Effects of beta-adrenergic stimulation with dobutamine on isovolumic relaxation in the normal and failing human left ventricle.

BACKGROUND. We tested the hypothesis that beta-adrenergic receptor-stimulated acceleration of left ventricular (LV) isovolumic relaxation (i.e., positive lusitropic response) is attenuated in patients with severe congestive heart failure (CHF) compared with patients without LV dysfunction or CHF. METHODS AND RESULTS. The beta-adrenergic agonist dobutamine was infused by the intracoronary route in 14 subjects (normal group, six; CHF patients, eight) and by the intravenous route in a second group of 14 subjects (normal group, four; CHF patients, 10). The positive inotropic response to intracoronary or intravenous dobutamine was substantially and significantly reduced in the patients with CHF. LV isovolumic relaxation rate was determined by the methods of Weiss (TL), Mirsky (T1/2), and by a nonlinear regression technique (TNL). LV isovolumic relaxation assessed by all three methods was significantly prolonged in CHF patients compared with normal subjects. Intracoronary and intravenous infusions of dobutamine caused significant acceleration of LV isovolumic relaxation in both normal subjects and patients with CHF. The magnitude of the dobutamine-stimulated acceleration of isovolumic relaxation in patients with CHF was comparable with that in normal subjects. CONCLUSIONS. These data demonstrate that beta-adrenergic receptor stimulation causes significant acceleration of LV isovolumic relaxation in both normal subjects and patients with severe CHF. Coronary to our hypothesis, the lusitropic response to beta-adrenergic stimulation is well preserved in patients with severe CHF despite substantial attenuation of the beta-adrenergic positive inotropic response. These findings have potentially important implications regarding the physiology and pharmacology of adrenergically mediated LV relaxation in humans.     

Introduction: the Israeli high-risk study

The literature on theories of the etiology of schizophrenia (the "nature-nurture dilemma") is reviewed, and the rationale is explicated for a study comparing the development and outcome of kibbutz- and town-reared children of schizophrenic parents. Various possible outcomes of the kibbutz-rearing experience in vulnerable children are discussed. The research team and the time table are described.     

Petit mal epilepsy: a review and integration of recent information

Petit mal (absence) epilepsy remains one of the most enigmatic of neurological disorders, and there is no widely accepted theory of its etiology. This review covers some of the current issues concerned with the disorder, including treatment and prognosis, neurochemical research, behavioral and psychophysiological effects of wave-spiked discharges, and EEG studies of seizure control. With respect to treatment, although effective drug therapy (valproic acid, ethosuximide) exists for the "pure" form of absence epilepsy, other forms, in which there is an admixture of grand mal seizures, are less amenable to pharmacotherapy. Moreover, the frequency of fatal hepatic toxicity following valproic acid therapy has been estimated at 1 in 20,000. With respect to prognosis, follow-up studies indicate that many patients do not outgrow the disorder but continue to suffer absence seizures well into adulthood. In recent years, there has been considerable research on the neurochemical basis of absence epilepsy. Current theories, including those that implicate gamma-aminobutyric acid, catecholamines, and "endogenous" epileptogens, are summarized; and requirements for an experimentally induced animal model of absence epilepsy are discussed. The majority of behavioral studies of the disorder have concerned the effects of petit mal-type discharges on sensory and cognitive processes. Some of these studies are reviewed; and recent work bearing on these issues, involving event-related brain potentials, is presented. Our review concludes with a discussion of research aimed at the development of electrophysiologically based approaches to the reduction of seizure frequency in patients with absence epilepsy.     

The structure of schizotypy: a pilot multitrait twin study

This report of a pilot study examines 29 pairs of twins from a population-based registry on whom four domains of schizotypy have been measured: personal interview using the Structured Interview for Schizotypy, self-report questionnaire formed from eight published self-report scales, attentional battery of eight individual tests, and root mean square error on smooth pursuit eye tracking. Analyzing the twins as individuals revealed two independent dimensions of clinically rated schizotypy (positive symptom schizotypy and negative symptom schizotypy) and two independent dimensions of self-rated schizotypy (positive trait schizotypy and trait anhedonia). Positive symptom schizotypy was highly correlated with positive trait schizotypy, but not with attentional dysfunction or eye-tracking error. By contrast, negative symptom schizotypy was significantly related to trait anhedonia, attentional dysfunction, and eye-tracking error. Correlations in monozygotic and dizygotic twins suggested that genetic factors were important in all four domains of schizotypy. Except for eye-tracking error, the results are more consistent with a dimensional than a "disease" model of schizotypy. Replication of these results with a larger group of subjects is needed.     

Screening protocol for MR imaging of the internal auditory canal

We have previously shown that 5 mm axial T1-weighted images following Gd-diethylenetriamine pentaacetic acid (DTPA) administration were sufficient as a screening examination of the internal auditory canal (IAC) and cerebellopontine angle cistern in 80% of cases with sensorineural hearing loss. In the remaining 20% of cases 3 mm slices were necessary for confirmation of the diagnosis. To reduce the number of cases requiring the additional examination, we have modified our protocol to include a coronal "scout" T1-weighted sequence followed by 5 mm axial sections angled through the IACs. Routine axial T2-weighted images of the posterior fossa were also obtained. One hundred eleven patients were studied with this protocol. In all but two of these the 5 mm sections unequivocally provided the diagnosis and in those two cases the coronal images confirmed the diagnosis suspected on the axial study. Three millimeter slices were not necessary in any patient. This three sequence, post-Gd-DTPA protocol, which requires only 12 min of scan time, is recommended as a screening protocol for IAC and cerebellopontine angle disease.     

Assessment of myocardial contractility in children and young adults from ventricular pressure recordings

The index V_pm (the actual or physiologic maximal shortening velocity of the contractile element) has been obtained from the analysis of left ventricular pressure recordings and then applied to the assessment of myocardial contractility in man. Pressures during the isovolumic period of ventricular systole were recorded during routine catheterization of 46 patients with a variety of cardiac lesions. The quantity V_pm, that is (dp/dt/kp)_max, was compared with the hemodynamic evaluation of each patient based on the left ventricular end-diastolic pressure, ejection fraction and left ventricular end-diastolic volume. V_pm was selected for this study since it appeared to be largely independent of load and does not require biplane angiocardiography and extrapolation analyses.