Training of supervisors in speech-language pathology and audiology.
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Biomedical subjects
Publications and source records attributed to J L Anderson.
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Two patients were treated with bretylium tosylate for malignant ventricular arrhythmias after inadequate response to conventional agents. In the first patient, two episodes of ventricular tachycardia requiring cardioversion occurred in close temporal sequence with administering bretylium. With drug rechallenge two days later, ventricular tachycardia recurred within minutes. In the second case, five cardiac arrests due to ventricular tachycardia and fibrillation occurred during several hours after beginning a trial of bretylium maintenance therapy for complex ventricular ectopy. Although transient increases in ectopy after bretylium therapy have been described, presumably due to catecholamine release, the occurrence of life-threatening ventricular arrhythmia leading to cardiac arrest has not previously been emphasized. There is potential for this side effect, and additional caution in the use of this drug should be followed.
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To compare the oral and intravenous disposition of bretylium tosylate in man, 10 normal male subjects were randomly assigned single doses of 5 mg/kg bretylium tosylate either orally or intravenously and crossed over 2 wk later to the opposite route (20 studies). Each experiment included sampling for drug in serum and urine over 48 hr. Bretylium tosylate was assayed by gas chromatography. Kinetic analysis provided the following mean [coefficient of variation] results: 100FPo, 22.6% [40.2%]; ClrIV, 300 ml/min [27.8%]; ClrPo, 1.268 mg/min [54.8%]; ClBIV, 299 ml/min [31.9%]; f, 101% [8.7%]; Vdss, 3.37 l/kg [30.5%]; lambda lIV 0.0510 [12.8%]; lambda lPG, 0.115 [52.7%]hr-1; elimination half-life (t 1/2) after intravenous bretylium tosylate, 13.6 hr, and after oral bretylium tosylate, 6.0 hr (harmonic means). Bretylium tosylate binding to plasma proteins in normal volunteer samples was found to be negligible. The results indicate extensive tissue binding of bretylium tosylate. Oral doses of bretylium tosylate are only partially absorbed. Bretylium tosylate is eliminated entirely by the kidneys as unchanged drug. The greater renal clearance after oral than intravenous bretylium tosylate, and the greater elimination rate constant and shorter oral bretylium tosyulate t 1/2 are of interest but no explanation is available.
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A review of lymphomas developing in recipients of cardiac allografts has yielded significant risk factors. Frequency varied strikingly according to original cardiac disease: lymphoma developed in 6 of 37 patients with prior idiopathic cardiomyopathy (I.C.M.) but in one of 54 patients with prior coronary-artery disease (C.A.D.). All patients who developed lymphomas were aged under 40. Combination of both risk factors (I.C.M. and age less than 40) produces a sub-group with a highly significantly increased risk of lymphoma. I.C.M., but not C.A.D., is characterised by a defect in mitogen-induced mononuclear-cell suppressor activity. It is postulated that defective regulation in the immune systems of younger patients under chronic alloantigen stimulation may allow lymphoid proliferation to proceed to lymphoreticular malignancy. Immunosuppressive agents such as azathioprine may exert a co-oncogenic effect.
Between Jan 6, 1968, and April 11, 1977, 124 patients underwent cardiac transplantation at Stanford University Medical Center, with a mean and median period of follow-up of 18.3 and 9.7 months, respectively. Malignant neoplasms developed in seven patients--three lymphoproliferative neoplasms, two skin cancers, one acute leukemia, and one colon carcinoma. Visceral tumors were often fatal and caused 11% of deaths after three months following transplantation. The incidence and spectrum of malignant neoplasms in this population are similar to those observed in recipients of renal homografts.
Further work on the phenomenon reported by Leith and Barrett, wherein tolerance was shown to develop to the well-known D-amphetamine-induced facilitation of self-stimulation, clearly indicates that the development of such tolerance is dependent on the location of the stimulating electrode. Thirty-seven Fisher or Harlan rats were trained to bar press for hypothalamic stimulation (60 Hz, AC). Following several sessions during which small doses of D-amphetamine were administered to demonstrate facilitation, the subjects were placed on a 4-day D-amphetamine regimen. During this time they were given three daily injections of continuously increasing doses of D-amphetamine (total 78 mg/kg). Subsequent tolerance was shown for electrodes stimulating dorsal or medial hypothalamic structures (H2 field of Forel, dorsal medial forebrain bundle, medial hypothalamic nuclei), but did not develop with ventral or lateral hypothalamic stimulation sites (fornix, ventral medial forebrain bundle).
A high Ca, semi-purified diet promoted greater egg production with thicker shells in Japanese quail hens. 7 ppm of dietary Se depressed egg weights with no effect on eggshell thickness. The addition of 20 ppm of MHg to either a low or high Ca diet containing Se depressed both egg production and eggshell thickness. Se residues of liver, kidney, and brain in Se-MHg fed quail were significantly higher than in Se treated quail, probably reflecting the ability of Se to bind with Hg. CA, an enzyme required for the formation of the carbonate radical of Ca carbonate in eggshells, was not reduced in the Se-MHg treated Japanese quail hens' blood or oviducts.
A 54 year old patient who experienced recurrent ventricular tachycardia subsequent to quinidine administration for conversion of atrial fibrillation is described. Over a 10 hour period, 25 sustained episodes of ventricular tachycardia occurred for which electrical cardioversion was required in addition to numerous self-terminating paroxysms. Medical therapy with lidocaine, procainamide and propranolol was unsuccessful in controlling the arrhythmia. However, placement of a transvenous right ventricular pacemaker with overdrive pacing at a rate of 110 beats/min abrupty terminated all further ventricular ectopic activity during the period of quinidine elimination. Temporary overdrive pacing may be the treatment of choice for refractory, recurrent, ventricular tachycardia associated with quinidine therapy.
The electrophysiologic properties of tocainide were evaluated by electrophysiologic studies in 11 patients before, during and after a constant intravenous infusion of the drug for 15 minutes. Peak plasma tocainide concentrations averaged 11.0 +/- 1.7 microgram/ml (SEM), range 3.7 to 22.7. AH, HV, QRS, QTc and RR intervals were measured every 5 minutes during sinus and atrial-paced rhythms and showed small changes which were not statistically significant for HV and QRS. Mild shortening of RR was significant (P less than 0.05) at 15 minutes only. AH tended to increase slightly for spontaneous (but not paced) rhythm, becoming significant at 15 minutes only (P less than 0.05). QTc decreased slightly, a change which was significant (P less than 0.05) for paced but not spontaneous rhythm. A progressive rise in mean arterial pressure occurred during infusion and persisted through 30 minutes (P less than 0.001). Comparison of electrophysiologic studies at 0 and 30 minutes showed decreased in mean effective refractory periods of atrium, A-V node, and right ventricle by 17, 22, and 23 msec, respectively (P less than 0.05, 0.01, 0.01). Functional refractory period of the A-V node showed an average decrease which was not significant. Sinus node recovery time and Wenckebach cycle length were unchanged. The drug was well tolerated in all 11 patients. Hypotension in a twelfth patient may or may not have been drug related. These results obtained at therapeutic plasma concentrations suggest qualitative similarities between the conduction system effects of tocainide and those published for lidocaine.
In order to evaluate its hemodynamic actions, tocainide, a new orally effective antiarrhythmic drug, was given intravenously over a 15 minute period to 12 patients with compensated left ventricular dysfunction. Doses were 0.5 (4 patients) or 0.75 (8 patients) mg/kg/min. Hemodynamics and drug plasma concentrations were measured at the end and 15 minutes after the end of the infusion. Tocainide infusion produced small but statistically significant increases in the pulmonary and systemic vascular resistance, aortic and pulmonary arterial pressure, and left and right ventricular end-diastolic pressure. There was no significant change in left ventricular dp/dt, heart rate, or cardiac index. In patients with compensated left ventricular dysfunction, tocainide produces a small rise in vascular resistance and arterial pressure. Overall cardiac function is maintained with a small increase in left ventricular end-diastolic pressure.
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