Frederick Leet Reichert

Disturbance of carbohydrate metabolism in normal dogs injected with the hypophyseal growth hormone.

Clinical and experimental data have been accumulating indicating a functional relationship between the anterior lobe of the hypophysis and the pancreatic islets. (See especially Houssay et al.) Due to the importance of such a relationship we think it justifiable to note briefly some remarkable findings bearing on this matter. Two litters of purebred dachshund, one consisting of 2 males, the other of 2 females were secured. One male and one female were injected daily intraperitoneal with the anterior hypophyseal growth hormone, 21 free of gonad stimulating hormone, for a period of about 8 months. Skeletal growth and body weight greatly exceeded that of the litter-mate controls, the weight of the injected animals soon being double that of their controls. Skin overgrowth and folding were present in both but was particularly prominent in the male. After 8 months of daily injection the male developed polydypsia, polyuria, polyphagia and became emaciated. The animal suffered from skin infection with loss of hair. He was inactive and evidently sick. Fehlings test of the urine was strongly positive. Only a trace of albumin was present in the urine. Fasting blood sugar was 232 mg. %. When injection was stopped for one week the animal improved, but rapidly failed again on resumption of injection. At present, 4 months after cessation of injection, the animal still has sugar in the urine. The test for albumin is now negative. The volume of urine has decreased and the animal has almost completely recovered. The female dachshund has now been injected one year. Though responding markedly to the growth hormone she has never shown clinical or laboratory evidence of disturbance of carbohydrate metabolism. Urine and blood sugar have remained normal.

Pathways for the Secretory Fibers of the Salivary Glands in Man

Summary 1. The rates of secretion of the salivary glands in man after unilateral section of the ninth nerve and chorda tympani indicate peripheral pathways for secretory fibers to these glands other than those accepted. 2. Section of the ninth nerve intra-cranially causes marked temporary diminution of salivation with partial recovery involving parotid, sublingual and submaxillary glands. 3. Section of the chorda tympani in the tympanic membrane causes marked permanent diminution of salivation involving the parotid, sublingual and submaxillary glands. 4. Therefore, it is concluded that the salivary glands receive their secretory fibers from both the seventh and ninth nerves.

Ineffectiveness of Prolan in Hypophysectomized Animals.

A complete hypophysectomy with cautery at the base of the brain was done by Frederick L. Reichert on a female collie (hybrid) puppy 7 weeks of age from a litter where fortunately we had a sister control. Every 2 weeks, weighings and radiographs of the leg and skull were taken. After 2 such periods it was evident that the hypophysectomy was complete. Six months after the operation daily administration of Prolan was begun and continued for 53 days. An average of 30 cc. was given daily. At this juncture an ovary and one uterine horn were removed and sectioned. The naked eye impression of infantilism in the genitalia was verified. The animal was allowed to rest for 2 weeks. For a month thereafter about 15 cc. daily of a more potent preparation of Prolan was administered. This was proven to contain 80 to 100 rat units per cc. Death from a pneumonia at this juncture terminated the experiment but examination of the remaining ovary and uterine horn showed essentially the same conditions as were previously found, i. e., a persisting true infantilism. Two other puppies were totally hypophysectomized at 6 weeks of age and subsequently similarly treated with Prolan—one of them a year after the operation and hence open to the objection that an irretrievable recession and fibrosis of the ovaries had resulted before treatment. The second puppy was hence treated 2 months after the operation but in spite of prolonged high dosage with Prolan the results were completely negative as in the first case reported.

Development of Cirrhosis in the Liver of Dogs Deprived of Both Pituitary and Thyroid Glands.

It was shown recently that the concentration of all lipid constituents (total fatty acids, phospholipids, free and esterified cholesterol) is greatly increased in the blood of the hypo-physectomized-thyroidectomized dog. 1 The present report deals with the condition of the livers of such animals. The livers of 9 dogs were examined at intervals of 70 to 419 days after they had been deprived of both pituitary and thyroid glands. The completeness of hypophysectomy in all dogs was established at necropsy. A fatty infiltration of the liver was observed in 8 of them. The livers of 6 contained abnormal amounts of fibrous tissue; all degrees of cirrhosis from early to advanced portal cirrhosis were found. The diet received by these dogs was adequate with respect to calories, proteins, salts, and vitamins and not high in fat. The details of the diet have been recorded elsewhere. 1 A section from a typical liver (dog HT8) is shown in Fig. 1. Excessive amounts of fat are present in the liver cells. The fat is distributed in both large and small droplets. There is a well developed cirrhosis with excessive amounts of fibrous connective tissue in the portal spaces. Fine ramifications of connective tissue radiate outward from the portal areas, in some instances connecting one area with another. The high fat content (11 to 52%; average 21%) found in the livers of the hypophysectomized-thyroidectomized dogs is in keeping with previous reports from these laboratories in which it was shown that a fatty infiltration precedes the formation of fibrous tissue in the liver of the dog. 2 , 3 Cirrhosis of the liver was not observed in dogs subjected to thyroidectomy alone but in these animals the fat content of the liver did not exceed 11%.

Effects of Anterior Pituitary Extract Upon an Hypophysectomized Puppy

Gigantism has been produced by Evans and Long 1 by the injections of an anterior pituitary extract in immature rats. The same result was obtained by Putnam, Teel and Benedict 2 , 3 when the extract was administered to a bulldog. Normal growth was induced by injections of this fluid in hypophysectomized rats although there was no evident repair of the thyroid, suprarenals or gonads. 4 Putnam, Teel and Benedict 2 state that “in hypophysectomized dogs and rats restoration of growth has been produced in preliminary experiments.” The effect of the anterior pituitary extract upon a hypophysectomized puppy has been studied over a period of 2 1/2 months. A sterile bovine extract of the anterior lobe, the preparation of which is given elsewhere, 5 was kindly furnished by Dr. H. M. Evans of the University of California. This extract has been found active for the growth hormone when administered to rats. By means of the intracranial approach of Dandy and Reichert 6 a total hypophysectomy was performed on an 8 weeks old female puppy. That a total extirpation was accomplished was indicated when the animal remained infantile and failed to grow over a period of 4 weeks. During this period the increase in length of both the femur and tibia, measured by skiagrams, was 6 mm. and of the skull 2 mm., while in the litter mate control the femur and tibia had lengthened 33 mm. and the skull 12 mm. The weight of the operated puppy increased 32 gm. while the control gained 88 gm. Daily intraperitoneal injections (25 cc.) of the anterior pituitary extract were given during the following 2 1/2 months. At the end of this period the operated puppy although quite thin appeared in size the same as the control.

Hepatic Fibrosis in the Persistently Non-Fatty Liver of the Hypophysectomized Dog

Summary 1. Fibrous-tissue proliferation is shown to occur in the livers of hypophysectomized dogs. Its development was not preceded by an increase in the fat content of the liver. 2. Hypothalamic damage as a cause of the fibrous-tissue proliferation was ruled out. 3. The development of hepatic fibrosis in these dogs fed a diet adequate in all respects and rich in proteins suggests that hypophysectomy induces either (a) a derangement in digestion and/or absorption, or (b) an increased need for certain dietary substances essential for the maintenance of a normal liver.

Effects of Daily Pituitary Heterotransplants on an Hypophysectomized Puppy.

Recent results obtained by Smith and Engle 1 by daily hypophyseal homeo and heterotransplants in mice and rats led to an investigation of the effect of daily injections of fresh rabbit pituitary gland on an hypophysectomized puppy. Aschner 2 published striking photographs of hypophysectomized puppies of various ages which had remained infantile in appearance and size until sacrificed. Evans and Long 3 found that fresh anterior lobe fluid given intraperitoneally to immature rats produced gigantism. Later, this extract was found to stimulate hypophysectomized rats to normal growth but failed to affect their sex glands. Smith, 4 using fresh pituitary glands of rats, was able completely or in large measure to cure the disabilities arising from hypophysectomy in immature rats. Smith and Engle 5 were able to induce precocious sexual maturity both in immature and in hypophysectomized rats, in 2 animals within 36 hours, by these fresh daily transplants. By means of the intracranial approach of Dandy and Reichert 6 a total hypophysectomy was performed on a 6 weeks old female puppy and the base of the brain in the infundibular region cauterized by heat. This animal was constantly kept with her control litter mate, also female. After months of observation, she remained infantile, failed to grow, retained the puppy face and hair, failed to erupt permanent teeth and exhibited infantile genitalia, indicative that a total hypophysectomy had been performed. Six months after hypophysectomy when 7 1/2 months old, weighing 4.2 kilos and when the control had attained adult size and weighed 9.3 kilos, fresh whole rabbits hypophysis was given subcutaneously every day by the technic described by Smith and Engle. 1 Within 48 hours the vulva were definitely swollen and within 3 days became so greatly distended as to protrude 3 cm. from the body.

Thermal Changes in Denervated and Sympathectomized Limbs With and Without Arterial Ligation

Summary Skin temperatures taken between the toes of dogs varied with the temperature of the room. The thermal vasodilation level of the normal limb of a short haired dog in a warm room was 36-39°C. The thermal vasoconstriction level was apparently 22-26°C. Section of the sciatic nerve or lumbar sympathectomy caused a relative hyperthermia in the limb of the operated side in dogs kept in a cold room. Following division of the femoral artery thermal responses paralleled those of the normal limb but were consistently slightly lower. Division of the femoral artery and ipsolateral lumbar sympathectomy or section of the sciatic nerve led to thermal responses to heat and cold similar to those obtained after division of the femoral artery alone. After division of the femoral arteries and unilateral lumbar sympathectomy the thermal responses were similar to, but more moderate than those after sympathectomy alone.

Role of the Pancreas in Prevention of Fatty Liver in the Hypophysecto-mized-Thyroidectomized Dog.

Summary 1. Dogs deprived of both thyroid and pituitary glands develop fatty livers. The livers of 2 such dogs that were fed a diet rich in lean meat for 750 to 840 days contained 22 and 25% fatty acids. 2. The addition of 2 g of methionine to each meal completely prevented the development of fatty livers in HT animals so fed. 3. The addition of 25 g of pancreas to the daily food intake also prevented the fatty livers. 4. The factors responsible for the accumulation of fat in the livers of hypophysectomized-thyroidectomized dogs are discussed.