Effect of barucainide on left ventricular ejection fraction in patients with ventricular cardiac arrhythmias]

We studied the effect of barucainide, an investigational class lb antiarrhythmic drug, on ventricular arrhythmias and left-ventricular ejection fraction in 10 patients with frequent and complex ventricular arrhythmias (Lown grade 4a/4b). The study was conducted as a single-blind and placebo-controlled trial. With placebo, mean frequency of ventricular arrhythmias was 6238 VPB/24 h, 510 couplets/24 h, and 24 salvos/24 h. Mean left-ventricular ejection fraction was 37.6%, ranging from 18% to 58%. Therapy with barucainide (300-400 mg/day) resulted in a significant reduction of ventricular arrhythmias in 7 of 10 patients; in one patient barucainide had a clear proarrhythmic effect. Over all, left-ventricular ejection fraction (37.6% +/- 12% with placebo vs 36.1% +/- 11% with barucainide) was not significantly altered. In one patient, however, it was depressed by more than 5%; one patient complained of shortness of breath during exercise. None of the four patients with an initial ejection fraction below 35% showed a drop of ejection fraction during therapy with barucainide. The only main adverse effect was a small, but significant (p less than 0.005) rise of serum-kreatinine (1.13 +/- 0.26 vs 1.39 +/- 0.38 mg%) in all patients. We conclude that barucainide has a good antiarrhythmic effect and is usually well tolerated in patients with markedly depressed left-ventricular function. The mechanism causing the rise of serum-kreatinin, however, needs to be clarified in further studies.     

The Na(+)-H+ exchanger is stimulated and cell volume increased in lymphocytes from patients with essential hypertension.

A stimulation of the Na(+)-H+ exchanger has been shown in platelets of hypertensive man and lymphocytes of spontaneously hypertensive rats. In the present paper, human mononuclear leukocytes (HML) were investigated in 12 patients with essential hypertension with regard to the activity of the Na(+)-H+ exchanger and HML volume. The swelling of HML in isotonic sodium propionate was determined using a Coulter Channelyzer. Compared with matched normotensives, the cell volume of HML in a physiological buffer was significantly increased in essential hypertension (P less than 0.05). The amiloride-inhibitable rate of cell swelling in isotonic sodium propionate was also increased in HML from hypertensives. Amiloride (400 mumol/l) abolished the difference in cell volume within 1 min. These data show a functional swelling of HML in essential hypertension, probably due to an activation of the Na(+)-H+ exchanger. If also representative of smooth muscle cells, these findings could explain hypertensive vessel wall hypertrophy, in part, as functional cell swelling.     

Treatment with the antigranulocyte monoclonal antibody RB6-8C5 impairs resistance of mice to gastrointestinal infection with Listeria monocytogenes.

Treatment with the antigranulocyte monoclonal antibody (MAb) RB6-8C5 increased the severity of infection in mice intragastrically inoculated with Listeria monocytogenes. Most MAb RB6-8C5-treated mice died when inoculated intragastrically with as few as 4 x 10(4) L. monocytogenes bacteria, whereas most control mice survived intragastric inoculation with 4 x 10(8) L. monocytogenes bacteria. The increased severity of infection in MAb RB6-8C5-treated mice appeared to result from listerial multiplication in the spleen and liver rather than from local proliferation in the intestinal tract or mesenteric lymph nodes.     

Altered calcium metabolism in red blood cells of hypertensives: Persistent marker or sequel of essential hypertension?

Summary The characteristics of the increased calcium (Ca) influx observed in metabolically depleted red blood cells (RBCs) of hypertensive patients were investigated. Twenty-four normotensives, 16 untreated essential hypertensives, and 10 essential hypertensives under sufficient blood pressure control by 50–100 mg/day atenolol were studied. Free intracellular concentrations of Ca, sodium (Na), and potassium (K) were assessed using ion-selective electrodes in freeze-thawed RBCs, which were metabolically depleted by 30 mM desoxy-glucose at 37°C for 48 h. In the treated hypertensives values for Ca and K at 24 and 48 h were not different from values for the normotensives, whereas elevated Ca was found in RBCs of untreated hypertensives. Na in treated hypertensives was significantly increased at 0 and 48 h, thus, being similar to values for untreated hypertensives. Additionally, RBCs of six normals were stressed in a glass/teflon potter. Before metabolic depletion electrolytes were not affected by this procedure, while Ca at 24 and 48 h of metabolic depletion increased to significantly higher values for the hypertensive patients as compared to the controls. These results suggest that the altered Ca metabolism in the RBCs of hypertensives may reflect a secondary phenomenon due to the mechanical damage to RBCs by the elevated blood pressure.     

Herpetic croup: two case reports and a review of the literature

Croup is an acute infectious illness usually occurring in children; it is characterized by brassy cough and stridor. The main pathogens include mainly parainfluenza and influenza viruses. Recently there have been reports of prolonged croup caused by the herpes simplex viruses. We report two cases of prolonged croup due to herpes simplex types 1 and 2. We also review and summarize the reported pediatric cases of herpetic croup.     

Medikamentöse Therapie tachykarder Herzrhythmusstörungen

Zusammenfassung Tachykarde Herzrhythmusstörungen lassen sich im wesentlichen auf eine Störung der Erregungsbildung — Fokusgenese — oder der Erregungsleitung — begünstigend für eine Kreiserregung —, zurückführen. Antiarrhythmika wirken diesen beiden entscheidenden Störungen entgegen. Auf Grund ihrer Hauptwirkung auf das Aktionspotential isolierter Herzmuskelzellen in therapeutischen Dosen lassen sich die Antiarrhythmika in 4 Gruppen einteilen. Beim Menschen läßt die schwerpunktmäßige Beeinflussung der Erregungsleitung in den verschiedenen Anteilen des Erregungsleitungssystems Anwendungsschwerpunkte begründen und Nebenwirkungen voraussagen. Die Antiarrhythmikawirkung auf die elektrophysiologischen Vorgänge am kranken menschlichen Herzen sind bisher noch unzureichend untersucht, so daß für die klinische Therapie letztlich die Empirie, d.h. die systematische therapeutische Anwendung entscheidet. Für die wichtigsten Antiarrhythmika haben sich so bevorzugte Indikationen ergeben. Unter bestimmten Voraussetzungen ist in der Klinik aber auch eine pathogenetisch differenzierende Therapie möglich, wenn auf Grund der bekannten spezifischen Wirkung eines Antiarrhythmikums ein Rückschluß auf die Pathogenese möglich wird; so u.a. beim Ansprechen auf Kalziumantagonisten, Typ Verapamil, die offenbar spezifisch auf sogenannte slow response Aktionspotentiale wirken. Vorbestehende TU-Abnormitäten im EKG weisen auf eine inhomogene Repolarisation als prädisponierenden Faktor für ventrikuläre Tachykardien durch Kreiserregung hin. Beim akuten Herzinfarkt kommt es zu wechselnden elektrophysiologischen Voraussetzungen für die Entstehung von Herzrhythmusstörungen, die eine therapeutische Beeinflussung durch ein einziges Antiarrhythmikum unwahrscheinlich erscheinen lassen. In der Hospitalphase ist eine ausreichend dosierte prophylaktische Gabe von Lidokain sinnvoll, in der prähospitalen Phase ohne Überwachungsmöglichkeit jedoch von zweifelhaftem Wert. Die prophylaktische Gabe von Betarezeptorenblockern kann in der posthospitalen Nachbehandlungsphase das Risiko des plötzlichen Herztodes um 50% senken. Auch bei anderen Risikopatienten mit ventrikulären Herzrhythmusstörungen ist eine konsequente antiarrhythmische Behandlung notwendig.     

Polymorphism in ospC gene of Borrelia burgdorferi and immunoreactivity of OspC protein: implications for taxonomy and for use of OspC protein as a diagnostic antigen.

The nucleotide sequences of the ospC gene from five Danish human Borrelia burgdorferi isolates representing all three B. burgdorferi genospecies (B. burgdorferi sensu stricto, Borrelia garinii sp. nov., and group VS461) and from the American type strain B31 were determined and compared with the published ospC sequence from the German B. burgdorferi isolate PKo (R. Fuchs, S. Jauris, F. Lottspeich, V. Preac-Mursic, B. Wilske, and E. Soutschek, Mol. Microbiol. 6:503-509, 1992). The ospC gene was present in all isolates, regardless of the presence or absence of its product, OspC. The deduced amino acid sequences of OspC from the seven isolates were aligned and revealed pairwise sequence identities ranging from 60.5 to 100%. Differences were scattered throughout the amino acid sequences. A phylogenetic tree was constructed and revealed three distinct phenotypic groups OspCI to OspCIII corresponding to the three delineated genospecies. Immunoblot analysis revealed that the seven OspC proteins tested have both common and specific epitopes. There is significant epitope diversity, since even polyclonal antisera showed serotype-restricted specificity. Therefore, a serodiagnostic assay for Lyme borreliosis utilizing OspC as a test antigen should include all three OspC phenotypes in order to obtain a species-wide sensitivity.     

The Dominant Epitope of Borrelia garinii Outer Surface Protein C Recognized by Sera from Patients with Neuroborreliosis Has a Surface-Exposed Conserved Structural Motif

Epitope mapping of outer surface protein C (OspC) by using sera from patients with neuroborreliosis led to the identification of one single major immunodominant epitope within the C-terminal 10 amino acid residues. Peptide binding studies and alanine replacement scanning of the C-terminal decapeptide, PVVAESPKKP, revealed a critical role for the PKKP sequence and its terminal carboxyl group for the binding of immunoglobulin M (IgM) antibodies from patients with Lyme borreliosis. Electron microscopy of antibody-labeled spirochetes indicated that the C-terminal region is exposed on the surface of the spirochete. Based on homology to proteins of known function, this region most probably adopts a polyproline II-like helix, which is found in surface-exposed structures involved in protein-protein interactions. This structural motif is highly conserved in Borrelia species causing Lyme borreliosis and subjected to purifying selection. We suggest that the abundance of the C-terminal region of OspC on the surface of B. burgdorferi allows a multimeric high-avidity interaction between the spirochete and surface Igs on B cells. The resulting cross-linking of surface Igs on B cells may induce a T-cell-independent B-cell activation without IgM-to-IgG switching, thus explaining the lack of IgG antibodies to OspC in neuroborreliosis.     

Peptide-Based OspC Enzyme-Linked Immunosorbent Assay for Serodiagnosis of Lyme Borreliosis

Sera from 210 patients with Lyme borreliosis (LB) were studied by an enzyme-linked immunosorbent assay (ELISA) based on a synthetic peptide (pepC10) comprising the C-terminal 10-amino-acid residues of OspC of Borrelia burgdorferi. We found that 36.3 and 45.0% of the serum samples from patients with erythema migrans (EM) and neuroborreliosis (NB), respectively, displayed immunoglobulin M (IgM) anti-pepC10 reactivities, while these samples rarely (≤8%) displayed IgG antibody reactivities. Sera from patients with acrodermatitis chronica atrophicans did not contain anti-pepC10 antibodies. The diagnostic performance of this newly developed peptide ELISA was compared with those of an ELISA based on the full-length recombinant OspC protein (rOspC) and a commercially available ELISA based on the B. burgdorferi flagellum (Fla). The sensitivity of the IgM pepC10 ELISA was slightly lower (P < 0.04) than that of the rOspC ELISA for EM patients (36.3 versus 43.8%), while there was no difference for NB patients (45.0 versus 48.0%). However, the optical density values obtained by the pepC10 ELISA were generally higher than those obtained by the rOspC ELISA, leading to a significantly better quantitative discrimination between seropositive patients with NB and controls (P < 0.008). The specificity of the pepC10 ELISA was similar to those of the rOspC ELISA and the Fla ELISA for relevant controls including patients with syphilis and mononucleosis. Although the overall diagnostic sensitivity of the Fla ELISA was superior, 8.8 and 12.0% of the EM and NB patients, respectively, were antibody positive only by the pepC10 ELISA. Thus, use of a diagnostic test for LB based on the detection of IgM antibodies to pepC10 and Fla has increased sensitivity for the diagnosis of early LB.     

Effects of iodide on class II-MHC antigen expression in iodine deficient hyperplastic thyroid glands

The expression of major histocompatibility complex class II molecules (Ia antigen) has been analyzed by immunoperoxidase staining in thyroids of normal C3H mice, of iodine-deficient mice with a hyperplastic goiter and of mice during goiter involution induced by administration of either a high iodide dose (HID, 10 micrograms/day) for 0.5 to 8 days or a moderate iodide dose (MID, 1 microgram/day) or triiodothyronine (T3, 1 micrograms/day) for 2 days. In normal and in hyperplastic thyroids, few interstitial cells were Ia positive (monoclonal antibodies, mAb, M5/114, ER-TR3). Their number was unchanged when goiter involution was induced by MID or by T3, but was significantly increased (p less than 0.05) after HID. It was maximal at days 1 and 2 of involution, decreased thereafter but remained higher (p less than 0.05) than in controls after 8 days. The Ia positive cells were mainly macrophages and, to a lesser extent, dendritic cells. Macrophages were identified by their heterogeneous content and their numerous lysosomes. They were stained with anti-Mac-1 (M1/70) and anti-Mac-2 (M3/38) mAb. Dendritic cells were characterized by their slender cytoplasmic processes, indented nucleus and pale cytoplasm. They were positive for NLDC-145 and MIDC-8 mAb whose specificity for dendritic cells has been demonstrated in lymphoid organs. During the whole period of involution analyzed, Ia antigens were not expressed on follicular cells. Since macrophages and dendritic cells are known to be involved in the pathogenesis of immune disorders, the inflammation induced by administration of HID to iodine-deficient mice could be considered as the early step of an immunological reaction.