William T. Newton

Radioimmunoassay for Prostaglandins

Antibodies to prostaglandin were obtained by immunization of rabbits with PGA1, PGA2, and PGE1, protein conjugates of prostaglandins. The antibodies demonstrated specificity toward both the cyclopentane ring and the aliphatic side chains. With the use of these antibodies a highly sensitive radio-immunoassay capable of measuring less than picomolar amounts of PGA1, PGA2, and PGE1 has been developed.

67Ga Citrate in Renal Allograft Rejection

Eight renal allograft recipients were examined on 31 occasions following administration of 99mTc sulfur colloid and 67Ga citrate. Transplant accumulation of each agent was compared and collated with the clinical diagnosis. The procedures matched in 25 instances (81%). Gallium accumulated in the graft producing a false positive result in 2 instances of acute tubular necrosis with anuria, and failed to accumulate within the graft in one case of chronic rejection and in 2 instances of acute rejection. Both radioagents failed to accumulate in 3 patients with acute rejection following heparin therapy. These data indicate that 99mTc sulfur colloid is superior to 67Ga citrate in establishing the diagnosis of transplant rejection and also provides more timely information.

Inhibition of Endogenous Gastrin Activity by Antibodies to the Carboxyl-Terminal Tetrapeptide Amide of Gastrin

Since incubation of gastrin with antibodies directed against its functional carboxyl-terminal tetrapeptide amide inhibits the gastric secretory effects of exogenous gastrin, this series of experiments was performed to determine whether the same antibody preparation also inhibits the physiological effects of endogenous gastrin. Endogenous gastrin release was stimulated in the perfused pylorus-ligated rat stomach by gastric irrigation with acetylcholine. The control rat experiments demonstrated that acid secretory responses to intragastric acetylcholine were reproducible and reliable; the second response in each rat varied from 10 % higher to 15 % lower than the first. In the experimental rats, passive administration of antibody-containing globulin during endogenous release inhibited the expected increase in acid secretion an average of 73 % (47 to 100 %). The experiments document that antibodies to the functional portion of the gastrin molecule inhibit the acid secretory effects of endogenous gastrin.

Allograft viability determined by enzyme analysis.

Enzymatic analysis of the venous effluent of ischemically injured kidney failed to predict accurately the ability of an isochemically injured kidney to support life. Postoperative serum assay of lactic dehydrogenase (LDH) is of value in the assessment of the functional status of the kidney and correlates with response of the rejection episode to immunosuppression. However, by itself it cannot be a sole guide to withholding of therapy. Successful treatment is associated with a decline in LDH level, and failure to return to base line serves as a guide to irreversibility of the rejection reaction.

Further Evaluation of 99mTc Sulfur Colloid Accumulation in Rejecting Renal Transplants in Man and a Canine Model1

Renal transplant accumulation of 99m-Tc sulfur colloid was evaluated in 41 patients. Ninety-five examinations were performed comparing transplant with bone marrow activity and clinical or pathological diagnosis. 99m-Tc sulfur colloid accumulated in acute or chronic rejection as long as the vascular supply of the grafted kidney was not severely impaired. Accumulation was marked in chronic rejection, slight in acute rejection and absent in normally functioning transplants or in those with acute tubular necrosis. In the 10 dog models, no accumulation was seen in autografted transplants and early accumulation was demonstrated within the hyperacutely rejecting kidneys of allografted dogs.

Acquired renovascular hypertension in a patient with renal allotransplantation

Abstract A case is reported of renovascular hypertension in a girl with nephrectomy with a successful renal allotransplant. Resection of the stenosis at the junction of the renal artery of the transplant and the hypogastric artery of the patient was followed by immediate and sustained relief of hypertension.

Lymph transfusion in patients with cancer.

Abstract Transfer of moderate amounts of lymph from one healthy person to his brother with metastatic cancer has been carried out in two donor-recipient pairs. Increase in the mean diameter of a pulmonary metastatic lesion ceased in one patient after lymph transfusion, but other metastases progressed until his death. Another patient with very slowly growing pulmonary metastasis showed no change in size of the tumor after lymph transfusion and he died of unrelated causes. Although no benefit is claimed in these recipients, the lack of adverse reaction provides a basis for investigation of a variety of applications of lymph transfusion to clinical problems.

Functional capacity of canine renal autografts after hypothermic perfusion.

Abstract 1. 1. Experiments were performed on dogs with chronic “split bladder” preparations to investigate the functional changes in transplanted kidneys, especially in the immediate post-transplant stage and the modification of the effects of ischemia by intra-arterial hypothermic perfusion. 2. 2. The ischemia incident to renal autotransplantation results in excretion of a more diluted urine with decreased glomerular filtration and effective renal plasma flow. The functional capacity of kidneys subjected to ischemia for less than forty-five minutes is gradually restored over a three to four week period. 3. 3. Intra-arterial perfusion of precooled electrolyte solutions containing heparin, papaverine and microdextran prior to transplantation affords some protection from ischemic change. 4. 4. There appear to be only minor differences in renal function in kidneys perfused at 4 °C. or 10 °C. in the time periods studied. Ischemic periods of two hours forty-five minutes were well tolerated by hypothermic kidneys. 5. 5. Denervated kidney transplants have the capacity to undergo compensatory increase in function on removal of other functioning renal tissue.

A method of facilitating renal transplantation with the use of stockinet

Summary During renal transplantation, placement of the kidney inside a sleeve of stockinet, with the artery and vein exiting through a side opening, improves exposure during vascular anastomosis, facilitates handling of the kidney, and permits the kidney to be surrounded by a cool, moist surface.

The Courage to Fail

Courage to Fail has been revised extensively. The authors have added results of their researches, obtained since their original work was published in 1968, in the maintenance of lives by the extraordinarily expensive transplantation of an organ from another person or by an artificial organ system. In particular, the authors have addressed themselves to the enactment of Public Law 92-603 in 1972, with its implied acceptance by the American people of the responsibility to extend, at enormous cost, the life spans of the relatively few citizens with end-stage renal disease. The last part of the book has been restructured to increase its sociomedical impact. Indeed, the time-budgeted browser can get most of the impact of the book by reading only the last section and perhaps only the last chapter, for this is a question book, not an answer book, and most of its questions are restated in the final chapter.