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M J Ahern

Publications and source records attributed to M J Ahern.

At least 55 records · Page 3Linked to original sources
PubMed1998

Pathogenic mechanisms in the rheumatoid nodule: comparison of proinflammatory cytokine production and cell adhesion molecule expression in rheumatoid nodules and synovial membranes from the same patient.

OBJECTIVE: To investigate the production of proinflammatory cytokines and expression of cell adhesion molecules in the rheumatoid nodule. METHODS: Cytokine content (tumor necrosis factor alpha [TNFalpha], interleukin-1beta [IL-1beta], and IL-1 receptor antagonist [IL-1Ra]), at the messenger RNA (mRNA) and protein levels, and cell adhesion molecule expression were studied in 16 rheumatoid nodules and 6 synovial membranes. RESULTS: Macrophages in the rheumatoid nodules contained TNFalpha, IL-1beta, and IL-1Ra mRNA and protein, particularly in perivascular cells of the stroma and in the palisading layer. All cell adhesion molecules studied were expressed in both the rheumatoid nodules and synovial membranes, with increased expression of E-selectin in the rheumatoid nodule compared with the synovial membrane, and with the absence of vascular cell adhesion molecule 1 expression on cells of the palisading layer in the rheumatoid nodule. CONCLUSION: The presence of similar proinflammatory cytokines and cell adhesion molecules in the rheumatoid nodule and synovial membrane suggests that similar pathogenic processes result in the chronic inflammation and tissue destruction in these lesions.

Adult↗
PubMed1998

South Australian Scleroderma Register: analysis of deceased patients.

The demographic, clinical, pathological and serological features of 123 decreased patients with systemic sclerosis have been analysed. These patients consisted of all identified patients dying with this disease in South Australia between 1983 and 1996 inclusive. There were 85 females and 38 males, with the ratio of limited:diffuse:overlap disease subset being 9:5:1. Disease characteristics revealed that patients with the limited disease tended to be female with high frequencies of the centromere autoantibody, while patients with the diffuse disease had equal gender representation with the frequent presence of nucleolar, speckled or homogeneous antinuclear antibody. Mean duration of disease and mean age of death for the limited:diffuse:overlap subsets differed significantly between groups (p < 0.05) and were 16.5, 9.3 and 10.9 years and 71.9, 57.8 and 52.8 years respectively. Cumulative survival curves for the subsets differed highly significantly, with patients with the limited diseases dying more commonly from right heart failure (documented terminally in 25% of the centromere positive limited subset), cardiovascular disease or cancer, while patients with the diffuse subset died from respiratory failure, renal failure or cardiovascular disease. In conclusion, this retrospective analysis has revealed that scleroderma is a relatively common but clinically heterogeneous disorder. There are important clinical and prognostic implications in defining limited versus diffuse versus overlap disease.

Adult↗
PubMed1997

Effects of pulse methylprednisolone on inflammatory mediators in peripheral blood, synovial fluid, and synovial membrane in rheumatoid arthritis.

OBJECTIVE: To establish whether the clinical efficacy of pulse methylprednisolone (MP; 1,000 mg intravenously) is related to the modulation of proinflammatory cytokines within the peripheral blood, synovial membrane, or synovial fluid compartments. METHODS: Eighteen patients with active rheumatoid arthritis (RA) were studied. Peripheral blood (11 patients) and knee synovial fluid (9 patients, 10 knees) were obtained before and at 4 and 24 hours after MP therapy. Interleukin-1beta (IL-1beta), IL-8, and tumor necrosis factor alpha (TNFalpha) were measured by enzyme-linked immunosorbent assay and biologic assays; prostaglandin E2 (PGE2) was measured by competitive radioimmunoassay. In 10 patients, arthroscopically directed synovial biopsies were obtained before and at 24 hours after treatment, at disease relapse (4 patients), and after retreatment (1 patient). Membranes were stained by immunohistochemical techniques with monoclonal antibodies against TNFalpha, IL-8, IL-1beta, and the IL-1 receptor antagonist protein (IL-1Ra). RESULTS: MP therapy was associated with a rapid (within 24 hours) and substantial decrease in the expression of TNFalpha in the lining and sublining regions of the synovial membrane, as well as substantial decreases in the levels of TNFalpha in serum and synovial fluid. There was also reduced IL-8 expression in the synovial lining, as well as reduced synovial fluid IL-8 levels. No effect on synovial membrane IL-1beta and IL-1Ra or synovial fluid IL-1beta and PGE2 was found. CONCLUSION: MP therapy rapidly reduces IL-8 and TNFalpha levels in the synovial compartment, with cytokine changes in the serum and synovial fluid reflecting the changes in the synovial membrane. Alterations in TNFalpha expression in the synovial membrane correlated with clinical response to, and subsequent relapse after, MP therapy.

Aged↗
PubMed1997

A technique for obtaining repeated liver biopsies from rats.

Many morphological, pharmacological and toxicological studies of hepatotoxicity require frequent sampling of liver over time. In the past this has been achieved by including large numbers of animals in the study and killing subgroups at different times. In this paper we describe a technique for repeated liver biopsy that procures sufficient liver tissue for histopathological assessment and for additional studies, for example measurement of hepatic iron concentration or vitamin A measurement. The advantages and disadvantages of this technique are discussed.

Animals↗
PubMed1997

Use of artificial sweeteners to promote alcohol consumption by rats.

Cirrhosis may be reliably produced in rats by exposing them intermittently to low levels of carbon tetrachloride vapour while feeding alcohol in the Lieber-DeCarli liquid diet. Providing the alcohol in drinking water that has been sweetened with sucrose is a cheaper and more convenient method but it does not yield reliable results. This study aimed to determine whether alcohol in drinking water sweetened with artificial sweeteners would give adequate alcohol intake to achieve the desired hepatic effects. Rats were fed alcohol (8% v/v) in drinking water sweetened with sucrose (5% w/v) (n = 12), or with one of the artificial sweeteners aspartame (0.025%), saccharin (0.025%) or cyclamate (0.05%) (n = 8 per agent). During the alcohol treatment the animals were exposed to carbon tetrachloride vapour, 40 ppm, six hours per night for five nights per week, over a period of 14 weeks. All groups achieved good alcohol intakes of 5-6 g/kg/day. Only one rat, in the aspartame group, became cirrhotic; all the others had varying degrees of fibrosis which did not differ significantly among the treatments. Although it was not effective in reliably achieving cirrhosis, sweetening the alcohol solution with artificial sweeteners led to reasonable alcohol intakes with resultant hepatic fibrosis, and without the high carbohydrate intake which occurs when sucrose is used.

Alcohol Drinking↗
PubMed1997

Dose-related effects of dietary iron supplementation in producing hepatic iron overload in rats.

The influence of varying the level of supplemental dietary iron on the development of hepatic iron overload was examined in rats. Two days after giving birth, Porton rats were fed a diet supplemented with 0, 0.5, 1 or 2% carbonyl iron, to institute dietary iron supplementation to the young via breast milk. After weaning, the offspring continued to receive the assigned diet until 32 weeks of age. Liver biopsies were taken from some rats at 8, 16 and 24 weeks of age and from all rats at 32 weeks of age, for assessment of iron overload. For both male and female rats, hepatic iron content was increased in a dose-related manner by feeding supplemented diet. Hepatic iron content of male rats tended to reach a plateau after 8, 16 weeks of supplementation, while that of female rats continued to rise throughout the experimental period, such that the hepatic iron content of female rats was 2.8-fold that of similarly treated males at 32 weeks of age. Iron supplementation was associated with only moderate retardation of growth. By choosing an appropriate level of iron supplementation, good (grade III-IV) hepatic iron loading can be achieved with minimal adverse effects on the animals' overall health.

Animals↗
PubMed1997

Variability in cytokine and cell adhesion molecule staining in arthroscopic synovial biopsies: quantification using color video image analysis.

OBJECTIVE: To investigate the variability in immunostaining for cytokines and cell adhesion molecules using multiple arthroscopically directed synovial biopsies from within a rheumatoid knee joint, quantitated by color video image analysis. METHODS: Needle arthroscopic biopsies were taken from multiple sites (4-7 sites) around a knee joint in 8 patients with rheumatoid arthritis (RA). In 5 patients, immunoperoxidase staining for the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin 8 (IL-8), and IL-1beta as well as the IL-1 receptor antagonist protein (IL-1ra) was performed. In 3 patients, immunoperoxidase staining for the cell adhesion molecules E-selectin (CD62E), P-selectin (CD62P), intercellular adhesion molecule 1 (ICAM-1, CD54), and platelet endothelial cell adhesion molecule (PECAM, CD31) was performed. Immunostaining was quantified using color video image analysis. RESULTS: The overall probability of paired biopsies from the same RA knee joint being significantly different from each other due to sampling variation was at most 22% for cytokine staining (usually less than 10%). There were no significant differences between intrabiopsy and interbiopsy variability for cell adhesion molecule staining of the sublining and vessels. CONCLUSION: The variability in cytokine and cell adhesion molecule staining within any single biopsy usually reflects the variability between biopsies taken from different sites in the same rheumatoid joint when the immunostaining is quantified using color video image analysis. Therefore, only a small number of synovial biopsies are required to accurately determine the cytokine and cell adhesion molecule expression in a single joint.

Aged↗
PubMed1996

Neutrophil trafficking into inflamed joints in patients with rheumatoid arthritis, and the effects of methylprednisolone.

OBJECTIVE: To investigate the trafficking of circulating blood neutrophils and synovial fluid neutrophils in rheumatoid arthritis (RA) patients and the influence of a 1,000-mg intravenous pulse of methylprednisolone succinate (MP). METHODS: Neutrophils were isolated from the circulation and from the knee synovial compartments of subjects with RA. Circulating neutrophils were labeled with technetium-99 hexametazime (99mTc-HMPAO) and reinjected intravenously. Synovial fluid neutrophils were labeled from indium-111 oxine and reinjected into the knee from which they were isolated. Gamma camera images were obtained at intervals up to 24 hours post MP. Each patient had a baseline study (no MP) and a study in which MP was administered either 4 hours before (2 patients), 10 minutes before (1 patient), or 30 minutes to 1.5 hours after (6 patients) injection of the radiolabeled neutrophils. Subsequent analysis allowed quantitation of the neutrophil uptake into and clearance from the knee as a function of time. RESULTS: Nine patients who had not received glucocorticoids in the previous 3 months were studied. MP significantly decreased neutrophil ingress in 13 of the 16 knees studied (almost total inhibition in 5 knees), and this occurred within 1.5 hours of MP administration in all except 1 knee. At 24 hours after MP administration, there was a significant increase in visual analog scale (VAS) scores for well-being and significant decreases in scores on the modified Health Assessment Questionnaire (P<0.05), tender joints (P<0.005), VAS for pain (p<0.005), and generalized stiffness (P<0.005), as well as a decrease in the C-reactive protein level (P<0.05). MP had no effect on neutrophil egress (2 patients). Two additional patients who were receiving oral glucocorticoids were studied. One of them was clinically unresponsive to oral prednisolone, and MP had no effect on neutrophil ingress. The other patient showed no neutrophil ingress during the baseline study. This was confirmed by the presence of a noninflammatory synovial fluid at arthrocentesis. CONCLUSION: Neutrophil ingress into and egress from inflamed joints can be accurately monitored using radiolabeled neutrophils and quantitative gamma camera imaging. MP rapidly and substantially decreases neutrophil ingress into inflamed joints. In contrast, MP has no effect on neutrophil egress from the joint.

Aged↗
PubMed1996

Effects of pulse methylprednisolone on cell adhesion molecules in the synovial membrane in rheumatoid arthritis. Reduced E-selectin and intercellular adhesion molecule 1 expression.

OBJECTIVE: To investigate the effects of a 1,000-mg intravenous pulse of methylprednisolone succinate (MP) on cell adhesion molecule expression on the synovial vascular endothelium in patients with rheumatoid arthritis (RA). METHODS: Sequential arthroscopic biopsy samples were taken before and 24 hours after MP administration (10 patients) and at the time of RA flare (2 patients) and after retreatment with MP (1 patient). Immunoperoxidase staining for E-selectin (CD62E), P-selectin (CD62P), intercellular adhesion molecule 1 (ICAM-1; CD54) and platelet-endothelial cell adhesion molecule (PECAM; CD31) was performed, and the staining was quantified by color video image analysis. RESULTS: MP caused a rapid (within 24 hours) and substantial decrease in the expression of E-selectin on the synovial vascular endothelium, with a smaller reduction in ICAM-1 expression on synovial vascular endothelium and the synovial lining. There were no similar effects on synovial membrane P-selectin or PECAM expression. CONCLUSION: A potential mechanism by which MP impairs neutrophil trafficking into inflamed RA joints might be by reducing E-selectin, and possibly, ICAM-1, expression in the synovial membrane.

Aged↗
PubMed1996

Rheumatic manifestations of the myelodysplastic syndromes: a comparative study.

BACKGROUND: The myelodysplastic syndromes (MDS) are a group of common haematological disorders that increase in incidence with age. Case reports have suggested an arthritis associated with myelodysplasia. This comparative study reviews patients with myelodysplasia and patients with a myeloproliferative disorder (MPD) as the control group. AIM: To document the rheumatological manifestations in patients with MDS and to determine if there is an association between MDS and an inflammatory arthritis/vasculitis. METHODS: Between July 1990 and July 1995 all patients with a known diagnosis of MDS and MPD attending the Haematology clinics of two teaching hospitals were reviewed. There were 87 MDS patients and 86 MPD patients identified. Twenty-six of the MDS patients and 28 of the MPD patients attended a clinical review by a single examiner. A history of joint symptoms, skin rashes, family and drug history was obtained. Physical examination and serology were routinely performed. The case notes of the remaining patients were reviewed by a single observer. Approval was obtained from the Ethics Committee at both hospitals. RESULTS: The two patient groups were matched for sex and age. There were equal numbers of patients with osteoarthritis, rheumatoid arthritis and crystal arthritis in the two groups. The significant finding was the presence of a seronegative inflammatory arthritis in five patients in the MDS group. One patient had both a seronegative arthritis and a cutaneous leukocytoclastic vasculitis, and another a cutaneous leukocytoclastic vasculitis only. These rheumatic manifestations were not seen in the MPD group. Five of six patients were treated with prednisolone and responded impressively. The rheumatological symptoms preceded the diagnosis of MDS in two of the six cases. CONCLUSIONS: A seronegative arthritis is an associated finding in MDS. The arthritis can precede the development of the bone marrow disorder, and can be a guide to the diagnosis of this haematological disorder in elderly patients presenting with an inflammatory arthritis and cytopenias.

Aged↗
PubMed1995

Effects of ex vivo manipulation on the expression of cell adhesion molecules on neutrophils.

In vitro studies of neutrophil adhesion generally utilise purified populations and are often performed at 37 degrees C. This study determines the effects of temperature changes and neutrophil separation procedures on the expression of cell adhesion molecules on neutrophils. We found that neutrophil separation procedures involving erythrocyte sedimentation and hypotonic lysis are associated with a significant increase in the expression of both a structural and functional epitope of the beta 2 integrin CD11b, an increase in the expression of sialyl Lewisx (CD15s) and the hyaluronate receptor (CD44) as well as a significant decrease in L-selectin (CD62L) expression. Separated neutrophils are also more resistant than unseparated neutrophils to PMA induced upregulation of a functional epitope of CD11b. Incubating neutrophils at 37 degrees C is associated with increases in the expression of structural and functional epitopes of CD11b. Neutrophil separation is also associated with increases in the expression of both structural and functional epitopes of CD11b which is greater when neutrophil separation is performed at room temperature compared with neutrophil separation at 0-4 degrees C. However, this difference is lost when the latter are incubated at 37 degrees C. Furthermore, neutrophil separation at both 0-4 degrees C and room temperature is associated with a significant increase in CD15s expression. This increase is less when separation is performed at room temperature. These findings suggest that neutrophil separation should be performed at room temperature unless the cells are going to be used at 0-4 degrees C. Researchers using purified neutrophil populations need to be aware of these significant structural and functional changes when extrapolating in vitro results to in vivo situations.

Antibodies, Monoclonal↗
PubMed1995

Regulatory effects of IL-13 on synovial fluid macrophages and blood monocytes from patients with inflammatory arthritis.

Activated macrophages are central to the destructive processes of chronic inflammatory arthritis. In this study, it was hypothesized that IL-13, a product predominantly of 'Th2-type' lymphocytes, may be used therapeutically to down-regulate monocyte/macrophage activities at sites of chronic inflammation. Synovial fluid mononuclear cells were isolated from 12 patients with chronic inflammatory arthritis. Peripheral blood mononuclear cells (PBMC) were isolated at the same time as synovial fluid cells from all 12 patients. IL-13 significantly inhibited lipopolysaccharide (LPS)-induced tumour necrosis factor-alpha (TNF-alpha) production by mononuclear cells from peripheral blood, but not synovial fluid. In contrast, IL-13 inhibited LPS-induced IL-1 beta production by all cells, and as a positive response to IL-13, CD23 expression was increased on both cell populations. Blood monocytes cultured for 7 days with granulocyte-macrophage colony-stimulating factor (GM-CSF) or M-CSF responded to IL-13 in a manner similar to that detected for synovial fluid-derived cells, with suppression of LPS-induced IL-1 beta, but not TNF-alpha, production. In all experiments, the responses to IL-13 were very similar to those detected to IL-4, but differed from those measured with IL-10. Thus, the responses to IL-13 by synovial fluid cells and cultured monocytes are not equal to those of blood monocytes. The similar responses to IL-4 and IL-13 support claims of a common element for signalling from the IL-4 and IL-13 receptors. Furthermore, the activity of a common receptor chain may be altered by monocyte activation and differentiation.

Antigens, CD↗
PubMed1995

A study of scleroderma in South Australia: prevalence, subset characteristics and nailfold capillaroscopy.

BACKGROUND: Scleroderma is a systemic rheumatic disorder seen in a wide range of clinical specialties. AIMS: To establish the prevalence and mortality rates of scleroderma in South Australia (SA), to determine the relative frequency and characteristics of the three principal subsets (diffuse, limited and overlap), and to examine the role of nailfold capillaroscopy in subset identification and implied prognosis. METHODS: Outpatient and discharge diagnostic indexes from five major teaching hospitals in SA were reviewed between February 1987 and November 1993. A total of 215 patients with scleroderma were identified. Case notes of 115 of these patients were reviewed in order to validate scleroderma diagnosis, and subset characteristics such as sex, mean age at diagnosis, extent of skin involvement, internal organ involvement and serology were analysed. Fifty-two of these patients were then examined prospectively to confirm positive discharge diagnosis, and nailfold capillaroscopy was performed on these patients. RESULTS: The point prevalence of scleroderma in SA for 1993 was estimated to be 208/10 This figure is a conservative estimate and is higher than most other reported series. The female to male ratio was 4:1. The majority of patients had limited disease with a ratio of 6:1:1.6 limited vs diffuse vs overlap. Systemic involvement excluding the oesophageal components limited disease was found predominantly in the diffuse group. Autoimmune serology was positive in 90% of patients, with Scl-70 being more common in diffuse scleroderma, anti-centromere antibody (ACA) in the limited form and anti-ribonucleoprotein (RNP) in the overlap form. Nailfold capillaroscopy was useful in predicting disease-subtype as capillary dilatation was observed predominantly in limited disease, capillary dropout in diffuse disease. CONCLUSIONS: Scleroderma is more common in SA than previously recognised. Limited disease is more common than diffuse or overlap disease, carries a better prognosis and in associated with ACA. Nailfold capillaroscopy is a useful tool in disease assessment and may provide useful diagnostic and prognostic information.

Adolescent↗