Circulating immune complexes after kidney transplantation.

Sera from patients who had received renal allografts were studied for the presence of circulating immune complexes by using platelet aggregation technique combined with density gradient centrifugation. A simple and highly reproducible modification of the platelet aggregation technique, employing the use of relatively small amounts of blood from pretested donors as the source for platelets, is described. Immune complexes were detected in post-transplantation sera from 3 out of 16 patients. The development of a persistent immune complex state as a consequence of grafting was concluded in one patient.

Sister chromatid exchange and chromosome abnormalities in uremic patients.

Chronic renal failure heightens the risk of malignancy. We therefore examined lymphocytes from 44 uremic patients and 24 normal controls for chromosome abnormalities and sister chromatid exchange (SCE) rate. This is the first report of SCE in uremia. Uremia was found to increase structurally abnormal chromosomes and elevate the rate of SCE. These cytogenetic changes in uremia may play a role in the heightened risk of cancer.

A simple technique of correcting complete gastric obstruction after gastric partitioning.

The use of autosuture staplers in intraabdominal surgery has become an accepted procedure for simplifying gastrointestinal surgery. Described in this report is a simple method of correcting unrelenting gastric obstruction that may occur after gastric partitioning for morbid obesity by utilizing the autosuture model EEA stapler to reestablish gastric continuity.

Physiologic response patterns to occlusion of clinically significant arteriovenous fistulas.

Seven patients with hemodynamically significant arteriovenous fistulas for dialysis angioaccess were studied by multivarient computer analysis of physiologic data derived from cardiogreen dye dilution curves and A-VO2 before and after acute occlusion of their fistulas and prior to clinical therapy. Three patterns of response were characterized. These patterns seemed to be related to the innate ventricular contractility status, the type of medications, the presence of autonomic neuropathy, and their interplay with alterations in preload and afterload with fistula occlusion. In one patient, the response pattern precluded banding or occlusion of the fistula. In the remainder, the physiolobic responses permitted treatment by banding or occlusion. It seems advisable to adequately evaluate the physiologic response patterns of patients with hemodynamically significant arteriovenous fistulas prior to definitive treatment.

Antibodies to saline extractable tissue antigen in sera of patients with renal diseases.

Multiple serum samples originating from 110 renal allograft recipients were examined against saline extract of normal human kidney by means of double diffusion gel precipitation. Eleven recipients were found to be positive; 99 of 106 sera from these patients were positive. Pretransplantation sera were available from 7 of these recipients and 6 patients were found "positive." The precipitation reaction was composed of one line. Identity reactions were formed between the lines produced by sera from all patients except 1. Sera of patients from end-stage renal disease produced similar reaction; however, only 3 of 234 sera from patients with nonrenal diseases precipitated the kidney extract. None of 154 normal sera were positive. Several positive sera also were positive in complement fixation tests with human kidney extract. Evidence was presented that the antibodies under study combined with a nonorgan-specific but species-restricted tissue antigen. The hypothesis was advanced that these antibodies are autoantibodies formed in response to a sequestered antigen released as a result of tissue damage. Apparently, the antigen is released frequently in immunogenic form from injury to kidney but infrequently from injury to other organs.

Unusual precipitins in pathological human sera.

In conducting double diffusion gel precipitation tests, unexpected, strong precipitation reactions were noticed between a serum originating from a renal graft recipient and many pathological human sera. The highest frequency of positive reactions were produced by sera of patients with infectious mononucleosis (83%), chronic Epstein-Barr virus infections (72%), rheumatoid arthritis (57%), lepromatous leprosy (57%), and AIDS (44%). The precipitin in these pathological sera was identified as an antibody of IgM variety and the precipitinogen in the transplantation serum was shown to be a thermostable component with beta-globulin mobility. No explanation of the nature of reactions observed can be given at present.

The alpha-interferon system in patients undergoing renal transplantation and treated with cyclosporine and prednisone.

The interferon system was investigated in 65 normal control patients and ten patients with chronic renal disease, approximately a half year after renal transplantation and treatment with prednisone and cyclosporine. In previous studies, comparable doses of prednisone had no effect on the interferon system. It was assumed that the changes observed were primarily the result of cyclosporine therapy. In contrast with normal persons, low levels of interferon-alpha (IFN-alpha) were found in the circulation of patients. It was thought that this may be related to low grade infections in immunosuppressed persons. In patients, the IFN-alpha synthesizing capacity of leukocytes was significantly decreased. IFN-alpha inhibitor level was slightly increased in two patients. Inhibition of IFN-alpha (IFN-alpha) synthesizing capacity may be part of the immunosuppression mechanism of action of cyclosporine in patients undergoing transplant.

"Heterophile" antigen in sera of human recipients of renal allografts.

It was noted that many sera of patients with renal allograft produce distinct precipitation lines in gel diffusion tests with about 20% of infectious mononucleosis sera. The antibodies in infectious mononucleosis sera were of IgM isotope, but, interestingly, they could be removed by guinea pig kidney homogenate, which indicated that the reactions studied were of the Hanganutziu-Deicher rather than of the Paul-Bunnell type. This contention was strengthened by the fact that positive transplantation sera reacted also with standard serum with Hanganutziu-Deicher antibodies. Thus far, the presence of the antigen in the transplantation sera could not be related to the clinical status of the patients, however, the antigen was noted primarily in those sera that did not contain heterophile transplantation antibodies. It was proposed that the antigen detected in the transplantation sera was an altered tissue antigen released from the grafted organ. Besides, interactions between two serum samples from the same patient were noted in immunodiffusion tests. These reactions occurred very seldom and were unrelated to heterophile transplantation antigens or antibodies.

Induction in human allograft recipients of unresponsiveness to anti-lymphocyte globulin.

The observations presented here confirm previous reports that polyclonal ALG prepared at the University of Minnesota or ATGAM of The Upjohn Co., administered as described, rarely induced sensitization of patients to the horse gamma globulin. In addition, the phenomena of transient antibody production prior to the onset of unresponsiveness and the induction of unresponsiveness in individuals with preexisting antibodies were observed.

Treatment of aluminum overload using a cartridge with immobilized desferrioxamine.

Intravenous desferrioxamine (DFO) is the method commonly used to treat aluminum toxicity. This laboratory has developed a hollow fiber device with immobilized DFO, an "Aluminum DFO-HP" (DFO-HP), for the purpose of removing aluminum without the chelator (DFO) entering the blood. With Food and Drug Administration approval, a polysulfone DFO-HP, placed in the extracorporeal circuit in series with the patient's customary dialyzer, was tested for its safety and ability to remove aluminum in patients with ESRD who had aluminum overload. During treatment with this device, no toxic reactions, side effects, or hematologic or clinical laboratory changes were seen other than those associated with dialysis. Average aluminum clearance with the DFO-HP device was 25.3 mL/min with a range of 7.2 to 52.4 mL/min, whereas aluminum clearance with the F-60 polysulfone high-flux dialyzer was 8.4 mL/min. Aluminum clearance of the cuprophane dialyzers in series with the DFO-HP was negligible. The amount of aluminum removed over a 2-h treatment with DFO-HP ranged from 94 to 628 micrograms, which corresponded to 32 to 199% of the initial aluminum in the circulation before that particular treatment. The excess 99% was provided from aluminum released from tissue sites into the circulation throughout the duration of the treatment. It is expected that, because of the efficiency and safety of the DFO-HP device, the time presently needed for aluminum depletion using intravenous DFO will be greatly shortened and the potential toxicity of intravenous DFO will be eliminated.

Treatment of lead poisoning with an immobilized chelator comparison with conventional therapy.

Lead poisoning is a global public health problem. In pregnant women it may result in developmental delays of the fetus, in children it my produce learning disability. Available chelators are nephrotoxic when eliminated as lead-chelator complexes. For safe removal of lead from the body we developed a "Lead-Hemopurifier" (L-HP), a device with an immobilized chelator. In vitro, applied to lead solutions, this device reduced the lead concentration. Applied to dogs with lead intoxication, Lead-HP-s removed lead from the blood; this was continuously replaced by lead from the bones until the skeleton was cleared from lead deposit. Treatment of lead poisoning in dogs with Lead-HP-s compared favorably with Versenate treatment of children with lead toxicity. This report demonstrates the in vivo efficiency and safety of this new detoxfication method. Methods to induce lead poisoning in dogs and procedures to identify lead released from skeletal deposits are described.

Typhlitis due to Balantidium coli in captive lowland gorillas.

Typhlitis caused by Balantidium coli and requiring surgical resection occurred in three captive lowland gorillas over a 30-month period. Not one of the other gorillas in the colony or their keepers was ill. B. coli is distributed widely geographically and widely among mammals. Asymptomatic commensalism predominates, but invasion of the colonic mucosa can produce diarrhea and dysentery and set the stage for local or systemic spread.

In vivo safety of hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase in a large animal model for phenylketonuria.

Hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase (PAL) were developed for the in vivo depletion of phenylalanine (Phe) in circulating blood. A series of experiments was conducted with a large animal model in order to explore its safety for clinical use. The level of red blood cells, white blood cells and platelets did not change during a 2-hr application of the reactors in anesthetized, heparinized dogs and monkeys with experimental hyperphenylalaninemia. No increase in blood urea nitrogen was observed due to generation of ammonia from PAL-catalyzed Phe breakdown. The other metabolic product, trans-cinnamic acid, was reported to be nontoxic. Repeated application of the PAL-reactors to the same animals did not produce untoward physiological or immunological reactions. These data suggest that PAL-reactors may be safe for in vivo use to control excess Phe brought about by fever, infection or pregnancy in phenylketonuric individuals otherwise balanced by a Phe-poor diet. Application of PAL-reactors may serve as a model for extracorporeal enzyme replacement in enzyme-deficiency diseases.

Histology of human tubulo-interstitial nephritis associated with antibodies to renal basement membranes.

Twenty-seven patients with diffuse "crescentic" glomerulonephritis (CSGN) were identified in 1,174 renal biopsies from nephritic patients. Patients were assigned to three groups on the basis of the immunofluorescent study of renal biopsy specimens and serologic findings. Group I included eight patients with antibodies to glomerular (anti-GBM) and tubular (anti-TBM) basement membranes; group II had eight patients with only anti-GBM antibodies; and group III had eleven patients with CSGN unassociated with antibodies to either GBM or TBM. Patients with anti-GBM/anti-TBM antibodies (group I) had severe tubulointerstitial (TI) nephritis, as characterized by the infiltration of polymorphonuclear leukocytes and macrophages along the TBM and peritubular vessels. In some patients, focal proliferation of epithelial cells of proximal convoluted tubules (PCT), gaps or extensive destruction of TBM, lesions in the walls of small peritubular vessels, and interstitial giant cells were also observed. Patients with anti-GBM antibodies (group II) had mild to moderate interstitial cellular infiltration and mild tubular changes. Five patients with CSGN not associated with antibodies to renal basement membranes (group III) had mild to moderate interstitial cellular infiltration and tubular changes. A sixth patient, with Wegener's disease had severe granulomatous TI lesions. The results of this study show that TI nephritis is most frequent and severe with anti-TBM antibodies are demonstrable and suggest that anti-TBM antibodies contribute to the development of TI lesions.