Biomedical subjects
Publications and source records attributed to J Weissenburger.
The very large number of medications recognized as hepatotoxic has required the establishment of microcomputerized data file. This file presently indexes 347 active principles contained in more than 1000 patent medications. It may be rapidly examined with microcomputer.
Hemodynamic drug-effect studies require repetitive measurements and time-consuming calculations, particularly for the indices of left ventricular (LV) contractility and relaxation. To save time, we have created a system of acquisition, calculation, storage, and report of hemodynamic data processing E.K.G, peripheral arterial pressure, and LV pressure signals using a standard microcomputer (Apple II+) and simple accessory devices. The master program is written in BASIC Applesoft, with Mem/Dos as the disk operating system. A suite of utility routines, written in machine language, are used to program the A/D converter and to perform the vectorial calculations on the data. The software, written to process single-dose drug-effect studies, performs 1) data acquisition and storage as vectorial arrays accessible using BASIC, 2) monitor display, 3) calculations of the peripheral pressure and of the LV contractility and relaxation indices, 4) storage of the calculated indices, and 5) print-out of a report (curves and tables) at the end of each experiment and cumulated results of all the animals included in a protocol. The drawback of such a low-cost system is essentially the lack of available memory and the relatively slow speed of the microprocessor, which hinders simultaneous processing of indices needing nonlinear curve fitting and adequate print-out of protocols that are not single dose.
The object of this study was to confirm the electrophysiological effects of sotalol, a betablocker which increases the duration of the action potentials of myocardial cells, and to investigate the relationship of these effects with the doses used and plasma concentrations (PC) of the drug. 13 patients (23 to 72 years) were divided into 3 groups: Group 1 (n = 5): 0.6 mg/kg; Group 2 (n = 4): 1.2 mg/kg; and Group 3 (n = 5): 1.8 mg/kg. Measurements were performed before and 35 minutes after starting a 15 minute intravenous infusion of sotalol. At all doses, sotalol decreased the heart rate (HR), increased the corrected sinus node recovery time (CSNRT), prolonged the effective refractory periods (ERPA) and functional refractory periods (FRPA) of the right atrium. Atrioventricular conduction was depressed; prolongation of AH at an imposed rate of 100/min, prolongation of the nodal refractory periods (ERPN and FRPN), and an earlier Wenckebach point. The corrected QT interval (QTc) and ventricular refractory period (ERPV) increased. The QRS complexes and HV intervals were unchanged. Increases of CSNRT, AH, ERPN, FRPN, QTc, and ERPV were observed after the first dose (Group 1). At the dose of 1.8 mg/kg (Group 3) all parameters were modified (except the QRS and HV). All patients increased their ERPV by more than 20 p. 100. The parameters which illustrated the dose-effect relationship were the HR, ERPA, FRPN, and CSNRT. The PC of sotalol measured 60 minutes after starting the infusion were 0.58 +/- 0.23 microgram/ml (Group 1), 0.78 +/- 0.32 microgram/ml (Group 2) and 1.73 +/- 0.43 microgram/ml (Group 3).(ABSTRACT TRUNCATED AT 250 WORDS)
The cortisol suppression index (CSI) (the ratio of pre- to postdexamethasone serum cortisol concentrations) was compared to the dexamethasone suppression test (DST) in endogenously depressed DST suppressors (N = 20) and nonsuppressors (N = 21) and in normal controls (N = 23). The 8 a.m. CSI detected 17.1% and 31.7% of endogenous depressives at the 4.0 and 6.0 thresholds; for the 4 p.m. CSI, rates were 48.8% and 65.9%. The 4 p.m. CSI produced 17.4% and 39.1% false positives in normal controls at the two thresholds, whereas the false positive rate for the DST was 4.3%. These data suggest that the CSI is not as specific as the standard DST for the detection of endogenous depression.
The purpose of this study is to monitor the haemodynamic changes that occur in pregnancy using ultrasound. Although all previous studies do demonstrate an increase in frequency and the volume of the cardiac output, the results seem to be different as far as variations in volume during systole occur and the mechanisms by which they occur. These differences can be explained by problems associated with the different methods used. Our study was carried out on ten pregnant women who were examined in each trimester (TM1, TM2, TM3) and post-partum (TM4). The results confirm that cardiac frequency rises (TM3 92 +/- 5 VS TM4 73 +/- 3 cpm p less than 0,01) and cardiac output does (TM3 7,2 +/- 0,6 VS TM4 4,8 +/- 0,3 Umm p less than 0,01). The volume in systolic ejection (VES) rises throughout pregnancy when the patient is lying on her left side (TM3 81 +/- 4 VS TM4 69 +/- 2 ml p less than 0,01). The rise in VES could be put down to an increase to the veinous return which itself is reflected by the left auricle (TM3 33,7 +/- 1,1 mm VS TM4 29,9 +/- 0,7 mm p less than 0,05) and in the left ventricle (TM3 48,7 +/- 0,6 VS TM4 46,3 +/- 0,3 mm p less than 0,01) and the sudden drop in the total peripheral resistance (TM1 950 +/- 50 VS TM4 1 335 +/- 95 dynes/sec. X cm-5 p less than 0,01). It does not seem as though there is any change in myocardial contractility.
Twenty-two patients with unipolar, non-psychotic major depression were evaluated with a neuropsychological test battery. The endogenous patients performed more poorly than the non-endogenous on the test battery as a whole. When compared to performance norms obtained from non-depressed controls, both E and NE groups showed performance impairments on the majority of subtests in the battery. The test battery employed in the present study may be clinically useful in assessing neuropsychological alterations in patients with mild to moderately-severe depression.
A 15 year old boy presented with palpitations of sudden onset and termination over a two month period. The heart was clinically and radiologically normal. The electrocardiogramme showed sinus rhythm with a short PR interval (0,11 sec) and narrow QRS complexes (0,08 sec) associated with an intermittent escape accelerated idioventricular rhythm (AIVR). During an attack of palpitations a regular tachycardia (250/min) with wide QRS complexes of the same configuration as those of the AIVR (left side delay). The diagnosis of ventricular tachycardia was retained. Endocavitary electrophysiological recording demonstrated preexcitation of the right ventricle associated with accelerated nodal conduction explaining the narrow QRS complexes in sinus rhythm. The wide complex tachycardias initiated and terminated by paired ventricular stimulation were identical to the spontaneous attacks and were attributed to an antidromic reciprocating rhythm. The hypothesis of a rhythm arising from the accessory pathway is suggested. This would explain the identical configuration of the QRS complexes of the AIVR and of the antidromic reciprocating-rhythm and the disappearance of the AIVR after surgical section of the accessory pathway.
The authors examined the effects of cognitive therapy and imipramine on hopelessness and self-concept in 35 unipolar nonpsychotic depressed outpatients who were treated with either modality over approximately 11 weeks. Compared with imipramine, cognitive therapy resulted in significantly greater improvements in hopelessness and more generalized gains in self-concept. Thus, cognitive therapy may offer a particular advantage in reducing hopelessness and improving low self-concept in depression.
Patterns of symptoms change were examined in 35 unipolar depressed outpatients treated with either cognitive therapy or pharmacotherapy (imipramine HCl). Cross-lagged panel analyses were used to evaluate the temporal relationships among changes in views of the self, hopelessness, mood, motivation and vegetative symptoms during treatment weeks 1-4. During cognitive therapy improvements in hopelessness, views of the self and mood generally preceded changes in vegetative and motivational symptoms. On the other hand, no consistent pattern of change was associated with pharmacotherapy. While these results are compatible with the notion that cognitive therapy initially alters negative thinking and mood, which secondarily leads to improvements in vegetative and motivational symptoms, further studies with a placebo or wait-list group are needed to determine if this is a unique effect of cognitive therapy.
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The effects of d,1-propranolol and 1-timolol on cardiac refractory periods (RP) were compared in 14 phentobarbital-anesthetized dogs using endocavitary His bundle electrograms and programmable electrical stimulation. Beta-blocking agents were injected at cumulative doses in each dog at 3 day intervals. A control group (6 dogs) received 4 successive saline injections at the same time intervals. RP measurements at a constant drive rate were done before and 10 minutes after each dose of either drug or saline. Propranolol and timolol produced a dose-dependent increase of atrial and atrioventricular nodal refractory periods; dose-response curves were parallel. Depending on the parameter chosen timolol exerted an 8--36 times more potent effect than propranolol. The effects of propanolol and timolol on ventricular effective (VERP) and functional (VFRP) RP were measured in 6 dogs. Both drugs increased VFRP significantly, but saline had the same effect. Only the higher doses of timolol increased VERP significantly. These data confirm that blockade of myocardial beta-adrenergic receptors exerts predominant effects on supraventricular refractoriness and that in anesthetized dogs timolol has more potent beta-blocking properties than does propranolol.
The comparative dromotropic activity of timolol (TML) and propranolol (PPL) was studied by means of His bundle electrograms in two groups of pentobarbital-anesthetized dogs: group I, 7 non-atropinized dogs; group II, 8 atropinized dogs. beta-Blocking agents were injected in 4 cumulative doses in each dog at 3 days' interval. The effects upon heart rate (HR), and A-V nodal (AH), His--Purkinje (HV) and intraventricular (QS) conduction times were measured. The dromotropic effects of PPL and TML during atrial electrical stimulation and their effects upon chronotropic and dromotropic isoprenaline-induced changes were compared. TML exerted a 9--10 times more potent negative chronotropic effect than PPL and a 4--5 times more potent negative dromotropic effect than PPL on AH conduction time. PPL and TML increased the duration of HV only in higher doses. This effect which was not modified by isoprenaline may be related to their membrane depressant effect. Neither TML, nor PPL nor isoprenaline modified QS duration. TML was 25 times more potent than PPL to antagonize the chronotropic action of isoprenaline and 11--8 times more potent than PPL to antagonize the dromotropic action of isoprenaline upon AH. Parasympathic blockade with atropine did not modify the negative dromotropic activity of PPL and TML but modified their chronotropic effects.
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Electrophysiological properties of quinidine and the two isomers of propranolol were compared in pentobarbital-anesthetized dogs using His bundle recordings and programmed stimulation in order to differentiate the effects resulting from beta-blockade from those related to nonspecific membrane-stabilizing effects. Quinidine in the plasma concentration range of 2.7-20 microM/liter resulted in concentration-dependent increases in atrionodal and His-Purkinje system conduction times and in the atrial effective refractory period. Quinidine did not produce any significant concentration-dependent change in atrioventricular (AV) nodal and ventricular refractory periods, sinus node automaticity, or QTc interval duration. Propranolol isomers in concentration range of 0.03-0.85 microM/liter produced a concentration-dependent increase in atrionodal conduction time but exerted no significant effect on His-Purkinje conduction time, QTc duration, or ventricular refractory period. Both isomers increased the atrial effective refractory period, but with slopes of concentration-response regression lines which were significantly different from those of quinidine. Only l-propranolol produced concentration-dependent increases in AV nodal refractory period, Wenckebach cycle length, and sinus node recovery time. These results suggest that the electrophysiological effects of propranolol isomers are related to beta-blockade and are significantly different from those resulting from the membrane-stabilizing effect of quinidine.
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