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Biomedical subjects

K Raza

Publications and source records attributed to K Raza.

At least 19 recordsLinked to original sources
PubMed2005

Infliximab leads to a rapid but transient improvement in endothelial function in patients with primary systemic vasculitis.

OBJECTIVE: To assess the immediate effects of tumour necrosis factor alpha (TNFalpha) blockade on endothelial function in systemic vasculitis. METHODS: Endothelial function was assessed by laser Doppler flowmetry in patients with active vasculitis after 10 infusions of infliximab. For comparison endothelial responses were assessed after five infusions of cyclophosphamide plus methylprednisolone. RESULTS: Endothelial dependent vasodilatation (EDV) improved significantly within 24 hours of infliximab infusion. The median change in red blood cell flux (interquartile range) was 5.7 (4.3-8.2) before infusion v 8.4 (7.5-10.9) at 24 hours; p=0.027. This was not maintained at day 14. No improvement was seen in EDV after cyclophosphamide plus methylprednisolone infusion. CONCLUSION: The rapid but transient improvement in EDV after TNFalpha inhibition suggests that TNFalpha may have a direct role in the impairment of endothelial function.

Adult↗
PubMed2003

Ultrasound guidance allows accurate needle placement and aspiration from small joints in patients with early inflammatory arthritis.

OBJECTIVES: To compare the accuracy of palpation-guided and high frequency ultrasound-guided needle placement in small joints and to develop a technique to obtain synovial fluid from these joints for diagnosis and research. METHODS: The accuracy of needle placement during palpation-guided proximal interphalangeal (PIP) or metacarpophalangeal (MCP) joint injection was assessed. This was compared with the accuracy of ultrasound-guided needle placement. A joint lavage technique was developed to obtain synovial fluid from these joints. RESULTS: Needle positioning was intra-articular in 59% of palpation-guided injections (6/12 PIP and 4/5 MCP joints). No fluid could be aspirated prior to injection. With ultrasound guidance, initial needle placement was intra-articular in 96% of cases (24/26 PIP and 27/27 MCP joints). Synovial fluid cells were lavaged from 63% of joints (19/25 PIP and 14/27 MCP joints). In only one case was a large effusion seen and this was aspirated directly. CONCLUSIONS: The use of high frequency ultrasound to guide needle placement within a small joint allows for significantly greater accuracy than a palpation-guided approach. When followed by lavage, synovial fluid cells and diluted synovial fluid can be obtained from the majority of small joints. This has important clinical and research implications.

Arthritis↗
PubMed2003

Diffuse endothelial dysfunction is common to ANCA associated systemic vasculitis and polyarteritis nodosa.

BACKGROUND: Excess cardiovascular mortality complicates systemic rheumatic disease, suggesting an accelerated atheromatous process, which it has been proposed relates to the vascular inflammation common in such diseases. Impaired endothelium dependent vasodilatation is an early marker of atheromatous disease. It has previously been shown that such endothelial cell dysfunction (ECD) occurring in the brachial artery can complicate primary systemic necrotising vasculitis (SNV). OBJECTIVE: To determine if ECD occurs in a wider spectrum of primary SNV, if it is restricted to the major arteries, and whether vasculitis subgroup, ANCA status, or renal involvement influenced the endothelial responses. METHODS: Fifty four patients attending the Birmingham vasculitis clinic, including patients with a range of ANCA and non-ANCA associated primary vasculitides, and a group of age matched controls were recruited. The length of patient follow up and disease activity was variable. Disease activity, damage scores, and cardiovascular risk factors were recorded before assessment of flow mediated brachial artery vasodilatation by high resolution ultrasound. Dermal microvascular responses to acetylcholine were also measured in 32 patients and 21 controls by laser Doppler flowmetry. RESULTS: ECD was demonstrated in all primary SNV subgroups of patients with ANCA associated vasculitis and in polyarteritis nodosa, compared with controls. Significant impairment occurred in both vascular beds, regardless of vessel size targeted in the inflammatory vasculitis, ANCA association and titre, or renal involvement. CONCLUSIONS: Diffuse endothelial dysfunction, a predictor of atherosclerotic disease, is found extensively in primary systemic vasculitis. Involvement of different vascular beds is independent of target vessel size or ANCA association, and is unrelated to local disease expression. It is suggested that this results from a systemic response that may be a consequence of primary vasculitis, but is distinct from the local inflammatory vasculitic process.

Adult↗
PubMed2002

The death-inducing signalling complex is recruited to lipid rafts in Fas-induced apoptosis.

Membrane microdomains known as lipid rafts have been shown recently to be involved in Fas signalling and apoptosis in T and B cell lines. Here, we have investigated further the role of lipid rafts in Fas-induced apoptosis in non-transformed human CD4 T cells. We show that Fas-induced apoptosis in CD4 T cells was inhibited by the lipid raft disrupter methyl-beta-cyclodextrin. When lipid rafts were isolated from control and Fas ligand treated cells, we found that a small proportion of Fas was present in the raft fraction in untreated cells and that this was greatly increased upon Fas ligation. The other components of the Death Inducing Signalling Complex (DISC), FADD, and procaspase 8, were also present at higher levels in the raft fraction isolated from Fas ligand treated cells. We conclude that formation of the DISC occurs in lipid rafts and that these membrane microdomains are required for efficient Fas signalling and apoptosis.

Apoptosis↗
PubMed2002

A regional audit of the prevention and treatment of corticosteroid-induced osteoporosis in patients with rheumatic diseases in the West Midlands.

BACKGROUND: Audit is an important tool in clinical governance. Combining resources from across a region may facilitate data collection and allow variation in practice between individual units to be analysed. This audit is the first such regional audit to be carried out in rheumatology in the West Midlands and the organization and value of regional audit is discussed. This audit assessed the prevention and management of corticosteroid-induced osteoporosis (CIOP). METHODS: Adult patients attending rheumatology follow-up clinics in 10 units, during a 2-week period were assessed using the 1998 National Osteoporosis Society (NOS) guidance on the prevention and management of CIOP. The audit standard adopted was that 80% of eligible patients should be on appropriate therapy. RESULTS: Data was collected on 1766 (95.2%) of 1855 patients during the audit period. Two hundred and thirty-five (13.3%) were currently being prescribed or about to commence >or=7.5 mg daily of oral prednisolone for >or=6 months. Dual X-ray absorptiometry scans were performed in 102 patients (43.4%). Of these, 53 (52%) had a T score of -1.5 or below at the hip or spine. Of the 235 patients, 202 (86%) were receiving osteoporosis treatment. One hundred and forty-eight patients (63%) were receiving appropriate osteoporosis medication according to the NOS 1998 guidelines and 87 (37%) were inappropriately treated. Of these, 71 (81.6%) were under-treated and 16 (18.4%) were over-treated. CONCLUSIONS: Overall, the Region failed to meet the audit standard. The audit highlighted a number of differences and potential problems in the West Midlands with regard to CIOP which are currently being addressed by individual units and the West Midlands Rheumatology Services and Training Committee (WMRSTC). The Committee plan to re-audit in 2 yr.

Female↗
PubMed2000

Suppression of inflammation in primary systemic vasculitis restores vascular endothelial function: lessons for atherosclerotic disease?

BACKGROUND: Chronic inflammatory rheumatic disorders are associated with excess cardiovascular mortality. This may result from arteriosclerosis following inflammatory damage to the vessel wall by vasculitis. Our hypothesis that vasculitis results in arteriosclerosis by causing vascular endothelial dysfunction was tested in patients with primary systemic necrotizing vasculitis (SNV). METHODS AND RESULTS: Endothelial function was assessed in cross-sectional and longitudinal studies of patients with primary SNV by measuring flow-mediated, endothelium-dependent brachial artery vasodilatation. These patients exhibited marked endothelial dysfunction compared with controls. Remission induction in patients with active primary SNV restored endothelial function. CONCLUSIONS: Endothelial function is significantly impaired in adults with primary SNV, supporting the hypothesis that premature arteriosclerosis in chronic inflammatory rheumatic disorders results from endothelial dysfunction secondary to vasculitis. Normalization of endothelial function after the treatment of primary SNV suggests that early suppression of disease activity in chronic inflammatory rheumatic disorders may reduce long-term vascular damage. The role of inflammation in atheroma formation is increasingly appreciated; this work raises questions regarding the potential for anti-inflammatory therapy in atherosclerosis itself.

Brachial Artery↗
PubMed2000

Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1.

Basal cell carcinoma is the most prevalent cancer in the western world, showing a rapid increase in incidence. Activation of the Sonic hedgehog/Patched (PTCH) signaling pathway because of PTCH1 inactivation is a key event in sporadic and familial basal cell carcinoma development in humans and is associated with transcriptional activation of specific target genes, including PTCH1 itself. These changes are analogous to the situation in Drosophila where hedgehog activates the zinc-finger transcription factor Cubitus interruptus, leading to increased transcription of target genes. In the present study, we show that mice ectopically expressing the human Cubitus interruptus homolog GLI-1 in the skin develop tumors closely resembling human BCCs as well as other hair follicle-derived neoplasias, such as trichoepitheliomas, cylindromas, and trichoblastomas. Furthermore, examination of the tumors revealed wild-type p53 and Ha ras genes. These findings firmly establish that increased GLI-1 expression is central and probably sufficient for tumor development and suggest that GLI-1-induced tumor development does not depend on additional p53 or Ha ras mutations.

Animals↗
PubMed2000

Percutaneous image-guided biopsy of lung nodules in the assessment of disease activity in Wegener's granulomatosis.

OBJECTIVE: In patients with known Wegener's granulomatosis (WG) and persistent chest radiographic abnormalities, assessment for disease activity is often difficult, prompting the need for histological diagnosis to determine appropriate treatment. Here we report the use of automated image-guided core needle biopsy of pulmonary lesions for the assessment of disease activity in WG, rather than for primary diagnosis. METHODS: Image-guided percutaneous core needle biopsy was performed on five occasions in four patients with thoracic WG and persistent radiographic abnormalities of the chest. Clinical features, indication for biopsy, radiographic abnormalities and pathological findings were recorded. RESULTS: Adequate pathological specimens were obtained, allowing exclusion of infection and tumour. Active chronic inflammation with or without vasculitis was demonstrated in each case, indicating the need for further immunosuppressive therapy. A small pneumothorax following biopsy in one case required no treatment. Follow-up chest imaging revealed a reduction in the extent of thoracic disease following therapy in all cases. CONCLUSIONS: The safety and diagnostic accuracy of image-guided core biopsy of thoracic lesions makes it a useful tool in the assessment of disease activity in WG patients with persistent chest radiographic lesions.

Adult↗
PubMed1999

Localized bowel vasculitis: postoperative cyclophosphamide or not?

We describe 2 patients with necrotizing vasculitis localized to the bowel, who were treated by excision of the involved tissue. Postoperatively, there was no evidence of active vasculitis, and both patients remain in remission on followup, without the use of immunosuppressive treatment. Evidence that an abnormal local microenvironment is necessary to sustain chronic inflammation may explain why surgical excision can be an important tool in the treatment of vasculitis.

Adult↗
PubMed1998

Cogan's syndrome with Takayasu's arteritis.

Cogan's syndrome may be associated with large-vessel arteritis. We describe a patient with ocular inflammation, sensorineural hearing loss and arm claudication in whom a diagnosis of 'atypical' Cogan's syndrome and Takayasu's arteritis was made. All symptoms resolved with treatment.

Angiography↗
PubMed1997

A flaccid arm.

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Arm↗