Mark V. Barrow

Metastatic tumors of the umbilicus

Abstract Three patients with umbilical metastasis from adenocarcinoma of the pancreas have been briefly presented and the literature on tumors of the umbilicus reviewed. In all, 667 cases of umbilical tumors have been reported with 32 per cent being endometriosis, 38 per cent being benign and 30 per cent being metastatic. Of the primary tumors, congenital polyps were most common but maligant primary tumors occurred in one-fifth of these. Of the metastatic lesions, carcinoma of unknown origin (29 per cent) was most common, followed by primary lesions being located in the stomach (25 per cent), ovary (12.4 per cent), colon (10 per cent), and pancreas (7.4 per cent) with decreasing frequency.

Ectopia cordis (ectocardia) and gastroschisis induced in rats by maternal administration of the lathyrogen, beta-aminopropionitrile (BAPN)

Abstract Beta-aminopropionitrile (BAPN) was given to pregnant rats via intubation on days 12 through 15 or using combinations on two consecutive days between 13 and 15. Given on both days 14 and 15 to 30 litters using a dose of 2,500 mg. per kilogram of body weight, BAPN produced 55 per cent resorptions and a 16 per cent incidence (in viable fetuses) of either ectocardia (11 fetuses), gastroschisis (3 fetuses), or both (11 fetuses). Larger doses produced predominantly resorptions. Single doses resulted in occasional animals with ectocardia. Control and treated litters (using 2,500 mg. per kilogram of body weight on days 14 and 15) were then killed on days 14, 15, 16, 17, and 21 and sagittal sections were examined histologically. Control animals showed a thin anterior chest wall membrane until day 17 when the wall thickened and mesenchymal condensations which would form the future sternum appeared. Twenty per cent of the BAPN-treated animals showed a rupture of the anterior chest or abdominal wall at various stages in the development of ectocardia or gastroschisis. An hypothesis to explain the pathogeneis of these malformations is as follows: BAPN, which interferes with collagen and elastin synthesis, interferes with the tensile strength of the anterior chest and abdominal wall. At times this wall may rupture and, in certain instances, the beating heart may play a significant role in instigating the rupture. The rupture, depending on the degree of rupture and the reparative process, may result in ectocardia, or in both ectocardia and gastroschisis, and rarely in gastroschisis alone.

The production of congenital heart defects with the use of antisera to rat kidney, placenta, heart, and lung homogenates

Abstract Pregnant Long-Evans rats received antisera to adult rat kidney, lung, and heart, rat placenta, and purified glomerular basement membrane on the ninth to eleventh days of gestation in doses ranging from 1 to 3 ml. per 100 Gm. The teratogenic antisera produced increased resorption rates, reductions in fetal weight, and significant malformations—with the exception of heart antiserum, which was not teratogenic in this experiment. Kidney and placenta antisera had a malformation rate of 76 and 80 per cent, with nearly three fourths of these being cardiovascular defects. Glomerular basement membrane and lung antisera were also teratogenic but less so. The cardiovascular malformations included situs inversus associated with truncus (4), as well as single ventricle (2), truncus arteriosus (8), various transpositions (7), interventricular septal defects (6), and several aortic outflow tract or proximal aorta abnormalities. These abnormalities were compared to those produced by trypan blue, which produces mostly transposition complexes, as well as to those produced by other teratogenic agents. The results suggest that antiserum produces its own unique spectrum of malformations, somewhat different from those produced by trypan blue, and therefore that the two agents may have different modes of action.

Anomalies of the internal organs and diminished calcification of vertebrae in fetuses after benzhydrylpiperazine treatment of pregnant rats

Abstract Indications of the effects of chlorcyclizine treatment of pregnant rats on the internal organs of the rat fetus were sought. Hydrocephalus, hydronephrosis, undescended testes, and the previously described cleft palate occurred at their highest incidences when chlorcyclizine was given late in the period of organogenesis (days 13–16). The same defects occurred when drug was administered for various intervals earlier in gestation (days 7–12), but a higher dose was needed. A low incidence of resorptions, placental effects (enlargment, hemorrhagic and polycystic), and alternate effects occurred following the earlier times of administration. Thus a relatively constant syndrome of higher incidence of internal and external effects is produced, and evidence of a fluid imbalance in the fetus is presented. The dry weights of the whole fetus and of the fetal kidneys and heart were also reduced following relatively low doses of chlorcyclizine, 10 and 20 mg/kg. Dry weight of the brain was reduced by 40 mg/kg. Only with doses above 70 mg/kg was there a marked general inhibition of growth. When the dose was 20 mg/kg, the kidney and heart dry weights were normal 20 days after birth. Few litters survived the first day after birth when the dose was 40 mg/kg. Thus, an organ-specific effect can occur when one-third to one-half of the threshold dose for cleft palate formation is used. Calcification of the central vertebral bodies was reduced by 40 mg/kg. The results are discussed from the standpoint of the relative constancy of the syndrome of effects rather than from that of a changing spectrum, and from the standpoint of the potential persistence of effects at the various dose levels. Some of the findings represent additional evidence and manifestations of fluid imbalance at the lower doses.