Leukokinetic Studies. VII. Morphology of the Bone Marrow and Blood of Dogs Given Vinblastine Sulfate

The effect of a single injection of vinblastine sulfate was studied in 50mongrel dogs. Nine of 34 dogs given 0.2 mg./Kg. of VLB died with gastrointestinal toxicity and the mortality rate increased as the dosage of VLB wasincreased. The morphologic pattern of leukocyte suppression and recovery inthe bone marrow and blood was studied in detail in surviving animals.

The cells of the bone marrow were markedly affected by VLB. Within 4hours there was an increase in the number of cells in metaphase and, by day1, virtually all proliferating leukocytes and erythrocytes had disappeared. Anorderly repopulation of the bone marrow followed.

The neutrophils, eosinophils, lymphocytes and monocytes of the blood wereall markedly altered in concentration after VLB. Each type of cell first decreased to abnormally small numbers and then increased to abnormally largenumbers in the blood. The curve of disappearance from and reappearance inthe blood differed for each cell type.

The changes in blood neutrophil number and morphology were correlatedwith changes in the blood neutrophil precursor cells of the marrow. The following conclusions were reached concerning the neutrophils and the assumptions implicit to these conclusions were detailed.

1. In the dog, the marrow contains enough post-mitotic granulocytes toreplace those lost from the blood for at least 3 to 4 days.

2. The release of mature neutrophils from the bone marrow is a functionof the rate at which blood neutrophils are lost and proceeds normally evenwhen the marrow granulocyte reserve is partially depleted.

Submitted on March 27, 1963 Accepted on August 20, 1963     

Safety and Effectiveness of Transvenous Lead Extraction in Octogenarians

Transvenous Lead Extraction . Introduction: As the population ages, the number of elderly patients with implantable cardiac devices referred for transvenous lead extraction will dramatically increase in Western countries. The safety and effectiveness of lead extraction in elderly patients has not been well evaluated. We report the safety and effectiveness of transvenous lead extraction in octogenarians. Methods and Results: From January 2005 to January 2011, we reviewed data from consecutive patients ≥ 80 years referred to our institutions for transvenous lead extraction because of cardiac device infection or lead malfunction. Clinical characteristics, procedural features, and periprocedural major and minor complications were compared between octogenarians and younger patients. Out of 849 patients undergoing lead extraction in the participating institutions during the study period, 150 (18%) patients were octogenarians (mean age 84 years; range 80–96; 64% males). A significantly higher percentage of octogenarians presented with chronic renal failure (55% vs 26%; P < 0.001), history of malignancy (22% vs 6%; P < 0.001), and chronic obstructive pulmonary disease (46% vs 19%; P < 0.001). Complete lead extraction rates were similar in the 2 age groups (97% in octogenarians vs 96% in patients <80 years; P = 0.39). Periprocedural death occurred in 2 (1.3%) patients ≥80 years and in 5 (0.72%) patients <80 years (P = 0.45 for comparison). No differences in terms of other periprocedural major and minor complications were found between the 2 age groups. Conclusion: Despite presenting with a significantly higher rate of comorbidities, transvenous lead extraction can be performed safely and successfully in octogenarians. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1103‐1108, October 2012)     

Heterozygous Beta-Thalassemia in Association with Hereditary Elliptocytosis: A Family Study

The association of the genes for beta-thalassemia and hereditary elliptocytosis are described in an Italian family. Genetic study of this family indicatesthat the involved genes are not allelic and are not closely linked. Clinicaland laboratory data further suggest that the effects of both genes are summated when present in the same individual.

Submitted on April 15, 1964 Accepted on June 26, 1964     

Digestion by pancreatic juice of a beta-casomorphin-containing fragment of buffalo beta-casein

Degradation by pig pancreatic juice of a beta-casomorphin-containing fragment (tryptic peptide corresponding to residues 49–68 of buffalo beta-casein) was investigated. The FAB/MS (fast atom bombardment mass spectrometry) technique was used to identify the fragments produced by the concerted action of pancreatic proteases. Pancreatic juice, under our experimental conditions, is not able to release beta-casomorphins or morphiceptin from the tryptic peptide sequence. Furthermore, the present report shows that the rapid hydrolysis of a peptide bond by a single protease can prevent the cleavage of peptide bonds by a different protease. Therefore the formation of some peptides in the gastrointestinal tract can depend on the protease ratio.     

Long-Term Results of Hybrid Therapy in Patients with Atrial Fibrillation Who Develop Atrial Flutter During Flecainide Infusion

The flecainide infusion test has been proposed to screen candidates for hybrid pharmacological and ablation therapy. We report the long-term follow-up of 154 consecutive patients with paroxysmal or persistent atrial fibrillation (AF) who developed atrial flutter (AFL) during flecainide infusion (IC AFL), treated with inferior vena cava-tricuspid annulus isthmus catheter ablation and oral flecainide (hybrid therapy). Over a mean of 54.1 ± 13.1 months 82 patients (53%) remained free of AF and AFL. Flecainide was discontinued because of adverse effects in 6 patients (4%). A history of persistent AF, and the documentation of ≥1 spontaneous AFL episode before the flecainide test were independent predictors of successful hybrid therapy. In patients with paroxysmal AF without documented spontaneous AFL, the long-term efficacy of hybrid therapy was 38.5% (P = 0.03). The flecainide infusion test reliably detects candidates for hybrid therapy. The efficacy of this therapy is maintained over the long-term with a high patient compliance.     

Determinants of Decreased Early Ventricular Filling in Man: A Role for External Forces

The determinants of reduced early left ventricular filling and their relative importance were examined in 14 subjects with an ejection fraction > 40%. Simultaneous high-fidelity left ventricular pressure, mitral annular Doppler velocity recordings, and two-dimensional echocardiographic data were used. Pressure-volume curves were created from pressure/echocardiographic/Doppler data and the chamber stiffness constant calculated. The influence of changing filling pressure was examined by studying subjects before and after ventriculography. The ventricular relaxation time constant, chamber stiffness constant, mean right atrial pressure (an index of pericardial restraint and/or ventricular interaction), pulmonary wedge pressure, and heart rate were analyzed for their influence on Doppler filling parameters: isovolumic relaxation time, peak early (E) and atrial (A) filling velocities, and the E/A ratio. The relaxation time constant was the primary determinant of isovolumic relaxation time (r = 0.82, P<0.001). Prolonged relaxation also caused a decrease in the E/A ratio (r=0.73, P<0.001) and early filling. Peak atrial filling velocity and its integral decreased as chamber stiffness rose (P<0.005). Pulmonary wedge pressure had only a modest influence on early filling (r=0.46, P<0.05). Ventriculography did not eliminate the influence of stiffness and relaxation on filling, although it caused early filling and the E/A ratio to rise and isovolumic relaxation time to shorten. Filling became earlier with increasing right atrial pressure and upward pressure-volume curve shifts. In multivariate regression the E/A ratio was influenced independently by relaxation, filling pressure, right atrial pressure, and chamber stiffness. We conclude that isovolumic relaxation time is a useful measure of ventricular relaxation. However, the E/A ratio is too complex to allow characterization of diastolic function when used alone. Finally, pericardial restraint and/or ventricular interaction during a volume load may confound the relationship between filling pattern and intrinsic ventricular diastolic properties.