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Biomedical subjects

M Gavin

Publications and source records attributed to M Gavin.

At least 19 recordsLinked to original sources
PubMed2005

Retinal toxicity during pegylated alpha-interferon therapy for chronic hepatitis C: a multifocal electroretinogram investigation.

BACKGROUND: Ocular side-effects in the form of retinal ischaemia and haemorrhages have been reported in patients undergoing standard alpha-interferon therapy. AIM: To assess the ocular impact of therapy with sustained release pegylated alpha-2a interferon (Pegasys) for chronic hepatitis C. METHODS: Ten patients receiving Pegasys and ribavirin and 10 healthy volunteers were recruited. Patients underwent full ophthalmic investigations and multifocal electroretinogram testing at baseline, at regular intervals during treatment and post-treatment. The multifocal electroretinogram maps retinal function. Responses were compared with sequential recordings from healthy volunteers. RESULTS: All patients had normal clinical ophthalmic investigations at baseline. During therapy a single patient experienced central visual disturbance lasting 24 h with no prolonged ill effect. No other patient was aware of any change in vision. Fundal abnormalities appeared in five patients during treatment. The multifocal electroretinogram showed reductions in retinal function in five patients. Nine of 10 patients exhibited abnormalities on at least one multifocal electroretinogram or fundoscopic investigation. CONCLUSIONS: Subclinical retinal toxicity during anti-viral therapy with pegylated alpha-interferon and ribavirin was frequent in this study and it suggests that patients should be warned of this risk and monitored during therapy.

Adult↗
PubMed2005

ANCA associated pauci-immune retinal vasculitis.

BACKGROUND: Antinuclear cytoplasmic antibodies (ANCA) are useful diagnostic serological markers for the most common forms of necrotising vasculitis. ANCA associated vasculitides represent distinctive clinicopathological categories--for example, Wegener's granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis, and idiopathic necrotising crescentic glomerulonephritis, collectively known as the small vessel pauci-immune vasculitides. METHOD: Three cases of ANCA associated pauci-immune retinal vasculitis are described. Their systemic features are described and the clinical significance of ANCA as a diagnostic test in relation to retinal vasculitis discussed. RESULTS: These three cases represent a spectrum of clinical features associated with retinal vasculitis. Two cases have evolved into clinical recognisable entities as microscopic polyangiitis. Adherence to the international consensus statement on testing and reporting of ANCA is recommended and the authors speculate that the incidence of microscopic polyangiitis may be underestimated because of the under-recognition of systemic involvement in patients with retinal vasculitis. CONCLUSION: The receipt of a positive ANCA result should always raise the suspicion of a pauci-immune systemic vasculitis and prompt appropriate investigation. The authors emphasise the importance of the evaluation of systemic features in these patients with retinal vasculitis, enabling earlier recognition and thereby preventing significant morbidity and mortality.

Adult↗
PubMed2003

Quantitation of PGE9509924, a novel, nonfluorinated quinolone, in rat plasma using liquid chromatography electrospray-tandem mass spectrometry following solid-phase extraction sample clean-up in a 96-well format.

PGE9509924, a novel nonfluorinated quinolone, is a potent antibacterial agent with a broad spectrum of activity. A semi-automated method using 96-well format, solid-phase extraction has been developed for quantitating PGE9509924 in rat plasma. The Waters Oasis HLB extraction plate containing a polymeric packing material was found to give the best overall recoveries. All liquid transfer steps other than aliquoting the plasma are accomplished using a 96-channel pipettor. Reverse-phase HPLC with electrospray/MS/MS detection using selective reaction monitoring is used to quantitate the samples. Stable isotopically labeled PGE9509924 is used as the internal standard. The assay is linear over the range from 0.01 to 10 ug/ml. Excellent precision is obtained within a single run and between multiple runs performed on different days. CVs of <6% were observed. The combination of the semi-automated, 96-well parallel sample processing and the short runtime on the LC/MS/MS results in a high throughput assay with reduced operator interaction.

Adsorption↗
PubMed2001

Linking the Rb and polycomb pathways.

Polycomb group (PcG) proteins associate to form complexes that repress Hox genes, thereby imposing the patterning of Hox expression required for development. However, these proteins have a second Hox-independent role in regulating cell proliferation. Our results suggest that association between Rb and PcG proteins forms a repressor complex that blocks entry of cells into mitosis. Also, we provide evidence that Rb colocalizes with nuclear PcG complexes and is important for association of PcG complexes with nuclear targets. The Rb-PcG complex may provide a means to link cell cycle arrest to differentiation events leading to embryonic pattern formation.

Alcohol Oxidoreductases↗
PubMed2001

Lansoprazole treatment of patients with chronic idiopathic laryngitis: a placebo-controlled trial.

OBJECTIVE: Previous uncontrolled studies suggested a therapeutic benefit for treating gastroesophageal reflux disease (GERD) among patients with laryngitis. The present study is the first randomized, placebo-controlled, double-blind study of gastric acid suppression among patients with laryngitis in the United States. METHODS: Patients diagnosed with idiopathic chronic laryngitis were randomized to receive either lansoprazole 30 mg p.o. b.i.d. or a matching placebo for 3 months. Before randomization, all patients underwent upper endoscopy, dual probe ambulatory 24-h esophageal pH-metry, and laryngoscopy, as well as completing a symptom questionnaire for GERD and laryngitis. The primary outcome of treatment was the complete resolution of laryngeal symptoms. RESULTS: A total of 22 patients with symptoms and signs of chronic laryngitis were enrolled, 20 of whom completed the study. At baseline, there were no significant differences between the two groups with regards to GERD symptoms, erosive esophagitis, proximal and distal esophageal pH-metry, or laryngeal signs and symptoms. In an intention-to-treat analysis, six patients in the lansoprazole group (50%) and only one patient (10%) in the placebo group achieved a complete symptomatic response, p = 0.04. Apart from receiving lansoprazole, there were no significant differences between responders and nonresponders in any of baseline esophageal or laryngeal signs and symptoms. CONCLUSIONS: Empirical treatment with lansoprazole is efficacious in relieving symptoms of laryngitis compared to placebo. Such treatment can be considered as a first-line option in managing patients with idiopathic chronic laryngitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF.

We present evidence that Rb forms a repressor containing histone deacetylase (HDAC) and the hSWI/SNF nucleosome remodeling complex, which inhibits transcription of genes for cyclins E and A and arrests cells in the G1 phase of the cell cycle. Phosphorylation of Rb by cyclin D/cdk4 disrupts association with HDAC, relieving repression of the cyclin E gene and G1 arrest. However, the Rb-hSWI/SNF complex persists and is sufficient to maintain repression of the cyclin A and cdc2 genes, inhibiting exit from S phase. HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF then appear to maintain the order of cyclin E and A expression during the cell cycle, which in turn regulates exit from G1 and from S phase, respectively.

Binding Sites↗
PubMed1999

Shared governance: time to consider the cons as well as the pros.

AIMS: This paper aims to provide a critical appraisal of an approach to the management and organization of nursing work known as shared governance (SG). BACKGROUND: This approach has its origins in the USA, where, during the past 20 years it has become increasingly influential. The advocates of SG claim that it can, inter alia, improve recruitment and retention rates, boost morale, and help raise clinical skills. Little wonder that SG in now beginning to make significant inroads into the NHS. ORIGIN OF INFORMATION: However, a trawl through the extensive US literature, using printed and online (e.g. BIDS, CINHAL, MEDLINE, etc.) bibliographical sources, suggests that the claimed benefits of SG should be treated with caution. KEY ISSUES: Much of the existing published research appears to be both methodologically flawed and lacking in any critical edge. While many researchers and commentators appear only too willing to highlight what they see as the promise of SG, they shy away from exploring any potential pitfalls. One consequence of this is that many of the putative benefits SG is said to confer, may in fact be more apparent than real. CONCLUSIONS: Nurses and nurse managers need to be apprised of and consider seriously, the possible cons as well as the potential pros of SG, if any promise it may have is to be realized.

Clinical Competence↗
PubMed1998

Minor histocompatibility antigens as targets for T-cell therapy after bone marrow transplantation.

In allogeneic bone marrow transplantation, differences between donor and recipient at minor histocompatibility loci, which encode allelic proteins containing variant peptide sequences, may result in adverse immune reactions such as graft-versus-host disease (GVHD), or graft rejection, but also a beneficial graft versus leukemia (GVL) response. Some minor H antigens are restricted in their expression to hematopoietic cells, including leukemic progenitors, suggesting it may be possible to separate GVHD and GVL responses. The antigenic peptides for a few human minor H antigens have been identified, and efforts to identify the genes encoding minor H antigens are being pursued. These advances promise to provide a more detailed understanding of the immunobiology and pathogenesis of GVHD and GVL responses and opportunities to selectively augment T-cell responses that promote a GVL effect by adoptive immunotherapy with T-cell clones specific for defined minor H determinants.

Adoptive Transfer↗
PubMed1997

Functional characterization of ETV6 and ETV6/CBFA2 in the regulation of the MCSFR proximal promoter.

The ETV6/CBFA2 (TEL/AML1) fusion gene occurs as a result of the chromosome translocation t(12;21)(p13;q22) in up to 30% of children diagnosed with B cell precursor (cd10+, cd19+) acute lymphoblastic leukemia. Leukemic cells that have acquired the t(12;21) usually demonstrate loss of the remaining normal ETV6 (TEL) allele. Using reporter gene assays we have functionally characterized both the normal ETV6 and ETV6/CBFA2 fusion proteins in the regulation of the MCSFR proximal promoter. Neither ETV6 or ETV6/CBFA2 has any significant, detectable effect on the promoter by itself. However, both ETV6 and ETV6/CBFA2 inhibit the activation of the promoter by CBFA2B(AML1B) and C/EBPa. We have shown that a 29-bp region of the MCSFR promoter containing the binding sites for CBFA2B and C/EBPa is sufficient for the inhibition by ETV6 and ETV6/CBFA2. Mutational analysis of the MCSFR promoter revealed that binding of both CBFA2B and C/EBPa to their respective sites is necessary for the inhibition by ETV6 and ETV6/CBFA2. Deletion of the helix-loop-helix (HLH) region from the cDNAs of ETV6 and ETV6/CBFA2 decreased but did not completely abrogate the ability of either construct to inhibit promoter activation. We also found that the ETS DNA binding region of ETV6 is necessary for inhibition of the promoter. Addition of ETS1 and FLI1, two ETS family members that have homology in the 5' HLH region, but not Spi1, an ETS family member without the 5' HLH region, also inhibited reporter gene expression. Our data show that the inhibition mediated by ETV6 and ETV6/CBFA2, in the context of the MCSFR promoter, depend on interactions with other proteins, not just CBFA2B. Our results also indicate that the transactivation characteristics of ETV6/CBFA2 are a combination of positive and negative regulatory properties.

3T3 Cells↗
PubMed1991

A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit.

We have cloned a receptor tyrosine kinase cDNA, designated fetal liver kinase 1 (Flk-1), from mouse cell populations enriched for hematopoietic stem and progenitor cells. Sequence analysis of this clone reveals strong homology to the c-Kit subfamily of receptor kinases, and in particular to the Flt gene product. Chromosomal mapping shows that the Flk-1, Kit, and Pdgfra genes are closely linked. Flk-1 mRNA is expressed in primitive and more mature hematopoietic cells as well as in a wide variety of nonhematopoietic tissues.

Amino Acid Sequence↗
PubMed1989

Extracranial and digital vascular events: an analysis of methods in BVP amplitude and biofeedback research.

The purpose of the present study was to assess and compare the effects of within and between-session exposure to environmental context on left temporal artery pulse amplitude, right temporal artery pulse amplitude, and left digital pulse amplitude. Subjects were individually tested for 20 min daily over a period of eight consecutive days. A significant interaction was found for Position X Interval. These results show that exposure to the experimental context occurs with diametrically opposite effects on temporalis and digital pulse amplitude within session. Moreover, these results would support the hypothesis that controversial findings within the headache and biofeedback literature may be partially attributable to methodological differences where, for example, different authors use different transducer locations and/or evaluate pulse amplitude at different points within or among sessions. Indeed, research on the effects or lack thereof of therapeutic manipulations may have little or nothing to do with the intervention or experimental manipulations themselves. These effects may be masked or augmented by subject and methodological confounds during baseline and testing conditions.

Adolescent↗
PubMed1985

A community-centered alcoholism assessment/treatment service: a descriptive study.

This paper describes socio-demographic, alcohol-related, legal, medical, behavioural and treatment characteristics of 407 patients with problems of alcoholism/drug abuse assessed over a period of three years in a community oriented assessment and treatment program. The results show that patients entering this program represent a cross section of alcoholics in the area. These patients are similar to those entering traditional outpatient and residential facilities on most demographic variables; severity of alcoholism, length of history, and previous treatment experience. However, they are slightly younger and differ significantly from the others on their sources of referral. Over the three year period a significant change has occurred in the relationship between the program and the sources of referral. The implications of these findings for planning comprehensive treatment services for alcoholism are discussed.

Adolescent↗
PubMed1981

Modification of the macaque's vestibulo-ocular reflex by picrotoxin.

The vestibulo-ocular reflex (VOR) in the macaque was tested by a modified Bárány spinning test before and after subcutaneous administration of 1 mg/kg of picrotoxin. The drug caused a decrease in the nystagmus time constant to a value near that of the cupula and a decrease in mystagmus asymmetry. Picrotoxin prevented diazepam from increasing the time constant of vestibular nystagmus. Furthermore, picrotoxin reduced the nystagmus time constant after vermisectomy, a lesion that increases the nystagmus time constant and prevents some VOR modifications. Because picrotoxin and diazepam interact antagonistically in the gamma-aminobutyric acid (GABA) neurotransmitter system, these results show a role of GABA in the neural network that transforms a short cupula time constant into a longer nystagmus time constant.

Animals↗
PubMed1980

Pre-participation sports assessment--an objective evaluation.

The yield from a pre-participation sports examination consisting of a review of the medical history, routine physical examination, musculoskeletal examination, laboratory screening and an assessment of fitness by evaluation of body composition, flexibility, and muscular strength testing was studied. There were 701 students evaluated. Two students (0.3%) were excluded from participation because of medical problems and seven (1%) because of orthopedic problems. Sixty students (8.6%) were referred for additional medical evaluation. Thirty-five students (5.0%) required further orthopedic evaluation. All of the students who required additional evaluations were eventually granted permission to participate. The review of the medical history was positive in seven of the restricted students and 40 of the referred students. The routine physical examination was normal in the two restricted students and abnormal in 14 of the referred students. The musculoskeletal examination was abnormal in all of the students restricted or referred for orthopedic problems. The assessment of physical fitness revealed that 32% of the students had excessive body fat, 10% to 15% of both boys and girls had excessive muscle tightness in either the upper or lower body and approximately 5% of the students had weakness in hip abductors or flexors. Significant unilateral strength deficits were also found. When performed for the purpose of restricting participation or referring students for additional evaluation, the medical history and musculoskeletal examination are the components of the pre-participation sports examination with the highest yield. Additionally, the aspects of the examination which related to fitness revealed a significant number of abnormalities.

Adolescent↗