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Biomedical subjects

S Lynch

Publications and source records attributed to S Lynch.

At least 19 recordsLinked to original sources

Use of enoxaparin for the chronically anticoagulated patient before and after procedures.

Patients who require chronic anticoagulation and a procedure have been traditionally managed either by stopping warfarin and starting intravenous standard heparin or by adjusted dose subcutaneous standard heparin or taken off all anticoagulation for a week before the procedure. Enoxaparin may be useful as an alternative method of anticoagulation, avoiding hospitalization and the need for frequent monitoring.

Adult

Associations between perfectionism, mood, and fatigue in chronic fatigue syndrome: a pilot study.

This study investigated possible associations between perfectionistic personality traits, mood, and fatigue in chronic fatigue syndrome (CFS). Forty CFS sufferers referred to tertiary care and 31 control healthy subjects completed the Multidimensional Perfectionism Scale (MPS), Chalder Fatigue Questionnaire, and Hospital Anxiety and Depression (HAD) scale. Total perfectionism scores did not correlate with fatigue, anxiety, or depression in either group. Other-oriented MPS scores were significantly lower among CFS sufferers (p = .0019), especially women, and correlated negatively with physical fatigue levels overall (R = -0.27, p = .02). Total and socially prescribed MPS scores correlated with age for the CFS group alone (p = .05). Possible reasons why this study did not confirm a positive association between perfectionism and CFS are discussed. The finding that CFS sufferers set lower standards and have lower expectations for significant others may have implications for rehabilitation and recovery from this disorder.

Adult

Spur cell anaemia and hepatic iron stores in patients with alcoholic liver disease undergoing orthotopic liver transplantation.

BACKGROUND: Following orthotopic liver transplantation (OLT) histological examination of explant livers from patients with alcoholic liver disease (ALD) sometimes shows extensive iron deposits in a distribution suggestive of homozygous haemochromatosis. AIMS: To use haemochromatosis gene (HFE) assays to distinguish between ALD with notable siderosis and hereditary haemochromatosis. To evaluate the possible influence of spur cell haemolytic anaemia on hepatic iron loading. PATIENTS: Thirty seven patients with ALD were abstinent for at least six months prior to OLT. Twenty three patients had transferrin saturations greater than 55%, 16 also had increased serum ferritin (>350 micrograms/l). Eight of 37 (22%) explant livers had grade 3 or 4 hepatic iron deposition, predominantly in hepatocytes. Of these, four had a hepatic iron index greater than 1. 9 and most seemed to have spur cell haemolytic anaemia. METHODS: Mutation analysis for C282Y and H63D mutations was performed on DNA extracts from peripheral blood or explant liver. Spur cell haemolytic anaemia was diagnosed when the haemoglobin was 105 g/l in the presence of notable acanthocytosis. RESULTS: None of the eight patients with grade 3 or 4 hepatic iron had evidence of the C282Y mutation. Two of the eight were heterozygous for H63D. None of the remaining 28 patients tested showed homozygous HFE mutations. Spur cell anaemia was present in six of the eight patients with heavy iron deposition and only one of the remaining patients. CONCLUSIONS: The HFE mutation was not present in these patients with advanced ALD and heavy iron loading. Spur cell haemolytic anaemia provides an alternative potential mechanism for the heavy iron loading.

Adult

Anorganic bovine bone supports osteoblastic cell attachment and proliferation.

BACKGROUND: It was the aim of these studies to examine the ability of an anorganic bovine bone matrix material as an alternative to autogenous bone grafts and demineralized cadaver bone to support the attachment, spreading, and proliferation of isolated osteoblastic cells. METHODS: Primary culture osteoblastic cells were isolated from neonatal rat calvaria by sequential collagenase digestion. In the attachment studies, cells which had been labeled with 3H-leucine were incubated with the matrix material in sterile microfuge tubes for 15, 90, or 180 minutes or 24 hours. The attached cells were released and the radioactivity measured by liquid scintillation spectrometry. In the proliferation experiments, the cells were cultured with the matrix material for 24 hours and 3H-thymidine was added during the last 2 hours of the incubation. The cells were released and the radioactivity measured by liquid scintillation spectrometry. Scanning electron microscopy (SEM) was employed to observe osteoblastic cell interaction with the anorganic bone matrix. In these studies the cells were seeded on the bone graft material, then the material was removed and processed for SEM after 30, 60 or 120 minutes, or 24 or 48 hours. RESULTS: The cells attached to the matrix material in a time-dependent manner. There were significantly (P<0.05) more cells attached after 180 minutes than after the 15 and 90 minute incubations. The matrix material also supported proliferation of the attached osteoblastic cells. Cells seeded onto 100 mg of anorganic bovine bone resulted in significantly (P<0.05) more measurable proliferation than cells seeded onto 10 mg of material. The cells appeared to be round as they attached, then flatten and spread over time. There was also evidence of cellular processes extending into the pores of the material. CONCLUSIONS: These results demonstrate that this anorganic bovine bone graft material is able to support the attachment and proliferation of osteoblastic cells.

Animals

Divergent effects of paracetamol on reactive oxygen intermediate and reactive nitrogen intermediate production by U937 cells.

We investigated the effects of paracetamol on reactive oxygen intermediate and reactive nitrogen intermediate production by U937 cells. Cells which had been treated with paracetamol (0.01 microM - 10 microM) exhibited a significant (p<0.001) increase in hydrogen peroxide production and a significant (p<0.001) increase in phorbol 12-myristate 13-acetate induced superoxide production. Conversely, paracetamol (0.01 microM - 10 microM) caused a significant (p<0.001) decrease in the amount of nitrite secreted into the culture medium. Our results indicate divergent effects of paracetamol on ROI and RNI production.

Acetaminophen

Low plasma ascorbic acid independently predicts the presence of an unstable coronary syndrome.

OBJECTIVES: This study sought to investigate the relations between plasma antioxidant status, extent of atherosclerosis and activity of coronary artery disease. BACKGROUND: Previous studies indicate that increased antioxidant intake is associated with decreased coronary disease risk, but the underlying mechanisms remain controversial. METHODS: Plasma samples were obtained from 149 patients undergoing cardiac catheterization (65 with stable angina, 84 with unstable angina or a myocardial infarction within 2 weeks). Twelve plasma antioxidant/oxidant markers were measured and correlated with the extent of atherosclerosis and the presence of an unstable coronary syndrome. RESULTS: By multiple linear regression analysis, age (p < 0.001), diabetes mellitus (p < 0.001), male gender (p < 0.001) and hypercholesterolemia (p = 0.02) were independent predictors of the extent of atherosclerosis. No antioxidant/oxidant marker correlated with the extent of atherosclerosis. However, lower plasma ascorbic acid concentration predicted the presence of an unstable coronary syndrome by multiple logistic regression (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.40 to 0.89, p = 0.01). The severity of atherosclerosis also predicted the presence of an unstable coronary syndrome (OR 1.7, 95% CI 1.14 to 2.47, p = 0.008) when all patients were considered. When only patients with significant coronary disease were considered (at least one stenosis >50%), ascorbic acid concentration (OR 0.56, 95% CI 0.37 to 0.85, p = 0.008) and total plasma thiols (OR 0.52, 95% CI 0.34 to 0.80, p = 0.004) predicted the presence of an unstable coronary syndrome, whereas the extent of atherosclerosis did not. CONCLUSIONS: These data are consistent with the hypothesis that the beneficial effects of antioxidants in coronary artery disease may result, in part, by an influence on lesion activity rather than a reduction in the overall extent of fixed disease.

Aged

Correlation of platelet Fc gammaRIIA polymorphism in refractory idiopathic (immune) thrombocytopenic purpura.

Fc gammaRIIA, a low affinity receptor for IgG, is a polymorphic molecule: Fc gammaRIIA-HH131, Fc gammaRIIA-HR131 and Fc gammaRIIA-RR131. This polymorphism influences the efficiency of the receptor to bind with IgG2. Recent reports on altered distribution amongst individuals with heparin-induced thrombocytopenia (HIT) prompted us to examine the Fc gammaRIIA polymorphism in a cohort of patients with refractory idiopathic (immune) thrombocytopenic purpura (ITP), in whom severe disease had required them to undergo splenectomy. 29 post splenectomy ITP individuals and 61 normal controls were investigated. Polymerase chain reaction (PCR) and a Southern blotting technique were used to determine the Fc gammaRII polymorphism. Although the distribution of the allotypes of Fc gammaRIIA in the control population was similar to that found in other European studies of Caucasian populations (15 (25%) HH131; 35 (57%) HR131; 11 (18%) RR131), the patient group was skewed towards the RR131 allotype which has least efficiency for IgG2 binding (3 (10%) HH131; 12 (42%) HR131; 14 (48%) RR131; P<0.005). These findings suggest that Fc gammaRIIA polymorphisms may be implicated in the pathophysiology of ITP or may be responsible for modulating the immune response in this heterogeneous autoimmune disease.

Adolescent

Diagnosis of gluten-sensitive enteropathy: is exclusive reliance on histology appropriate?

OBJECTIVE: Coeliac disease is a prevalent disorder but frequently remains undiagnosed because of varied modes of clinical presentation. In this study, methods for the detection of coeliac disease were evaluated in a clinical practice setting. METHODS: Small intestinal histology, IgA anti-endomysial and IgG anti-gliadin antibody tests were performed on 441 unselected, consecutive patients under investigation for small intestinal disease. Response to treatment and other clinical events were monitored over the ensuing years. RESULTS: Untreated coeliac disease was diagnosed in 97 patients and was excluded in 344. At clinical presentation, the endomysial antibody test was positive in 84 of the 97 untreated coeliac patients (sensitivity 87%) and negative in 340 of the 344 non-coeliac patients (specificity 99%). A typical histological lesion was found in 83 of the 97 coeliac patients (sensitivity 86%) but was absent in all 344 non-coeliacs (specificity 100%). The sensitivity of the gliadin antibody test was 69% and the specificity was 71%. CONCLUSIONS: In unselected patients attending a gastroenterology clinic, small bowel histology and endomysial antibody serology show similar predictive value in the diagnosis of coeliac disease. These results emphasize that a combination of clinical, histological and serological criteria are required for effective diagnosis of this disorder. Exclusive reliance on histology or serology will result in failure to make a diagnosis in a significant proportion of patients.

Adolescent

Fetal pyelectasis: comparison of postnatal renal pathology with unilateral and bilateral pyelectasis.

The aim of this study was to determine the prenatal fetal pyelectasis which requires postnatal evaluation. This was a retrospective analysis involving 65 infants with complete urological follow-up; 59 had shown prenatal evidence of pyelectasis using previously published standards. Males were more common in both the normal (75 per cent) and the abnormal (77 per cent) postnatal outcome groups. Unilateral prenatal lesions were less common than bilateral, but had significant postnatal pathology in 47 and 26 per cent, respectively (n.s.). Persistent dilatation was likely to be associated with postnatal pathology. A 6 mm threshold of dilatation predicted the 19 infants with significant postnatal pathology. The majority of fetuses with pyelectasis in the study had normal outcomes, with males often showing 'transitory pyelectasis'. A repeat prenatal scan at 30-40 weeks' gestation is recommended for all fetuses where 6 mm or more of renal pelvic dilatation is detected prior to 28 weeks. Postnatal follow-up is required for persistent pyelectasis.

Dilatation, Pathologic

Human small intestinal epithelial cells secrete interleukin-7 and differentially express two different interleukin-7 mRNA Transcripts: implications for extrathymic T-cell differentiation.

The small intestinal epithelium, composed of epithelial cells (EC) and intraepithelial T lymphocytes, is exposed to numerous ingested antigens. Small intestinal EC may act as accessory and/or antigen presenting cells for intestinal T cells, some of which may mature extrathymically and regulate local immunity and tolerance. Since interleukin-7 (IL-7) plays an essential role in T cell maturation and activation, we examined its expression by human small intestinal EC. IL-7 was detected by ELISA in supernatants from 4 of 4 epithelial layer (EpL) cultures. Using RT-PCR, IL-7 mRNA was detected in 4 EpL studied, and two distinct IL-7 transcripts were identified in 3 of the 4. The ratios of the intensities of the larger to the smaller bands varied amongst individuals. Furthermore, the intensity ratios were higher in whole-thickness intestine and lamina propria preparations than in their corresponding EpL. This is the first report of the expression of two IL-7 transcripts in human intestine and of IL-7 secretion by human small intestinal EpL cells. This supports the hypothesis that small intestinal EC may influence differentiation and/or activation of neighboring T cells. The differential expression of the two transcripts may have important implications for immune regulation in the intestinal epithelium.

Biopsy

Endotoxin levels in donors and recipients during orthotopic liver transplantation.

BACKGROUND: The hypothesis being tested in this paper is that endotoxin levels in donors and in recipients during liver transplantation influences postoperative outcome. METHODS: Endotoxin levels in systemic venous and portal venous blood were measured using in 46 adult donors and 44 adult recipients (47 liver transplants) during the period 1992-95. Endotoxin was measured using a modification of the Limulus amoebocyte lysate (LAL) assay. RESULTS: In the donor, systemic endotoxin levels were above normal levels at 10.0 +/- 1.3 pg/mL from the start and rose to 15.8 +/- 2.9 pg/mL after dissection of the hilar structures, but fell to 10.6 +/- 0.8 pg/mL just prior to the removal of the liver (control = 7.8 pg/mL). The mean portal venous endotoxin levels were 18.2 +/- 3.4 pg/mL after dissection of the hilar structures and 12.6 +/- 0.9 pg/mL after cannulation of the portal vein. In the recipients, the highest level in the portal venous blood occurred at the end of the anhepatic phase (46.5 +/- 6.7 pg/mL). The systemic venous samples in the recipients were elevated to start with, but fell rapidly to 19.3 +/- 1.5 pg/mL 24 h postoperatively, and to 13.2 +/- 1.0 pg/mL by day 7. The endotoxin concentrations were higher in recipients who developed complications. CONCLUSIONS: Endotoxin is elevated throughout the recipient transplantation procedure and up to 7 days postoperatively. High levels of endotoxin at induction, the anhepatic phase and at certain time points correlated with patients who developed postoperative complications.

Adolescent

Serum levels of interleukins 8 and 10, interferon gamma, granulocyte-macrophage colony stimulating factor and soluble CD23 in patients with primary sclerosing cholangitis.

The presence of auto-antibodies and hypergammaglobulinaemia in patients with primary sclerosing cholangitis (PSC) suggest an overactive humoral immune system. Serum cytokines, measured using in-house double monoclonal sandwich ELISA, were used to assess the state of cellular and humoral immunity in this condition by comparison with sex and age matched normal controls and patients with alcoholic cirrhosis (AC). Soluble CD23 (sCD23) as a marker of humoral immunity was significantly elevated in PSC (N = 31) relative to patients with AC (N = 12) and the control group (N = 20) (P < 0.0001 and P < 0.001 respectively). Serum interleukin (IL) 10, as an anti-inflammatory cytokine and IL8, as a marker of neutrophil activation were significantly elevated in patients with PSC relative to those with AC and the controls (P < 0.001 and P < 0.05 respectively). Interferon gamma, as a marker of cellular immunity, and granulocyte-macrophage colony stimulating factor, a marker of monocyte/macrophage function were similar in all the groups. Cytokines and sCD23 were no different between patients with AC and the control group. While more than two thirds of the patients with PSC were positive for ANCA, there was no correlation between the presence of ANCA or ANCA titre and serum levels of either IL8, IL10 and sCD23. These results suggest exaggerated humoral immunity in PSC. The raised levels of IL10 and IL8 in PSC are discussed in the context of inflammatory bowel disease and liver dysfunction.

Adolescent