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Biomedical subjects

H Takiff

Publications and source records attributed to H Takiff.

At least 37 records · Page 2Linked to original sources

Donor factors.

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.

ABO Blood-Group System↗

Low-dose cyclosporine maintenance therapy after immunosuppressive induction in a rat cardiac transplant model.

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.

Animals↗

Dominant effect of histocompatibility on ten-year kidney transplant survival.

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.

Actuarial Analysis↗

Examination of the clonal deletion hypothesis following transfusions in rat cardiac transplants.

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.

Animals↗

The nature of shared kidneys.

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.

Cyclosporins↗

Surgical management of peritoneal dialysis catheters in children: five-year experience with 1,800 patient-month follow-up.

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.

Adolescent↗

Esophageal replacement with colon interposition in children.

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.

Adolescent↗

Factors important in 10-year kidney transplant survival.

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)

Adolescent↗

Original disease of the recipient.

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.

Diabetes Mellitus↗

Early graft function.

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.

Creatinine↗

Aortic mural thrombus: an occult source of arterial thromboembolism.

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.

Aorta, Abdominal↗

Mesenteric cysts and intra-abdominal cystic lymphangiomas.

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.

Abdominal Neoplasms↗

Choledochal cysts: results of primary surgery and need for reoperation in young patients.

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.

Adolescent↗

Fecal adenoviruses from a longitudinal study of families in metropolitan Washington, D.C.: laboratory, clinical, and epidemiologic observations.

During a 29-month period, we studied enteric infection in 70 families from a pediatric practice in suburban Washington, D.C. Fecal adenoviruses were detected in stools of 18 patients by tissue culture and electron microscopic procedures. From 6 through 11 months of age, the incidence of fecal adenoviruses associated with enteritis was seven per 100, and of confirmed enteric adenoviruses (EAds), three per 100 individuals per year. All EAds belonged to subgenus G (type 41). All three patients with EAds had diarrhea; two had vomiting and one had fever, but none required hospitalization. Ten of the 15 patients with non-EAds were younger than 2 years, and 60% had diarrhea, 40% had vomiting, and 20% had fever. Combined gastrointestinal and respiratory symptoms occurred more often in those who shed non-EAds (three of 11) than in matched controls (two of 48, P = 0.04). An adenovirus was detected in approximately 6% of gastroenteritis episodes, and confirmed EAds were present in approximately 2% of episodes of gastroenteritis in children younger than 2 years of age. None of the contacts of patients with non-EAds shed such virus in their stools. None of nine family contacts of those with EAd appeared to shed adenovirus in stool. In contrast, rotavirus spread readily to exposed adults (25% of 65) and children (56% of 62) when a child in similar families had rotavirus infection.

Adenoviridae↗

Acute renal dysfunction after major arteriography.

The incidence of acute renal dysfunction (ARD) after major arteriography was evaluated by assessment of the change in serum creatinine in 364 patients undergoing arteriography. Major arteriography was defined as abdominal aortography, abdominal aortography with lower-extremity runoff, aortic arch studies, or aortic arch plus selective carotid angiography. The influence of the volume of contrast material received, hydration, and associated risk factors was evaluated. In the entire group, the frequency of postarteriographic ARD was 7.1%. Although most patients recovered, 1.4% required renal dialysis. The frequency of renal dysfunction was significantly higher in patients with preexisting renal disease (14.8%), and 3.7% of these patients went on to require dialysis. In the total group and in those with normal renal function prearteriographically, the frequency of ARD was found to be related to the volume of iodinated contrast material received. Hydration before, during, and after angiography did not prevent this complication. Several risk factors, namely preexisting renal disease, advanced age, volume of contrast material used, type of study performed, diabetes mellitus, and coexistent heart disease were found to be associated with a statistically significant increased risk of postangiographic ARD.

Acute Kidney Injury↗