Carvedilol Versus Metoprolol in Patients Undergoing Direct Percutaneous Coronary Interventions for Myocardial Infarction: Effects on QT Dynamicity

Beta-adrenergic blockers exert significant antiarrhythmic activity during ischemia and reperfusion. To further explore the beneficial effects conferred by alpha-1-adrenoceptor blockade on ventricular repolarization dynamicity in the acute phase of myocardial infarction (AMI), we compared carvedilol with metoprolol in the setting of primary percutaneous coronary intervention (PCI). In a prospective study, 100 consecutive patients undergoing primary PCI for AMI were randomized to metoprolol 200 mg/day versus carvedilol 25 mg/day. The first oral dose of study drug was administered and a 24-hour ambulatory electrocardiogram recorded upon hospital admission. Slopes of the linear QT/RR regression were determined before and after reperfusion. A total of 38 recordings of patients treated with metoprolol and 34 recordings of patients with carvedilol were eligible for analysis of QT/RR slopes. The two study groups were similar with respect to age, gender, TIMI perfusion grades, ventricular function, duration of ischemia, and site and size of infarction. Mean RR- and QT-intervals were similar to the metoprolol and carvedilol groups, before and after PCI. Likewise, there was no significant difference in QT/RR slopes between the metoprolol and carvedilol groups before PCI. In contrast, after PCI, there was a trend toward lower QT/RR slopes in the metoprolol group (from 0.18 ± 0.07 to 0.17 ± 0.08), and a significant decrease in QT/RR slopes in the carvedilol group (from 0.17 ± 0.07 to 0.14 ± 0.09). In patients undergoing successful direct PCI for AMI, treatment with carvedilol, in contrast to metoprolol, was associated with a significant decrease in QT–RR slopes, suggesting greater cardiac electrical stability.     

Growth and Differentiation of Transplanted W/Wv Marrow

This paper reports new data on the effect of the action of the mutant genesW and W^v on murine hemopoiesis. Our studies demonstrate that the presenceof these mutant genes produces: (1) a macrocytic anemia with neithergranulocytopenia nor thrombocytopenia; (2) a severe defect in the earlystages of hemopoietic repopulation manifested by (a) an apparent block inthe differentiation of immature cells into erythroid precursors, and (b) a greatly reduced rate of proliferation of differentiated hemopoietic elements.

These data demonstrate the existence of genetic influence on repopulationand differentiation of transplanted marrow and suggest that severe anemia mayresult not only from defects in the late stages of erythroid development butalso from abnormalities in the early stages of erythroid maturation andhemopoietic repopulation.

Submitted on February 15, 1967 Accepted on May 5, 1967     

Life Span of Reticulocytes in Paroxysmal Nocturnal Hemoglobinuria

Two patients with PNH were transfused with young and old Cr⁵¹-labeledred cells. The young red cells (reticulocytes) were destroyed more rapidlythan the older red cells. In vitro studies also revealed that the reticulocytewas more susceptible to acid hemolysis in acidified serum.

In contrast the Cr⁵¹-labeled reticulocytes in 3 patients with perniciousanemia responding to cyanocobalamin showed a normal life span.

In the patients with PNH and pernicious anemia, no sequestration of Cr⁵¹-labeled reticulocytes was noted in the liver or spleen by surface scanning.

Submitted on June 2, 1964 Accepted on September 18, 1964     

Interferon-γ signal transduction during parasite infection: modulation of MAP kinases in the infection of human monocyte cells (THP1) by Toxoplasma gondii

We assayed mitogen-activated protein (MAP) kinase phosphorylation in a human monocyte cell line (THP1) during their infection by Toxoplasma gondii . In addition, we tested the effect of specific MAP kinase inhibitors (PD098059 and SB203580) on parasite invasion. MAP kinase phosphorylation was increased in the cytosol and membrane fractions of THP1 infected with T. gondii . The MAP kinase phosphorylation of uninfected THP1 cells was not significantly modified by incubation for 20 h with 1000 U/ml of IFN-γ. However, IFN-γ treatment of infected cells significantly reduces the increase in phosphorylation caused by parasite infection. There was also MAP kinase activity in the cytosol and membrane fractions of extracellular T. gondii tachyzoites. IFN-γ altered the distribution of activity in subcellular fractions of extracellular T. gondii tachyzoites. This indicates that IFN-γ directly affects parasite MAP kinase activity. The results provide evidence that MAP kinase pathways participate in the infection by T. gondii and that the decrease in MAP kinase activity in infected cells caused by IFN-γ may be involved in mediating their protective signals .     

Comparison of Fixed Tilt and Tuned Defibrillation Waveforms: The PROMISE Study

Comparison of Defibrillation Waveforms . Background: All modern defibrillation systems use biphasic shock waveforms. Typically a fixed tilt waveform is used for implantable defibrillators (ICDs), but a tuned waveform with duration based on shock impedance may be superior based on theoretical calculations. Objective: The objective of this study was to compare defibrillation efficacy of fixed tilt and tuned waveforms. Methods: PROMISE was designed as a prospective, within‐patient, randomized study of defibrillation thresholds (DFTs) comparing a tuned (assuming a 3.5 milliseconds membrane time constant) versus a 50/50% tilt waveform. All patients had a left pectoral implant (active can) and testing was performed with a single coil shocking configuration (“SVC coil OFF”). DFTs were measured in random order with a binary search method in 52 patients, using the high‐voltage lead impedance to select the pulse widths for both waveforms. Results: At the DFT, the tuned waveform had similar delivered energy (10.5 ± 6.3 vs 9.5 ± 5.5 J, P = 0.47), stored energy (13.6 ± 7.9 vs 11.3 ± 6.3 J, P = 0.06), peak current (7.5 ± 3.0 vs 6.8 ± 2.2 A, P = 0.09), and delivered voltage (451.0 ± 134.5 vs 411.5 ± 120.7 V, P = 0.05) compared with the 50/50% tilt waveform. Conclusion: The DFTs for 3.5‐millisecond time constant based tuned and 50/50% tilt waveforms are similar using a single coil, left pectoral active can. (J Cardiovasc Electrophysiol, Vol. 24, pp. 323‐327, March 2013)     

DERMIS-FAT GRAFT: EVOLUTION OF A LIVING PROSTHESIS

Over the past two years 15 dermis-fat grafts were performed Ten were primary grafts, two were implanted because of migrated implants, two for extruding implants and one to correct deep superior sulcus recession.
Our experience showed dermis-tat grafts to be an effective method of correcting orbital volume deficit, of maintaining satisfactory prosthetic motility and of preventing the development of conjunctival deficiency.
In primary dermis-tat grafts fat atrophy was less than 70%, whilst in secondary implants fat atrophy was less than 30% Complications were minimal in our small series