William R. Waddell

Sulindac for polyposis of the colon.

The effect of sulindac, a nonsteroid antiinflammatory drug, on colon polyposis has been evaluated in seven patients after subtotal colectomy and ileoproctostomy and in four patients with intact colons. The patients all had Gardners syndrome or familial polyposis coli. All polyps were eliminated, except for a few that arose in the rectal mucosa and the anal canal. No cancers developed in these patients on follow-up.

Testolactone, sulindac, warfarin and vitamin K1 for unresectable desmoid tumors

Ten patients with large inoperable desmoid tumors in various body locations were treated with testolactone. Four tumors (40%) responded with major regressions, i.e., more than 50% reduction in volume. Eight patients received nonsteroid anti-inflammatory drugs (indomethacin, sulindac, or sulindac with warfarin and vitamin K1 [Mephyton]) for periods of 2 to 91 months. There was one major regression, one partial regression, and three instances of tumor growth arrest over periods up to 8 years. Seven patients were treated with nonsteroid anti-inflammatory drugs concurrent with or after testolactone or tamoxifen. There were five major regressions and one partial regression with extensive central necrosis of an enormous intra-abdominal tumor. The last patient has been treated for only 12 months, with no change in tumor volume. It appears that estrogens function as growth factors for desmoid tumors, and that minimization of these effects inhibits tumor growth in some, but not all, cases. In those instances where antiestrogens were not effective as single agents, the tumors usually responded to subsequent nonsteroid anti-inflammatory drug therapy. Withdrawal of estrogen may be followed by inhibition of transcription of genes that support tumor cell proliferation, and sulindac and indomethacin may augment these effects by inhibiting prostaglandin and cyclic AMP synthesis and the activity of protein kinase C. Warfarin may function as a protonophore to acidify the cytoplasm and prevent the alkalinization that is necessary to initiate DNA synthesis and cell cycle progression, again an impairment of the transcription process.

Accidental hepatic artery ligation in humans

Abstract Despite the vast amount of information from experimental animals, it has been difficult to obtain a clear-cut picture of the effects of ligation of the hepatic artery in humans with relatively normal livers. The last complete review of this subject in 1933 indicated that a mortality in excess of 50 per cent could be expected in non-cirrhotic patients with injury of the hepatic artery or its principal branches. Five cases of dearterialization of the normal human liver have been observed. These were due to accidental interruption of the right hepatic artery in four and the proper hepatic artery in one. The injured vessel was repaired in one case and ligated in the others. In four of the five patients the vascular disruption was the sole injury. In the other the common bile duct was also lacerated. There was no evidence of hepatic necrosis in any case although one patient died from complications of common duct repair. Transient changes in SGOT and temporary low grade bilirubinemia were commonly noted. In addition, all cases of ligation of the hepatic artery reported since 1933 have been compiled. On the basis of reviewed, as well as the presently reported cases, it is concluded that ligation of the hepatic artery or one of its branches in the patient with relatively normal hepatic function is not ordinarily fatal in the otherwise uncomplicated case. Adequate perfusion of the liver can usually be provided by the remaining portal venous flow and whatever arterial collaterals are present, unless additional factors further reduce the portal venous flow or increase hepatic oxygen need. These factors include fever, shock and anoxia. The key to therapy in unreconstructed injuries to the hepatic artery is avoidance of these secondary influences.

Renal Homotransplantation: Late Function and Complications

Fifty-one patients were treated with homografts obtained from both related and nonrelated volunteer donors in the interval from November 24, 1962, to February 10, 1964. Thirty-three of the 51 patients lived for 4 or more months postoperatively, and 30 of these are still living on June 10, 1964. The three deaths which occurred after 4 months were due to a combination of gastrointestinal hemorrhage and sepsis in one; to a cerebrovascular accident of undetermined etiology in the second; and to uncontrolled late rejection in the third, which was first diagnosed 229 days after operation, 66 days before death. The two homografts examined at autopsy after 207 and 295 days were both enlarged and showed glomerular hypertrophy, tubular atrophy, mild cellular infiltrations, marked interstitial fibrosis, and destruction of peritubular capillaries. The case that died in uncontrolled rejection also showed interstitial edema and a spectrum of vascular lesions. Late nonfatal rejection was observed in five other cases 112 to 300 days postoperatively. In all these cases, and in the unsuccessfully treated one as well, certain consistent features were present. There had always been a preceding alteration in steroid dose, prednisone having been discontinued in five of the six patients from 16 to 154 days previously. Progress of the rejection was slow, and the proper diagnosis depended most strongly upon demonstration of a gradual fall in creatinine clearance. Elevations in blood pressure, transplant wound tenderness, fluid accumulation, alopecia, polyarthritis, fever, malaise, and anorexia were all observed. Azotemia was a late finding. The diagnosis of late rejection is one of exclusion. Pyelonephritis, vascular anastomotic failure, and ureteral obstruction are first ruled out. The last possibility is a particularly important one since 4 of the 33 patients who lived for 4 months or longer have been shown to have partial ureteral obstruction which required secondary repair. In one case, there was strong evidence that the stricture resulted from healing of an earlier ureteral rejection. If diagnosed promptly, late homograft rejection can be reversed. The crucial step in the treatment of rejection is the resumption or increase of steroid dosage. In addition, local irradiation to the graft and intravenous actinomycin C are both of use as emergency therapy. The chronic administration of azathioprine has thus far appeared to be very well-tolerated by those patients who are receiving only this drug, although its ultimate toxicity will take years to determine. The superimposition of steroid therapy, in those patients whose homograft function cannot be otherwise maintained, adds a serious risk. Gastrointestinal hemorrhages, infections, aseptic bone necrosis, potentiation of hypertension, and severe obesity have all been observed. The course of five patients who received preliminary thymectomy and who survived more than 4 months is compared to that of the other recipients who did not receive this additional operation. One of the patients who had thymic excision died after 207 days of nonrenal complications. The other four had steroids discontinued in 9 months or less, and none have had any evidence of delayed rejection 14 to 18 months after operation. The 6 examples of late rejection all occurred in the other 28 long-surviving patients who did not have removal of the thymus gland. The possible role of thymectomy in influencing these late events remains to be determined. Renal function ranged from adequate to essentially normal levels in all patients who survived longer than 4 months, except the one who died of uncontrolled late rejection. In four cases, in which late renal function was tested at a time when rejection was not present, the results in paired donors and recipients were almost identical, suggesting hypertrophy in the homograft as well as in the donor’s residual kidney. These results indicate that considerably more than half the patients who are treated with renal homotransplantation can be brought into a chronic stage, even when the statistics are unfavorably altered by the use of a substantial number of nonrelated donors as was the case in the present series. The data also indicate that overoptimism must be avoided in assessing the future role of this form of therapy since it is quite evident that many adverse factors still exist in the residual group of living patients, and that life-threatening late complications are going to be common. These include toxicity from drugs, especially if indefinite steroid therapy is required; late rejection; urologic complications; and subtle subclinical progression of pathologic alterations in the homograft.

Gastric secretory and other laboratory studies on two patients with Zollinger-Ellison syndrome.

THE first cases of gastrointestinal ulceration associated with gastric hypersecretion and tumors of the pancreas were described in 1955 by Zollinger and Ellison.1 In the following year Ellison2 dis...

Oral contraceptives and gastrointestinal disorders.

4 case histories of gastrointestinal abnormalities which developed in association with the use of oral contraceptives are presented. These were all cases of mesenteric vascular disease confirmed through operative diagnosis. 2 cases exhibited massive bowel infarction necessitating resectioning.

Preparation of fat emulsions for intravenous alimentation

SummaryDescriptions are given of the high pressure homogenization equipment used and of the actual procedure followed in the preparation of fat emulsions suitable for intravenous nutrition. Such emulsions contain 10–15% oil (w/v) dispersed in particles less than one micron in diameter. They are made under nitrogen and subsequently autoclaved to ensure sterility.Procedures are also given for screening each batch of emulsion by means of tests performed on rats, dogs, and rabbits. Emulsions of the type described have found extensive application in the clinic with a low incidence of unfavorable reactions.

Effect of insulin on clearance of emulsified fat from the blood in depancreatized dogs.

Summary Emulsified fat infused into pancreatectomized dogs is cleared from the blood at a normal rate if the animal is receiving insulin whereas without insulin the injected fat is cleared slowly. It thus appears that the clearance of fat from the blood is dependent upon normal carbohydrate utilization. Serum cholesterol levels rise following infusion of fat in diabetic animals deprived of insulin. Serum cholesterol concentration falls following infusion of fat into pancreatectomized animals receiving insulin. Observations on fat metabolism in which the fat is administered intravenously give data comparable to those obtained following oral administration of fat and the mechanisms of clearance seem identical by the two methods.

Immunological Studies of Gastrin

Hog gastrin prepared by the Gregory method stimulates antibody production in rabbits. Rabbit anti-hog gastrin serum which was reacted with hog, dog, and human gastrins in vitro caused reduction of their gastric stimulatory effect, indicating a biological cross reaction among these species.

Pancreaticoduodenectomy for traumatic lesions

Simultaneous injury of the duodenum and head of the pancreas and severe injury to either structure alone, are attended by high morbidity and mortality. Either penetrating wounds or blunt trauma may produce sufficient tissue destruction to necessitate removal of the head of the pancreas or duodenum with diversion of biliary, pancreatic, and alimentary flow. Although application of such extensive procedures has been advocated, and experimental studies have proved their efficacy, there are only six well documented cases on the use of pancreaticoduodenectomy for extensive trauma. This report details three additional cases. Two patients were injured by high velocity missiles and a third by the steering wheel of an automobile.