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J Moore

Publications and source records attributed to J Moore.

At least 19 recordsLinked to original sources
PubMed2006

Gender differences in long-term beneficial effects of erythropoietin given after neonatal stroke in postnatal day-7 rats.

Recently, we reported that erythropoietin attenuates neonatal brain injury caused by focal cerebral ischemia. The long-term effects of erythropoietin on focal cerebral ischemia-induced injury to the developing brain and the potential gender differences in these long-term effects have not been studied in detail. The current study demonstrated a similarity in the mean infarct volume in both the vehicle-treated male and female rats at 6 and 12 weeks after focal cerebral ischemia. On the other hand, erythropoietin treatment (1000 U/kg x three doses after focal cerebral ischemia) caused a significant reduction in the mean infarct volume in both males and females at 6 weeks after focal cerebral ischemia when compared with the corresponding vehicle-treated animals (males: 141.4+/-48.2 mm3 vs. 194.0+/-59.2 mm3, P<0.05; females: 85.4+/-31.6 mm3 vs. 183.4+/-46.3 mm3, P<0.05). Interestingly, the reduction in the mean infarct volume in the erythropoietin-treated males was significantly less than that in the erythropoietin-treated females at 6 weeks after focal cerebral ischemia (141.4+/-48.2 mm3 vs. 85.4+/-31.6 mm3, P<0.05). At 12 weeks after focal cerebral ischemia, the mean infarct volume in the erythropoietin-treated males significantly increased to 181.0+/-50.4 mm3 (P<0.05). In contrast, the mean infarct volume in the erythropoietin-treated females remained stable (87.0+/-41.7 mm3). Additionally, erythropoietin treatment significantly improved sensorimotor function recovery with a misstep number similar to the sham-operation group at 6 and 12 weeks after focal cerebral ischemia. Moreover, the mean number of missteps in the erythropoietin-treated females was less than that in males at 6 (13.5+/-2.0 vs. 24.5+/-2.5, P<0.05) and 12 (12.5+/-2.0 vs. 20.0+/-2.0, P<0.05) weeks after focal cerebral ischemia. These results indicate that erythropoietin administration after focal cerebral ischemia produces a significant long-term neuroprotective benefit on the developing brain, and that this effect is more beneficial in the female rats.

Animals↗
PubMed2006

Asymmetric reduction of alpha, beta-unsaturated ketone to (R) allylic alcohol by Candida chilensis.

A pilot scale whole cell process was developed for the enantioselective 1,2-reduction of prochiral alpha,beta-unsaturated ketone to (R) allylic alcohol using Candida chilensis. Initial development showed high enantiomeric excess (EE > 95%) but low product yield (10%). Process development, using a combination of statistically designed screening and optimization experiments, improved the desired alcohol yield to 90%. The fermentation growth stage, particularly medium composition and growth pH, had a significant impact on the bioconversion while process characterization identified diverse challenges including the presence of multiple enzymes, substrate/product toxicity, and biphasic cellular morphology. Manipulating the fermentation media allowed control of the whole cell morphology to a predominantly unicellular broth, away from the viscous pseudohyphae, which were detrimental to the bioconversion. The activity of a competing enzyme, which produced the undesired saturated ketone and (R) saturated alcohol, was minimized to < or =5% by controlling the reaction pH, temperature, substrate concentration, and biomass level. Despite the toxicity effects limiting the volumetric productivity, a reproducible and scaleable process was demonstrated at pilot scale with high enantioselectivity (EE > 95%) and overall yield greater than 80%. This was the preferred route compared to a partially purified process using ultra centrifugation, which led to improved volumetric productivity but reduced yield (g/day). The whole cell approach proved to be a valuable alternative to chemical reduction routes, as an intermediate step for the asymmetric synthesis of an integrin receptor antagonist for the inhibition of bone resorption and treatment of osteoporosis.

Biotransformation↗
PubMed2006

DNA hypermethylation in the normal colonic mucosa of patients with colorectal cancer.

The CpG-island methylator phenotype (CIMP+) in colorectal cancer (CRC) is characterised by frequent hypermethylation of promoter regions in tumour suppressor genes. Low level methylation of some CpG islands is also seen in the normal colonic mucosa and increases with age; however, it is still unclear what other factors regulate this phenomenon. The first aim of our study was to determine whether the level of promoter methylation is elevated in the normal colonic mucosa of patients with CIMP+ tumours. The second aim was to investigate whether common, functional polymorphisms in genes involved in methyl group metabolism are associated with the level of methylation in this tissue. CpG islands within the ERalpha, MYOD, P16(INK4A), MLH1, APC, P14(ARF), DAPK and TIMP3 genes were quantitatively evaluated for methylation in normal colonic mucosa from a large series of CRC patients using the MethyLight assay. Genotyping was carried out for polymorphisms in the MTHFR, TS, MS, MTHFD1 and DNMT3b genes. Methylation of ERalpha and MYOD in normal colonic mucosa increased with age and was higher in female subjects. Methylation of P16(INK4A), MLH1, TIMP3 and DAPK in normal mucosa occurred at a lower level than ERalpha and MYOD but also increased with age and was significantly higher in patients with CIMP+ tumours. The DNMT3b C46359T polymorphism was associated with significantly less methylation of MYOD and MLH1 and with trends for lower methylation in each of the other CpG islands examined. Our results demonstrate that age, gender and genetic factors can influence the methylation level of CpG islands in gene promoter regions of normal colonic mucosa. Further work is required to determine whether such methylation is associated with the development of CIMP+ CRC.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Prospective evaluation of quality of life in patients with localized oesophageal cancer treated by multimodality therapy or surgery alone.

BACKGROUND: Health-related quality of life (HRQL) outcomes are important in assessing new approaches to the treatment of cancer. Neoadjuvant therapy is being used increasingly before surgery in patients with localized oesophageal cancer. This prospective non-randomized study evaluated HRQL in patients treated by preoperative chemotherapy and radiation therapy followed by surgery (multimodal therapy) or by surgery alone. METHODS: Data from European Organization for Research and Treatment of Cancer quality of life questionnaires QLQ-30 and QLQ-OES24 were collected prospectively. Questionnaires were completed at diagnosis, after chemoradiotherapy where applicable, and at 3, 6 and 12 months after surgery. RESULTS: The study included 202 consecutive patients with oesophageal cancer considered suitable for curative (R0) resection at the time of staging. Eighty-seven patients received chemotherapy combined with external-beam radiotherapy before surgery. At baseline, 75 (86 percent) of 87 patients in the multimodal group completed questionnaires, compared with 72 (62.6 percent) of 115 in the surgery-alone group. There were no significant differences in baseline global HRQL scores between groups. Preoperative chemoradiotherapy significantly reduced physical (P=0.004) and role (P=0.007) functioning before surgery, despite a significant (P=0.043) improvement in the dysphagia score. Oesophageal resection had a negative impact on global, functional and symptom HRQL scores at 3 months in both groups. Most variables had recovered by 6 months in the two groups, but at 12 months physical and role functioning remained impaired in the surgery-alone group, and social functioning and financial worries in the multimodal group. CONCLUSION: Although the multimodal regimen had a negative impact on HRQL before surgery, postoperative quality of life in patients who had multimodal therapy was similar to that in those who had surgery alone.

Adult↗
PubMed2006

Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates.

Glial cell line-derived neurotrophic factor (GDNF) has been shown to increase the survival and functioning of dopamine neurons in a variety of animal models and some recent human trials. However, delivery of any protein to the brain remains a challenge due to the blood/brain barrier. Here we show that human neural progenitor cells (hNPC) can be genetically modified to release glycosylated GDNF in vitro under an inducible promoter system. hNPC-GDNF were transplanted into the striatum of rats 10 days following a partial lesion of the dopamine system. At 2 weeks following transplantation, the cells had migrated within the striatum and were releasing physiologically relevant levels of GDNF. This was sufficient to increase host dopamine neuron survival and fiber outgrowth. At 5 weeks following grafting there was a strong trend towards functional improvement in transplanted animals and at 8 weeks the cells had migrated to fill most of the striatum and continued to release GDNF with transport to the substantia nigra. These cells could also survive and release GDNF 3 months following transplantation into the aged monkey brain. No tumors were found in any animal. hNPC can be genetically modified, and thereby represent a safe and powerful option for delivering growth factors to specific targets within the central nervous system for diseases such as Parkinson's.

Animals↗
PubMed2005

Non-Dupuytren's disease of the palmar fascia.

The typical Dupuytren's disease patient is of Northern European descent with bilateral progressive multiple digital contractures and is genetically predisposed, with a family history. Palmar fascial proliferations sometimes present as a different entity without the typical Dupuytren's disease characteristics. We identified 39 patients (20 women and 19 men) over a 4-year period with "Non-Dupuytren's palmar fascial disease", with unilateral involvement, without family history or ectopic manifestations. Twenty-three patients presented with unrelated complaints and were discovered, incidentally, to have the condition. In 28 patients, prior ipsilateral hand surgery or trauma precipitated the condition. Other related factors were diabetes mellitus and cardiovascular disease. Ten patients had skin tethering and subcutaneous thickening akin to Dupuytren's nodules and 29 had palmar fascial thickening into ill-defined pretendinous cords. The diseased tissue was in the line of the ring finger in 30 patients. The time from insult to onset of contracture averaged 3.6 months and from onset to follow-up averaged 5.3 years. The condition was non-progressive, or partially regressive, in 33 patients. Seven patients had operations for unrelated conditions and underwent simultaneous fasciectomy without recurrence. Environmental factors, especially trauma, surgery and diabetes, are important in the pathogenesis of Non-Dupuytren's palmar fascial disease, but these patients do not appear to be genetically predisposed for Dupuytren's disease. Typical Dupuytren's disease and Non-Dupuytren's palmar fascial disease are two clinical entities that run different courses and do not share a similar prognosis. This should be taken into account in future epidemiological and outcome studies.

Adult↗
PubMed2005

Autologous hematopoietic stem cell transplantation for autoimmune diseases.

Experimental data and early phase I/II studies suggest that high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) can arrest progression of severe autoimmune diseases. We have evaluated the toxicity and disease response in 473 patients with severe autoimmune disease treated with autologous HSCT between 1995 and 2003, from 110 centers participating in the European Group for Blood and Marrow Transplantation (EBMT) autoimmune disease working party database. Survival, transplant-related mortality, treatment response and disease progression were assessed. In all, 420 patients (89%; 86+/-4% at 3 years, median follow-up 20 months) were alive, 53 (11%) had died from transplant-related mortality (N=31; 7+/-3% at 3 years) or disease progression (N=22; 9+/-4% at 3 years). Of 370 patients, 299 evaluable for response (81%) showed a treatment response, which was sustained in 213 (71% of responders). Response was associated with disease (P<0.001), was better in patients who received cyclophosphamide during mobilization (relative risk (RR)3.28 (1.57-6.83)) and was worse with increasing age (>40 years, RR0.29 (0.11-0.82)). Disease progression was associated with disease (P<0.001) and conditioning intensity (high intensity, RR1; intermediate intensity, RR1.81 (0.96-3.42)); low intensity, RR2.34 (1.074-5.11)). These data from the collective EBMT experience support the hypothesis that autologous HSCT can alter disease progression in severe autoimmune disease.

Autoimmune Diseases↗
PubMed2005

Neutrophil cell death, activation and bacterial infection in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is characterised by chronic endobronchial bacterial infection and neutrophil mediated inflammation. Neutrophil apoptosis is essential for the resolution of inflammation. This study assessed the relationship between levels of neutrophil apoptosis and sputum microbiology in matched clinically stable patients with CF. METHODS: Sputum was induced from 34 patients (nine with no Gram negative infection, 10 colonised with Pseudomonas aeruginosa, 10 with Burkholderia cenocepacia, and five with other infections). Apoptotic neutrophils measured by flow cytometric Annexin V/propidium iodide staining and morphology were similar in all groups. RESULTS: Patients infected with P aeruginosa or B cenocepacia had a significantly lower percentage of viable neutrophils in the sputum than those with no Gram negative infection (Kruskal-Wallis p = 0.01, median (interquartile range (IQR)) 14.2% (9.4-21.6), 15.8% (12.3-19.5), and 48.4% (23.0-66.4); p = 0.003 and p = 0.002, respectively). They also had significantly higher levels of secondary necrotic granulocytes in sputum than patients with no Gram negative infection (Kruskal-Wallis p<0.0001, median (IQR) 55.5% (48.4-64.5), 50.4% (44.6-61.9), and 24.8% (14.4-30.5); p<0.0001 and p<0.0001, respectively). Neutrophils (x 10(6)/g sputum) in P aeruginosa infected patients (Kruskal-Wallis p = 0.05, median (IQR) 6.3 (3.5-12.7)) and B cenocepacia infected patients (5.7 (1.5-14.5)) were significantly higher than in the group with no Gram negative infection (0.5 (0.5-4.3), p = 0.03 and 0.04, respectively). CONCLUSION: These results suggest that cell death and clearance may be altered in patients with CF colonised with P aeruginosa and B cenocepacia compared with those with no Gram negative infection.

Adult↗
PubMed2005

Structure and function of the esophagus of the American alligator (Alligator mississippiensis).

Esophageal structure and function were studied in juvenile American alligators (Alligator mississippiensis). The anatomy of alligators differs from humans in several important aspects: the crocodilian esophagus is more muscular and is composed entirely of smooth muscle. Functionally, the crocodilian esophagus is similar to that of mammals, but alligators have peak esophageal peristaltic pressures that are 2-3-fold greater than pressures in the human esophagus. As is found in humans, the incidence of esophageal reflux increased in postprandial animals compared with the fasting state. We observed a large increase in pressure in the lower esophageal sphincter (LES) during ventilation that ranged from 200% to 3000% of the pressures measured during apnea. These pressure changes appear to be intrinsic to the LES. Alligators lack a mammalian-type diaphragm; thus, there is no crural diaphragmatic contribution to LES pressure. These features recommend the alligator as a useful model for the study of regulation of the LES.

Alligators and Crocodiles↗
PubMed2004

Open vs. closed lateral internal sphincterotomy for idiopathic fissure-in-ano: a prospective, randomized, controlled trial.

PURPOSE: Internal sphincterotomy remains the "gold standard" for treatment of anal fissure but is associated with a risk of imperfect continence. Recent studies have suggested that surgical technique (open vs. closed) may influence incontinence rates after sphincterotomy. This study was designed to assess the short-term and long-term incidence of incontinence after open and closed internal sphincterotomy. METHODS: Seventy-nine patients were randomly assigned to open or closed internal sphincterotomy, performed in standardized fashion by trainee staff. Standardized questionnaires assessing continence (modified Wexner score) were administered preoperatively and at 1, 6, and 52 weeks. Postoperative stay, pain scores, complications, and fissure healing were prospectively assessed by an independent observer. RESULTS: Three patients were lost to follow-up, leaving 36 closed (16 males; mean age, 45.1 years) and 40 open (21 males; mean age, 47.9 years) internal sphincterotomy patients for assessment. All operations were performed as day case procedures with no readmissions. At six weeks postoperative, 96 percent of fissures had healed. There were no significant differences in pain scores between closed and open internal sphincterotomy at Day 1 or Day 3 postoperative. New incontinence of any grade was seen in 6.8 percent of patients at 52-week follow-up. Three patients (4.1 percent, 1 closed, 2 open) suffered major incontinence at 52 weeks. There were no significant differences in continence at 1, 6, or 52 weeks, although more open patients experienced minor imperfections at 1 week. CONCLUSIONS: Incontinence after internal sphincterotomy is not insignificant. The technique (closed vs. open) does not seem to influence incontinence rates.

Adult↗
PubMed2004

Quantitation of circulating DNA in the serum of breast cancer patients by real-time PCR.

The purpose of this study was to quantify the level of serum DNA in different groups of primary breast cancer patients and in healthy controls using real-time quantitative PCR in order to determine whether such measurements have diagnostic or prognostic value. A total of 96 serum samples of patients with primary breast cancer before surgery (with positive or negative lymph nodes and with high or low relapse-free survival) as well as 24 healthy controls were analysed. DNA concentrations in the serum of the patients differed significantly from the concentration of serum DNA in the controls (medians were 221 and 63 ng x ml(-1), respectively, P<0.001 M-W test). However, no statistically significant difference was observed between the patient groups (P=0.87, M-W test). The serum DNA levels were elevated independently of the size of primary tumour or lymph node metastases. The overall survival of patients with serum DNA concentrations >221 ng x ml(-1) was better than patients with serum DNA concentration <or=221 ng ml(-1) (Kaplan-Meier, P=0.028).

Adult↗
PubMed2004

Temporary mental nerve paraesthesia secondary to orthodontic treatment--a case report and review.

Patients complaining of facial paraesthesia may present to the dental practitioner. The differential diagnosis includes malignant neoplastic disease and therefore warrants prompt hospital referral. Mental nerve paraesthesia during orthodontic treatment is a very rare occurrence. A case of mental paraesthesia during fixed upper and lower orthodontic treatment is presented. This report highlights the importance of thorough investigation of patients presenting with a history of facial numbness, and provides a review of the aetiology and management of this problem for the dental practitioner. Guidelines for referral have been suggested where orthodontic treatment is suspected as the cause.

Adolescent↗
PubMed2004

Clinical and psychometric validation of a questionnaire module, the EORTC QLQ-STO 22, to assess quality of life in patients with gastric cancer.

The purpose of this study was to define the measurement properties and clinical validity of the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire module to assess health-related quality of life (HRQL) in gastric cancer. The EORTC gastric cancer module, QLQ-STO 22, was administered with the QLQ-C30, core questionnaire, to 219 patients undergoing treatment with curative or palliative intent before and after treatment. Reliability and validity of the module was tested and patients' debriefing comments analysed. Compliance rates were high, questionnaires well accepted and less than 4% of items had missing data. Multi-trait scaling analyses and face validity refined the module to five scales and four single items. Scales distinguished between clinically distinct groups of patients and demonstrated treatment-induced changes over time. Test-retest scores demonstrated good reliability. The EORTC QLQ-STO 22 demonstrates psychometric and clinical validity that supports its use to supplement the EORTC QLQ-C30 to assess quality of life in patients with gastric cancer undergoing surgery, surgery and chemoradiotherapy, palliative chemotherapy, palliative surgery and best supportive care.

Adult↗
PubMed2004

A phase II study of Rituximab in rheumatoid arthritis patients with recurrent disease following haematopoietic stem cell transplantation.

Haematopoietic stem cell transplantation (HSCT) has been used recently as an effective therapy in patients with resistant rheumatoid arthritis (RA). Although disease control occurs in the majority of cases, recurrence is common, often coinciding with B-cell reconstitution. We hypothesized that Rituximab, a monoclonal anti-CD20 antibody, would have activity in this group of patients. We treated 10 RA patients (8F:2M, median age 46.5 years), who had recurrent disease post HSCT. All patients received two doses of Rituximab 1 g, 2 weeks apart with no major adverse sequelae and were followed for 12 months. A total of eight out of 10 patients experienced major clinical responses as measured by the American College of Rheumatology (ACR) criteria, with 50-70% improvement in disease parameters. Responses were equivalent to previous responses attained with HSCT. Disease responses were maximal at 4-8 months post Rituximab and correlated with B-cell lymphopenia and a reduction of rheumatoid factor titre. Disease recurrence occurred in 6/9 responders within 12 months and four patients were subsequently retreated, with major responses again attained. This study provides further evidence that B-cell depletion leads to a significant improvement in disease activity in patients with severe RA and provides data for future trials of HSCT and Rituximab therapy.

Adult↗
PubMed2004

Parastomal hernia repair.

OBJECTIVE: The aim of this study was to audit the results of parastomal hernia repair. METHODS: A retrospective review was made of all patients having parastomal hernia repair at 2 teaching hospitals over a 12-year period. RESULTS: Forty-three patients had 51 parastomal hernia repairs. Three types of hernia repair were used: 14 (28%) local suture, 19 (37%) local mesh repair and 18 (35%) stoma relocation. Three patients died and significant complications occurred in 65% of repairs. Parastomal hernia recurred in 18 (38%) of repairs. This was greatest with a sutured repair (59%) and least in patients having stoma relocation (24%). Repair with mesh was associated with a 39% recurrence rate. No significant statistical difference was found for the results of these repairs. CONCLUSION: Parastomal hernia repair is associated with high rates of morbidity, mortality and recurrence. Repair should not be undertaken without a good indication.

Adult↗