Biomedical subjects

M J Ahern

Publications and source records attributed to M J Ahern.

At least 73 records · Page 4Linked to original sources

PubMed1995

Illness behaviour in patients with arthritis.

OBJECTIVES: To determine if there are specific patterns of illness behaviour in patients with arthritis, and if abnormal patterns of illness behaviour are associated with withdrawal from trials of anti-inflammatory drugs, and to examine which aspects of illness behaviour are perceived by rheumatologist to be related to the disease process. METHODS: The illness behaviour questionnaire (IBQ) was administered to 211 patients with rheumatoid arthritis (RA) and 107 patients with osteoarthritis (OA) participating in five drug trials of NSAIDs at the beginning of the studies, and was commented upon by 17 clinical rheumatologists. RESULTS: Factor analysis of 211 patients with RA produced a unique factor solution. RA patients were more preoccupied with their illness and its effects and worried more about their health than patients with OA. Patients who withdrew from drug trials showed behaviour patterns similar to those of chronic pain patients, and different from those of patients who completed the studies. When asked to account for a rheumatoid patient's response to the IBQ, rheumatologists focused on physical symptoms and did not recognise some of the psychological issues which patients saw as being relevant. CONCLUSIONS: We have demonstrated differences in illness behaviour between patients with OA and with RA. Patients withdrawing from drug trials of NSAIDs showed differences in illness behaviour compared with those successfully completing the trials. Rheumatologists underestimated the impact of the disease on their RA patients' psychological well being.

Adolescent↗

PubMed1995

Comparison of the suppressive effects of interleukin-10 and interleukin-4 on synovial fluid macrophages and blood monocytes from patients with inflammatory arthritis.

This study determined the potential capacity of interleukin-10 (IL-10), compared with IL-4, to control the production of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-1 receptor antagonist (IL-1ra) and the expression of major histocompatibility complex (MHC) class II antigens by monocytes/macrophages isolated from synovial fluid of patients with rheumatoid or other forms of chronic inflammatory arthritis. Mononuclear cells were isolated from synovial fluid and peripheral blood and incubated with or without lipopolysaccharide (LPS), and with or without IL-10 (100 U/ml, 10 ng/ml) or IL-4 (10 ng/ml) for 22 hr. TNF-alpha, IL-1 beta and IL-1ra levels were measured by enzyme-linked immunosorbent assay (ELISA) in the culture supernatants, and MHC class II expression was examined on the monocytes/macrophages by flow cytometry. IL-10, unlike IL-4, decreased TNF-alpha production by LPS-stimulated synovial fluid cells to the same extent as by LPS-stimulated peripheral blood cells from the same patients. IL-10 and IL-4 suppressed equally IL-1 beta production by the same cells. However, only IL-4 significantly increased IL-1ra production by synovial fluid mononuclear cells. Synovial fluid cells expressed increased levels of MHC class II antigen, and these levels were not as efficiently suppressed by IL-10 as they were for peripheral blood cells. Because IL-10 and IL-4 differentially regulate TNF-alpha and IL-1ra production by synovial fluid mononuclear cells, selective use of either IL-10 or IL-4 in the treatment of chronic inflammatory conditions will depend on whether TNF-alpha or IL-1, respectively, is established as primarily responsible for the maintenance of the chronic inflammatory condition.

Arthritis↗

PubMed1994

Cirrhosis in patients with rheumatoid arthritis receiving low dose methotrexate.

We describe three patients with RA who developed cirrhosis while taking low dose methotrexate (MTX). This report includes a review of the risk factors for cirrhosis occurring in association with MTX. Two of these patients were part of a prospective study to quantify changes in pericellular and total collagen in 76 patients with RA receiving low dose pulse MTX, giving a point prevalence of cirrhosis of 2.63%.

Aged↗

PubMed1994

Dose-response relationships in hepatic injury produced by alcohol and carbon tetrachloride.

Dose-response relationships were examined for the production of hepatic fibrosis and cirrhosis by combined exposure of male Porton rats to alcohol and carbon tetrachloride. Alcohol was administered orally in Lieber-DeCarli liquid diet at levels of 75, 150, or 300 kcal/liter, giving mean daily intakes of 2.29, 4.61, and 8.16 g/kg/day, respectively. Carbon tetrachloride was administered by inhalation at concentrations of 10, 20, or 40 ppm, 6 hr/night, 5 nights/week. Liver biopsies were taken at intervals up to a maximum treatment period of 20 weeks. All four rats that received the high dose of both agents, and 1 of 4 that received the medium alcohol and high carbon tetrachloride treatments, were cirrhotic by 10 weeks. Two of the 4 rats that received the low alcohol and high carbon tetrachloride dose were cirrhotic at 20 weeks. Cirrhosis was not observed in rats that received the low or medium carbon tetrachloride dose, but some degree of hepatic fibrosis was observed in all treatment groups. Severity of fibrosis was significantly associated with both dose of alcohol and dose of carbon tetrachloride received. It is concluded that, in the alcohol-carbon tetrachloride rat model for chronic liver injury, both alcohol and carbon tetrachloride contribute to the response in a dose-related manner. Hepatic injury was observed even when relatively low doses of these agents are administered together.

Alcohol Drinking↗

PubMed1994

The longterm effect of pulsed corticosteroids on the efficacy and toxicity of chrysotherapy in rheumatoid arthritis.

OBJECTIVE: To follow those patients who participated in a randomized, double blind placebo controlled trial investigating the effect of pulse methylprednisolone treatment in 60 patients with rheumatoid arthritis (RA) starting chrysotherapy. METHODS: Following completion of the original 24-week trial, 47 of the original 60 patients were reexamined between 32 and 67 weeks after completion of the original study. Patients were assessed by a composite clinical score, the Health Assessment Questionnaire (HAQ), erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor levels. RESULTS: At the end of the 24-week trial, the number of patients who responded well to therapy was significantly greater (p < 0.05) in the patients who had received methylprednisolone (17/30) compared with the placebo group (8/30). At the longterm followup assessment, the mean disability score (HAQ) was significantly less (p < 0.05) in patients receiving the initial steroid pulses. No significant difference in drug toxicity or the length of time that patients remained on gold, was observed between the 2 treatment groups. CONCLUSION: Our study supports a beneficial adjunctive role of pulse corticosteroids in patients with RA starting gold therapy.

Adult↗

PubMed1993

Synovial fluid macrophages and blood monocytes differ in their response to IL-4.

IL-4 has been described as a potential anti-inflammatory molecule because of its ability in vitro to down-regulate human monocyte production of proinflammatory mediators. In this study, the activity of IL-4 on mononuclear cells and CD14+ macrophages from a site of chronic inflammation, namely, the joints of patients with rheumatoid and psoriatic arthritis, was investigated and compared directly with its activity on PBMC and monocytes from the same patients. In contrast to the response by blood monocytes, the response to IL-4 by synovial fluid cells was selective; IL-4 did not significantly suppress LPS-induced TNF-alpha production, but decreased CD14 expression to a similar extent in the two cell populations. IL-4 induction of monocyte/macrophage CD23 expression was investigated as a stimulatory response to IL-4, and although significantly increased on synovial fluid CD14+ cells by IL-4, the induction was considerably reduced compared with that measured for blood cells. Activation and differentiation in vitro of blood monocytes reduced their response to IL-4 for decreased TNF-alpha production and induction of CD23 and suggested that these biologic phenomena may contribute to the decreased responsiveness to IL-4 by synovial fluid monocytes/macrophages. Thus, IL-4 does not have the same anti-inflammatory properties in vitro on synovial fluid cells as on blood monocytes.

Antigens, CD↗

PubMed1993

Clinical rheumatology training of Australian medical students. A national survey of 1991 graduates.

OBJECTIVE: To describe Australian medical graduates' knowledge, experiences and practical training in rheumatology and their attitudes towards rehabilitation and disability. DESIGN: Cross-sectional survey of all interns at randomly selected hospitals in each State. PARTICIPANTS: 382 Australian interns at 12 hospitals surveyed in the first week of their 1991 internship. RESULTS: New interns demonstrated little experience with soft tissue rheumatism, with only 45% reporting they had examined a patient with bursitis and 22% one with epicondylitis. There was considerable dissatisfaction with the teaching of assessment of low back pain, regardless of the amount of formal rheumatology teaching the graduates had experienced, with only 22% rating it as good or excellent. There was little evidence that students are exposed to the social dimensions of chronic illness; only 32% of students reported that they had been shown how to assess a patient's psychological adjustment to illness. Only 22% felt competent at assessing disability and handicap and less than half of the graduates studied had ever attended a clinic where there was a physiotherapist. Graduates who had never been attached to either a rheumatology ward or an outpatients clinic (17%) were less likely to have examined a patient with gout (P < 0.001), osteoarthritis (P < 0.01), or chronic low back pain (P < 0.05), and were more likely to report dissatisfaction with training in rheumatology. CONCLUSION: This survey suggests that there are significant problems in the training of medical students in musculoskeletal disorders, particularly in relation to the assessment of disability and the appreciation of psychosocial factors.

Adult↗

PubMed1993

The influence of renal function on the enantioselective pharmacokinetics and pharmacodynamics of ketoprofen in patients with rheumatoid arthritis.

1. Single oral doses of 100 mg racemic ketoprofen were given to 15 patients (age range: 51-79 years) with rheumatoid arthritis and a range of creatinine clearances (CLCR) from 26 to 159 ml min-1. 2. The fractions unbound of (R)- and (S)-ketoprofen in plasma were determined for each subject after in vitro addition of rac-ketoprofen (enantiomer range: 1.00-6.00 micrograms ml-1) to pre-dose plasma. 3. An index of the antiplatelet effect of ketoprofen in vitro was measured as inhibition of platelet thromboxane B2 (TXB2) generation during the controlled clotting of whole blood (pre-dose) spiked with rac-ketoprofen. 4. In vivo studies revealed significant associations (P < 0.05) between the reciprocal of AUC for both unbound and total (bound plus unbound) (S)-ketoprofen and CLCR. Corresponding relationships were also observed for the (R)-enantiomer of ketoprofen. In addition, the half-life of each enantiomer was negatively correlated with CLCR. There was a positive relationship between the 24 h urinary recovery of combined non-conjugated and conjugated (R)-ketoprofen and CLCR while that for the (S)-stereoisomer failed to reach statistical significance (P > 0.05). 5. There was no difference between AUC for (R)- and (S)-ketoprofen for either unbound or total drug. 6. The mean +/- s.d. percentage unbound of (S)-ketoprofen in plasma (0.801 +/- 0.194%) exceeded (P < 0.05) the corresponding value for its optical antipode (0.724 +/- 0.149%). The percentage unbound of the (S)-enantiomer was higher at 6.00 micrograms ml-1 than that at enantiomer concentrations of 3.50 micrograms ml-1 and below, where it was invariant. The percentage unbound of (R)-ketoprofen was independent of plasma concentration up to 6.00 micrograms ml-1. There were no correlations between the percentage unbound of each enantiomer and either serum albumin concentration or CLCR. 7. The relationship between the serum concentration of unbound (S)-ketoprofen and the percentage inhibition of platelet TXB2 generation was described by a sigmoidal Emax equation for each patient. There was no correlation between the unbound concentration of (S)-ketoprofen in serum required to inhibit platelet TXB2 generation by 50% (EC50) and CLCR. The mean +/- s.d. EC50 was 0.216 +/- 0.143 ng ml-1. 8. These data indicate that diminished renal function is associated with an increased exposure to unbound (S)-ketoprofen, presumably due to regeneration of parent aglycone arising from the hydrolysis of accumulated acyl-glucuronide conjugates. The apparent sensitivity of platelet cyclo-oxygenase to the inhibitory effect of (S)-ketoprofen was not influenced by renal function.

Administration, Oral↗

PubMed1992

Comparative evaluation of CD5 B cells in patients with rheumatoid arthritis and essential mixed cryoimmunoglobulinemia using FACS analyzer and FACSCAN flow cytometer.

In this study, using both a FACSCAN flow cytometer and the FACS analyzer, and two-color fluorescence, CD5 B cells have been enumerated in the peripheral blood (PB) of normal controls (NC) and patients with rheumatoid arthritis (RA) or essential mixed cryoimmunoglobulinemia (EMC). Using a FACSCAN flow cytometer, no significant difference was observed between the percentage of CD5 B cells in the NC (21.24% +/- 3.71) and RA (24.83% +/- 3.85), or EMC (21.03% +/- 6.38). Using the FACS analyzer, however, there was significant difference between the NC (9.14% +/- 3.82) and EMC (2.84% +/- 2.58) (p less than 0.05), but no significant difference between the NC and RA (7.17% +/- 2.55). Further analysis of 10,000 B cells selected by live gating showed that there were three populations of B cells, with the majority of B cells unstained, a small number of cells brightly stained for CD5 in the NC (3.78% +/- 1.09) or RA (2.80% +/- 0.96), and about 6.45% to 9.43% with intermediate staining in patients with RA and the NC, respectively. In addition, serum low molecular weight IgM (LMW IgM) from patients with RA was detected by an enhanced chemiluminescence detection system combined with a modified immunoblot technique. A significant linear correlation was observed between the percentage of CD5 B cells and the height of LMW IgM peak (r = 0.69, p less than 0.05).

Antigens, CD↗

PubMed1992

Rheumatic manifestations of infective endocarditis.

Rheumatic manifestations are common and varied in infective endocarditis. We performed a retrospective case analysis on 87 patients with 93 episodes of infective endocarditis admitted to Flinders Medical Centre over an 11 year period (1980-1990). Disabling musculoskeletal symptoms and signs were documented in 22 (25%) of the patients. Thirteen patients developed severe or moderately severe low back pain during their illness, two with radiological evidence of a septic discitis or vertebral osteomyelitis. Two patients developed polyarthralgia/arthritis, four had septic arthritis (all with acute Staphylococcus aureus endocarditis), three developed severe loin pain, two acute gout, two had severe buttock pain and sacroiliac joint tenderness and two each developed disabling jaw/facial pain, neck/scapular pain and flank pain respectively. Five patients presented initially to the orthopaedic or rheumatological unit for management of their musculoskeletal symptoms. Four of seven patients with Streptococcus bovis endocarditis demonstrated prominent low back pain supporting a previously noted association between this organism and back symptoms. Furthermore, in one patient who had three separate episodes of endocarditis involving three different organisms, florid back symptoms were only seen in the infective episode involving Streptococcus bovis.

Aged↗

PubMed1992

High dose oral methylprednisolone in patients with rheumatoid arthritis: pharmacokinetics and clinical response.

A commercially available 1.0 g intravenous (i.v.) dosage formulation of methylprednisolone, as the sodium hemisuccinate salt (Solu Medrol, Upjohn) was administered both parenterally and orally (pulse steroid therapy) on separate occasions, to eight elderly (mean 65 y) patients with active rheumatoid arthritis. The relative oral bioavailability of the sterol was 69.2%. Elimination of methylprednisolone was prolonged when given orally; the mean residence times were 7.23 h and 3.94 h for oral and i.v. administrations, respectively. Clinical response to pulse steroid therapy was no different with respect to route of administration. There were no significant differences in standard clinical and laboratory assessments of disease activity when the two therapies were compared. Oral administration of methylprednisolone in patients requiring high-dose pulse steroid therapy is convenient and avoids the discomfort and inconvenience associated with i.v. administration.

Administration, Oral↗

PubMed1992

A comparison of ketoprofen SR and sulindac in the elderly with rheumatoid arthritis.

The elderly (age > 65 years) are more vulnerable to side-effects induced by non-steroidal anti-inflammatory drugs (NSAIDs). We therefore performed a double-blind comparative study of ketoprofen SR and sulindac in patients with active rheumatoid arthritis, 65 years of age or older. Sulindac was chosen because of its possible renal sparing effects, and ketoprofen SR because of its short half life and sustained release delivery system. Eighty patients were entered. More patients withdrew from the study due to side-effects in the sulindac group; both treatment groups had a high incidence of side-effects during this study and during previous exposure to other NSAIDs, demonstrating that the elderly are susceptible to side-effects from NSAIDs.

Aged↗

PubMed1991

Hepatotoxicity in a rat model caused by orally administered methotrexate.

We undertook a dose-response study in Wistar rats to develop an animal model for methotrexate hepatotoxicity. Rats were given oral methotrexate in 300, 200, 150 and 100 micrograms/kg/day doses for variable lengths of time. The 300 micrograms/kg/day dose produced systemic toxicity; the animals needed to be killed early, and hepatotoxicity was not observed. The lower doses of methotrexate were tolerated for longer durations and were associated with hepatotoxicity in five of the five rats receiving 200 micrograms/kg/day, four of the five rats receiving 150 micrograms/kg/day and five of the five rats on 100 micrograms/kg/day. Within each treatment group the liver injury ranged in severity from focal necrosis of some zone 3 hepatocytes to confluent necrosis of zone 3. All five rats that received 100 micrograms/kg/day methotrexate for 6 wk showed continuing liver injury in the form of focal necrosis, cell lysis and enlarged Kupffer cells. In addition, three of the rats showed evidence of early hepatic fibrosis. We believe that this is the first experimental model in which oral methotrexate administration has been associated with hepatotoxicity. Further development of this model should provide valuable insights into the pathogenesis of methotrexate hepatotoxicity.

Administration, Oral↗

PubMed1991

A randomised double-blind trial of cyclosporin and azathioprine in refractory rheumatoid arthritis.

Fifty-two patients with severe rheumatoid arthritis (RA) from four Australian centres were randomised to receive cyclosporin A (CSA) (n = 25) or azathioprine (AZA) (n = 27) for six months. Initial mean doses of CSA and AZA were 4.2 mg/kg and 1.7 mg/kg respectively. The mean doses of CSA and AZA at six months were 3.4 mg/kg and 1.9 mg/kg. Assessments of side-effects and outcomes of benefit were made monthly by independent, blinded observers. Both treatment groups exhibited statistically significant improvement in standard outcome parameters when compared with baseline values. However, there were no statistically significant differences in these parameters between the two groups. There was a mean increase in serum creatinine concentration associated with CSA; no persons were withdrawn from the study for this reason. Seven CSA recipients (three gastrointestinal symptoms, two neurological symptoms, two other) and 12 AZA recipients (six gastrointestinal symptoms, four inefficacy, two other) withdrew from treatment prematurely. Seven CSA recipients became hypertensive and four required anti-hypertensive therapy. Adverse events not requiring cessation of therapy were more commonly seen among CSA patients. In this group of severely affected patients with RA both cyclosporin and azathioprine were effective therapies. CSA toxicities were predictable and manageable but required close monitoring.

Adult↗

PubMed1991

The musculo-skeletal examination: a neglected clinical skill.

One hundred and sixty-six patients admitted to general medical wards of a teaching hospital were examined on the day of discharge to determine whether they had been assessed for musculoskeletal disorders during their admission. Of these patients, 54.8% had musculo-skeletal symptoms with 17.5% having a significant rheumatological disorder which had been ignored. A history of musculo-skeletal symptoms was recorded in 40.4% of all patients and the examination in only 14.5%. This contrasted with the documentation of the cardiovascular (99.4%), respiratory (100%), gastrointestinal (97.6%) and central nervous (53%) systems' examination. Eighty per cent of symptomatic patients received either no treatment for their rheumatic disorder, or treatment that we regarded as suboptimal or inappropriate. Musculo-skeletal symptoms are common in patients admitted to medical wards, but are being inadequately assessed or at worst ignored. The omission of the musculo-skeletal system examination, in contrast to the almost universal inclusion of other systems' examination, demands correction. Undergraduate and postgraduate training programmes require re-evaluation. The implications of these findings are discussed.

Adult↗

PubMed1991

Two methods of assessment of methotrexate hepatotoxicity in patients with rheumatoid arthritis.

Serial liver biopsy specimens from 18 patients with rheumatoid arthritis receiving a weekly dose of methotrexate 7.5-20 mg for a minimum of 12 months were assessed semiquantitatively and by a microcomputer image analysis system. The semiquantitative histological method showed a significant increase in pericellular collagen and in overall disease while morphometry showed a significant increase in pericellular, perivenular, and portal tract collagen. There was a significant correlation between the two methods, but morphometry had the advantage of objectivity and efficiency. There was no correlation between the increase in collagen and the accumulated dose of methotrexate, which suggests that other factors in addition to methotrexate may contribute to liver injury.

Adult↗

PubMed1991

Hepatic methotrexate content and progression of hepatic fibrosis: preliminary findings.

Liver tissue from 16 patients with rheumatoid arthritis was studied. The patients had received low dose methotrexate weekly for a minimum of 12 months between two liver biopsies. The progression of pericellular fibrosis was measured by computerised image analysis. Extracts of these liver biopsy specimens were pooled into five samples according to the progression of hepatic fibrosis and analysed by high performance liquid chromatography. The concentrations of methotrexate, 2,4 diamino-N(10)-methylpteroic acid, and methotrexate polyglutamate were markedly increased in the samples obtained from the three patients who recorded the greatest increase in fibrosis. These preliminary data suggest that progression of hepatic fibrosis is related to the retention of methotrexate and metabolites in the liver.

Adult↗

PubMed1990

Autoantibodies in patients with juvenile chronic arthritis and their immediate family relatives.

Antibodies to nuclear antigens were assessed in 23 children with juvenile chronic arthritis (JCA) and 66 of their first degree relatives. Serum samples from 16 patients with JCA (70%) and nine relatives (14%) had antinuclear antibodies by indirect immunofluorescence. Antibodies against nuclear antigens in rabbit thymus extract or an erythroblastoid cell line (K562) were detected by countercurrent immunoelectrophoresis and immunoblotting in 16 patients (70%) and 39 family relatives (59%). Immunoblotting did not show any banding patterns common to all patients with JCA, though bands in the 43-45 kD range were detected in 5/23 patients. Anticardiolipin antibodies were found in 7/23 patients. In total, 18/20 families (90%) had members other than the probands with detectable autoantibodies. In five families immunoblotting showed common banding patterns between the probands and other members. This suggests that there might be an inherited trend towards autoimmune responses in some families of patients with JCA.

Antibodies, Antinuclear↗