Pulmonary edema in man: Comparison of capillary filtration pressure, quantification by means of the double indicator-dilution method, and clinical observations

In three groups of patients, one with no signs of pulmonaryedema (n = 11), one with acute myocardial infarction but withoutpulmonary edema (n = 6) and one with recent myocardial infarctionand clinical signs of pulmonary edema (n = 13), investigationswere performed to determine the degree of pulmonary edema: Pulmonary capillary wedge pressure (PC W), plasma colloid osmoticpressure (COP), and critical pressure (CrP) defined as CrP =PCW – COP. The double indicator dilution method with ¹³¹/ albumin as anintravascular indicator and tritiated water (THO) as a diffusingindicator. Clinical estimates such as radiological and auscultatory criteria. Monitoring of PCW and plasma COP appears to give valuable informationon whether or not pulmonary edema fluid is being generated atthe moment when these measurements are being made. On the otherhand, the information obtained by the double indicator-dilutionmethod proved insufficient to warrant its adoption for routineclinical use. Even the difference in mean transit limes of thetwo indicators was found to be a better measurement of the degreeof pulmonary edema.     

Calcium sensitization with pimobendan: pharmacology, haemodynamic improvement, and sudden death in patients with chronic congestive heart failure

Calcium sensitization increases myocardial contractility byimproving energy utlization of the myocardium, without an increasein intracellular concentrations of cyclic adenosine monophosphate.The calcium sensitizer most extensively studied up to now ispimobendan (UD-CG 115 BS). Vasodilatation results primarilyfrom phosphodiesterase III inhibition Orally administered pimobendan appears rapidly in plasma. Apeak concentration is reached 1.5 h after drug intake; eliminationfrom the plasma compartment has a half-life of 1.5 h. First-passhepatic O-desmethylation of pimobendan produces the active metaboliteUD-CG 212; plasma concentration curves of UD-CG 212 are similarto those of pimobendan, with apeak concentration 1–2 hlater than the peak concentration of the parent compound. In patients with chronic congestive heart failure, pimobendanproduces a dose-dependent and prolonged decrease in pulmonarycapillary wedge pressure and an increase in cardiac output.Maintenance doses ofpimobendan are well tolerated and may leadto lasting symptomatic improvement in patients with heart failure;open and blinded trials show that exercise tolerance increases.No attenuation of these effects is seen during long-term therapywith pimobendan. Patients in chronic congestive heart failure frequently diesuddenly; many inotropic agents increase the incidence of suddendeath in these patients. Although proarrhythmia has never beenobserved with pimobendan, arrhythmia suppression with amiodaroneseems prudent in heart failure patients receiving maintenancedoses of pimobendan.     

Flecainide: one-year efficacy in patients with chronic ventricular arrhythmias

During a one-week short-term in-hospital period, 60 patientswith chronic ventricular arrhythmias were treated with 200 mgflecainide twice a day. Flecainide reduced premature ventricularcomplexes (PVCs) by more than 85% without causing importantside-effects in 47 patients, who entered a one-year follow-upperiod and were followed with bimonthly 24-h ECGs. Median PVC-frequencyremained reduced by more than 99% during the follow-up period.Repetitive ventricular beats and ventricular tachycardia werepresent in 83% and 42% of patients, respectively, before flecainide.During follow-up, these arrhythmias were seen in less than 32%and less than 10% of patients, respectively, at each 24-h ECG.Furthermore, the mean number of hours with repetitive ventricularbeats and ventricular tachycardia remained reduced by more than76% and more than 79%, respectively, throughout the follow-upperiod. Ventricular arrhythmias remained suppressed despitea gradual reduction in flecainide dosages (to a median of 300mg day^–1) and flecainide plasma levels. In nine out of47 patients, an increase in ventricular arrhythmias above baselinevalues on one or more occasions was observed. During a flecainidewithdrawal period, a 65-fold increase in median PVC-frequencywas observed and ventricular tachycardia reappeared in 18 patients.Subjective side-effects were acceptable except for two patients.During the follow-up period, one patient developed reversibleheart failure and sinus node dysfunction. During the total studyperiod, four patients, with either severe coronary artery disease(2) or cardiomyopathy (2) developed lethal arrhythmias (3) orischaemic events (1). We conclude that prolonged flecainidetreatment is effective in a high proportion of patients withchronic ventricular arrhythmias. In some patients an arrhythmogeniceffect may occur.     

Responses of an AV Universal (DDD) Pulse Generator (Cordis 233D) to Programmed Single Ventricular Extrastimuli

To evaluate factors playing a role in initiation and perpetuation of pacemaker-mediated tachycardias (PMTs), 22 consecutive patients with symptomatic conduction disorders were studied after implantation of an AV universal (DDD) pulse generator (Cordis 233D). Patients were divided into two groups, depending upon the presence or absence of ventriculo-atrial (VA) conduction during electrophysiological study (EPS) performed before pacemaker implantation. PMTs could be initiated in six of eight patients of Group I and in none of 14 patients of Group II. Initiation and perpetuation of PMTs during DDD pacing were dependent upon the capacity of the patient to conduct ventricular premature beats (VPBs) and subsequent paced ventricular beats retrogradely to the atria, and upon three programmable parameters of the pulse generator (AV delay period, upper rate limit, tachycardia response). Programmed single ventricular extrastimulation demonstrated that: (1) merely the presence of VA conduction during EPS, although necessary, was not sufficient to induce PMTs after DDD pacemaker implantation; (2) VPBs introduced late rather than early in the cardiac cycle initiated PMTs in a different way; (3) the initiation of PMTs could be prevented during study by adjusting the programmable parameters (AV delay period, upper rate limit, tachycardia response); (4) one of the two available tachycardia responses of the pulse generator (gradual fall-back response) was able to terminate and initiate PMTs consistently. These observations helped in understanding the responses of the Cordis 233D pulse generator to ventricular premature beats. They indicate that additional refinement of the pulse generator is necessary to solve the problem of PMT.     

Pacemaker Electrocardiography of Rate Smoothing During DDD Pacing

A rate smoothing option is available in a new bipolar AV universal (DDD) pacemaker. In three patients, two with intact retrograde conduction and one with retrograde block, rate smoothing values of 3% and 6% were programmed. Irregular pacemaker-mediated tachycardia occurred in one patient and AV synchrony was temporarily lost in the other two patients. In this report, we describe the pacemaker electrocardiography of rate smoothing during DDD pacing.     

Fentanyl-etomidate anesthesia for cardioversion

The effectiveness and safety of anesthesia with fentanyl andetomidate were evaluated in 44 patients undergoing electivecardioversion. No drop in blood pressure was observed; endotrachealintubation was never necessary, and ambu bag assisted ventilationwas needed in only five patients. Anesthesia was induced within7 min in all patients with a mean dose of0.9 mg of fentanyland 15.4 mg of etomidate. After cardioversion, naloxone 0.2mg intravenously was used to antagonize fentanyl; patients werefully awake on average 9 min after the last cardioversion discharge.Complete amnesia was observed in all patients, both 1 hour aftercardioversion and the next morning. For cardioversion, fentanyl-etomidate is as safe, more effectiveand less time-consuming than diazepam.     

Atrioventricular and Ventriculo-Atrial Conduction in Patients with Symptomatic Sinus Node Dysfunction

In 14 patients with symptomatic sinus node dysfunction—sinus bradycardia, sino-atrial exit block, or sinus arrest—electrophysiological studies were performed before implantation of a pacemaker. In 8 patients incremented high right atrial pacing showed AV-nodal Wenckebach at pacing rates equal to or above 130/min (group I); in 6 patients AV-nodal Wenckebach was reached at pacing rates Jess than 130/min (group II). During ventricular pacing at a rate 10–15% faster than the existing sinus rate, ventriculo-atrial (VA) conduction was present in all patients of group I, while VA conduction was present in only 2 patients of group II (p < 0.05). Patients with symptomatic sinus node dysfunction but with intact AV conduction frequency show VA conduction during ventricular pacing and thus are particularly at risk for developing a pacemaker syndrome when a ventricular demand (VVI) pacemaker is implanted. This complication can be avoided by atrial demand (AAI) pacing or A V sequential (DVI) pacing. When adequate experience has been gathered with A V universel (DDD) pacemakers, the indications for selection of a pacemaker in patients with symptomatic sinus node dysfunction will probably change.     

BCL6 gene rearrangements also occur in marginal zone B-cell lymphoma

Marginal zone B-cell lymphoma (MZBCL) represents a distinct subtype of B-cell non-Hodgkin's lymphoma (NHL) which has been recently recognized and defined as a disease entity. Cytogenetically, these lymphomas reveal a high prevalence of trisomy 3, and recent data obtained by comparative genomic hybridization indicate that the chromosomal regions 3q21-23 and 3q25-29 might be of particular pathogenetic significance. We identified structural chromosomal abnormalities involving the region 3q27 and rearrangements of the BCL6 proto-oncogene in three out of 34 (9%) well-defined cases of extranodal, nodal and splenic MZBCL using cytogenetic analysis, Southern blot, and fluorescence in situ hybridization (FISH). All three cases were characterized by a t(3;14)(q27;q32). Two of them showed additional chromosomal abnormalities including trisomy 3, which was found in one case. The patients displayed extranodal disease and did not demonstrate any striking clinical and histological differences when compared with MZBCL lacking BCL6 rearrangement. The present study for the first time demonstrates the occurrence of t(3;14)/ BCL6 gene rearrangement in MZBCL, thus suggesting a role of the BCL6 proto-oncogene in the pathogenesis of MZBCL.     

Cytogenetic clonality analysis: typical patterns in myelodysplastic syndrome and acute myeloid leukaemia

The cell morphology and karyotype of bone marrow samples from 24 patients with myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) were studied simultaneously with a combined technique of May-Grünwald-Giemsa (MGG) staining and fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes. This enabled us to investigate cell lineage involvement in three malignant conditions: MDS ( n  = 12), leukaemia-transformed MDS (LT-MDS) ( n  = 5) and de novo AML ( n =7). In MDS we found blasts and often significant proportions of mature granulocytic and erythroid cells to be cytogenetically abnormal. Percentages of granulocytic and erythroid cells with cytogenetic aberrations were generally less than those of blasts. These data support the involvement of a transformed pluripotent stem cell that has retained maturation abilities. In two patients with chronic myelomonocytic leukaemia (CMMoL) the clonal involvement of monocytes was predominant. Results in the five patients with LT-MDS were similar to those in MDS. In the bone marrow of five of the seven de novo AML patients the cytogenetic abnormalities were restricted to the blasts and did not include the more mature granulocytic or erythroid populations. In the other two patients with AML, both with a t(8;21) and a loss of the Y chromosome, high percentages of mature neutrophils were cytogenetically abnormal. These patterns of clonal lineage involvement in MDS, LT-MDS, t(8;21) AML and AML appear typical and may be of clinical use, for example, for distinguishing LT-MDS from de novo AML in newly presenting patients.