Biomedical subjects
Publications and source records attributed to H Takiff.
A 44-year-old white female developed hepatic hemorrhage due to focal hepatic necrosis. This is the only reported case of its kind we have found. No other underlying processes were identified except for the chronic use of oral conjugated estrogens. The possible role of steroids and a possible relationship to the pathogenesis of peliosis hepatis is discussed.
Thrombosis of the hepatic artery during the early post hepatic transplant period results in massive hepatocyte necrosis, bile duct damage and subsequent graft loss. The incidence of this complication is increased when hepatic arterial reconstruction is possible only by the placement of an interposition infrarenal iliac artery graft. We describe 45 hepatic transplants with difficult arterial reconstruction in which the supraceliac aorta was used for arterial reconstruction. Indications for using the supraceliac aorta as the primary site for arterial reconstruction were inadequate inflow through a narrow recipient common hepatic artery in 51 per cent, previously thrombosed common hepatic artery in 27 per cent, mechanical obstruction of the celiac axis in 13 per cent or intimal dissection in 9 per cent. Direct anastomosis of the donor hepatic artery to the supraceliac aorta was achieved in 22 patients, reducing the need for a graft by 49 per cent. Short segments of iliac artery graft (17 patients) or aortic conduit (six patients) to the supraceliac aortas were required because of insufficient length of the donor artery. The incidence of arterial thrombosis and graft loss were zero per cent in adults and 12.5 per cent in children, both significantly less when compared with the 23.0 to 70.0 per cent thrombosis rate when graft is placed in an infrarenal position. We conclude that routine use of the supraceliac aorta for difficult hepatic arterial reconstruction decreases the need for arterial grafts, the incidence of hepatic arterial thrombosis and loss of hepatic grafts.
The data of the UCLA Kidney Transplant Registry were reviewed with regard to sharing. The percentage of first-cadaver cyclosporine-treated transplants since 1984 with long cold ischemia time increased with sharing distance: 25% of unshared grafts, 40% of locally shared, and 61% of distantly shared ones had cold ischemia times over 24 hr; for cold ischemia times over 36 hr the numbers were 6%, 12%, and 24%, respectively. The immediate function rate did not parallel sharing distance the way cold ischemia time did: 85.7% without sharing, 74.4% with local sharing, and 83.5% with distant sharing. The percentage of well-matched (0 HLA-B,DR mismatches) transplants was low (3-5%) regardless of sharing status. Well-matched shared grafts with cyclosporine immunosuppression had a 9% survival advantage at one year compared with poorly matched unshared ones (85% vs. 76%). Long-term, well-matched shared grafts had a half-life of 11.9 years compared with 7.5 years for poorly matched unshared ones (reflecting graft loss from 3 to 10 years posttransplant). We conclude that sharing for histocompatibility has an overall beneficial effect.
1. Although kidneys from Black donors had a lower one-year survival rate, their early function (as measured by the days of first and best function) was similar to White donors but their hospitalization was longer. 2. Kidneys from donors in the 16-20 year old age group had the best survival rate and early function with falloff as donor age increased and decreased. 3. Trauma death donors yielded better survival rates but similar early graft function and hospitalization to nontrauma death donors. 4. Sharing, even at extended distances, did not adversely effect survival, early graft function, or length of hospitalization.
An immuno-reduction-suppression protocol using spleen cell infusion followed by cyclophosphamide (CP) or azathioprine (AZ) to reduce the immunocompetent cells and maintenance suppression with low-dose cyclosporine (CsA) was highly effective in a rat cardiac transplant model. Following one or two spleen cell infusions, AZ or CP treatment was given before transplantation. After transplantation the animals were maintained with low-dose CsA. Among those treated with AZ, five of eight survived greater than 100 days, and among those treated with CP, six of eight survived greater than 100. These two protocols were far superior to 28 other permutations of treatment consisting of 164 transplants, such as infusions plus AZ without CsA and infusions without AZ but with CsA. We conclude that CsA can most effectively be used in low dose as a maintenance drug and that immunoreduction therapy is optimized by prestimulation and expansion of reactive cells. Another important feature of this proposal is that the immunoreductive risk phase, performed before transplantation, can be separated from the operative risk period. This avoids the conventional superimposition of the two risks.
Using actuarial methods, factors influencing long-term graft survival were examined in 33,594 recent (since 1974) kidney transplants reported to the University of California, Los Angeles, Transplant Registry. One- and 10-year graft-survival rates as well as late (from 3 through 10 years) graft-loss rates (half-lives) were determined. The donor-recipient relationship had the greatest influence on long-term graft survival. Transplants between HLA-identical siblings had graft-survival rates of 89% at 1 year and 68% at 10 years, compared with 76% and 43% for parental donors, and 58% and 26% for cadaver donor transplants, respectively. These differences were also evident from the graft half-lives, which were 22 years for HLA-identical sibling, 12 years for parental, and 8 years for cadaver donor allografts. In cadaver donor transplants, matching for HLA-A,B antigens had the greatest influence on long-term graft survival, with a 15% 10-year graft survival (39% vs. 24%) and 7-year half-life (14 vs. 7 years) advantage seen with the best (zero HLA-A,B mismatches) compared with the worst (4 HLA-A,B) cases, respectively. Some of the factors studied, such as transplant number and pretransplant transfusions, tended to influence the short- rather than long-term graft-survival rates. Others, including HLA-A,B matching, early graft function and the recipient's original disease, influenced both early and late graft survival. Over all, histocompatibility between donor and recipient had by far the greatest influence on the long-term success of renal allografts.
To test the clonal deletion hypothesis, different levels of immunization were carried out by 0, 1, 2, or 3 transfusions preoperatively, together with 10 methods of immunosuppression. In this way, it was hoped that we could determine the optimal way to immunize and the optimal immunosuppressant treatment to deactivate the responding cells. With the Buffalo-to-Lewis rat heart allograft model, the control mean survival rate was 7 days. Rats with 2 or 3 transfusions had 5- and 12-day survival rates, respectively. If azathioprine was given in addition before grafting, 19- and 18-day survival rates were seen, and if azathioprine was given after grafting, extended survivals of 33 and 34 days were achieved. The longest survival rate of greater than 52 days was obtained by a single transfusion and 25 mg/kg/day of cyclophosphamide given before transplantation. Splenectomy following 2 or 3 transfusions prolonged survival rates to 16-18 days, suggesting that mechanical removal of immunized cells is somewhat effective. Most of the antibody produced by one transfusion was IgM, as were antibodies that resulted from transfusions followed by azathioprine. It is possible that reduction of IgG-producing cells is important. These results are consistent with the clonal deletion theory, although they do not necessarily provide final proof. The experiments suggest that the optimal transfusion effect may be obtained with minimal immunization (1 transfusion) and proper immunosuppression before transplantation.
1. Sharing for histocompatibility is underutilized. 2. Sharing results in more transplants with long cold ischemic time. 3. Early graft function does not appear to be adversely affected by sharing and the attendant longer cold ischemic time. 4. Panel reactive antibody levels are not being utilized as a criterion for sharing. 5. Blood type and HLA-DR type do not significantly influence sharing.
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Currently at our institution more than 90% of the children with end-stage renal disease are managed with continuous ambulatory peritoneal dialysis (CAPD) in preference to hemodialysis until a successful transplant is accomplished. Recent refinements in CAPD catheters and dialysis techniques have greatly added to the many medical, psychological, and economic advantages of CAPD compared with chronic hemodialysis. Ninety-three patients less than 21 years of age underwent insertion of 167 peritoneal dialysis (PD) catheters over a 5-year period. A variety of PD catheters were used, including 121 (73%) double-cuff Tenckhoff catheters, 22 (13%) single-cuff, and 24 (14%) column disc catheters (Lifecaths, Physio-Control Corp, Redmond, WA). There were three (3%) noncatheter-related mortalities and minimal significant morbidity during the 1,819 patient-months of catheter use. Exit site infections (61%) and peritonitis (59%) were frequent but minor complications, occasionally requiring catheter replacement. Other noninfectious complications included abdominal hernias (42%), dialysis leaks (14%), distal cuff extrusion (11%), catheter obstruction (7%), and hydrothorax (2%). Forty-five of the 60 hernias (75%) were surgically repaired in patients while receiving CAPD. Persistent or recurrent peritonitis was common with Pseudomonas, Serratia, and fungal infections and often resulted in catheter removal and loss of the peritoneal dialysis membrane. Catheter survival for the double-cuff Tenckhoff was significantly better (P .005) than the single-cuff or Lifecath. Based on this experience we have found that using specific operative techniques for CAPD catheter placement and early surgical management for severe peritonitis reduces the incidence of complications and modality failure.
During a 21-year period, 39 colon interposition operations were performed on 37 children at the UCLA Medical Center and the Childrens Hospital of Los Angeles. The average age at the time of operation was 5.8 years. The indications for operation were esophageal atresia in 23 patients and other benign strictures in 14 patients. The duration of patient follow-up ranged from 6 months to 21 years (mean: 9.7 years). The most common complications were esophagocolonic anastomotic leak (12), esophagocolonic anastomotic stricture (14), pneumonia, and pneumothorax. Fourteen of the 25 patients with retrosternal colon interposition had complications (56%), whereas 10 of 14 patients with left thoracic colon interposition had complications (71%). One patient died (mortality: 3%) after left thoracic interposition because of severe respiratory distress associated with other malformations. Each of the 18 patients with isoperistaltic colon interposition showed rapid transit and emptying, provided that obstruction or extensive dilatation did not occur; reverse colon segments were more dilated and emptied more slowly. The 25 patients with retrosternal colon segments had less colonic distension with better emptying than did the 14 patients with left thoracic interposition. Thirty-two of the 36 children increased their weight percentile after colon interposition. Within 2 years after cervical anastomotic stricture or leak, 78% of these children were asymptomatic and gaining weight. Thirty-one of the 37 patients (84%) had excellent results with colon interposition, with a mean follow-up of 9.7 years. Most of the major postoperative complications occurred within the first few weeks and were corrected during the first few months after operation. Preservation of the esophagus should be the surgeon's first priority; however, prolonged attempts to elongate the esophagus for anastomosis in certain patients with long-gap esophageal atresia have been more hazardous in our experience than has colon interposition.
We reviewed 14,005 renal grafts with the temporal opportunity for 10-year survival (transplanted 1975 and earlier) and analyzed 10-year actuarial graft survival and the rate of late (3- through 10-year) graft loss as reflected by half-life. The 10-year graft survival for first transplants in HLA-identical siblings was 67% versus 38% for parental donors and 20% for cadaver donors. Factors with substantial influence on 10-year graft survival include transplant number, transfusions (0, 17%; greater than or equal to 1,33%), HLA-A,B mismatches (0, 29%; 1-2, 20%, 3-4, 17%), cold ischemia time (0-3 hours, 32%; 4-6 hours, 27%; 7-12 hours, 21%; greater than 12 hours, 16%), preservation method if CIT is no more than 24 hours (cold storage, 22%; machine, 17%), recipient race (Caucasian, 23%; black, 11%), original disease, recipient age, recipient sex, donor race, and the quality of early graft function (less than or equal to one month). Factors not significantly influencing 10-year graft survival were panel-reactive antibodies, warm ischemia time, preservation method if CIT was more than 24 hours, and donor sex.(ABSTRACT TRUNCATED AT 250 WORDS)
1. The influence that a patient's original disease had on the outcome of kidney transplantation was small when recent transplants (1983 to present) were examined. A difference of only 5% was seen in one-year graft survivals of first cadaver donors. The average one-year survival was 70%; patients with pylonephritis having the best (75%) and SLE patients the worst (65%) survival rates among the major disease categories. 2. There was little difference observed in patient survivals or functional graft survivals in first cadaver transplants among patients with different original diseases. This was also the case with cadaver regrafts; with the exception of polycystic kidney patients who had quite poor graft survival (41% at one year) with regrafts. Pretransplant blood transfusions resulted in increased cadaver graft survival; however the low number of nontransfused patients in many disease categories presented difficulties in examining this effect. 3. The use of cyclosporine resulted in increased cadaver graft survival in all disease categories. One-year cadaver graft survival of cyclosporine-treated patients averaged 75% compared to 63% with noncyclosporine-treated patients. A beneficial effect of cyclosporine use was not consistently seen in transplants involving living-related donors, although perhaps larger numbers of patients are required in order to confirm this observation. 4. Graft survival in diabetic patients was quite good in this analysis of recent transplants. First cadaver one-year graft survival in diabetics was only 4% below the overall average and 2% less with cyclosporine. Patients with both juvenile (75% one-year graft survival) and adult-onset (78% one-year graft survival) forms of the disease had good graft survival when cyclosporine was used for immunosuppression.
1. The average serum creatinine level during the first 20 days after transplantation was lower in HLA-identical siblings than in parental donor transplants, suggesting an early effect of histocompatibility. 2. In rather small numbers of patients, the daily average serum creatinine values were not different with HLA-DR mismatching and HLA-B,DR mismatching, but were lower in the better matched transplants for the HLA-A,B loci and the HLA-A,B,DR loci. 3. The average serum creatinine values in the first 20 days after transplantation were correlated with the one-year graft survival rates. Those patients with serum creatinine levels less than 2.4 mg/dl had one-year graft survival rates of over 80% compared with those with serum creatinine levels above 7.5 mg/dl after the first week who had one-year graft survival rates about 30% less. Intermediate serum creatinine values yielded intermediate one-year graft survival rates. 4. The cyclosporine dosage in the first month after transplantation varied considerably among the four centers studied here. These values were not directly correlated with the one-year graft survival rate, average serum creatinine levels or cumulative rejection rates in this preliminary examination. 5. Patients who rejected transplants 11 to 60 days posttransplant had been given lower cyclosporine dosages than those who rejected early or who had no rejections. 6. Although firm conclusions cannot be drawn from the small numbers of patients encompassed in this study, we hope the potential value of this type of analysis will be realized.
During a 28-year period from 1955 to 1983, two cases of massive repetitive arterial thromboembolism from nonaneurysmal aortic mural thrombus were diagnosed antemortem and successfully corrected at the University of California, Los Angeles Medical Center. Within the same time period, 48 cases of nonaneurysmal aortic mural thrombus were identified in 10,671 consecutive autopsies (0.45% incidence). Eight of these patients had evidence of distal embolization (17%), and three had major thromboembolic occlusions, which were considered the proximate cause of death (6%). The latter three patients represented 9% of autopsy-confirmed deaths from peripheral arterial thromboembolism. The diagnosis was established in a 49-year-old man and a 51-year-old woman after a long course marked by recurrent arterial embolization. Despite multiple evaluations, which included angiography, the diagnosis remained elusive until clinical suspicion resulted in complete biplane aortographic survey. Although the morphologic characteristics of this lesion are quite striking, subtle angiographic changes and lack of familiarity with the clinical presentation contribute to the difficulty and infrequency of diagnosis. This unique lesion comprises an important segment of the so-called cryptogenic sources of arterial embolization and can be corrected by a definitive surgical procedure.
Although mesenteric cysts and intra-abdominal cystic lymphangiomas are uncommon and clinically confusing lesions, histologic and ultrastructural evidence suggests that they are pathologically distinct. Differentiation of these lesions is important since lymphangiomas may follow a proliferative and invasive course. Of 28 cases documented at laparotomy, histologically eight patients (29%) had cystic lymphangiomas and 20 patients (71%) had mesenteric cysts. Lymphangioma was found to be exclusively a disease of childhood and young adulthood (mean age, 10 years); mesenteric cyst was found in all age groups (mean age, 44 years), and two thirds of these patients were over 40 years old. Patients with lymphangiomas more frequently were male (75% vs 30%), symptomatic (88% vs 35%), and had ascites (50% vs 0%) and larger lesions (mean, 8.8 vs 4.7 cm) when compared with patients with mesenteric cysts. Complete excision was possible in all but four patients, with no operative deaths and a postoperative complication rate of 7%. After a mean follow-up period of four years, there were no recurrences among 16 patients who had undergone complete excision.
The UCLA Medical Center experience in the surgical treatment of 23 young patients with choledochal cysts over a 28 year period has been reviewed. All patients had saccular or fusiform extrahepatic cysts, and one patient also had a diverticular cyst. Eleven patients had no intrahepatic dilatation, whereas 9 had cylindrical and 3 cystic intrahepatic dilatation. There were 39 operations for biliary drainage performed: 17 Roux-Y choledochojejunostomies, 7 choledochoduodenostomies, 7 excisions, and 8 miscellaneous procedures. The morbidity for initial operations was 17 percent and for reoperations, 31 percent. Biliary calculi were found after 2 of 23 primary operations (9 percent) and 6 of 16 reoperations (37.5 percent). All developed while enteric drainage was present and were primary bile duct stones. No reoperation was necessary after cyst excision. An intrahepatic cholangiocarcinoma developed in one patient treated with enteric drainage. Three of 10 patients who did not undergo cholecystectomy at their initial operation later required laparotomy for cholecystectomy alone. We recommend cholecystectomy and cyst excision when technically feasible for primary operative treatment of choledochal cysts.