Electrophysiological characteristics of asymptomatic Wolff--Parkinson--White syndrome

Although most asymptomatic patients with the Wolff—Parkinson—Whitesyndrome have a good prognosis, some die suddenly. Electrophysiologicaltesting may identify patients at possible risk of sudden death.The mechanism of sudden death in these patients is believedto result from ventricular fibrillation due to atrial fibrillationwith rapid anterograde conduction over the accessory pathway.Consequently, we performed electrophysiological studies in 40asymptomatic patients with the Wolff—Parkinson—Whitesyndrome. Certain electrophysiological properties clearly identifiedthese patients: (1) in most patients sustained reciprocatingtachycardia could not be induced and this explains the absenceof symptoms of regular fast palpitations; (2) the incidenceof inducible sustained atrial tachyarrhythmias (30%), of shortRR intervals between pre-excited beats (20%) and of risk ofsudden death (12.5%) was similar to the incidence in symptomaticpatients with the Wolff—Parkinson—White syndromeand reciprocating tachycardia. Because of the ease with which transoesophageal study can beperformed we think that the asymptomatic Wolff— Parkinson—Whitesyndrome should be systematically evaluated so as to reassurepatients with the benign form that they can lead a normal lifeand take part in sport and secondly to define the real prognosisof the patients whose characteristics suggests a risk of suddendeath.     

ERRATUM

Rajapakse C, Al Balla S, Al—Dallan A, Kamal H. Streptococcalantibody cross—reactivity with HLA—DR4+ve B—lymphocytes.Basis of the DR4 associated genetic predisposition to rheumaticfever and rheumatic heart disease". The last—named author of the above article should readHalim K and not Kamal H.     

INTERLEUKIN-6 ACTIVITY IN PAIRED SAMPLES OF SYNOVIAL FLUID. CORRELATION OF SYNOVIAL FLUID INTERLEUKIN--6 LEVELS WITH CLINICAL AND LABORATORY PARAMETERS OF INFLAMMATION

Paired synovial fluid (SF) samples obtained from the knees of12 arthritis patients were studied to establish a relation betweenparameters of local inflammatory activity and SF interleukin—6(IL—6) levels. Local disease activity was scored usingjoint temperature, swelling and pain as clinical parametersof inflammation. SF samples were assayed for laboratory parametersof inflammation such as leucocyte content, the percentage polymorphonuclearcells, the pH, and for immu—noglobulin levels (IgG, IgM).SF IL—6 concentrations were determined using the B9—bioassay.Within individual patients the local activity of inflammationas measured using clinical parameters was found to be relatedto the local SF IL—6 level. When considering the totalgroup of patients, a correlation (P<0.001) was found betweenthe clinical parameters of local inflammation and the SF IL—6levels. Furthermore, IL—6 levels were found to correlatewith leucocyte counts (P<0.02), the percentage of polymorphonuclearcells (P<0.10), the pH value (P<0.01), but not with SFIgM and IgG concentrations. KEY WORDS: Rheumatoid arthritis, Interleukin-6, Synovial fluid     

Sudden death in a young competitive athlete with Wolf--Parkinson--White syndrome

The case history is documented of a young competitive athleteknown to have the electrocardiographic pattern of the Wolff—Parkinson—Whitesyndrome, but considered asymptomatic. On that basis competitivesport was not proscribed. In retrospect, he had experiencedoccasional tachycardias which were of short duration and endedspontaneously. He never requested medical advice. The boy wasfirst admitted for an attack of rapid heart beating which didnot readily subside. He was medicated with prajmalium and leftthe hospital in stable condition. He died suddenly 10 days afterdischarge. Autopsy examination of the heart revealed an accessoryatrioventricular connection in the posterior septal region.The case history underlines that in some patients with the Wolff—Parkinson—Whitesyndrome the clinical manifestation can be minimal and may beeasily ignored by the patient. In retrospect, benign episodesof rapid heart beating most likely were due to a circus movementtachycardia, related to an accessory atrioventricular connection.The sudden death can be attributed to atrial fibrillation withrapid ventricular response via the anomalous connection, despitemedical treatment. The observation endorses the potential dangerof the Wolff—Parkinson—White syndrome in patientswith minimal clinical manifestations. A meticulous histologicstudy of the atrioventricular function in hearts of young athleteswith sudden and unexplained death is a necessity.     

Errors in gated equilibrium radionuclide measurements of resting left ventricular ejection and filling

An assessment was made of the reproducibility (between studydifferences) interobserver variability and intraobserver variabilityof 7 radionuclide measurements describing both resting leftventricular ejection (ejection fraction — EF, averageejection rate — AVER, peak ejection rate — PER,time to peak ejection rate — TPER) and filling (averagefilling rate — AVFR, peak filling rate — PER, timeto peak filling rate — TPFR). Gated blood pool studieswere performed one week apart in 42 patients and between studycorrelation coefficients for these measurements ranged fromv=0.58 (TPER) to r=0.99 (PFR) but there were spontaneous changesin measurements of up to 82% (AVER). Interobserver variabilitywas determined in 44 studies. Correlation coefficients for measurementsobtained by two independent observers in 44 studies rangedfrom r=0.87 (AVER) to r=0.96 (TPFR) but spontaneous changesof up to 52% occurred (AVFR). Intraobserver variability wasdetermined in 53 studies and correlation coefficients rangedfrom r=0.95 (AVER) to r=0.99 (AVFR, PER). The maximum percentagedifference between observations was 46%(AVER). Use of correlation coefficients alone to assess the reproducibilityof these measurements fails to highlight the marked spontaneouschanges which occur in left ventricular function. Changes inradionuclide indices describing left ventricular function inresponse to a therapeutic intervention must be interpreted inthe light of these findings.     

Relationship between the most proximal His bundle and the morphology of intracavitary pressure curves

A precise localization of the most proximal His bundle (HB)is useful both for diagnostic and for therapeutic purposes,allowing the modification of atrioventricular (AV) nodal conduction.For selective diagnosis a bipolar lead is utilized; for therapy,a unipolar lead. The aim of the present study was to determinethe relationship between the most proximal HB and the morphologyof intracavitary pressure curves. In 15 patients (aged 64 ± 10 years), both bipolar andunipolar H-V intervals were continuously recorded while graduallywithdrawing the catheter, which detected the pressure at itstip, from the right ventricle to the atrium. The longest bipolarH—V was 55.5±13 ms and the shortest 44.5±11ms (P<0.001); the longest unipolar H—V was 56.5 ±14 ms and the shortest 46.2±11 ms (P<0.001). During unipolar recording, H deflection was present in all patientsat the same time as ventricular, transvalvular and atrial pressurecurves; during bipolar recording, the H electrogram was notpresent in only one patient concomitantly with the atrial curve.During bipolar recording, the atrial H—V interval wasgreater than transvalvular H—V in nine patients (meandifferences: 6 ± 2 ms) and they were equal in five; withunipolar recording the atrial H—V interval was greaterthan transvalvular H—V in 13 patients (mean difference:8 ± 6 ms) and they were equal in two. In all patients,the H wave amplitude diminished from the transvalvular areato the atrial one. These data suggest that the values of the H—V intervalrecorded in the past have been underestimated. Furthermore,in order to modify AV nodal conduction selectively without damagingthe HB it might be useful to record, in addition to the H deflection,the intracavitary pressure curves so as to deliver energy onlywhen the tip of the catheter picks up an atrial curve.     

Raised levels of antistreptokinase antibody and neutralization titres from 4 days to 54 months after administration of streptokinase or anistreplase

Streptokinase and anistreplase are antigenic and their administrationoften leads to antibody formation. These can cause allergicreactions and/or neutralization of streptokinase with resultingsuboptimal treatment. Currently, streptokinase re-administrationis considered appropriate for up to 5 days and from 1 year aftera previous dose. Antistreptokinase antibody and neutralizationtitres (NT) were measured in three groups of patients to determineif this practice is appropriate: 1. (early)—36 patientswhose titres were measured for at least 5 days after thrombolysis;2. (late)—57 patients who received thrombolysis 12–54months previously; 3. (controls)—182 consecutive suspectedmyocardial infarction patients (without previous exposure tothrombolysis). Results were as follows (mean±SEM): 1. (early)—theantibody and/or NT were raised by day 4 in 19.4% of the patients.One patient could have neutralized 1.97 million units (MU) ofstreptokinase by day 4. (Day 4—antibody 1:39±11,NT 0.19±0.05 MU; day 5–1:136±41 and NT 0.7±0.43MU respectively.) 2. (late)—23 patients (40%) had eitherantibody titres 1:160 and/or NT> 1.5 MU. (12–23 months—antibody1:243±43, NT 0.63±0.15 MU; 24–35 months—1:98±31and 0.69±0.22 MU; 36–54 months—1:87±14and 0.54±0.12 MU.) All titres were significantly higherthan the controls (antibody 1:25±3. NT 0.14±0.01MU, P<0.01). After streptokinase or antistreplase, antibodies are raisedfrom 4 days to at least 54 months. It would seem prudent toavoid their re-administration during this time interval.     

Ig CH AND D14S1 VARIANTS IN RHEUMATOID ARTHRITIS--LINKAGE AND ASSOCIATION STUDIES

We have looked for an effect of 14th chromosomal genes linkedto immunoglobulin heavy chain (Ig CH) or D14S1 regions on susceptibilityto rheumatoid arthritis (RA) by both linkage (sibling pair analysis)and association studies. There was no overall linkage betweenRA and either Ig CH or D14S1. However, Gm haplotype similarityin affected siblings appeared greater in either DR4—positiveas compared to DR4—negative sibships or in sibships withoutclinical or serological evidence of autoimmune thyroid diseasewhen compared to sibships with such evidence. In associationstudies there were no associations at the D14S1 locus. Withinthe Ig CH region there were no overall associations. However,within the RA population Glm (z) and G3m (g) both appeared lessfrequent in DR4—negative RA versus both DR4—positiveRA and versus control groups. Analysis of DNA variants at IgCH loci showed differences at the gamma 4 locus with a 9.0 kbfragment appearing less frequently in DR4—positive RAersus DR4—negative RA and control groups. The resultssuggest a weak or HLA-DR dependent effect of genes linked tethe Ig CH region on susceptibility to RA. KEY WORDS: Rheumatoid arthritis, Genetic susceptibility, Chromosome 14, Immunoglobulin heavy chain, Gm, D14S1     

ARTICULAR DISEASE SEVERITY IN RHEUMATOID SUBJECTS WITH AND WITHOUT FELTY'S SYNDROME

Articular disease severity as measured by a radiographic scoreof hands and feet was compared in rheumatoid subjects with (21)and without (170) Felty's syndrome. Disease duration was a majordeterminant of joint destruction. When this was taken into considerationradiographic scores were no higher in the Felty's group thanin rheumatoid subjects without Felty's syndrome. Immunogeneticassociations previously described in Felty's syndrome are unlikelytherefore to represent non—specific markers of diseaseseverity and more likely to represent markers of extra—articulardisease. KEY WORDS: Radiological scoring, Felty—s syndrome     

The RR index test for the differentiation of atrioventricular nodal block from His--Purkinje block during incremental atrial pacing in patients with bifascicular block

AIMS: His—Purkinje block induced by incremental atrial pacingis highly predictive of an impending high degree atrioventricularblock in patients with bifascicular block. The His potentialis, however, sometimes not measurable or is lost in the ventriculardepolarization. The aim of this study was to evaluate whetherthe comparison of RR intervals before and after atrioventricularblock, induced by incremental atrial pacing, could differentiatebetween atrioventricular nodal and His—Purkinje blockin patients with bifascicular block. METHODS AND RESULTS: In 98 patients with bifascicular block, incremental atrial pacingwas performed as part of an invasive electrophysiological study.An ‘RR index’ was constructed by calculating thenumerical difference between the RR interval immediately beforeand after the atrioventricular block divided by the RR intervalimmediately before the pacing-induced block. Endocavitary recordingof the His bundle potential was used for defining the levelof atrioventricular block. The median RR index was 0·98(range 0·88–1·02) in recordings with His—Purkinjeblock and 0·49 (range 0·11–0·89)in recordings with atrioventricular nodal block (P<0·001).An RR index of 0·85 had a sensitivity of 100% and a specificityof 99% for the identification of atrioventricular block localizedto the His—Purkinje system. CONCLUSION: The use of an RR index is a helpful tool in the differentiationof His—Purkinje from atrioventricular nodal block in patientswith bifascicular block undergoing incremental atrial pacingas part of an invasive electrophysical study.     

MODERN THERAPEUTICSIN RHEUMATIC DISEASE. Edited by G. C. Tsokos, L. W. Moreland and G. M. Kammer. {pound}118.00. Humana Press, Totowa, NJ, USA, 2002. 672 pages. ISBN 0-89603-916-1.

This multi-author text provides a unique mixture of insightsinto current management across the spectrum of rheumatic diseases.I found the book extremely accessible. It is divided into threemain therapy sections—rheumatoid arthritis (RA), osteoarthritis(OA) and connective tissue diseases. There is also an extensivesection on gene therapy. The RA and OA sections     

Starch Block Electrophoresis of Plasma and Serum Clotting Factors. Separation of Activated PTC (PTC')

1. Plasma clotting factors separate into two groups on starch block electrophoresis. The contact activation factors—Hageman factor, PTA, and activatedPTA—remain around the origin, whereas the vitamin K-dependent factors—prothrombin, proconvertin, Stuart factor, and PTC—migrate between the-globulins and albumin. AHG, proaccelerin, and thrombin are not recovered.

2. The electrophoretic pattern of serum differs from that of plasma mainly inthe absence of prothrombin and in the presence of activated PTC (PTC’).

3. The electrophoretic mobility of PTC’ is found to differ from that ofnative PTC. This difference may be exploited to separate PTC’ from its nativeform and from Stuart factor.

Submitted on May 12, 1964 Accepted on July 26, 1964     

ISOLATED ACTH DEFICIENCY PRESENTING WITH BILATERAL FROZEN SHOULDER

We describe a 55—year—old female who presented witha 1—year history of tiredness, depression and painfulstiff joints. The most striking clinical abnormality was bilateralfrozen shoulders, local corticosteroid treatment of which providedthe first diagnostic clue. She was found to have profound diminutionof plasma cortisol secondary to an isolated deficiency of ACTH.There was no obvious cause for this. Steroid replacement eradicatedher lethargy within 3 months and evidence of frozen shouldersresolved completely. KEY WORDS: Shoulder pain, Cortisol, Corticotrophin releasing factor, ACTH, Hydrocortisone     

Too many decades or too little joined up thinking?

SIR, Most rheumatologists know—or should know—thatthis is the Bone and Joint Decade. Those who are leading thisinitiative have rightly made claims for the importance of improvingbone and joint disease     

Dry eyes and mouth syndrome or sicca,asthenia and polyalgia syndrome?

SIR, We read with great interest the recent paper by Price andVenables who proposed a new term—dry eyes and mouth syndrome(DEMS)—to apply to patients presenting with sicca symptomsbut not fulfilling international criteria of Sjögren'ssyndrome (SS) [1].     

Gaps in myocardial infarction care: how might we best EFFECT change?

Despite medical advances, coronary artery disease continuesto burden us. Millions worldwide have a myocardial infarctioneach year, and millions suffer the ravages of atherosclerosis:stable and unstable angina, congestive heart failure, and suddencardiac death. Combating this plague has always required attentionto research—biology of atherosclerosis, drug development,clinical trials—and attention to implementation—accessto care, guideline dissemination, and treatment standardization. The story of ST-elevation myocardial infarction (STEMI) illustratesthe difficulty of doing this. The science has been, in relativeterms, easy. Investigators have steadily progressed from usingaspirin to administering thrombolytics and to employing primarypercutaneous intervention; these advances, along with adjunctivetherapy such as beta-blockers     

Open access: the die is cast

Alea iacta est—‘the die is cast’—GaiusJulius Caesar is quoted as saying as he crossed the Rubiconto invade Rome in 49 BC. The past year has seen momentous changesin the world of journal publishing. The NIH in the USA and theResearch Councils UK (RCUK) and the Wellcome Trust in the UKhave launched their plans for     

Platelet activation in angina at rest. Evidence by paired measurement of plasma beta-thromboglobulin and platelet factor 4

Indexes of in vivo platelet activation, beta-thromboglobulinand platelet factor 4 were measured in triplicate in plasmafrom venous blood of 69 patients with proven ischaemic heartdisease (IHD), discarding samples with a ratio of the plasmaconcentrations of the two proteins <2.6, in order to ruleout sampling artifacts. Compared with 60 control volunteers,differences were not significant [for beta-thromboglobulin controls(ng ml^–1, mean±SD) 27.8–8.6, ischaemic patients32.3±17.1; for platelet factor 4 controls 4.3±1.4,ischaemic patients 5.9±5.7]. However, when patients werestratified according to disease activity (Group I—;patientswithout spontaneous ischaemic episodes at rest during 4 daysof continuous electrocardiographic monitoring; Group II—patientswith <l ischaemic episode/day; Group III—patients with>l episode/day), these indexes were increased in ‘active’patients (for beta-thromboglobulin, in Group II—32.4±10.5ng ml^–1, P<0.05 vs. Group I; in Group III—42.6±14.6ng ml^–1, P<0.01 vs. Group I, P<0.05 vs. control.Platelet factor 4 was increased only in Group III—8.9±7.2ngml^–1, P<0.05 vs. control). Beta-thromboglobulin andplatelet factor 4 were 25.0±6.7 ng ml^–1 and 4.9±4.8ng ml^–1, respectively, in Group I (P=NS vs. control).A relationship with the number of spontaenous ischaemic episodesat rest was confirmed by linear regression analysis (in GroupIII patients for beta-thromboglobulin: r=0.76, P<0.01, andfor platelet factor 4 r=0.62, P<0.01). Levles were not elevatedin patients with pervious myocardial infarction without ischaemiaat rest and/or patients with stable angina, and were not influencedby the occurrence of a positive exercise stress test. Coronaryangiograms of ischaemic patients were analyzed to assess theextent and severity of atherosclerotic involvement; for bothextent and severity, involvement was similar in the three groups.These data support the hypothesis of the occurrence of plateletactivation in patients with spontaneous angina at rest, butnot in other subsets of IHD patients, and establish the possibilityof detecting in vivo platelet activation in IHD by means ofsuch circulating markers.     

Evaluation of three methods for quantifying valvular regurgitation using gated equilibrium radionuclide ventriculography

The non-invasive quantification of mitral and aortic regurgitationusing the left-to-right stroke count ratio (SCR) calculatedwith gated equilibrium radionuclide ventriculography (RNV),is affected by the overlap of atria and ventricles and the consequentdifficult definition of the ventricular regions of interest(ROI). Various solutions of the problem have been proposed.In this study we evaluated the results obtained with a techniquebased on visual inspection of the RNV images (variable ROI method—VRI)and those of two approaches which utilize functional images(stroke volume image method—SVI—and Fourier amplituderatio—FAR), by comparing them with the invasive quantificationof valvular regurgitation according to Sandier et al.^[1] (strokevolume ratio — SVR). Forty patients (15 controls and 25valvular patients) were studied.In the control group the rangeof the SVR wasO.81±1.11 (mean±lSD=1.01±0.08).The SCR was O.83–1.28 (1.03±0.15) with VRI, 1.10–1.15(1.30±0.14) with SVI and 1.11–1.58 (1.35±0.17)with FAR. The correlations between SVR and SCR were r=0.47 (P<0.05),r=0.62 (P<0.001) and r=0.55 (P<0.01) respectively withVRI, SVI and FAR. The SCR of valvular patients fell in the rangeof controls in 11/25 using VRI, 6/25 using SVI and in 4/25 usingFAR. This overlap was present in 2/25 with the invasive quantification.Irrespective of the method used, a reliable assessment of thevalvular regurgitation was not possible in two patients withseverely depressed left ventricular function. We conclude thatthe use of techniques based on functional images clearly improvesthe effectiveness of the non-invasive quantification of valvularregurgitation with the SCR even if this cannot be regarded asa substitute for invasive quantification and has a limited reliabilityin particular groups of patients.     

Evaluation of three methods for quantifying valvular regurgitation using gated equilibrium radionuclide ventriculography

The non-invasive quantification of mitral and aortic regurgitationusing the left-to-right stroke count ratio (SCR) calculatedwith gated equilibrium radionuclide ventriculography (RNV),is affected by the overlap of atria and ventricles and the consequentdifficult definition of the ventricular regions of interest(ROI). Various solutions of the problem have been proposed.In this study we evaluated the results obtained with a techniquebased on visual inspection of the RNV images (variable ROI method—VRI)and those of two approaches which utilize functional images(stroke volume image method—SVI—and Fourier amplituderatio—FAR), by comparing them with the invasive quantificationof valvular regurgitation according to Sandier et al.^[1] (strokevolume ratio — SVR). Forty patients (15 controls and 25valvular patients) were studied.In the control group the rangeof the SVR wasO.81±1.11 (mean±lSD=1.01±0.08).The SCR was O.83–1.28 (1.03±0.15) with VRI, 1.10–1.15(1.30±0.14) with SVI and 1.11–1.58 (1.35±0.17)with FAR. The correlations between SVR and SCR were r=0.47 (P<0.05),r=0.62 (P<0.001) and r=0.55 (P<0.01) respectively withVRI, SVI and FAR. The SCR of valvular patients fell in the rangeof controls in 11/25 using VRI, 6/25 using SVI and in 4/25 usingFAR. This overlap was present in 2/25 with the invasive quantification.Irrespective of the method used, a reliable assessment of thevalvular regurgitation was not possible in two patients withseverely depressed left ventricular function. We conclude thatthe use of techniques based on functional images clearly improvesthe effectiveness of the non-invasive quantification of valvularregurgitation with the SCR even if this cannot be regarded asa substitute for invasive quantification and has a limited reliabilityin particular groups of patients.