Peter Heinbecker

Arteriography and Microangiography of Gastric and Colonic Lesions

Arteriography of the gastrointestinal tract is still basically an experimental procedure. It has not assumed the role of peripheral arteriography in the study of tumors of the extremities (6, 9), of aortography in the evaluation of diseases of the kidney, or of carotid angiography in cerebral abnormalities (1). The explanation is simple and largely a technical one. It is difficult to inject selectively the superior (10) or inferior mesenteric arteries. When such an injection is performed, the resulting arteriogram shows only a maze of superimposed vessels coursing in all directions, following the many loops of the intestine. Fine differences in vascular patterns are not discernible. Previous studies by Margulis and Heinbecker (7) showed the value of operative mesenteric arteriography and demonstrated that it is possible to differentiate inflammatory from neoplastic and benign from malignant tumors of the stomach and colon. Arteriography offers advantages over conventional studies of the gastrointestinal t...

Further clinical and experimental studies on the pathogenesis of Cushing's syndrome

Abstract Cushings syndrome may have three primary causes, a tumor of the adrenal cortex, atrophy of the paired paraventricular hypothalamic nuclei or a tumor of the ovary secreting progesterone. These primary causes effect an endocrine imbalance characterized by overaction of the hypophysial eosinophile cells and underaction of the hypophysial basophile cells. Later, because of atrophic changes in the thyroid gland and the gonads, the basophile cells may increase above normal numbers. In spite of this increase in numbers these cells are hyalinized and functionally depressed, possibly because of the associated depression of the secretion of the neural hypophysis. The imbalanced relationship between the hypophysial eosinophile and basophile cells results in an augmentation of function of those structures to which the eosinophiles normally are trophic, namely, the adrenal cortex, the corpora lutea, the androgenic cells and the renal tubule cells. Depression of hypophysial basophile cell function results in a depression of the thyroid gland and a failure of maturation of the ova and of the seminiferous tubule cells. Overaction of the eosinophile cells depresses the islet cells of the pancreas and the thymus gland. Underaction of the hypophysial basophile cells allows overaction of the parathyroid glands. These endocrine imbalances result in the signs and symptoms which characterize Cushings syndrome such as polyuria, polydipsia, polyphagia, obesity, diabetes mellitus, diastolic hypertension, arteriosclerosis, osteoporosis and a depression of maturation of the ova or of the spermatogenic cells. It is stressed that a dual origin, primary either in the central nervous system or in a peripheral endocrine gland, pertains not only to Cushings syndrome but also to many other endocrine disorders. Experimentally in the dog many of the bodily changes which characterize Cushings syndrome in man result from either denervation of the entire neural hypophysis with retrograde degeneration of the supraoptic and paraventricular hypothalamic nuclei or interruption of afferent pathways caudal to the paired paraventricular nuclei. Tumors of the thymus or of the pancreas occasionally found in association with Cushings syndrome are not considered to be primary causes of the syndrome but are believed to arise in these structures coincidentally. It is of interest to note that in Cushings syndrome these structures are depressed by the eosinophile cells of the glandular hypophysis which normally are inhibitory to them. Tumors of the parathyroid gland are believed to arise because of the lessening of inhibitory influences from the hypophysial basophile cells. Based on the experimental and clinical observations herein reported, a concept is offered to explain the pathogenesis of the various pathologic states such as obesity, polyuria, diabetes mellitus, diastolic hypertension and osteoporosis which develop in persons with Cushings syndrome.

Effects of Intra-Arterial Injection of Miokon, Hypaque, and Renografin in the Small Intestine of the Dog

Intestinal vessels were first made radiopaque by translumbar aortography. The contrast media employed in the early days were sodium iodide and iodopyracet (Diodrast). Necrosis and perforation of the small intestine occasionally attended their use. This was thought to be due either to the inherent toxicity of the medium or to its excess concentration (9). It was hoped that sodium acetrizoate (Urokon) would be less dangerous, but intestinal necrosis and deaths were reported following the injection of 70 per cent Urokon into the mesenteric arteries. When sodium diprotrizoate (Miokon), sodium diatrizoate (Hypaque), and methylglucamine diatrizoate (Renografin) became available, they were believed to be safer than sodium iodide, Diodrast, or Urokon. Lloyd (6) in comparative studies showed Hypaque to be less toxic than Miokon, and this was confirmed by Stokes (13) and Chaplin and Carlsson (1). Fischer and Eckstein (3) found fewer systemic effects with Renografin in cerebral angiography than with either Urokon or...

Effects of Hypophysectomy on Some Renal Functions.

We have reported 1 that diodrast (D) and inulin plasma clearances are markedly reduced in hypophysectomized dogs. It was not determined whether the low D clearance was due to a low renal plasma flow (RPF) or to a diminished renal extraction of D, or to both. The present paper reports on the effects of “simple” hypophysectomy (section of stalk with removal of dependent gland) and of complete hypophysectomy (includes destruction of median eminence) on D plasma clearance, plasma D extraction, RPF, tubular extraction of D, maximum tubular excretory rate for D (D Tm), inulin clearance, filtration fraction and blood volume. It also reports on the question of glomerular intermittence after hypophysectomy, with the finding that intermittence does not occur. Since no certain difference in effects of simple and of complete hypophysectomy was observed on any of the processes studied, no distinction will be made in the present report: the effects are apparently due to loss of anterior lobe, although further observations are required before a final statement can be made. Six dogs have been studied; pre-hypophysectomy observations of most of the processes studied were made on the same animals. Diodrast plasma clearance. In 15 post-hypophysectomy clearance periods on 3 dogs (K6. K10 and K11) taken at 7 to 93 days after operation, D plasma clearance has averaged 141 cc/min./M2, where the normal was 258. The clearance of one completely hypophysectomized dog (K8) on the 4th postoperative day was 155, normal 222; a “simple hypophysectomy” dog (K9) on the 3rd day showed 191 cc/min./M2, where normal had been 208. One dog (K1), with a normal clearance of 232, had a unilateral nephrectomy on 7/22/40 and a simple hypophysectomy on 7/26/40; on 9/4/40 her D clearance was 107.

Properties of Unmyelinated Fibers of Nerve.

Previous reports on the physiology of nerve by Erlanger, Gasser and Bishop 1 have dealt with the properties of the myelinated fibers. In this paper are presented data on the properties of fibers characteristic of the involuntary nervous system especially the unmyelinated ones. The analyses have been made by means of the cathode ray oscillograph and the use of amplification greater than was usually considered necessary for the study of the myelinated fibers. The unmyelinated fibers can be identified by a conduction rate slower than that of the ordinary myelinated fibers of peripheral nerves (1.5 to 0.2 M. per sec. in the turtle). These rates are comparable to the rates reported by Chauchard, A. et B., 2 as determined from the effect of stimulation at different levels along the course of nerves containing unmyelinated fibers. A second characteristic of these fibers is their high threshold. An induction shock at least 10 to 100 times that of the most irritable fibers in the same nerve is required for a threshold response in the turtle, in the cat 50 to 100 times. A more suitable method of stimulating these fibers is by the galvanic current. The nerve is arranged in a bridge balanced for resistance and capacity as described by Bishop. 3 Relative thresholds can then be measured either by change in duration or by change in intensity of stimulating current. On the basis of either threshold or conduction rate the fibers, if myelinated, would have to be not more than 0.1μ in diameter in order to fit the size conduction rate ratio of Gasser and Erlanger 4 for the myelinated fibers. Myelinated fibers of this diameter are not found in the nerves under consideration. Using the galvanic current in the manner indicated above, the chronaxie of these fibers can be measured.

Differentiation Between Types of Fibers in Certain Components of Involuntary Nervous System.

Criteria discussed in a previous report 1 have been employed to distinguish between 3 different types of fibers which occur together in nerves of the involuntary nervous system. Comparative measurements of threshold 2 have also been extended to these fibers. The cervical sympathetic trunk of one variety of turtle serves as a typical nerve containing such axons, recognizable by 3 groups of waves in their conducted action potential record on the oscillograph. These groups will be designated as the A, B, and C groups. A second type of turtle has only 2 groups of waves in the cervical sympathetic nerve trunk, the second and third. Sections of the first type of nerve∗ show scattered, larger, and for the most part thinly myelinated fibers, with islands well marked off by trabeculae containing unmyelinated and small myelinated axons. Sections of the second type show only such islands containing practically no large fibers. The second and third groups of waves in these nerves are therefore inferred to correspond to the thinly myelinated and unmyelinated axons respectively of these islands. The relative areas of potential of the third wave in various other nerves studied corresponds in general to the relative number of unmyelinated axons. In the second type turtle the third wave group is larger than the second in area. The white and gray rami of the frogs 7th nerve consist almost exclusively of these typical islands of myelinated and unmyelinated fibers, and Gasser and Erlanger (personal communication) have observed B and C waves in a gray ramus. Certain dorsal roots of bullfrog and turtle also have similar thinly myelinated axons which are being studied as a possible source of sympathetic outflow.

THE INFLUENCE OF SUCCINYLSULFATHIAZOLE (SULFASUXIDINE) UPON THE RESPONSE OF CANINE SMALL INTESTINE TO IRRADIATION

A study was carried out to determine whether the injury attending intense segmental intestinal irradiation could be reduced by diminishing and altering the intestinal bacterial flora. Sulfasuxidine administration for 3 days before and 6 weeks after irradiation of isolated segments of canine ileum with 4000 r significantly reduced the lethality attending the irradiation of 15- cm lengths of ileum and reduced the inflammatory cell infiltration and edema and increased the vascularity of the granulation tissue internally lining the mucosally denuded areas of 5-cm lengths of ileum. Following the rapid complete loss of mucosa attending irradiational injuries of 4000 r, the size of the mucosally denuded area was reduced by exponential longitudinal shortening by the absorption of the irradiated muscle and connective tissue. An almost complete spontaneous anastomosis of proximal and distal nonirradiated intestine was effected 8 months after the irradiation of 5-cm lengths of ileum. The administration of Sulfasuxidine did not influence this rate of absorption. The mechanisms of the obstruction of the irradiated intestines are discussed. (M.C.G.)

Correlation between Threshold and Conduction Rate in Myelinated Nerves

In observing the effects of stimulating a nerve in the body, it is possible to lead off the cut end of the nerve into the oscillograph and thus correlate the potential form with the functional result of stimulation. Since the different fibers of a nerve are stimulated at different threshold strengths, if the difference in thresholds of different fibers were known, the oscillograph or other potential recorder could be dispensed with except for an occasional observation of threshold for the most irritable fibers, and the experimental procedure thus simplified. With this end in view, we have examined the ratios between the threshold of the first fibers stimulated in a nerve and that of other fibers, taking as criteria the thresholds of the first fibers in the various potential waves which represent fiber size groups. Gasser and Erlanger 1 have shown that the conduction rates of different fibers tend to vary as the fiber diameters, and by correlating the thresholds and conduction rates of different waves it should be possible to find the relationship between threshold and fiber size. For the potential waves of 4 bullfrog sciatic nerves, the averages of the ratios of the α/β and β/γ conduction rates are 1.64 and 1.60, respectively. The same ratios for similar nerves for which the data are obtained from the table in Gasser and Erlangers 2 paper are 1.62 and 1.60. This is approximately the ratio of fiber diameters shown in Gasser and Erlangers charts of size distribution. The β/δ ratios of conduction rate for 2 nerves available are 1.45 and 1.40. The ratio of average thresholds for β/α for the first 4 nerves above is 1.63, but the γ/β ratio is 2.3. No data are available for δ.

Influence of Eosinophile Cells of Hypophysis on Kidney Function

White, Heinbecker and Rolf 1 reported that removal of the glandular division of the hypophysis in dogs resulted in a reduction of 50% or more in inulin and diodrast clearances and in maximal tubular excretion of diodrast at high plasma levels. These changes indicate a depression of renal blood flow and of renal tubular excretory capacity and were in evidence within 7 days after the removal of the glandular hypophysis. They have persisted under observation for a period of 2 years. It can be stated, therefore, that the glandular hypophysis exercises a humoral influence on the kidney. Evidence that the eosinophile cells of the hypophysis are responsible for this influence is presented in this paper. Observations on the urea clearance of 5 patients with acromegaly revealed values of 130, 83, 135, 231, and 100%, respectively, of the normal standard. Three of these values are definitely above the upper limit of normal. An eosinophil tumor was found at autopsy in the first of these patients. The kidneys weighed 420 g. Microscopically the glomeruli and tubules were slightly hypertrophied. There was generalized arteriosclerosis of the renal vessels. Some increase in kidney size is a usual finding in acromegaly. Since eosinophil cell hyperplasia or eosinophil tumor formation has been found in all cases of acromegaly 2 coming to autopsy, the increase in renal function and in renal size observed in this disease perhaps may be attributed to hyperfunction of the eosinophil cells of the glandular hypophysis. The degree of secretory activity of the hypophysial tumor should be reflected in the extent of increase in renal function. Winternitz and Waters 3 and White, Heinbecker and Rolf 4 have shown that in dogs a single remaining kidney fails to hypertrophy after removal of the glandular division of the hypophysis.

Nature and Function of Certain Fibers of the Vagus--A New Concept in Peripheral Nerve Organization

All analysis of the vagus nerves of the cat and turtle (Hein-becker 1 ) demonstrated 3 distinguishable potential complexes. The first had physiological properties characteristic of somatic nerve fibers, the other 2 had properties of a much slower order, properties which our subsequent investigations have associated with autonomic motor functions. A correlation between potential form and nerve fiber type as revealed in osmicated cross sections of nerve indicates that the first potential complex is derived from larger myelinated fibers, the second from small thinly myelinated fibers and the third from non-myelinated fibers. Experiments have been performed on the cat in which stimulating and recording electrodes were placed on the central portion of one cervical vagus nerve in an animal in which both nerves were cut. The potential record of the nerve was observed coincidentally with the physiological effects in the animal resulting from electrical stimulation. The afferent fibers whose activity is responsible for respiratory and vascular reflex effects are found to fall in the group giving rise to the first potential complex. No further effects are elicited by stimuli strong enough to excite the fibers giving rise to the second and third potential complexes. The vagus nerve above the nodose ganglion was sectioned in cats and after sufficient time for degeneration the vagus nerve trunk in the neck was studied functionally. In such preparations adequate stimuli failed to cause slowing of the heart rate, but normal results from the fibers responsible for certain motor effects in the lungs and duodenum were still obtained. Section of vagus roots at their exit from the brain stem after sufficient time for degeneration had a similar effect, indicating that the fibers responsible for slowing of the heart rate have their cells of origin within the central nervous system.