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Islets of Langerhans from unrelated donor rhesus monkeys were transplanted into the portal vein of five rhesus monkeys which had been made diabetic by partial pancreatectomy and Streptozotocin. There was definite improvement of the diabetic state with an increase in the mean KT1/2 from 0.71 to 1.52 percent per minute. The islets were isolated by a more efficient digestion-filtration process than previously had been described. This process has allowed, for the first time, successful isolation of large masses of islets permitting islet transplants in subhuman primates.

The occurrence of perforated sigmoid diverticulitis in a renal transplant recipient stimulated a review of colorectal complications in renal allograft recipients. One hundred twenty-five renal transplantations were performed in 113 patients between January 1968 and December 1975. Six patients (5%) were identified as having colorectal complications and five of these patients died as a direct result. Chart analysis of these 113 transplant recipients identified 55 patients as having undergone colonic evaluation (contrast enema, postmortem examination), with seven of these 55 (13%) found to have diverticulosis and major colonic complications eventually developing in four of these seven. Since the mortality from the complications of colorectal diseases in immunosuppressed patients is so prohibitive, in patients with diverticulosis and a previous history suggestive of diverticulitis, consideration should be given to exclusion from transplantation or elective segmental colectomy prior to transplantation.

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.

In the course of 184 renal transplantations performed in St. Louis since 1963, twenty-six minor and twenty-three major complications have occurred. As a result of these complications four kidneys have been lost and 1 patient has died. Aggressive therapy has been utilized in the management of all but two of the major complications and is associated with one death and the loss of two kidneys. On the basis of these results intensive therapy for genitourinary complications is encouraged, and the principles of therapy are discussed.

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.

Local flow characteristics were studied in 21 patients with end-to-side cephalic vein to radial artery fistulas, constructed in the wrist for chronic hemodialysis. Intraoperative electromagnetic flow studies indicated a mean fistula flow of 242+/-72 milliliters per minute. Approximately two-thirds of the total fistula flow was derived from antegrade flow in the proximal part of the radial artery and one-third from retrograde flow in the distal part of the radial artery. Temporary occlusion of the distal part of the radial artery caused a 36% decrease in total fistula flow. Ten patients had an initial spasm of the radial artery which abated after 20 minutes. Calculations of a cross sectional area indicate that the size of the radial artery is more important than the size of the cephalic vein or the anastomosis in limiting total fistula flow. End of vein to side of artery anastomoses are preferred to end-to-end anastomoses because immediate retrograde flow in the distal part of the radial artery contributes significantly to total fistula flow.

Renal cell carcinoma may develop in up to 25% of patients with Lindau-von Hippel disease who survive the earlier manifestations of this disease, and this neoplasm may frequently be bilateral. With early detection of such lesions, operative cure of renal cell carcinoma is more likely in these patients. However, some patients may need to undergo bilateral nephrectomy for cure. Such a patient may benefit from cadaver renal transplant in spite of the increased risk of cancer in immunosuppressed patients. We present such a case in a patient with Lindau-von Hippel disease.

Blood flows were measured in 75 arteriovenous dialysis fistulas (AVF) at the time of fistula construction. End cephalic vein to side of radial artery AVF had a mean flow of 242 +/- 89 ml. per minute which was similar to bovine heterograft AVF that also originated from the radial artery (291 +/- 67 ml. per minute). AVF originating from the brachial artery had flow rates twice those originating from the radial artery (599 +/- 163 vs. 251 +/- 89 ml. per minute), respectively). Flow rates were similar for straight arm (641 +/- 111 ml. per minute), curved forearm (561 +/- 187 ml. per minute), and curved thigh (592 +/- 134 ml. per minute) bovine AVF. Initial blood flow through arteriovenous dialysis fistulas is too low to cause heart failure, except in patients with previously compromised cardiac function. In such patients AVF from the radial artery theoretically would be preferred over brachial or femoral artery AVF.

A series of 125 renal transplants were analyzed in order to ascertain the characteristics of accelerated allograft rejection. An intense accelerated rejection could be identified within the first five days in 12 of 67 transplants (18%) with good immediate renal function. Accelerated rejection differed from the usual acute rejection reaction by higher fever, increased duration and intensity of the rejection, and increased difficulty in reversing the reaction. Accelerated rejection was reversible and associated with satisfactory renal function one year posttransplant in 58% of patients. Lymphocytotoxic and heterophil antibodies in preoperative serum and eluates of removed kidneys were not present. Contrary to recent reports, accelerated renal allograft rejection is a potentially reversible process and not necessarily due to humoral antibody presensitization.

It seems timely and pertinent to review the long-term follow-up of four patients who were deliberately exposed before transplant to donor antigens in an "enhancement" protocol. Not only were there no adverse effects observed, but three of the four patients never had an identifiable rejection episode. One of the successful allograft recipients had cytotoxic antibodies to his donor's cells. These appear to have been cold, T- and B-cell-reactive antibodies of doubtful significance. Both long-term surviving recipients showed weakness in degree of mitogenesis in mixed culture of donor and recipient peripheral blood mononuclear cells, which does not appear to be related to a macrophage defect but may be related to a lack of active rosette-forming T cells.

The diagnostic accuracy, ease, and technical feasibility of imaging with 131I-or 125 I-fibrinogen, 99mTc-sulfur colloid, and 67 Ga-citrate in renal transplant rejection are compared. Radiofibrinogen data resulted from literature review, radiocolloid data from 125 studies in 52 transplant patients, and gallium citrate data from 24 examinations in seven renal transplant patients performed simultaneously with the radiocolloid studied. Specificity of graft labeling during rejection appears to be similar with radiofibrinogen, 99mTc-sulfur colloid, and 67Ga-citrate. For routine clinical use 99mTc-sulfur colloid surpasses radiofibrinogen and radiogallium because of its better imaging qualities with a permissible radiation dose, leading to better separation of positive and negative results. The 99mTc-sulfur colloid accumulates in areas of intravascular fibrin thrombosis in acute and chronic rejecting renal transplants. Hence, the mechanisms for accumulation of 99mTc-sulfur colloid and labeled fibrinogen in rejecting transplants would seem to be similar. Such physiologic properties as rapid blood clearance and such physical properties as short physical half-life combine to produce reliable graft visualization with adequate definition, thus favoring 99mTc-sulfur colloid as the single agent of choice for clinical evaluation of renal transplant rejection at this time.

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.

The relationship between serum lactic dehydrogenase (SLDH) values and renal allograft rejection was examined in the dog and in man. Nine dogs with renal allografts and four with autografts had similar maximal elevations of SLDH during the first five postoperative days (mean, 420 +/- 213 and 433 +/- 80 I.U. per liter, respectively). During rejection of the allografts between days 7 and 14 the maximum SLDH was 810 +/- 285 I.U. per liter, and in autografts the peak SLDH was 233 +/- 22 I.U. per liter (p less than 0.01). The isoenzyme pattern of maximum SLDH during rejection was prominent in LDH5 and corresponded with renal tissue LDH isoenzyme composition. In 93 episodes of initial acute human renal allograft rejection reactions, the SLDH peaked above 500 I.U. per liter in 23 cases and remained below 500 I.U. per liter in 70 cases. SLDH levels above 500 I.U. per liter were associated with complete rejection of the kidney in 91 percent of patients and SLDH levels persistently below 500 I.U. per liter corresponded with reversal of rejection reaction in 99 percent of patients (p less than 0.01). Marked SLDH elevation is associated with severe, usually complete renal allograft rejection and may be useful in identifying patients with irreversible rejection reactions.

Nine patients with high-output cardiac failure from arteriovenous forearm dialysis fistulas are reviewed, and six new cases are presented. Decreases in cardiac output with temporary fistula occlusion ranged from 0.3 to 11.0 liters/min (mean, 2.9 liters/min); fistula flow rates varied from 0.6 to 2.9 liter/min (mean, 1.5 liters/min). Surgical correction of high-flow fistulas resulted in notable improvement of cardiac failure in 13 of 14 patients. Although cardiac failure in individuals who are receiving long-term dialysis treatment is usually caused by intrinsic cardiac disease, volume overload, or anemia, forearm fistulas with large flow rates may be an important contributing factor. Correction of these large flow rates may be an important contributing factor. Correction of these large flow rates by banding or closure can substantially improve cardiac function in selected patients.