Acute appendicitis in the renal allograft recipient.
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Biomedical subjects
Publications and source records attributed to L J Perloff.
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Retroperitoneal lymphoceles developed in 12 renal allograft recipients during the last nine years. The interval between transplantation and the development of symptoms averaged seven months. The specific syndrome suggesting the presence of a lymphocele included lower abdominal swelling, weight gain, and, occasionally, fever without an obvious source of infection. Although these symptoms mimicked allograft rejection, diagnosis was easily made by ultrasound and intravenous pyelogram. Surgical marsupialization of the lymphocele with drainage into the peritoneal cavity proved to be an effective treatment.
To determine the extent to which pretransplant immunity resulting from natural infection protects against cytomegalovirus (CMV) disease, we analyzed CMV serology on 153 kidney donor and recipient pairs and followed transplant patients to determine incidence and severity of CMV disease. The overall incidence of CMV disease was 22%. Significant differences occurred in CMV disease incidence and severity, depending on the immune status of the kidney donor and recipient. Among recipients of kidneys from seropositive donors, immunity offered significant protection from CMV disease, reducing its incidence from 61% in nonimmune to 24% in immune patients (P less than 0.01). Pretransplant immune patients also had fever CMV-related complications. Among recipients of kidneys from seronegative donors, pretransplant immunity conferred a significant risk of CMV disease; immune patients had a 20% incidence of CMV disease compared with 2% in nonimmune patients (P less than 0.02). Disease was generally mild in all patients receiving kidneys from CMV infection had a 3-fold higher incidence of CMV disease than patients with reactivation infection (P less than 0.01). The incidence of CMV disease was similar in immune patients, whether they received a kidney from a seropositive or a seronegative donor. However, an important observation was that disease was significantly more severe in immune patients receiving a kidney from a seropositive donor (P less than 0.05). This indicates that if kidneys from seropositive donors are selected for use only in seropositive recipients, this places the immune patient at a higher risk for severe CMV disease. We conclude that pretransplant immunity offers a significant advantage to patients receiving kidneys from seropositive donors.
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Reports of improved survival of allografts in recipients of donor-specific blood prompted an attempt to determine the relationship of the antigenic composition of the blood product transfused to the development of immunologic unresponsiveness in rats. Cardiac allografts were transplanted from Fischer, Brown-Norway (BN), and Lewis (L) X BN (LBN) f1 hybrids to recipients treated with three weekly transfusions of 1 ml of donor-specific whole blood, erythrocytes, or ultraviolet-irradiated whole blood. Despite moderate improvement in survival with whole blood alone in the LBN- greater than L group (11.6 +/- 1.0 days), it was only with the ultraviolet-irradiated whole blood that marked prolongation was seen in all three strain combinations: Fischer- greater than L: 25.5 +/- 5.2, LBN- greater than L: 17.3 +/- 1.2, and BN- greater than L: 11.1 +/- 0.4 days compared with respective controls: 10.3 +/- 1.2, 7.3 +/- 0.5, and 7.4 +/- 0.6 days. Unlike reports for renal allografts, erythrocyte suspensions provided minimal protection for the cardiac allografts (14.2 +/- 0.8, 9.0 +/- 1.1, and 11.0 +/- 0.4 days, respectively), and adjunctive treatment with antilymphocyte serum had a similar small effect (16.3 +/- 1.4, 13.4 +/- 1.9, and 8.3 +/- 0.8 days, respectively). The elimination or inactivation of functional class 2 major histocompatibility complex antigens from the blood used for donor-specific blood transfusion may be an effective means of prolonging allograft survivals over those seen with whole blood alone; however, the degree of resultant unresponsiveness is still clearly influenced by dosage schedule, the organ transplanted, histocompatibility barrier, and adjunctive immunosuppression.
In an attempt to study the generality of effect of donor-specific blood transfusions (DSBT) in inducing immunologic unresponsiveness, the survival rates of heart, pancreas, and skin allografts were compared in blood-pretreated animals. DSBT, when given in a single-dose or multiple-dose protocol, prolonged cardiac allograft survivals in some strain combinations (F----L, LBN----L), but not in others (BN----L, ACI----L, ACI----WF). Antilymphocyte serum further prolonged survivals in protocols in which blood pretreatment was effective, and proved capable of reversing a state of sensitization in rats treated with multiple small-volume transfusions. In no case did the protection afforded the cardiac allografts extend to pancreatic or skin allografts, even with the use of nonspecific immunosuppression and a weak histocompatibility barrier. Third-party cardiac allografts were not protected by the blood pretreatment, attesting to the specificity of the transfusion effect. Addition of azathioprine during the blood pretreatment neither interfered with nor significantly improved the results seen with transfusion alone. The graft prolongation that follows blood pretreatment appears to be influenced by many factors, such as donor-host histocompatibility, the specific tissue transplanted, the blood transfusion schedule, and the use of adjunctive immunosuppression--but presently it is an unpredictable phenomenon.
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Primary mycobacterial infections developed in five of 565 patients who had transplants during a 15-year period. All had negative PPDs and normal chest roentgenograms; none had tuberculosis before transplantation. Atypical mycobacteria were cultured in three of five infections. All were treated with a multiple-drug regimen, including isoniazid, rifampin, ethambutol, and streptomycin sulfate. In four of five patients, there were serious drug-related complications. No major initial alteration of immunosuppressive therapy was necessary in any of the patients. During the study, a treatment policy was followed that included one year of isoniazid treatment of all recipients with a positive PPD, history of tuberculosis, chest x-ray film suggestive of tuberculosis, or PPD-positive donor. An additional 14 transplant recipients were treated in accordance with this policy without complications or subsequent mycobacterial infections (32-month average follow-up). Despite the low incidence of mycobacterial infection in this series, the potential lethality and morbidity mandate constant vigilance.
Glutaraldehyde-tanned, mesh-reinforced, mandrel-grown ovine collagen conduits were compared with tanned human umbilical arteries and polytetrafluoroethylene (PTFE) grafts in the aorta of rat recipients. All grafts had 100% patency and became lined by a cellular neointima. The mean maximum thickness of the neointima of the tanned human umbilical artery, ovine collagen graft, and the PTFE grafts was 68, 57, and 13 micrometer, respectively. Neointimal proliferation was complete for the two biosynthetic grafts, but none was seen in the center of the PTFE grafts as late as ten weeks. The mean increase in lumen cross-sectional area was 49% for the umbilical artery grafts, 23% for ovine collagen conduits, and 4% for the PTFE grafts. Longer follow-up periods will be required before unqualified support can be given to clinical trials of these small-diameter prostheses; however, long-term patency for synthetic grafts of such a small caliber is encouraging for future microvascular applications and for study of host-prosthesis interactions.
Since June 1979, percutaneous transluminal angioplasty (PTA) has been the procedure of choice for renal transplant artery stenosis (RTAS) at the Hospital of the University of Pennsylvania. Of 241 renal allograft recipients, 17 (7%) when studied by arteriogram because of suspected RTAS proved to have significant stenosis (the mean reduction in luminal width for the group being 68%) and underwent PTA. RTAS was equally prevalent in cadaver and related kidney allografts and was no less common in HLA-identical related donor grafts, arguing against the importance of immune factors in etiology. RTAS was equally prevalent whether the anastomotic technique was end to end or end to side. However, when RTAS occurred after end to side anastomoses, it was usually postanastomotic. Fifteen of 17 of the attempts at dilation by PTA were successful by angiographic analysis. Thirteen of the 15 successfully dilated patients had long-term allograft survival and in all of these instances blood pressure (BP) was decreased after PTA. After a mean of 67 weeks, BP decreased from a systolic of 184 +/- 24 mm Hg pre-PTA to 135 +/- 15 mm Hg (P less than 0.001) and from a diastolic of 115 +/- 10 mm Hg pre-PTA to 87 +/- 11 mm Hg (P less than 0.001). The majority of patients continue to require antihypertensive drugs but in a less vigorous regimen than pre-PTA. Serum creatinine level fell following PTA from 1.9 +/- 0.6 to 1.7 +/- 0.5 mg/100 ml (P less than 0.01). Repeat angiographic study was done in nine patients, an average of 61 weeks after PTA, and no recurrent RTAS was identified. Three minor complications of PTA occurred but none led to long-term sequelae. Thus, we believe PTA of RTAS is relatively safe, carrying less mortality and morbidity than operative treatment, and is capable of improving BP control and renal allograft function.
Seventeen patients with acute peripheral arterial or graft occlusion were treated with local low-dose intra-arterial streptokinase. The series includes eight patients with native vessel occlusion, six patients with vein graft occlusion, two patients with prosthetic graft occlusion, and one patient with renal allograft artery occlusion. The duration of occlusion prior to streptokinase therapy varied from 2 hours to 5 weeks. The treatment was successful in 14 of the 17 instances. In conjunction with the successful thrombolytic therapy, percutaneous transluminal angioplasty was performed subsequently in 10 of the patients and reconstructive surgery in three. One major and five minor hemorrhagic complications occurred and were considered to be secondary to the streptokinase therapy. In follow-up of up to 9 months, 11 of the 14 successfully treated patients continued to have a good result, without any indication of recurrent arterial occlusion. Two patients have died of causes unrelated to thrombolytic therapy and one patient required bypass grafting for recurrent thrombosis. None of the successfully treated patients lost a limb. Of the three patients in whom thrombolysis was unsuccessful, two required amputation. Local intra-arterial low-dose streptokinase appears to be a promising alternative to immediate operative treatment in carefully selected cases of arterial occlusion. Definitive treatment of the underlying cause of the thrombus usually is required and changes of success may be enhanced by the thrombolytic therapy.
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The clinical results of vascularized pancreas transplants have improved somewhat during the last 5 years, the but technical problems of handling the pancreatic duct remain difficult. Clinical isolated islet allografts have rarely if ever succeeded. Rejection appears to be a more severe problem in pancreas or islet transplants than in other pancreas transplants. Nevertheless, if nonendocrine cells can be completely removed, transplanted beta-cells might have prolonged survival, since they probably lack Ia antigens that may be necessary to evoke an immune response. An additional biologic problem is the possible destruction (independent of rejection) of transplanted islet cells by autoimmune insulitis. This has been found to occur in spontaneously diabetic rats who received transplanted islets. Study of this animal model may provide important clues to the etiology and treatment or prevention of diabetes.
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A new modification of the mandril-grown vascular prosthesis appears to combine the best features of presently available synthetic vascular replacement materials. Glutaraldehyde-tanned polyester mesh-supported conduits (diameters 4, 6, and 8 mm) grown in the subcutaneous tissue of sheep, maintain 100% patency in the aortic, aortoiliac, and common iliac positions of canine recipients for over 2 years. One-millimeter diameter grafts placed in the infrarenal abdominal aorta of rat recipients were patent in 72% for 6-month follow-up periods. The grafts maintained a modicum of antigenicity despite tanning, as evidenced by the slightly elevated hemagglutination (0 to 2 dilutions) titers against sheep red blood cells in ovine graft recipients and the accelerated rejection of the donor strain skin grafts in Fischer rats receiving Brown-Norway conduits. Finally, in a limited clinical study, 21 of 24 femoropopliteal and three of three femoroposterior tibial grafts remained patent in short follow-up periods (2 to 16 months). Two aortocoronary bypass grafts have continued to function in one patient for 19 months. Minimal inflammatory reaction and no aneurysmal degeneration were found in the material studied.