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Summary The data adduced in Part I of this paper together with the evidence previously collected by the authors indicate that in man the "non-parietal component" of the gastric juice is not a uniformly constituted "alkaline constituent", i.e. a functional and specific entity secreted mainly for the purpose of diluting and buffering the parietal acid secretion of the stomach. The calculation of the acid-binding capacity of the gastric mucous substances dissolved in the gastric juice and its correlation with the organically bound chlorides and the combined acidity of the gastric juice have indicated a limited role of the nondialyzable components of gastric mucin in the binding of the hydrochloric acid in the stomach of humans. According to evidence in the literature and our own studies at least four different non-parietal component secretions can be distinguished with a reasonable degree of probability in the human stomach, the mixture of which with the parietal secretion forms the gastric juice: 1) peptic glandular secretion from the chief cells of gastric glands, containing mainly pepsin and some electrolytes; 2) mucoid glandular secretion from the mucoid cells of the neck of fundal glands, containing neutral chlorides and the "glandular mucoprotein"; according to the recent evidence presented elsewhere by the authors this mucoprotein carries Castle's intrinsic hematopoietic factor, or is intimately related to it; 3) mucous secretion from cardiac and pyloric glands, containing unidentified mucous substances, bicarbonates and possibly gastrin from pyloric glandular elements; 4) mucous secretion from columnar cells of the surface epithelium, comprising surface epithelium mucus, its dissolution and degradation product-gastric mucoproteose, desquamated epithelial cells, calcium salts, bicarbonates and phosphates, and probably also neutral chlorides and lysozyme. The "non-parietal component" of gastric secretion, therefore, is not a specific secretory entity which may be compared or opposed to the "parietal component" of the gastric juice. It is rather a mixture of at least four component secretions, each of which is more or less complex in composition, but strictly defined in respect to its cellular source in the gastric mucosa, the mechanism by which its secretion is governed, as well as to its physiological significance.

1. Twenty patients with pernicious anemia were treated under rigidly controlled conditions by administering small oral doses of vitamin B12 in combination with intrinsic factor containing mucinous materials processed from the hog stomach. This study was undertaken in view of our earlier observation concerning the relationship of one of the mucin fractions of the human stomach (glandular mucoprotein) to Castle’s intrinsic factor. The following sources of intrinsic factor from animal stomach were used: (a) commercial gastric mucin; (b) acetic acid extracts of hog pyloric mucosa; (c) mucinous materials precipitated by acetone or by saturation with ammonium sulfate from hydrochloric acid extracts of the hog pyloric mucosa; (d) mucous fractions obtained by further fractionation in the electroconvection apparatus of the above mucinous materials precipitated with ammonium sulfate; (e) an intrinsic factor concentrate from the hog stomach in combination with small doses of vitamin B12, processed under the trade name of Bifacton. 2. Results obtained in this study indicate the feasibility of attaining complete clinical remission and suboptimal or optimal hematopoietic responses in patients with pernicious anemia in relapse when small daily doses (below 20 µg.) of vitamin B12 are given orally in combination with mucinous materials processed by various technics from the hog stomach and containing intrinsic factor. The provisions are that: (1) the doses of both vitamin B12 and intrinsic factor containing materials be adequate and optimal in regard to their mutual ratio; (2) the process involved in processing intrinsic factor containing materials not impair their activity and yield a product sufficiently concentrated. 3. The hematopoietic responses and clinical remissions obtained in six cases of pernicious anemia with Bifacton (vitamin B12 with intrinsic factor concentrate) in different batches were uniform in our hands. The doses employed were marginal, in order to detect differences in potency, and although the reticulocyte responses were frequently suboptimal and protracted, the increases in red cells were roughly equivalent to those obtained with daily administration of approximately 1 unit of a standard oral antianemia preparation. Bifacton is supplied in strikingly smaller dosages than the standard liver or stomach oral preparations, and is fully active in a total daily oral dose of about 50 mg. of intrinsic factor concentrate with 15 µg. vitamin B12. 4. Preliminary studies on two patients with pernicious anemia tend to indicate that the administration of massive single oral doses of Bifacton repeated at intervals of one week may imitate even more closely the results of parenteral treatment with injectable liver concentrates or vitamin B12 than does the administration of this concentrate in small daily doses. The single dose of Bifacton which was given once a week to one of these patients contained 150 µg. vitamin B12 with approximately 250 mg. of intrinsic factor concentrate. Five consecutive single doses administered at intervals of from seven to ten days induced a complete clinical and hematologic remission. 5. The studies on two patients with pernicious anemia indicate that Bifacton is resistant to boiling and that it preserves its hematopoietic activity after being boiled in water for from thirty to forty-five minutes at 95 to 100°C. This suggests either that the intrinsic factor of the animal stomach becomes thermostable after the interaction in vitro with vitamin B12, or that the product of this binding is thermostable under conditions described. 6. The data reported here indicate that various extraction and precipitation procedures may be applied to hog stomach tissue to obtain materials which will exhibit definite intrinsic factor activity in patients with pernicious anemia. Although at present some such extracts are active orally in such small doses as from 40 to 50 mg. per day, still further refinement appears to be possible.

SummaryIn cats and dogs Viscum album produces a characteristic high take-off. If this is distinctly developed, one can no longer recognize a disturbance of intraventricular conduction (bundle-branch block) and stimulation of the accelerans does not alter the shape of the terminal deflection.

1. 1. A statistical survey has been made of the clinical and pathologic features of 111 cases of aneurysm of the pulmonary artery in which the diagnosis was confirmed by autopsy. 2. 2. Some of the features of thirty cases in which a clinical diagnosis of aneurysm of the pulmonary artery was made have been summarized. 3. 3. Two cases of aneurysm of the pulmonary artery are reported.

The important clinical features of 413 cases of esophageal carcinoma have been analyzed and allusion made to some other similar studies in the literature. Stress has been laid upon the interpretation of major symptoms in the hope that more early diagnoses will be reached.

Comment and conclusionsThe simultaneous determination of thermal coagulation of blood serum in a large series of cases by the measurement of thermal coagulation point and iodoacetate index has shown similarity of results. There was an inverse relationship, in most instances, between the level of the thermal coagulation point of serum and the concentration of iodoacetate necessary to prevent heat coagulation. The dissociation between the results of both technics appeared exclusively in the group of cases showing a moderate defect in thermal coagulation. This could have resulted, in part, from calculation of the thermal coagulation defect, in the case of the iodoacetate index, in terms of total proteins content, and the omission of the protein factor in the estimation of the thermal coagulation point of serum. It must have been due at times, however, to the results obtained with the iodoacetate technic, which, for unknown reasons, are not always reproducible(7, 9). The percentage of abnormalities found in t...

THE anti-inflammatory effect of parenterally given proteases has evoked considerable clinical interest. In a recent review article Moser1 termed enzyme therapy "a new avenue of therapeutic approach to the problems of thromboembolism and inflammation." According to Kramer and de Madeiros,2 "numerous contributions have proven the value of enzymes in edema, cellulitis and particularly in hemorrhagic extravasations in the tissues." Several workers have investigated the possibility that the anti-inflammatory effect of proteolytic enzymes is due, in part, to their effect on tissue permeability.3 , 4 Indeed, the addition of streptokinase tended to restore permeability after reduction in the permeability of connective tissue by . . .

An intravenous injection of insulin represents a powerful stimulus for secretion of gastric acidl 8• The action of insulin arising through the central stimulative effect of hypoglycemia on the cerebral vagal centers5 differs from humoral and peripheral vagotropic stimuli which act directly upon parietal cells or peripheral autonomic ganglia. This difference of action found application in a test for determining the thoroughness of vagotomy9, 10 as well as in tests to evaluate the vagal mechanism of gastric secretionU 13 and for testing the functional status of all cellular secretory elements of gastric glands14. The last application of insulin is possible because it represents the most comprehensive gastric secretory stimulus known, for its action is not limited to an evocation of hydrochloric acidl 8 but it also affects pepsin12, 16, 16 and gastric mucoprotein16 , 18. The negative results obtained by some authors12, 17 in respect to the influence of insulin on gastric mucin components are now known to depend upon an inadequate technic for mucin determination18. Recently gastric mucoprotein has been separated from the total dissolved mucin of human gastric juice18 , 19. Being probably identical with the mucoprotein isolated from canine gastric juice after sham feeding20 human gastric mucoprotein is closely related to but different from gastric pepsin16, 21. Gastric mucoprotein has nothing in common with the secretion of surface epithelium, i.e. the visible surface epithelium mucus and its dissolution and split product, the dissolved gastric mucoproteose19 , 22. Apparently it is a secretory product of the gastric glands located in the fundus and body of the stomach and it is strongly under direct vagal influence18. Testing the mucoprotein and acid response to insulin has been suggested as a new test for evaluation the secretory status of the fundal glands23, and various patterns of mucoprotein and acid response to insulin were observed23 , 24: a) positive pattern characterized by a rise in mucoprotein concentration and gastric acidity; b) dissociated pattern characterized by a positive mucoprotein and negative acid response to insulin; c) negative pattern characterized by a negative response of mucoprotein and acid to insulin. In the present paper an attempt will be made to correlate the results of this test with the underlying gastric pathology in the nonoperated normal and pathological stomach.

The concentration of vitamin B12 in blood serum and its excretion in the urine were assayed by the E. coli mutant technic in two patients after total gastrectomy and by use of the more sensitive Euglena gracilis method in four cases of pernicious anemia in relapse and 1 case of well controlled nutritional macrocytic anemia. Following parenteral administration of 100 µg. vitamin B12 intramuscularly to two patients with total gastrectomy, much higher blood levels were observed within the first few hours than those reported by others under similar circumstances in normals. Following oral administration of vitamin B12 together with a potent intrinsic factor concentrate from hog stomach, a rise in blood levels of vitamin B12 was observed in patients with pernicious anemia. The normal serum levels of vitamin B12 could not be maintained, however, for the entire duration of the oral treatment, in spite of the apparent hematologic and clinical remission. The urinary output of vitamin B12 was in all instances less than 0.5 per cent of the total dose of vitamin B12 ingested during the experimental period, in spite of an optimal or suboptimal hematopoietic response obtained. A similar situation existed in patients with total gastrectomy, as well as in the patient with controlled macrocytic nutritional anemia, when vitamin B12 was ingested alone or with intrinsic factor concentrate. The intensity of the obtained hematopoietic response in patients with pernicious anemia indicates the absorption of much larger amounts of vitamin B12 from the intestine than is indicated by the total urinary output of vitamin B12; therefore the anchorage and retention of a large part of vitamin B12 in the storage depots of the body after its absorption from the intestine must occur. A sharp increase in the urinary output of vitamin B12 was observed during or immediately following the hematopoietic response in all patients with pernicious anemia treated orally with vitamin B12 and intrinsic factor concentrate, i.e., coincident with or immediately following the reticulocyte peak in blood. Similar observation was reported by the authors in the previous series of investigations. Of many possible interpretations of this finding, the most plausible appears to be the metabolic release of free vitamin B12 from its complex binding in the body during hyperactivity of the hematopoietic organs and its escape through the kidneys.

1. New, previously untreated cases of pulmonary tuberculosis were treated with a cycloserine-isoniazid combination given orally. 2. Eighty-one cases have been treated for from six weeks to 16 months, with but a single reaction, which did not necessitate discontinuance of treatment. 3. Clinical improvement, reduction of fever, lessening of the volume of sputum, and gain in weight occurred promptly in every case. In addition, the administration of a single capsule containing cycloserine and isoniazid, twice daily, was more acceptable to the patients than the usual INH-PAS combination. 4. Within six weeks, 40 per cent of the x-ray films showed evidence of improvement. The figure rose to 74 per cent in 12 weeks, and to 93 per cent of 48 subjects treated for six months. 5. Evidence of reduction in the bacillary content of the sputum was obtained within six weeks of treatment. Within three months, 80 per cent of 64 sputa were negative on culture, and at six months the figure rose to 87 per cent. 6. Bacillary sensitivity to cycloserine fell slowly and slightly during prolonged treatment with the larger doses. From 0.5 Gm. of cycloserine per day, there was no evidence of decreased sensitivity. 7. Resistance to INH developed during the administration of the cycloserine isoniazid combination at approximately the same rate as is seen when INH is given alone. 8. It is our conclusion that a combination of 0.25 Gm. of cycloserine and 0.15 Gm. of INH given twice daily is effective and safe therapy against previously untreated cases of pulmonary tuberculosis. We feel that our clinical results were superior to the usual INH-PAS therapy, both in speed and degree of response, as gauged by x-ray film changes and sputum conversion.

1. The distribution of radioactive vitamin B12 in humans was studied by scintillation counting of radioactivity over various skin projections of underlying organs in five individuals, following parenteral administration of radioactive vitamin B12. The results of these investigations showed that the scintillation surface measurements of the radioactivity following parenteral administration of radioactive vitamin B12 may be profitably applied to the study of the metabolic turnover of vitamin B12 under normal and pathological conditions in humans. 2. In two young normal control subjects over 96 per cent of the parenterally administered radioactive vitamin B12 (5 and 10 µg. containing 0.925 µc. of Co60) disappeared from the site of the intramuscular injection within three to four hours, and during that time radioactivity rose to its peak value over the areas corresponding to kidney, spleen and iliac crest, and somewhat later over the muscles of the extremities. Subsequently, a gradual decline of radioactivity was observed over the spleen, kidney and extremities, so that at the end of three months in the normal subject from ⅓ to ½ of radioactivity as compared to peak values was observed over the spleen and left kidney and about ¼ over the calf muscle. The projection areas of the liver differed from all the other areas of the body in requiring about five to six days to build up the peaks of radioactivity. These exceeded counts over the kidney and spleen about 2½ times, counts over the iliac crest approximately 7 times, and those over the calves about 17 times. The decline of radioactivity over the liver and iliac crest was very slow and small. 3. The patterns of the uptake of injected radioactive vitamin B12 by the totally gastrectomized patient were grossly similar to those observed in normal controls, except for possibly slightly faster absorption of the injected material from the site of injection, and somewhat faster and larger accumulation, but also faster discharge of radioactivity from the liver area. 4. In a patient with pernicious anemia in partial remission who received three parenteral doses of 2 respectively 10 µg. radioactive vitamin B12 (0.185-0.925 µc. Co60), the uptake of the radioactive vitamin B12 by the kidney and spleen area was slightly higher than that of the normal controls, that of the liver similar to the normal, and that over the iliac crest showing a significantly faster decline than in normals during the course of study. The uptake of radioactive vitamin B12 in the same patient following intravenous injection of the same dose of radioactive vitamin B12 was grossly similar to that following intramuscular injection of the same dose of radioactive material, except for the faster accumulation of radioactivity over the kidney area. 5. From 65 to 86 per cent of the peak radioactivity persisted over the liver 2-3 months after parenteral administration of radioactive vitamin B12 to two control subjects. After five months 60 per cent of the initial peak of radioactivity was still observed over the liver in the patient with anemia of sprue in remission, 85 per cent in a patient with pernicious anemia in partial remission, and at the end of eight months still 35 per cent of the peak liver count in a patient with total gastrectomy without anemia. This does not take into account the normal decay of Co60 which is about 1 per cent per month. 6. If the presence of Co60 in the liver indicates the deposition of Co60-B12 in this organ, which is most probable, then the long storage of vitamin B12 in the liver may explain the long time needed in humans for depletion of hepatic stores of vitamin B12, as well as for long remissions observed in pernicious anemia following parenteral treatment with liver extracts or vitamin B12.

Largely through the work of Ranson and his associates (1), inability of the kidney tubule d to resorb water in normal quantity has been established as the primary functional disturbance in the patient suffering from the syndrome of diabetes insipidus. Because of the large volume of urine thus secreted, such subjects seem peculiarly adapted to a study of the action of hormones and other agents which are apparently capable of affecting water and electrolyte balance in the body. Three patients with diabetes insipidus, two of the persistent and one of the intermittent type, have served as the basis of the study. In each of these three patients the presence of diabetes insipidus has been proven by the use of water-deprivation and saltloading tests when the patients have been successively on a dietary of average, low, and high salt content, respectively. methods and procedure Each of the three patients with proven diabetes insipidus was hospitalized for several weeks prior to a study of the influence of various...

1. A special pancreatic-pepsin preparation (P. P. tablet) was given to each of 30 patients with an active peptic ulcer. A moderate to marked relief of pain occurred in 70% of the cases, which indicates that this form of therapy is rather effective in the treatment of peptic ulcer.

Since weakening of the heart muscle leads to incomplete emptying and progressive dilatation, which in turn results in impaired conduction, arrhythmias, and auricular fibrillation, it is conceivable that these conditions would be improved by increasing the force of the heart and slowing its rate by digitalis, or by relieving its load.In order to accomplish the latter we have bled 5-10 cc. per kg. or changed the distribution of the blood in the active circulation by snake venom (Lachesis colatitudes), histamine, peptone and nitrites.∗ These drugs were injected into the femoral vein of cats previously anesthetized with urethane. Respiration and blood pressure curves were taken and checked up by simultaneous electrocardiograms.After a normal tracing and electrocardiogram were taken, cardiac arrhythmias were produced by chloral or aconitine, mostly the former because of its more uniform results. Fifty mg. of chloral hydrate per kg. was the initial dose used. Occasionally this was sufficient to cause an irregul...

Manche Arzte sind noch im Zweifel, ob man zwischen diesen beiden Zustanden eine scharfe Trennungslinie ziehen konne. Wir ziehen ihre Erorterung als gesonderte Krankheitsbilder trotz vielen und starken, gegen eine solche Einteilung sprechenden Argumenten vor.

Eine wesentliche Eigentumlichkeit des Herzmuskels ist die Fahigkeit der Anpassung seiner Tatigkeit an die Erfordernisse des Organismus. Diese Anpassungsfahigkeit macht das Leben erst moglich, da sie dem Herzen die Vergroserung des Schlag- und Minutenvolumens gestattet, wodurch es groseren Beanspruchungen wahrend korperlicher Anstrengung, Verdauung, Schwangerschaft und zahlreicher anderer Situationen nachzukommen vermag. Die vom Herzen geforderte Blutmenge kann von 5 bis 7 Litern in der Minute bei Ruhe ohne weiteres auf 25 bis 30 Liter bei starker Anstrengung ansteigen. Der Herzmuskel nutzt bei Ruhe nicht alle seiner Moglichkeiten aus; er verfugt uber eine Reservekraft, welche immer dann zur Anwendung kommt, wenn die Fullung des Herzens zunimmt. Innerhalb gewisser Grenzen gilt fur das gesunde Herz das Starlingsche Gesetz. Eine starkere Dehnung der Herzmuskelfasern infolge vermehrter Herzfullung lost eine kraftigere Kontraktion aus.

In den vergangenen Jahren, seit der Entwicklung und immer haufigeren Anwendung der Rontgenologie, wird die Perkussion der Herzgrenzen an vielen Instituten kaum mehr gelehrt oder geubt. Man nannte sie eine „aussterbende Methode“, welche in der Vergangenheit ihren Dienst getan hat, jetzt aber „aus der grosen und anwachsenden Zahl der brauchbaren klinischen- und Laboratoriumsmethoden verdrangt werden sollte“.

SummaryThe scintillation measurements of the hepatic uptake of C060-B12 following its oral and parenteral administration to 20 normal humans, indicate that the efficiency of intestinal absorption of vit. B12 decreases sharply on increase of the intake. The peak of the absorption curve of vit. B12 was found at the oral dose of 0.5 μg, at which the hepatic uptake was found equivalent to 90.5 ± 5.8% of that observed following intramuscular injection of a similar dose of this vitamin. With the increase of the dose, a progressive decline in absorption followed a hyperbolic regression curve, so that at the oral dose of 50 μg B12 the hepatic uptake was equivalent to only 3.0 ± 0.7% of that found after intramuscular injection of a similar dose of this vitamin. The data obtained indicate that the increment in the oral dose of vit. B12 from 0.5 to 50.0 μg, results apparently in an increase of the amount absorbed of only 1.0 μg. It is suggested that in addition to Castle's gastric intrinsic factor, an intramural “in...

Die Dilatation einer Herzkammer ist haufig ein Ereignis, welches das Herz in die Lage versetzt, sich einer veranderten Situation anzupassen. Sie kann verschiedene Grunde haben. Zunachst fuhrt ein vermehrter Zustrom zum Herzen (bei arteriovenosen Anastomosen, beim offenen Ductus arteriosus, nach ausgiebigen intravenosen Infusionen) zu einer starkeren Herzfullung und zu einer Vermehrung der Residualblutmenge am Ende der Systole. Die sich daraus ergebende erhohte Anspannung der Muskelfasern hat (nach dem Starling’schen Gesetz) eine kraftigere Kontraktion zur Folge, und innerhalb weniger Schlage hat sich das Herz an die starkere Fullung angepast. Die zuruckbleibende Dilatation ist minimal. Auf diese Weise bewaltigt der linke Ventrikel seine vermehrte Fullung bei einer Mitral- oder Aorteninsuffizienz. Wenn das Herz gegen einen erhohten Widerstand zu arbeiten hat (Hypertonie, Aortenstenose), entsteht eine andere Dilatationsform. Unter solchen Umstanden wird die Residualblutmenge groser; die resultierende starkere Fullung fuhrt zu einer kraftigeren Systole. Die zunachst verminderte Herzleistung wird rasch wieder normal. Innerhalb weniger Wochen entwickelt sich dann sekundar eine Hypertrophie. Bleibt diese jedoch aus, so nimmt die Dilatation zu.