Biomedical subjects
Ali S M Jawad
Publications and source records attributed to Ali S M Jawad.
Measurement of S-nitrosothiols in extracellular fluids from healthy human volunteers and rheumatoid arthritis patients, using electron paramagnetic resonance spectrometry.
In human tissues, S-nitrosothiols (RSNOs) are generated by the nitric oxide (NO.)-dependent S-nitrosation of thiol-containing species. Here, a novel electron paramagnetic resonance spectrometry assay for RSNOs is described, together with its application to studies of human health and disease. The assay involves degrading RSNOs using N-methyl-d-glucamine dithiocarbamate (MGD) at high pH and spin trapping the NO. released using (MGD)2-Fe2+. Because dietary nitrate might contribute to tissue RSNOs, the assay was used to monitor the effect of Na15NO3 ingestion on plasma and gastric juice RSNOs in healthy human volunteers. Na15NO3 ingestion (2 mmol) increased gastric RS15NO concentrations (p<0.01), but there was no significant effect on plasma RS15NO concentrations. Having established that dietary nitrate was not a confounding factor, we applied the RSNO assay to matched plasma and knee-joint synovial fluid (SF) from rheumatoid arthritis (RA) patients, with healthy subjects as controls. Clinical markers of RA inflammatory disease activity were quantified, as were plasma and SF NO2- and NO3-. Median RSNO concentrations were 0 (interquartile range 68) nM, 109 (282) nM, and 309 (470) nM in normal plasma, RA plasma, and SF, respectively. The median RSNO concentration was significantly elevated in RA SF compared with RA plasma (p<0.05) and in RA plasma compared with normal plasma (p<0.05). SF RSNO concentrations correlated positively with SF neutrophil counts (rs=0.55, p<0.05) and inversely with blood hemoglobin concentrations (rs=-0.52, p<0.05), but not with NO2- or NO3-. Thus the raised levels of RSNOs in RA SF correlate with some established markers of inflammation, suggesting the described RSNO assay may have applications in rapid clinical monitoring of NO metabolism in human inflammatory conditions.
Temporal arteritis associated with systemic necrotizing vasculitis.
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Teaching clinical skills to preregistration house officers.
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Analgesics and osteoarthritis: are treatment guidelines reflected in clinical practice?
Osteoarthritis (OA) treatment is complex and multifactorial, with pharmacological regimens requiring sufficient flexibility to be adapted to individual disease progression, flare ups, and response to treatment. Coexisting conditions are common and can lead to problems regarding polypharmacy. Several guidelines have been published for the management of OA pain. While differences exist, most recommend paracetamol as the initial oral drug for OA, based on its efficacy, tolerability, and cost; in patients who respond inadequately to paracetamol, supplementary or replacement analgesics should be recommended. This article considers the reality of analgesic use for OA in clinical practice and the extent to which guidelines are followed both in primary and secondary care. An international survey of rheumatologists (n = 610) found that paracetamol was recommended as first-choice analgesic for OA by 82% of those surveyed. Similarly, in a survey of French GPs, 90% of those surveyed recommended paracetamol first line; NSAIDs were recommended more frequently for stronger pain relief but were also recommended alongside paracetamol as a first-line treatment of mild to moderate pain by 43% of GPs. Finally, a UK patient survey, conducted at a London hospital (n = 200), found that 64% of patients were taking more than 1 drug for treatment of painful OA of the knee or hip; 76% were taking paracetamol and 40% were taking an NSAID. A further 39% had used an NSAID in the past but switched treatment, primarily due to side effects. These findings reinforce the case for the simple analgesic paracetamol to be seen as the cornerstone of pharmacological OA treatment, both as a first-line analgesic and as a foundation to which additional treatment modalities, including NSAIDs, can be added if and when necessary.