpatient clinics in district general and teaching hospitals. SAMPLE: Twenty-six women with CPP. METHODS: Semistructured individual interviews were conducted. Data gathering and analysis followed a grounded theory approach. MAIN OUTCOME MEASURES: Women's wishes regarding their care and their actual experiences of care. RESULTS: Four main themes emerged. The women wanted (a) personal care, which they often did not receive; (b) to feel understood and to be taken seriously, although they often felt dismissed, which applied both to women with and without an explanation for their pain; (c) explanation as much as cure, but an adequate explanation was often not provided; and (d) to be reassured, which often they were not. Effective reassurance was complex as it included general reassurance and specific reassurance about cause and treatment. CONCLUSIONS: Improvements are needed in the outpatient care of women presenting with CPP. Changes should focus on providing more personal care, so that presenting problems are seen to be taken seriously, findings and management are appropriately explained, and women are more effectively reassured. Interventions need to be developed that meet these needs and tested to determine if they are feasible, acceptable, and improve outcomes.

Adult↗
PubMed2006

A comparative study of pregnant women attending a tertiary obstetric unit and a district general hospital with a previous history of postnatal depression.

The aim of this study was to compare pregnant women with a previous history of postnatal depression, attending a Tertiary Obstetric Unit in Belfast and a District General Hospital in Newry. Women with a previous history of postnatal depression recorded at booking for their most current pregnancy were studied between January 2001 and May 2002. A total of 443 women (6.6%) in Belfast had a history of postnatal depression, compared with 113 women (6%) in Newry. The most common age range was 31 - 35 years in both centres. Some 69% of women in Belfast compared with 81% of women in Newry were given treatment. Fluoxetine was the commonly prescribed drug for each centre. During this subsequent pregnancy, 19 women (4.3%) in Belfast and five women (4.4%) in Newry remained on antidepressants. There was one woman in each centre who took an overdose during this pregnancy. More women in Newry were given treatment. During the subsequent pregnancy, the percentages of women from each unit requiring antidepressant therapy were similar.

Adult↗
PubMed2005

Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide.

Endothelial dysfunction (ED) is an early feature of cardiovascular risk and diabetes. Hyperglycemia and hyperlipidemia are causative factors. Excessive endothelial mitochondrial superoxide (ROS) production with hyperglycemia and hyperlipidemia is a key mechanism. Inositol components of an insulin inositol glycan mediator, d-chiro-inositol (DCI) and 3-O-methyl DCI (pinitol), decrease hyperglycemia and hyperlipidemia. We tested whether these, myoinositol and dibutyryl DCI (db-DCI), would prevent or reverse ED in diabetic rats and rabbits. Oral inositols reduced hyperglycemia and hypertriglyceridemia with different potencies and prevented ED in rat aortic rings and mesenteric beds. Inositols added in vitro to five diabetic tissues reversed ED. Relaxation by Ach, NO, and electrical field stimulation was potentiated by inositols in vitro in rabbit penile corpus cavernosa. Inositols in vitro restored impaired contraction by the eNOS inhibitor l-NAME and increased NO effectiveness. DCI and db-DCI decreased elevated ROS in endothelial cells in high glucose and db-DCI reduced PKC activation, hexosamine pathway activity, and advanced glycation end products to basal levels. Xanthine/xanthine oxidase generated superoxide was reduced by superoxide dismutase or inositols, with db-DCI efficacious in a mechanism requiring chelated Fe(3+). Histochemical examination of rat aortic rings for protein SNO demonstrated a decrease in diabetic rings with restoration by inositols. In summary, inositols prevented and reversed ED in rat and rabbit vessels, reduced elevated ROS in endothelial cells, potentiated nitrergic or vasculo-myogenic relaxations, and preserved NO signaling. These effects are related to their metabolic actions, direct superoxide scavenging, and enhancing and protecting NO signaling. Of the inositols tested, db-DCI was most effective.

Animals↗
PubMed2005

Allosteric activation of protein phosphatase 2C by D-chiro-inositol-galactosamine, a putative mediator mimetic of insulin action.

Insulin-stimulated glucose disposal in skeletal muscle proceeds predominantly through a nonoxidative pathway with glycogen synthase as a rate-limiting enzyme, yet the mechanisms for insulin activation of glycogen synthase are not understood despite years of investigation. Isolation of putative insulin second messengers from beef liver yielded a pseudo-disaccharide consisting of pinitol (3-O-methyl-d-chiro-inositol) beta-1,4 linked to galactosamine chelated with Mn(2+) (called INS2). Here we show that chemically synthesized INS2 has biological activity that significantly enhances insulin reduction of hyperglycemia in streptozotocin diabetic rats. We used computer modeling to dock INS2 onto the known three-dimensional crystal structure of protein phosphatase 2C (PP2C). Modeling and FlexX/CScore energy minimization predicted a unique favorable site on PP2C for INS2 in a surface cleft adjacent to the catalytic center. Binding of INS2 is predicted to involve formation of multiple H-bonds, including one with residue Asp163. Wild-type PP2C activity assayed with a phosphopeptide substrate was potently stimulated in a dose-dependent manner by INS2. In contrast, the D163A mutant of PP2C was not activated by INS2. The D163A mutant and wild-type PP2C in the absence of INS2 had the same Mn(2+)-dependent phosphatase activity with p-nitrophenyl phosphate as a substrate, showing that this mutation did not disrupt the catalytic site. We propose that INS2 allosterically activates PP2C, fulfilling the role of a putative mediator mimetic of insulin signaling to promote protein dephosphorylation and metabolic responses.

Amino Acid Substitution↗
PubMed2005

Current practice relating to equine castration in the UK.

This study aimed to characterise current practice relating to equine castration in the UK. A questionnaire was posted to all 655 veterinary practices specified to provide veterinary care for horses, or classified as specialist equine practices. Respondents were asked to cite the number of equine castrations performed annually by the practice, describe techniques used for castration, outline anaesthetic/sedative/analgesic drug protocols used and provide details of post-operative medication. There was a 43% response rate to the questionnaire. Considerable variation in techniques and analgesia provision was identified, with the majority of respondents using a number of sedation/anaesthetic protocols rather than a single technique. This characterisation of current practice provides a useful platform from which subsequent investigations into welfare implications of current equine castration techniques can be directed.

Analgesics↗
PubMed2004

Exploring the mechanisms regulating regeneration of deer antlers.

Deer antlers are the only mammalian appendages capable of repeated rounds of regeneration; every year they are shed and regrow from a blastema into large branched structures of cartilage and bone that are used for fighting and display. Longitudinal growth is by a process of modified endochondral ossification and in some species this can exceed 2 cm per day, representing the fastest rate of organ growth in the animal kingdom. However, despite their value as a unique model of mammalian regeneration the underlying mechanisms remain poorly understood. We review what is currently known about the local and systemic regulation of antler regeneration and some of the many unsolved questions of antler physiology are discussed. Molecules that we have identified as having potentially important local roles in antlers include parathyroid hormone-related peptide and retinoic acid (RA). Both are present in the blastema and in the rapidly growing antler where they regulate the differentiation of chondrocytes, osteoblasts and osteoclasts in vitro. Recent studies have shown that blockade of RA signalling can alter cellular differentiation in the blastema in vivo. The trigger that regulates the expression of these local signals is likely to be changing levels of sex steroids because the process of antler regeneration is linked to the reproductive cycle. The natural assumption has been that the most important hormone is testosterone, however, at a cellular level oestrogen may be a more significant regulator. Our data suggest that exogenous oestrogen acts as a 'brake', inhibiting the proliferation of progenitor cells in the antler tip while stimulating their differentiation, thus inhibiting continued growth. Deciphering the mechanism(s) by which sex steroids regulate cell-cycle progression and cellular differentiation in antlers may help to address why regeneration is limited in other mammalian tissues.

Animals↗
PubMed2004

Exercise therapy for chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is an illness characterised by persistent medically unexplained fatigue. CFS is a serious health-care problem with a prevalence of up to 3%. Treatment strategies for CFS include psychological, physical and pharmacological interventions. OBJECTIVES: To investigate the relative effectiveness of exercise therapy and control treatments for CFS. SEARCH STRATEGY: CCDANCTR-Studies and CENTRAL were searched using "Chronic Fatigue" and Exercise. The Journal of Chronic Fatigue Syndrome and CFS conferences were handsearched. Experts in the field were contacted. Clinicaltrials.gov and controlled-trials.com were searched. SELECTION CRITERIA: Only Randomised Controlled Trials (RCT) including participants with a clinical diagnosis of CFS and of any age were included. DATA COLLECTION AND ANALYSIS: The full articles of studies identified were inspected by two reviewers (ME and HMG). Continuous measures of outcome were combined using standardised mean differences. An overall effect size was calculated for each outcome with 95% confidence intervals. One sensitivity analysis was undertaken to test the robustness of the results. MAIN RESULTS: Nine studies were identified for possible inclusion in this review, and five of those studies were included. At 12 weeks, those receiving exercise therapy were less fatigued than the control participants (SMD -0.77, 95% CIs -1.26 to -0.28). Physical functioning was significantly improved with exercise therapy group (SMD -0.64, CIs -0.96 to -0.33) but there were more dropouts with exercise therapy (RR 1.73, CIs 0.92 to 3.24). Depression was non-significantly improved in the exercise therapy group compared to the control group at 12 weeks (WMD -0.58, 95% CIs -2.08 to 0.92). Participants receiving exercise therapy were less fatigued than those receiving the antidepressant fluoxetine at 12 weeks (WMD -1.24, 95% CIs -5.31 to 2.83). Participants receiving the combination of the two interventions, exercise + fluoxetine, were less fatigued than those receiving exercise therapy alone at 12 weeks, although again the difference did not reach significance (WMD 3.74, 95% CIs -2.16 to 9.64). When exercise therapy was combined with patient education, those receiving the combination were less fatigued than those receiving exercise therapy alone at 12 weeks (WMD 0.70, 95% CIs -1.48 to 2.88). REVIEWERS' CONCLUSIONS: There is encouraging evidence that some patients may benefit from exercise therapy and no evidence that exercise therapy may worsen outcomes on average. However the treatment may be less acceptable to patients than other management approaches, such as rest or pacing. Patients with CFS who are similar to those in these trials should be offered exercise therapy, and their progress monitored Further high quality randomised studies are needed.

Depression↗
PubMed2003

Expression of the POU domain transcription factor, Oct-6, is attenuated in the adult mouse telencephalon, but increased by neurotoxic damage.

Oct-6 is a POU III domain transcription factor expressed in embryonic stem cells, Schwann cells, and neuronal subpopulations during telencephalic development. Its role is unknown except in Schwann cells where it is thought to regulate myelin-specific gene expression. Expression of Oct-6 was recently discovered in neurons in postmortem human schizophrenic brain while being undetectable in matched controls. This study of human tissue contrasted in a number of regards with earlier studies of rodent brain and questioned what we can consider to be normal adult expression of this gene. In this study, we have investigated Oct-6 expression in normal adult mice and in mice treated with neuractive compounds. We show that Oct-6 is widely expressed in young adults but that its expression subsequently becomes restricted to specific neuronal subpopulations. Contrary to earlier reports, however, this specific expression is transient and is eventually completely lost from telencephalic neurons. The OCT-6 protein, somewhat surprisingly, is found to be cytoplasmic as well as nuclear in certain neuronal subpopulations. Finally, we report that neurotoxic doses of anticonvulsants reactivate OCT-6 expression in adult mouse brain.

Age Factors↗
PubMed2003

Characteristics of patients presenting to a cardiac clinic with palpitation.

BACKGROUND: Palpitation is a very common presenting symptom in primary care and in cardiac clinics, associated with marked disability. Although serious arrhythmias are uncommon causes, treatment of persistent palpitation is difficult. AIM: To describe the cardiological, behavioural and psychological characteristics of consecutive patients presenting to a cardiac clinic with the main complaint of palpitation. DESIGN: Prospective evaluation of consecutive out-patients. METHODS: Participants were 184 consecutive patients with the complaint of palpitation referred to an out-patient cardiac clinic. Three assessments were used. Three to four weeks prior to clinic attendance, measures of symptoms, distress and disability were gathered, and a heart rate perception test was conducted. At the out-patient clinic, a routine clinical assessment was made. Three months later, patients received a questionnaire which included baseline measures of symptoms, distress and disability. RESULTS: Palpitation was associated with arrhythmias in 62 patients (34%), extrasystoles in 75 patients (41%) and awareness of sinus rhythm in 47 patients (26%). Distress and disability were common and persistent. There were significant differences in the characteristics of the three groups. DISCUSSION: Most patients presenting to secondary care with palpitation do not have serious underlying cardiovascular conditions. Concurrent psychological problems are common and persistent. Aetiology may be seen as an interaction of pathology, awareness of normal physiology, and psychological variables. Few patients require specialist cardiological treatment, but simple reassurance is of limited effectiveness. A stepped care approach may improve outcomes and needs rigorous evaluation.

Adult↗
PubMed2003

Accident and emergency departments are still failing to assess asthma severity.

OBJECTIVES: To quantify the documentation of vital signs in children attending accident and emergency (A&E) for asthma and to assess whether indicators of severity were used appropriately. METHODS: Records of all children aged 3 to 14 attending A&E for the treatment of asthma in four London hospitals over a three month period were examined for documentation of heart rate, respiratory rate, peak expiratory flow rate, oxygen saturation, and fraction of inspired oxygen. The relation between severity indicators and whether the child was admitted or not was examined. RESULTS: There were 255 attendances in 229 children. Heart rate, respiratory rate, and oxygen saturation were recorded on most attendances (94.5%, 85.5%, and 96.8%) but fraction of inspired oxygen and peak flow were recorded in few children (48.6% and 48.5%). Heart rate and respiratory rate were higher and oxygen saturation lower in children who were admitted compared with those who were not. CONCLUSIONS: Assessment of airways obstruction is inadequate in children but when measured may be used appropriately to guide admission. There is a need for interventions to improve assessment of children attending A&E for asthma.

Adolescent↗
PubMed2002

Pilot epidemiological study of attitudes towards pain in horses.

This preliminary study investigated the attitudes, and evaluated the current practice of a sample of the veterinary profession in the UK in relation to the management of pain in horses. In June 2001, a questionnaire was posted to 260 veterinarians in specialised equine practice, and 140 veterinarians in general practice with a significant equine caseload. There was a 25 per cent response rate to the questionnaire, which recorded information about the availability and prescription of analgesic drugs, the factors influencing the selection of analgesics and their administration, and estimates of the severity of pain associated with selected clinical conditions. There were considerable variations in the practices applied to manage pain in horses, implying that there are similar attitudinal barriers to the optimal management of pain in horses as have been identified in other domestic spedes.

Adult↗
PubMed2002

Perioperative fluid volume optimization following proximal femoral fracture.

BACKGROUND: Proximal Femoral Fracture (PFF) or 'hip fracture' is a frequent injury, and adverse outcomes are common. Many patients are elderly, with significant comorbidity. Several factors suggest the importance of developing appropriate techniques to optimize intravascular fluid volume. These may include protocols that enhance the efficacy of clinicians' assessments, invasive techniques such as oesophageal Doppler or central venous pressure monitoring, or advanced non-invasive techniques such as plethysmographic pulse volume determination. OBJECTIVES: To determine the optimal method of fluid volume optimization for adult patients undergoing surgical repair of hip fracture. Comparisons of fluid types (e.g. crystalloid vs. colloid) or of blood transfusion strategies or of other pharmacological interventions (e.g. inotropes) are not considered in this review. SEARCH STRATEGY: Randomized controlled trials (RCTs) since 1985 were identified by searching MEDLINE, EMBASE, the Cochrane Library, the Cochrane Anaesthesia Group's specialized Controlled Trials Register and bibliographies of retrieved articles. Relevant journals and conference proceedings were handsearched. SELECTION CRITERIA: RCTs comparing a fluid optimization intervention with normal practice (control) or with another fluid optimization intervention, in patients following PFF undergoing surgery of any type under anaesthesia of any type. DATA COLLECTION AND ANALYSIS: Searches and exclusion of clearly irrelevant articles were performed by one reviewer. Two reviewers examined independently the remaining studies, extracting study quality and results data. A wide range of short- and long-term outcome data was sought. Study quality was assessed using a ten-point instrument and studies were excluded if they did not meet the study criteria or if results were likely to be biased. Due to a lack of consistency in reporting, combination of data was not generally possible. MAIN RESULTS: Searches identified only four trials, of which two studies, randomizing a total of 130 patients, were of adequate quality and addressed the review question. Both studies were of invasive advanced haemodynamic monitoring during the intraoperative period only. One study randomized patients to 'normal care' or optimization using oesophageal Doppler; the second study randomized patients to 'normal care', oesophageal Doppler or central venous pressure monitoring. In each study, invasive monitoring led to a significant increase in volume of fluid infused and a reduction in length of hospital stay. The pooled Peto odds ratio for in-hospital fatality was 1.44 (95% confidence interval 0.45-4.62). Neither study followed patients beyond hospital discharge or assessed functional outcomes (for example return to previous accommodation). No serious complications were reported to be directly attributable to the monitoring interventions. There were no studies of protocol-guided fluid optimization or of advanced non-invasive techniques. REVIEWER'S CONCLUSIONS: Invasive methods of fluid optimization during surgery may shorten hospital stay, but their effects on other important, patient-centred, longer-term outcomes are uncertain. An adverse effect on fatality cannot be excluded. Other fluid optimization techniques have not been evaluated. The lack of randomized studies of adequate quality addressing this important question is disappointing given the high incidence and frequently adverse outcome of PFF. More research is needed.

Blood Volume↗
PubMed2002

A feline assay using osteoclasts generated in vitro from peripheral blood for screening anti-resorptive agents.

Musculo-skeletal diseases are a major cause of pain and suffering in cats and several conditions involve increased bone resorption by osteoclasts. However, little is known about the biology of these cells in the cat. In this study we established a method to generate feline osteoclasts from blood mononuclear cells stimulated by macrophage colony stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL). Cultured osteoclasts are multinucleated, express tartrate resistant acid phosphatase (TRAP), form F-actin rings and resorb bone. They express alpha(v)beta3 vitronectin receptor and osteoclast enzymes, cathepsin K and MMP9; the myeloid antigen, CD18, and the megakaryocyte/platelet integrin, CD41, are absent. This phenotype is typical of osteoclasts from other species. Three resorption inhibitors were examined for activity against feline osteoclasts. Calcitonin, bisphosphonate and RGD integrin inhibitory peptide all reduced bone resorption at doses similar to those efficacious in rabbit or human. We conclude that blood-derived osteoclast cultures are a suitable in vitro system for assessing the ability of drugs to inhibit bone resorption in domestic cats.

Acid Phosphatase↗
PubMed2002

A randomized controlled trial of a brief educational and psychological intervention for patients presenting to a cardiac clinic with palpitation.

BACKGROUND: We sought to determine whether a brief psycho-educational intervention reduced disability in patients with benign palpitation. METHOD: In a pragmatic randomized controlled trial within a cardiology clinic at a district general hospital, 80 consecutive patients diagnosed as having benign palpitation--either palpitation due to awareness of extrasystoles or sinus rhythm--with associated distress or disability were randomized to an intervention group (usual care plus nurse-delivered intervention based on cognitive-behavioural principles) or to a control group (usual care). Principal outcome was difference in proportion of participants with good or excellent researcher-rated activity levels at 3 months. Subsidiary outcomes were self-rated symptoms, distress and disability, researcher-rated unmet treatment needs. RESULTS: The principal outcome showed a statistically and clinically significant benefit for the intervention group, with a number needed to treat of 3 (95% CIs 2 to 7). All but one subsidiary outcomes also showed a difference in favour of the intervention group, and several differences reached statistical significance. Significantly more of the control group had unmet treatment needs at 3 months. CONCLUSIONS: A brief, nurse-delivered, psycho-educational intervention, was an effective treatment for benign palpitation. Further evaluation, including assessment of cost-effectiveness, is needed. The findings have application to the care of patients presenting with other types of 'unexplained' medical symptoms.

Adult↗