Samuel J. Fogelson

Treatment of Peptic Ulcer with Gastric Mucin.

In the literature on gastric secretion, the capacity of mucus to lower the free acid in the stomach is repeatedly suggested. While working on the “Relationship between Gastric Secretion and Basal Secretion of the Stomach” Lim determined that the concentration of the mucus in the stomach is highest at the lower secretion rates. The problem here was to determine the effect of increasing the mucus content of the stomach upon the free HCl. To evaluate the antacid effect of gastric mucin, it was necessary to either stimulate the secretion of mucin or to administer mucin by mouth. In these experiments attempts at stimulation failed to give consistent results, therefore a neutral preparation of hog mucin was prepared. Two ounces of this mucin in the stomach of Pavlov pouch dogs, after stimulation with 1 mgm. of histamine, was found sufficient to keep the stomach free of free HCl despite the fact that the pouches in these dogs showed adequate gastric secretion. Free HCl would always be present if the same experiment were performed and egg albumen, gelatin or meat substituted for the mucin. When half an ounce of mucin mixed with a pound of meat was fed the dogs, no free HCl was present during an observation period of 5 to 7 hours. Since January, 1930, twelve patients with definite ulcer histories and typical roentgen findings of peptic ulcer were available for study. In addition to the customary bland diet, one ounce of powdered mucin was added to each meal and about 1 gm. of mucin in tablet form given hourly. All these patients were relieved of subjective symptoms within 3 days of treatment and as yet there has been no recurrence of the pain in observation periods of 2 to 5 months.

Studies on peptic inhibition.

Conclusions 1. Aluminum hydroxide, aluminum phosphate, magnesium trisilicate, and mucin inhibited peptic activity by altering the pH, the percent of inhibition being directly related to change in pH. 2. Of these 4, magnesium trisilicate was the most effective inhibiting agent, exerting the greatest effect on the pH. 3. Of the substances used, sodium lauryl sulfate alone completely inhibited peptic activity without any alteration in pH.

A method for the quantitative determination of lysozyme activity in blood.

The above described bacteriolytic (turbidimetric) method of determining the lysozyme activity in the blood has been proven to be reliable, reproducible and applicable simultaneously to a large number of determinations. A wide range of concentration of crystalline egg-white lysozyme which had been added to whole blood was recovered quantitatively.

A statistical comparison of the blood Lysozyme activity of normal adults and of patients with Localized and generalized carcinomatosis

The results indicate that patients with localized and/or generalized carcinoma have statistically a higher blood lysozyme activity which is neither diagnostic nor clinically significant. Attention is, however, directed to the finding that none of the 35 carcinoma patients had less than four micrograms of lysozyme per ml. of blood and that none of the normal individuals had over 12 micrograms of lysozyme per ml. of blood (Table 1). We believe this original observation significant enough to stimulate other investigations to repeat similar studies on larger series of classified carcinoma patients.

The effect of chloride concentration in the determination of lysozyme activity

The phosphate buffer used in the determination of lysozyme by the method of Smolelis and Hartsell was modified by the addition of a given concentration of NaCl. This change was shown necessary in determining the lytic activity present in gastric juice, when it was observed that very low as well as high chloride concentrations in the buffer solution alter lysozyme activity considerably.

Gastric Mucin Secretion in Gastro-duodenal Ulcerative Disease

It was shown 1 that commercial gastric mucin when subjected to peptic digestion and subsequent precipitation with alcohol at 70% concentration, yielded upon hydrolysis characteristic values for total nitrogen and total reducing substances. This suggested the use of a reduction method for the quantitation of mucin. Obviously before such a method can be applied to gastric juice, it is necessary to remove all other reducing substances, or to use a procedure for obtaining gastric juice not subject to their presence. The former procedure would be capable of wider application and work is in progress with this end in view. Our present interest is in the variations in mucin content of gastric secretion, when juice is obtained from the fasting stomach by means of an alcohol test meal under conditions excluding other reducing substances. In following the curve of mucin secretion, the stomach is emptied after a nights fast, basal secretory rate established, then 250 cc. of 7% ethyl alcohol is given and samples removed through a Rehfuss tube at 15 minute intervals for a period of 2 hours. Determinations of total and free acidity, and pepsin, are made. The mucin secretion is followed by the determination of total reducing substances according to the following method: The gastric sample (5 cc. if available) is diluted with an equal volume of 4 N H2SO4. It is then hydrolyzed in a boiling water bath for 2 ½ to 3 hours using an air condenser. After cooling, 2 cc. aliquot samples are pipetted into test tubes, the acidity neutralized to phenolphthalein with 1 N KOH or NaOH, and the reduction estimated by the Somogyi modification of the Shaffer-Hartmann method. 2 The results are expressed in milligrams of reducing substances (calculated as glucose) per cubic centimeter of gastric juice. To illustrate values found, the accompanying graphs are appended.

Role of Detergent Complexes in Experimental Gastric and Duodenal Ulcers.

Summary The results obtained from mucosulf therapy of experimental ulcer for-mation show that there is a decrease in total available pepsin and in pepsin concentration, but only a decrease in total available gastric acidity and not in its concentration. Total available lysozyme was decreased but not its concentration. The volume of gastric juice was decreased while its viscosity was increased. Total available mucin was increased as was its concentration.

A Method for the Assay of Commercial Gastric Mucin

Following the introduction by Fogelson 1 of gastric mucin therapy for gastro-duodenal ulcerative disease, a method for the assay of commercial preparations became desirable. The commercial gastric mucin is prepared by following the customary procedure for commercial pepsin, in which the mucin dough is separated from the pepsin by precipitation at its iso-electric point. It is then purified by repeated washing with 70% alcohol; 2 mixed with required base, and diluted with peptone to decrease the viscosity to a practical state for administration to patients. Although it is the opinion of Hurst 3 that “mucus differs from other proteins in the extreme slowness with which it undergoes peptic digestion…,” nitrogen and reduction values to be presented for commercial mucin suggest the possibility of a partial digestion, when compared with values obtained for gastric mucin by Webster and Komarov. 4 This phase of the subject is being investigated. Commercial samples were found to vary greatly as to viscosity, acid combining power, sulphur, nitrogen, and mucoitin content. Methods were therefore sought by which mucin could be separated from the commercial diluents and contaminants before assay. For this purpose we have used an additional peptic digestion followed by precipitation with 70% alcohol. By weighing the precipitated material, comparative values for the mucin content of the samples may be obtained. Our data shows this procedure to give a product with characteristic N2 content and reduction values. Details of the procedure are as follows: Dissolve 1 gm. commercial mucin and 0.1 gm. pepsin (Wilsons 10,000 units/gram) together in 25 ml. of 0.25% (0.068 N) HC1. This strength acid was found to give a pH approximating 2 with most samples. Digest in the incubator at 37°C. over night, then pipette 10 cc. aliquot samples into weighed 50 cc. centrifuge tubes, and add 28 ml. of 95% alcohol. The contents of the tubes are thoroughly mixed and centrifuged at high speed until the precipitate is well packed (5-10 min.).

Digestibility of gastric mucin in vivo.

We have previously reported studies indicating that gastric mucin (hog) is relatively resistant to enzymatic hydrolysis in vitro. 1 However, indirect evidence suggests more complete digestion in the gastrointestinal tract. 1 To further investigate the digestion of mucin we have fed purified gastric mucin as the source of nitrogen, to a series of albino rats, and from nitrogen analyses of the urine and feces determined its degree of digestibility in vivo. Our experimental procedures differed little from those commonly employed in the determination of utilization, digestibility and biological value of proteins. Young growing albino rats weighing 40–60 gm. were placed in cages so designed that urine and feces could be collected separately. Nitrogen intake was calculated from the weight of food consumed. The small amount spilled was corrected for by determining its nitrogen content and subtracting from the calculated food nitrogen. All nitrogen analyses were by the Kjeldahl method. The purified mucin 2 used in the preparation of the mucin diet gave the following analyses: Nitrogen 7.50%. Reduction after acid hydrolysis (Shaffer-Hartmann) 35.4% (as glucose) and ash 2.51%. The diet was designed to be complete for the rat exclusive of its protein content. This necessitated the addition of a small amount of yeast concentrate (Yeast Vitamin-Harris), the amount added being sufficiently small to be disregarded for practical purposes. 3 A preliminary period on a diet similar except for the absence of mucin was employed in order to determine the fecal nitrogen on a nitrogen-free diet, or the so-called metabolic nitrogen. Four-day periods were allowed between changes in diets to insure the attainment of equilibrium. Collection periods were each of one weeks duration. The compositions of the diets were as follows:

Cholecystography as an aid in determining gall bladder stasis in pregnancy

T HE greater incidence of cholelithiasis in women, is undoubtedly secondary to pregnancy. Courvoisier found cholelithiasis present in every fourth woman and in every twelfth man in 16,025 autopsies. Schroeder found gallstones in 20 per cent of all females and 4.4 per cent of all males autopsied. W. Mayo reports that 90 per cent of 3075 female gall-bladder patients had their first symptoms during pregnancy. Peterson in 1910 reviewed this subject and reported his observations based upon the examination of the gall bladders of women he operated upon for a gynecologic complaint. He found that pregnancy increased the incidence of gallstones about 10 per cent, and further determined that about one-third of the patients could report the onset of a biliary attack when the uterus reached the umbilicus, thus pressing upon the gall bladder and biliary ducts.14 Of all the possible factors in pregnancy which can be blamed in the etiology of gallstones, stasis is generally accepted as most significant. Practically all authorities agree that such a stasis is present but differ in explaining its origin. Prior to the last few years the general consensus of opinion was that this stasis resulted from mechanical pressure of the gravid uterus upon the gall bladder or its ducts. Cannon in his text upon mechanical factors in digestion demonstrated that an increased intraabdominal pressure would affect the gall bladder and ducts equally, thus eliminating itself as a factor in causing ,stasis. In 1922 Westphal I9 fluoroscoped gravid women in the ninth month of pregnancy when the uterus was highest and noted that quite frequently there was no direct pressure of the uterus upon the lower liver surface. In his experimental work he demonstrated an increased tone of the sphincter of Oddi and believed that in this way bile was dammed back into the biliary system. With the advent of cholecystography and with Boyden’s observations upon the emptying of gall bladders by fat meals,l there was afforded, for the first time, the opportunity of definitely observing the behavior of the human gall bladder and noting whether or not there was stasis present as compared to normal. It is of interest that recently Mann and HigginsI in animal experiments, using 40 per cent iodized oil, found that pregnancy consistently delayed the emptying time of the gall bladders and that balloons the size of the gravid