Colorectal complications of renal allograft transplantation.

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.     

The binding and processing of monoclonal human IgG1 by cells of a human macrophage-like cell line (U937)

The goal of these experiments was to assess the relationship between the binding and processing of IgG by Fc-receptor-bearing cells. Cells of the U937 human macrophage-like cell line were incubated with 125I- labeled monomers, dimers, oligomers (composed of 2-4 IgG1 subunits), and HP (heavy polymers composed of 5 or more subunits per polymer) of monoclonal human IgG1 in vitro. Binding was assessed by spinning cells through a layer of phthalate oils. Internalization of IgG1 was assessed by quantitating residual binding to cells after surface-bound IgG was removed by a brief treatment with a solution containing 0.25 M acetic acid and 0.5 M sodium chloride. Catabolism was assessed by measuring the release of radioactive fragments of IgG1, which were not precipitated by 10% trichloroacetic acid. Unstimulated U937 bound about 10,000 molecules per cell of IgG1 monomer, with an equilibrium binding constant (Ka) of 5 X 10(8) M-1. After stimulation with a conditioned medium in vitro, binding per cell was increased 3-7--fold, and the Ka was decreased 2-4--fold. Both unstimulated and stimulated cells internalized and catabolized labeled IgG1 HP, but stimulated cells internalized and digested much more IgG1 HP per cell than unstimulated cells. Both monomers and dimers of IgG1 were internalized and degraded very slowly by stimulated cells, even though both preparations readily bound to cells. In contrast, oligomers and (to an even greater extent) IgG1 HP were internalized and degraded much more rapidly. Internalization of IgG1 HP was markedly inhibited by incubation at 4 degrees C, but not by incubation with a variety of metabolic inhibitors. Catabolism was inhibited by chloroquine and monensin (inhibitors of lysosomal acidification) and by cytochalasin (an inhibitor of microfilament polymerization). Binding to the surface of cells was not markedly inhibited by any agent tested. The capacity of cells to bind labeled IgG1 was markedly reduced by prior incubation in the presence of unlabeled IgG1. This reduction was in part due to the steric blockade of receptors caused by the avid, but reversible, binding of IgG1. In addition, IgG1 oligomers or HP (but not IgG1 monomers or dimers) also caused an irreversible reduction in the number of Fc receptors by a process analogous to receptor down-regulation, as observed in other receptor--ligand systems.     

Possibility of selection against mtDNA mutations in tumors

Several studies of tumors have revealed substantial numbers of clonally expanded somatic mutations in mitochondrial DNA (mtDNA), not observed in adjacent intact tissues. These findings were interpreted as indicating the involvement of mtDNA mutations in tumorigenesis. Such comparisons, however, ignore an important confounding factor: the monoclonal origin of tumors as opposed to the highly polyclonal nature of normal tissues. Analysis of recently published data on the incidence of somatic mutations in nontumor monoclonal cells suggests that, contrary to the prevailing view, the process of tumorigenesis may be accompanied by active selection against detrimental mtDNA mutations.     

Peptic ulcer disease following transplantation: the role of cimetidine

Of 253 consecutive renal transplants performed in 209 patients between January 1971 and December 1980, symptomatic gastroduodenal ulcerations developed in 22 (8.7 percent). Time of presentation ranged from 5 days to 9 years (mean 225 days) following transplantation with 16 of these patients presenting within the first 3 months. Nine (Group I) patients were diagnosed before the administration of H2 antagonist cimetidine. Mode of presentation in this group was upper gastrointestinal bleeding in each instance. Thirteen patients (Group II) were diagnosed after the clinical use of cimetidine was established. The mode of presentation in this group was bleeding in 11 patients and abdominal pain in 2 patients. In Group I, one patient died from liver failure and an ulcer was not contributory. The remaining eight patients were treated with antacids and blood transfusions (mean 12.7 units). Five patients in this group demonstrated ulcer healing, whereas three patients (37.5 percent) required emergency operations with two postoperative deaths. In Group II, one patient died from hemorrhagic shock before therapy could be instituted. In the other 12 patients treatment consisted of antacids, cimetidine, and blood transfusions (mean 6.8 units). Ten patients had relief of symptoms, whereas two patients (16.7 percent) required emergency operations with no deaths. During cimetidine therapy, two patients had rejection episodes that were reversible, and the remaining patients had no significant alterations in renal function. To conclude, cimetidine is a safe and effective adjunct in the treatment of peptic ulceration in renal transplant recipients.