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Biomedical subjects

R Robinson

Publications and source records attributed to R Robinson.

At least 19 recordsLinked to original sources
PubMed2006

Distal adenomatous polyps are rare in patients with inflammatory bowel disease.

OBJECTIVE: There is an increased risk of colorectal cancer in patients with inflammatory bowel disease (IBD). The aim of this study was to compare the prevalence of left sided adenomas in patients with IBD aged 55-64 years with a local age matched control population. METHOD: A review of clinical notes. The prevalence of adenomas in patients with IBD attending for either sigmoidoscopy or colonoscopy was compared with local age matched controls that participated in the national screening trial for colorectal cancer with flexible sigmoidoscopy. RESULTS: Of 106 patients (61 male, 45 female, mean age of 59 years), 80 suffered from ulcerative colitis, 20 from Crohn's disease, and six from indeterminate colitis. All patients had undergone at least one flexible sigmoidoscopy and 75 had a colonoscopy. Distal adenomas were found in three patients with ulcerative colitis compared with 67 of 749 controls (2.8% v 8.9%, chi(2) = 4.6, p = 0.03). CONCLUSIONS: The results suggest that distal adenomatous polyps are rare in patients aged 55-64 years with IBD compared with a control population. This supports the hypothesis that lesions other than polyps are important for the development of colorectal cancer in patients with IBD.

Adenomatous Polyps↗
PubMed2004

Anti-VEGF antibody bevacizumab (Avastin) with 5FU/LV as third line treatment for colorectal cancer.

BACKGROUND: To evaluate the activity and safety of bevacizumab when given with standard 5FU/leukovorin (LV) regimens in patients with metastatic colorectal cancer who have failed irinotecan and oxaliplatin-based treatments. METHODS: Bevacizumab was given at 5 mg/kg as an IV infusion every 2 weeks. Patients received 5FU according to Roswell Park or the de Gramont regimen. RESULTS: Nineteen patients enrolled, median age 60, median PS: 1. Most common toxicity attributable to bevacizumab was mild hypertension, epistaxis and mild proteinuria; 1 patient had a CNS haemorrhage. The median number of cycles was 1 (8 weeks). Clinical benefit as disease stabilisation lasting 2-6 months was noted in 9 patients, whereas 10 progressed (median f/u: 5 months). TTP was 16 weeks, and the overall survival has not been reached (24+ weeks). CONCLUSIONS: Bevacizumab may result in growth arrest and clinical benefit in a substantial proportion of patients with colorectal cancer and no alternative treatment.

Aged↗
PubMed2004

Validation of binary ethyleneimine (BEI) used as an inactivant for foot and mouth disease tissue culture vaccine.

The complete inactivation of Foot and Mouth Disease (FMD) virus is a critical requirement in the production of FMD vaccine to ensure the safety of the product. Binary ethyleneimine (BEI) is an aziridine compound, produced from bromoethylamine hydrobromide (BEA) commonly used for the inactivation of FMD virus during vaccine manufacturing. The validation of BEI, when used as an inactivant, is essential to ensure the quality of the inactivating agent and the validity of the process. In the present study, the inactivation kinetics of Foot and Mouth Disease virus (O, A and Asia-1 serotypes) were determined for different concentrations of BEI (0.4 mM, 0.8 mM, 1.2 mM, 1.6 mM and 2.0 mM). Statistically significant differences in the inactivation kinetics were observed between 0.4 mM and 1.6 mM of BEI. The results indicated that BEI at 1.6 mM was able to inactivate the FMD virus within 8-10 h. Increasing the concentration of BEI beyond 1.6 mM did not appreciably improve the inactivation process. No differences in the inactivation kinetics were found between the various serotypes studied. This study can be used as a guideline for routine procedures for validating the quality of BEA and the inactivation process.

Animals↗
PubMed2003

Sodium channel alpha1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms.

BACKGROUND: Mutations in SCN1A, the gene encoding the alpha1 subunit of the sodium channel, have been found in severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). Mutations in SMEI include missense, nonsense, and frameshift mutations more commonly arising de novo in affected patients. This finding is difficult to reconcile with the family history of GEFS+ in a significant proportion of patients with SMEI. Infantile spasms (IS), or West syndrome, is a severe epileptic encephalopathy that is usually symptomatic. In some cases, no etiology is found and there is a family history of epilepsy. METHOD: The authors screened SCN1A in 24 patients with SMEI and 23 with IS. RESULTS: Mutations were found in 8 of 24 (33%) SMEI patients, a frequency much lower than initial reports from Europe and Japan. One mutation near the carboxy terminus was identified in an IS patient. A family history of seizures was found in 17 of 24 patients with SMEI. CONCLUSIONS: The rate of SCN1A mutations in this cohort of SMEI patients suggests that other factors may be important in SMEI. Less severe mutations associated with GEFS+ could interact with other loci to cause SMEI in cases with a family history of GEFS+. This study extends the phenotypic heterogeneity of mutations in SCN1A to include IS.

Amino Acid Sequence↗
PubMed2003

[Epidemics of acute respiratory infections in Madagascar in 2002: from alert to confirmation].

UNLABELLED: An epidemiological investigation (Ministry of Health/Institut Pasteur de Madagascar (IPM)) was conducted in July 2002, in two districts of a same province (Fianarantsoa: Fianarantsoa II and Ikongo) considering the high frequency of deaths linked with acute respiratory infection (ARI). Morbidity and mortality data was collected in the Centre de Santé de Base (CSB) which gave the alert (village of Sahafata, district Fianarantsoa II). Analysis of monthly activity reports (MAR) allowed calculation of incidence rates of ARI/pneumonia in Fianarantsoa province. Virological data was based on the analysis of nasopharyngeal samples collected during the investigations. Clinical symptoms and homogeneity of laboratory results are consistent with an origin of these epidemics being related to the circulation of an influenza virus A subtype H3N2. Attack rates were very high. CFR was significantly higher in individuals of less than 1 year and more than 65 years. This data was confirmed by posterior investigations of teams from MoH/WHO. Surprisingly, this large epidemic was due to a known influenza virus that previously circulated in countries of northern hemisphere (the year before) and even in Antananarivo weeks before. Different hypothesis could be proposed to explain such phenomenon: great restriction of exchanges between different geographical zones, nutritional status.... CONCLUSION: The epidemic episodes of acute respiratory infections in Madagascar in July 2002 were due to an influenza virus A subtype H3N2 without any genotypic or phenotypic features. Various factors, could explain the importance of the epidemic and particular high lethality found in some age groups. This epidemic illustrates the relative incapacity for a developing country, to face and manage a flu epidemic caused by a classical influenza virus.

Acute Disease↗
PubMed2002

Teaching paediatric dentistry by multimedia: a three-year report.

Clinical cases can now be simulated utilising multimedia and used to teach case management to dental students. The modules developed should provide intellectual stimulation, user-interaction and immediate feedback, in addition to being intuitively navigated and user-helpful. Five paediatric dental case modules (early childhood caries, anterior trauma, anterior coronal fragment, anterior crossbite and dentigerous cyst) were created, installed in a multimedia presentation tool, PathFinder (from Westmead Hospital Dental Clinical School, New South Wales, Australia), and used to teach three classes of fourth year dental students at The University of Melbourne. Questionnaires, focus groups and a review were conducted by an external educational expert. Students responded anonymously to general learning questions and case specific questions using a five-point Likert scale (strongly agree to strongly disagree). Student responses indicated they were very enthusiastic about learning via multimedia, although a few students disliked this educational approach. Focus groups and external review indicated that the modules were navigated readily and were suitably interactive.

Case Management↗
PubMed2002

A case of cough, lymphocytic bronchoalveolitis and coeliac disease with improvement following a gluten free diet.

Chronic cough is a common reason for presentation to a respiratory clinic. In up to 20% of cases the cause remains unclear after investigations. We report one such case where there was bronchoscopic evidence of lymphocytic airway inflammation in association with newly diagnosed coeliac disease. All features improved markedly on a gluten free diet, suggesting a causal relationship between coeliac disease, cough, and lymphocytic bronchoalveolitis.

Aged↗
PubMed2001

Peptides from the amino terminal mdm-2-binding domain of p53, designed from conformational analysis, are selectively cytotoxic to transformed cells.

We have synthesized three peptides from the mdm-2 binding domain of human p53, residues 12-26 (PPLSQETFSDLWKLL), residues 12-20, and 17-26. To enable transport of the peptides across the cell membrane and at the same time to maximize the active mdm-2 binding alpha-helical conformation for these peptides, each was attached at its carboxyl terminus to the penetratin sequence, KKWKMRRNQFWVKVQRG, that contains many positively charged residues that stabilize an alpha-helix when present on its carboxyl terminal end. All three peptides were cytotoxic to human cancer cells in culture, whereas a control, unrelated peptide attached to the same penetratin sequence had no effect on these cell lines. The same three cytotoxic peptides had no effect on the growth of normal cells, including human cord blood-derived stem cells. These peptides were as effective in causing cell death in p53-null cancer cells as in those having mutant or normal p53. Peptide-induced cell death is not accompanied by expression of apoptosis-associated proteins such as Bax and waf(p21). Based on these findings, we conclude that the antiproliferative effects of these p53-derived peptides are not completely dependent on p53 activity and may prove useful as general anticancer agents.

Amino Acid Sequence↗
PubMed2001

A low-temperature neutron diffraction study of Mn12-acetate.

In the low-temperature region, where the dodecanuclear mixed-valence manganese carboxylate hexadecaacetatotetraaquadodecaoxododecamanganese bis(acetic acid) tetrahydrate, [Mn(12)O(12)(C(2)D(3)O(2))(16)(H(2)O)(4)].2C(2)HD(3)O(2).4H(2)O, displays unusual magnetic properties, its structure is similar to that previously determined at room temperature [Lis (1980). Acta Cryst. B36, 2042-2046], differing only by a small change in the configuration of one of the coordinated acetate groups, related to the formation of additional hydrogen bonds, and by the orientation of the methyl groups. Since most of the magnetization density of this system resides on the Mn atoms, the consequences of these rearrangements for the magnetic properties of the compound are small.

Journal Article↗
PubMed2001

Safety and immunogenicity trial in adult volunteers of a human papillomavirus 16 L1 virus-like particle vaccine.

BACKGROUND: Studies in animal models have shown that systemic immunization with a papillomavirus virus-like particle (VLP) vaccine composed of L1, a major structural viral protein, can confer protection against subsequent experimental challenge with the homologous virus. Here we report results of a double-blind, placebo-controlled, dose-escalation trial to evaluate the safety and immunogenicity of a human papillomavirus (HPV) type 16 (HPV16) L1 VLP vaccine in healthy adults. METHODS: Volunteers were given intramuscular injections with placebo or with 10- or 50-microg doses of HPV16 L1 VLP vaccine given without adjuvant or with alum or MF59 as adjuvants at 0, 1, and 4 months. All vaccine recipients were monitored for clinical signs and symptoms for 7 days after each inoculation. Immune responses were measured by an HPV16 L1 VLP-based enzyme-linked immunosorbent assay (ELISA) and by an HPV16 pseudovirion neutralization assay. The antibody titers were given as the reciprocals of the highest dilution showing positive reactivity in each assay. All statistical tests were two-sided. RESULTS: The prevaccination geometric mean ELISA titer for six seropositive individuals was 202 (range, 40--640). All vaccine formulations were well tolerated, and all subjects receiving vaccine seroconverted. Serum antibody responses at 1 month after the third injection were dose dependent in recipients of vaccine without adjuvant or with MF59 but were similar at both doses when alum was the adjuvant. With the higher dose, the geometric means of serum ELISA antibody titers (95% confidence intervals) to purified VLP 1 month after the third injection were as follows: 10,240 (1499 to 69 938) without adjuvant, 10,240 (1114 to 94 145) with MF59, and 2190 (838 to 5723) with alum. Responses of subjects within each group were similar. Neutralizing and ELISA antibody titers were highly correlated (Spearman correlation =.85), confirming that ELISA titers are valid proxies for neutralizing antibodies. CONCLUSIONS: The HPV16 L1 VLP vaccine is well tolerated and is highly immunogenic even without adjuvant, with the majority of the recipients achieving serum antibody titers that were approximately 40-fold higher than what is observed in natural infection.

Adjuvants, Immunologic↗
PubMed2001

Plasmid expression of a peptide that selectively blocks oncogenic ras-p21-induced oocyte maturation.

PURPOSE: We have previously found that a synthetic peptide corresponding to ras-p21 residues 96 110 (PNC2) selectively blocks oncogenic (Val 12-containing) ras-p21 protein-induced oocyte maturation. With a view to introducing this peptide into ras-transformed human cells to inhibit their proliferation, we synthesized an inducible plasmid that expressed this peptide sequence. Our purpose was to test this expression system in oocytes to determine if it was capable of causing selective inhibition of oncogenic ras-p21. METHODS: We injected this plasmid and a plasmid expressing a control peptide into oocytes either together with oncogenic p21 or in the presence of insulin (that induces maturation that is dependent on normal cellular ras-p21) in the presence and absence of the inducer isopropylthioglucose (IPTG). RESULTS: Microinjection of this plasmid into oocytes together with Val 12-p21 resulted in complete inhibition of maturation in the presence of inducer. Another plasmid encoding the sequence for the unrelated control peptide, X13, was unable to inhibit Val 12-p21-induced maturation. In contrast, PNC2 plasmid had no effect on the ability of insulin-activated normal cellular or wild-type ras-p21 to induce oocyte maturation, suggesting that it is selective for blocking the mitogenic effects of oncogenic (Val 12) ras p21. CONCLUSION: We conclude that the PNC2 plasmid selectively inhibits oncogenic ras-p21 and may therefore be highly effective in blocking proliferation of ras-induced cancer cells. Also, from the patterns of inhibition, by PNC2 and other ras- and raf-related peptides, of raf- and constitutively activated MEK-induced maturation, we conclude that PNC2 peptide inhibits oncogenic ras p21 downstream of raf.

Amino Acid Sequence↗
PubMed2001

Administration of exogenous endothelin-1 following vascular balloon injury: early and late effects on intimal hyperplasia.

Administration of exogenous endothelin-1 (ET-1) has been shown to stimulate neointimal hyperplasia following arterial balloon angioplasty (BA). However, the specific effects of ET-1 on the cellular and extracellular matrix response of the vessel wall after balloon injury and the persistence of these ET-1 effects have not been studied. The objectives of this study were to determine the acute (1 week) and long term (10 weeks) effects of administering exogenous ET-1 after arterial BA on neointimal hyperplasia, collagen synthesis and content, cellular proliferation, and ET(A) and ET(B) receptor expression. Thirty-one rabbits were randomized to receive subcutaneous ET-1 (500 pmol/kg/day for 1 week) or placebo time-release pellets and sacrificed at either 1 or 10 weeks after BA. At 1 week, there was a significant two-fold increase in intimal cross-sectional area (CSA) in ET-1 treated animals compared with placebo. ET-1 treated animals showed significant increases in collagen synthesis (ten-fold) and collagen content (three-fold) compared to placebo treated animals. ET-1 treated animals also had a significant increase (two-fold) in proliferation rates. In addition, ET(A) and ET(B) receptor expression were significantly upregulated in ET-1 treated animals. By 10 weeks these stimulatory effects on intimal CSA and collagen content were no longer evident with a 'catch up' phenomenon observed in the placebo treated animals. Similarly, ET(A) and ET(B) mRNA levels had declined significantly in both groups. Therefore, exogenous ET-1 acutely stimulates extracellular and cellular processes including increased expression of ET(A) and ET(B) receptors contributing to intimal hyperplasia. However, these effects are transient and not maintained long term after withdrawal of exogenous ET-1 stimulation.

Analysis of Variance↗