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C Wright

Publications and source records attributed to C Wright.

At least 91 records · Page 5Linked to original sources
PubMed1999

PDX-1 and Msx-2 expression in the regenerating and developing pancreas.

We have observed pancreatic duct cell proliferation and islet regeneration in transgenic mice whose pancreata produce interferon gamma (IFNg mice). We have previously demonstrated that new islet cells derive from endocrine progenitor cells in the pancreatic ducts of this model. The current study was initiated to define these endocrine progenitor cells further and to identify novel markers associated with pancreatic regeneration. Importantly, we have found that PDX-1, a transcription factor required for insulin gene transcription as well as for pancreatic development during embryogenesis, is expressed in the duct cells of IFNg mice. This striking observation suggests an important role for PDX-1 in the marked regeneration observed in IFNg mice, paralleling its critical function during ontogeny. Also demonstrated was elevated expression of the homeobox-containing protein Msx-2 in the pancreata of fetal mice as well as in adult IFNg mice, identifying this molecule as a novel marker associated with pancreatic development and regeneration as well. The identification of PDX-1 and Msx in the ducts of the IFNg transgenic pancreas but not in the ducts of the non-transgenic pancreas suggests that these molecules are associated with endocrine precursor cells in the ducts of the IFNg transgenic mouse.

Animals↗
PubMed1999

Competition between positive and negative reinforcement in the treatment of escape behavior.

We compared the effects of reinforcing compliance with either positive reinforcement (edible items) or negative reinforcement (a break) on 5 participants' escape-maintained problem behavior. Both procedures were assessed with or without extinction. Results showed that compliance was higher and problem behavior was lower for all participants when compliance produced an edible item rather than a break. Treatment gains were achieved without the use of extinction. Results are discussed regarding the use of positive reinforcement to treat escape behavior.

Adolescent↗
PubMed1998

Expression of the ErbB-neuregulin signaling network during human cerebellar development: implications for the biology of medulloblastoma.

The four receptor tyrosine kinase I receptors, ErbB-1, ErbB-2, ErbB-3, and ErbB-4, which have been implicated in the development of a variety of normal and malignant tissues, are activated through ligand mediated homo- and heterodimerization. We have previously reported the frequent coexpression, heterodimerzation, and prognostic significance of ErbB-2 and ErbB-4 in childhood medulloblastoma, an embryonal tumor of the cerebellar external granule cell layer (EGL). In the present study, we have used immunohistochemistry and Western blotting analysis to analyze the expression of the ErbB receptors and neuregulin (NRG) 1-alpha and NRG1-beta ligands during normal human cerebellar development. We demonstrate that ErbB-1, ErbB-3, ErbB-4, and NRG1-beta display specific temporal and topographical distribution in the cerebellum during intrauterine and postnatal life, and that normal ErbB-NRG signaling in the EGL multiplying zone is likely to be mediated by ErbB-4 and NRG1-beta. In contrast, ErbB-2, which is expressed in 86% of medulloblastomas, could not be detected at any stage of cerebellar development. Therefore, we propose that positive deregulation of ErbB-2 expression in the cerebellar EGL, leading to the formation of a NRG41-beta-driven ErbB-2/ErbB-4 autocrine loop, is an important factor in medulloblastoma tumorigenesis. In further support of this hypothesis, we provide evidence using reverse transcription-PCR analysis that expression of the ErbB-2 and ErbB-4 receptors, but not ErbB-1 or ErbB-3, is deregulated in medulloblastoma compared with normal developing cerebellum. We also demonstrate NRG1-beta expression in 87% (n = 46 of 48) of medulloblastoma primary tumors, with the greatest expression levels occurring in tumors with high ErbB-2 and ErbB-4 receptor coexpression. Furthermore, the expression of all three components of the proposed autocrine loop (ie., ErbB-2, ErbB-4, and NRG1-beta) was significantly related to the presence of metastases at diagnosis (P < 0.05).

Blotting, Western↗
PubMed1998

Cross-clade p17 peptide recognition by antisera to HGP-30, a 30-amino acid synthetic peptide antigen from HIV type 1 p17.

HGP-30, a 30-amino acid synthetic peptide analog of HIV-1SF2 p17 (aa 86-115), was used to immunize both mice and humans. Since the amino acid sequence of HGP-30 is relatively conserved among different HIV-1 strains and clades, experiments were carried out to determine if antisera obtained by immunizing animals and humans can recognize HGP-30-related peptide consensus sequences belonging to different clades. Results show that antisera from mice immunized with HGP-30 can recognize clade B and C and to a lesser degree clade A and E consensus sequences of HIV-1, in addition to recognizing HGP-30 sequence. The cross-clade recognition was higher in mouse sera obtained on day 42 than on day 14 or 28. MPL/SE and Novasomes were better adjuvants than alum in inducing antibodies that showed cross-clade recognition and IgG2a and IgG2b antibody isotypes. Similar cross-clade recognition was observed in several sera from humans immunized with an HGP-30/KLH/alum formulation. The human sera from HGP-30-immunized subjects evaluated for cross-clade recognition of HGP-30 peptides were from subjects whose cells showed significant protection from HIV infection on virus challenge in the hu-PBL-SCID mouse model. These studies suggest that HGP-30 may be useful as a candidate vaccine antigen for populations in countries with prevalence of different HIV clades.

AIDS Vaccines↗
PubMed1998

Mental health. Commissioned for service.

GPs often lack the data to make well-informed judgements about commissioning mental health services. A multi-agency group, including a multifund, health authority and social services, has developed service agreements which are proving useful to practices. The system provides primary care commissioners with clinical information linked to expenditure for all patients with a mental illness.

Contract Services↗
PubMed1998

The DNA intercalating alkaloid cryptolepine interferes with topoisomerase II and inhibits primarily DNA synthesis in B16 melanoma cells.

Cryptolepine hydrochloride is an indoloquinoline alkaloid isolated from the roots of Cryptolepis sanguinolenta. It is characterized by a multiplicity of host-mediated biological activities, including antibacterial, antiviral, and antimalarial properties. To date, the molecular basis for its diverse biological effects remains largely uncertain. Several lines of evidence strongly suggest that DNA might correspond to its principal cellular target. Consequently, we studied the strength and mode of binding to DNA of cryptolepine by means of absorption, fluorescence, circular, and linear dichroism, as well as by a relaxation assay using DNA topoisomerases. The results of various optical and gel electrophoresis techniques converge to reveal that the alkaloid binds tightly to DNA and behaves as a typical intercalating agent. In DNAase I footprinting experiments it was found that the drug interacts preferentially with GC-rich sequences and discriminates against homo-oligomeric runs of A and T. This study has also led to the discovery that cryptolepine is a potent topoisomerase II inhibitor and a promising antitumor agent. It stabilizes topoisomerase II-DNA covalent complexes and stimulates the cutting of DNA at a subset of preexisting topoisomerase II cleavage sites. Taking advantage of the fluorescence of the indoloquinoline chromophore, fluorescence microscopy was used to map cellular uptake of the drug. Cryptolepine easily crosses the cell membranes and accumulates selectively into the nuclei rather than in the cytoplasm of B16 melanoma cells. Quantitative analyses of DNA in cells after Feulgen reaction and image cytometry reveal that the drug blocks the cell cycle in G2/M phases. It is also shown that the alkaloid is more potent at inhibiting DNA synthesis rather than RNA and protein synthesis. Altogether, the results provide direct evidence that DNA is the primary target of cryptolepine and suggest that this alkaloid is a valid candidate for the development of tumor active compounds.

Alkaloids↗
PubMed1998

Ultrasound-guided compression of femoral pseudoaneurysm: an audit of practice.

OBJECTIVE: To audit the practice of ultrasound-guided compression of femoral pseudoaneurysm in a specialist cardiac hospital. BACKGROUND: Femoral pseudoaneurysm is an important complication of invasive cardiac procedures. This may require surgical repair but more recently ultrasound-guided compression for ablating pseudoaneurysms has been described. We investigated the success of such a procedure. METHODS AND RESULTS: In a 26-month period, 56 patients were referred for ultrasound scanning to exclude the formation of a femoral pseudoaneurysm following transfemoral cardiac procedures. During this period, 5756 diagnostic cardiac catherisations and 1165 coronary angioplasties were performed in our hospital (total of 6921 procedures). Of the 56 patients, 20 patients (0.3% of 6921) were found to have a pseudoaneurysm. Ultrasound-guided compression was attempted in 11 patients and was successful in 7 patients (64%). Of the patients who had failed ultrasound-guided compression, 2 proceeded to surgical closure and 2 were treated conservatively with compression stockings to facilitate thrombosis of the pseudoaneurysm. Of those who did not have an attempted ultrasound-guided compression of the pseudoaneurysm (n=9), a conservative approach consisting of resting the leg was adopted to facilitate spontaneous thrombosis of the pseudoaneurysm; repeat ultrasound scanning was needed for follow-up and 1 patient required surgical closure in this group. CONCLUSIONS: In patients with a femoral pseudoaneurysm following an invasive cardiac procedure, ultrasound-guided compression may be useful as an immediate step to ablate the pseudoaneurysm. This avoids either prolonged leg rest and repeated ultrasound scanning or surgical intervention. However, ultrasound-guided compression is not always successful; in these patients, a period of conservative management with repeat ultrasound scanning is appropriate to allow for the possible spontaneous thrombosis of the pseudoaneurysm. Surgical closure is needed in those patients whose pseudoaneurysm is enlarging, painful or remain patent.

Adult↗
PubMed1998

Combined therapy with deferiprone and desferrioxamine.

In a proportion of transfusion-dependent patients iron chelation with daily doses of deferiprone of 75 mg/kg body weight (b.w.) is inadequate. The effects on iron status of increasing the daily oral dose of deferiprone and/or combining deferiprone therapy with subcutaneous infusions of desferrioxamine have been studied in 13 transfusion-dependent patients. Raising the daily dose of deferiprone in nine patients from 75 mg/kg to 83-100 mg/kg resulted in a fall in serum ferritin in all nine patients (t test for paired samples, P = 0.0022). Combined therapy of daily deferiprone with subcutaneous desferrioxamine on 2-6 d each week in five patients (with an increased dose of deferiprone in three patients) resulted in a fall in serum ferritin in all five patients studied after 7-15 months (P=0.0791). No toxic side-effects attributable to either drug occurred in these five patients or in the nine patients in whom the dose of deferiprone was increased. The effects of the drugs given on the same day on urine iron excretion were additive. These results suggest that increasing the dose of deferiprone or combining subcutaneous desferrioxamine with deferiprone therapy are two methods by which efficacy of iron chelation with deferiprone can be improved in patients inadequately chelated by a daily dose of deferiprone of 75 mg/kg b.w. More extensive trials including full metabolic balance studies are needed to establish the safety and efficacy of long-term combined therapy.

Adolescent↗
PubMed1998

How easy is it for young people to obtain cigarettes, and do test sales by trading standards have any effect? A survey of two schools in Gateshead.

Smoking prevalence among young people continues to rise and cigarettes are easily available from many shops. Test sales are used by trading standards departments to try to reduce under-age sales, but it is not known whether this has any real impact on cigarette purchase and consumption. This study aims to evaluate the impact of test sales on purchase and consumption of cigarettes by young people. A survey of two schools in Gateshead, one in the intervention area and one acting as a control was carried out. A series of test sales were targeted to shops within 1.5 km of the intervention school. A questionnaire was administered in both schools among year 10 pupils, age 14-15 years, prior to the intervention and again 1 year later. The outcomes measured were number of successful test sales, reported availability of cigarettes and change in smoking prevalence following the intervention. Some 224 pupils from both schools were surveyed in 1995 and 163 pupils from the new cohort of year 10 pupils in 1996. Prior to the intervention, the levels of regular smoking in the intervention school were 39% for girls and 26% for boys. In the control school these levels were 24% and 14%, respectively. The intervention by trading standards resulted in no purchases and hence no prosecutions, but children reported being able to buy cigarettes with ease from the nearby shops; only three (2.5%) reported sales refused in 1995 and five (5.8%) in 1996. Not surprisingly there was no significant change in smoking prevalence in either school in 1996. This study suggests that test sales may not be effective in modifying cigarette availability to young people and that they are not a reliable measure of access to cigarettes by children.

Adolescent↗
PubMed1998

Long-term prognosis in unstable angina. The importance of early risk stratification using continuous ST segment monitoring.

AIMS: To assess the ability of clinical characteristics, admission ECG and continuous ST segment monitoring in determining long-term prognosis in unstable angina. METHODS: Two hundred and twelve patients with unstable angina (mean age 59 years), presenting within 24 h of an acute episode of angina were recruited at three hospitals and treated with standardized medical therapy. All patients kept chest pain charts and underwent ST segment monitoring for 48 h. The occurrence of death, myocardial infarction, and need for revascularization was assessed over a median follow-up of 2.6 years. RESULTS: The risk of death of myocardial infarction was greatest in the first 6-8 weeks after admission. Admission ECG ST depression and the presence of transient ischaemia predicted increased risk of subsequent death or myocardial infarction, whereas a normal ECG predicted a good prognosis. In 14 patients, ST segment monitoring provided the only evidence of recurrent ischaemia, and 72% of this group suffered an adverse event. Transient ischaemia and a history of hypertension were the most powerful independent predictors of death or myocardial infarction. CONCLUSIONS: Adverse events in unstable angina occur early after admission and can be predicted by clinical and ECG characteristics, and by the presence of transient ischaemia during ST segment monitoring. Risk stratification by these simple assessments can identify patients with unstable angina at high risk.

Adult↗
PubMed1998

Long-term (5 year) effects of transient (silent) ischaemia on left ventricular systolic function in stable angina. Clinical and radionuclide study.

AIMS: (a) to assess short (1 year) and long-term (5 year) changes in left ventricular ejection fraction in patients with stable coronary disease with or without ECG evidence of transient ischaemia during daily life on routine therapy, and (b) to assess whether patients with recurrent transient ischaemic episodes have a particular propensity to gradual deterioration in left ventricular ejection fraction in the absence of infarction. METHODS AND RESULTS: One hundred and forty eight patients (127 males; mean age 59 years), part of a natural history cohort of 172 patients who had undergone exercise testing, 48 h ambulatory ST monitoring, and resting radionuclide ventriculography at baseline, and who had not suffered any intervening cardiac event, underwent repeat radionuclide ventriculography at 1 year follow-up on identical or very similar medications. Furthermore, 56 patients (50 males; mean age 65 years) of this cohort, who had ischaemia both on exercise testing and ambulatory monitoring at baseline (n=33), or no ischaemia on either test at baseline (n=23), and who had suffered no intervening event, underwent repeat exercise testing, ambulatory monitoring and radionuclide ventriculography at a mean of 61.8 months follow-up. In 38 of these 56 cases, long-term testing mirrored baseline testing in terms of presence or absence of ischaemia (both tests +, n=25; both tests -, n=13). At one year there was no change in left ventricular ejection fraction, either for the whole group (n=148; left ventricular ejection fraction 47=11.6% - 47.13+11.07%, P=ns) or for subgroups with (n=62; left ventricular ejection fraction 48+12.1%-48.5+10.5%, P=ns) and without (n=86; left ventricular ejection fraction 46.2+10.4%-46.2+11.3%, P=ns) evidence of transient ischaemia at baseline. At 61 months, there was a small fall in mean left ventricular ejection fraction for the total study group (n=56; left ventricular ejection fraction 45.8+9.3%-42.1+8.8%, P<0.05); however, this fall was not significant for those patients with both baseline and 5 year evidence of transient ischaemia (n=25; left ventricular ejection fraction 44.9+8.7%-41.3+7.5%, P=0.056). CONCLUSION: In medically treated stable coronary patients who do not suffer any intervening cardiac event, recurrent transient (silent) ischaemic episodes do not, in themselves, lead to gradual deterioration in left ventricular systolic function over a 1-5 year period.

Adult↗
PubMed1998

Increased platelet responsiveness following coronary stenting. Heparin as a possible aetiological factor in stent thrombosis.

AIMS: Platelet activation may be a determinant of thrombotic and restenotic complications following intracoronary stenting. In order to measure the effect of stenting on platelet activation antigen expression we used whole blood flow cytometry in 18 patients undergoing Palmaz-Schatz stenting (treated with full anticoagulation) and compared these with a group of 18 patients undergoing elective angioplasty. The effects of low molecular weight heparin and unfractionated heparin on platelet behaviour were also studied, both in vitro and in vivo to determine the contribution of prolonged heparin therapy to platelet activation following stenting. METHODS AND RESULTS: Fibrinogen binding to activated GPIIb-IIIa, and surface expression of P-selectin, GPIb and GPIIb-IIIa antigens were measured in unstimulated peripheral blood samples (rest) and on stimulation with adenosine diphosphate (0.1-10 micromol x 1(-1)) and thrombin (0.02-0.16 U x ml(-1)). No changes were seen in resting samples following angioplasty or stenting. Agonist responsiveness was unaltered after angioplasty, but in stented patients antigen expression in response to thrombin was significantly reduced (P< or =0.04), whilst the adenosine diphosphate response was significantly increased (P=0.01). Similar effects were observed in patients with unstable angina treated with either low molecular weight heparin or unfractionated heparin in vivo. In vitro, both unfractionated and low molecular weight heparin inhibited thrombin-induced platelet activation, but stimulation of adenosine diphosphate responses was more marked with unfractionated than low molecular weight heparin. CONCLUSIONS: There was a significant increase in platelet responsiveness to adenosine diphosphate following intracoronary stenting in patients treated with conventional anticoagulants. This was probably a consequence of treatment with heparin. Activation of platelets by heparin may explain the increased rate of stent thrombosis in patients treated with anticoagulant therapy. Low molecular weight heparins stimulate platelets less than unfractionated heparin.

Adenosine Diphosphate↗
PubMed1998

Primary extrarenal Wilms' tumor of the uterus presenting as a cervical polyp.

Extrarenal Wilms' tumor is rare in any site, and only three cases arising within the uterus have been reported. Two of the previous cases were in adolescent girls, appearing as polypoid vaginal masses, and the third was in a 22-year-old woman who had menometrorrhagia. An extrarenal Wilms' tumor in an 11-year-old girl that initially appeared as a 10-cm polyp protruding through the cervix is described. Triphasic differentiation with mesenchymal stroma showing rhabdomyoblastic differentiation both morphologically and immunohistochemically was demonstrated. Epithelial differentiation with focal glomerular differentiation also was present. Most of the primary tumor and almost the entire recurrent tumor were composed of blastemal cells. The diagnosis of an extrarenal Wilms' tumor should be entertained when examining a polypoid tumor of the cervix or a polypoid mass within the vagina in an adolescent patient.

Biomarkers, Tumor↗
PubMed1998

Terminal ileal imaging with ileoscopy versus small-bowel meal with pneumocolon.

Disease of the terminal ileum can be diagnosed by ileocolonoscopy or barium radiography. We compared the diagnostic accuracy in the terminal ileum of ileocolonoscopy and small-bowel meal with pneumocolon. Consecutive patients during an 18-month period who had both ileocolonoscopy and small bowel meal with pneumocolon were identified and their colonoscopy reports, radiographs, and ileal biopsies reviewed blindly by paired gastroenterologists, radiologists, and pathologists, respectively. A gold-standard diagnosis was determined for each patient by consensus. Of 48 study subjects, 14 (29.2%) had Crohn's disease, 5 (10.4%) had lymphoid nodular hyperplasia, and 29 (60.4%) were normal. The sensitivity for a diagnosis of Crohn's ileitis was 92.9% for ileocolonoscopy and 100% for small-bowel meal, while their specificities were 100% and 97.1% respectively. The gold standard diagnosis confirmed ileocolonoscopic findings in 45 patients (93.8%) and radiographic findings in 42 patients (87.5%). Agreement between ileocolonoscopy and small bowel meal occurred in 39 cases (81.2%). By combining histology with ileocolonoscopy, the sensitivity and specificity could be increased to 100% for all diagnoses. Ileocolonoscopy and small-bowel meal with pneumocolon are complementary techniques for imaging the terminal ileum. A prospective comparative trial is now needed to more objectively assess their accuracy, cost effectiveness, and adverse effects.

Adolescent↗
PubMed1998

Implementing a clinical pathway for congestive heart failure: experiences at a teaching hospital.

Clinical pathways are processes of care that use a multidisciplinary team effort to move patients toward a designed outcome. This article details the challenges of a Quality Enhancement and Clinical Resource Management Team in designing and implementing a successful congestive heart failure pathway at a teaching hospital. Academic institutions have the resources as part of their research mission, to enhance the development of clinical pathways and assess their outcomes.

Aged↗