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D W Hanto

Publications and source records attributed to D W Hanto.

At least 37 records · Page 2Linked to original sources
PubMed1996

Primary hepatic pheochromocytoma?

We report a case of a single intrahepatic pheochromocytoma in the absence of an adrenal lesion and no evidence of metastatic disease. The patient had strong clinical and biochemical evidence of a pheochromocytoma. A CT scan was abnormal but nondiagnostic for pheochromocytoma. An 123I-metaiodobenzyl guanidine (MIBG) scan was falsely negative, but an MRI scan showed a definitive hepatic abnormality. After confirmation of endocrine activity by venous sampling, the tumor was surgically removed. The patient's symptoms have resolved and her plasma catecholamine levels as well as her 24-h urine catecholamine excretion have normalized. The case shows an unusual location of an isolated pheochromocytoma and provides an example of a false negative I-123 MIBG scan.

Adult↗
PubMed1995

Classification of Epstein-Barr virus-associated posttransplant lymphoproliferative diseases: implications for understanding their pathogenesis and developing rational treatment strategies.

The Epstein-Barr virus (EBV) is associated with a spectrum of B-cell lymphoproliferative diseases (LPD) that develop following organ transplantation. A classification scheme for these disorders has been developed based on the clinical, histologic, immunologic cell-typing, cytogenetic, immunoglobulin gene-rearrangement, and virologic characteristics of these LPD. Four disease groups have been identified: (a) uncomplicated posttransplant infectious mononucleosis, (b) benign polyclonal polymorphic B-cell hyperplasia, (c) early malignant transformation in polyclonal polymorphic B-cell lymphoma, and (d) monoclonal polymorphic B-cell lymphoma. This classification has furthered our understanding of the pathogenesis of these diverse LPD and has allowed the development of rational treatment protocols.

Cell Transformation, Neoplastic↗
PubMed1995

Alloresponses in vitro and in vivo show restricted T-cell receptor V beta gene usage.

Our studies of V beta restriction in alloresponses have demonstrated that V beta restriction in H-2 + Mls-1a, class I and class II responses in MLC and in H-2 + Mls-1a disparate sponge matrix allografts, supporting the hypothesis that certain alloresponses in vitro and in vivo have more restricted V beta gene usage than previously thought.

Animals↗
PubMed1994

Variations in serum OKT3 concentration based upon age, sex, transplanted organ, treatment regimen, and anti-OKT3 antibody status.

An essential parameter of the efficacy of OKT3 therapy is serial determinations of serum OKT3 levels. We hypothesized that precise monitoring of these levels would optimize treatment protocols. Therefore, enzyme-linked immunosorbent assay (ELISA) technology was utilized to measure OKT3 serum concentrations daily during 263 OKT3 treatment courses in recipients of solid organ grafts. Patient characteristics were: mean age 33 years (0.1-71), 147 male/116 female, 134 kidney/82 liver/47 heart, 122 prophylaxis/141 rejection, and 213 conventional dosing/50 increased dosing. Mean OKT3 levels were higher in women than in men at all time points from day 1 to day 14, reaching the greatest difference between groups on day 7 (849 versus 598 ng/ml, p = 0.004). Patients receiving OKT3 as a component of a prophylactic protocol had higher levels than those receiving the drug for treatment of rejection from day 1 to day 6, with the greatest difference between groups occurring on day 1 (678 versus 333 ng/ml, p < 0.00001). However, from day 7 to day 14 patients receiving OKT3 prophylactically had lower mean OKT3 levels than did those receiving OKT3 for rejection, with the greatest difference between groups occurring on day 11 (555 versus 784 ng/ml, p < 0.05). Liver transplant recipients had significantly higher OKT3 levels than did kidney or heart transplants at all time points. However, more liver patients required increased OKT3 doses to modulate peripheral blood CD3+ cells to < 25/mm3. Kidney recipients had higher levels than did heart recipients. Children < 10 years of age had higher OKT3 levels than did older patients at all time points.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Induction immunosuppression with antilymphocyte globulin or OKT3 in cadaver kidney transplantation. Results of a single institution prospective randomized trial.

Improved cadaver kidney allograft survival rates, shorter duration of acute tubular necrosis, and a reduction in the incidence of rejection have been achieved using "quadruple sequential therapy"--AZA, prednisone, and antilymphocyte globulin (ALG) induction followed by the delayed addition of CsA. OKT3 has been shown to be effective in preventing and treating rejection, including steroid- and ALG-resistant rejection episodes. A single institution prospective randomized trial comparing ALG and OKT3 prophylaxis in first cadaver kidney allograft recipients was performed to assess their relative advantages and disadvantages. First cadaver kidney allograft recipients were prospectively randomized to receive 7 days of either ALG (n = 58) or OKT3 (n = 59) as part of a quadruple therapy protocol that included AZA, prednisone, and oral CsA. Patient characteristics, patient survival and causes of death, graft survival and causes of graft loss, incidence of and time to rejection and response to treatment, incidence of infections and their type, renal function, and antibody formation to ALG and OKT3 were examined. The 1-, 2-, and 3-year actuarial patient survival rates were 96% in the ALG group and 98% in the OKT3 group. The graft survival rates were 81.1%, 78.4%, and 78.4% in the ALG group and 84.1%, 78.7%, and 78.7% in the OKT3 group. In ALG-treated patients, 63% never had rejection, compared with 49% in the OKT3 patients (P = NS). In the ALG group 31% had a single rejection, 6% had 2 rejections, and none had 3 rejections, compared with 37%, 12%, and 2% in the OKT3 group. In the ALG group, 43% were steroid responsive compared with 65% in the OKT3 group (P = 0.08). There were 1.44 infections per patient in the ALG group compared with 0.76 in the OKT3 group (P = 0.0004). In the ALG group, 37% of patients developed CMV disease compared with 10% in the OKT3 group (P = 0.001). In donor-positive/recipient-negative patients, 8/10 (80%) in the ALG group developed CMV infection, of which 6 (75%) had severe or moderate CMV disease, compared with 2/15 (13%) patients in the OKT3 group (P = 0.002), of whom only one (6.7%) developed moderate disease. In donor-positive/recipient-positive patients, 8/23 (35%) in the ALG group developed CMV infection, of whom 5/8 (62.5%) developed severe or moderate disease compared with 1/21 (4.8%) in the OKT3 group (P = 0.02). Antibody formation to ALG and OKT3 occurred in 11% and 8% of patients, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1994

Soluble interleukin-2 receptor monitoring during bacterial and viral infections in liver transplant recipients: a comparative evaluation.

We evaluated the significance of serial sIL-2R serum levels as a differential marker of immune activation during bacterial versus viral infections in liver transplant recipients. A comparative evaluation of sIL-2R levels was performed in 76 liver transplant recipients (51 pediatric and 27 adult) during bacterial versus viral infections at 7 days prior to infection diagnosis (DAY-7), the day of diagnosis (DAY 0), peak sIL-2R level and at the end of therapy (END). There were no significant elevations at any time point during bacterial infections in either adult or pediatric transplant recipients. However, adult recipients demonstrated significant elevations during viral infections when comparing DAY-7 to PEAK (3840 +/- 830 vs 7225 +/- 2814 p = 0.03), with PEAK levels significantly higher during viral versus bacterial infections in this population (7225 +/- 2814 vs 4195 +/- 1819). Pediatric recipients demonstrated similar increases in sIL-2R serum levels during viral infections from DAY-7 to PEAK (4932 +/- 887 vs 11323 +/- 2794 p = 0.0012). Significant decreases from PEAK to END were noted during viral infections in both adult and pediatric recipients (7225 +/- 2814 vs 2911 +/- 1376 p = 0.01 and 11323 +/- 2794 vs 5214 +/- 2403 p = 0.006). Pediatric recipients had higher mean sIL-2R levels than adult recipients at all time points during viral infections. In conclusion, significant elevations in mean sIL-2R serum levels were observed during viral but not bacterial infections in pediatric and adult liver transplant recipients. This suggests that serial sIL-2R monitoring is a valuable immunologic marker of viral pathogenesis and may be useful in monitoring the progression of viral infections as well as response to antiviral therapy.

Adolescent↗
PubMed1993

Failure of high-dose oral acyclovir with or without immune globulin to prevent primary cytomegalovirus disease in recipients of solid organ transplants.

PURPOSE: To assess the efficacy of acyclovir and intravenous immune globulin (IVIG) for cytomegalovirus (CMV) prophylaxis in high-risk recipients of solid organ transplants. PATIENTS AND METHODS: We randomized 21 CMV-seronegative organ transplant recipients with seropositive donors (D+R-) to receive oral acyclovir, 800 mg four times daily, or, in addition to acyclovir, IVIG, 300 mg/kg, every 2 weeks for six doses. Patients were followed closely for the development of CMV infection and disease. RESULTS: All but one prophylactically treated patient (95%) developed CMV infection. Fifteen of 21 patients (71%) who received prophylaxis fulfilled criteria for CMV disease. Disease onset was delayed in those who received IVIG, but this did not reach statistical significance. Ganciclovir was used for treatment in 15 of the 21 patients (71%). CONCLUSIONS: Acyclovir, with or without IVIG, did not prevent primary CMV infection or disease in D+R- solid organ transplant recipients at our institution. Moreover, most patients were treated with ganciclovir despite the use of prophylaxis. Given the ready availability of ganciclovir to treat CMV disease, we recommend a reappraisal of the role of CMV prophylaxis by these means in the solid organ transplant population.

Acyclovir↗
PubMed1993

Symptomatic cytomegalovirus infection in renal transplant recipients given either Minnesota antilymphoblast globulin (MALG) or OKT3 for rejection prophylaxis.

To compare the impact of using Minnesota antilymphoblast globulin (MALG) versus the monoclonal antibody, OKT3, on the development of symptomatic cytomegalovirus (CMV) infection, we reviewed a cohort of 130 cadaveric renal transplant recipients enrolled in a prospective comparison of MALG versus OKT3 for rejection prophylaxis. Among the 112 patients at risk for CMV, prophylactic MALG was associated with an increased risk of symptomatic infection (relative hazard [rh] = 3.31; 95% confidence interval CI], 1.50 to 7.30; P = 0.003). Transplantation of kidneys from CMV-seropositive donors into CMV-seronegative recipients (rh = 5.22; 95% CI, 2.34 to 11.63; P = 0.00004), first transplantation (rh = 4.76; 95% CI, 1.06 to 21.3; P = 0.039), and acute rejection therapy (rh = 2.03; 95% CI, 0.98 to 4.21; P = 0.055) were also associated with an increased risk. Prophylactic MALG followed by treatment with any agent for acute rejection was strongly correlated with symptomatic CMV infection (rh = 4.46; 95% CI, 3.71 to 5.21; P = 0.00006). Symptomatic CMV infection was not only more frequent, but more severe in recipients of prophylactic MALG, and more MALG recipients were treated with ganciclovir. There was no difference in rejection rate for the two rejection prophylaxis regimens (P = 0.625). Prophylactic OKT3 results in less risk of symptomatic CMV infection than prophylactic MALG in cadaveric renal transplant recipients who are seropositive for CMV or whose donors are seropositive for CMV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Probable antibody-mediated failure of two sequential ABO-compatible hepatic allografts in a single recipient.

Two sequential ABO-compatible orthotopic liver allografts failed, despite excellent initial posttransplant function, in a patient with preformed donor-specific alloantibodies. There was no evidence of cell-mediated rejection. Retrospective crossmatching of recipient serum, obtained immediately prior to the first transplant, revealed the presence of lymphocytotoxic antibodies directed against donor class I HLA B17, at a titer of greater than 1:32,768. Similarly, lymphocytotoxic antibodies directed against the second donor's class I HLA A2 phenotype were detected on retrospective crossmatching utilizing both the three-wash Amos technique (TWA-CDC), and the anti-human immunoglobulin augmented technique (AHG-CDC), at a titer of greater than 1:32,768. Anti-class I specific alloantibodies were eluted from both failed liver grafts at titers of 1:256. The hepatic necrosis in zones 3 and 2 that were observed on histologic examination, and the profound refractory consumptive thrombocytopenia subsequent to each transplant may have been the result of antibody-mediated rejection by preformed lymphocytotoxic antibodies. Despite the liver's remarkable capacity to withstand antibody-mediated injury, primary humoral rejection following ABO compatible liver transplantation may occur if extremely high titers of performed allospecific lymphocytotoxic antibodies are present.

ABO Blood-Group System↗
PubMed1992

Mediation of skin allograft rejection in scid mice by CD4+ and CD8+ T cells.

We analyzed the role of CD4+ and CD8+ T cells in H-2-disparate skin allograft rejection in the mutant mouse strain C.B-17/Icr scid with severe combined immunodeficiency. On the day of skin allografting, scid mice were adoptively transferred with negatively selected CD4+ or CD8+ splenocytes from normal unsensitized C.B-17/Icr mice. These populations were obtained using a double-mAb--plus--complement elimination protocol using anti-CD4 or anti-CD8 mAb that resulted in no detectable CD4+ or CD8+ cells by FACS and negligible numbers of cytolytic T lymphocytes by limiting dilution analysis in anti-CD8 treated populations. Spleen cells were removed from grafted mice at the time of rejection and were tested in vitro for antidonor reactivity in several assays: mixed lymphocyte culture, cell-mediated lympholysis, and LDA for CTL and for IL-2-producing HTL. The presence of Thy 1.2+, CD4+, or CD8+ cells was determined by FACS. All control C.B-17 mice and scid mice adoptively transferred with nondepleted CD4+, and CD8+ cells rejected skin allografts with similar mean survival times (15.6 +/- 1.5, 18.8 +/- 3.4, 18.0 +/- 5.4, respectively), whereas control scid mice retain skin allografts indefinitely (all greater than 100 days). C.B-17 syngeneic grafts survived indefinitely in all groups. At the time of rejection, splenocytes from scid mice receiving CD4+ cells had negligible donor-specific cytotoxicity in CML and negligible numbers of CTL by LDA, but demonstrated a good proliferative response in MLC and IL-2-producing cells by LDA (frequency = 1/1764). There were no detectable CD8+ cells present by FACS analysis. Conversely, splenocytes from scid mice adoptively transferred with CD8+ cells had strong donor-specific cytotoxicity in CML (58.8% +/- 16.1%) and CTL by LDA (frequency = 1/3448), but no significant proliferation was detected in MLC. There were no detectable CD4+ cells by FACS, but there were small numbers of IL-2-producing cells by LDA (frequency = 1/10,204). These data demonstrate that CD4+ cells adoptively transferred into scid mice are capable of mediating skin allograft rejection in the absence of any detectable CD8+ cells or significant functional cytolytic activity. The adoptive transfer of CD8+ cells also results in skin allograft rejection in the absence of detectable CD4+ cells. The detection of small numbers of IL-2 secreting cells in these mice may indicate that CD(8+)-mediated allograft rejection in this model is dependent on IL-2-secreting CD8+ cells.

Animals↗
PubMed1992

Day-5 protocol liver allograft biopsies document early rejection episodes and are predictive of recurrent rejection.

METHODS: The day-5 posttransplant protocol biopsy specimens and clinical courses of 27 consecutive orthotopic liver transplant recipients followed up at least 6 months were reviewed. RESULTS: Twelve (44%) of 27 patients had histologic evidence of rejection on the day-5 biopsy; 8 (67%) of these 12 patients required OKT3 for reversal of the rejection. No significant differences in biochemical liver test results, bile output, or cyclosporine levels were observed between this group and the 15 patients (56%) without histologic evidence of rejection on day 5. Eight (67%) of the 12 patients with rejection had recurrent rejection episodes, with one recurrence each in six patients, two recurrences in one patient, and three recurrences in one patient. Of the 15 patients without rejection on day 5, nine (60%) subsequently had rejection at 10 days, 14 days, and 1 1/2, 3 1/2, 4, 5, and 11 months after transplantation. Only one (11%) of these nine patients had a recurrent rejection episode. There were no differences in the incidence of posttransplant cytomegalovirus infections between the two groups. Two cases of posttransplant lymphoma were seen; they developed in two patients without rejection on the day-5 biopsy. No patients or allografts were lost to acute or chronic rejection. No complications occurred as a result of the day-5 protocol biopsy. CONCLUSION: The day-5 protocol biopsy is useful in detecting rejection episodes that may not otherwise be clinically apparent.

Adult↗
PubMed1991

Renal transplantation for systemic lupus erythematosus and recurrent lupus nephritis. A single-center experience and a review of the literature.

Prior to 1975 patients with systemic lupus erythematosus were generally not considered candidates for renal transplantation because of concern that immune complex deposition would rapidly destroy the allograft. However, recent evidence suggests that good patient and graft survival rates can be achieved comparable to other renal diseases. Between September 23, 1963 and July 31, 1990, 1070 renal transplants were performed at Washington University Medical Center (WUMC). During this period, 14 patients with SLE (12 female and 2 male) received 16 renal transplants (7 living-related donor [LRD], 1 living-unrelated donor [LURD], and 8 cadaver [CAD]). The mean age at the time of the first transplant was 32.5 +/- 10.3 years. The duration of disease prior to transplant was 88.0 +/- 45.9 months and the duration of hemodialysis prior to transplant was 36.0 +/- 33.7 months. Of these patients, 7/14 (50%) had negative and 3/14 (21%) positive SLE serology pre- and post-transplant, 3/14 (21%) had negative serology pretransplant that became positive posttransplant, and 1/14 (2%) was positive pretransplant and became seronegative posttransplant. Patient survival was 92.8% (13/14), and of the 16 kidneys transplanted 62.5% (10/16) are still functioning with a mean follow-up period of 43.7 +/- 45 months. The current mean serum creatinine was 1.4 +/- 0.26 mg/dl. One noncompliant patient developed recurrent lupus nephritis bringing the total number of cases reported in the literature to seven. The present study demonstrates that patients with SLE can be transplanted with excellent patient and graft survival and function and a low rate of recurrent lupus nephritis. From a review of the literature, there appears to be an association between positive SLE serology pre- and posttransplant and recurrent lupus nephritis.

Adult↗
PubMed1991

Low-attenuation periportal collar in transplanted liver is not reliable CT evidence of acute allograft rejection.

Recent reports indicate that the presence or absence of a periportal low-attenuation rim ("periportal collar" sign) on CT scans is of variable reliability in predicting rejection after liver transplantation. To study this matter further, we reviewed 178 CT scans in 68 patients (74 allografts) after hepatic transplantation. One hundred twenty-one scans were obtained within 7 days of liver biopsy. The presence or absence of a central or peripheral periportal collar on these scans was correlated with the presence or absence of acute rejection found at biopsy. A central periportal collar was defined as an abnormally large amount of low-attenuation material surrounding the main portal vein, the right portal vein, or the left portal vein. A peripheral periportal collar was defined as a low-attenuation area surrounding a portal vein branch distal to the left or right portal veins. A weak, but statistically significant correlation between the presence of a peripheral periportal collar and acute allograft rejection was shown in patients in whom CT scans were obtained within 3 days of biopsy. However, the sensitivity, specificity, accuracy, and positive predictive value of the presence of a peripheral collar in this group were 60%, 67%, 64%, and 63%, respectively. The sensitivity, specificity, accuracy, and positive predictive value of the presence of a central collar in patients scanned within 3 days of biopsy were 74%, 35%, 54%, and 52%, respectively. Negative predictive values of peripheral and central collars were 65% and 59%, respectively. Our study shows that a periportal collar is seen more commonly in patients with recently transplanted allografts (mean interval after transplantation, 46 days for peripheral collars and 57 days for central collars) and in patients with ascites. The presence of a central or peripheral periportal collar on CT is not sufficiently sensitive, specific, or accurate to reliably diagnose or exclude acute allograft rejection.

Adolescent↗
PubMed1991

Immunology of renal allograft rejection.

Allograft rejection remains the critical problem of renal transplantation. The immunologic mechanisms that underlie renal allograft rejection are heterogeneous and involve the humoral and cellular limbs of the immune response. Antibody-mediated hyperacute rejection is now rare owing to improved prospective cross-matching. Chronic rejection, characterized by intrarenal arterial fibrosis, is still poorly understood. Knowledge of the afferent and efferent processes involved in rejection has led to effective therapeutic and experimental strategies that employ monoclonal antibodies and other pharmacologic agents to reverse, or prevent, acute allograft rejection. In addition, allospecific tolerance has been achieved experimentally and clinically in a variety of manners. Preliminary studies on the mechanism of allograft tolerance induced by donor-specific blood transfusions before transplantation suggest a role for an immunoregulatory cell population that specifically down regulates cytotoxic lymphocyte responses to donor antigens in some recipients. A role for noninherited maternal antigens and anti-idiotypic antibodies in down regulating immune responses to allografts have also been reported by several studies. An improved understanding of allograft rejection and tolerance may identify approaches to prolong allograft survival without the morbidity and mortality associated with present-day immunosuppression.

Animals↗