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Biomedical subjects

P F Ryan

Publications and source records attributed to P F Ryan.

At least 19 recordsLinked to original sources
PubMed2000

Clinical manifestations of gout and their management.

Gout is an inflammatory response to deposition of monosodium urate crystals in and around joints. It is primarily a disease of adult men. In acute gout, treatment options include non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and corticosteroids, administered either intra-articularly, orally or parenterally. Asymptomatic hyperuricaemia does not require specific treatment, but should prompt screening for atherosclerosis risk factors, and general lifestyle modification to reduce serum urate levels. Gout presents differently in the elderly. Both women and men are affected, attacks are frequently polyarticular and in the upper limbs, and the gout may be associated with diuretic use, hypertension and renal impairment. In patients with peptic ulcer disease, selective COX-2 inhibitors provide another treatment option. In the presence of renal impairment, allopurinol is the treatment of choice for urate lowering therapy, but doses of allopurinol and colchicine must be adjusted. Urate lowering therapy should only be used if recurrent episodes of gout occur despite aggressive attempts to reverse or control the underlying causes. It should not be introduced or discontinued during an acute episode of gout, and gout prophylaxis (NSAIDs or colchicine) should be prescribed during the introduction of urate lowering therapy.

Adult↗
PubMed2000

Expression of osteoclast differentiation factor at sites of bone erosion in collagen-induced arthritis.

OBJECTIVE: To investigate the cellular mechanism of bone destruction in collagen-induced arthritis (CIA). METHODS: After induction of CIA in DA rats, a histologic study of the advanced arthritic lesion was carried out on whole, decalcified joints from the hindpaws of affected animals. To conclusively identify osteoclasts, joint tissue sections were stained for tartrate-resistant acid phosphatase (TRAP) enzyme activity, and calcitonin receptors (CTR) were identified using a specific rabbit polyclonal antibody. The expression of messenger RNA (mRNA) for the osteoclast differentiation factor (also known as receptor activator of nuclear factor kappaB ligand [RANKL]) was investigated using in situ hybridization with a specific riboprobe. RESULTS: TRAP-positive and CTR-positive multinucleated cells were invariably detected in arthritic lesions that were characterized by bone destruction. Osteoclasts were identified at the pannus-bone and pannus-subchondral bone junctions of arthritic joints, where they formed erosive pits in the bone. TRAP-positive multinucleated cells were detected within synovium and at the bone erosive front; however, CTR-positive multinucleated cells were present only at sites adjacent to bone. RANKL mRNA was highly expressed in the synovial cell infiltrate in arthritic joints, as well as by osteoclasts at sites of bone erosion. CONCLUSION: Focal bone erosion in CIA is attributed to cells expressing definitive features of osteoclasts, including CTR. The expression of RANKL by cells within inflamed synovium suggests a mechanism for osteoclast differentiation and activation at sites of bone erosion. Inhibitors of RANKL may represent a novel approach to treatment of bone loss in rheumatoid arthritis.

Acid Phosphatase↗
PubMed2000

Post-cardiac transplantation gout: incidence of therapeutic complications.

OBJECTIVE: To study the clinical impact of gout treatment following cardiac transplantation. METHODS: We performed an audit of all cardiac transplant recipients of the Alfred Hospital before August 1998 who lived in Victoria. RESULTS: We studied 225 patients (81% men), with a mean post-transplant follow-up of 50.8 months (SD 36). Forty-three (19%) had pre-transplant gout, 19 recurring post-transplantation. Twenty-three patients developed gout de novo. Of the 24 patients who received allopurinol, 6 developed pancytopenia and required hospitalization. Fourteen received a change in immunosuppression: in 5 patients following pancytopenia, and in 9 to enable safe use of allopurinol. Thirty-two patients received colchicine; 5 developed neuromyopathy. Impaired renal function, diuretic use, and hypertension were more common in this sub-group. Non-steroidal anti-inflammatory agents, used in 16 patients, caused serious complications in 1 patient (life-threatening peptic ulceration and hemorrhage, precipitating dialysis-dependent chronic renal failure). CONCLUSIONS: Cardiac transplant recipients, when treated for gout, are at high risk of therapeutic complications. Thus, gout treatment significantly affects care, health, and immunosuppression of these patients.

Adolescent↗
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↗
PubMed1998

Malignancy-associated remission of systemic lupus erythematosus maintained by autologous peripheral blood stem cell transplantation.

Many investigators worldwide are currently exploring the role of peripheral blood stem cell transplantation (PBSCT) in managing autoimmune diseases. We report the case of a woman with systemic lupus erythematosus (SLE) with mucocutaneous and renal involvement, who underwent PBSCT for stage IVB Hodgkin's disease. Following the development of the lymphoma, she has had a prolonged clinical and serologic remission of the SLE. The potential effects of lymphoproliferative disorders and PBSCT on the course of SLE are considered.

Adolescent↗
PubMed1998

The deleterious effects of low-dose corticosteroids on bone density in patients with polymyalgia rheumatica.

The beneficial effects of corticosteroid therapy in the treatment of rheumatic diseases may be offset by the occurrence of corticosteroid-related osteoporosis. This problem may be overcome by using low-dose corticosteroids; however, the dose of corticosteroids that is both efficacious and skeletal sparing is uncertain. Therefore, the aim of this study was to determine whether low-dose prednisolone treatment results in bone loss and modifies bone turnover. Nineteen patients (12 female, seven male) suffering from polymyalgia rheumatica received 10 mg or less daily, given in reducing dosage, with a range of 2.5-10 mg and an average of 6.0+/-0.2 mg daily (+/-S.E.M.). Prior to the commencement of therapy and at regular intervals during treatment, bone mineral density (BMD) using dual X-ray absorptiometry and circulating biochemical and hormonal determinants of bone turnover were measured. The patients were followed for 14.4+/-1.6 months (range 6-27). They were compared to 19 age-matched controls. Despite a mean exposure dose of 6 mg/day and disease remission, BMD decreased in the patients at the lumbar spine (2.6+/-0.8%, P < 0.01), femoral neck (2.9+/-1.5%, P=0.06), Ward's triangle (5.5+/-2.9%, P=0.06) and the trochanter (4.3+/-1.9%, P < 0.05). Total body bone mass decreased by 50+/-19 g in the first 6 months (P < 0.02), and by 39+/-30 g in the remaining 8 months of follow-up [not significant (NS)]. In the first 6 months, BMD decreased at the lumbar spine (1.7+/-0.9%, P = 0.06). From 6 months to the end of follow-up, BMD decreased by 8.5+/-3.5% at Ward's triangle (P < 0.05) and by 4.8+/-2.5% at the femoral neck (P=0.08). The fall in BMD correlated with the cumulative prednisolone dose at trabecular-rich regions (trunk r=-0.72, P < 0.001; ribs r=-0.53, P < 0.05). Bone resorption, assessed by urinary cross-laps, was 54.7% higher than controls before treatment was started (P < 0.05) and decreased by 23.5+/-7.1% in the first month of treatment when the mean prednisolone dose was 9.1 mg/day, range 5-10 (P < 0.0001). Serum osteocalcin was not suppressed by disease before treatment, decreased by 27.4+/-5.1% during the first month of treatment (P < 0.001), remained suppressed while the daily dose of prednisolone was > 5 mg/day, but returned to baseline below this dose. Serum parathyroid hormone was 19.3% lower in the patients than controls at baseline (NS), and increased by 46.1% (P < 0.05) but was no higher than controls at any time. Muscle strength increased by 20-60% (P < 0.05 to < 0.01). Prophylaxis should be considered in patients receiving > or = 5 mg/day prednisolone daily as bone loss is 2- to 3-fold expected rates. Earlier trabecular bone loss may predispose to spine and rib fracture; later cortical bone loss may predispose to hip fractures. Doses of prednisolone of < 5 mg daily may be skeletal sparing, but may not be efficacious.

Aged↗
PubMed1998

Systemic lupus erythematosus (SLE): changing concepts and challenges for the new millennium.

SLE is still the prototype experimental animal and human autoimmune disease. The clinical manifestations are so diverse that some have come to regard it as the incumbent 'luetic heir apparent' of the late 20th century. The aberrations of the immune disturbance have up until now defied clear explanation but have certainly generated a level of academic and research interest far greater than the frequency of the disease would initially suggest. The clear understanding of the immune derangements in SLE will probably lead to the understanding of the core mechanisms of the immune system and thus to better ways of its specific manipulation in the management of many other conditions including cancer. Research currently being undertaken on the mechanisms of control of immunologically mediated inflammation and the possible use of immunogenetic therapy in the treatment of various forms of SLE will hopefully further improve SLE related morbidity and mortality.

Adult↗
PubMed1998

Collagen induced arthritis in rats. Contrasting effect of subcutaneous versus intradermal inoculation of type II collagen.

OBJECTIVE: To determine the effect of subcutaneous (s.c.) as compared to intradermal (i.d.) inoculation of collagen type II (CII) in induction of collagen induced arthritis (CIA). METHODS: Dark Agouti (DA) and Lewis rats were injected with CII either i.d. or s.c.. A group of s.c. inoculated DA rats was re-injected with CII intradermally 45 days after first injection (s.c./i.d.). Arthritis was assessed by macroscopic scoring, histology, and immunohistochemistry. Levels of anti-CII antibody subtypes were measured by ELISA. RESULTS: Intradermal but not s.c. inoculation of CII resulted in histologically confirmed erosive arthritis in both Lewis and DA strains. Subcutaneous/intradermal inoculated DA rats developed mild CIA with lower arthritic scores and delayed onset. Lewis rats injected s.c. had lower levels of total Ig, IgG, IgG2a, and IgG2b and similar titers of IgG1 compared to i.d. inoculated rats. In contrast, only IgG2b levels were lower in s.c./i.d. compared to i.d. rats. CONCLUSION: Our data suggest that s.c. administration of CII tolerises animals against autoimmune CIA.

Animals↗
PubMed1997

Vasculitis and thrombotic thrombocytopenic purpura in a patient with limited scleroderma.

Inflammatory vasculopathy and thrombotic thrombocytopenic purpura (TTP) are rare complications of scleroderma. We report a 54-year-old woman with limited cutaneous scleroderma who developed medium size and small vessel vasculitis. Inflammatory changes of medium size muscular arteries presented as ovarian vasculitis and mononeuritis multiplex, while arteriolar involvement presented as TTP with associated central nervous system involvement. In addition, possible noninflammatory involvement of small muscular arteries was expressed as Raynaud's phenomenon.

Female↗
PubMed1994

Yttrium synovectomy in haemophilic arthropathy.

Between 1987 and 1991 we performed Yttrium-90 (Y-90) silicate radionuclide synovectomies on 40 joints of 20 haemophiliac patients with haemophilic arthropathy. All were male, their mean age was 31 yr and 15 of the 20 (75%) were HIV antibody positive. The number of joint bleeds and amount of factor (VIII and IX) replacement given in the 6 months pre- and 6 and 12 months post-radionuclide synovectomy was compared. Y-90 silicate synovectomy was shown significantly to reduce both the number of joint bleeds (P < 0.001) and factor usage (P < 0.001) in the 6 months after the procedure, a result maintained up to 12 months. Depot methyl prednisolone was co-administered with Y-90 but thought unlikely to contribute to joint response beyond 6 months. The reduction of joint bleeds and factor usage was even more dramatic in the 6- to 12-month period post-synovectomy although this was not reflected by the P value (P < 0.001). The reduction of joint bleeds and factor consumption post-synovectomy was most obvious in elbow joints, although the other joints as a group showed a significant reduction. Patients who were HIV antibody positive showed considerable improvement up to 12 months post-treatment, both in reduction of joint bleeds and as a consequence factor consumption. This improvement was seen to a lesser extent in the smaller HIV-negative group.

Adolescent↗
PubMed1993

Methotrexate therapy in rheumatoid arthritis: a life table review of 587 patients treated in community practice.

To determine whether methotrexate (MTX) maintains its effectiveness in rheumatoid arthritis (RA) in the setting of community based private rheumatology practice we used life table analysis to review the combined experience of a group of these practices. Of 587 patients with RA who started to take MTX, total termination rate at 70 months was 24.4% with most terminations prompted by drug toxicity. Older age (greater than 65 years) was associated with higher rates of toxicity. Treatment termination rates varied substantially between rheumatologists. We conclude that MTX therapy for RA is well tolerated and maintains effectiveness for at least 70 months.

Adult↗
PubMed1992

Systematic comparison of ILWAS, MAGIC, and ETD watershed acidification models: 3. Mass balance budgets for acid neutralizing capacity.

Three watershed acidification models-ILWAS, MAGIC, and ETD-were quantitatively compared to determine model structural differences by using a combination of input mapping and ANC mass balance budgets. Input mapping is a set of rules and algorithms to ensure that consistent input values were simultaneously derived for all three models. ANC budget analysis under current SO4(2-) deposition and a 70% reduction in SO4(2-) deposition allows examination of the relative importance of biogeochemical processes in affecting predictions of ANC or predicted changes in ANC. Model inputs were based on two dissimilar watersheds having characteristics typical of watersheds in the northeastern US. After mapping inputs, the three models predicted values of outflow ANC fluxes that were similar among the models for each watershed and deposition scenario. Within each watershed, the changes in outflow ANC fluxes between the scenarios were similar for the three models. Terrestrial weathering was the major source of ANC for all three models for both watersheds and deposition scenarios. The contributions of other processes to the ANC of the two watersheds were, under certain conditions, model-specific. Cation exchange was responsible for changes in ANC when deposition decreased for the three models. Other processes responsible for changes in ANC between scenarios were SO4(2-) sorption (for MAGIC) and in-lake weathering (for ETD). The processes responsible for the change in ANC from a change in deposition (cation exchange, SO4(2-) sorption, and in-lake weathering) were different from the processes contributing to the absolute ANC for a given deposition scenario (terrestrial weathering). The budget analysis complements an earlier Monte Carlo analysis that showed that the three models are structurally different and that predictions viewed on a relative scale are more similar than absolute scale predictions.

Journal Article↗