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Biomedical subjects

A Ramsay

Publications and source records attributed to A Ramsay.

At least 19 recordsLinked to original sources
PubMed2002

Triple cycle audit of primary retinal detachment surgery.

PURPOSE: To determine the effect of increasing subspecialisation on the results of retinal detachment surgery in one city. METHODS: Three audit cycles over a 10-year period when major subspecialisation and organisational changes were occurring. Retrospective case note reviews of all primary surgery for rhegmatogenous retinal detachments in each of the audit periods. Statistical analyses used contingency table/chi-square methods for comparing all three audits and Fisher's exact test/mean odds ratio with 95% confidence intervals (CIs) for the Audit 1 vs Audit 3 comparison. RESULTS: A marked improvement in success rates occurred: primary reattachment rose from 67% in Audit 1 to 87% in Audit 3 (P = 0.0004), and final success from 84% to 97% (P = 0.0003). There was a dramatic change in operative techniques over the same period: the percentage of vitrectomies increased from 1.5% in Audit 1 to 48% in Audit 3, while that of 'open' conventional procedures decreased from 78% to 32%. However, the improvement in anatomical success was not mirrored by an increase in the percentage of patients with 6/12 or better visual acuity postoperatively (55% in Audit 1, 49% in Audit 3; P = 0.34, mean odds ratio = 0.78; 95% CI 0.48-1.2). The percentage of patients with 6/18-6/36 post op visual acuity did increase in Audit 3 (18% in Audit 1; 29% in Audit 3; P = 0.03, mean odds ratio = 1.9; CI 1.1-3.3), and the percentage with 6/60 or worse decreased (27% in Audit 1, 20% in Audit 3; P = 0.26, mean odds ratio = 0.71; CI 0.40-1.2). CONCLUSIONS: With increased subspecialisation there has been an increase in anatomical success, but the goal of 100% reattachment is still not being attained. There remains scope for further improvement in anatomical and functional outcomes.

England↗
PubMed2001

Melioidosis and Pandora's box in the Lao People's Democratic Republic.

Melioidosis has not been recognized previously in Laos, but within months of starting a prospective study of community acquired septicemia in Vientiane, 2 patients with melioidosis were identified. One was a previously healthy, 44-year-old female rice farmer who presented with supraclavicular lymphadenitis and the other was a 74-year-old man with diabetes and renal calculi who was receiving corticosteroids and had septicemia and septic arthritis.

Adult↗
PubMed2001

PAX3-FKHR induces morphological change and enhances cellular proliferation and invasion in rhabdomyosarcoma.

Alveolar rhabdomyosarcoma (ARMS) is consistently associated with the characteristic translocations t(2;13)(q35;q14) and t(1;13)(p36;q14), which encode for the PAX3-FKHR and PAX7-FKHR fusion oncoproteins respectively. We have investigated the relationship between PAX3-FKHR expression and ARMS histogenesis in primary tumors and cell culture systems. In a blinded histological review of discrepant primary tumors in which there was PAX3-FKHR expression but embryonal histology, we found small areas of alveolar histology in 6 of 11 cases. This suggests that histology alone may under-represent the association between PAX3-FKHR and ARMS, and we investigated this link by examining the effect of ectopic PAX3-FKHR expression on RMS cells. Two cell lines, RD and HX170C, were stably transfected with a PAX3-FKHR expression construct. In cloned transfectants derived from both lines, PAX3-FKHR expression resulted in increased proliferative rate in vitro and promoted cell growth in the absence of added growth factors. Tumors that formed as xenografts in immunodeficient mice were faster growing, more locally invasive, and had a denser, more pleomorphic architecture than untransfected or empty vector transfected tumors. The characteristic clefts and alveolar spaces of ARMS, however, were not seen. In contrast, tumors grown as xenografts from individual clones derived from ARMS cell lines showed all of the classical morphological features of ARMS suggesting divergence in vivo from precursor cells propagated in culture.

Animals↗
PubMed2001

Fatal graft-versus-host disease following HLA-mismatched donor lymphocyte infusion.

We report the case of a 10-year-old boy with molecular relapse of CML following unrelated donor BMT who developed fatal grade 4 acute GVHD of the gut and liver following one antigen-mismatched donor lymphocyte infusion. Previous experience of donor lymphocyte infusion in the HLA-mismatched setting is reviewed and the role of adoptive immunotherapy in this situation is discussed.

Bone Marrow Transplantation↗
PubMed2001

Dextran sulphate sodium-induced colitis is ameliorated in interleukin 4 deficient mice.

The importance of IL-4 and its effects in inflammatory bowel disease (IBD) was studied using the dextran sulphate sodium-induced model of experimental colitis. The model resembles ulcerative colitis in humans. IL-4 deficient mice and IL-4+/+ littermates were used to induce colitis. Activity of disease, extent of tissue damage, immunoglobulin isotypes, IFNgamma and IL-10 production was assessed. Both disease activity index (DAI) and histological scores were consistently lower in the IL-4 deficient mice than in the IL-4+/+ littermates. Furthermore, the lower histological scores reflected the milder inflammatory lesions and decreased ulceration found in the IL-4 deficient mice. Analysis of immunoglobulin subtypes showed that IgG1 was almost absent in the sera of IL-4 deficient mice. IFNgamma contents was much higher in colonic tissues from IL-4 deficient mice. Dextran sulphate sodium-induced colitis is ameliorated in IL-4 deficient mice. IL-4 either directly or through its effects on T and B cells influences its severity. It is unclear if the higher immunoglobulin-producing cells in the colonic tissues of IL-4 deficient mice before colitis was induced could have influenced the outcome of the disease. The high IFNgamma contents in colonic tissues of IL-4 deficient mice argue against the role of this cytokine as a crucial mediator of tissue damage during the acute phase of colitis.

Animals↗
PubMed2001

Failure of antiretroviral therapy to control Varicella zoster retinitis.

The term necrotizing herpetic retinopathies encompasses a spectrum of diseases which includes cytomegalovirus (CMV) retinitis, acute retinal necrosis (ARN) and Varicella zoster retinitis (VZR). Varicella zoster retinitis is a rapidly progressive, necrotizing condition most commonly reported in patients with AIDS. A case of vitreous biopsy-proven VZR is reported in a patient with AIDS that progressed despite immune recovery on highly active antiretroviral therapy (HAART) to a viral load < 50 copies/mL and a CD4 count of 230 cells/microL. This is in contrast to CMV retinitis in which maintenance therapy appears unnecessary once the CD4 count rises and the viral load falls on HAART. Patients with VZR and AIDS should therefore be monitored for reactivation of retinal disease despite HAART-induced remission.

AIDS-Related Opportunistic Infections↗
PubMed2000

Immunotherapy with mannan-MUC1 and IL-12 in MUC1 transgenic mice.

Mice immunised with oxidised mannan-MUC1 fusion protein (M-FP) develop MHC restricted CD8(+) cytotoxic T cells. We now demonstrate that in MUC1/HLA-A2 transgenic mice, IL-12 gives enhanced CTL, CTLp and tumor protection. CTLp in MUC1 transgenic mice with M-FP were 1/55,000, and with IL-12, this increased to 1/19,000, with improved tumor protection. Thus, IL-12 is important for effective CTL responses to MUC1 in transgenic mice.

Animals↗
PubMed2000

Mature B-cell lymphoma/leukemia in children and adolescents: intergroup pathologist consensus with the revised European-American Lymphoma Classification.

BACKGROUND: The Revised European-American Lymphoma (R.E.A.L.) Classification criteria were evaluated in the international protocol FAB LMB 96 Treatment of Mature B-cell Lymphoma/Leukemia: A SFOP LMB 96/CCG-5961/UKCCSG NHL 9600 Cooperative Study. This includes B-lineage lymphomas: Burkitt's lymphoma (including ALL-L3); high-grade B-cell lymphoma, Burkitt-like; diffuse large B-cell lymphoma (excluding anaplastic large cell Ki-1 lymphoma). PATIENTS AND METHODS: Cases were independently reviewed by eight hematopathologists from the three cooperative national groups (two SFOP, two CCG, four UKCCSG), without prior discussion of classification criteria or guidelines for case rejection. Consensus diagnosis was determined by each national cooperative group, and final consensus diagnosis established when at least two national consensus diagnoses were in agreement, or following group agreement at a multiheaded microscope. RESULTS: Two hundred eight cases were reviewed, with final consensus diagnosis established in two hundred three. The percent agreement of each group's national consensus diagnosis with final consensus diagnosis was 86%, 86% and 71%. The percent agreement of the group's national consensus diagnosis with final consensus diagnosis for Burkitt's and diffuse large B-cell lymphoma were 88% and 80%, respectively, but only 42% for Burkitt-like lymphoma. CONCLUSIONS: International panel review of mature B-cell lymphoma/leukemia in children and adolescents highlighted difficulties in subclassification, particularly with Burkitt-like, which is a 'provisional entity' in the R.E.A.L. Classification. The absence of previous discussion of classification and guidelines for case rejection may in part explain the discrepancy between pathologists. These results underline that morphology may need to be complemented by other studies, such as molecular genetic and cytogenetics, to discriminate between the mature B-cell lymphomas.

Adolescent↗
PubMed1999

The clinical utility of the Revised European-American Lymphoma (R.E.A.L.) Classification: preliminary results of a prospective study in patients with non-Hodgkin's lymphoma from a single centre.

BACKGROUND: The clinical applicability of the Revised European-American Lymphoma (R.E.A.L.) Classification has been demonstrated in several retrospective studies. The present, ongoing study was initiated to evaluate the clinical and pathological utility of the R.E.A.L. Classification compared with the Working Formulation (WF) in a prospective fashion, in an unselected patient population treated at a single institution. PATIENTS AND METHODS: Prospective data were collected on 596 biopsies from 557 patients referred with an initial diagnosis of lymphoma. After initial histologic review, 465 biopsies from 441 patients were confirmed as non-Hodgkin's lyphoma (NHL), 412 of which could be classified in R.E.A.L. and WF. RESULTS: According to WF criteria, 25% were low grade, 58% intermediate grade and 2% high grade, 14% could not be allocated to a WF subtype. According to R.E.A.L., 46% were diffuse large B cell, 19% follicle centre lymphoma, 6% marginal zone, 6% small lymphocytic, 4% mantle cell, and 3% T-cell anaplastic large cell. For those with B-cell NHL, 7% were unclassifiable in WF compared with 1% in R.E.A.L. Corresponding figures for T-cell NHL were 68% and 3%, respectively. CONCLUSIONS: Preliminary results confirm the clinical utility of the R.E.A.L. Classification in a single institution setting, demonstrating that cases were more readily sub-typed in R.E.A.L. compared with WF. Frequencies are comparable with I.L.S.G. data. Further follow up with large patient numbers is on-going to analyse survival data with reference to clinical prognostic factors.

Adolescent↗
PubMed1999

Use of recombinant viruses to deliver cytokines influencing the course of experimental bacterial infection.

The feasibility of using viral constructs expressing cytokine genes to influence the course of bacterial infection was tested in mice. The mice were first infected with vaccinia or fowlpox viruses expressing the cytokine of interest, then challenged with the facultative intracellular bacterial pathogen Listeria monocytogenes. The course of infection was assessed by subsequent bacterial counts. Expression of IFN-gamma or TNF was protective. Vaccinia virus was more efficient at delivering IFN-gamma-mediated protection than was fowlpox virus, which is unable to proliferate in mammalian cells. The effect of vaccinia-IFN-gamma was more apparent in the liver, where vaccinia proliferates to high titres (> 109), than in the spleen, where only 103 vaccinia were isolated. Vaccinia virus expressing IL-4 exacerbated infection. Interleukin-4 exacerbation was T cell independent and was reflected in the failure of macrophage activation, possibly due to suppression of NK cells, which are a source of IFN-gamma early in infection. The clear indication of protection by some cytokines in this prophylactic model appears to justify further study of the therapeutic effects of cytokine-expressing viruses in chronic bacterial infections, especially where a cytokine defect is suspected.

Animals↗
PubMed1997

Community hospitals and general practice: extended attachments for medical students.

The first year experience of an innovative experiment in undergraduate medical education is described. The study investigated the educational effectiveness of prolonged clinical attachments for medical undergraduates in community hospital-based general practice. It has also assessed the ability of students to take some responsibility for their own learning in a clinically challenging environment. A retrospective evaluation of the experience obtained during the 3 month attachments for a self-selected group of fourth year Dundee medical school undergraduates was made. These undergraduates were placed in 10 mainly rural Scottish general practices with attached community hospitals providing a wide spectrum of inpatient and outpatient medical and surgical care. Students were assessed on the satisfactory completion of a portfolio of learning experiences and a practical clinical skills list. They were also required to submit a clinical project based on some aspect of their work during the attachment. The initial results showed a high degree of student and tutor satisfaction with the attachments. The assessment of all 10 of the students' educational achievements in their attachment were regarded as satisfactory and two were assessed as outstanding. Tutor assessment confirmed the validity of the initiative. Prolonged attachments in community hospital-based general practice for medical undergraduates have proved educationally valid and popular with both students and tutors. The development and dissemination of this model on a wider scale has resource issues which require to be addressed.

Community Medicine↗
PubMed1996

Ocular tumoral calcinosis. A clinicopathologic study.

Tumoral calcinosis is a rare systemic disorder characterized by para-articular ectopic soft-tissue calcification. This case report describes the ophthalmic features (palpebral conjunctival calcific nodules, the white limbal girdle of Vogt, disc drusen, and angioid streaks) in a 38-year-old Asian woman who had tumoral calcinosis associated with hyperphosphatemia. A morphologic study of the calcified nodules on the palpebral conjunctiva disclosed deposition of hydroxyapatite crystals in an extracellular matrix (deposit) containing alcianophilic mucopolysaccharides. Excision of the eyelid nodules was not followed by recurrence.

Adult↗
PubMed1995

Therapy of human B-cell lymphoma bearing SCID mice is more effective with anti-CD19- and anti-CD38-saporin immunotoxins used in combination than with either immunotoxin used alone.

The CD19+ CD38+ human Burkitt's lymphoma cell line Ramos grows aggressively when injected intravenously (i.v.) into severe combined immunodeficient (SCID) mice, killing 100% of animals within a 33-42 day period with widely disseminated disease. Treatment commencing 7 days after i.v. injection of Ramos cells, with 3 doses of an anti-CD19 immunotoxin (IT; BU12-SAPORIN) or an anti-CD38IT (OKT10-SAPORIN) led to a significant prolongation of survival compared with sham-treated controls; the anti-CD38 IT gave the greatest prolongation of survival, but all treated animals eventually succumbed to disease. When both ITs were used in combination at equivalent dose levels, the therapeutic outcome was significantly improved over that obtained for single IT therapy, with 20% of animals surviving disease-free to 300 days. When anti-CD38 IT was given in combination with anti-CD19 antibody there was no therapeutic improvement over anti-CD38 IT used alone. However, when anti-CD19 IT was given in combination with CD38 antibody, a significant prolongation of survival ensued over that obtained with anti-CD19 IT alone, though this was not as significantly pronounced as that obtained when both ITs were used in combination and was only as good as the survival obtained with OKT10 antibody used alone. CD19 and CD38 are expressed on the surface of the vast majority of B-cell lymphoma and common acute lymphoblastic leukaemia cells, and our findings provide a sound rationale for a combination immunotoxin trial in these diseases directed against both these target molecules.

ADP-ribosyl Cyclase↗