Characteristics of Bifocal Pacing:

Bifocal RIGHT ventricular stimulation (BRIGHT) is an ongoing, randomized, single-blind, crossover study of atrial synchronized bi-right ventricular (RV) pacing in patients in New York Heart Association heart failure functional class III, a left ventricular ejection fraction <35%, left bundle branch block and QRS complexes ≥120 ms. This analysis compared the electrical and handling characteristics, and the complications of pacing at the RV apex (Ap) with passive, versus RV outflow tract (OT) with active fixation leads. A mean of 1.6 ± 0.9 and 2.2 ± 2.0 attempts were needed to position the Ap and OT leads, respectively (ns). R-wave amplitudes at Ap versus OT were 23 ± 13 mV versus 14 ± 8 mV (n = 36, P < 0.001). R-wave amplitudes at the Ap remained stable between implant and M7. R-wave amplitudes at the OT could not be measured after implantation. In two patients, atrioventricular block occurred during active fixation at the OT. Conduction recovered spontaneously within 4 months. Ventricular fibrillation was induced in one patient during manipulation of an Ap lead in the RV. Marked differences were found between leads positioned in the OT versus Ap, partly related to the difference in lead design. Mean R-wave amplitude was higher at the Ap that at the OT. Ease and success rate of lead implant was similar in both positions.     

Job stress, absenteeism and coronary heart disease European cooperative study (the JACE study): Design of a multicentre prospective study

Background: The motives, objectives and design of a multicentreprospective study on job stress, absenteeism and coronary heartdisease in Europe (the JACE study) is presented in this paper.Some specific gaps in the reviewed literature are explicitlytapped into by the JACE study. Its objectives are i) to comparethe distributions of the Karasek job stress scales for the samebroad categories of occupations in different European countries(in males and females), ii) to study the predictive power ofthe job stress scales and the job strain model for one yearof sickness absence (in males and females) and iii) to studythe predictive power of the job stress scales and the job strainmodel for a three year incidence of coronary heart disease (Inmales only). Methods: In answering these questions, relationsare studied controlling for gender, age, level of education,company size, physical work risks and shift work, as well astraditional risk factors for CHD (i.e serum cholesterol, serumHDL cholesterol, smoking habits and blood pressure). The JACEstudy is a Biomed 1 concerted action. The JACE group consistsof eight participating centres from six countries, i.e. fromBelgium and Sweden (two centres), France, Italy, Spain, Swedenand The Netherlands (each one centre). The coordination of thegroup is in Brussels. The participating centres brought in over15, 000 European workers to test the hypotheses.     

Hookworm Anemia: Iron Metabolism and Erythrokinetics

Iron metabolism, balance of red cell production and destruction and ironabsorption from hemoglobin were determined in 11 patients with heavy hookworm infection and severe anemia.

The plasma iron, total iron binding capacity, bone marrow hemosiderinand plasma Fe⁵⁹ clearance are in agreement with the idea that the anemia associated with hookworm infection is of the iron deficiency type.

The rate of red cell production measured by the E/M ratio, absolute reticulocyte count and plasma iron turnover showed an increase to about twicenormal, while the rate of destruction estimated by the T erythrocytesurvival showed a destruction about 5 times normal. This unbalance betweenproduction and destruction could explain the severity of the anemia.

The increase of fecal urobilinogen output to twice normal was interpretedas due to the metabolism of the hemoglobin lost into the intestine rather than toan increase of hemolysis.

The estimation of fecal blood loss in the patients whose red cells weretagged with Cr⁵¹ and Fe⁵⁹, showed that the radioactivity counted with Fe⁵⁹was only about 63 per cent of the radioactivity counted with Cr⁵¹. This difference was interpreted as due to iron absorption from the hemoglobin lostinto the intestine.

The mean daily fecal excretion of iron reaches 4.7 mg. Since the ironmetabolism in these patients is in equilibrium, we have concluded that theiron loss is replaced by the iron from food; this is in addition to the 3 mg.hemoglobin iron which is reabsorbed from the blood lost into the gut.

Submitted on January 9, 1961 Accepted on April 2, 1961     

The influence of HLA-matched sibling donor availability on treatment outcome for patients with AML: an analysis of the AML 8A study of the EORTC Leukaemia Cooperative Group and GIMEMA

To determine whether patients with a HLA-identical sibling donor have a better outcome than patients without a donor, an analysis on the basis of intention-to-treat principles was performed within the framework of the EORTC-GIMEMA randomized phase III AML 8A trial. Patients in complete remission (CR) received one intensive consolidation course. Patients with a histocompatible sibling donor were then allocated allogeneic bone marrow transplantation (alloBMT), the patients without a donor were randomized between autologous BMT (ABMT) and a second intensive consolidation (IC2). 831 patients <46 years old and alive >8 weeks from diagnosis were included. HLA typing was performed in 672 patients. AlloBMT was performed during CR1 in 180 (61%) out of 295 patients with a donor. Another 38 patients were allografted: five in resistant disease, 14 during relapse and 19 in CR2. ABMT was performed in 130 (34%) out of 377 patients without a donor in CR1, in six (2%) patients during relapse and in 38 (10%) patients during CR2. The disease-free survival (DFS) from CR for patients with a donor was significantly longer than for patients without a donor (46% v 33% at 6 years; P = 0.01, RR 0.78, 95% confidence interval 0.63–0.96). The overall survival from diagnosis for patients with a donor was longer, but not statistically significant, than for patients without a donor (48% v 40% at 6 years; logrank P = 0.24). When patients were stratified according to prognostic risk groups, the same trend in favour of patients with a donor was seen for survival duration and the DFS remained significantly longer for this group of patients.     

Hereditary Spherocytosis: Observations on Hemolytic Mechanisms and Iron Metabolism

1. Two healthy patients with hereditary spherocytosis were phlebotomizeduntil they developed iron deficiency and the erythrocytes became hypochromic.The hereditary spherocytes were no longer spheroidal: they became thin, andthe fragility tests improved. However, the life span of the cells in the circulation was not improved. Later, splenectomy corrected the hemolytic disease.

2. In both patients, prior to the experiment, the hemolytic disease wascompensated. There was no anemia despite the rapid turnover of red cells.In one of the patients, whose average red cell life span was only five days, theoutput of hemoglobin must have been exceedingly high. It was computed tobe 135 Gm. per day, or 20 times the normal rate.

3. Some aspects of iron metabolism in hereditary spherocytosis are discussed.

4. The shape of the red cell in HS does not appear to be responsible for itspremature destruction by the spleen. Iron deficiency corrects the spherocytosis,but it does not correct the hemolytic disease. Splenectomy corrects the hemolytic disease, but it does not correct the spherocytosis.

     

A method to estimate binding constants at variable protein concentrations

The association constants of the binding of chlorpromazine and imipramine to serum albumin at low saturation of the protein were determined by a new experimental approach with the protein concentration rather than the ligand concentration being varied. This approach is suitable for estimating binding constants in systems with one class of binding sites. In addition, the method is proposed to complement conventional binding studies of systems with two classes of binding constant with higher accuracy.     

Peptide-lanthanide cation equilibria in aqueous solution

Lanthanide ion complexes of α-L-aspartyl-L-phenylalanine methyl ester have been characterized in the pH range 2.50-7.00. Proton resonance shifts in D₂O and DMSO were used to determine the conformational mobility and a tentative structure in solution is proposed. The observed trends in the magnitude of the shift ratios and the rotamer population suggested that the metal ion Pr(III) or Dy(III) bound to the carboxylate group and gave information about the peptide backbone. The result of this analysis has been used to select a preferential conformation of the molecule: ø₁? 60d?, φ₂? -150d?, C^βCγLn = 140d?± 10d?, C^αC^βC^γLn = 10d?± 20d? (hindered rotation), Cγ-Ln = 2.85Ad?± 0.1Ad?.     

Reflex Cardiac Asystole

In this report we present the case of a patient with recurrent syucopal episodes. During one of the attacks the patient was monitoring by telemetry and the ECC lead showed asvstole for more than 7 seconds. As in cases of the carhlinhibitory type of hypersenstive carolid sinus svndrome [HCSS]. asvstole may represent suppression of the sinus node or suppression of both sinus and atioventricular [AV] node. Unfortunately, in contrast to HCSS, there is no maneuver that can reproducibly induce episodes of asystole. Consequentlty, very little is known about the occurrence of AV block in the presence of sinus arrest. In the patient described in this report. We were able to demonstrate that suppression of sinus and AV nodes occured simultaneously. This is interesting to note that in this type of syneope data from noninvasive and invasive techniques in assessing sinus nodal and AV nodal conduction may note be conclusive. In the group of patients with this type of syncope, permanent artial demand pacing is constraindicated.     

Mode Switch Despite Undersensing of Atrial Fibrillation in ODD Pacing

Mode switching algorithms are commonly used to protect the ventricles against high rates induced by atrial tachycardia. In the case of atrial fibrillation (AF), the response of these algorithms depends on the quality of atrial sensing. The Chorum 7234 DDDR pacemaker uses a new mode switching algorithm, based on a statistical analysis of the atrial rhythm. It includes two criteria of diagnosis: "high" if more than 28 of 32 cycles are abnormally accelerated; and "low" if more than 36 of 64 cycles are abnormally accelerated. Methods: From a taped database of electrophysiological studies, episodes of AF lasting more than 2 minutes were selected. A tape recorder replayed the atrial signals into an external Chorum device. Each episode was replayed eight times with a programmed atrial sensitivity increasing from 0.4 –2.0 mV. For each criterion of diagnosis and each programmed sensitivity, the percentage of atrial sensing, the time to switching, and the mean ventricular rate were measured. Ten episodes of AF from 10 patients (9 men and 1 woman; ages 62 ± 16 years) were included: 1.95 ± 0.97 mV and 196 ± 64 ms. The sensitivity of the algorithm to diagnose atrial tachycardia reached 100%, for an atrial sensitivity set between 0.4 and 1.0 mV. The mean percentages of atrial sensed events were 74%± 18% and 46%± 9% for the "high" and "low" criteria, respectively. The mean diagnostic times were 28 ± 26 seconds and 68 ± 27 seconds, respectively. Sensing of < 23% of AF events resulted in failure to diagnose the arrhythmias by both algorithms. In the event of diagnostic failure, the mean ventricular pacing rate was 79 ± 9 ppm. Conclusion: Up to an atrial sensitivity of 1 mV, 100% of AF episodes were diagnosed. The Chorum mode switching algorithms are 100% reliable if > 45% of the AF waves are sensed. In the event of switching failure, the ventricle is protected by an average rate remaining below 80 ppm. (PACE 1996;