William H. Dearing

Effect of preoperative antibiotic regimen on development of infection after intestinal surgery: Prospective, randomized, double-blind study.

A prospective, randomized, double-blind study was performed to compare preoperative antibiotic preparation with neomycin (group 1), neomycin and tetracycline (group 2), and placebo (group 3) in patients undergoing elective intestinal surgery. The 196 patients were approximately equally distributed among the three study groups, which proved similar to each other in terms of age, sex, diagnosis, site of lesion, and operative procedure. There were significantly (P < 0.01) fewer patients with postoperative wound sepsis in the neomycin-tetracycline group (group 2) than in either of the two other groups. Postoperative wound infection rates in groups 1 and 3 were nearly identical. Most infections contained both aerobic and anaerobic bacteria. Eight of nine episodes of septicemia due to Bacteroides fragilis occurred in patients in groups 1 and 3.

Experiments with calculated therapeutic and toxic doses of digitalis: I. Effects on the myocardial cellular structure

No microscopic pathologic changes were found in the myocardiums or coronary arteries of the control animals. No evidence of histologic changes was found in the myocardiums of the experimental animals after the administration of calculated therapeutic amounts of digitalis (30 per cent of minimal lethal dose) in single or divided doses, given over a period of forty-eight hours. The histologic studies were made after a minimum of six days and a maximum of fifty-six days. Myocardial lesions were not produced in our experimental animals when they were digitalized rapidly with a calculated therapeutic dose of digitalis, and were then given daily maintenance doses of the drug which were estimated to correspond to either 1 or 2 cat units for a man weighing 70 kg. The histologic studies were made after a minimum of nineteen days and a maximum of sixty days. In our experiments, 60 per cent of the minimal lethal dose was the smallest amount of digitalis which, when given as a single dose, produced definite evidence of myocardial lesions. This dose of digitalis is in the toxic range. The frequency with which myocardial lesions occurred increased as the size of the single dose of digitalis was increased to 80 per cent of the minimal lethal dose. Myocardial lesions were not found until five or more days after the single toxic doses of digitalis had been administered. Histologic changes were not observed in the hearts of all the animals which had received toxic amounts of digitalis, even when the quantity of the drug was 80 per cent of the minimal lethal dose. Histologic changes were produced in the myocardium when the animals were digitalized rapidly with a calculated therapeutic dose of digitalis, and were then given daily quantities of the drug which were estimated to correspond to 3, 4, 5.5, or 6 cat units for a man weighing 70 kg. The equivalent of 3 cat units daily of parenterally administered digitoxin caused myocardial lesions within five days in one animal, whereas the same amount of orally administered tincture of digitalis produced myocardial lesions within eleven days in another animal. The digitalized animals in this group which received daily doses of digitalis in the toxic range had their myocardiums examined microscopically after a minimum of five days and a maximum of thirty days. Histologic changes in the heart were produced by digitalis whole leaf or by crystalline products of digitalis (digitoxin, lanatoside A, lanatoside B, and lanatoside C). The sequence of pathologic changes in the myocardium after the administration of toxic doses of digitalis was studied. The observations of Levitski1 and Bu¨chner3 were confirmed. The myocardial lesions were focal in distribution, and were more frequent in the papillary muscles and in the left ventricular wall than in other regions. This also confirmed the observations of Levitski and Bu¨chner. Animals which survived the toxic doses of digitalis recovered completely in three or more weeks. Animals which had myocardial scars produced by digitalis (healed lesions) appcared entirely normal after three to four or more weeks. Myocardial lesions were more prone to develop in old animals after the administration of digitalis than in young ones. This difference in sensitivity to the drug was not related to arteriosclerosis, for no evidence of this disease was found in the cardiac arteries or arterioles of any of the cats. Experimental hyperthyroidism increased the sensitivity of the animals to digitalis. Myocardial lesions were found after the administration of calculated therapeutic doses of digitalis to hyperthyroid cats. No evidence of anatomic changes was seen in the skeletal musculature or the smooth musculature of any of the animals which had received digitalis in therapeutic or toxic quantities.

Serum α1-Acid Glycoprotein in Chronic Ulcerative Colitis

Serum α1-acid glycoprotein was studied in 31 controls and 130 patients with chronic ulcerative colitis (no liver disease) judged clinically to be either quiescent (25 cases), mildly (38 cases), moderately (34 cases), and severely (33 cases) active. This serum glycoprotein is increased in ulcerative colitis when the disease process is active. For example, the highest observed value in the 31 controls was 111 mg per 100 ml, the lowest value in the 34 moderately active cases was 149, and the lowest value in the severely active cases was 290. After colectomy and proctectomy for chronic ulcerative colitis, serum values declined to normal range (25 cases). In the presence of hepatic disease (cholestasis and chronic hepatitis, both with and without cirrhosis), serum glycoprotein values tended to reflect the degree of activity of the ulcerative colitis (17 cases). The serum value for α1-acid glycoprotein is a more reliable index to the degree of activity of the inflammatory process in ulcerative colitis than is the sedimentation rate. It might serve as a guide to the efficacy of controllable therapeutic procedures for chronic ulcerative colitis, since it has been shown that surgical removal of actively diseased colon and rectum produces glycoprotein values within the normal range and that the receding of severely active chronic ulcerative colitis to the quiescent phase induces glycoprotein values within or slightly above the normal range.

Experiments with calculated therapeutic and toxic doses of digitalis: V. Comparative effects of toxic doses of digitalis and of pitressin on the electrocardiogram, heart, and brain

Abstract Histologic changes were observed in the myocardium after the repeated injection of large doses of pitressin. The myocardial lesions resembled those which occurred after the administration of toxic doses of digitalis. They were focal in distribution and were most prominent in the subendocardial layer of the left ventricular musculature. The following is a summary of the changes in the RS-T segment and T wave after large doses of pitressin: (1) decrease or increase of the height of the T wave; (2) elevation of the RS-T segment (not of the plateau type) in one or more leads; (3) simple inversion of the T wave in one or more leads; (4) depression of the RS-T segment in one or more leads; (5) cove-plane, negative T 2 and T 3 ; and (6) cove-plane, negative T 1 and T 2 . Cellular degeneration was observed in the cerebral cortex after the repeated injection of large doses of pitressin. Myocardial and cerebral lesions were not observed in all the animals which received large doses of pitressin. Myocardial lesions were produced in the older, but not the younger, animals. Gastric lesions were observed after the injection of large doses of pitressin. This confirms the observation of Dodds and his associates.

Experiments with calculated therapeutic and toxic doses of digitalis: VI. Comparative effects of toxic doses of digitalis and of prolonged deprivation of oxygen on the electrocardiogram, heart, and brain

Abstract Histologic changes were observed in the myocardiums of animals which were subjected to prolonged systemic deprivation of oxygen over periods of three or more days. An endeavor was made to keep the concentration of oxygen near 4 to 5 per cent. One animal, which died one and a half hours after the inhalation of low percentages of oxygen, did not show any evidence of anatomic changes in the myocardium. The myocardial lesions produced by deprivation of oxygen resembled those found in the heart after the administration of toxic doses of digitalis. They were focal in distribution and were most prominent in the papillary muscle and in the left ventricular wall. The following is a summary of the prominent changes in the RS-T segment and the T wave after prolonged systemic deprivation of oxygen: (1) decrease or increase in the height of the T waves in one or more leads, (2) simple inversion of the T waves in one or more leads, (3) depression of the RS-T segment in one or more leads, (4) cove-plane, negative T2 and T3, and (5) negative T1 and positive T3. The electrocardiographic changes, as a rule, disappeared when atmospheric air was introduced into the chamber. Cellular changes were observed in the central nervous system after prolonged deprivation of oxygen. The changes were similar to those described by others after anoxia and to those observed after the administration of toxic doses of digitalis. Old animals were more sensitive to deprivation of oxygen than young ones.

Experiments with calculated therapeutic and toxic doses of digitalis: IV. Effects on the cellular structure of the central nervous system☆

Abstract No significant cellular changes were observed in the brain and spinal cord after the administration of calculated therapeutic amounts of digitalis (30 per cent of the minimal lethal dose) in single or in divided doses. The histologic studies were made after a minimum of six days and a maximum of fifty-six days. No cellular changes were produced in our experimental animals when they were digitalized rapidly with a calculated therapeutic dose of digitalis and then were given maintenance doses of the drug which were estimated to correspond to either 1 or 2 cat units for a man weighing 70 kg. The histologic studies were made after a minimum of nineteen days and a maximum of sixty days. In our experiments, 60 per cent of the minimal lethal dose was the smallest amount which, when given as a single dose, produced definite evidence of cellular degeneration in the cerebral cortex. This dose of digitalis was in the toxic range. The frequency with which lesions of the central nervous system occurred increased as the size of the single dose of digitalis was increased to 80 per cent of the minimal lethal dose. Cerebral lesions were not observed until six or more days after single toxic doses of digitalis had been administered. Histologic changes were not observed in the central nervous systems of all of the animals which had received toxic amounts of digitalis, even when the quantity of the drug was 80 per cent of the minimal lethal dose. Degenerative changes were produced in the central nervous system when the animals were digitalized rapidly with a calculated therapeutic dose of digitalis and then were given daily quantities of the drug which were estimated to correspond to 3, 4, 5.5 or 6 cat units for a man weighing 70 kg. The equivalent of 3 cat units daily of parenterally administered digitoxin caused lesions in the brain and spinal cord within five days in one animal, and a corresponding daily dose of orally administered tincture of digitalis produced cellular changes in the central nervous system within eleven days in one animal. The central nervous systems of the digitalized animals in the group which had received daily doses of digitalis in the toxic range were examined microscopically after a minimum of five days and a maximum of thirty days. The cellular changes in the brain after the administration of digitalis were not specific. The following cellular alterations were observed in the large and small pyramidal cells of the cerebral cortex: swelling of the cell body; vacuolization of the cytoplasm; varying grades of cytoplasmic and nuclear degeneration, up to complete liquefaction of the cell; pyknosis of the cells; and cellular degeneration plus satellitosis. The cerebral changes often occurred in localized zones, with normal cortical cells in the surrounding tissue. The lesions were at times diffuse when large doses of digitalis had been administered. Old animals were more prone than young ones to manifest cerebral lesions after the administration of digitalis. This difference of sensitivity to the drug was not related to arteriosclerosis; at least no evidence of this disease was observed in any of the arteries or the arterioles of the central nervous system. Drowsiness and spastic reflexes were observed in the animals which were markedly intoxicated with digitalis. Animals which survived the administration of the toxic doses of digitalis recovered completely in three to four weeks.

Experiments with calculated therapeutic and toxic doses of digitalis: III. Effects on the coronary blood flow☆

Abstract Calculated therapeutic doses of digitalis did not produce a significant change in the coronary blood flow of the dog. This confirms the results of Essex, Herrick, Baldes, and Mann. 28 Calculated toxic doses of digitalis decreased the coronary blood flow of dogs four to six hours after the drug had been administered. The diminution of flow persisted for several days after a single toxic dose of the drug. No myocardial lesions were observed after a therapeutic dose of digitalis, nor were they observed in one animal which received a toxic dose of digitalis. In the latter animal the coronary blood flow returned to the preinjection level within two days. Myocardial lesions were observed in one animal in which the coronary blood flow was kept well below the control level for twelve days by repeated injections of digitalis (toxic range). The diminution of coronary blood flow after the injection of toxic doses of digitalis could not be correlated consistently with changes in the pulse rate or systemic blood pressure. After the injection of toxic doses of digitalis the coronary blood flow returned to the control level in several experiments, and the animals recovered completely.

Myocardial Lesions Produced by Digitalis in the Presence of Hyperthyroidism: An Experimental Study

Calculated therapeutic doses of digitalis and its derivatives did not produce demonstrable microscopic changes in the myocardium of experimental animals. Toxic doses of digitalis (twice a therapeutic dose) induced myocardial lesions in animals. In those animals with experimentally induced mild to moderate hyperthyroidism, calculated therapeutic doses of digitalis did produce myocardial lesions. Toxic doses of digitalis administered to animals with mild to moderate hyperthyroidism caused extensive degenerative changes in the myocardium or promptly killed the animals without associated microscopic lesions.

Micrococcic (staphylococcic) enteritis following the use of aureomycin or terramycin.

Summary We have accumulated evidence that resistant strains of Micrococcus pyogenes have developed in our hospitalized patients as a result of administration of aureomycin or terramycin and that these resistant strains of micrococci, when present in the intestine in more or less pure culture, may produce varying degrees of gastrointestinal and systemic reactions. The administration of erythromycin by mouth in doses of 300 to 400 mg., four times daily, will eliminate the micrococci from the intestine and alleviate the untoward symptoms.