Lindane toxicity to four-month-old calves.
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Biomedical subjects
Publications and source records attributed to R Frank.
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Between 1976 and 1978, 248 harp seals were sampled from 5 locations in the Northwest Atlantic and Arctic for organochlorine (OC) residue analysis in tissue. Blood, kidney, brain, muscle and blubber samples were analysed for PCB, DDT, dieldrin, hexachlorobenzene (HCB), and heptachlor epoxide. Levels were generally greatest in blubber tissue. Overall, mean levels of DDT and PCB were greater than those of other OC. A barrier prevented OC compounds from accumulating in the brain to the level one might expect in lipid tissues. Positive correlations were found between 1: DDT and PCB, 2: DDT and dieldrin, and 3: PCB and deildrin. Male harp seals bioaccumulated DDT, PCB, heptachlor epoxide and dieldrin with age. As a group, adult males sampled in the Gulf of St. Lawrence carried the highest concentrations of all OC, except that chlordane did not appear to bioaccumulate and levels of hexachlorobenzene were minimal. Females generally ceased exhibiting significant bioaccumulation once breeding age was reached, due to transplacental and transmammary residue transfer of OC from mother to pup. There were some significant differences in OC levels between locations with DDT: Gulf greater than Front; PCB: Gulf greater than Front; dieldrin: Gulf greater than Front; heptachlor epoxide: Front greater than Gulf. No significant differences were found, however, when northern locations (Grise Fiord, Northwest Greenland, Pangnirtung) were compared to southern (Gulf, Front) on a group basis. The latter is not surprising in view of the harp seals extensive cyclical annual migration between the southern breeding grounds and the High Arctic.
Between 1976 and 1978, 249 harp seals were sampled from five locations in the Northwest Atlantic and Arctic for heavy metal and selenium residue analyses in tissue. Significant loading was apparent only in blood, brain, kidney, liver and muscle. Samples were analysed for mercury (Hg), selenium (Se), copper (Cu), cadmium (Cd) and lead (Pb). The seals carried higher levels of Cd than of the other metals. Residue levels of Cd were highest in kidney tissue; levels of other metals were highest in liver. Both males and females bioaccumulated Cd, Hg and Se. Cd, Hg, Se and Cu residues were detected in tissue from neonatal seals, indicating that transplacental and transmammary transfer of these elements had occurred. Despite the passage of residues from mother to pup, females bore significantly higher levels of Hg and Cd than males. Conversely, levels of Cu, Se or Pb did not appear to differ significantly between sexes. There was considerable individual variation in residue levels. This, coupled with the extensive annual migration undergone by these animals, made it difficult to arrive at definite conclusions regarding geographic accumulation patterns.
Occupational exposures to herbicides were measured among 12 applicators in 1979 and 24 applicators in 1980, who were applying the three herbicides, 2,4-D, dichloroprop and picloram to electric power transmission rights of ways. In 1979 only urine was analyzed but in 1980 both breathing-zone air samples and urine were analyzed for herbicide residues. Dermal absorption was found to be the major absorption route being up to 50 times greater than exposure by the inhalation route when using a hand gun sprayer. Even with the mist blower herbicide application method, dermal absorption was 4 and 11 times greater than exposure by the inhalation route. Worker education on hazards of skin contact and improved protective equipment significantly reduced the 1980 urine concentrations of herbicide residues. A model is presented to relate the urinary concentrations to equivalent daily exposure levels.
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Arrhythmogenic right ventricular dysplasia (ARVD) is a recently individualised clinical entity which sometimes presents with episodes of ventricular tachycardia (VT). These attacks may be resistant to anti-arrhythmic therapy and new therapeutic approaches have been developed for the treatment of this condition. These new methods are mainly surgical, based on the analysis of the electrical activation of the heart in sinus rhythm and during VT. This approach has increased our understanding of the physiopathology of VT, not only in the context of ARVD, but also in the most commonly encountered clinical setting of VT, after myocardial infarction. Electrophysiological study of the epicardial activation of the dysplastic zones has demonstrated the presence of delayed potentials recorded after the end of the QRS complex. This can be explained by the histopathology of these tissues. ARVD is characterised histologically by partial degeneration of the myocardial wall. Most of the muscle fibers are replaced by fatty tissue in the middle of which some healthy fibers survive. These changes are mainly observed in the intramyocardial and subepicardial layers, the subendocardium being almost normal. Strands of isolated muscle fibers within the non-conducting fatty degeneration may lead to very delayed activation with respect to the adjacent healthy tissues. The propagation of activation is delayed as it passes through this plexiform structure and in the zones adjacent to healthy muscle were reentry phenomena may arise. In ARVD, these changes are mainly located over the right ventricle, so explaining the right ventricular origin of most forms of VT observed in this condition. However, we have also observed a case which suggested an isolated arrhythmogenic left ventricular dysplasia. Epicardial mapping localizes the point of origin of VT in zones situated between the slow and normally conducting tissues. Simple ventriculotomy, a full thickness section of the ventricular wall, at the point of epicardial breakthrough of the VT prevents recurrence in the great majority of patients. The same pathophysiological concepts may be applied to VT complicating myocardial infarction but in this situation the myocardial fibers capable of slowly conducting the activation are isolated within the fibrous tissue in the border zone of the infarct. The point of origin of VT is usually within the interventricular septum with a point of epicardial breakthrough which could be located some distance away. Different surgical techniques have been developed to deal with this condition. Encircling endocardial ventriculotomy isolates the arrhythmogenic zone from the rest of healthy tissues by tracin
Correlations between surface ECGs, epicardial mapping and histological data in 15 cases of arrhythmogenic right ventricular dysplasia (ARVD) provide information about the possible mechanism of intraventricular conduction defects in about one third of cases. Two cases in this series had complete right bundle branch block and 4 cases showed diffuse intraventricular conduction defects. The other cases had normal ECGs. The point of origin of the activation in 11 cases was situated in the left ventricle, even in 6 of the 9 cases with normal ECGs. The points of latest activation were located over the right ventricular free wall near the atrio-ventricular groove. However, in all cases but one, a normal right ventricular point of origin was observed, suggesting participation of the right bundle within a free wall showing delayed activation. This activation showed very irregular delayed propagation due to the zones of dysplasia. These results suggest that in ARVD, the mechanism of the conduction defects is not disease of the bundle branch itself but a distal block probably situated in the right ventricular wall. This hypothesis is supported by the histological appearances of the dysplastic zones.
Endocavitary catheter ablation is a new method of treating cardiac arrhythmias. It may be used indirectly, interrupting conduction through the His bundle in supraventricular arrhythmias, or directly by altering the arrhythmogenic substrate to prevent ventricular tachycardia or fibrillation. We have observed, together with other workers, that changes in the electrical properties of the catheters used to deliver the endocavitary electrical discharge. This was unexpected as the shock was delivered through a unipolar electrode with the indifferent electrode placed on the patient's back. An analysis of the morphology of the discharge impulse in intensity and voltage at increasing energy values showed that the unconnected electrodes of the multi-electrode catheter were raised to approximately the same voltage as the indifferent electrode. The change in electrical properties of some catheters was therefore the result of an insulation defect between the conducting wires leading to the electrodes. A study of the rupturing voltage of 32 USCI endocavitary catheters showed that 5 were able to sustain repeated shocks of 2 Kv and that 3 were able to sustain 3.5 Kv. The insulation of Cordis catheters was good but problems were encountered due to the resistance of the wires leading to the electrodes which dissipated an abnormally high amount of energy, so reducing the energy actually reaching the myocardium. These observations may explain the inconsistency of results obtained by different groups performing endocavitary catheter ablation with material not designed specifically for this purpose.
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Endocavitary diathermy consists of transmitting the energy of a defibrillator shock to the tip of an intracardiac catheter. The circuit is completed via a neutral plate placed under the patient's back. Energies in the order of 200 to 300 joules produce an electric arc at the catheter tip which causes an abrupt variation in pressure and the creation of a shock wave which modifies the myocardial structures directly in contact with the catheter. This method, which was originally used to treat supraventricular arrhythmias by interrupting the conduction in the His bundle, has recently been extended to the treatment of resistant ventricular tachycardia, and has even been used to interrupt the accessory pathway in certain cases of Wolff-Parkinson-White syndrome. The authors report the basic experimental data and the clinical results obtained with this method in the treatment of 20 cases of arrhythmia, especially in various types of ventricular tachycardia. The very promising results obtained, particularly in cases of ventricular tachycardia, suggest that this is a radical method which can be extended to patients unable to support a surgical operation. Although the follow-up period is only short, these results are encouraging. They confirm the basic principle of diathermy in the treatment of supraventricular tachycardia by interruption of the conduction in the His bundle and for the radical treatment of chronic ventricular tachycardia unresponsive to medical treatment. However, a longer follow-up period is required before we can demonstrate the long term effectiveness of this new therapeutic method.
A new approach is described which will allow the simultaneous synthesis of large numbers of pre-defined oligonucleotide chains. No machine aid is needed. The simultaneous syntheses can be performed by one person and do not require much more time than is currently needed for the synthesis of just one oligonucleotide in existing strategies. The general idea is the following: One uses noninterchangeable polymeric entities from each of which enough OD units can be isolated after completion of the syntheses. Whenever growing chains on different entities have to be elongated with the same building block these entities are gathered in the same reaction vessel. After such a common reaction cycle the entities are separated and now combined according to the next common building blocks etc. The practicability of this approach is demonstrated by the synthesis of d(T-A-A-T-A-T-T-A) and d(T-A-G-T-A-C-T-A) on cellulose filter disks following the phosphotriester approach.
Intensity difference thresholds were assessed behaviorally in 7 painted turtles (Chrysemys picta) before and after lesions of nucleus rotundus thalami or control lesions. Three subjects with control lesions and two subjects with slight bilateral damage to nucleus rotundus showed no permanent elevation of threshold postoperatively. In contrast, two subjects with severe damage to nucleus rotundus showed threshold elevations postoperatively and did not recover with further training. The impairment shown by these subjects with damage to nucleus rotundus appeared to be only on the more difficult problems; they performed as they had preoperatively on easy discriminations.
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The effects of inhaled sulfur dioxide (SO2) on pulmonary function in nine adolescent subjects with extrinsic asthma were studied. The exposure modes, inhaled via a mouthpiece, were (1) 1 mg/m3 sodium chloride solution droplet aerosol (NaCl); (2) 0.5 ppm SO2 + NaCl; or (3) 1.0 ppm SO2 + NaCl. All exposures were at greater than or equal to 75% relative humidity and approximately 22 degrees C. The following pulmonary functional measurements, with the subject seated in a body plethysmograph, were recorded: total respiratory resistance (RT), functional residual capacity (FRC), maximal flow at 50% and 75% expired vital capacity (Vmax50 and Vmax75), and forced expiratory volume in one second (FEV1). Following 10 min of exposure to either SO2 mode during moderate exercise on a treadmill, statistically significant changes in all pulmonary functional measurements except FRC were seen. There were no statistically significant changes following 10 min of exposure during moderate exercise to the NaCl droplet aerosol alone. Since the average pulmonary changes following exposure to 0.5 ppm SO2 mixture during moderate exercise ranged from 8 to 47%, we conclude that this dose of SO2 is above the response threshold for these subjects. To explore the effects of nasal (or oronasal) inhalation on the SO2-induced pulmonary functional changes, 7 of the 9 subjects inhaled 0.5 ppm SO2 + NaCl via a face mask with no nose clips. The average percentage changes in pulmonary functional values seen after exposure via face mask were similar to those seen after exposure via mouthpiece. However, the changes seen after exposure via face mask were not as consistent as following inhalation via mouthpiece and not statistically different from baseline. We conclude that oral, and to a lesser degree oronasal, inhalation of 0.5 ppm of SO2 elicits SO2-induced changes in pulmonary function in these subjects.