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Biomedical subjects

A Shaked

Publications and source records attributed to A Shaked.

At least 91 records · Page 5Linked to original sources
PubMed1994

UCLA liver transplantation: analysis of the first 1,000 patients.

Graft and patient survival rates for Black patients were higher than for any group. This may be due to the younger age distribution among Black transplant recipients versus other races at UCLA. Graft and patient survival for Asian patients were significantly lower than for any other group. However, this result was not totally accounted for by the rapid recurrence of disease in hepatitis B patients. Patients with a positive flow cytometry crossmatch had significantly lower first and second graft survival rates due to early graft loss. Patients with PRA of more than 10% had a higher proportion of positive flow crossmatches. However, as a group, patients with more than 10% PRA did not demonstrate decreased graft survival. Consideration should be given to prospectively flow crossmatching the more than 10% PRA group. Patients with zero-DR mismatches had better survival than patients with one- and 2-DR mismatches. Prospective HLA matching in OLT patients is not currently done.

Adolescent↗
PubMed1994

In vivo adenoviral-mediated human p53 tumor suppressor gene transfer and expression in rat liver after resection.

BACKGROUND: The aim of this study was to establish a clinically relevant model for gene transfer to liver with an adenoviral vector encoding wild-type p53 as a first step toward use of this class of gene products in the treatment of primary and metastatic liver tumors. METHODS: Full-size or 50% hepatectomized rat livers were subjected to asanguineous portal perfusion with a replication-defective adenoviral vector encoding wild-type p53 (Ad5p53), whereas control animals received adenoviral vector encoding Escherichia coli beta-galactosidase (beta-gal) (Ad5LacZ) or Ringer's lactate only. Liver biopsy specimens, blood samples, and liver weight were serially obtained. Gene transfer and expression were confirmed by X-Gal staining for gamma-gal, DNA/RNA polymerase chain reaction, (PCR) and Western blots for p53 and beta-gal. Liver integrity was assessed by histologic findings, serum transaminase levels, and synthetic function. RESULTS: The gene transfer rate in whole liver and after hepatectomy ranged from 20% to 40%. DNA PCR showed Ad sequences in livers transduced with Ad5p53 and Ad5LacZ. RNA PCR and Western blot confirmed expression and production of recombinant wild-type p53. Liver regeneration was not affected by p53 gene transduction. Liver histologic findings and synthetic function were not different between transduced and control groups. CONCLUSIONS: Ad5p53 gene transfer to full-size or hepatectomized livers is efficient. Liver regeneration and hepatocyte function are unaffected by overexpression of p53. Adenovirus-mediated tumor-suppressor transduction of the liver is a safe and promising adjuvant in cancer gene therapy.

Adenoviridae↗
PubMed1994

Role of 99mTc-labeled DISIDA scan in the assessment of marginal liver grafts after orthotopic transplantation.

Accurate prognostic indicators are lacking for livers with early marginal graft function, making the decision to re-transplant a difficult one. Therefore, we studied 99mTc-labeled DISIDA scanning as a predictor of recovery of marginal grafts. Records of 28 liver transplant recipients with prolonged periods of marginal graft function after liver transplantation were analyzed. Twelve of 28 (Group I) had delayed PNF and were re-transplanted within 3-8 days (mean 5.3) of surgery. The remaining 16 (Group II) recovered slowly, with normal graft function at 1 month. All patients received DISIDA scans 2 to 5 d after surgery. Clearance of tracer from the blood pool was slower in Group I patients (77S +/- 241 sec) than in Group II (260 +/- 38 sec; p < 0.01). Qualitative differences in the pattern of parenchymal uptake were also noted. Homogenous uptake, consistent with cholestasis, was seen in 15/16 (94%) Group II patients, with improved uptake after 7-35 d. In contrast, 11/12 Group I patients had non-homogenous uptake, consistent with multiple liver infarctions. This pattern correlated with higher peak SGOT in Group I (4358 +/- 658 U/dl vs 1636 +/- 127 U/dl p < 0.01), and PT (20 +/- 0.7 sec vs. 16.5 +/- 0.36 sec; p < 0.01). In summary, delays in DISIDA tracer clearance from blood, and non-homogenous hepatic uptake correlate with elevated liver function tests and with delayed PNF. Homogenous uptake correlates with graft recovery. DISIDA scans may, therefore, be useful in predicting recovery of marginal grafted livers.

Adult↗
PubMed1993

Diagnosis and treatment of bowel perforation following pediatric orthotopic liver transplantation.

OBJECTIVE: Bowel perforation is a frequent cause of mortality after pediatric orthotopic liver transplantation. The aims of this study were to identify the cause of this phenomenon and to examine current methods of treatment. DESIGN: This is a retrospective analysis of 246 pediatric patients who underwent orthotopic liver transplantation at a large, urban, tertiary care medical center between 1984 and 1992. We examined the frequency of bowel perforations after transplantation and identified predisposing factors and signs. In this series, bowel perforations occurred in 24 of 246 recipients and were common in those who had previous liver-related surgery (22 patients). Clinical signs included fever (13 patients), leukocytosis (14 patients), and free air on abdominal roentgenograms (11 patients). RESULTS: Perforation occurred at the Roux-en-Y limb in 15 of 24 recipients as well as in the right transverse colon (five patients), terminal ileum (three patients), and duodenum (one patient). The repair was resection and/or primary closure (18 patients), or diversion (six patients). Recurrent perforations (nine patients) could not be attributed to the method of the repair. Perforation-related sepsis was the primary cause of death in 12 patients (50%) and was more common among patients who developed recurrent perforation (seven [78%] of nine patients). CONCLUSIONS: The occurrence and location of bowel perforation after pediatric orthotopic liver transplantation suggests that the cause is related to bowel injury during difficult hepatectomy. Mortality may be reduced by early second-look operations in high-risk patients.

Child↗
PubMed1993

Celiac compression syndrome and liver transplantation.

OBJECTIVE: The authors assessed the prevalence and clinical significance of the celiac compression syndrome in liver transplantation patients. SUMMARY BACKGROUND DATA: Compression of the celiac axis by the median arcuate ligament of the diaphragm, causes a decrease in celiac artery blood flow which may lead to hepatic artery thrombosis in patients undergoing orthotopic liver transplantation. METHODS: From July 1991 to July 1992, 17 (10%) cases of celiac compression syndrome were identified among 164 consecutive adult patients who underwent liver transplantation. The diagnosis was confirmed by blood flow recording demonstrating a typical pattern of accentuated decrease in celiac blood flow during expiration. RESULTS: Surgical transection of the median arcuate ligament resulted in normalization of the hepatic artery blood flow. In two cases (11.7%), an interposition iliac graft from the recipient supra-celiac aorta was used for the arterial reconstruction. During the follow-up period of up to 15 months, there was no incidence of hepatic artery thrombosis. CONCLUSIONS: The clinical significance of the celiac compression syndrome is evident in liver transplantation in which the collateral circulation to the liver is compromised and the celiac artery remains the only source of arterial blood. It is imperative to identify and remove the obstruction of the celiac axis to prevent severe complications and potential graft loss.

Adult↗
PubMed1993

Endoscopic management of biliary fistulas complicating liver transplantation and other hepatobiliary operations.

OBJECTIVE: This study was undertaken to prospectively evaluate the efficacy and safety of endoscopic management of biliary fistulas complicating liver transplantation and other hepatobiliary operations. SUMMARY BACKGROUND DATA: Surgical therapy has been the traditional approach to large or unresolving biliary fistulas complicating liver transplantation. Although endoscopic management is rapidly becoming an acceptable alternative to surgery for the treatment of biliary fistulas complicating non-liver transplant hepatobiliary operations, it has received limited attention in the liver transplant setting. METHODS: During a 15-month period, 146 adults underwent liver transplantation with biliary reconstruction by end-to-end choledochocholedochostomy over a T-tube. Inadvertent T-tube migration or intentional T-tube removal resulted in bile peritonitis in 18 patients. The patients were treated with a nasobiliary tube (n = 13), internal stent plus endoscopic sphincterotomy (n = 3), or internal stent alone (n = 2). Thirteen patients had a biliary fistula after other hepatobiliary operations and underwent endoscopic therapy during a similar period. All 13 had an endoscopic sphincterotomy with removal of obstructing stones when present (n = 6). Twelve patients also had stents placed. All patients were prospectively followed after hospital discharge and assessed for recurrent symptoms suggestive of biliary tract disease and procedure-related complications. RESULTS: Endoscopic retrograde cholangiopancreatography (ERCP) identified a biliary fistula at the T-tube insertion site into the bile duct in all 18 liver transplant patients. Seventeen patients had resolution of their symptoms within 12 hours of therapy. The fistula sealed in 94.4%. In the other hepatobiliary operation group, ERCP demonstrated contrast extravasation from the biliary tree in 12 of 13. The biliary fistula closure rate was 92.3%. The endoscopic complication rate for the two groups was 3.2%. During a mean follow-up of 9 months, recurrent biliary tract complications occurred in 11.1% of the liver transplant group and 0% in the other hepatobiliary operation group (p > 0.05). The 30-day mortality rate was 0%. CONCLUSIONS: The results of this study support the application of endoscopic management of biliary fistulas complicating orthotopic liver transplantation and other hepatobiliary operations. This approach was relatively safe and obviated the need for surgical intervention.

Adolescent↗
PubMed1993

Arterial ketone body ratio in pediatric liver transplantation.

Arterial ketone body ratio (AKBR) was measured serially in 49 pediatric orthotopic liver transplantations. The AKBR pattern correlated with hepatic synthetic function, as well as with short-term graft and patient survival. A rapid recovery pattern of AKBR to above 1.0 within 40 hr after reperfusion was associated with 94% graft and patient survival. Pediatric liver grafts were found to have better tolerance to low energy levels when compared with previously published data for adult OLT. The salvage rate of pediatric grafts exhibiting a slow recovery pattern (AKBR 0.7-1.0) was 71%. No recovery pattern (AKBR < 0.7) was seen in all 6 cases of primary nonfunction, and in 3 of 4 cases of early hepatic artery thrombosis (HAT). All these grafts were lost; however, 56% of the children in this group survived retransplantation. Unlike the PNF grafts, the no recovery pattern after HAT was characterized by gradual improvement of the synthetic function, despite the low energy state.

Arterial Occlusive Diseases↗
PubMed1993

Differences in oral FK506 dose requirements between adult and pediatric liver transplant patients.

The oral dose recommendation for FK506 (Fujisawa Pharmaceutical, Deerfield, IL) after liver transplantation has, to date, made no distinction between adult and pediatric patients. Sixteen pediatric and 33 adult liver transplant patients treated long term with oral FK506 were studied. Initial FK506 doses were 0.3 mg/kg/day p.o. or 0.15 mg/kg/day i.v. Thereafter, doses were adjusted to achieve therapeutic FK506 serum levels (0.5-3.0 ng/ml, ELISA liquid/liquid separation) and to maintain an acceptable serum creatinine. FK506 (in mg/kg/day), FK506 levels, and liver function were assessed at monthly intervals on outpatient visits. The mean age of 16 pediatric patients was 5.3 +/- 3.5 years and of 33 adult patients was 49 +/- 12 years. Mean days of FK506 therapy were 284 +/- 136 for pediatric patients and 239 +/- 112 for adult patients. For each time period, pediatric patients required a significantly higher dose of FK506 compared to adult patients (P < 0.001). The overall mean pediatric dose for the first year was 0.46 +/- 0.4 mg/kg/day compared to the mean adult dose of 0.13 +/- 0.01 mg/kg/day. The ratio of pediatric to adult oral FK506 dose requirements ranged from 2.7 to 4.4 over the 1 year of followup. FK506 levels monitored at the same time points showed no significant differences at any month between pediatric and adult patients. We conclude that the oral dose per kilogram per day of FK506 required to maintain similar FK506 levels is significantly greater in pediatric patients compared to adult recipients during the first year of follow-up. Pediatric recipients require substantially more, and adult recipients substantially less, than the recommended oral FK506 dose to achieve a therapeutic effect.

Administration, Oral↗
PubMed1993

A comparison of renal function in cyclosporine- and FK-506-treated patients after primary orthotopic liver transplantation.

In this randomized controlled trial comparing FK-506 to CsA, we report parameters of nephrotoxicity in adult patients surviving > 90 days after orthotopic liver transplant (OLT). Patients randomized to FK-506 first received 0.15 mg/kg IV/day followed by 0.3 mg/kg PO/day. Doses were modified to avoid toxicity and to achieve FK-506 levels of 0.5 to 1.5 ng/ml. CsA was administered in the usual manner with dose adjustments to whole blood HPLC levels. A pre-OLT glomerular filtration rate (GFR) of > or = 30 ml/min/1.73/m2 and/or serum creatinine < or = 2.0 mg/dl were required for inclusion in the study. GFRs were obtained at post OLT days 28, 180, and 360. Other parameters of renal function evaluated were creatinine, magnesium, serum electrolytes, blood pressure, use of antihypertensives, and magnesium supplements. There were 38 patients in the FK-506 group and 34 in the CsA group. The mean days of follow up for each group was similar: 456 +/- 135 days for the FK-506 group and 451 +/- 112 days for the CsA group. The mean oral dose for the FK-506 group ranged from 0.13-0.16 mg/kg/day with mean FK-506 levels of 0.6-0.8 ng/ml. In the FK-506 group, there was a significant fall in the pre-transplant GFR from 89 +/- 31 ml/min/173 m2 to 43 +/- 15 ml/min/173 m2 at day 360. Similarly, for the CsA group, the pre-transplant GFR of 75 +/- 31 ml/min/1.73 m2 fell to 49 +/- 17 ml/min/1.73 m2 at day 360. At each time point studied, there was no significant difference in mean GFR between the two groups. There were no significant differences in the monthly mean values for creatinine, electrolytes, magnesium, or blood pressure between the two groups. Magnesium levels were in the low normal range (1.4-1.6 mEq/L), and the mean potassium levels in the high normal range (4.4-4.7 mEq/L). In both groups, a similar number of patients required magnesium supplementation or hypertensive medications. The nephrotoxicity of FK-506 given at low oral doses and with concomitant low levels was comparable to that of CsA. The two drugs were remarkably similar in their spectrum of electrolyte disturbances and incidence of hypertension.

Adult↗
PubMed1993

Radical resection combined with liver transplantation for foregut tumors.

Between February 1984 and July 1992, six adults with advanced pancreatic adenocarcinoma (n = 1), pancreatic neuroendocrine tumor (n = 2), and cholangiocarcinoma (n = 3) underwent radical foregut resections (n = 3) or radical pancreaticoduodenectomy (n = 3) combined with liver transplantation. The major postoperative complications included diarrhea (n = 4), pancreaticojejunostomy leak (n = 3), infection (n = 7), malnutrition (n = 3), refractory ascites (n = 2), and late hepatic artery thrombosis (n = 1). Tumor recurrence occurred in one patient. The actuarial survival for the group is 82 per cent at 1 year and 55 per cent at 2 years. The results demonstrate that radical pancreaticoduodenectomy/foregut resections combined with liver transplantation offer potential surgical cure of malignancies involving these organs. However, the procedure is formidable, with frequent complications.

Adenocarcinoma↗
PubMed1993

The role of combined liver/kidney transplantation in end-stage hepato-renal disease.

The study describes the indications and results of combined liver/kidney transplantation in eight patients suffering from end-stage hepato-renal diseases. The causes of primary renal failure were hyperoxaluria type I (2/8), diabetic nephropathy (2/8), glomerulonephritis (2/8), congenital pyelonephritis (1/8), and polycystic kidneys (1/8). Only five of these patients were on chronic dialysis prior to transplantation. The indication for kidney transplantation in the other three patients was low GFR (< 20 mL/min) and the anticipation of further deterioration of the renal function after liver transplantation as a result of cyclosporine toxicity. The end-stage liver diseases were chronic active hepatitis (4/8) and alcoholic cirrhosis (2/8). There was no evidence for liver failure in two patients undergoing combined transplants for primary hyperoxaluria. The 1-year patient survival rate is 75 per cent, and at that time, kidney and liver function were found to be within normal range. In conclusion, excellent long-term patient survival, as well as kidney and liver graft function, can be achieved in patients suffering from complex end-stage disease of both organs who undergo combined liver and kidney transplantation.

Adult↗