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K Gaffney

Publications and source records attributed to K Gaffney.

At least 19 recordsLinked to original sources
PubMed2006

Low-dose infliximab treatment for ankylosing spondylitis--clinically- and cost-effective.

OBJECTIVES: Infliximab has been shown to be effective in the treatment of ankylosing spondylitis (AS) when treated in a dose of 5 mg/kg at 6 weekly intervals. This dose of infliximab has not been determined by any structured randomized trials and has significant cost implications. We describe our experience of treating AS with low-dose infliximab (3mg/kg at 8 weekly intervals). The efficacy and cost implications are discussed. METHODS: Patients who had active AS [Bath AS Disease Activity Index (BASDAI) > or = 4] were treated with infliximab 3 mg/kg at 0, 2, 6 weeks and thereafter at 8 weekly intervals. Response to treatment was defined as 50% improvement in BASDAI. Other response criteria such as ASAS 20, 40 and five of the six criteria were also assessed. Direct drug costs for infliximab were determined. RESULTS: Twenty-two consecutive AS patients received infliximab. All 22 completed treatment for 3 months, 15 patients for 6 months and 14 for 12 months. Mean age was 45 years (range 21-62) and mean disease duration 14.5 years (range 2-43). Of the patients, 54% achieved a 50% BASDAI response at 3 months and the benefit was sustained at 12 months in 63%. Similar response rate was seen with the other assessment criteria. Direct drug costs were significantly lower when low-dose infliximab regimen was used. CONCLUSIONS: Low-dose infliximab (3 mg/kg at 8 weekly infusions) is effective in the treatment of AS. Higher doses are required in a small proportion of patients when treatment is only partially effective. Titrating the dose and frequency of infusions may be required in individual patients to achieve optimal response. Using low-dose infliximab has significant economic implications.

Adult↗
PubMed2005

Methotrexate-induced pancytopenia: serious and under-reported? Our experience of 25 cases in 5 years.

OBJECTIVE: To ascertain the extent of methotrexate (MTX)-related pancytopenia at the Norfolk and Norwich University Hospital (NNUH) between 1999 and 2004. METHODS: Patients were identified by a department database search, review of pharmacy records and personal communication. Pancytopenia was defined as white blood cell count (WBC) <3.5 x 10(9)/l, haemoglobin (Hb) <11 g/dl and platelet count <130 x 10(9)/l. Severe pancytopenia was defined as WBC <2.0 x 10(9)/l, Hb <10 g/dl and platelet count <50 x 10(9)/l. RESULTS: Twenty-five patients had MTX-induced pancytopenia. Eleven patients were taking folic acid and one folinic acid. The median dose of MTX was 12.5 mg weekly (interquartile range 5.625 mg) and median duration of treatment 36 months (interquartile range 40.5 months). The severity of pancytopenia correlated with the dose (P = 0.04). The numbers of patients with potential risk factors were: renal insufficiency, 8; pre-existing folate deficiency, 7; age >75 yr, 15; hypoalbuminaemia, 18; pre-existing infection with hip prosthesis, 1; possible drug interactions, 18; dosing errors, 1; and polypharmacy, 15. Pancytopenia was detected by routine blood monitoring in nine patients. There were seven deaths (28% mortality), five from sepsis and two from acute myeloid leukaemia. CONCLUSION: This is the largest reported individual case series of MTX-induced pancytopenia. With the increasing long-term use of MTX, it is important that patients be monitored for haematological side-effects as pancytopenia can be a late manifestation. Pharmacogenetics may hold the answer to predicting who is at risk of this potentially fatal complication of MTX.

Aged↗
PubMed2004

Chronic periaortitis.

Chronic periaortitis commonly involves the infrarenal portion of the abdominal aorta. Idiopathic retroperitoneal fibrosis, inflammatory abdominal aortic aneurysm and perianeurysmal retroperitoneal fibrosis are its various clinical presentations. They present as a non-specific systemic inflammatory disorder and may lead to ureteric obstruction and consequent renal failure. An exaggerated inflammatory response to advanced atherosclerosis has been thought to be the main pathogenetic process. Autoimmunity has also been proposed as a contributing factor. Contrast-enhanced CT scanning is the diagnostic test of choice. Steroids and immunosuppressive agents are successfully used in the treatment of idiopathic retroperitoneal fibrosis and selected cases of inflammatory abdominal aortic aneurysm, and surgery is used in others. Early diagnosis is important in order to reduce morbidity from complications such as renal failure and mortality from aortic rupture.

Aged↗
PubMed2003

A near fatal case of the dapsone hypersensitivity syndrome in a patient with urticarial vasculitis.

Dapsone (4,4'-diaminodiphenyl sulphone) is used for a variety of dermatological conditions including immunobullous diseases and urticarial vasculitis. Side-effects are common and include lethargy, headaches, methaemoglobinaemia and haemolysis. Severe adverse effects are rare but the dapsone hypersensitivity syndrome is well recognized. Symptoms include fever, haemolytic anaemia, lymphocytosis and hepatitis. We report a near fatal case of the dapsone hypersensitivity syndrome in a patient with urticarial vasculitis. This diagnosis should be remembered in any patient who becomes unwell whilst taking dapsone.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Osteopontin gene is expressed in the dermal papilla of pelage follicles in a hair-cycle-dependent manner.

Hair follicle formation and maintenance involve intimate interactions between follicular epithelial cells and a group of specialized mesenchymal cells known as the dermal papilla. Using the random primer polymerase chain reaction, we have identified an approximately 1.4 kb osteopontin mRNA that is present in large quantities in cultured rat vibrissa dermal papilla cells but undetectable in cultured rat skin fibroblasts. In situ hybridization showed that the osteopontin gene is expressed in dermal papilla cells of pelage follicles during catagen but not in anagen or telogen. As an acidic glycosylated RGD-containing extracellular matrix protein, osteopontin can function both as a cell attachment protein and as a soluble cytokine playing roles in signaling, cell migration, tissue survival, anti-inflammation, and T-cell-mediated cellular immunity. Our results indicate that the comparison of the mRNA of cultured dermal papilla cells and fibroblasts can lead to the identification of not only anagen-specific genes (e.g., nexin 1), but also a catagen-specific gene. We have thus provided evidence that specific genes are turned on during catagen, which is therefore not simply a passive "degenerative" phase. The functional role of osteopontin in catagen is unclear but it may promote the formation of a tightly aggregated dermal papilla, and/or protect the dermal papilla cells from apoptosis induced by cytokines or hypoxia during catagen.

Alopecia↗
PubMed2001

Benchmarking: the five year outcome of rheumatoid arthritis assessed using a pain score, the Health Assessment Questionnaire, and the Short Form-36 (SF-36) in a community and a clinic based sample.

BACKGROUND: Treatment, and therefore outcome, of rheumatoid arthritis (RA) will improve in the next few years. However, improvement in outcome can only be judged against the probability of certain outcomes with current conventional treatment. AIM: To document the five year outcome of RA in the late 1990s. SETTING: Norfolk Arthritis Register (NOAR). DESIGN: Longitudinal observational cohort study. METHODS: 318 patients with recent onset inflammatory polyarthritis recruited by NOAR in 1990-91 completed five years of follow up. Four groups were assessed: the whole cohort, all those referred to hospital, those who satisfied criteria for RA at baseline, and those referred to hospital who satisfied criteria for RA at baseline. Outcome was assessed with a visual analogue scale for pain, the Health Assessment Questionnaire (HAQ), and the Short Form-36 (SF-36). RESULTS: Of the RA hospital attenders, 50% had a visual analogue scale pain score of 5 cm or less and an HAQ score of 1.125 or less. SF-36 scores were reduced in all domains. Results are presented as cumulative percentages. CONCLUSIONS: These results can be used for comparison and to set targets for improvement.

Adult↗
PubMed2001

A swollen leg unmasks longstanding SLE.

We report a case of long-standing SLE which presented with symptomatic muscle vasculitis on a background of photosensitivity, arthralgia and myalgia. The diagnosis was complicated by cardiomyopathy, nephrotic syndrome and diabetes. We highlight the benefits of aggressive treatment in severe disease and the importance of recognising and treating comorbidity especially ih relation to atherosclerosis.

Adult↗
PubMed1998

Quantitative assessment of the rheumatoid synovial microvascular bed by gadolinium-DTPA enhanced magnetic resonance imaging.

OBJECTIVE: To examine the relation between rate of synovial membrane enhancement, intra-articular pressure (IAP), and histologically determined synovial vascularity in rheumatoid arthritis, using gadolinium-DTPA enhanced magnetic resonance imaging (MRI). METHODS: Dynamic gadolinium-DTPA enhanced MRI was performed in 31 patients with knee synovitis (10 patients IAP study, 21 patients vascular morphometry study). Rate of synovial membrane enhancement was quantified by line profile analysis using the image processing package ANALYZE. IAP was measured using an intra-compartmental pressure monitor system. Multiple synovial biopsy specimens were obtained by a blind biopsy technique. Blood vessels were identified immunohistochemically using the endothelial cell marker QBend30 and quantified (blood vessel numerical density and fractional area). RESULTS: Median blood vessel numerical density and fractional area were 77.5/mm2 (IQR; 69.3-110.7) and 5.6% (IQR; 3.4-8.5) respectively. The rate of synovial membrane enhancement (median 2.74 signal intensity units/s, IQR 2.0-3.8) correlated with both blood vessel numerical density (r = 0.46, p < 0.05) and blood vessel fractional area (r = 0.55, p < 0.02). IAP did not influence the rate of enhancement. CONCLUSIONS: Gadolinium-DTPA enhanced MRI may prove to be a valuable technique for evaluating drugs that influence angiogenesis.

Adult↗
PubMed1997

A modified form of low-density lipoprotein with increased electronegative charge is present in rheumatoid arthritis synovial fluid.

Reactive oxygen species (ROS) are pro-inflammatory factors in the pathogenesis of rheumatoid arthritis. During inflammation, the amount of low-density lipoprotein (LDL) in the inflamed joint is increased. LDL is known to be susceptible to oxidation by ROS. Oxidized LDL may serve as a mediator for joint damage, further exacerbating the inflammatory process. LDL isolated from synovial fluid and plasma from individual patients (paired samples) with rheumatoid arthritis or osteoarthritis was characterized by crossed immunoelectrophoresis. On analysis by this technique, synovial fluid LDL from most patients with rheumatoid arthritis contained two peaks: one corresponding to normal plasma native LDL, and the other having an increased electrophoretic mobility associated with oxidized LDL. Paired plasma LDL samples contained native LDL alone, as did paired synovial fluid and plasma LDL from patients with osteoarthritis. Thus, in addition to native LDL, a second form of LDL was shown to be present in rheumatoid synovial fluid, which had properties consistent with those of oxidized LDL.

Aged↗
PubMed1997

Intra-articular pressure profile of the knee joint in a spectrum of inflammatory arthropathies.

OBJECTIVES: The intra-articular pressure (IAP) rises significantly after isometric quadriceps contraction in patients with rheumatoid synovitis, a process that may temporarily impede synovial blood flow and cause oxidative injury. In acute traumatic knee effusions (ATE) pressure rises are trivial. This study compared the IAP profiles of patients with ATE with three different populations--an acute synovitis on the background of a chronic inflammatory arthropathy, a chronic low grade inflammatory arthropathy, and an acute intermittent inflammatory arthropathy. The study objective was to discover if the pressure profiles observed in these groups reflect an influence of the inflammatory process or time or both. METHODS: Thirty three patients were studied. These were divided into four subgroups; group 1: five acute traumatic knee effusions (ATE); group 2: acute effusions on the background of a chronic inflammatory arthropathy: seven rheumatoid arthritis (RA), five psoriatic arthritis (PsA); group 3: seven osteoarthritis (OA) and group 4: acute effusions on the background of an intermittent inflammatory arthropathy: seven pyrophosphate arthropathy (PA), one amyloid (AA), one Behcet's (B). IAP was measured (mm Hg) at rest and during isometric quadriceps contraction using the hand held portable 295-1 intra-compartmental pressure monitor system (Stryker UK). The volume of synovial fluid aspirated was recorded. RESULTS: Expressed as medians (inter-quartile range). Resting IAP was; ATE 6 (2-12), RA 8 (5-47), PsA 18 (11-31), OA 17 (7-21), PA 25 (9-29), AA 14, and B 12. IAP increased in all subjects during isometric contraction; ATE 9 (7-16), RA 56 (33-150), PsA 52 (43-85), OA 56 (20-116), PA 53 (41-65), AA 47, B 57 and the IAP rise was significant (p < 0.05) in all except the ATE group (p > 0.05). The volume of synovial fluid aspirated in groups 2, 3, and 4 correlated significantly with the magnitude of the IAP change (r = 0.45, p < 0.05). CONCLUSION: The IAP rise during isometric quadriceps contraction is a feature of all patients with an inflammatory based effusion irrespective of the duration of the effusion. This is not the case in patients with an ATE. In inflammatory synovitis the rise in intra-articular pressure with isometric quadriceps contraction relates to effusion volume. It is concluded that the inflammatory process prevents reflex muscle inhibition, a locally protective mechanism that minimises the potential for intermittent ischaemia/oxidative injury.

Acute Disease↗
PubMed1996

Activation of the transcription factor nuclear factor-kappaB in human inflamed synovial tissue.

OBJECTIVE: The transcription factor nuclear factor kappaB (NF-kappaB) has been implicated in the inflammatory response and is known to be activated by a process involving reactive oxygen intermediates. The purpose of the present study was to demonstrate the presence and distribution of activated NF-kappaB in synovium samples from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and from autopsy subjects with no known history of arthritis. METHODS: Immunohistochemical staining was performed using both polyclonal and monoclonal "activity-specific" antibodies to the Rel-A (p65) subunit of NF-kappaB (anti-Rel-A nuclear location sequences). Histologic features of inflammation were also scored. RESULTS: Both antibodies demonstrated positive staining of synovial tissue, with a cellular distribution that was nuclear. The staining was associated with specific cell types within the tissue, in particular, type A synoviocytes and vascular endothelium. Notably, lymphoid aggregates were unstained. Using the monoclonal antibody, a further study was carried out to investigate the distribution of staining in tissues from patients with different disease activities and clinical diagnoses, as well as in normal control tissue obtained at autopsy. Patients with acute RA more commonly showed vessel staining (P = 0.05) and, conversely, showed less frequent staining of the synovial lining (P < 0.005) compared with OA patients. Synovial tissue from controls exhibited either no staining or only weak staining in the synovial lining. CONCLUSION: The activation of NF-kappaB in vascular endothelium and type A synovial lining cells is a feature of synovial tissue from both RA and OA patients. The distribution of this staining appears to be related to the clinical diagnosis.

Aged↗