The timing of glucocorticoid administration in rheumatoid arthritis

OBJECTIVE—To test the hypothesis that the timing of prednisolone administration might be critical in determining its effect on the diurnal rheumatoid inflammatory process.
METHODS—26 patients with rheumatoid arthritis were randomly divided into two equal groups and allocated to low doses of prednisolone at either 2.00 am or 7.30 am. Because of the diurnal variation in disease activity in rheumatoid arthritis, assessments of the two study groups were performed at 7.30 am both at the start of the study (day 1) and after four doses of prednisolone (day 5). The study protocol differences in the time period from the last dose of prednisolone to assessment were 5.5 hours in the 2.00 am group and 24 hours in the 7.30 am group.
RESULTS—Administration of low doses of prednisolone (5 or 7.5 mg daily) at 2.00 am had favourable effects on the duration of morning stiffness (P << 0.001), joint pain (P < 0.001), Lansbury index (P << 0.001), Ritchie index (P << 0.001), and morning serum concentrations of IL-6 (P < 0.01). The other study group showed minor but significant effects on morning stiffness (P < 0.05) and circulating concentrations of IL-6 (P < 0.05). Modest and similar improvements of C reactive protein, serum amyloid protein A, and erythrocyte sedimentation rate were seen in both study groups.
CONCLUSIONS—Administration of low doses of glucocorticoids with a rather short biological half life seems to improve acute rheumatoid arthritis symptoms if it precedes the period of circadian flare in inflammatory activity, as defined by enhanced IL-6 synthesis. Further studies are needed to test the relative merits of different timing protocols of glucocorticoid administration in rheumatoid arthritis.

     

Functional assessment of coronary artery stenosis by Doppler derived absolute and relative coronary blood flow velocity reserve in comparison with 99mTc MIBI SPECT

OBJECTIVE—To determine the relation between the relative and absolute coronary blood flow velocity reserve (CFVR) compared with the results of ^99mTc MIBI single photon emission computed tomography (SPECT).
METHODS—In 37 patients with one vessel disease, ^99mTc MIBI SPECT was performed before angioplasty, two to three weeks after angioplasty, and at six months' follow up. CFVR was measured distal to the stenosis (dCFVR) as well as in a reference coronary artery before angioplasty, immediately after angioplasty, and at late follow up. Relative CFVR (rCFVR) was calculated as the ratio between dCFVR and CFVR measured in the reference coronary artery. The optimal thresholds for reversible perfusion defects were calculated using receiver operating characteristic curves.
RESULTS—The agreement for the full range of coronary artery stenosis (n = 107, mean (SD) diameter stenosis 48 (28)%, range 0-98%) between dCFVR (cut off value 1.9) and rCFVR (cut off value 0.65) with ^99mTc MIBI SPECT was 81% and 85%, respectively. In intermediate lesions (n = 49, diameter stenosis range 30-75%) the agreement between dCFVR (cut off value 2.0) and ^99mTc MIBI SPECT was 72%, which increased to 78% using the rCFVR (cut off value 0.65).There was a strong linear relation between dCFVR and rCFVR (r = 0.93, p < 0.0001).
CONCLUSIONS—A best cut off value for dCFVR of 1.9 corresponds with a best cut off value of 0.65 for rCFVR, within the full range of coronary narrowings. Intracoronary blood flow velocity analysis could obviate the need for additional myocardial perfusion scintigraphy in the majority of patients.


Keywords: intracoronary Doppler; relative coronary blood flow velocity reserve; ^99mTc MIBI single photon emission computed tomography     

Intrapulmonary arteriovenous shunting may be a universal phenomenon in patients with the superior cavopulmonary anastomosis: a radionuclide study

OBJECTIVE—To evaluate the extent of intrapulmonary right to left shunting in children after bidirectional cavopulmonary anastomosis (BCPA).
DESIGN—Prospective study of patients who underwent BCPA in a single centre.
PATIENTS—17 patients with complex cyanotic congenital cardiac malformations who underwent BCPA at 1-45 months of age (median 21 months) were evaluated 15-64 months postoperatively (median 32 months). Five children between 1 and 10 years (median 5 years) with normal or surgically corrected intracardiac anatomy and peripheral pulmonary circulation who required V/Q scanning for other reasons were used as controls.
INTERVENTIONS—All patients underwent cardiac catheterisation to exclude angiographically demonstrable venovenous collaterals followed by pulmonary perfusion scanning using ^99mtechnetium (^99mTc) labelled albumen microspheres to quantify the intrapulmonary right to left shunt.
MAIN OUTCOME MEASURE—Percentage of intrapulmonary right to left shunt.
RESULTS—The mean (SD) level of physiological right to left shunting found in the control group was 5.4 (2.3)%. All patients with BCPA showed the presence of a significantly higher level of intrapulmonary shunting (26.8 (16.9)%, p < 0.001). The degree of shunting was significantly increased in the subgroup of 11 patients with BCPA as the only source of pulmonary blood flow (34.9 (15.8)%), when compared to the six remaining patients with an additional source of pulmonary blood supply (12.0 (2.6)%, p < 0.001). There was a negative correlation between age at BCPA and the shunt percentage found in the patients with a competitive source of pulmonary blood flow (r = −0.63, p < 0.01).
CONCLUSIONS—Intrapulmonary right to left shunting develops in all patients following BCPA. This may be caused by a sustained and inappropriate vasodilatation resulting from absence or decreased levels of a substance that inhibits pulmonary vasodilatation. Augmenting BCPA with an additional source of blood flow containing hepatic factor limits the degree of intrapulmonary arteriovenous shunting and may help provide successful longer term palliation.


Keywords: congenital heart defects; cavopulmonary anastomosis; pulmonary arteriovenous malformations; radionuclide scan     

T cell derived cytokines in psoriatic arthritis synovial fluids

OBJECTIVE—The aim of this study was to investigate the concentrations of T cell derived cytokines in the synovial fluids (SFs) of patients with psoriatic arthritis (PsA) in comparison with rheumatoid arthritis (RA) and osteoarthritis (OA).
METHODS—Th1 type cytokines (interleukin 2 (IL2), tumour necrosis factor β (TNFβ), and interferon γ (INFγ)) and Th2 type cytokines (IL4, IL10) were measured by means of enzyme linked immunosorbent assays.
RESULTS—IL2 was usually not detectable in any of the disease groups. TNFβ was found in 3 of 31 PsA SFs (mean (SEM) 11.1 (2.3) pg/ml) and in a significantly lower concentration than in 20 of the 40 RA SFs (42.2 (15.6) pg/ml; p < 0.002). INFγ was measurable in 2 of 10 PsA and 6 of 16 RA SFs (p > 0.05). IL4 was present at low concentrations in 4 of 22 PsA SFs (0.41 (0.8) pg/ml), and in 15 of 20 RA SFs (0.63 (0.09) pg/ml; p < 0.01). IL10 was found in 4 of 27 PsA SFs (12.3 (0.9) pg/ml) and in 27 of 32 RA SFs (37.3 (4.9) pg/ml; p < 0.0001). In all OA SFs cytokine concentrations were below the limit of detection.
CONCLUSION—The pattern of T cell derived cytokines in PsA SFs was similar to that of RA SFs. However, both the frequency and the concentrations of cytokines were lower in PsA SFs than in RA SFs, while OA SFs generally lacked any detectable T cell cytokines altogether. The presence of Th1 and Th2 cell derived cytokines in PsA SFs suggests the presence of activated T cells in the inflamed joint tissues and their participation in the immunoinflammatory events.

Keywords: psoriatic arthritis; rheumatoid arthritis; cytokines; T cells; synovial fluids     

β Blockade in congestive heart failure: persistent adverse haemodynamic effects during chronic treatment with subsequent doses

Objective—To determine whether the acute adverse haemodynamic effects of β blockade in patients with congestive heart failure persist during chronic treatment.
Design—Sequential haemodynamic evaluation of heart failure patients at baseline and after three months of continuous treatment with the β₁ selective antagonist metoprolol.
Setting—Cardiac care unit in university hospital.
Patients—26 patients with moderate to severe congestive heart failure (New York Heart Association grade II to IV) and background treatment with digoxin, diuretics, and angiotensin converting enzyme inhibitors, and with a left ventricular ejection fraction < 25%.
Methods—Baseline variables included a six minute walk, maximum oxygen consumption, and right heart catheterisation. All patients received metoprolol 6.25 mg orally twice daily initially and the dose was gradually increased to a target of 50 mg twice daily. Haemodynamic measurements were repeated after three months of treatment, both before (trough) and after drug readministration.
Results—Long term metoprolol had functional, exercise, and haemodynamic benefits. It produced decreases in heart rate, pulmonary capillary wedge pressure, and systemic vascular resistance, and increases in cardiac index, stroke volume index, and stroke work index. However, when full dose metoprolol was readministered during chronic treatment, there was a reduction in cardiac index (from 2.8 (SD 0.46) to 2.3 (0.38) l/min/m², p << 0.001) and stroke work index (from 31.4 (11.1) to 26.6 (10.0) g.m/m², p < 0.001) and an increase in systemic vascular resistance (from 943 (192) to 1160 (219) dyn.s.cm⁻⁵, p << 0.001).
Conclusions—Adverse haemodynamic effects of β blockers in heart failure persist during chronic treatment, as shown by worsening haemodynamic indices with subsequent doses.

Keywords: heart failure;  β blockers;  adverse effects     

The functional affinity of IgM rheumatoid factor is related to the disease duration in patients with rheumatoid arthritis

OBJECTIVE—To determine the relevance of the functional affinity of IgM rheumatoid factor (RF) to the clinical and serological characteristics of patients with rheumatoid arthritis.
METHODS—The functional affinity of IgM RF of 57 seropositive rheumatoid arthritis patients was evaluated by an enzyme linked immunosorbent assay based on the use of a chaotropic agent. The inhibition index was taken as an estimate of functional affinity. The patient group was divided into high functional affinity subgroup 1 (functional affinity < 0.5, n = 37) and low functional affinity subgroup 2 (functional affinity > 0.5, n = 20). The medical records of all patients were reviewed with a particular note of the disease activity and the articular damage score.
RESULTS—The disease duration was shorter (P < 0.01) in subgroup 1 patients [7.9 (SD 6.4) years] than in subgroup 2 patients [13.4 (11.29) years], so that Ritchie's, Lee's, and Steinbrocker's indices were lower in the former than in the latter (P < 0.01, 0.001, and 0.01, respectively). In contrast, erythrocyte sedimentation rates, C reactive protein concentrations, antinuclear antibody, and HLA DR4 prevalences were similar in the two subgroups.
CONCLUSIONS—Different forms of RF are present during progression of the disease.

     

Ventricular mass and diastolic function in patients infected by the human immunodeficiency virus

OBJECTIVE—Echocardiographic and Doppler analysis of myocardial mass and diastolic function in patients infected with HIV.
DESIGN—Case-control study.
SETTING—Tertiary referral centre, Huelva, Spain.
PATIENTS—61 asymptomatic patients with HIV infection and 32 healthy controls.
MAIN OUTCOME MEASURES—Time motion, cross sectional, and Doppler echocardiographic studies were performed, and left ventricular mass and diastolic function variables determined (peak velocity of early and late mitral outflow and isovolumic relaxation time).
RESULTS—Left ventricular mass index (LVMI) was decreased in patients compared with healthy controls (mean (SD): 76.7 (23.6) v 118.8 (23.5) g/m², p < 0.001). Linear regression analysis showed a correlation between LVMI and brachial fat and muscle areas. The ratio of peak velocities of early and late mitral outflow was decreased in HIV infected patients compared with controls (1.19 (0.44) v 1.58 (0.38), p < 0.001). This ratio was exclusively related to haemodynamic variables (heart rate, systolic and diastolic blood pressures). HIV infected patients had a prolonged isovolumic relaxation time (103.0 (10.5) v 72.9 (12.9) ms, p < 0.001). Isovolumic relaxation time was correlated only with brachial muscle area on multivariate analysis.
CONCLUSIONS—HIV infected patients had a reduced left ventricular mass index and diastolic functional abnormalities. These cardiac abnormalities are predominantly related to nutritional status.


Keywords: HIV infection; cardiac function; nutrition     

Left ventricular function in adults with mild pulmonary insufficiency late after Fallot repair

OBJECTIVE—To assess left ventricular function in adult Fallot patients with residual pulmonary regurgitation.
SETTING—The radiology department of a tertiary referral centre.
PATIENTS—14 patients with chronic pulmonary regurgitation and right ventricular volume overload after repair of tetralogy of Fallot and 10 healthy subjects were studied using magnetic resonance imaging.
MAIN OUTCOME MEASURES—Biventricular volumes, global biventricular function, and regional left ventricular function were assessed in all subjects.
RESULTS—The amount of pulmonary regurgitation in patients (mean (SD)) was 25 (18)% of forward flow and correlated significantly with right ventricular enlargement (p < 0.05). Left ventricular end diastolic volume was decreased in patients (78 (11) v 88 (10) ml/m²; p < 0.05), ejection fraction was not significantly altered (59 (5)% v 55 (7)%; NS). No significant correlation was found between pulmonary regurgitation and left ventricular function. Overall left ventricular end diastolic wall thickness was significantly lower in patients (5.06 (0.72) v 6.06 (1.06) mm; p < 0.05), predominantly in the free wall. At the apical level, left ventricular systolic wall thickening was 20% higher in Fallot patients (p < 0.05). Left ventricular shape was normal.
CONCLUSIONS—Adult Fallot patients with mild chronic pulmonary regurgitation and subsequent right ventricular enlargement showed a normal left ventricular shape and global function. Although the left ventricular free wall had reduced wall thickness, compensatory hypercontractility of the apex may contribute to preserved global function.


Keywords: left ventricular function; pulmonary insufficiency; tetralogy of Fallot; magnetic resonance imaging     

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.

Keywords: magnetic resonance imaging; rheumatoid arthritis; synovitis; vascularity     

Initiation and perpetuation of rat adjuvant arthritis is inhibited by the anti-CD2 monoclonal antibody (mAb) OX34

OBJECTIVE—The purpose of this study was to investigate the therapeutic potential of the anti-CD2 mAb OX34 first with regard to bone protection in established rat adjuvant arthritis (AA) and secondly with regard to prevention of AA induction.
METHODS—Established AA was treated with dexamethasone (1 mg/kg body weight) for two days plus OX34 mAb or control mAb over three days (2 mg and then 1 mg) starting at different time points of the disease. For prevention studies animals were injected as above with mAb before induction of AA. Arthritis score (AS), hindpaw thickness, and body weight were blindly measured three times per week. Flow cytometry and hindpaw radiography were performed at the end of the study (day 29).
RESULTS—Treatment of early AA with OX34 mAb combined with dexamethasone but not dexamethasone plus control mAb dramatically suppressed established AA as assessed by AS and hind paw thickness (>65% and >80% reduction, respectively; p < 0.05). Most importantly, early treatment in the course of AA almost completely prevented bone destruction in established AA. When given before AA induction OX34 alone prevented the initiation of arthritis compared with controls (AS reduction 83-95%, p < 0.05). In addition, OX34 plus dexamethasone treatment resulted in depletion of CD4⁺ T cells but not CD8⁺ T cells. IL2R⁺ and CD45RC^-(`memory') T cells were significantly reduced.
CONCLUSIONS—Anti-CD2 mAb treatment prevents AA induction confirming the role of CD4⁺ T cells in the induction phase of AA. In addition, early OX34 plus dexamethasone treatment resulted in pronounced clinical improvement and joint protection. OX34 treatment therefore inhibits the initiation and the perpetuation of rat AA.

     

Inactivation of antithrombin III in synovial fluid from patients with rheumatoid arthritis

OBJECTIVE—To investigate the thrombin inhibitory capacity of antithrombin III in the inflamed human joint.
METHODS—Thrombin inhibitory capacity was measured, using a kinetic spectophotometric method, in matched plasma and synovial fluid samples of patients with rheumatoid arthritis (n=22) and osteoarthritis (n=16), together with normal control plasma samples (n=13). In the same samples, the concentration of antithrombin III was also determined by the method of radial immunodiffusion. The combination of these measurements allowed the calculation of the specific thrombin inhibitory capacity of these samples.
RESULTS—An increased concentration of antithrombin III in rheumatoid compared with osteoarthritic synovial fluid was noted (p<0.05). However, there was a significant depression in the specific activity of antithrombin III in rheumatoid synovial fluid when compared with matched plasma samples (p<0.001) or with osteoarthritic synovial fluid (p<0.05).
CONCLUSION—In rheumatoid synovial fluid the thrombin inhibitory capacity of antithrombin III is disproportionately depressed relative to the concentration of antithrombin III, indicating the inactivation of antithrombin III in the rheumatoid joint.

Keywords: antithrombin III; thrombin; rheumatoid arthritis; synovial fluid     

Four year follow up of aortic valve replacement for isolated aortic stenosis: a link between reduction in pressure overload, regression of left ventricular hypertrophy, and diastolic function

OBJECTIVE—To evaluate changes in left ventricular function and the impact of ventricular hypertrophy and pressure gradient early and late after aortic valve replacement in patients with isolated aortic stenosis.
DESIGN—41 patients with isolated aortic stenosis and normal systolic function underwent cross sectional and Doppler echocardiography two months before and two weeks and four years after aortic valve replacement.
RESULTS—Early after the operation, left ventricular mass index (mean (SD)) decreased from 187 (44) g/m² to 179 (46) g/m², because of a reduction in end diastolic diameter (p < 0.05). Aortic pressure gradients were reduced, as expected. Isovolumic relaxation time was reduced from 93 (20) ms to 78 (12) ms, and deceleration time from 241 (102) ms to 205 (77) ms (p < 0.05). At four years, left ventricular mass index was further reduced to 135 (30) g/m² (p < 0.01) as a result of wall thickness reduction in the interventricular septum (from 14 (1.6) mm to 12 (1.4) mm, p < 0.01) and the posterior wall (from 14 (1.6) mm to 12 (1.3) mm, p < 0.01). Diastolic function, expressed by a reduction in isovolumic relaxation time from 93 (20) ms to 81 (15) ms (p < 0.01) and deceleration time from 241 (102) ms to 226 (96) ms (p < 0.05), remained improved. Prolonged isovolumic relaxation time was associated with significant septal and posterior wall hypertrophy (wall thickness > 13 mm) (p < 0.05), whereas prolonged deceleration time was related to high residual gradient (peak gradient > 30 mm Hg ) (p < 0.01).
CONCLUSIONS—Left ventricular diastolic function improves early after surgery for aortic stenosis in parallel with the reduction in the aortic gradient. However, prolongation of Doppler indices of myocardial relaxation and ventricular filling is observed in patients with significant left ventricular hypertrophy and a residual pressure gradient early after surgery. At four years postoperatively, diastolic function remains improved.


Keywords: diastolic function; hypertrophy regression; aortic valve replacement; aortic stenosis     

A quantitative method for detecting deposits of amyloid A protein in aspirated fat tissue of patients with arthritis

OBJECTIVE—To describe a new, quantitative, and reproducible method for detecting deposits of amyloid A protein in aspirated fat tissue and to compare it with smears stained with Congo red.
METHODS—After extraction of at least 30 mg of abdominal fat tissue in guanidine, the amyloid A protein concentration was measured by a monoclonal antibody-based sandwich ELISA.
RESULTS—The concentrations in 24 patients with arthritis and AA amyloidosis (median 236, range 1.1-8530 ng/mg tissue) were higher (p<0.001) than in non-arthritic controls, uncomplicated rheumatoid arthritis, and other types of systemic amyloidosis (median 1.1, range 1.1-11.6 ng/mg tissue). Patients with extensive deposits, according to Congo red staining, had higher concentrations than patients with minute deposits.
CONCLUSION—This is a new, quantitative, and reproducible method for detecting deposits of amyloid A protein in aspirated fat tissue of patients with arthritis, even when minute deposits are present as detected in smears stained with Congo red.

Keywords: amyloid A protein; fat tissue; arthritis     

Mitral regurgitation after anthracycline treatment for childhood malignancy

OBJECTIVE—To investigate the new onset of mitral regurgitation in patients with otherwise normal echocardiograms after anthracycline treatment and to assess its relation to other selected indicators of myocardial damage.
DESIGN—Prospective echocardiographic and electrocardiographic study.
SETTING—Tertiary paediatric cardiac referral centre.
PATIENTS—305 patients, aged 2-33 years (median 14 years), treated with cumulative anthracycline doses of between 150-450 mg/m² (median 180 mg/m²) for childhood malignancy.
MAIN OUTCOME MEASURES—Colour flow Doppler detection of mitral regurgitation and its relation to changes in echocardiographic indices of left ventricular function (systolic and diastolic dimensions, fractional shortening) and to changes in the 12 lead ECG; and the prevalence of mitral regurgitation in the anthracycline treated patients in comparison with previously studied normal volunteers of similar age.
RESULTS—34 patients (11.6%) developed ultrasound detectable mitral regurgitation, which was not apparent clinically, during or after anthracycline treatment, compared with only 1.8% of a normal population of similar age (p < 0.0001). Nine of the 34 also developed non-specific T wave abnormalities. All 34 patients had normal systolic function at the time of initial detection of mitral regurgitation, but four later developed impaired left ventricular function (5, 11, 20, and 27 months after the first detection of mitral regurgitation).
CONCLUSIONS—Mitral regurgitation occurs much more often in patients treated with anthracyclines than in the normal population. Echocardiographic detection of new mitral regurgitation with or without ECG abnormalities may be an early predictor of anthracycline cardiomyopathy.


Keywords: anthracyclines; mitral regurgitation; cardiomyopathy     

Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease

Background—Reactive oxygen species contribute totissue injury in inflammatory bowel disease (IBD). The tripeptideglutathione (GSH) is the most important intracellular antioxidant.
Aims—To investigate constituent amino acid plasmalevels and the GSH redox status in different compartments in IBD withemphasis on intestinal GSH synthesis in Crohn's disease.
Methods—Precursor amino acid levels were analysedin plasma and intestinal mucosa. Reduced (rGSH) and oxidisedglutathione (GSSG) were determined enzymatically in peripheral bloodmononuclear cells (PBMC), red blood cells (RBC), muscle, and innon-inflamed and inflamed ileum mucosa. Mucosal enzyme activity ofγ-glutamylcysteine synthetase (γGCS) and γ-glutamyl transferase(γGT) was analysed. Blood of healthy subjects and normal mucosa froma bowel segment resected for tumour growth were used as controls.
Results—Abnormally low plasma cysteine and cystinelevels were associated with inflammation in IBD (p<10^-4).Decreased rGSH levels were demonstrated in non-inflamed mucosa (p<0.01) and inflamed mucosa (p=10^-6) in patients withIBD, while GSSG increased with inflammation (p=0.007) compared withcontrols. Enzyme activity of γGCS was reduced in non-inflamed mucosa(p<0.01) and, along with γGT, in inflamed mucosa(p<10^-4). The GSH content was unchanged in PBMC, RBC, and muscle.
Conclusions—Decreased activity of key enzymesinvolved in GSH synthesis accompanied by a decreased availability ofcyst(e)ine for GSH synthesis contribute to mucosal GSH deficiency inIBD. As the impaired mucosal antioxidative capacity may further promote oxidative damage, GSH deficiency might be a target for therapeutic intervention in IBD.

Keywords:Crohn's disease; ulcerative colitis; glutathione; amino acids; γ-glutamylcysteine synthetase; mucosa

     

Impaired cardiac adrenergic innervation assessed by MIBG imaging as a predictor of treatment response in childhood dilated cardiomyopathy

OBJECTIVE—To evaluate the prognostic value of metaiodobenzylguanidine (MIBG) imaging in childhood cardiomyopathy.
DESIGN—Prospective cohort study.
SETTING—Tertiary referral centre.
PATIENTS—40 children (21 boys, 19 girls; mean (SD) age, 7.0 (5.6) years) with heart failure resulting from idiopathic dilated cardiomyopathy (n = 23) or various other disorders (n = 17).
METHODS—At the initial examination, cardiac ¹²³I-MIBG uptake and release, circulating noradrenaline (norepinephrine) concentration, x ray cardiothoracic ratio, and echocardiographic variables were recorded. Cardiac MIBG uptake was obtained by measuring the heart to mediastinum activity ratio on the planar image obtained four hours after MIBG injection. MIBG washout rate was evaluated using relative decrease in cardiac activity measured at 20 minutes and four hours. Patients were treated with angiotensin converting enzyme inhibitors, diuretics, and digitalis, and were followed up for 12 (10) months. Fifteen patients did not respond to medical treatment (12 heart transplants; three deaths), and 25 did respond (improved or stable).
RESULTS—Cardiac MIBG uptake was positively correlated with x ray cardiothoracic index (r = 0.55, p = 0.0008) and echocardiographic left ventricular fractional shortening (r = 0.68, p < 0.0001). Among all the clinical and laboratory variables tested, multivariate discriminant analysis showed that the only independent predictor of an unfavourable outcome was a low MIBG uptake (p < 0.001). Survival curves had a mean threshold value of 1.54 for MIBG uptake.
CONCLUSIONS—Impaired cardiac adrenergic innervation is strongly related to adverse outcome in children with dilated cardiomyopathy, independently of the aetiology. MIBG imaging may help to stratify risk in such patients.


Keywords: noradrenaline; MIBG; single photon imaging; children; cardiomyopathy     

Improved functional outcome in patients with early rheumatoid arthritis treated with intramuscular gold: results of a five year prospective study

OBJECTIVE—To determine whether there is a relation between disease duration and functional outcome in patients with rheumatoid arthritis (RA) treated with intramuscular sodium aurothiomolate (gold) for five years.
METHODS—440 patients with RA were enrolled in a prospective trial of gold treatment. Initial demographic details were recorded. Disease activity was assessed at yearly intervals using a combination of clinical (pain score, Ritchie articular index, duration of morning stiffness) and laboratory (erythrocyte sedimentation rate, C reactive protein) parameters. Change in functional status was assessed using the health status questionnaire (HAQ). Patients were stratified according to disease duration at outset (group 1= 0-2 years n=106, group 2 = >2-5 years n=93, and group 3= >5 years n=235).
RESULTS—There were no significant differences between the groups at outset. A total of 160 patients completed five years of treatment (group 1 n=44 (42%), group 2 n=37 (40%), and group 3 n=79 (34%)). Patients in group 1 had a significantly lower HAQ from year 1 to year 5 with a mean improvement of 30% at the end of the study (p<0.001). Neither group 2 nor group 3 had a significant change in their HAQ at study end. There were significant improvements in all other variables (p<0.05) in each group apart from pain in group 2.
CONCLUSION—Patients with early RA have a larger reversible component to their HAQ. Only patients with disease duration of up to two years have a longlasting improvement in their functional ability after starting intramuscular gold treatment.

Keywords: gold; rheumatoid arthritis; function; HAQ     

Haemodynamic and hormonal effects of adrenomedullin in patients with pulmonary hypertension

OBJECTIVE—To investigate whether infusion of adrenomedullin, a potent vasorelaxant peptide, has beneficial haemodynamic and hormonal effects in patients with pulmonary hypertension.
PATIENTS AND DESIGN—The haemodynamic and hormonal responses to intravenous infusion of adrenomedullin (0.05 µg/kg/min) or placebo were examined in 13 patients with precapillary pulmonary hypertension.
RESULTS—Infusion of adrenomedullin produced a 44% increase in cardiac index (mean (SD) 1.8 (0.2) to 2.6 (0.3) l/min/m², p < 0.05) and a 32% decrease in pulmonary vascular resistance (19.7 (1.4) to 13.4 (1.3) units, p < 0.05), with a 4% reduction in mean pulmonary arterial pressure (62 (4) to 59 (4) mm Hg, NS). Adrenomedullin also decreased mean systemic arterial pressure (81 (3) to 72 (4) mm Hg, p < 0.05) and increased heart rate (73 (4) to 79 (4) beats/min, p < 0.05). Adrenomedullin decreased plasma aldosterone (9.8 (2.5) to 7.1 (1.5) ng/dl, p < 0.05) without significant changes in plasma renin activity. Plasma atrial and brain natriuretic peptides tended to decrease with adrenomedullin, although these changes did not reach significance. The haemodynamic and hormonal variables remained unchanged during placebo infusion.
CONCLUSIONS—Intravenous adrenomedullin has beneficial haemodynamic and hormonal effects in patients with precapillary pulmonary hypertension.


Keywords: adrenomedullin; pulmonary hypertension; haemodynamics     

Randomised comparison of coronary stenting with and without balloon predilatation in selected patients

BACKGROUND—The SWIBAP (stent without balloon predilatation) prospective randomised trial was designed to compare direct coronary stenting with stenting preceded by lesion predilatation with an angioplasty balloon.
OBJECTIVE—To determine the feasibility and safety of direct stenting in non-complex coronary lesions in a prospective study.
PATIENTS AND DESIGN—All patients < 76 years of age scheduled to undergo angioplasty of a non-complex, non-calcified lesion in a coronary artery of > 3.0 mm, who granted their informed consent, were randomised into the trial. In group I, the stent was placed without balloon predilatation, while in group II stent implantation was preceded by balloon predilatation. The primary end point was the angiographic result according to procedure assigned by randomisation. An intravascular ultrasound substudy was performed in 60 patients.
RESULTS—Stent implantation was successful without predilatation in 192 of the 197 group I patients (97.5%), and with predilatation in 197 of the 199 group II patients (99%) (NS). No in-hospital stent thrombosis or death occurred. Overall procedural times, fluoroscopy times, and volumes of contrast agent given (mean (SD)) in group I v group II were 23.50 (13.54) min v 27.96 (15.23) min (p = 0.002), 6.04 (4.13) min v 6.67 (3.65) min (NS), and 135 (65) ml v 157 (62) ml (p < 0.001), respectively. No major adverse cardiovascular events had occurred by 30 days.
CONCLUSIONS—The feasibility and safety of direct stenting of selected and non-complex coronary lesions is confirmed. This technique was as successful as the conventional approach and was associated with a minor reduction in fluoroscopic exposure and procedure time and the administration of less contrast agent.


Keywords: coronary artery angioplasty; stent; coronary artery ultrasound     

Combination treatment with trimetazidine and diltiazem in stable angina pectoris

Objective—To assess antianginal efficacy and possible adverse haemodynamic effects of combination treatment with trimetazidine and diltiazem in patients with stable angina.
Design—Double blind, randomised, placebo controlled trial of four weeks duration.
Setting—Outpatient department of two Indian hospitals.
Subjects—64 male patients with stable angina, uncontrolled on diltiazem alone.
Interventions—Diltiazem 180 mg and trimetazidine 60 mg, or diltiazem 180 mg and placebo daily.
Main outcome measure—Change in exercise time to 1 mm ST segment depression.
Results—33 patients (55%) had no exercise induced angina at 3 mm ST segment depression at inclusion in the study (silent ischaemia). Intention to treat analysis showed that of 32 patients in each treatment group, the number (%) of patients responding to trimetazidine compared to placebo was: for anginal attacks, 28 (87.5) v 15 (46.9), p < 0.001; for exercise time to 1 mm ST segment depression, 21 (65.6) v 9 (28.1), p < 0.003; for exercise time to angina, 12 (37.5) v 5 (15.6), p < 0.05; and for maximum work at peak exercise, 17 (53.1) v 8 (25), p < 0.02. Compared to placebo, there was net improvement with trimetazidine in mean anginal attacks of 4.8/week (95% confidence interval (CI) 7.5 to 2.1; p < 0.002); in mean exercise times at 1 mm ST segment depression of 94.2 seconds (95% CI 182.8 to 5.6; p < 0.05), and at onset of angina of 113.1 seconds (95% CI 181.6 to 44.6; p < 0.02); and in mean maximum work at peak exercise of 1.4 metabolic equivalents (95% CI 2.4 to 0.3; p < 0.05).
Conclusions—Patients with stable angina uncontrolled with diltiazem had a clinically important improvement after combination treatment with trimetazidine, without adverse haemodynamic events or increased side effects.

Keywords: trimetazidine;  diltiazem;  blood pressure;  stable angina;  treatment