Biomedical subjects
Publications and source records attributed to M Weiss.
Angioaccess for hemodialysis in infants can be accomplished by percutaneous insertion of an Uldall catheter if certain modifications are made. We have used this technique in six children for 2 to 9 weeks until either fistulas matured for chronic dialysis, transplantation could be accomplished, or uremia resolved.
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Several lines of evidence suggest that there might be immunologic cross-reactivity between the thyroid plasma membrane in humans and antigenic determinants in the enteric pathogen Yersinia enterocolitica. Studies were therefore performed to determine whether Y. enterocolitica, like the thyroid membrane, contains a thyrotropin binding site. A saturable binding site for bovine thyrotropin was indeed demonstrable, particularly in preparations of the organism that have been treated with ethylenediaminetetraacetate and lysozyme. Hormonal specificity of the binding site, as judged from the inhibition of binding of 125I-labeled bovine thyrotropin, was similar to that of the thyrotropin receptor in human thyroid tissue.
Using a volume-controlled infusion pump, a mean serum plateau level of digoxin of 4-5 ng/ml was rapidly achieved and maintained in 6 healthy volunteers. The infusion scheme was calculated on the basis of data published on the pharmacokinetics and pharmacodynamics of digoxin following bolus intravenous injection. The magnitude of the response (change in electromechanical systole) at the end of the plateau phase was comparable to that observed with the concentration in the therapeutic range at steady state.
Using a nonclassical statistically based pharmacokinetic concept, a theory is presented which can be applied to the analysis of concentration-time data fitted by power functions of time C = At-ae-bt, which is shown to be equivalent to the assumption of gamma distributed residence times of drugs. The shape and scale parameters a and b, respectively, are interpreted physiologically in terms of a recirculatory model. It is shown how the shape parameter a, which is only dependent on the coefficient of variation of residence times, is affected by the processes of drug distribution and elimination. The time course of the blood concentration following multiple doses and continuous infusion is predicted for gamma-like drug disposition curves. The assumption of gamma distributed disposition residence times is theoretically based on a random walk model of circulatory drug transport, and the conditions are investigated under which gamma curves can be empirically fitted to oral concentration-time data. The parameters of concentration-time profiles following solid dosage forms, for example, are explained by the means and coefficients of variation of the disposition residence time and dissolution time distribution, respectively. The advantages of this concept compared to the conventional method of fitting sums of exponentials to the data are described.
Based on a recirculatory pharmacokinetic model, a physiologically realistic definition of the initial distribution volume has been developed to characterize the overall distribution process occurring shortly after rapid bolus injection of a drug. This apparent volume of distribution, which refers to the peak right atrial blood concentration, depends on the cardiac output and basic pharmacokinetic parameters usually derived from the whole blood concentration vs time curve. The initial distribution process appears to be affected by changes in the variance of the distribution of residence times of the drug in the body. The influence of the site and time of early blood sampling on the estimated initial distribution volume is discussed. This relatively simple a priori model should prove useful in predicting to a first approximation the principal characteristics of the initial distribution process.
A recirculation model of drug disposition is used to interpret the physiological meaning of the variance of residence time distribution (VDRT). The pharmacokinetic parameter VDRT is determined by the means and variances of the transfer times across the organs, as well as by the respective blood flow and extraction ratios. The model is illustrated for a specified distribution of organ transit times assuming flow limited mass transport. Based on data from the literature, the influence of changes in cardiac output and its regional distribution on the variance of recirculation and residence times, respectively, is predicted for lidocaine. Thereby the study is focused on the effect of certain cardiovascular states (shock, hypoxia, exercise, sympathomimetic drugs). Unlike pharmacokinetic parameters derived from the zeroth and first curve moments, the relative residence time dispersion is found to be affected by a redistribution of the blood flow among the noneliminating organs. The equations presented allow a simple and rapid calculation of clinically relevant pharmacokinetic parameters from physiological and physicochemical data.
The effects of harmaline, an indoleamine and a MAOI, were tested on the acoustic startle pattern. EMG measures of the startle reflex, the pinna reflex as well as the characters of the vertex evoked responses to brief intense tone bursts (60 msec, 110 dB, 8000 Hz) were simultaneously studied in 4 alert guinea-pigs. The basic experimental design was a 4 by 4 latin square, with the treatments being given at 2 day intervals. The four harmaline-HCl treatments were isotonic saline, 0.25, 5.0, and 10.0 mg/kg. Compared with saline baselines, all the doses resulted, throughout the 60 min session, in overall high significant depressions of the startle reflex, the pinna reflex and the initial wave of the acoustic evoked potential at the vertex. In contrast, harmaline had little or no influence on amplitude and latency of the late wave of the vertex response. The effects of harmaline on the general behavior of the guinea-pig are also reported. These results may support an involvement of serotonergic systems in the modulation of the sensory-motor reactivity at the brainstem level. Nevertheless, the probably more complex cortical processes involved in startle responsiveness do not appear univocally affected by the indoleamine drugs such as harmaline.
The effect of direct electrostimulation of the median nerve in a group of tetraplegic patients is described. In all cases there was an increase in the force, and a prolongation of the period of maintenance, of the maximum movement developed by the stimulated muscles. The method was considered to be sufficiently effective to indicate that programmed stimulation by implanted electrodes would permit functional use of the hand.
A prospective study of 213 patients with severe head injury and Glasgow Coma Scores of 8 or less was conducted to identify, at 24 hours postinjury, the favorable and unfavorable clinical factors that relate to outcome one year later. According to the Glasgow Outcome Scale, 35 percent were classified Moderate Disability or Good Recovery, 13 percent were classified Severe Disability or Vegetative State, and 52 percent had died. The presence of intact brain-stem reflexes 24 hours postinjury in comatose patients with head injury is a prognostic sign for a good recovery. Favorable clinical signs include eye opening, pupillary reactivity, spontaneous eye movement, intact oculovestibular reflexes, and motor responses such as localizing. A prognosis of poor recovery is associated with nonreactive pupils, absent oculovestibular reflexes, and motor response of extension or no response at all. These negative signs, when present individually, were associated with only a 3 to 4 percent Moderate Disability or Good Recovery rate and an 85 to 91 percent mortality rate. The Glasgow Outcome Scale was also used to define recovery patterns at intervals during the first year after injury. Ninety percent of patients reached their highest outcome category by six months. The most frequent one-month outcome category for survivors was Severe Disability. By six months postinjury, 68 percent of these patients had made sufficient neurological progress to change their classification to Moderate Disability or Good Recovery. The 16 percent of patients classified at one month as in a persistently Vegetative State had a prognosis of poor outcome. Only 28 percent of these patients progressed in one year to the Severe Disability classification.
Barbiturate therapy has been employed for reduction of increased intracranial pressure (ICP) after acute brain injury and also for cerebral resuscitation. However, this treatment may be complicated by hypotension with an adverse impact on survival. We, therefore, investigated the acute hemodynamic effects of pentobarbital (PB) when administered in loading doses of 4-7 mg/kg and maintenance doses of 1-4 mg/kg. After pentobarbital therapy, HR, mean arterial pressure (MAP), and rectal temperature were significantly reduced. Four episodes of hypotension and 6 episodes of oliguria were observed during the initial 12 h of therapy in close relationship to reduced cardiac output, stroke volume, and MAP. These abnormalities were corrected by infusion of colloid-containing fluids. We postulate that increases in venous capacitance, hypovolemia, and decreased barostatic reflexes, rather than depression of myocardial function, accounted for the hemodynamic abnormalities.
In Berne (Switzerland), a virus was isolated from a horse which was found to be serologically unrelated to known equine viruses. Its growth was unaffected by iododeoxyuridine and it was inactivated by organic solvents. A purification procedure involving ammonium sulphate precipitation and sucrose gradient equilibrium centrifugation was developed and viral activities were monitored using infectivity and enzyme-linked immunosorbent assays. Purified virions of density 1.16 g/ml were shown by negative staining electron microscopy to be roughly spherical and to measure 120 to 140 nm in diameter; projections (peplomers, about 20 nm long) were identified on the virion surface. In thin sections, an envelope and an elongated core structure could be distinguished. The core, measuring about 23 nm across and 104 nm in length, appears to assume a rod-, crescent- or open ring-shape within the envelope. It has a tubular structure and shows a transverse striation (periodicity 4.5 nm). Binding at the plasma membrane was observed. Berne virus is considered as a representative of a hitherto undefined family of widespread animal viruses serologically related to recent bovine isolates in Ames, Iowa (U.S.A.) and Lyon (France).
24 adult dogs were randomly divided into 4 groups and submitted to angioplastic replacement of a 2- to 3-cm segment of the right or left pulmonary artery by three kinds of autogenous biomaterials; azygous vein, jugular vein and pericardium, and by a synthetic arterial prosthesis in a control group. In vivo evaluation was carried out by catheterization with a balloon catheter allowing successive intraluminal occlusion of the pulmonary branches, and by cineangiopneumography. There was a good correlation between evaluation techniques. Final evaluation after a follow-up of 5-20 months was based on postmortem measurement of the anastomosis diameter and histologic examination. In each group, the results were classified into four grades, numbered 0-3, and compared statistically. The results show that in this experimental model: (a) none of the autogenous tissues (selected for their potential ability to grow) proved better than the control Dacron arterial prosthesis, and (b) of the three biomaterials, the azygous vein was superior to the jugular vein and pericardium.
Four patients with elevated creatine phosphokinase (CPK) values and recurrent chest pain were found to have thoracic outlet syndrome. This association of abnormal CPK levels and chest pain due to thoracic outlet syndrome has not been previously reported. Symptoms and CPK values improved with anti-inflammatory medications and/or proper posture instruction. It is proposed that CPK values become elevated by ischemic or neurologic compromise of muscles supplied by the subclavian artery or brachial plexus respectively. Accordingly, chest pain in the same dermatomal distribution as that of angina pectoris may be simulated by ischemic skeletal muscle. Thoracic outlet syndrome therefore should be suspected in any patient with chronically abnormal CPK values and chest pain in whom no other etiology can be determined.
The results of high-dose small-volume 60Co teletherapy in a series of 176 patients with carcinoma of the urinary bladder are reported. Five-year survival rates without evidence of disease were 26.9 per cent in stage B, 20.3 per cent in stage C, and 14.3 per cent in stage D. The most common cause of treatment failure was pelvic recurrence, which was observed alone in 58.2 per cent and together with distant metastases in 5.2 per cent of the patients.
The harmaline-induced tremor of antagonistic muscles is studied in the anaesthetized rat. By recording simultaneously both the rhythmic EMG-activities in flexor and extensor muscles and the concomitant tremorogenic bulbar reticular discharges, we discovered two facts. 1) The extensor burst precedes the flexor muscle discharge by about 10 msec, contrarily to the close synchrony expected from anterior descriptions of harmaline tremor. 2) The previously observed periodical modulation of olivary and Purkinje cell rhythmic activities is transferred, through the reticular formation to the spinal level, in the form of an alteration of periods with tremor and periods with tonic coactivation of antagonistic muscles. The implication of the myotatic loop in the second fact is discussed.