Effects of chronic sympatho-inhibition on reflex control of renal blood flow and plasma renin activity in renovascular hypertension

Background and purpose:

We determined if chronic sympatho-inhibition with rilmenidine has functional significance for the kidney by altering responses of renal blood flow (RBF) and plasma renin activity (PRA) to stress and acute hypotension in rabbits with renovascular hypertension.

Experimental approach:

RBF to each kidney and renal sympathetic nerve activity (RSNA) to the left kidney were measured in rabbits in which a renal artery clip induced hypertension (2K1C) and in sham-operated rabbits. After 2 weeks, a subcutaneous minipump was implanted to deliver rilmenidine (2.5 mg·kg⁻¹·day⁻¹) to 2K1C rabbits for 3 weeks.

Key results:

After 5 weeks of renal artery stenosis, mean arterial pressure (MAP) was 23% higher and PRA 3-fold greater than in sham-operated rabbits. Blood flow and renal vascular conductance in the stenosed kidney were lower (−75% and −80%) compared with sham, and higher in the non-clipped kidney (68% and 39%). Responses of RBF and PRA to hypotension were similar in 2K1C and sham rabbits. Airjet stress evoked a greater increase in MAP in 2K1C rabbits than sham controls. Chronic rilmenidine normalized MAP, reduced RSNA and PRA, and did not reduce RBF in the stenosed kidney. Responses of RBF (clipped and non-clipped kidney), RSNA and PRA to hypotension and airjet were little affected by rilmenidine.

Conclusions and implications:

Our observations suggest that chronic sympatho-inhibition is an effective antihypertensive therapy in renovascular hypertension. It normalizes MAP and reduces basal PRA without compromising blood flow in the stenosed kidney or altering responses of MAP, haemodynamics and PRA to acute hypotension and stress.     

Association between anti-tumour necrosis factor therapy and risk of ischaemic stroke in patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Registers-Rheumatoid Arthritis (BSRBR-RA)

BackgroundPeople with rheumatoid arthritis are at increased risk of cardiovascular morbidity and mortality, including stroke (cerebrovascular accident [CVA]). Anti-tumour necrosis factor (anti-TNF) therapy may influence the risk of CVA by reducing inflammation. The aim of the analysis was to study the association of anti-TNF therapy with risk of ischaemic CVA in rheumatoid arthritis.MethodsThe British Society for Rheumatology Biologics Registers-Rheumatoid Arthritis (BSRBR-RA) is an ongoing national prospective observational cohort study. Patients with rheumatoid arthritis recently started on anti-TNF therapy and a biologic-naive comparator group treated only with non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) were recruited to the BSRBR-RA from 2001 to 2008. Patients were followed by physician and patient questionnaires and also linked to the national death register. Incident CVAs were identified from all three sources of follow-up. CVAs were validated against WHO criteria for CVA and further classified as ischaemic CVA using CT brain reports or if ischaemic CVA was reported as the underlying cause of death from death certificates according to International Classification of Diseases 10 (ICD-10) code I63. Patients with a previous CVA were excluded. Risk of ischaemic CVA was compared between the nbDMARD cohort and people ever exposed to anti-TNF using a Cox regression model. Missing baseline data were replaced by multiple imputation. Adjustment was made for confounders using propensity scores stratified by deciles.FindingsTo Oct 31, 2010, 130 verified incident ischaemic CVAs (21 in 3271 nbDMARD patients, 109 in 11 642 anti-TNF patients) had occurred during 11 973 and 61 226 person-years of observation, respectively (incidence rate 175 vs 178 per 100 000 person-years). After adjustment for confounders, there was no association between ever exposure to anti-TNF and ischaemic CVA risk (hazard ratio 0·88 [95% CI 0·46–1·71]).InterpretationExposure to anti-TNF therapy does not appear to be associated with risk of ischaemic CVA when compared with nbDMARD therapy. Further follow-up is needed to assess time-varying risk.FundingBritish Society for Rheumatology.     

Pre‐emptive ibuprofen arginate in third molar surgery: a double‐blind randomized controlled crossover clinical trial

Background: This study evaluated the effectiveness of 400 mg ibuprofen arginate either as a pre‐emptive (PRE group) or postoperative (POST group) analgesic using a common dental pain model. Methods: A randomized double‐blind crossover clinical trial involving a series of consecutive patients admitted for bilateral third molar surgery. Results were analysed according to the self‐reported pain score and the pattern of rescue medication taken. Results: The mean pain score ranged from 0.73 to 1.60 for the PRE group and 0.47 to 1.41 for the POST group among 30 included subjects. The mean time point when first rescue medication taken was 7.3 hours and 8.3 hours postoperative, respectively. Nine patients (30 per cent) in the PRE group and 12 patients (40 per cent) in the POST group took no rescue medication. There was no statistically significant difference for all parameters between groups, while a majority (53 per cent) found the drug “good” to “excellent” in both groups. Conclusions: Ibuprofen arginate may be considered effective in reducing surgically induced moderate to severe pain when administered either pre‐operatively or postoperatively due to the reported relatively low pain score, less consumption of rescue medication, delayed onset of pain, good number of pain‐free patients and a high rating in the global assessment score.     

Development and psychometric evaluation of the Bipolar Functional Status Questionnaire (BFSQ)

Goldberg JF, McLeod LD, Fehnel SE, Williams VSL, Hamm LR, Gilchrist K. Development and psychometric evaluation of the Bipolar Functional Status Questionnaire (BFSQ). Bipolar Disord 2010: 12: 32–44. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Persistently impaired psychosocial functioning has been recognized in many individuals with bipolar disorder. However, existing measures of functional disability have been adapted for use in bipolar disorder based mainly on those developed for use in other conditions. The present study involved the development and validation of a new patient self‐report measure specific to bipolar disorder, the Bipolar Functional Status Questionnaire (BFSQ). Methods: Relevant constructs were identified, evaluated, and refined through an expert advisory panel in conjunction with patient interviews. Questionnaire items were vetted through iterative patient interviews. Psychometric properties were determined based on patient responses from implementation of the proposed 33‐item questionnaire in an 11‐site study of 596 patients with bipolar disorder across varied phases of illness. Results: Eight constructs were identified as fundamental to functional status in bipolar disorder: cognitive function, sleep, role functioning, emotional functioning, energy/vitality, social functioning, personal management, and sexual functioning. Psychometric validation supported item reduction to a 24‐item unidimensional scale, with high internal consistency (coefficient α’s = 0.93–0.95), high test‐retest reliability (intraclass correlation coefficient = 0.86, 95% confidence interval = 0.82–0.89), strong convergent validity with other functional disability measures (r’s > 0.70), and highly significant discriminant validity across illness phases, with large effect sizes (Cohen’s d > 0.70). Conclusions: The BFSQ is a psychometrically sound self‐report measure that can be used to effectively quantify functional status across different clinical states in patients with bipolar disorder.