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Biomedical subjects

G O Littlejohn

Publications and source records attributed to G O Littlejohn.

At least 19 recordsLinked to original sources
PubMed2000

Longterm methotrexate use in rheumatoid arthritis: 12 year followup of 460 patients treated in community practice.

OBJECTIVE: To extend our observations on the longterm tolerability of methotrexate (MTX) and reasons for discontinuation in a cohort of 460 patients with rheumatoid arthritis (RA). METHODS: We studied all patients with RA who started MTX before June 1986 and attended the community based private practices of 6 rheumatologists in Melbourne. Information to at least April 1, 1995, or within one year of death was updated from the patient's medical records to include MTX discontinuation and reasons for discontinuation. Addition of disease modifying antirheumatic drugs (DMARD) concomitant with MTX was noted. Survival analyses based upon life table methods were used with MTX discontinuation as the observable endpoint. Three different definitions of MTX discontinuation were used (1) according to whether the patient was taking the drug at last followup irrespective of any periods of temporary discontinuation; (2) MTX discontinuation for > 3 months considered to be a treatment endpoint; and (3) addition of concomitant DMARD considered to be only partial success of MTX (as a need for additional therapy to meet treatment goals). RESULTS: At 12 years, 53% of patients were continuing to take MTX (irrespective of any periods of temporary discontinuation). If discontinuation of the drug for 3 or more months was considered a treatment termination then 38% were still taking the drug at 12 years, and if addition of concomitant DMARD was regarded as a treatment endpoint only 17% of patients were continuing MTX at 12 years. Withdrawal for gastrointestinal toxicity declined over time but the risk of other adverse effects appeared to persist over time. CONCLUSION: MTX in RA is well tolerated over the longer term, with > 50% of patients starting MTX in a community based rheumatology private practice continuing to take it 12 years later. However, a substantial number of patients had 2nd line therapies added over this time. Monitoring for toxicity should continue throughout the course of therapy.

Antirheumatic Agents↗
PubMed1999

Three year follow-up of body composition changes in pre-menopausal women with systemic lupus erythematosus.

OBJECTIVES: To measure the change in body composition in a pre-menopausal female systemic lupus erythematosus (SLE) population over 3 yr, and to identify predictors of change in body composition including the effects of disease-, corticosteroid (CS)- and patient-related variables. METHODS: All 55 pre-menopausal females with SLE who participated in a cross-sectional study of body composition in 1994 were invited to undergo interview, examination, medical record review, and body composition assessment by dual-energy X-ray absorptiometry (DXA). RESULTS: Twenty-eight subjects participated with a mean (S.E.M.) age of 34.4 (1.6) yr, duration of SLE of 6.8 (0.8) yr and mean (range) time to follow-up of 3.2 (2.9-3.4) yr. Seventeen subjects were exposed to CS during the study period with a mean (range) daily dose of prednisolone of 12.0 (2.8-22.9) mg. There was a significant increase in body mass index (BMI) (24.53+/-0.83 vs 25.37+/-1.04, P = 0.03) and fat-free mass (41.04+/-0.83 vs 41.53+/-0.92, P = 0.05) over the 3 yr period. Univariate analysis revealed that change in fat-free mass was significantly associated with change in total body bone mineral density (BMD) (P = 0.03). Stepwise multiple linear regression analysis revealed a significant independent association of disease activity with increases in both BMI (r2 = 0.41, P = 0.006) and fat mass (r2 = 0.39, P = 0.007), and of exercise and Modified Health Assessment Questionnaire with an increase in fat-free mass (r2 = 0.51, P = 0.007). Age at SLE diagnosis and smoking were significant independent predictors for loss of total body BMD, while CS duration was predictive of an increase in total body BMD (r2 = 0.80, P < 0.0001). CONCLUSION: In this SLE population, disease activity was predictive of deleterious changes in body composition, including increases in BMI and fat mass. Patient-related variables were also important predictors of body composition change with exercise independently predicting an increase in fat-free mass, and smoking predictive of loss of total body BMD. In contrast, CS-related variables were not found to have harmful effects on body composition. Change in fat-free mass, and not fat mass, was predictive of change in total body BMD.

Absorptiometry, Photon↗
PubMed1999

Stress system response and rheumatoid arthritis: a multilevel approach.

A growing body of research indicates that the stress system, and its interactions with the immune system, play a pivotal role in the aetiology and progression of rheumatoid arthritis (RA). The stress system has multiple levels and comprises physiological, psychological and environmental components. However, most investigations in RA that involve the stress system tend to focus on the interrelationships between neuroendocrine and immune function, and related disease activity, with little regard for the role of other aspects of stress system activation, including psychological variables. This is despite the fact that psychological stressors, and related psychological variables, are known to influence RA disease activity. This article aims to explore the multiple levels of stress system activation and how they may ultimately influence disease-related outcomes in RA. Some measurement issues of psychological stress will also be examined.

Arthritis, Rheumatoid↗
PubMed1999

The safety and efficacy of cyclosporine (Neoral) in rheumatoid arthritis.

OBJECTIVE: To assess the safety and efficacy of cyclosporine (Neoral), its steroid sparing effect, and its usefulness in combination therapy with methotrexate (MTX) in the treatment of refractory rheumatoid arthritis (RA). METHODS: All patients given cyclosporine for refractory RA over a 21 month period were included in an open, prospective study. Patients were reviewed initially fortnightly then monthly with clinical evaluation and serum creatinine. There were no restrictions on the use of other disease modifying agents, nonsteroidal antiinflammatory drugs, or corticosteroids. RESULTS: Forty-six patients with severe RA were included in the study, 33 (72%) female and 13 (28%) male, with a mean age of 54.8 years (range 20-74). At the completion of the study 30 (65%) were still taking cyclosporine at a mean dose of 2.94 mg/kg/day for a mean duration of 10.5 months. Thirteen patients discontinued cyclosporine due to side effects, most commonly gastrointestinal, and 3 due to inefficacy. Thirty-seven of the 46 patients were taking prednisolone at the start of the study at a mean dose of 10.36 mg/day, which decreased to 7.068 mg/day at the end of the study (p < 0.001). Thirty patients used cyclosporine in combination with MTX. The mean dose of MTX decreased from 15.08 to 13.67 mg/wk (p = 0.02). The mean serum creatinine increased by 13% from 74 to 83.7 micromol/l. Patients who continued therapy had a shorter duration of disease, with a mean of 9.93 years compared to 15.73 years in those who stopped therapy (p = 0.004). CONCLUSION: Cyclosporine (Neoral) was a safe and effective therapy in this population of patients with RA refractory to standard therapy. We observed a significant steroid sparing effect and have shown that combination therapy with MTX does not increase side effects and allows for a decrease in MTX dose. Renal function is not adversely affected if guidelines are followed.

Adult↗
PubMed1998

Pregnancy outcome in systemic lupus erythematosus (SLE): a review of 54 cases.

AIM: To compare the pregnancy outcome, in particular gestational age and birth weight in women with systemic lupus erythematosus (SLE) diagnosed before and after pregnancy, and to review data on presence or absence of the antiphospholipid (aPL) antibody and flares of disease activity. METHOD: Case histories were reviewed of women with a diagnosis of SLE and an obstetric event attending Monash Medical Centre (MMC) over an eight year period (1988-96). Fifty-four pregnancies in 28 women were studied, with 44 occurring after the diagnosis of SLE (Group 1) and ten prior to the diagnosis of SLE (Group 2). RESULTS: In Group 1 there were 25 live births (63%) with 16 full term and nine premature deliveries, 12 spontaneous abortions, three foetal deaths in utero and four elective terminations. In Group 2 there were seven live births (70%), two spontaneous abortions and one foetal death in utero. The mean gestational age of live births was 35.8 weeks and 39.2 weeks respectively (p < 0.001). The mean birth weight of live births was 2448 g and 3030 g respectively (p < 0.023). a PL antibodies were positive in eight of 26 women tested with three live births and were negative in 18 of 26 women with 12 live births. Flares of disease activity occurred in 17 of 28 pregnancies. CONCLUSION: Pregnancy in women with a predisposition to SLE have a high risk of an adverse outcome. Clinical disease confers an additional risk. The mean gestational age and birth weight were significantly less in women with established disease. Mild flares in disease activity resulted in a favourable outcome while renal flares had a worse outcome.

Adult↗
PubMed1998

The antiphospholipid antibody syndrome.

BACKGROUND: Recurrent miscarriages cause enormous distress and despair for sufferers. In a small number of patients this condition forms part of the antiphospholipid antibody syndrome. The anticardiolipin antibodies became quantifiable in 1983, which has meant that those suffering with this condition could be identified. OBJECTIVE: This article reviews the current understanding of this condition and offers an approach for managing patients with various components of this syndrome. DISCUSSION: The decision to screen for these antibodies is sometimes difficult as they can be presented in the normal population. However, by identifying the patient suffering with this condition, treatment can offered which may prevent a further miscarriage or a pregnant patient suffering a thromboembolic episode.

Abortion, Habitual↗
PubMed1997

Methotrexate use in systemic lupus erythematosus.

Low dose pulse oral methotrexate (MTX) is a well established treatment for rheumatoid arthritis, and short term open studies have suggested beneficial effects of MTX in SLE. This study was designed to investigate MTX treatment maintenance rates in SLE using life table analysis, and to determine whether MTX use was associated with a dose reduction of concomitant steroid therapy. All SLE patients managed by physicians affiliated with a single centre were studied cross-sectionally. Information regarding disease variables and drug use were ascertained by interview and chart review. Drug therapy data including dates of treatment and indications for treatment were analysed using Kaplan-Keier life table methods. Among 101 subjects with SLE, 25 MTX treatment episodes were observed in 24 subjects. The period studied totalled 19766 patient-days, with a median (range) duration of observed MTX treatment of 14.4 (5.1-41.6) months. The median (range) initial and peak MTX doses with 7.5 (2.5-10)mg/wk and 10 (7.5-15) mg/week respectively. The principal indication for commencing methotrexate therapy was arthritis. Only two subjects terminated treatment for toxicity, with the most common reason for termination being remission. The cumulative probability of continuing treatment was 68% at 12 months and 61% at 24 months, or 75% and 71% respectively if cessations for remission were excluded. The median (interquartile range) monthly steroid intake during MTX therapy [279.4 (193.4-492.9)mg] was somewhat lower than during the 6 months prior to [298.1 (237.9-531.4)428.8)mg] MTX therapy, but this difference was not significant. A total of 36% of subjects reduced their steroid dose during MTX therapy, but this reduction was not significant. Treatment of SLE with MTX, predominantly for arthritis, was well tolerated over prolonged periods of observation. Toxicity of sufficient severity to lead to treatment termination was uncommon. A subset of subjects were able to reduce steroid intake during MTX therapy, but no overall reduction in steroid dose was observed.

Adult↗
PubMed1995

A database for fibromyalgia.

FMS is a complex condition mainly characterized by the presence of chronic pain. The nature of this complaint thus demands assessment in a hierarchal fashion of the various components of the pain system ranging from the nociceptor through to complex central pain-processing mechanisms. The condition is common and represents the most important defined chronic pain syndrome. Elucidation of the mechanisms and better management of FMS will result in improved knowledge of a whole range of related chronic pain syndromes. The database in FMS is necessarily large but does need to be focused according to the need of the person constructing the database and the need of the individual with FMS. As our understanding of FMS evolves, better ways of assessing the various dimensions of the problem will be devised. Perhaps the challenge we face is to bring all the parts together. In doing so, we may find there is a single essential component that links all the clinical features together, which correlates well with severity, disability and outcome, which is amenable to treatment programs, and which is measurable. The search for the soul of the "elephant" of FMS continues.

Disability Evaluation↗
PubMed1994

Flow cytometric detection of anti-neutrophil cytoplasmic autoantibodies.

An intracytoplasmic immunofluorescence staining technique which allows the detection and quantification of anti-neutrophil cytoplasmic autoantibodies (ANCA) by flow cytometry is described. A polymorph neutrophil population from human peripheral blood was used in this study as indicator cells. These were fixed and permeabilized by paraformaldehyde, Tween 20 and saponin, to allow ANCA in the patients sera to reach their intracellular antigen targets. The numbers of indicator cells remained unaltered by the permeabilization protocol and no cell aggregation or loss of intracellular antigenicity was observed. An excellent agreement (91% (207/228)) between ANCA detection by immunofluorescence microscopy (IF) and flow cytometry was noted. Compared with IF assay, the flow cytometric method has a sensitivity of 93% (42/45) and a specificity of 90% (165/183). Although not able to discriminate between P-ANCA or C-ANCA, this flow cytometric method has the advantage of providing an objective, reproducible and quantitative measure of ANCA, which makes it an ideal technique for screening of patients sera for ANCA reactivities.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Altered heat pain thresholds and cerebral event-related potentials following painful CO2 laser stimulation in subjects with fibromyalgia syndrome.

A decrease in mechanical pressure pain thresholds, particularly over pre-designated tender points, is one of the defining characteristics of fibromyalgia syndrome (FS); however, changes in thermal pain sensitivity have not been investigated. The present study examined heat pain thresholds and cerebral event-related potentials following CO2 laser stimulation in 10 subjects with FS and 10 age-matched control volunteers. The results indicate that patients with FS exhibit a significant reduction in heat pain threshold when tested on the dorsal surface of the hand. In accordance with previous research, we also found a decrease in mechanical pain threshold over pre-designated tender points and at control sites as well as a significantly larger mechanically induced neurogenic flare response. These measures were highly correlated with thermal pain threshold even though different anatomical sites were stimulated. Hence, it seems likely that FS patients display a multimodal change in pain sensitivity which is generalized rather than anatomically restricted. Patients with FS also displayed a significant increase in the peak-to-peak amplitude of the cerebral potential evoked by CO2 laser stimulation at pain threshold intensity and 1.5 times pain threshold intensity. These findings suggest a greater activation of central nervous system (CNS) pathways following noxious input. Putative explanations for the increased CNS response are discussed, including mechanisms of peripheral nociceptor sensitization, altered CNS function and the role of psychological factors.

Adult↗
PubMed1994

Fibromyalgia syndrome and disease activity in systemic lupus erythematosus.

To study the effect of fibromyalgia syndrome (FS) on the expression of systemic lupus erythematosus (SLE) and on the measurement of disease activity, we performed a cross-sectional study of subjects with SLE. Eighty-seven subjects were studied and 22 (25.3%), all female, had FS (Yunus' criteria). Disease activity and organ system involvement were assessed using the systemic lupus activity measure (SLAM) and using 10 cm visual analogue scales (VAS) completed by both physician and patient. No significant difference between FS and non-FS groups in the objective measurement of disease activity was present, median (range) SLAM scores being 5 (0-18) and 6 (0-24), respectively (NS). Similarly, expression of SLE, as measured by the prevalence of specific organ system involvement, was similar in the two groups. In contrast the prevalence of glucocorticoid use, antibodies to DSDNA and fulfilling four ACR criteria was higher in the non-FS group. The rating of SLE disease activity was affected by concomitant FS. Physician and patient disease activity VAS correlated significantly with SLAM scores in non-FS subjects (P < 0.001, Spearman analysis), whereas in FS subjects, neither physician nor patient VAS correlated with SLAM scores. We conclude that FS is prevalent in individuals with SLE and does not affect disease expression but may interfere with the rating of disease activity.

Adult↗