Gustave J. Dammin

PROLONGED SURVIVAL OF SKIN HOMOGRAFTS IN UREMIC PATIENTS

In the studies by Hume el al.’ on the functional survival of renal homotransplants in patients with chronic renal insufficiency, it was observed that the period of homotransplant function in 4 of 9 recipients ranged from 5 to 25 weeks. The course of the renal homotransplant in the normal dog contrasts with this wide range and long duration of the period of functional survival of renal homotransplants in the uremic patient. Irrespective of the manner in which the donor and/or recipient have been modified, including procedures known to suppress antibody formation, functional survival of the renal homotransplant in the dog seldom exceeds 1 week. Since there has been no uniformly successful experimental counterpart of chronic renal insufficiency in the dog, no information is presently available on the renal homotransplant function in the dog under these circumstances. In man, when the recipient does not have a chronic renal insufficiency, as exemplified by the case of Michon et aE.,2 the renal homotransplant functions well for about 3 weeks and then ceases to function rather abruptly, with the homotransplant showing the same morphologic pattern of rejection seen in the dog. This pattern has been interpreted as a morphologic representation of an antigen-antibody reaction; the immune response of the recipient to the renal homotransplant is believed to be the basis for the rejection. A delayed rejection or prolonged acceptance, therefore, may well represent an impaired immune response. Homotransplantation studies by Dempster3 and Simonsen4 have established a close antigenic relationship between the kidney and the skin. Should this relationship apply in man, one would expect the uremic recipient, if the prolonged functional survival is a manifestation of an impaired immune response, likewise to show a prolonged survival of skin homografts. I t was on this basis that the study to be described was undertaken. The first group of patients studied had chronic renal insufficiency with uremia that ranged from 4 months to 6 years in duration (TABLE 1). It may be noted that a variety of chronic lesions is represented, with uremia a common denominator. Skin homografts were accompanied by skin autografts in each case. The grafts were approximately square with an area of 3 to 4 sq. cm. The bed of the recipient site was subcutaneous tissue, and the grafts were full thickness. Biopsies from the homograft and the autograft were obtained simultaneously. Tissues were fixed in buffered 10-per cent formalin and processed through a modified Bouin solution. Hematoxylin and eosin, periodic acid-Schiff, Verhoeff-van Gieson, reticulum, and Feulgen stains were used. TABLE 2 summarizes the data on the recipient, donor type of homograft, the time interval to biopsy, and the estimate of the degree of homograft survival. “Pure” refers to grafts obtained from normal donors, “cortisone” to grafts from

Kidney Transplantation in Modified Recipients

Kidney Transplantation in Modified Recipients Joseph Murray;John Merrill;Gustave Dammin;James Dealy;Guy Alexandre;J. Harrison; Annals of Surgery

Consequences of ethylene glycol poisoning: Report of four cases and review of the literature

Abstract Four cases are described which illustrate the major clinical and pathologic manifestations of ethylene glycol poisoning. The high toxicity of ethylene glycol for even the healthy young adult is illustrated by these cases. The findings on microscopic examination of the kidney, when viewed in relationship to the clinical observations, are pathognomonic. Alterations in the glomerular tuft, not cited heretofore, may be the basis for the findings in the urine in the initial phase of the clinical picture of ethylene glycol poisoning. In addition, myocardial lesions, observed in these cases, may explain the prominence of cardiopulmonary symptoms noted also during an early phase. Tenderness of the muscles may occur on the basis of a myositis, as noted in the two fatal cases described. The symptoms related to the central nervous system, which are invariably the first to appear, have anatomic correlates which are specific only in that calcium oxalate crystals are demonstrable in the tissue. The toxicity of ethylene glycol is probably related to the intermediary metabolites as well as to the end product, oxalic acid. Early therapy consists of correction of the acidosis; later treatment is concerned with the careful management of renal failure. The importance of proper labeling of anti-freeze containers, and of education of the public to the potential hazard of ethylene glycol ingestion, is stressed.

Mucormycosis: Two cases of disseminated disease with cultural identification of rhizopus; review of literature

Abstract 1.1. Two cases of mucormycosis, a usually fatal infection reported with increasing frequency, are presented. In one, a young woman with post-abortal necrosis of the spleen, kidneys and adrenals, and severe uremia, mucormycosis was thought to contribute to the fatal outcome. The second case was a young man with hepatic disease, possibly toxic in origin, and ischemic tubular necrosis. In both cases mucormycosis was disseminated, involving the respiratory and gastrointestinal tracts. 2.2. Rhizopus arrhizus was identified in the second case. This is the sixth case of visceral mucormycosis in which the organism has been identified by culture. 3.3. Clinical and pathologic features of fifty-five cases of mucormycosis reported in the English literature are summarized. In twenty-one of these cases diabetes was present and in thirteen, leukemia or lymphoma. The role of these conditions, as well as that of cortisone and antibiotics in the pathogenesis of mucormycosis, is discussed. 4.4. The most frequently involved sites have been the brain and meninges, usually in diabetic patients. Pulmonary and disseminated forms have predominated in non-diabetic subjects. 5.5. The diagnosis of mucormycosis should be suspected in the diabetic patient who presents a triad of orbital cellulitis, ophthalmoplegia and meningoencephalitis. Some of these patients may have ulceration of the nasal mucosa and here the diagnosis may be established by histologic examination and culture of biopsy material or scrapings. The diagnosis in the pulmonary and gastrointestinal forms of infection remains difficult. 6.6. The experimental data are summarized. Alterations resulting from acute alloxan diabetes, acid osis in the form of ketosis, leukopenia, hyperglycemia and cortisone administration have been found to decrease host resistance to mucormycosis. 7.7. Recovery has been reported in three patients with cerebral mucormycosis. The treatment recommended includes control of the underlying disease, use of vaccines, amphotericin B and iodides.

Renal adenocarcinoma containing a parathyroid hormone-like substance and associated with marked hypercalcemia

Abstract A case of renal adenocarcinoma with marked hypercalcemia is described in which there was absence of bony metastases, bone resorption and new bone formation. Bone from this patient, although histologically and roentgenographically normal, had elevated metabolic rates in vitro , similar to those seen in experimental hyperparathyroidism. Four parathyroid glands showing evidence suggestive of regression were identified. Immunologic assay of the primary tumor and of a pulmonary metastasis revealed the presence of an antigen indistinguishable from parathyroid hormone.

Coagulation Studies in the Hyperacute and Other Forms of Renal-Allograft Rejection

Abstract Nine renal-allograft recipients were studied for consumption coagulopathy and fibrinolysis, which should be present if rejection is associated with the generalized Shwartzman phenomenon. One of two patients with hyperacute rejections had renal arterial and venous blood sampled during transplant nephrectomy. Peripheral blood samples from three patients with acute and one with hyperacute rejections were examined before and after transplantation. Serial observations of fibrinogen, platelets and factors II, V and VIII failed to show consumption coagulopathy in either hyperacute or acute rejections despite morphologic and immunohistochemical evidence of extensive renal cortical vascular thrombosis. Euglobulin lysis times, plasminogen levels and fibrinogen split products did not provide evidence for systemic fibrinolysis. In one patient with chronic refractory rejection, renal venous blood contained small amounts of fibrinogen split products, suggesting localized fibrinolysis. Intravascular coagulation...

Acute diffuse interstitial nephritis: Review of the literature and case report

Abstract A case of acute oliguric renal failure due to acute diffuse interstitial nephritis is described. Of the possible pathogenetic mechanisms regarded as responsible for the unusual renal lesion in this case, sensitivity to methicillin is considered the most likely. Despite the alarming histologic pattern which characterizes this diffuse interstitial lesion, careful observation usually reveals minimal damage to the parenchyma. This suggests a high degree of reversibility of the lesion, even though the intense cellular infiltration of the interstitial tissue may be accompanied by focal necrosis of tubules and hemorrhage. Thus, efforts to tide the patient over an oliguric or anuric period with dialysis and other measures employed in acute renal failure are likely to be rewarding. The additional manifestation of ureteral inflammation as part of the hypersensitivity reaction, causing possible obstruction, is discussed. Acute diffuse interstitial nephritis was more common before the introduction of drugs to control streptococcal and other infections which were causally related to this lesion in the past. However, the wider use of antibiotics and other drugs carries with it the hazard of sensitivity reactions which may result in this form of nephritis.

Reversibility of the kidney homograft reaction by retransplantation and drug therapy.

In the course of study of kidney homotransplants during the past four years, reversibility of the rejection pattern within the kidney has been produced in the dog and possibly in man. In the laboratory canine renal homotransplants that were retransplanted back to the original donor after one to eight days of temporary residence in the homologous host lose the cellular infiltrate characteristic of the well established rejection process and can function as life-sustaining transplants. In the human, the microscopic characteristics of the rejection process have been improved by high doses of a purine analog. These clinical and experimental observations suggest that the homograft rejection process is not an inexorable, irreversible, “all-or-none” phenomenon; on the contrary the homograft reaction may more properly be considered as a disease process of varying severity, amenable to proper and timely therapy. This report deals principally with the laboratory data obtained from the retransplantation of dog kidneys back to the original donors after several days residence in a homologous host. The study was originally designed to extend the extracorporea1 perfusion methods of kidney preservation.‘-s The time interval in the temporary host has been correlated with the histological picture and function of the retransplant. An observation on a human renal homograft which is pertinent to the experimental data is included.

Paradoxical embolism with renal failure caused by occlusion of the renal arteries

Abstract A case is reported of renal failure due to the passage of emboli from a thrombus in the deep calf veins, through a patent foramen ovale, to occlude both renal arteries in an obese woman following fracture of the fibula. Paradoxical embolism had been reported and proved at autopsy in 100 previous cases. In 35 per cent of these the kidneys were involved. In no case, however, was the kidney the only organ involved, or did renal insufficiency result, with death from renal failure. An analysis of all the data available on paradoxical embolism shows that it occurs predominantly in middle-aged women. The lungs, brain, kidneys and spleen are the organs most frequently involved by emboli. A rise in right atrial pressure is necessary to cause the blood to flow from right to left, thus carrying the emboli to the arterial circulation. The possible mechanism causing this rise in cases when there is no evident pulmonary embolization is discussed.

Alterations in human serum β1C-globulin (C′3) in renal transplantation

Abstract Fifteen recipients of renal transplants were studied serially to determine the effect of rejection on the complement system, as manifested by specific alterations in β 1C -globulin (C′ 3 ) during rejection episodes, β1Cβ1A-globulin levels rose at the time of rejection to an average of 58 ± 18 per cent above the mean, declined below the mean six days after the maximal intensity of rejection, and fell to a minimum of 41 ± 16 per cent below the mean 22 ± 6 days after rejection began. An acute rise in β 1C -globulin did not occur (1) in a patient who had an acute exacerbation of glomerulonephritis in his isogeneic graft, (2) as a result of surgery per se , (3) during acute bacterial infections in some of the patients, or (4) in patients with no rejection episode. Although the return of β 1C -globulin to its previous level after rejection-related depression was associated with clinical improvement, stability of the level was the most important criterion of sustained control of rejection and thus it may be a useful guide in planning therapy. Immunoglobulin levels were not generally altered in these patients, although some depression of IgG and IgA occurred in cases of prolonged and poorly controlled rejections. In patients with chronic renal disease the IgM level was low initially and rose after successful transplantation. Although low titer latex reactions were found in seven of nine patients at variable intervals after transplantation, none of them had clinical manifestations of rheumatoid disease.