Association of penicillin tolerance with failure to eradicate group A streptococci from patients with pharyngitis

Despite uniform susceptibility of group A streptococci to penicillin, failure to eradicate group A streptococci is not uncommon in patients receiving penicillin for treatment of pharyngitis. We explored the possibility that penicillin tolerance could explain this phenomenon. We examined 48 group A streptococcal isolates from 48 patients successfully treated with penicillin (streptococci eradicated) and 92 isolates from 37 patients (one to four isolates per patient) who failed to respond to penicillin therapy (streptococci not eradicated). Penicillin tolerance was recognized by the gradient-replicate plate method and by time-kill experiments with penicillin concentrations of 16 times the minimal inhibiting concentrations. Tolerance was identified in 25% (23 of 92) of the isolates from the treatment failure group, in contrast to none of the strains from the treatment success group. Characterization of the strains by M and T typing revealed no predominant type(s) among the tolerant strains. These findings suggest that penicillin tolerance may be responsible for some instances of failure of penicillin to eradicate group A streptococci from the upper respiratory tract of individuals with streptococcal tonsillitis or pharyngitis.     

Leukocytic epinephrine receptors of normal and asthmatic individuals.

To determine if the hypothesized beta adrenergic blockade in asthma is located at the level of the hormone receptor, we have compared the number and binding affinity of leukocytic epinephrine receptors in normal and asthmatic subjects. Human leukocytes, but not human erythrocytes, possess low-affinity epinephrine receptors. When saturated, each leukocyte binds approximately 1.0 times 10-6 molecules of epinephrine. Binding of 3H DL-epinephrine was largely inhibited by excess unlabeled L-epinephrine. The binding was reversible and involved both the D and L forms of 3H DL-epinephrine. Inhibition studies with nonradioactive isoproterenol, norepinephrine, propranolol, and tolazoline produced results consistent with the interpretation that the leukocytes contained both alpha and beta adrenergic receptors. Two procedures, subcellular fractionation of lymphocytes and incubation of leukocytes in 0.1 per cent trypsin, permitted the demonstration that most of the catecholamine binding occurred at the plasma membrane. Thin-layer chromatography of the bound 3H DL-epinephrine after its extraction from the leukocytes permitted the interpretation that the hormone had fully retained its chemical structure. In addition, epinephrine binding was associated with cAMP production. Leukocytic epinephrine receptors of 10 asthmatic and 9 normal individuals were compared and found not to be substantially different in number or binding affinity.     

The incidence and significance of contraction bands in endomyocardial biopsies from normal human hearts

With increasing use of myocardial biopsy as a diagnostic tool, different criteria of pathology have evolved from tissues obtained from biopsy and postmorten specimens. We reported that contraction bands may be produced artifactually by the biopsy procedure in the fresh, but not the postmorten or perfused fixed normal rat and dog hearts. Contraction bands have been used as a morphological index of pathology. From 12 normal human transplant donors endomyocardial biopsy samples were obtained from the right ventricle, were fixed immediately and then processed for light and electron microscopy. Contraction bands were quantitated by assigning 0, 1, 2, and 3 to represent 0, 1 to 5, 6 to 10, and 11 or more cells per square millimeter with contraction bands. A large number of contraction bands were present in 11 out of 12 hearts; 3rd, 2nd, 1st, and zero degrees of contraction bands were present in 11, 0, 1, and 0 samples, respectively. We conclude that contraction bands may be produced artifactually in normally human hearts, and based upon the rat and dog study, that the determinants of contraction band formation are activation of the contractile machinery by the biopsy procedure, together with sarcomeres capable of hypercontraction because their shortening is unopposed.Furthermore, contraction bands may be considered a morphological index of pathology in tissue obtained postmortem and after perfusion fixation, but not in tissue obtained from biopsies.     

Evaluation of bepridil,a new antianginal agent: Clinical and hemodynamic alterations during the treatment of stable angina pectoris

The antianginal effects of bepridil, a new calcium entry blocker, were evaluated in 20 patients with chronic stable angina in a single-blind trial that was placebo-controlled within patients. Of the 20 patients, 13 also underwent rest and exercise gated blood pool scintigraphy to assess the effects of the agent on left ventricular (LV) performance. Mean anginal frequency was significantly reduced, from 7.3 to 3.1 episodes/week (p < 0.01). Total work performed increased from 410 to 581 kpm (p < 0.005), and exercise time increased from 5.3 to 6.6 minutes (p < 0.005). Supine resting LV enddiastolic volume index, end-systolic volume index, stroke volume index, cardiac index and ejection fraction (EF) were not altered by bepridil. During supine exercise, EF decreased from 60 to 55 % during placebo therapy. Despite an increase in total work, the mean EF increased from 60 to 62 % (p < 0.05 vs exercise placebo) during exercise with bepridil therapy. Maximal exercise stroke volume index and cardiac index were significantly greater during bepridil therapy. Exercise resulted in new or increased LV wall motion abnormalities in 7 of 13 patients during placebo therapy. During bepridil therapy, only 4 new or increased wall motion abnormalities were noted despite the increase in total work performed. Thus, bepridil is an effective antianginal agent. The drug allows an increase in exercise work load and preserves LV performance.     

Noninvasive measurement of the rest and exercise peak systolic pressure/end-systolic volume ratio: a sensitive two-dimensional echocardiographic indicator of left ventricular function

Thirty-five patients with previous myocardial infarction and 25 normal subjects underwent subcostal view two-dimensional echocardiography at rest and at peak up-right bicycle exercise. The purpose was to assess changes in left ventricular volume with maximal upright bicycle exercise and to compare the utility of the peak systolic pressure/end-systolic volume index ratio and ejection fraction as indicators of left ventricular function. With exercise, normal subjects had a decrease in end-systolic volume index (22 +/- 8 to 11 +/- 3 ml/m2) (p less than 0.001); the normal ejection fraction (59 +/- 9 to 72 +/- 8%, p less than 0.001) and the pressure/volume ratio (6 +/- 3 to 18 +/- 6, p less than 0.001) increased. In patients with prior myocardial infarction there was no change in end-systolic volume index, ejection fraction or pressure/volume ratio with exercise. Although at peak exercise significant differences between normal subjects and patients with prior infarction were demonstrated in end-systolic volume index (p less than 0.001), ejection fraction (p less than 0.001) and pressure/volume ratio (p less than 0.001), the pressure/volume ratio provided sharper delineation between the two groups than did ejection fraction. The exponential relation of the pressure/volume ratio and ejection fraction at peak exercise demonstrates that the pressure/volume ratio is more sensitive as an indicator of normal or borderline left ventricular function and that ejection fraction is more sensitive in quantifying the degree of left ventricular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)