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Showing papers on "Transplantation published in 1972"




Journal ArticleDOI
TL;DR: AAUTOTRANSPLant of omentum to a LARGE SCALP DEFECT, with MICROSURGICAL REVASCULARIZATION DONALD McLEAN and HARRY BUNCKE.
Abstract: AUTOTRANSPLANT OF OMENTUM TO A LARGE SCALP DEFECT, WITH MICROSURGICAL REVASCULARIZATION DONALD McLEAN;HARRY BUNCKE; Plastic and Reconstructive Surgery

365 citations



Journal ArticleDOI
TL;DR: It seems clear that the predominant etiology was chronic immunosuppression post-transplantation, and drastic reduction or even discontinuance of immunOSuppression should be considered in the management of these latter tumors.
Abstract: De novo malignant tumors have been observed throughout the world in 75 chronic survivors of organ transplantation, including 16 of our own patients. The incidence of tumors was approximately 80 times greater than in the average population in a comparable age range. Chronic uremia may have predisposed to the development of some of the tumors, but this has not yet been proved. It seems clear that the predominant etiology was chronic immunosuppression post-transplantation. Forty-four of the patients had epithelial tumors and in 31 the lesions were of mesenchymal origin. On the average the malignancies appeared 29 months after transplantation. Lymphomas showed an unusual predilection for involvement of the central nervous system. Carcinomas of the skin, lip, and uterine cervix were successfully treated by conventional techniques. On the other hand, carcinomas of the thoracic or abdominal organs and mesenchymal tumors led or contributed to early death in most cases. For this reason drastic reduction or even discontinuance of immunosuppression should be considered in the management of these latter tumors.

290 citations


Journal ArticleDOI
TL;DR: Subsequent kidney specimens after transplantation obtained from two of these patients with recurrent nephrotic syndrome showed focal segmental glomerulosclerosis limited primarily to the juxtamedullary glomeruli—a feature further suggesting recurrence of the original disease in the transplanted kidney, suggesting the pathogenesis of the steroid-resistant idiopathic nephRotic syndrome may involve systemic circulating factors.

288 citations


Journal ArticleDOI
TL;DR: All 4 patients with complete marrow failure showed prompt engraftment indicated by a return of marrow cellularity and a rise of peripheral blood-counts, confirmed by cytogenetic analysis.

240 citations


Journal ArticleDOI
TL;DR: These studies demonstrate the sustained capacity of the transplanted human heart to support normal physical activity late in the postoperative period and demonstrate atypical adaptive mechanisms characteristic of the denervated heart responds in a directionally appropriate manner to the metabolic demands of exercise.
Abstract: Cardiac catheterization studies were performed in eight patients 1 year after cardiac transplantation and in two of these again at 2 years. Intracardiac pressures at rest were normal in all patients, both 1 and 2 years postoperatively. Average cardiac index at rest at 1 year was 2.3 liters/min/m2 and average heart rate was 90 beats/min. Responses to amyl nitrite, atropine, and tyramine failed to demonstrate efferent autonomic reinnervation of the donor hearts. Findings associated with a 10-min period of submaximal supine bicycle exercise 1 year after transplantation included: (1) a gradual rise in heart rate throughout most of the exercise period; (2) prompt elevation of left ventricular end-diastolic pressure by an average increment of 10 mm Hg, followed by a decrease during late exercise in some patients; (3) a progressive increase in LV systolic pressure throughout the first half of the exercise period; (4) a continuously positive change in LV rate of pressure change (dp/dt) throughout exercise; (5) an average 44% increase in stroke volume; and (6) an average 92% increase in cardiac output. The slope of the regression of cardiac output on oxygen uptake during exercise was within the range of normal. Cardiac output, however, was lower than normal both at rest and during exercise, and the arteriovenous oxygen diflerence was accordingly widened. In one patient studied 1 and 2 years after transplantation, hemodynamic findings were comparable on both occasions. In the other, however, the cardiac output response to exercise was distinctly diminished at 2 years as compared to 1 year, due almost entirely to failure of the stroke volume to increase. Coronary arteriography in this recipient revealed evidence of occlusive coronary disease compatible with graft atherosclerosis. These studies demonstrate the sustained capacity of the transplanted human heart to support normal physical activity late in the postoperative period. Although utilizing atypical adaptive mechanisms characteristic of the denervated heart, the transplanted heart responds in a directionally appropriate manner to the metabolic demands of exercise.

190 citations


Journal Article
TL;DR: The growth of an implanted, isologous Lewis lung carcinoma in C57BL/6 mice was followed by serial tumor diameter measurements, and the number of tumor cells which had metastasized to lungs and kidneys was follow by serial quantitative transplant bioassay, pointing to the importance of nonimmunological systemic factors that influence tumor growth rate.
Abstract: Summary Previous studies have shown that the growth of a solid tumor is characterized by progressive slowing of the rate of growth as the tumor increases in size, but it is not clear to what extent local or systemic factors determine this slowing of growth rate. In this study, the growth of an implanted, isologous Lewis lung carcinoma in C57BL/6 mice was followed by serial tumor diameter measurements, and the number of tumor cells which had metastasized to lungs and kidneys was followed by serial quantitative transplant bioassay. Tumor diameter data were converted to tumor weight by a previously derived formula. Synchronous slowing of the rate of growth of the implanted tumor and its metastases was observed. Early after transplantation, the implanted tumor grew exponentially, and early lung metastases grew exponentially at a similar rate. Later, as the growth rate of the large implanted tumor slowed, a similar degree of slowing of the growth rate of metastases in lung and kidney was observed, even though these metastatic foci were microscopic in size. Host immunological factors did not seem to be involved, since challenge of animals at various stages of tumor growth with graded doses of tumor cells showed no evidence of transplantation resistance. Synchronous slowing of tumor growth rate was also demonstrated in experiments in which metastases were simulated by a 2nd implant. Following removal of the primary tumor, this slowing of tumor growth was reversible in both the lung metastases and the simulated metastases. These studies point to the importance of nonimmunological systemic factors (nutritional deficiencies or tumor by-products) that influence tumor growth rate.

180 citations


Journal ArticleDOI
TL;DR: Experiments involving brain transplantation and selective illumination of parts of the body showed that the brain directly receives the light information which is necessary for the entrainment of the clock.
Abstract: 1. In silkmoths the gating of adult eclosion by light-dark cycles persists after extirpation of the compound eyes, frontal ganglion, subesophageal ganglion, or corpora allata-corpora cardiaca complex. Removal of the brain abolishes gating and such moths emerge irrespective of time of day or night. 2. Implantation of a brain into the abdomen of a debrained animal restores the ability both to entrain to a light-dark cycle and to free-run under conditions of continuous darkness. 3. Implantation of pieces of brain which contain the cerebral lobes likewise restored to debrained moths the ability to entrain and to free-run. But the synchrony was not as sharp as that observed in moths which had received implants of the entire brain. 4. Transection of the brain lateral to each median neurosecretory cell cluster yields pieces which are apparently incapable of gating the eclosion of debrained moths. Both moths receiving the median piece and those receiving the lateral pieces showed a randomized distribution of eclosion. 5. Experiments involving brain transplantation and selective illumination of parts of the body showed that the brain directly receives the light information which is necessary for the entrainment of the clock. 6. In theCecropia moth, the lights-on signal serves to stimulate eclosion and thus partially masks the output of the clock. This effect is mediated solely by light which is perceived by the compound eyes.

163 citations


Journal ArticleDOI
TL;DR: The major complication, acute hemorrhagic pancreatitis, can be partially prevented by carefully ligating tributaries in the vicinity of the pancreas, reducing the is chemic time, perfusing with cold saline, and using a no-touch technique.
Abstract: SUMMARY A technique for pancreaticoduodenal (PD) transplantation in the rat is presented. The rejection reaction in pancreatic grafts in inbred strains of rats is described. The major complication, acute hemorrhagic pancreatitis, can be partially prevented by carefully ligating tributaries in the vicinity of the pancreas, reducing the is chemic time, perfusing with cold saline, and using a no-touch technique.

Journal ArticleDOI
TL;DR: A preliminary report on the experimental transplantation of free periosteum was given, stripped from the tibia with the aid of a scalpel and transplanted to soft tissues.
Abstract: A preliminary report on the experimental transplantation of free periosteum is given. The literature concerning the subject is reviewed. 152 rabbits with ages ranging between 11 and 149 days were used. The periosteum was stripped from the tibia with the aid of a scalpel and transplanted to soft tissues. Bone formation occurred in all series, and was studied by X-ray, histology and autofluorescence. Some clinical use has been discussed.

Journal Article
TL;DR: Vascular wall ischemia due to interruption of vasa vasorum during transplantation appears to initiate these medial changes, and much more slowly, intimal thickening by myointimal cells and collagen may reduce the graft lumen to a variable extent.
Abstract: The histologic fate of venous grafts used for coronary artery bypass has been observed with light and electron microscopy in dogs. Endothelial damage and thrombosis were chiefly limited to the first postoperative week. The muscular media uniformly suffered extensive necrosis and inflammatory cell infiltration during the first week. Its smooth muscle cells either hypertrophied, died or underwent apparent fibroblastic transformation, with eventual fibrous replacement, to a variable degree, of the vein wall. Vascular wall ischemia due to interruption of vasa vasorum during transplantation appears to initiate these medial changes. Much more slowly, intimal thickening by myointimal cells and collagen may reduce the graft lumen to a variable extent.


Journal ArticleDOI
22 Jan 1972-BMJ
TL;DR: This study indicates that the kidney has a role in the degradation of gastrin, as measured by radioimmunoassay in patients with chronic renal failure.
Abstract: Fasting serum gastrin was measured by radioimmunoassay in 89 patients with chronic renal failure. When the serum creatinine level was used as an index of the degree of renal impairment serum gastrin rose proportionately with the degree of renal failure. Haemodialysis did not significantly alter serum gastrin levels but renal transplantation tended to return them towards normal. This study indicates that the kidney has a role in the degradation of gastrin.

Journal ArticleDOI
05 Jul 1972-Nature
TL;DR: In many cases, in transplantation and tumour immunology, direct reactivity may be absent in spite of the presence of the antigen, and comparable demonstration of specificity has been very difficult.
Abstract: SPECIFICITY is one of the chief hallmarks of immune reactions. In many cases, specificity has been defined by reactivity against some antigens and not against others, but the results of direct tests may be misleading. In many cases, in transplantation and tumour immunology, direct reactivity may be absent in spite of the presence of the antigen. With HL-A antigens, the CYNAP phenomenon (cytotoxicity negative, absorption positive) has been described1. Virus-induced tumours may have relatively small amounts of tumour specific cell surface antigens which are detectable only by absorption tests2,3. In addition, immune reactions may occur against a particular antigen on one material and against different antigens on another material. With antibody reactions, specificity can be confirmed by the appropriate absorption experiments4,5. With cellular immune reactions, comparable demonstration of specificity has been very difficult.

Journal ArticleDOI
TL;DR: In severe chronic renal failure loss of weight is common due to a reduction in body fat and fat-free solids and changes in body composition closely resemble those found in malnutrition and it is suggested that the abnormalities of body composition found in Chronic renal failure are attributable to protein-calorie deficiency.
Abstract: In severe chronic renal failure loss of weight is common due to a reduction in body fat and fat-free solids. The lean body mass forms an increased proportion of body weight. Body water is relatively increased largely due to an excess extracellular fluid. Intracellular fluid is reduced relative to standard weight in the majority of patients. The exchangeable sodium is increased. The changes are not confined to patients with terminal uraemia but are most marked in those who have received prolonged treatment with low-protein diets. After the start of regular haemodialysis body weight falls because of losses of body water from both extracellular and intracellular spaces. Thereafter body weight increases, due to gains in body fat and fat-free solids. Changes in exchangeable sodium are variable. Intercurrent illness, poor dialysis, or fluid indiscretions rapidly induce a return of the original abnormalities and recovery is slow. Similar changes in body composition are observed after renal transplantation though these may be modified by large doses of prednisone. In general, transplantation is more effective in restoring body composition to normal than haemodialysis. These changes closely resemble those found in malnutrition and it is suggested that the abnormalities of body composition found in chronic renal failure are attributable to protein-calorie deficiency.


Journal ArticleDOI
TL;DR: A higher incidence of malignancy as well as greater susceptibility to infection has been found to be associated with primary immunodeficiencies, and the two adaptive processes have an essential relationship that must be elucidated.
Abstract: A higher incidence of malignancy as well as greater susceptibility to infection has been found to be associated with primary immunodeficiencies. An increased incidence of leukemia has been associated with X-linked infantile agammaglobulinemia-an isolated defect of humoral immunities. An increased frequency of a wide variety of malignancies have been found to accompany several different forms of primary immunodeficiency. Secondary immunodeficiencies produced by immunosuppressant therapy to facilitate renal transplantation have also been found to have far too much cancer to be explained by chance assocaition. Many experimental associations between immunity and malignancy have also been encountered, indicating that these two adaptive processes have an essential relationship that must be elucidated.


Journal ArticleDOI
TL;DR: Graft-vs-host reaction should be added to Lyell's group of systemic diseases associated with TEN, and cutaneous histopathology early in the clinical course showed changes of GVH.
Abstract: Toxic epidermal necrolysis (TEN) occurred in a patient with graft-vs-host reaction (GVH). Certain factors link TEN and GVH in this patient. A 22-year-old man with acute lymphocytic leukemia, treated with allogeneic bone marrow transplantation, developed GVH as manifested by diarrhea, hepatitis, lymphopenia, and a progressive cutaneous eruption. The initial morbilliform eruption later became intensely erythematous, and massive desquamation of large sheets of epidermis, typical of TEN, ensued. Cutaneous histopathology early in the clinical course showed changes of GVH. Later biopsies were also consistent with the diagnosis of TEN. Experimental models of TEN accompanying GVH and a discussion of pathogenesis are included. Graft-vs-host reaction should be added to Lyell's group of systemic diseases associated with TEN.


Journal ArticleDOI
TL;DR: Bacteremia occurred in thirty-seven of 140 patients with renal homotransplants seen over a five and a half year period; it was fatal in thirteen patients as discussed by the authors.

Journal ArticleDOI
TL;DR: Results of physical analysis indicate that the precursors of B lymphocytes described here may not be pluripotent stem cells for the immune system, and these cells were found in bone marrow and spleen but could be detected in peripheral lymph nodes.
Abstract: A cell transfer assay system was developed to study the precursors of bone marrow-associated (B) lymphocytes in the adult mouse. The rationale of the assay is to inject into irradiated mice a cell suspension depleted of B lymphocytes, to wait a period of time to let precursor cells differentiate to B lymphocytes, then to correlate the number of B cells present in the recipient mice with the number of precursor cells injected. The assay as described was shown to be linear in the range of 105–3 x 106 fractionated bone marrow cells. Kinetic studies indicated that precursor cells start producing detectable numbers of B cells within 3 days after transplantation; B cell activity then increases with a doubling time of 24 hr. Physical characterization of that precursor cell has shown that it is lighter and sediments faster than small lymphocytes. Precursor cells were found in bone marrow and spleen but could not be detected in peripheral lymph nodes. Results of physical analysis also indicate that the precursors of B lymphocytes described here may not be pluripotent stem cells for the immune system.

Journal ArticleDOI
TL;DR: Recipients of cadaver kidneys who had not developed cytotoxic antibodies during haemodialysis treatment of more than one year before transplantation subsequently had a high kidney-transplant survival-rate at one year of 85% in contrast to a 50% survival- rate for recipients who did not develop cytotoxins during a haemmodialysis period of less than oneyear.



Journal ArticleDOI
TL;DR: The results suggest that long-term allotype suppression resulting from perinatal exposure of offspring to specific anti-allotype antibody (anti-Ig-1b), is not due merely to an absence of Ig-1B-producing cells or their progenitors, but appears to be an active process, which dominates physiologically over normal production.
Abstract: Long-term (chronic) allotype suppression, previously reported only in rabbits, is shown here to occur in at least one strain combination of mice as well. Close to 50% of the offspring of SJL (Ig(b)) males mated to BALB/c (Ig(a)) females immunized against the paternal allotype were found to be suppressed for Ig-1b (gammaG(2a)) at 6 months of age. These mice are called "chronically" suppressed. The percentage of offspring in this strain combination suppressed for the paternal allotype at 8 wk of age is the same as that seen in an earlier strain combination tested, [(C57 x BALB/c)F(1)], in which all mice recover from suppression by 10-12 wk. After 8 wk, two distinct patterns of long-term (chronic) suppression emerge in (SJL x BALB/c)F(1) mice: a small number of these mice never produce detectable amounts of Ig-1b throughout their lives, while the majority produce detectable Ig-1b sporadically, sometimes over a period of several weeks, the level of which eventually falls below detectability. Attempts to "cure" suppression by destroying the existent lymphoid population and forcing endogenous repopulation in chronically suppressed animals were unsuccessful. Furthermore, attempts to restore Ig-1b production by injection of cells from syngeneic Ig(a)/Ig(b) donors into irradiated, chronically suppressed recipients were also unsuccessful, although the same cell inocula, when injected into irradiated BALB/c (Ig(a)/Ig(a)) mice produced high levels of gamma globulin carrying the allotype. These results suggest that long-term allotype suppression resulting from perinatal exposure of offspring to specific anti-allotype antibody (anti-Ig-1b), is not due merely to an absence of Ig-1b-producing cells or their progenitors, but appears to be an active process, which dominates physiologically over normal production.


Journal ArticleDOI
TL;DR: In several patients synchronization of the recipient atrial rate with the donor heart rate has been observed during exercise when these rates approached a similar level, and diastolic heart sounds related to recipients atrial contraction were noted clinically and recorded on phonocardiograms.
Abstract: During cardiac transplantation the posterior and lateral portions of the recipient's right and left atria and a posterior rim of interatrial septum are left intact. Persistent electrophysiologic activity of these residual recipient atrial remnants has been manifest as P waves dissociated from the donor heart rhythm and recorded in both standard and intracardiac electrocardiograms. Physiologically appropriate changes in recipient atrial rate have occurred in response to the respiratory cycle, donor heart systole, atropine, tyramine, amyl nitrite, carotid sinus pressure, the Valsalva maneuver and exercise. In several patients synchronization of the recipient atrial rate with the donor heart rate has been observed during exercise when these rates approached a similar level. Fibrillation and flutter of the recipient atria, independent of the donor heart rhythm, have been observed in 3 recipients. In 4 patients studied by cardiac catheterization 1 year postoperatively mechanical effects of recipient atrial contractions were detected in both right- and left-sided pressure measurements. Recipient left atrial contraction occurring simultaneously with donor atrial systole increased left ventricular end-diastolic pressure by 2 to 4 mm Hg and produced significantly greater peak left ventricular and arterial systolic pressures as well as augmented left ventricular ejection times. In several patients, especially during episodes of threatened graft rejection, diastolic heart sounds related to recipient atrial contraction were noted clinically and recorded on phonocardiograms. Such recipient atrial gallop sounds simulated both atrial and ventricular gallop sounds of donor heart origin, and occurred in addition to both to produce hybrid diastolic gallop rhythms. The physiologic mechanisms and implications of recipient atrial behavior are discussed.