Electrocardiographic and Clinical Predictors of Torsades de Pointes Induced by Almokalant Infusion in Patients with Chronic Atrial Fibrillation or Flutter: A Prospective Study

The aim of this study was to identify predictors of torsades de pointes (TdP) in patients with atrial fibrillation (AF) or flutter exposed to the Class III antiarrhythmic drug almokalant. TdP can be caused by drugs that prolong myocardial repolarization. One hundred patients received almokalant infusion during AF (infusion 1) and 62 of the patients during sinus rhythm (SR) on the following day (infusion 2). Thirty-two patients converted to SR. Six patients developed TdP. During AF, T wave alternans was more common prior to infusion (baseline) in patients developing TdP (50% vs 4%, P < 0.01). After 30 minutes of infusion 1, the TdP patients exhibited a longer QT interval (493 ± 114 vs 443 ± 54 ms [mean ± SD], P < 0.01), a larger precordial QT dispersion (50 ± 74 vs 27 ± 26 ms, P < 0.05), and a lower T wave amplitude (0.12 ± 0.22 vs 0.24 ± 0.16 mV. P < 0.01). After 30 minutes of infusion 2, they exhibited a longer QT interval (672 ± 26 vs 489 ± 74 ms, P < 0.001), a larger QT dispersion in precordial (82 ± 7 vs 54 ± 52 ms, P < 0.01) and extremity leads (163 ± 0 vs 40 ± 34 ms, P < 0.001), and T wave alternans was more common (100% vs 0%, P < 0.001). Risk factors for development of TdP were at baseline: female gender, ventricular extrasystoles, and treatment with diuretics; and, after 30 minutes of infusion: sequential bilateral bundle branch block, ventricular extrasystoles in bigeminy, and a biphasic T wave. Patients developing TdP exhibited early during almokalant infusion a pronounced QT prolongation, increased QT dispersion, and marked morphological T wave changes.     

Acute Myocarditis

ABSTRACT In a prospective study, 57 patients with a preliminary diagnosis of myocarditis were investigated. Twenty-four patients were considered to have an acute myocarditis, 14 had a suspected myocarditis, while in 19 patients myocarditis was excluded. Episodes of frequent supraventricular and/or ventricular extrasystoles during hospital stay were seen in 8/24 cases (33%) with myocarditis and in 1/19 cases (5%) without myocarditis. On follow-up 1 month later, no supraventricular extrasystoles were observed in either group. Echocardiographic signs consistent with left ventricular insufficiency were noted in 7/24 cases (29%) with myocarditis, in 1/14 cases (7%) with suspected myocarditis and in no case without myocarditis. With a “routine” serologic test battery covering influenza viruses A and B, adenovirus, Coxsackie virus group B, ECHO viruses, Chlamydia psittaci, Mycoplasma pneumoniae and hemolytic streptococci group A, a possible etiology could be documented in 9/24 cases (38%) with myocarditis and in 4/19 cases (21%) without myocarditis. Enterovirus-specific IgM was detected with solid-phase reverse immunosorbent test (SPRIST) in 12/23 (48%) cases with myocarditis and in 3/16 cases (19%) without myocarditis. In SPRIST-IgM-positive cases, IgM antibodies were detected in 15/20 (75%) of the sera taken on admission. The overall serological results indicated a recent infection in 16/24 cases (67%) with myocarditis and in 5/19 cases (26%) without myocarditis (p < 0.05).     

Cyclic Neutropenia Terminating in Permanent Agranulocytosis

ABSTRACT A patient with cyclic neutropenia was followed for 20 years. After 16 years she developed a permanent agranulocytosis, and lived for nearly four years without neutrophils in the peripheral blood. Neither prednisone, lithium nor Jeuco- and plasmapheresis had any effect on the neutrophil count.     

Effects of 4-aminopyridine on contractile response and action potential of rabbit papillary muscle

The effects of 4-aminopyridine (4-AP) were studied on isolated papillary muscles from the heart of reserpinized rabbits (at 37°C). The preparations were paced to contract at 0.67 Hz under isometric conditions and the muscle length was adjusted to 95 % of the length for optimum force production. Simultaneous recordings of isometric force and membrane potentials were performed. 4-AP (50 μM) increased peak force by approximately 20% of the control and prolonged the action potential by 20%. Higher concentrations of 4-AP (800 μ.M) resulted in further increments of force and action potential duration (60 and 70% of controls, respectively). Prolongation of the action potential and potentiation of the isometric force was still present one hour after withdrawal of the drug from the perfusate. The results are consistent with the view that 4-AP prolongs the action potential by inhibiting the late repolarizing potassium current. It is suggested that the calcium uptake by the ventricular cell during the prolonged action potential is increased and that this leads to the positive inotropic effect.     

Withdrawing Long-Term Diuretic Treatment Among Elderly Patients in General Practice

The aim of this study was to elaborate, implement and evaluatea strategy for discontinuation of long-term diuretic treatmentin elderly patients in general practice. Thirty-three patientswere enrolled for a supervised step-down and withdrawal of diuretics.After withdrawal, the patients were followed up for 6 monthsor until diuretic treatment was re-established. Withdrawal wassuccessful according to the protocol in 18 cases. Diuretic withdrawalfailed and the treatment was re-established in 15 cases, fourof which were sudden cardiovascular events. Most withdrawalfailures were identified by routine examinations through thefollow-up programmes, thus they had few consequences for thepatients. This demonstrates that careful follow-up is essentialafter diuretic withdrawal. Our findings support the view thata large proportion of elderly patients on diuretics may notneed such treatment.     

Phagolysosomal pH and Location of Particles in Alveolar Macrophages

Phagolysosomal pH and Location of Particles in Alveolar Macrophages.NYBERG, K., JOHANSSON, U., JOHANSSON, A., AND CAMNER, P. (1991).Fundam. Appl. Toxicol. 16, 393–400. Fluorescein-labeledsilica particles (FSP) were instilled into the tracheae of rabbits.Groups of four rabbits were killed after 24 hr, 1 week, 1 month,or 3 months and their lungs were lavaged. Phagolysosomal pHin the alveolar macrophages (AM) was measured using microscopefluorometry with FSP as a probe. Due to the marked decline ofthe fluorescence intensities from the FSP between 1 and 3 monthsafter instillation, it was not possible to measure pH at 3 months,but the values from 24 hr, 1 week, and 1 month were quite similar,with group means of 4.8 and 4.9, respectively. PhagolysosomalpH in AM which phagocytized the FSP in vitro showed values abouthalf a pH unit higher. AM from rabbits lavaged at 1 week hadmore lysosomes in contact with the FSP-containing phagolysosomesand a higher degree of vacuolization between the FSP and thephagolysosomal membrane than AM lavaged at 1 day. The locationof the FSP in the AM appeared to be similar in rabbits lavagedafter 1 week and 3 months. In histologic sections from the lungsthe large majority of the FSP were within cells at all timepoints.     

Increased lymphatic vascular density is seen before colorectal cancers reach stage II and growth factor FGF‐2 is downregulated in tumor tissue compared with normal mucosa

Lymphangiogenesis is an important event in progression of colorectal cancer (CRC), and the estimated lymphatic vascular density (LVD) probably indicates facilitated lymphatic tumor cell invasion and metastasis. However, at what time point during tumor progression this process is triggered, is unclear. The aim of this study was twofold. Firstly, to examine LVD in paired samples of CRC tissue and normal mucosa with specific emphasis on possible difference in LVD between tumors stages II and III, and secondly, the expression of the lymphangiogenic growth factor fibroblast growth factor‐2 (FGF‐2). Eighteen patients were studied. Immunostaining for podoplanin was performed to highlight lymphatic vessels. FGF‐2 mRNA expression was determined by quantitative real‐time RT‐PCR, whereas protein expression was quantitatively assessed by densitometric analysis of Western blot signal intensity. The immunoblots were further validated by FGF‐2 immunostaining of histological sections. LVD was significantly increased in tumor tissue compared with the normal mucosa but no changes in LVD between stages II and III CRC was observed. FGF‐2 was found to be downregulated both at the mRNA and protein level in tumor tissues compared with normal mucosa. Lymphangiogenesis was triggered early in tumor development. An increased LVD was established before the tumor reached stage II. FGF‐2 was downregulated in tumor tissue. The importance of this finding remains unclear.     

Vasotocin analogues which competitively inhibit vasopressin stimulated uterine activity in healthy women

Summary. Three analogues of posterior pituitary hormones, 1 - deamino - 2 - D - Tyr(OEt) - 4 - Val - 8 - Om - vasotocin(dE - VVT), l-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-vasotocin(dE-TVT) and 1-deamino-2-D-Tyr(OEt)-oxytocin(dE-OXY) were compared for their inhibitory effects on vasopressin (VP)-induced uterine activity in healthy women. At menstruation, during recording of intrauterine pressure (18 recording sessions in 11 women), intravenous infusion of lysine vasopressin (LVP, 1 ng/min/kg/body weight) induced an increase of the uterine activity and dysmenorrhoea-like symptoms. Intravenous injections of all analogues (10 μg/kg body weight) caused relief of symptoms and inhibition of uterine activity, dE-TVT was the most effective and dE-OXY was least active. With dE-TVT almost complete inhibition of contractions was seen during the first 10 min after injection. The duration of effect was also greatest with that analogue (40–50 min). Only dE-OXY had an agonist effect on spontaneous uterine activity. Pharmacokinetic studies of intravenous dE-TVT (10 ng/kg body weight) showed that the plasma half-life was approximately 16 min and the clearance 30 1/h. The bioavailability of 100 ng/kg given intra-nasally was about 5·5%. Further studies are recommended.