Victor G. Haury

Effect of Nephrectomy on Duration of Action of Barbitals

Fitch and Tatum 1 have divided the barbitals into 2 groups based upon the duration of their action and upon the manner in which they cause death. They found that the longer acting barbitals (especially phenobarbital and barbital, ethyl-n-butyl barbital (neonal), isoamyl barbital (amytal), ethyl iso-propyl barbital (barbituric acid of ipral), and also iso-propyl bromallyl barbital (noctal) cause death from pulmonary oedema, while the other barbitals, which they group as the short acting barbitals, when injected intraperitoneally in toxic doses cause death from depression. Our finding that there is a marked difference in action of magnesium sulphate when administered to normal and to nephrectomized rabbits and to nephritic patients 1 , 2 , 3 led us to try this method of testing barbital action. Nephrectomy in etherized rabbits was done through a lumbar incision and was greatly accelerated by the use of a specially devised kidney fork. This was made from an ordinary table fork the first and third tynes of which were sawed off completely, the second and fourth being sharpened and bent around to form a semicircle of 3 cm. diameter. This was inserted through the lumbar incision so as to grasp the kidney, the renal pedicle passing through the space left by removal of the third tyne of the fork. A plate of spring phosphor bronze 7 cm. long and 2 cm. wide, sliding on a collar surrounding the handle of the fork was then pressed down so as to grasp the kidney completely, the kidney was drawn up through the incision and the renal pedical ligated. The incision was then sutured. The operation requires 15 to 20 minutes. The animals were allowed to recover completely from the ether anesthetic and the barbital was injected subcutaneously on the following day.

Action of Apomorphine Hydrochloride on the Intact Intestine in Unanesthetized Dogs.

Summary and Conclusions 1. The results of these experiments support the findings published by Gruber and Brundage 1 and by-Slaughter and Gross. 2 2. Apomorphine when injected intravenously may either increase or decrease the general tonus of the intact intestine, depending upon the animal and the condition of the animal at the time of the injection. Some animals respond to apomorphine only by increased tonus, others by decreased tonus, and still others by either or both responses. 3. The peristaltic contractions may be augmented by apomorphine especially when the general tonus is diminished. 4. Borborygmi are commonly noted following the intravenous injection of apomorphine.

Effect of Parathyroid Hormone on Diffusion of Calcium, Magnesium and Phosphorus into the Peritoneum. I

Eight adult dogs were given intraperitoneal injections of 2.5% dextrose and 0.9% NaCl solution in the dosage of 100 cc per kg. After 16 hours, 20 cc of blood were withdrawn from the femoral artery and 20 cc of fluid from the peritoneum. Five hundred units of parathyroid hormone 4 were then injected intramuscularly. Similar blood and fluid samples were obtained hourly for 8 hours and were examined for Ca, Mg and inorganic P content. Magnesium. The control values for serum Mg were 2.1-3.26 mg %. In 6 cases parathyroid administration was followed by a fall in serum Mg, the maximum decrease being 0.35-0.8 mg % at 1-6 hours, with a tendency to return to normal at 3-8 hours. In one case the serum Mg increased (0.3 mg). No significant change occurred in one case. The control values for peritoneal fluid Mg were 1.75-2.0 mg %. These increased in each instance, the maximum increase being 0.17-1.02 mg %, the peak occurring at 5-8 hours. The control ratio of fluid to serum Mg was 57-87%, the mean being 75%. This ratio rose in each case, the maximum rise being 12-46% at 5-7 hours. The relatively slight changes in serum Mg after parathyroid hormone administration are in accord with previous reports. 1 , 2 , 3 However, these described a primary increase in serum Mg followed by a decrease, whereas the opposite occurred in the majority of animals in the present series. The most consistent change was an increase in the amount of diffused Mg, suggesting that the parathyroid hormone increases the diffusibility of serum Mg. Inorganic P. Control values for serum P were 3.1-5.4 mg %. These fell in every case after parathyroid administration, the maximum decrease being 0.6-1.1mg.

The toxicity of digitalis and ouabain in animals under sodium thiopentobarbital and sodium pentobarbital anesthesia

Abstract 1. 1. Dogs are not satisfactory animals for the bio-assay of digitalis. 2. 2. Anesthetic agents play a role in determining the toxicity of digitalis and ouabain. When sodium thiopentobarbital is used the amounts of either digitalis or ouabain which are needed to bring about cessation of cardiac activity are much less than those required when sodium pentobarbital is the anesthetic agent.

Some Observations Upon Blood Glucose in Epilepsy

Pigott 1 has recently reported low blood sugar in epileptic convulsions and regards hypoglycemia as a possible etiological factor. In our series of 25 cases in which 3 or more determinations have been made in each case we do not confirm this view. The blood glucose was determined by the method of Gibson. 2 Determinations were made before, during and after seizures and in each case the blood glucose was within normal limits (90 to 110 mg. per 100 cc. blood) before convulsions, and rose during the convulsions. The rise of blood sugar was roughly proportional to the severity of the seizure, and after termination of the convulsion the blood sugar returned to normal in two to four hours. In 4 cases of status epilepticus the blood sugar value before seizure was 95.0 to 100.0 mg. per 100 cc. blood. After about one hour of status the values rose to 139.0 to 190 mg. per 100 cc. and after three hours of status the values were 150 to 240 mg. per 100 cc. In 21 cases having moderate to very severe isolated seizures the blood sugar rose from the average of 92.5 mg. per 100 cc. blood before seizures to 168.0 mg. per 100 cc. during convulsions. In 7 cases the elevation of blood sugar was above 185 mg. per 100 cc. during the height of the convulsions. In no instance was hypoglycemia found either before or during the convulsions.

Variations in Plasma Magnesium and Potassium in Epilepsy

McCollum and his collaborators, 1 , 2 and also Greenberg and Tufts 3 have produced hyperirritability and convulsions in rats fed on a diet deficient in magnesium. Since we have found neuromuscular twitchings and convulsions in cases of clinical hypomagnesaemia, 4 since McQuarrie 5 believes that in epilepsy there is a “leakage of potassium” through the cell membrane, and since Hirschfelder 6 has shown that potassium salts can antagonize the narcotic action of magnesium, we have investigated the plasma magnesium and potassium in clinical epilepsy. We determined magnesium by the method of Hirschfelder, Serles and Haury 7 † and potassium and calcium by those of Kramer and Tisdall. 8 , 9 Total magnesium 1.7 mg. Mg or below 100 cc. plasma and ultrafiltrable Mg 0.7 or below were regarded as low; K above 30 mg. was regarded as high. In epileptics whose plasma was collected during or just before convulsions we found the following deviations from normal: In 5 cases of status epileptics low magnesium (1.2 to 1.7 mg.) occurred in 4, high potassium (35 to 68.5 mg.) occurred in 5, high potassium/magnesium ratio occurred in 5. In 13 epileptics with very severe convulsions, low magnesium (1.3 to 1.7 mg.) occurred in 9, high potassium (31.7 to 63.6 mg.) occurred in 6, high potassium/magnesium ratio occurred in 13. In 12 moderately severe epileptics low magnesium (1.6 to 1.7 mg.) occurred in 3, high potassium (31.6 to 52.8 mg.) occurred in 8, high potassium/magnesium ratio occurred in 11. In 5 epileptics with mild convulsions, low magnesium (1.6 to 1.7 mg.) occurred in 2, high potassium (31.7 to 40.2) occurred in 3, high potassium/magnesium ratio occurred in 4.

Protective Action of Mercury and Lead Salts Against Procaine Convulsions.

Recently Beutner, Landay and Lieberman 1 reported that hydroxy mercuri-methoxy-propyl carbamyl phenoxy acetate (salyrgan) will act as an anticonvulsant drug. They found that salyrgan prevented the usual procaine convulsions if the two drugs are mixed prior to the injection. They also noted that if the salyrgan is injected separately before that of procaine, it afforded no protective action against the procaine. They concluded from these experiments that the “anticonvulsant” action of salyrgan is not through a renal diuretic action but rather by virtue of a “tissue diuretic” action, i. e., decreased cellular permeability. A series of experiments was performed in our laboratory in which the following intramuscular injections were made into guinea pigs: (1) procaine alone, (2) procaine and salyrgan into separate areas of the body, (3) procaine and salyrgan mixed before the injection, (4) procaine and mercuric chloride mixed before the injection, and (5) lead nitrate and procaine mixed before the injection. Results. Our experiments confirm Beutner, et al., that salyrgan will protect an animal against procaine convulsions if the 2 drugs are mixed before being injected, but not if the 2 drugs are injected separately in different regions of the body. In 17 experiments performed on as many guinea pigs, 150 mg per kilo of procaine (10% solution) were injected intramuscularly into the right rear leg. Sixteen of the animals showed violent convulsions, from which they recovered in 15 to 40 minutes. In 12 experiments 20 mg per kilo of a 10% solution of salyrgan were injected intramuscularly and immediately following 150 mg of procaine per kilo were injected intramuscularly into the opposite extremity. All of these animals had convulsions which were as severe and lasted as long as those in which procaine was injected alone.

Effect of Parathyroid Hormone on Diffusion of Calcium into the Peritoneum. II

Two adult dogs, which had been subjected to repeated (7 times each) filling and emptying of the peritoneal space (dextose, 2.5%-NaCl, 0.9% solution, 100 cc per kg) during the preceding 3 weeks, were treated as indicated in Fig. 1. The purpose of the repeated filling and evacuation of the peritoneum, particularly during the 24 hours preceding the injection of parathyroid hormone, was to determine whether the removal, by this means, of diffusible calcium from the blood would influence the response to parathyroid hormone.∗ In Dog 19 (18 kg), a total of 183 mg, and in Dog 20 (18 kg), 201 mg of calcium was removed in the peritoneal fluid in the 24 hours immediately preceding the intramuscular injection of parathyroid hormone. No food and only distilled water were allowed during the experimental period. Three points of interest are revealed by these data. (1) Under certain conditions, the administration of parathyroid hormone may result in hypocalcemia. That these animals were not refractory to the hormone was indicated by the fact that changes occurred in the serum and peritoneal fluid magnesium which were identical with those observed in a series of cases in which hypercalcemia was produced by the hormone. 1 (2) A fall in serum calcium may be accompanied by a fall in the peritoneal fluid calcium. This is of importance in view of the doubt as to whether the concentration of calcium in the fluid is capable of changing, and especially of decreasing rapidly simultaneously with corresponding changes in the diffusible fraction of serum calcium. (3) An actual and significant increase in “diffused” calcium may occur following parathyroid hormone administration with a constant (Dog 19) or a falling (Dog 20) serum calcium concentration.

Magnesium as a Bronchodilator Agent in Perfused Guinea Pig Lungs

Conclusion Magnesium is an effective antagonist to pilocarpine and barium constriction, and less effective against histamine constriction.