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Biomedical subjects

J Moore

Publications and source records attributed to J Moore.

At least 55 records · Page 3Linked to original sources
PubMed2001

Testing a preoperative pain management intervention for elders.

The investigators examined whether elders who have been taught pain management communication skills and pain management information obtain greater postoperative pain relief than elders not taught this information. Thirty-one elders were randomly assigned preoperatively to a control or communication group in this posttest-only experiment with repeated measures. Communication group participants were taught pain management, pain communication skills, and the use of two pain-intensity scales. Control group participants were taught to use the two pain-intensity scales. Pain was measured with the McGill Pain Questionnaire Short Form. The communication group elders reported less postoperative pain over the course of their hospital stay. Pain management knowledge alone may have enabled the elders to obtain greater pain relief. Nurses may want to incorporate similar pain management information and pain communication skills when teaching elders how to obtain greater postoperative pain relief.

Aged↗
PubMed2001

BW373U86, a delta opioid agonist, partially mediates delayed cardioprotection via a free radical mechanism that is independent of opioid receptor stimulation.

Opioids have been shown to produce both an early and delayed phase of cardioprotection; however, the signaling pathways involved, particularly in the delayed response, have not been well defined. Therefore, we investigated the potential of BW373U86 (BW), a potent delta opioid agonist, to produce delayed cardioprotection and characterized the role of opioid receptors and oxygen-derived free radicals (OFRs) in this delayed response. All rats underwent 30 min of ischemia followed by 2 h of reperfusion. The rats were divided into four groups. First, rats were pretreated with selective opioid receptor antagonists or the antioxidant, 2-mercaptopropionyl glycine (2-MPG), in the presence of BW and allowed to recover for 24 h before the ischemia-reperfusion protocol. Second, rats were pretreated with BW, allowed to recover for 24 h, and subsequently treated with either opioid antagonists or 2-MPG, 10 min prior to the ischemia-reperfusion protocol. Third, rats underwent ischemic preconditioning (IPC) (1x5 min occlusion) both with and without 2-MPG to determine the role of OFRs in acute cardioprotection. Fourth, rats were pretreated with TAN-67, an opioid agonist known to signal through the delta1 opioid receptor in the presence and absence of 2-MPG. Control rats were injected with saline and allowed to recover for 24 h. BW produced a bell-shaped dose-related reduction in infarct size with a maximal reduction observed at 0.1 mg/kg v control (16+/-3%v 60+/-3%, P<0.001). Surprisingly, the delayed protection induced by BW was only partially blocked by pretreatment with the delta1-selective antagonist, BNTX; however, it was completely blocked by pretreatment with 2-MPG (47+/-5%, P<0.001). Only naloxone given acutely inhibited the protective effects of BW; however, at the dose used, 2-MPG partially reduced the protective effect of acute IPC. TAN-67 (0.1 mg/kg) also produced a significant reduction in infarct size compared to control (18+/-4%v 60+/-3%, P<0.001). This protection was blocked by pretreatment with 2-MPG (42+/-4%, P<0.001). These data suggest that BW and TAN-67 mediate delayed cardioprotection via a free radical mechanism that appears to be only partially dependent on delta opioid receptor stimulation. Furthermore, it is the early burst in OFRs that is crucial to initiating the protective effect.

Animals↗
PubMed2001

General practitioners' and patients' models of obesity: whose problem is it?

Primary care literature emphasises the importance of agreement and shared models in the consultation. This study compared general practitioners' (GPs') and patients' models of obesity. Questionnaires concerning beliefs about the causes, consequences and solutions to obesity were completed by 89 general practitioners (GPs) and 599 patients from practices across UK. In terms of causes, the results showed that the patients were more likely to attribute obesity to a gland/hormone problem, slow metabolism and stress than the GPs, whereas the GPs were more likely to blame eating too much. In terms of consequences, the patients rated difficulty getting to work more highly whereas the GPs regarded diabetes as more important. For the solutions to obesity, the two groups reported similar beliefs for a range of methods, but whereas the patients rated the GP and a counsellor as more helpful, the GPs rated the obese person themselves more highly. It is argued that patients show a self serving model of obesity by blaming internal uncontrollable factors for causing obesity yet expecting external factors to solve it. In contrast, GPs show a victim blaming model by attributing both cause and the solution to internal controllable factors. Such differing models have implications regarding the form of intervention likely to be used in primary care and indicate that whereas patients would prefer a more professional based approach, GPs would prefer a more patient-led one. Further, the results suggest that even if an intervention could be negotiated, success rates would be low as either the patient or the GP would be acting in contradiction to their beliefs about the nature of obesity.

Adult↗
PubMed2001

Lack of efficacy of twice-weekly urokinase in the prevention of complications associated with Hickman catheters: a multicentre randomised comparison of urokinase versus heparin.

Hickman catheters (HC) are associated with complications, in particular infection, occlusion and thrombosis. We tested the hypothesis that regular flushing of catheters with urokinase would reduce the frequency of these complications. Patients who required a double-lumen HC for (1) bone marrow or peripheral blood progenitor cell transplantation or (2) intensive combination chemotherapy for haematological malignancies were randomised to receive twice-weekly flushes of either urokinase (5000 units) or heparin (50 units). HC-survival analysis was determined by Cox regression. 100 patients were enrolled (urokinase=52; heparin=48) and treated for a mean of 8.5 weeks. No significant difference was observed in the incidence of HC-associated septicaemic events, which occurred in 8/52 in the urokinase group and 9/48 in the heparin group (actuarial incidence 20% versus 25%, P=0.50). Similarly, there was no differences in the incidence of exit site infections (urokinase=27/52 and heparin=28/48, P=0.122); HC-septic thromboses (urokinase=2/52 and heparin=4/48, P=0.34); lumen occlusion (urokinase=30/52 and heparin=30/48, P=0.681); or venous thrombosis (urokinase=8/52 and heparin=6/48, P=0.726). Overall, a high incidence of HC-related complications was seen in both groups; 40/52 in the urokinase group and 40/48 in the heparin group (actuarial incidence 80% versus 90%, P=0.367). Despite this only 18% of HC required early removal due to complications (urokinase=8, heparin=10). There was no difference in the incidence of complications in patients undergoing transplantation (n=68) compared with chemotherapy alone (n=32). Patients with haematological malignancies were more likely to have HC-related infective complications (P=0.006), and patients with solid tumours more likely to have venous thrombosis (P=0.027). The cumulative incidence of HC-related complications in this prospective study was higher than in previously reported series. Urokinase did not appear effective in reducing the frequency of these complications.

Anticoagulants↗
PubMed2001

Changes in myofibrillar structure and function produced by N-terminal deletion of the regulatory light chain in Drosophila.

The similarity of amino acid sequence and motifs of the N-terminal extensions of certain class II myosin light chains, found throughout the animal kingdom, suggest a common functional role. One possible role of the N-terminal extension is to enhance oscillatory work and power production in striated muscles that normally operate in an oscillatory mode. We conducted small-angle X-ray diffraction experiments and small-length-perturbation analysis to examine the structural and functional consequences of deleting the N-terminal extension of the myosin regulatory light chain (RLC) in Drosophila flight muscle. The in vivo lattice spacing of dorsal longitudinal muscle (DLM) of flies lacking the RLC N-terminal extension (Dmlc2delta2-46) was approximately 1 nm less than that of wild type (48.56 +/- 0.02 nm). The myofilament lattice of detergent-treated, demembranated DLM swelled, with the DmlcdeltaA2-46 lattice expanding more than wild type and requiring roughly twice the concentration of Dextran T500 to restore its lattice to in vivo spacing (9-10% vs. 4% w/v). The calcium sensitivity and maximum amplitude of net oscillatory work near the in vivo lattice spacing was significantly lower in Dmlc2delta2-46 compared to wild type (pCa50 shifted by approximately one-third of a pCa unit; amplitude reduced by approximately one-half). These changes were in contrast to the lack of effect reported in a previous study carried out in the absence of Dextran T500. The results are consistent with the N-terminal extension interacting with actin to increase the probability that crossbridges form during stretch-activated oscillatory work and power production, especially at submaximal levels of calcium activation.

Animals↗
PubMed2001

Nitric oxide enhancement of fludarabine cytotoxicity for B-CLL lymphocytes.

Fludarabine is active but not curative in the treatment of chronic lymphocytic leukemia (B-CLL). Nitric oxide (NO) supplied from exogenous, NO-donating pro-drugs can also induce apoptosis and death of acute leukemia cells. This study investigated combinations of fludarabine with NO-donating pro-drugs for their cytotoxicity against freshly isolated B-CLL lymphocytes following a 72 h exposure in vitro. The median IC(50)for fludarabine was 2.2 microM (n = 85). The nitric oxide donors DETA-NO, PAPA-NO, and MAHMA-NO were also cytotoxic, and their effects were inversely related to rates of NO release. Neither DETA-NO depleted of NO nor DETA itself was effective, indicating that NO was required for cytotoxicity. Drug interactions were evaluated by a modified combination index method. Synergy was observed in combinations of fludarabine or nelarabine (506U78) with DETA-NO in 52% and 88% of samples, respectively. Interestingly, the combination of fludarabine and DETA-NO was more cytotoxic in B-CLL cells less sensitive to fludarabine. DETA-NO did not enhance the activity of other DNA anti-metabolites, topoisomerase I and II inhibitors, or alkylating agents. Finally, the anti-leukemic activity of fludarabine alone or in combination with DETA-NO was found to correlate with inhibition of cellular RNA synthesis. These results indicate that NO donors could enhance fludarabine therapy for B-CLL.

Adult↗
PubMed2001

No more tears: a randomized controlled double-blind trial of Amethocaine gel vs. placebo in the management of procedural pain in neonates.

AIM: During a comparative double-blind study, the efficacy of Amethocaine local anaesthetic gel was compared with that of a placebo gel to establish their effect on the reduction of behavioural and physiological responses to pain in neonates. METHOD: Forty infants were included in the trial, 20 being randomly assigned to each group. After topical application of either Amethocaine or the placebo for 30 minutes, cannulation was performed using a 24 gauge cannula. Assessment of pain was made with the aid of four point assessment tool incorporating facial expression, cry and heart rate changes and ease of cannulation. Additional baseline data were obtained including sex, gestation, weight and previous experience of cannulation, and analysed using Statistical Package for Social Sciences (SPSS). RESULTS: Good analgesic effects were demonstrated in the Amethocaine group, as there was a high level of significance (P < 0.01) in the difference in pain scores between the two groups using a Mann-Whitney U-test. There was no correlation between gestation or weight and the degree of pain experienced during painful procedures. No significant relationship was found between cannulation and the degree of pain experienced. CONCLUSION: It can, therefore, be concluded that Amethocaine gel is an effective local anaesthetic in the management of skin puncturing procedural pain in neonates, and that all infants regardless of maturity, weight or previous experiences probably experience a similar degree of pain and therefore warrant effective and appropriate analgesic intervention.

Administration, Cutaneous↗
PubMed2001

Epidermal H(2)O(2) accumulation alters tetrahydrobiopterin (6BH4) recycling in vitiligo: identification of a general mechanism in regulation of all 6BH4-dependent processes?

It has been shown in vivo that patients with the depigmentation disorder vitiligo accumulate hydrogen peroxide (H(2)O(2)) accompanied by low catalase levels and high concentrations of 6- and 7-biopterin in their epidermis. Earlier it was demonstrated that epidermal 4a-OH-tetrahydrobiopterin dehydratase, an important enzyme in the recycling process of 6(R)-L-erythro 5,6,7,8 tetrahydrobiopterin (6BH(4)), has extremely low activities in these patients concomitant with a build-up of the abiogenic 7-isomer (7BH(4)), leading to competitive inhibition of epidermal phenylalanine hydroxylase. A topical substitution for the impaired epidermal catalase with a pseudocatalase effectively removes epidermal H(2)O(2), yielding a recovery of epidermal 4a-OH-tetrahydrobiopterin dehydratase activities and physiologic 7BH(4) levels in association with successful repigmentation demonstrating recovery of the 6BH(4) recycling process. Examination of recombinant enzyme activities, together with 4a-OH-tetrahydrobiopterin dehydratase expression in the epidermis of untreated patients, identifies H(2)O(2)-induced inactivation of this enzyme. These results are in agreement with analysis of genomic DNA from these patients yielding only wild-type sequences for 4a-OH-tetrahydrobiopterin dehydratase and therefore ruling out the previously suspected involvement of this gene. Furthermore, our data show for the first time direct H(2)O(2) inactivation of the important 6BH(4) recycling process. Based on this observation, we suggest that H(2)O(2) derived from various sources could be a general mechanism in the regulation of all 6BH(4)-dependent processes.

Biopterins↗
PubMed2001

Stem cells in the aetiopathogenesis and therapy of rheumatic disease.

Animal models of autoimmune disease and case reports of patients with these diseases who have been involved in bone marrow transplants have provided important data implicating the haemopoietic stem cell in rheumatic disease pathogenesis. Animal and human examples exist for both cure and transfer of rheumatoid arthritis, systemic lupus erythematosus (SLE) and other organ-specific diseases using allogeneic haemopoietic stem cell transplantation. This would suggest that the stem cell in these diseases is abnormal and could be cured by replacement of a normal stem cell although more in vitro data are required in this area. Given the morbidity and increased mortality in some patients with severe autoimmune diseases and the increasing safety of autologous haemopoietic stem cell transplantation (HSCT), pilot studies have been conducted using HSCT in rheumatic diseases. It is still unclear whether an autologous graft will cure these diseases but significant remissions have been obtained which have provided important data for the design of randomized trials of HSCT versus more conventional therapy. Several trials are now open to accrual under the auspices of the European Bone Marrow Transplant Group/European League Against Rheumatism (EBMT/EULAR) registry. Future clinical and laboratory research will need to document the abnormalities of the stem cell of a rheumatic patient because new therapies based on gene therapy or stem cell differentiation could be apllied to these diseases. With increasing safety of allogeneic HSCT it is not unreasonable to predict cure of some rheumatic diseases in the near future.

Animals↗
PubMed2001

All angiogenesis is not the same: Distinct patterns of response to antiangiogenic therapy in experimental neuroblastoma and Wilms tumor.

BACKGROUND/PURPOSE: Neuroblastoma and Wilms tumor exhibit different patterns of metastasis, invasion, and therapeutic response. Vascular endothelial growth factor (VEGF) is an angiogenic factor expressed in both tumors. The authors hypothesized that because the clinical behavior of these tumors differs, the response to anti-VEGF therapy would be distinct, and tumor vascular architectures would reflect this distinction. METHODS: Xenografts were induced by intrarenal injection of cultured cells in athymic mice. After 1 week, anti-VEGF antibody or vehicle were administered for 5 weeks before sacrifice. Additional animals were maintained for 3 weeks after termination of antibody injections to assess rebound growth of tumors. Fluorescein angiography was performed in selected animals. RESULTS: Neuroblastoma control and treated tumor weights were not significantly different (1.48 g v 0.77 g, P =.34). By comparison, as previously reported, antibody-treated Wilms tumors were growth inhibited. Angiograms of treated (but not control) neuroblastomas displayed novel rounded structures at vessel branches, which the authors term terminal vascular bodies (TVBs). Wilms tumor vessels displayed no such alteration. CONCLUSIONS: Neuroblastoma xenografts are less effectively suppressed by anti-VEGF antibody than Wilms tumors. Neuroblastoma vascular architecture displays a novel alteration during antibody administration, which attenuates when antibody is withdrawn. These studies suggest that angiogenesis is differently regulated in experimental neuroblastoma and Wilms tumor.

Angiogenesis Inhibitors↗
PubMed2001

Highly specific antiangiogenic therapy is effective in suppressing growth of experimental Wilms tumors.

BACKGROUND/PURPOSE: Pathologic angiogenesis in tumors is a potential target for novel therapies. Vascular endothelial growth factor (VEGF) is an angiogenic promoter present in a wide variety of human tumors. VEGF is expressed as 4 isoforms; one of these, VEGF165, predominates in human tumors. The authors hypothesized that antagonism of VEGF165 by a specific aptamer would block tumor growth in an experimental model of Wilms tumor. METHODS: VEGF isoform expression in clinical (n = 2) and experimental tumors were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Tumors were induced in NCR nude mice (n = 32) by intrarenal injection of 10(6) cultured Wilms tumor cells. At 1 week, aptamer (n = 16) or vehicle (n = 16) treatment was started and continued daily for 5 weeks. RESULTS: At 6 weeks tumors weighed 84% less in treated versus control animals (0.69 v 4.41 g; P <.028), without observed adverse effects and similar to suppression previously reported using nonisoform-specific anti-VEGF antibody (94% to 96%). CONCLUSIONS: Anti-VEGF165 aptamer effectively suppressed primary tumor growth in experimental animals with no observed adverse effects. Development of highly specific antiangiogenic therapies may be of particular benefit to pediatric patients.

Angiogenesis Inhibitors↗
PubMed2001

Effective therapy of a vascular tumor of infancy with vincristine.

Vascular tumors are common in infancy, affecting as many as 10% of children. These lesions often follow a benign course, with an initial proliferative phase followed by spontaneous involution, and require no therapy. Others manifest explosive early growth and Kasabach-Merritt phenomenon, requiring therapeutic intervention. Occasionally, some bulky tumors threaten life or vision because of mass effect, also mandating intervention. Steroids are the mainstay of therapy, but often are ineffective. Interferon alpha (2a and 2b) has been used as second-line therapy in cases of steroid failure. However, interferon therapy has been associated with a significant incidence of spastic diplegia. The authors present the case of a 3-month-old girl in whom respiratory distress secondary to tracheal compression developed. Magnetic resonance imaging and magnetic resonance angiography showed a large cervicothoracic lesion encasing the great vessels and displacing the airway. She did not display associated Kasabach-Merritt phenomenon. The lesion proved refractory to standard steroid therapy, but responded dramatically to 4 cycles of vincristine (0.05 mg/kg). Although this agent has been used in children with life-threatening Kasabach-Merritt phenomenon, this is the first time it has been described in the setting of compromised vital function. Vinca alkaloids recently have been shown to have potent antiangiogenic activities in experimental models. Given the low predicted incidence of side effects at this dose, vincristine used as an antiangiogenic agent may prove an attractive alternative therapy for patients with life-threatening vascular tumors of infancy.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Investigation of infection with Campylobacter jejuni in a man with hypogammaglobulinaemia using PCR-single-stranded conformational polymorphism (PCR-SSCP) typing.

This study investigated several episodes of infection of Campylobacter jejuni in an immunocompromised male with hypogammaglobulinaemia, presenting with diarrhoea and bacteraemia over a 16-month period, by employing three phenotyping and four genotyping schemes, including the single-stranded conformational polymorphism (SSCP) technique to establish if infection was reinfection or persistent infection. Four isolates from blood culture and two faecal isolates of Campylobacter jejuni were obtained from the patient by direct selective plating on Skirrow Selective agar. Isolates were characterised at the sub-species level by Penner serology, Preston biotyping, Preston phage-typing, as well as E3CJC2 restriction fragment length polymorphism (RFLP), 16S ribotyping, flagellin (flaA) RFLP and single-stranded conformational polymorphism (SSCP) analyses. Phenotyping and genotyping sub-species analyses demonstrated that the patient was infected with at least two different strains of Campylobacter jejuni, i. e. one strain that persisted throughout the 16-month period and another strain that was transient suggesting reinfection from a different source. SSCP analysis was the most discriminatory of all the typing schemes examined and demonstrated an altered genotype of the persistent strain, whereby there were subtle modifications to the hypervariable regions of the flaA gene. Overall, as SSCP examines the hypervariable region of the flaA gene and as this technique can detect point mutations, differences between SSCP banding patterns may represent markers and thus examine mutations that occur under immune selection, thereby permitting the C. jejuni to evade the host immune response. In conclusion, this study describes the novel use of SSCP genotyping of C. jejuni and demonstrated that this method is a highly discriminatory technique which may be beneficial in outbreak characterisation, but which is not suitable to examine the clonal patterns of C. jejuni over a long period of time.

Agammaglobulinemia↗
PubMed2001

Successful PCR amplification of genomic DNA from Cryptosporidium parvum oocysts extracted from a human faecal sample: a rapid and simple method suited for outbreak analysis.

A method to extract genomic DNA from oocysts of Cryptosporidium parvum in human faecal material was developed and consisted of a simple alkali wash, freeze/boil technique. This method was simple, quick, sensitive, inexpensive and resulted in the production of genomic DNA which was free of PCR inhibitors and as such was a suitable template for the detection of C. parvum by various PCR amplification targets.

Animals↗
PubMed2001

Molecular detection of Campylobacter spp. in drinking, recreational and environmental water supplies.

A molecular detection assay was performed on 207 samples of drinking, recreational and environmental waters collected in Northern Ireland. The water sources which were PCR positive for Campylobacter spp. included 2/91 (2.2%) drinking water from domestic household taps, 5/57 (8.8%) swimming pool water, 1/23 (4.3%) lake water and 1/1 water from a jacuzzi. Extracted DNA from all water samples was amplified employing a sequence-specific PCR assay based on a 206 bp conserved region of the flagellin A-flagellin B (flaA/flaB) loci for Campylobacter jejuni, C. coli and C. lari. Given the physiological and cultural fragile nature of these species, no waters were cultured using conventional methods due to concern for reversion to non-culturability from time of collection to laboratory analysis. As this genus has been demonstrated to form a 'viable but non-culturable' (VBNC) form, failure to culture organisms conventionally from water does not necessarily equate to a negative result, hence molecular detection assays, especially those which can demonstrate cell viability, may be useful in helping to elucidate potential epidemiological sources and reservoirs of this organism, especially where water is suspected as being the vehicle of transmission.

Anti-Bacterial Agents↗