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Biomedical subjects

R B Freeman

Publications and source records attributed to R B Freeman.

At least 37 records · Page 2Linked to original sources
PubMed1999

Acute transjugular intrahepatic portosystemic shunt migration into pulmonary artery during liver transplantation.

Transjugular intrahepatic portosystemic shunt has become an accepted intervention to treat sequelae of end-stage liver disease such as refractory ascites and esophageal varices for patients awaiting liver transplantation. Technical difficulties in such patients at the time of transplantation are usually limited to malpositioning of the stent requiring modification of the usual vascular anastomoses. Migration of the stent intraoperatively has not been a reported complication in the literature. We report a case in which a patient with a previously placed transjugular intrahepatic portosystemic shunt underwent successful liver transplantation complicated by intraoperative migration of the stent into the left pulmonary artery. The stent was removed from the pulmonary artery postoperatively using interventional radiology techniques.

Foreign-Body Migration↗
PubMed1999

Tumor necrosis factor genetic polymorphisms correlate with infections after liver transplantation. NEMC TNF Study Group. New England Medical Center Tumor Necrosis Factor.

Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory mediator of the immune response to allogenic and infectious stimuli. Non-immunosuppressed individuals possessing a NcoI restriction enzyme site in the TNF gene locus produce less TNF-alpha in vitro and in vivo compared with individuals lacking this restriction site. We performed polymerase chain reaction amplification and restriction enzyme fragment length analysis of the TNF locus from 86 liver transplant recipients to determine if presence of the NcoI site is associated with the frequency of rejection or infection, time to rejection or infection, and patient and graft survival. We controlled for recipient primary diagnosis, age, sex, United Network for Organ Sharing status, year of transplant, type of immunosuppression, use of anti-lymphocyte agents, and graft ischemia time. Fifty-six recipients possessed the NcoI+/low TNF-alpha genotype and 30 were NcoI-/high TNF-alpha genotype. In the first year after transplant, there were no significant differences in the frequency, or time to first rejections or the overall number of rejection episodes between the two genotypes. NcoI+/low TNF-alpha genotype recipients had significantly more infections (1.52 vs. 0.87, P=0.014). In a linear regression, multivariate model controlling for all marginally significant variables, the NcoI+/low TNF-alpha genotype was still associated with significantly more infections (P=0.0031). Patient and graft survival were equal for the two groups. One implication of this study, in individuals genetically predetermined to be low TNF-alpha producers, is that additional inhibition of TNF-alpha production by routine immunosuppression may be excessive, rendering these individuals less able to respond to infectious stimuli. These patients may benefit from lower doses or withdrawal of corticosteroids.

Adult↗
PubMed1999

A review of interleukin-2 receptor antagonists in solid organ transplantation.

Daclizumab and basiliximab, engineered human IgG monoclonal antibodies to the interleukin-2 (IL-2) receptor alpha-subunit, were approved to prevent acute rejection after renal transplantation. Daclizumab was studied in adult and pediatric renal allograft recipients, liver allograft recipients, and calcineurin-sparing protocols in renal transplant recipients. Basiliximab was studied in renal allograft recipients and subgroups of recipients of living-related and cadaveric transplants, and in patients with diabetes mellitus. Both agents reduced acute rejection and were associated with few adverse effects. However, information regarding their long-term effects on infection, malignancy, chronic rejection, and patient survival must be available before a final decision is made regarding their proper administration. We propose that a likely role the drugs will play in the field of solid organ transplantation is in new protocols that allow sparing of other more toxic immunosuppressive agents.

Adult↗
PubMed1998

Renal tubular dysfunction in patients with cystic disease of the kidneys.

OBJECTIVE: To define the renal tubular functional abnormalities in patients with cystic disease of the kidneys. METHODS: Patients with autosomal dominant polycystic kidney disease (ADPKD) (n = 4) and medullary sponge kidneys (MSK) (n = 3) with normal glomerular filtration rate (GFR), determined by inulin clearance, and effective renal plasma flow (ERPF), measured by p-aminohippurate clearance, underwent measurement of proximal and distal tubular functions. Proximal tubular functions were determined by the maximum reabsorption of glucose (TmGlucose) and the maximum secretion of p-aminohippurate (TmPAH). Distal tubular functions were measured by the maximum urinary concentrating and diluting mechanisms, and the urinary acidification response to acid load. RESULTS: TmGlucose was low in both groups (209 +/- 25 mg/min/1.73 m2 in the ADPKD group and 110 +/- 28 mg/min/1.73 m2 in the MSK, compared with 375 +/- 40 mg/min/1.73 m2 in healthy controls; P < 0.05). Likewise, TmPAH was significantly diminished in patients with ADPKD (72 +/- 6 mg/min/1.73 m2) and MSK (63 +/- 5 mg/min/1.73 m2) when compared with healthy controls (89 +/- 4 mg/min/1.73 m2; P < 0.05). Urinary maximum concentration after fluid deprivation was impaired in both ADPKD and MSK patients, but the diluting mechanism was intact. Finally, the ability to excrete urinary ammonium and titratable acids following an oral acid load was inadequate in both the ADPKD and MSK groups. CONCLUSIONS: Proximal and distal tubular functions are impaired in patients with ADPKD and MSK when GFR and ERPF are normal, indicating tubular disruption by the cysts and the alteration of the tubulo-interstitial vascular relationship.

Adult↗
PubMed1997

How much do immigration and trade affect labor market outcomes?

"This paper provides new estimates of the impact of immigration and trade on the U.S. labor market.... We examine the relation between economic outcomes for native workers and immigrant flows to regional labor markets.... We...use the factor proportions approach to examine the contributions of immigration and trade to recent changes in U.S. educational wage differentials and attempt to provide a broader assessment of the impact of immigration on the incomes of U.S. natives." Comments and discussion by John DiNardo, John M. Abowd, and others are included (pp. 68-85).

Americas↗
PubMed1996

A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection. A report of the Tacrolimus Kidney Transplantation Rescue Study Group.

A multicenter trial was conducted to evaluate the efficacy and safety of tacrolimus in the treatment of refractory renal allograft rejection. Renal transplant recipients experiencing biopsy-proven recurrent acute allograft rejection were eligible if the current rejection episode was refractory to corticosteroids. A total of 73 patients were enrolled, of whom 59 (81%) had previously received at least one course of antilymphocyte antibody as rejection therapy. One-year follow-up was available in 93% of patients. Median time to tacrolimus rescue therapy was 75 days after transplantation (range, 18-1448 days). Therapeutic responses to tacrolimus included improvement in 78% of patients, stabilization in 11%, and progressive deterioration in 11%. The risk of experiencing progressive deterioration was related to the pretacrolimus serum creatinine level: serum creatinine < or = mg/dl, 3%; 3.1-5 mg/dl, 16% (P < 0.04); > 5 mg/dl, 23% (P < 0.02). Twelve-month (from the time of initiation of tacrolimus therapy) actuarial patient and graft survival rates were 93% and 75%. Graft loss occurred in 19 patients (25%) at a median time of 108 days. Fourteen episodes of recurrent rejection were diagnosed in 10 patients (14%), at a median time of 101 days. Eleven episodes of recurrent rejection were treated (three patients underwent transplant nephrectomy), with resolution achieved in nine patients. Antilymphocyte antibody therapy was not used to treat recurrent rejection. Serum creatinine values improved during tacrolimus therapy: median serum creatinine level before tacrolimus, 3.2 mg/dl; median at 1 year after tacrolimus, 1.8 mg/dl. Twelve infections were documented in 11 patients (15%), including cytomegalovirus infection in three patients (4%). Posttransplant lymphoproliferative disorder was diagnosed in a single patient. Tacrolimus whole blood levels averaged 15.0 +/- 9.9 ng/ml at day 7 of tacrolimus therapy and 9.4 +/- 5.1 ng/ml at 1 year, and were consistent among individual centers. Treatment outcome did not correlate with tacrolimus blood levels. The most commonly observed adverse events were neurological and gastrointestinal. Seventy-four percent of patients received tacrolimus for at least 1 year. Tacrolimus therapy was discontinued in 18% of patients for rejection (11% for progressive, unrelenting rejection, and 7% for recurrent rejection). Tacrolimus therapy was discontinued in 8% of patients due to adverse events. In conclusion, tacrolimus rescue therapy provides (1) prompt, effective reversal of refractory renal allograft rejection, (2) good long-term renal allograft function, (3) a low incidence of recurrent rejection, and (4) an acceptable safety profile in renal allograft recipients experiencing refractory rejection.

Acute Disease↗
PubMed1996

The Kaposi sarcoma-associated herpesvirus (KSHV) is present as an intact latent genome in KS tissue but replicates in the peripheral blood mononuclear cells of KS patients.

Short DNA sequences have been identified, originally in association with Kaposi's sarcoma (KS) biopsies, that are highly homologous to oncogenic, lymphotropic herpesviruses. Recently a virus, Kaposi sarcoma associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8), bearing these sequences has been identified in a cell line derived from a body cavity-based lymphoma. In this report, we show that the same sequences are present in KS biopsies as DNA molecules of a form and size characteristic of latent herpesviruses-large, covalently closed, circular episomes. The genomes migrate with an apparent size larger than the herpesvirus Epstein-Barr virus (172 kb). This form of the viral genome was found in four of four biopsies and three of five peripheral blood samples from KS patients. Linear forms of the viral genome, characteristic of viral replication, were not detected in the biopsies, but were present in the peripheral blood of three out of five patients. The sequences for KSHV/HHV-8 were also detected in the blood of four of five allograft patients and three of five healthy donors without KS suggesting that the virus is widespread throughout the human population.

Base Sequence↗
PubMed1996

Serum hepatitis C RNA titers after liver transplantation are not correlated with immunosuppression or hepatitis.

The degree to which immunosuppression and/or rejection influences recurrent hepatitis C (HCV) after liver transplantation (LT) for end-stage HCV cirrhosis remains poorly defined. We quantified serum HCV-RNA in 84 serum samples from 28 anti-HCV-positive patients taken 223 days prior to and up to 1719 days after liver transplantation to determine if cumulative immunosuppression, rejection, or histologic recurrence correlated with HCV-RNA levels. Histologic, serum chemistry, cumulative steroid, and OKT3 and alpha-interferon (INF) dose data were collected at the time of HCV-RNA sampling. Eighteen of 24 evaluable patients (75%) had HCV-RNA detected in their sera after transplant. Eight patients had 14 rejection episodes, 9 patients received OKT3, and 5 were given INF for histologically moderate hepatitis. Five patients died - two of recurrent hepatitis C - and no retransplants were performed for recurrent hepatitis. Of the 23 survivors, 7 have histologic hepatitis - 2 with persistent ascites, and 2 with mild fibrosis. We could show no correlation between HCV-RNA levels and any of the variables examined although a trend toward increasing HCV-RNA levels with increasing numbers of rejection episodes was observed. In addition, histologic recurrence occurred more frequently for patients treated with OKT3. We conclude that the quantity of circulating viral genome is not influenced by immunosuppressive load and does not correlate with laboratory or histologic signs of recurrence. The roles that rejection, and possibly OKT3, play in the recurrence of HCV after liver transplant need further study.

Female↗
PubMed1996

A regional experience with emergency liver transplantation.

Liver transplantation for patients requiring life-support results in the lowest survival and highest costs. A ten year (1983-1993) regional experience with liver transplantation for critically ill patients was undertaken to ascertain the fate of several subgroups of patients. Of the 828 liver transplants performed at six transplant centers within the region over this period, 168 (20%) were done in patients who met today's criteria for a United Network of Organ Sharing (UNOS) status 1 (emergency) liver transplant candidate. Recipients were classified according to chronicity of disease and transplant number (primary-acute, primary-chronic, reTx-acute, reTx-chronic). Overall one-year survival was 50% for all status 1 recipients. The primary-acute subgroup (n = 63) experienced a 57% one-year survival compared with 50% for the primary-chronic (n = 51) subgroup (P = 0.07). Of the reTx-acute recipients (n = 43), 44% were alive at one year in comparison with 20% for the reTx-chronic (n = 11) group (P = 0.18). There was no significant difference in survival for the following: transplant center, blood group compatibility with donors, age, preservation solution, or graft size. For patients retransplanted for acute reasons (primary graft nonfunction (PGNF) or hepatic artery thrombosis [HAT]), survival was significantly better if a second donor was found within 3 days of relisting (52% vs. 20%; P = 0.012). Over the study period progressively fewer donor organs came from outside the region. No strong survival-based argument can be made for separating, in allocation priority, acute and chronic disease patients facing the first transplant as a status 1 recipient. Clearly patients suffering from PGNF or HAT do far better if retransplanted within 3 days. Establishing an even higher status for recipients with PGNF, perhaps drawing from a supraregional donor pool, would allow surgeons to accept more marginal donors, thus potentially expanding the pool, without significantly compromising patient survival. Retransplantation of the recipient with a chronically failing graft who deteriorates to the point of needing life-support is nearly futile, and in today's health care climate, not an optimal use of scarce donor livers.

Acute Disease↗
PubMed1996

Hepatitis C viral infection in liver transplantation.

OBJECTIVE: To study the outcomes of patients who underwent liver transplantation for the primary diagnosis of chronic active hepatitis secondary to hepatitis C virus (HCV). DESIGN AND SETTING: Retrospective review within a university medical center. PATIENTS: Seventy-four adult recipients who received 78 orthotopic liver allografts for the primary diagnosis of chronic active hepatitis secondary to HCV between January 1990 and December 1994. Sixty-seven patients (91%) survived more than 2 months and were analyzed further for recurrent HCV infection. MAIN OUTCOME MEASURE: Recurrence of HCV infection, hepatitis, or cirrhosis and survival rates for patients who were undergoing orthotopic liver transplantation for chronic active hepatitis secondary to HCV. RESULTS: Actuarial survival rates for the entire group were 79.3%, 70.9%, and 64.5% at 1,2, and 3 years, respectively. Four patients (5% underwent retransplantation with an actuarial survival rate of 14.3% at 1 year (P<.05). Thirty-eight patients (57%) had evidence of posttransplant HCV infection, 31 patients (46%) showed histologic evidence of viral hepatitis, and 11 patients (16%) experienced portal fibrosis or cirrhosis. Seven (33%) of the deaths and all retransplantations were secondary to recurrent HCV infection. There were no significant differences in age, sex, United Network of Organ Sharing status, associated diagnoses, intraoperative packed red blood cell requirements, OKT3 use, or 1-, 2-, and 3-year survival rates in the recurrent vs nonrecurrent HCV infection groups. A higher incidence of posttransplant cirrhosis was observed in patients who were treated with tacrolimus (FK 506) (31.8% vs 8.9%, P<.05). Twenty-one patients (70%) received interferon alfa antiviral therapy with a significant benefit in the liver function test results during therapy (P<.01). CONCLUSIONS: Despite recurrence of HCV infection in most patients after transplantation, survival following primary orthotopic liver transplantation for chronic active hepatitis secondary to HCV infection remains favorable, and these patients should continue to be candidates for liver transplantation. In contrast, survival following retransplantation for HCV infection is poor and should be reconsidered. There is an apparent association between the intensity of immunosuppression and recurrent HCV infection and cirrhosis that warrants continued evaluation. Interferon therapy appears to afford benefit to patients in whom recurrent HCV hepatitis develops after transplantation.

Actuarial Analysis↗
PubMed1996

Neuroimaging findings in patients on immunosuppressive therapy: experience with tacrolimus toxicity.

OBJECTIVE: The purpose of this study is to describe the neuroimaging (CT and MR imaging) findings in liver transplant patients who develop severe neurologic side effects during immunosuppressive therapy with tacrolimus and to correlate these findings with clinical signs and tacrolimus levels in blood. SUBJECTS AND METHODS: Brain CT and/or MR imaging was performed on six patients who developed neurologic symptoms while receiving tacrolimus in the post-transplant period. All patients were evaluated by the neurology staff, and imaging studies were independently interpreted by three neuroradiologists. Trough tacrolimus levels in blood were measured with the IMX immunoassay and were correlated with neurologic symptoms and imaging findings. RESULTS: Imaging abnormalities were observed in five of six patients during the course of their neurologic illnesses. For each patient, neurologic symptoms began when the tacrolimus level in blood was at a peak, exceeding the therapeutic limit in all but one case. In five patients, neurologic symptoms eventually resolved after the tacrolimus dose was reduced or after the drug was stopped. Multifocal low attenuation of white matter was the predominant finding seen on CT images, and matching hyperintense white matter foci were observed on long-TR MR images. In three patients, clinical recovery was accompanied by reversal of the white matter abnormalities seen on CT and MR images. CONCLUSION: Immunosuppressive therapy with tacrolimus may produce neurologic side effects that are associated with brain CT and MR imaging abnormalities. Resolution of symptoms and reversal of imaging findings occur when the tacrolimus dose is reduced.

Adult↗
PubMed1995

Multiple organ failure after liver transplantation.

OBJECTIVE: To examine the effect of multiple organ failure after liver transplantation on mortality and resource utilization. DESIGN: Retrospective cohort study. SETTING: Surgical intensive care unit in a tertiary care university hospital. PATIENTS: Consecutive series of 113 adults undergoing liver transplantation between 1984 and 1992. Patients were excluded if they died intraoperatively (n = 2), required retransplantation (n = 8), or had incomplete records (n = 7). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We prospectively developed definitions for organ failure, and quantitated the frequency and related outcomes for mortality and resource utilization. Multiple organ failure was defined as the presence of two or more organ failures. Patients were grouped according to the presence (n = 31) or absence (n = 65) of multiple organ failure. Preoperative severity of illness was assessed by the Acute Physiology and Chronic Health Evaluation (APACHE II) and United Network for Organ Sharing (UNOS) scoring systems. Postoperative outcome data, including hospital survival rate, hospital length of stay, and charges were recorded. The frequency of multiple organ failure after liver transplantation was 32%. The mortality rate in the patients who developed multiple organ failure was 42% vs. only 2% in those patients without multiple organ failure (p < .0001). Patients with four or more organ failures had a 100% mortality rate. Postoperative multiple organ failure was associated with increased hospital length of stay (46 +/- 7 days vs. 29 +/- 2 days; p = .026) and increased hospital charges ($271,497 +/- 29,994 vs. $136,372 +/- 8,310; p < .0001). Higher preoperative APACHE II and UNOS scores predicted postoperative multiple organ failure, but were less accurate tools for predicting risk of death. CONCLUSIONS: Multiple organ failure is associated with death and increased resource utilization in liver transplantation. Pretransplantation severity of illness, as measured by APACHE II and UNOS scoring systems, is an important determinant of postoperative multiple organ failure and outcome.

APACHE↗
PubMed1995

Hemodynamic correlates of outcome in patients undergoing orthotopic liver transplantation. Evidence for early postoperative myocardial depression.

OBJECTIVE: To describe the hemodynamic and oxygen transport patterns in survivors and nonsurvivors following liver transplantation (LT) and to assess their relationship to organ failure and mortality. DESIGN: Retrospective cohort. SETTING: Surgical ICU in a tertiary care university teaching hospital. PATIENTS: Consecutive series of 113 adults undergoing LT between 1984 and 1992. Patients were excluded if they died intraoperatively (n = 2), required retransplantation (n = 8), or their records were incomplete (n = 7). MEASUREMENTS AND MAIN RESULTS: Preoperative severity of illness was assessed by the acute physiology and chronic health evaluation (APACHE) II scoring system. Hemodynamic and oxygen transport variables were recorded immediately preoperatively and sequentially every 12 h during the first 2 postoperative days. Organ failures (pulmonary, renal, cardiovascular, hepatic, and central nervous system) were assessed for patients in the postoperative period. Patients were grouped as survivors (n = 82) or nonsurvivors (n = 14) with a mortality rate of 15%. Preoperative APACHE II scores were significantly lower in survivors compared with nonsurvivors (7 +/- 0 vs 11 +/- 2; p = 0.029). Both preoperatively and postoperatively, survivors sustained a relatively higher mean arterial pressure, stroke volume index, left ventricular stroke work index, cardiac index, and oxygen delivery as compared with nonsurvivors (p < 0.01). The postoperative decline in systemic blood flow that was seen in both groups was particularly prominent in nonsurvivors during the first 12 h following LT (p < 0.03). Nonsurvivors sustained an approximately fivefold increase in the rate of organ failure (p < 0.0001); all patients (n = 6) with 4 or more organ failures died. CONCLUSION: Nonsurvivors of LT have less cardiac reserve pretransplant; postoperatively, they demonstrate early myocardial depression and subsequently lower levels of cardiac index and oxygen delivery. Patients who develop these hemodynamic patterns are more prone to organ failure and death.

APACHE↗
PubMed1994

Is the transjugular intrahepatic portocaval shunt procedure beneficial for liver transplant recipients?

Recent reports document the efficacy of transjugular intrahepatic portocaval shunts (TIPS) for the prevention of portal hypertensive bleeding and have advocated its use as a bridge to liver transplantation. There are no reports, however, analyzing liver transplant results for patients with indwelling TIPS. We reviewed the records of all adult primary recipients with a history of portal hypertensive bleeding or unmanageable ascites transplanted since the TIPS procedure became available in our institution in July 1991. Seven of 20 recipients underwent TIPS before transplant. There were no significant differences between patients with or without TIPS in age, United Network for Organ Sharing status, Child-Pugh score, preoperative prothrombin time, operative time, operative blood product requirement, overall length of stay, and 6-month patient survival after transplant. We noted a trend toward less operative red cell (26.0 +/- 26.2 vs. 31.8 +/- 38.1 U, mean +/- SD) and autologous blood (4,762 +/- 3,335 vs. 13,355 [corrected] +/- 20,460 ml) transfusion and improved patient survival for those with a TIPS. Patients with a TIPS in place waited significantly longer for their transplant (282 +/- 113 vs. 149 +/- 113 days, P = 0.014). There were 2 technical complications related to the TIPS, 1 in a patient who died after rupture of the suprahepatic vena caval anastomosis where the device had traversed the caval/hepatic vein junction and weakened the tissues, and the other in a survivor in whom the device extended into the right atrium and was extracted during the transplant procedure. Three patients with TIPS in place died of sepsis while waiting for a donor organ. We conclude that while the TIPS offers benefits for the liver transplant recipient, placement of the device in small shrunken cirrhotic livers must be precise. Immediate benefits for the transplant candidate may be offset by increased waiting time and technical complications at the transplant operation.

Adult↗