Gold treatment, nephrotic syndrome, and multi-organ failure in a patient with adult onset Still's disease.
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Biomedical subjects
Publications and source records attributed to K Raza.
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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.
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.
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.
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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.
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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.
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OBJECTIVE: To define the sex ratio of juvenile onset ankylosing spondylitis (AS) among a large population. METHODS: Using a standard questionnaire, data were collected from 3362 subjects, members of the National Ankylosing Spondylitis Society and patients at a tertiary referral center. RESULTS: Of 3362 patients, 2461 (73%) were male; male:female sex ratio was 2.7:1. Of the total, 379 (11%) had disease onset between the ages of 5 and 16 years. Of these, 278 were boys and 101 girls, giving an overall male:female ratio, in juvenile AS, of 2.6:1. For those with onset ages 5-13 years there was a ratio of 2.1:1, while for those aged over 14 years at onset, the ratio was 3.2:1. CONCLUSION: Older published ratios, ranging from 4.5:1 to 6:1, used smaller samples, focusing only on subjects who were juveniles at the time of the study. Our data collection method, which recruits from 2 sources and includes adults with juvenile onset, attempts to avoid these methodological problems. The data suggest a higher incidence of juvenile AS among females than previously described.
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Magnetic Resonance Imaging (MRI) examination was carried out on 44 patients who had spinal injuries with neurological involvement. The technique provided valuable information about the nature of the injuries and, in particular, about the state of the spinal cord. The appearances of the cord on MRI ranged from normal, to oedema, to more severe damage such as cord haemorrhage or transection or, in later cases, myelomalacia. The appearance of the cord on MRI correlated strongly with both the severity of the neurological deficit and also the degree of subsequent recovery. In the assessment of the acute spinal injury, MRI has been shown to be a good prognostic indicator; it may also help to identify which patients are likely to benefit from early decompression.
Cataract is the major cause of blindness worldwide. Non-enzymic modification of lens proteins leading to a disruption of their short range order is an important route to cataract formation. A reaction between lens proteins and a compound found in the lens indicates a potential role for that compound in cataract formation. The reactions of glucose and fructose with lens protein in vitro were investigated. Fructose bound to lens protein at pH 6.9 in a time-dependent fashion over a period of 20 days. The reactions of both glucose and fructose with lens proteins and bovine serum albumin led to the formation of coloured and fluorescent compounds. The formation of such compounds was greater with fructose than with glucose. The kinetics of the reactions of lens proteins and bovine serum albumin with fructose as measured by the formation of the above compounds were not identical. This point must be appreciated when attempting to extrapolate from results obtained with bovine serum albumin as to the reactions of lens proteins. The incubation of lens proteins with fructose led to an enhancement of protein aggregation. The implications of the reactions between lens proteins and fructose for the formation of cataract in diabetics are discussed. Ibuprofen intake is associated with protection against cataract. At relatively high concentrations (10-20 mM) ibuprofen decreased the binding of fructose to lens protein: this decrease was statistically significant at selected times (Student's t-test, P less than 0.05). The formation of fluorescent compounds in the presence of fructose was also decreased by ibuprofen.(ABSTRACT TRUNCATED AT 250 WORDS)