Jens G. Rosenkrantz

Azathioprine (Imuran) and pregnancy.

Abstract The results of treatment of pregnant Swiss-Webster mice with various doses of azathioprine are described. Skeletal anomalies, cleft palate, and apparent decrease in thymic size were noted in the fetus when the drug was administered during the embryonic period of development. Equally significant, hydrops fetalis, anemia, and severe hematopoietic depression in the absence of significant maternal hematopoietic depression were observed after administration of the drug in certain phases of fetal development. Fertility of male and female animals was not affected by the dose used, nor was the estrus cycle changed. The possible effects of this drug on the embryo and fetus should be considered whenever it is used for immunosuppression among human females of childbearing age.

Hepatic arterial interruption in the fetus—An attempt to simulate biliary atresia

Abstract Investigation of biliary atresia is hampered by the lack of suitable experimental models. The development of a technic of producing biliary atresia artificially would be extremely useful. Extrahepatic biliary atresia can be simulated by ligation of the common bile duct; intrahepatic atresia by selective destruction of the intrahepatic bile ducts. Since the work of Cameron and Mayes, 1 it has been appreciated that the intrahepatic biliary tree and the hepatic parenchyma enjoy different blood supplies, 2 ligation of the hepatic artery should produce selective ischemia of the intrahepatic bile ducts. Such ligation in the postnatal animal has often resulted in necrosis of both hepatic parenchyma and biliary ducts. 3–5 However, the fetal mammal, with highly oxygenated umbilical venous blood in communication with the portal veins, might suffer ischemia of the biliary tree without parenchymal necrosis. Ischemia of a fetal tissue frequently results in atrophy of that tissue without inflammaton; 6,7 therefore, ischemia of the fetal biliary tree might lead to disappearance of the intrahepatic ducts without infarct. This paper reports an effort to test these hypotheses in the fetal rabbit. The rabbit was selected because of efficiency of breeding, with the realization that the anatomy of the hepatic artery and its collateral circulation is variable in the rabbit, that rabbits have poor maternal instincts, and that this animal is susceptible to coccidiosis, a necrotizing disease of bile ducts and liver. Despite these handicaps, the experiments have yielded encouraging results which warrant report.

Fetal surgery in the pig with a review of other mammalian fetal technics

Abstract During the past several years there has been a reawakening of interest in the performance of surgery on mammalian fetuses. Fetal surgery has traditionally centered around efforts to understand fetal physiology and biochemistry and to produce laboratory models of clinically important congenital abnormalities. More recently, the mammalian fetus has been found an excellent subject for studies on immunology. Finally, with the demonstration that fetal surgery is possible 1 and successful 2,3 in the human, a new area of medicine has developed and investigators are beginning to speak seriously about the diagnosis and management of human fetal illness. For all these reasons, it becomes important to discuss the technics by which fetal surgery is successfully accomplished and the physiologic reactions of the fetus to surgical trauma. It is the purpose of this paper to review briefly the technical history of mammalian fetal surgery, to present technics evolved in this laboratory for the performance of certain fetal operations in the pig, and to discuss various aspects of mammalian fetal surgery as they pertain to postoperative fetal survival.

Replantation of an Infant's Arm

SINCE the first successful replantation of a human arm in 19621 reports of similar cases have appeared.2 3 4 5 6 7 Success after replantation near the shoulder has been limited by varying degrees of neurologic deficit. The patient described in this paper, considerably younger than those in previous reports, demonstrated some of the hazards of replantation of extremities. However, her remarkable degree of reinnervation confirms a clinical impression that the indications for replantation should be more liberal in children than in adults. Case Report A 21-month-old, 9.8-kg. girl was admitted to the hospital on April 10, 1965, approximately 20 minutes after amputation of the .xa0.xa0.

Hypoxic pulmonary hypertension: its modification by dipyridamole.

A POTENT STIMULUS for the development of pulmonary hypertension in animals [14], acute hypoxia is felt to be central to the development of respiratory insufficiency in a variety of clinical conditions. The response is prcsent in isolated perfused lungs and in the intact animal after adrenergic blockade [8, 111. Although the mechanism whereby pulmonary vascular resistance is elevated with hypoxia is unknown, it has been suggested that the hypertensive response to hypoxia is an intrinsic property of pulmonary vascular smooth muscle [l]. Indeed this response to hypoxia has been reduced by an agent which acts directly on the vascular smooth muscle [3]. During experiments on the isolated, perfused rat lung, Hauge and Melmon [6] demonst’rated that platelets were necessary in the perfusate for hypoxic pulmonary hypertension. These experiments stimulated our own interest in a study to determine if drugs known to alter platelet function could alter hypoxic pulmonary hypertension. Dipyridamole (Persantine, Geigy) was found to bc capable of altering the pulmonary vascular response to hypoxia, and the results of these experiments are here reported.

Early repair of ventricular septal defect due to nonpenetrating trauma

Rupture of the ventricular septum of the heart is a rare result of nonpenetrating trauma to the chest. In almost all cases a varying degree of congestive heart failure develops due to the sudden development of a systemic-pulmonary shunt. Most patients respond well to decongestive measures; operative closure of any residual defect can, if indicated, be postponed until a time of election. Some patients, however, develop progressive cardiac failure despite vigorous medical management and will not survive without early operative intervention. This article describes the second reported case of early surgical repair for this condition.

Congenital anomalies in the pig: Teratogenic effects of trypan blue

Abstract The laboratory production of congenital anomalies serves several purposes. First, it often gives insight into abnormal morphogenesis. This occurred with Louw and Barnards studies on intestinal atresia, 1 following the work of Fraser on cleft palate in inbred murine strains, 2 and as a result of investigations on the embryology of transposition of the great vessels in rodents. 3 Secondly, physiologically important congenital defects can be studied in laboratory animals, as Jackson did with aortic coarctation in dogs. 4 Careful measurements of abnormal physiology, not possible in the human, can be made and the results of therapy can be appraised in the laboratory before clinical trial. For this second purpose, it is important to study an animal similar to the human in the area studied. In many ways, the pigs cardiovascular physiology bears close resemblance to that of the human. 5,6,7 The size of miniature pigs of various ages, the long fetal period and the hardiness of the newborn pig make this animal suitable for detailed physiologic study at various prenatal and postnatal ages. The reproductive cycle of the pig, with heat every three weeks, makes this species a desirable one for teratologic investigation. For these reasons we tried, in the miniature pig, to produce clinically significant congenital cardiac lesions by the administration of a teratogenic drug in early pregnancy. Since the demonstration that the disazo dye, trypan blue, was teratogenic in rats, 8 the effects of this drug have been studied in various mammals. 9 The types of anomalies produced by the dye have varied according to species and strain but cardiovascular defects are prominent among the abnormalities. After a long trial-and-error process, it was found that intravenous administration of 100 mg./Kg. of trypan blue on the 10th day of pregnancy gave an increased incidence of cardiovascular and hindgut anomalies among the offspring.

Superior mesenteric arterial embolectomy in an infant

Abstract Ryvlyn 30 in 1943 and Blinov 5 described patients in whom embolectomy from the superior mesenteric artery was attempted unsuccessfully. In 1951 and 1953, Klass 17,18 reported two patients in whom this operation was carried out. Both patients died, but it was evident that blood flow had been restored to the ischemic bowel. Stewart, 35 in 1960, described a patient who underwent superior mesenteric embolectomy in 1951 and survived. Since this first successful case, a number of patients have been relieved of acute occlusion of the superior mesenteric artery and have survived. 1–4,6,7,9,12,13,20–24 29,31–34,36,38–41 Success in such cases seems to depend on early diagnosis and operation, on recognition at operation, or at subsequent re-exploration, of frankly necrotic intestine, and on careful postoperative management of these critically ill patients. So far, all reports of superior mesenteric thrombectomy have concerned adults. Acute obstruction of the superior mesenteric artery in infants and children is rare, but a number of such cases has been reported, 8,14,15,25–28 In most, the diagnosis has been made at the autopsy table. In many, laparotomy has been undertaken, the hopelessness of the situation recognized, and the child allowed to die without definitive therapy. In a few, where the area of infarction was localized, resection of necrotic bowel has been carried out with success. This report concerns an infant who underwent superior mesenteric arterial embolectomy. Although he died because a short length of necrotic bowel was not resected, it was evident that a considerable length of intestine was revascularized as a result of the embolectomy. This paper is written to underscore the feasibility of superior mesenteric thrombectomy in infants and children.

Pectus Excavatum and Cardiac Function

AT present it is generally agreed1 2 3 that there is no objective evidence that mild to moderate degrees of pectus excavatum (funnel chest) have any demonstrable influence on cardiopulmonary func...