Acute intracranial complications of temporal bone trauma

BACKGROUND: A total of 110 patients, in whom kidneys from 95 living related and 15 cadaver donor, had experienced renal transplantation between February 1985 and October 1996 in our clinic. This study was conducted to evaluate the influence of the various pre-operative factors to the graft survivals and clinical course of patients in living related renal transplantation. METHODS: In 95 recipients, 17 adult patients had long term graft survivals over 5 years including 6 recurrent or denovo nephritis without chronic allografts nephropathy. Eight failed to graft loss attributed to chronic allografts nephropathy diagnosed within 5 years. Retrospective analysis were performed to elucidate the differences of these recipients. RESULTS: Donors of long graft survival recipients were younger (49.1 +/- 12.1 v.s. 58.9 +/- 10. 2) and had a better renal function evaluated by preoperative creatinine clearance in living related donors (115.5 +/- 37.0 v.s. 79.7 +/- 22.0 1/day). Graft long survival recipients had experienced less frequencies of acute rejection within 6 months (0.53 +/- 0.62: 8 patients, 9 times) compared with chronic allografts nephropathy recipients (1.00 +/- 0.53: 7 patients, 8 times). Long graft survival recipients had better responses to the antirejection therapy. Additionally acute rejection over 6 months were experienced only in chronic allografts nephropathy recipients. Higher serum creatinine level was revealed in recipients with chronic allografts nephropathy at 1 year after transplantation (1.27 +/- 0.27 v.s. 1.88 +/- 0.42 mg/dl). CONCLUSIONS: We concluded that donor age and renal function are related to the graft long survival as background factors. Long graft survival recipients had less frequency of acute rejection and good response to the antirejection therapy. In recipients with of acute rejection and good response to the antirejection therapy. In recipients with chronic allografts nephropathy, serum cretine level had already increased gradually within 1 year.     

A study comparing mycophenolate mofetil to azathioprine in simultaneous pancreas-kidney transplantation

BACKGROUND: Mycophenolate mofetil (MMF; Cell-Cept) is a potent and selective inhibitor of B and T lymphocyte proliferation that has proven effective in reducing the incidence of acute rejection in cadaveric kidney transplant recipients in several randomized, blinded clinical studies. Because the frequency and characteristics of rejection episodes may be different and more severe after combined pancreas-kidney transplantation, we hypothesized that MMF would have a significant impact on pancreas-kidney rejection and graft outcome. Therefore, we compared the efficacy of MMF versus azathioprine (AZA) in cyclosporine-treated simultaneous pancreas-kidney transplantations. METHODS: A retrospective comparison of 358 consecutive primary SPK transplantations performed from 1990 to 1997 was conducted. Patients received either MMF (n=109, 3 g/day) or AZA (n=249, 2 mg/kg q.d.) in combination with cyclosporine-based immunosuppression. All patients received a quadruple-drug sequential induction protocol with either OKT3 or Atgam. Several outcome parameters, including patient and graft survival rates and frequency of rejection, were analyzed. RESULTS: MMF-treated patients demonstrated a markedly reduced rate of biopsy-proven kidney rejection (31 vs. 75% AZA, P=0.0001), clinically significant pancreas rejection (7 vs. 24% AZA; P=0.003), and steroid-refractory rejection (15 vs. 52% AZA; P=0.01). As a result, kidney and pancreas allograft survival was significantly better in MMF patients compared with AZA patients (2-year survival rates: kidney, 95 vs. 86%; and pancreas, 95 vs. 83%). Although surgical infections after transplantation were more frequent in MMF patients, MMF patients were more likely to have undergone enteric drainage. Importantly, we did not observe an increased incidence of any of the bacterial, fungal, or viral infections that typically plague immunosuppressed transplant recipients. CONCLUSIONS: This retrospective study demonstrates that MMF is a highly effective immunosuppressant in SPK transplantation. It is not associated with an increased risk of opportunistic infections when a balanced immunosuppressive management approach is used. MMF strikingly reduces the frequency of acute cellular and steroid-resistant rejection. As a result of this combined experience, it is not unexpected then that we observe significantly improved graft survival rates in MMF-treated SPK patients compared with patients receiving a more traditional immunosuppressive regimen.     

The great success of Asian kidney transplant recipients

BACKGROUND: Little has been written about allograft survival in non-African-American minority groups. We examine the success of kidney transplantation in 1900 Asian recipients. METHODS: Data from 42,252 cadaveric and 16,115 live donor kidney transplant recipients were monitored from the United Network for Organ Sharing Scientific Renal Transplant Registry from 1991 through 1996. RESULTS: Asian recipients exhibited the highest cadaveric allograft survival rates (89% 1-year and 83% 3-year survival) and the longest mean allograft half-life (18 years). Asian women had the highest mean graft half-life (23 years). Asians were less likely to be broadly sensitized and had a high incidence of IgA nephropathy causing end-stage renal disease. Although it has been suggested that their low body weights may help explain the excellent allograft outcome, Asians exhibited superior graft survival rates even when compared with low body weight recipients of other races. CONCLUSION: Asian renal allograft recipients, particularly Asian females, have the highest allograft survival rates of all racial groups.     

Long-term improvement in renal function after cyclosporine reduction in renal transplant recipients with histologically proven chronic cyclosporine nephropathy

BACKGROUND: Chronic cyclosporine (CsA) nephropathy, which has been unequivocally documented in recipients of heart, heart-lung, liver, or bone marrow transplants, as well as in nontransplant situations, usually results in a progressive deterioration of renal function. In this study, we assessed the potential reversibility of chronic CsA nephropathy in renal transplant recipients. PATIENTS AND METHODS: Twenty-three renal transplant patients with biopsy-proven CsA nephropathy associated with long-term CsA administration (27+/-4 months) were followed up for more than 2 years after CsA reduction (18/23 patients) or withdrawal (5/23 patients) and addition of azathioprine. Changes in effective renal plasma flow and glomerular filtration rate were assessed before and 2 years after CsA reduction, whereas serum creatinine, proteinuria, blood pressure, and CsA concentrations were monitored up to 5 years. RESULTS: At 2-year follow-up, glomerular filtration rate increased from 40+/-3 to 47+/-4 (P<0.05) and effective renal plasma flow from 217+/-23 to 244+/-24 ml/min/1.73 m2 (NS). Mean arterial pressure significantly decreased from 98.7+/-2.9 to 93.1+/-2.7 mmHg (P<0.05). There was no significant change in renal vascular resistance, filtration fraction, or albumin excretion. A significant decrease in serum creatinine was also observed during the whole follow-up (73+/-6.5 months). CsA reduction was followed by only one episode of acute reversible rejection; chronic rejection developed in three patients 2 years or later after CsA reduction. CONCLUSIONS: These data suggest that CsA nephropathy participates in graft dysfunction in a small group of renal transplant recipients. In addition, graft dysfunction may be reversible when CsA dosage is reduced early after diagnosis of chronic CsA nephropathy.     

Living unrelated renal donation: the University of Wisconsin experience

BACKGROUND: Living unrelated renal donation (LURD) has the potential to reduce the current waiting list significantly for kidney transplantation. The purpose of this study was to examine the long-term results of 150 LURDs performed at our center during a 16-year period. METHODS: From Dec 23, 1981, to Feb 13, 1998, 150 LURDs, 219 human leukocyte antigen (HLA)-identical, 577 haploidentical, and 1789 cadaveric kidney transplant procedures were performed. Surgical complications, rejection episodes, infectious complications, and the cause of graft loss and death were examined. Ten-year patient and graft survival rates between groups were compared. RESULTS: Fourteen surgical complications including lymphocele (n = 7), ureteral stricture (n = 4), and ureteral leak (n = 3) were seen. Seventy-eight patients (52%) had 123 rejection episodes and 66 patients (44%) had 1 or more infections. Thirty-six allografts were lost and 25 deaths occurred. Patient survival rates at 10 years for HLA-identical, haploidentical, LURD, and cadaveric transplant procedures were 86%, 82%, 63%, and 64%, respectively. Allograft survival rates at 10 years for HLA-identical, haploidentical, LURD, and cadaver transplant procedures were 75%, 59%, 56%, and 44%, respectively. CONCLUSIONS: Long-term LURD allograft survival rates are lower than those for HLA-identical but equivalent to those of haploidentical and better than those of cadaveric kidney transplantations. Spousal and nonspousal LURDs should be actively encouraged to help alleviate the current donor kidney shortage.     

Center-specific graft and patient survival rates: 1997 United Network for Organ Sharing (UNOS) report

CONTEXT: Multiple comprehensive, risk-adjusted studies evaluating short-term surgical mortality have been reported previously. This report analyzes short-term and long-term outcomes, both nationally and at each individual transplant program, for all solid organ transplantations performed in the United States. OBJECTIVES: To report graft and patient survival rates for all solid organ transplantations, both nationally and at each specific transplant program in the United States, and to compare the expected survival rate with the actual survival rate of each individual program. DESIGN AND SETTING: Multivariate regression analysis of donor and recipient factors affecting graft and patient survival of all kidney, liver, pancreas, heart, lung, and heart-lung transplants reported to the United Network for Organ Sharing from 742 separate transplant programs. PATIENTS: A cohort of 97587 solid organ transplantations performed on 92966 recipients in the United States from January 1988 through April 1994. MAIN OUTCOME MEASURES: Short-term and conditional 3-year national and individual transplant program graft and patient survival rates overall and from 2 separate eras (era 1, January 1988-April 1992; era 2, May 1992-April 1994); comparison of actual center-specific performance with risk-adjusted expected performance and identification of centers with better-than-expected or worse-than-expected survival rates. RESULTS: One-year graft follow-up exceeded 98% and conditional 3-year follow-up exceeded 91% for all organs. Graft and patient survival improved significantly in era 2 compared with era 1 for all cadaver organs except heart, which remained the same. One-year cadaveric graft survival ranged from 81.5% for heart to 61.9% for heart-lung and 3-year conditional graft survival ranged from 91.3% for pancreas to 74.7% for lung. The percentage of programs whose actual 1-year graft survival was not different from or was better than their risk-adjusted expected survival ranged from 98.3% for heart-lung to 75.7% for liver. Most kidney, liver, and heart programs whose actual survival was significantly less than expected performed small numbers (less than the national average) of transplantations per year. CONCLUSIONS: Graft and patient survival for solid organ transplantations showed improvement over time. Conditional 3-year graft and patient survival rates were approximately 90% for all organs except for lung and heart-lung. The conditional 3-year survival rates were better than 1-year survival rates, indicating the major risk after transplantation occurs in the first year. The majority of transplant programs achieved actual survival rates not significantly different from their expected survival rates. Center effects were most significant within the first year after transplantation and had much less influence on long-term survival outcomes.     

Donor age and graft function

We evaluated survival and renal function of cadaveric donor grafts according to donor age. The median age of the pediatric donors was 7.0 (0.7-16) years in 46 patients [median age 11.8 years (range) 3-16.8 years]. The median age of the adult donors was 34.4 (19-54) years in 59 patients [median age 12.1 years (range) 7-17.3 years]. Thirty patients were treated with azathioprine and prednisolone and 75 with cyclosporine A and prednisolone. The glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) were determined by the clearances of 51chromium-EDTA and 125iodine-hippurate 1-48 months after kidney transplantation. There was no difference in graft survival between pediatric and adult grafts. There were also no differences in GFR in patients receiving grafts from pediatric or adult donors; 2-3 months after transplantation the GFR in recipients of pediatric grafts was 62 +/- 20 ml/min per 1.73 m2 compared with 61 +/- 21 in those receiving adult grafts. The ERPF in recipients of adult grafts was significantly higher in the 1st month after transplantation: 486 +/- 239 versus 362 +/- 158 ml/min per 1.73 m2. From the 4th to the 6th month after transplantation this difference disappeared: the ERPF of grafts from pediatric donors was 279 +/- 131 ml/min per 1.73 m2 compared with 273 +/- 123 ml/min per 1.73 m2 in grafts from adult donors. Using the single-kidney GFR and ERPF on an age-matched group of probands with minor diseases as references, 2-3 months after transplant the mean GFR of grafts from pediatric donors increased to 118% +/- 51%, whereas the GFR of adult donor grafts fell to 60% +/- 22% over the same period. After 4-6 months the ERPF in pediatric grafts was 96% +/- 55% compared with 50% +/- 22% in adult grafts. We conclude that graft survival and function in children with either a pediatric or an adult graft may not differ because graft function adapts to the requirement of the recipient.     

Objectives to direct the training of emergency medicine residents on off-service rotations: surgery, Part 3

Immunoglobulin A nephropathy (IgAN) frequently recurs in patients after renal transplantation (RT) on a conventional regimen of immunosuppressive therapy, but little is known about the influence of cyclosporine (Cs) on such a recurrence. We studied 84 patients retrospectively who underwent RT for renal failure attributable to IgAN (n = 71) or Henoch-Sch?nlein purpura nephropathy (HSPN) (n = 13) in two transplantation units, between January 1985 and June 1991 and were treated with Cs. Four patients died 3 months to 8 years after RT. Graft survival was 88% at 1 year, 75.2% at 5 years, and 63% at 8 years. Fifty patients underwent at least one graft biopsy, but studies with immunofluorescence were performed on only 28 (23 IgAN and 5 HSPN). After a mean follow-up of 68.1 +/- 37.2 months, mesangial IgA deposits recurred in 13 of the 28 patients (12 IgAN and 1 HSP) (prevalence, 46.4%). Among the 13 patients with recurrence of IgA deposits, all but 4 had urinary abnormalities. Light microscopy showed mesangial deposits and focal and segmental glomerular changes in 9 cases. Four patients lost their graft function 69 to 119 months after RT, and 2 had severe graft dysfunction. The rates of graft failure and mean serum creatinine at 1, 5, and 8 years were similar in the 13 patients with recurrence and the 15 patients without proven recurrence. In conclusion, Cs did not reduce the incidence or severity of IgAN recurrence. The latter was the cause of graft loss or dysfunction in 46.1 % of the patients with recurrent IgA deposits. Recurrent glomerulonephritis did not influence the 8-year graft survival in patients with IgAN or HSPN, but it may be an important cause of graft loss as evidenced by more extended follow-up.     

Analysis of the relationship between chimerism and the allgeneic humoral response

BACKGROUND: Persistence of antigens has been suggested to play a role in two opposing immunological phenomena: tolerance and memory. Therefore, we studied the impact of chimerism on alloreactive antibody (allo-Ab) production in kidney transplant patients. METHODS: Thirty-five female renal transplant recipients of male donor organs were classified into the following groups: group 1, 13 sensitized uremic patients on dialysis; group 2, 5 nonsensitized uremic patients on dialysis; group 3, six sensitized patients experiencing graft rejection (3 acute vascular, 1 acute cellular, and 2 chronic); and group 4, 11 nonsensitized with functioning allografts (9 with good function, 1 with acute cellular rejection, and 1 with chronic rejection). Mean duration of dialysis after graft failure was similar in groups 1 (56+/-29.7 months) and 2 (41.8+/-42.4 months), as was dialysis efficiency. Chimerism was measured indirectly in the peripheral blood lymphocytes by polymerase chain reaction amplification of a specific Y chromosome DNA gene sequence with a detection sensitivity limit of 1 male cell per 1 million female cells. Allo-Ab production was measured by the PRA-STAT enzyme-linked immunosorbent assay (Sangstat) method. RESULTS: Chimerism was observed in 60% of groups 1 and 2, 83% of group 3, and 82% of group 4. Among all groups, graft existence, irrespective of its function, positively predicted chimerism in 92% with a sensitivity of 88% and a specificity of 78%. In group 3, all three patients with acute vascular rejection had chimerism and donor-specific allo-Abs. In group 4, eight of the nine patients with no rejection had chimerism. CONCLUSION: Chimerism relates to persistence of allogeneic stimulus irrespective of its function. Chimerism did not confer protection against allo-Ab production or vascular rejection, and its existence was not crucial for sustenance of allo-Ab production.     

Risks of subsequent pregnancies on mother and newborn in female heart transplant recipients

BACKGROUND: Female heart transplant recipients are able to carry pregnancies successfully. This study evaluates the effect of subsequent pregnancies on newborn and maternal outcomes and graft survival. METHODS: Subjects were identified through a previously reported multicenter study, case reports from literature review, and recipients entered in the National Transplantation Pregnancy Registry. A retrospective analysis was completed of 35 heart transplant recipients with first pregnancies (FP) and 12 who had one or two additional pregnancies (P>1). Newborns were assessed for gestational age, neonatal birth weight, and complications. Maternal data included pregnancy outcome, peripartum complications, including infection and rejection, current graft function, and recipient survival. RESULTS: Forty-seven pregnancies (35 FP and 12 P>1) from 35 heart transplant recipients were studied. FP outcomes included 26 live births (one set of twins), four miscarriages, and six therapeutic abortions, whereas P>1 outcomes included 11 live births (one set of twins), and two miscarriages. There was no significant difference between mean birth weights (2353+/-986 gm vs 2588+/-521 g, P>1 vs FP; mean+/-SD; p=NS) or prematurity incidence (<37 weeks; 50% vs 40%; p=NS) for the live-born infants. Compared with the FP group, there was a trend toward increased neonatal complications in P>1 (40% vs 12%; p=NS). Complications were significantly more common in premature newborns compared with full-term newborns (33% vs 5%; p < 0.05). No structural malformations were identified in the live-born infants. Maternal complication rates were the same in both groups (40%). Of 28 recipients available for follow-up, the maternal survival rate was 75% for the FP group and 89% for the P> group. Mean rejection rate per year was slightly increased after pregnancy in the P>1 group. Surviving recipients had similar graft function by echocardiographic left ventricular ejection fraction. CONCLUSIONS: Post-heart transplantation pregnancies often have successful outcomes, but there is a high incidence of prematurity and low birth weight. Subsequent pregnancies do not seem to significantly increase the incidence of complications in either the newborn or mother or increase graft rejection or failure. Larger studies of posttransplantation pregnancies may provide more definitive information.     

Superior outcomes in pediatric renal transplantation

BACKGROUND: Nationally, results of renal transplantation in children, particularly in small children, are inferior to those obtained in adults. OBJECTIVE: To determine factors important for success in renal transplantation in children. DESIGN: Results of 108 consecutive renal transplantations performed in patients aged 7 months to 18 years were reviewed and compared with those reported by the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), the national registry. RESULTS: One-, 2-, and 3-year graft survival rates (+/-SE) were 99% +/- 1%, 95% +/- 3%, and 93% +/- 4%, respectively, for living donor grafts and 97% +/- 3%, 92% +/- 6%, and 92% +/- 6%, respectively, for cadaver grafts. Incidence of acute rejection was half that reported by NAPRTCS. There were no graft losses for technical reasons (19% in NAPRTCS). Twelve percent of patients were younger than 2 years (6% in NAPRTCS); 17% were 2 to 5 years old (16% in NAPRTCS). Most small children received an adult-sized kidney. Ninety-three percent of recipients weighing 15 kg or less received postoperative mechanical ventilation assistance to optimize fluid resuscitation and perfusion of adult-sized kidneys. Structural abnormalities of the urinary tract were present in 53.7% of the patients (48.5% in NAPRTCS; adults, 5.3%). Nephroureterectomy was required in 38 children; in 27 (71%) of them, it was performed at the time of transplant surgery. CONCLUSIONS: Excellent results can be obtained in pediatric renal transplantation by strict adherence to surgical detail, tight immunosuppressive management, aggressive fluid management in the small child, and careful integration of urologic and transplant surgery.     

Importance of T cells to accelerated rejection and acceptance of renal allografts in sensitized rat recipients

BACKGROUND: Sensitized recipients often experience fulminant allograft loss by yet ill-defined cellular and/or humoral immune mechanisms. In this study, we analyzed the contribution of cellular elements, in particular T cells, to the accelerated rejection of renal allografts in sensitized rats. METHODS AND RESULTS: LEW rats sensitized with BN skin grafts died of uremia in 3.3+/-0.9 days after transplantation of a BN kidney, similarly to bilaterally nephrectomized animals. Adoptive transfer of 10(6) graft-infiltrating mononuclear cells as well as their CD25+ subset into otherwise normal LEW recipients accelerated rejection of BN test cardiac allografts (5.4+/-0.5 days to 6.6+/-0.4 days vs. 7.8+/-0.8 days in controls, P<0.0007), while the CD25- population was ineffective (8.0+/-0.6 days, NS). Furthermore, alpha/beta-T-cell receptor (TCR)-targeted therapy with R73 monoclonal antibody abrogated accelerated rejection, and produced long-term survival in sensitized animals treated before kidney engraftment (day -7 to day -1). Long-term survival was associated with an up-regulation of intragraft interleukin-4 and interleukin-10 expression in conjunction with depressed Th-1-type cytokines. In addition, alpha/beta-TCR-targeted therapy even in low subtherapeutic dose decreased IgM alloantibody levels, and prevented the switch from IgM to IgG alloantibody response. CONCLUSIONS: This is the first report that documents the striking efficacy of alpha/beta-TCR-targeted therapy in sensitized rat renal transplant recipients. The results provide evidence for a critical role of T cells for both accelerated rejection and long-term graft survival. Up-regulation of Th2-type cytokine profile may, at least in part, contribute to the acquisition of immune unresponsiveness after alpha/beta-TCR-targeted therapy in this well-defined rat renal transplant model.     

Histopathologic findings from 2-year protocol biopsies from a U.S. multicenter kidney transplant trial comparing tarolimus versus cyclosporine: a report of the FK506 Kidney Transplant Study Group

BACKGROUND: This paper reports the histopathologic results of 2-year protocol biopsies from patients who were enrolled in the U.S. FK506 kidney transplant study . METHODS: Recipients of cadaveric kidney transplants were randomized to tacrolimus or cyclosporine therapy. Patients active in the trial at 2 years after transplantation were approached for a protocol biopsy. Biopsies were scored by the Banff classification in a blinded fashion by one pathologist. RESULTS: A total of 144 patients (41.3% of those active at 2 years) had a 2-year protocol biopsy performed; 79 patients were treated with tacrolimus and 65 patients were treated with cyclosporine. Evidence of acute rejection was found in seven (8.9%) of the 2-year biopsies in tacrolimus-treated patients and six (9.2%) cyclosporine-treated patients. Chronic allograft nephropathy was found in 49 (62.0%) tacrolimus biopsies and 47 (72.3%) cyclosporine biopsies (P=0.155). There were no apparent histopathologic differences between the tacrolimus and cyclosporine biopsies. The occurrence of chronic allograft nephropathy was significantly higher in patients who received a graft from an older donor (P<0.01), who experienced presumed cyclosporine or tacrolimus nephrotoxicity (P<0.001), who developed a cytomegalovirus infection (P=0.038), or who experienced acute rejection in the first year after transplantation (P=0.045). A multivariate analysis showed that nephrotoxicity and acute rejection were the most significant predictors for chronic allograft nephropathy. CONCLUSIONS: The occurrence of histologic acute rejection was rare at 2 years, confirming the absence of subclinical acute rejection in these late biopsies. A majority of the biopsies showed features consistent with chronic allograft nephropathy that was associated with acute rejection (particularly in cyclosporine-treated patients), nephrotoxicity, and cytomegalovirus infection in the first year. This suggests that nonimmunologic factors, such as drug-induced toxicity, may play an important role in chronic allograft nephropathy.     

Temporomandibular joint derangement after air bag deployment: report of two cases

BACKGROUND: The outcome of 60 renal transplantations in 53 patients with end-stage renal disease (ESRD) because of lupus nephritis was studied retrospectively and compared with 106 controls matched for age, sex, maximum panel-reactive antibody (PRA) level, and date of transplantation. METHODS: The patients received their transplants over a 260-month period (21.5 years) between October 1971 and August 1993. The population was predominantly women (90%), and the mean age at the time of the transplantation was 33.2 years (range: 21-54 years). Fifty-six transplants (93%) were from cadaveric donors, and 4 (7%) were from living-related donors; 46 patients (86%) had primary allografts, and 7 (14%) received a second allograft. The duration of disease before transplantation was 93.6+/-6.2 months, and the duration of dialysis before transplantation was 48+/-6 months. RESULTS: No patient had clinically active systemic lupus erythematosus (SLE) at the time of transplantation. The 1-year graft and patient survival rates were 83% and 98%, and the 5-year graft and patient survival rates were 69% and 96%. Actuarial graft and patient survival rates in SLE patients were not significantly different from those of the matched control group. Chronic rejection was the major risk factor for graft loss. Lupus nephritis recurred in the graft of one patient 3 months after transplantation, and there were extrarenal manifestations of SLE in four others. CONCLUSIONS: The present study confirms that patients with SLE can receive transplants with excellent graft and patient survival rates and a low rate of clinical recurrent lupus nephritis.     

Association of cytomegalovirus genotype with graft rejection after liver transplantation

BACKGROUND: The envelope glycoprotein gB of human cytomegalovirus (CMV) occurs as one of four main genotypes. Some previous studies have proposed a relationship of CMV gB genotype to the frequency of symptomatic infection and to clinical outcomes in both transplant and human immunodeficiency virus-infected populations. Our aim was to define the distribution of CMV gB genotypes and the impact on acute cellular rejection and graft/patient survival after orthotopic liver transplantation (OLT). METHODS: Between October 1988 and December 1996, 325 patients underwent cyclosporine-based OLT at our center. CMV infection was surveyed prospectively and defined as viral isolation from blood or urine; 53 (16%) patients had detectable CMV. Isolates were genotyped by polymerase chain reaction amplification and restriction digest analysis. RESULTS: The distribution of CMV genotypes was: gB1, 19 (36%) patients; gB2, 15 (28%) patients; gB3, 13 (24%) patients; and gB4, 4 (8%) patients. Two patients (4%) had mixed infection (1 + 3, 1 + 4). Age, preOLT diagnosis, use of ganciclovir prophylaxis, basal immunosuppression, mean number of HLA donor/recipient mismatches, and United Network of Organ Sharing status were comparable among patients with different genotypes. Patients with gBl had a significantly higher mean number of acute rejection episodes (1.52+0.30 vs. 0.67+0.22; P=0.027). However, there was no difference in rejection severity, including OKT3 usage or FK506 conversion, or development of chronic rejection among patients with different genotypes. The gB genotype did not affect the development of symptomatic or tissue-invasive CMV disease, detected in 15 patients. Actuarial rates of patient (odds ratio [OR] 3.0; confidence interval [CI] 1.49-6.0) and graft (OR 2.57; CI 1.25-5.22) survival were significantly diminished in the group with CMV infection versus those without CMV (P<0.0001 for both), but there was no association with CMV genotype. CONCLUSIONS: (1) Patients with CMV infection had significantly reduced patient and graft survival rates at 1 and 5 years after OLT as compared with OLT recipients without CMV infection. (2) CMV genotype gB1 was associated with a higher mean number of acute rejection episodes.     

Prednisone withdrawal 14 days after liver transplantation with mycophenolate: a prospective trial of cyclosporine and tacrolimus

BACKGROUND: The long-term complications of immunosuppressive therapy such as diabetes, hypercholesterolemia, and hypertension are a major source of morbidity in liver transplant recipients. In this prospective, randomized, open-label study we completely withdrew prednisone (PRED) 14 days after liver transplantation in an effort to decrease these metabolic complications. Patients were maintained on mycophenolate mofetil (MMF) in combination with either cyclosporine (CsA; Neoral formulation) or tacrolimus (TAC). Thus, we also were able to compare CsA to TAC in patients not receiving PRED with respect to efficacy, toxicity, and effect on posttransplant metabolic complications. METHODS: A total of 71 patients were randomized to receive either TAC-MMF (n=35) or CsA-MMF (n=36) after liver transplantation and were analyzed for patient and graft survival. Fifty-eight patients continued the immunosuppressive protocol for at least 6 months after transplantation and were analyzed for the incidence of acute rejection and the prevalence of diabetes, hypertension, and hypercholesterolemia. RESULTS: The 6-month patient survival rates were 94.4% for CsA-MMF and 88.6% for TAC-MMF. Corresponding 6-month graft survival rates were 88.7% and 85.71% with no immunologic graft losses in either group. The incidence of biopsy-proven acute rejection was 46% for CsA-MMF and 42.3% for TAC-MMF. Six patients were converted from CsA to TAC (four for recurrent rejection) and seven patients were converted from TAC to CsA (four for neurotoxicity). Only one patient (in the TAC-MMF group) developed new-onset posttransplant diabetes. In contrast, four of eight patients in the CsA-MMF group who were diabetic before transplant became nondiabetic in the first 3 months after transplant. The mean serum cholesterol level was significantly lower in the TAC-MMF group than in the CsA-MMF group (145.2+/-41.8 mg/dl and 190.3+/-62.2, respectively; P<0.001) and the incidence of hypertension was lower in the TAC-MMF group (12% vs. 30.3% in the CsA-MMF group, P<0.01). Both groups had a lower incidence of metabolic complications compared with a historical group (n=100) maintained on CsA and PRED (10 mg/day at 6 months). CONCLUSIONS: MMF in combination with either TAC or CsA allows withdrawal of PRED 14 days after liver transplantation with a moderate rejection rate and no immunologic graft losses. Early PRED withdrawal decreases posttransplant diabetes, hypercholesterolemia, and hypertension, but patients maintained on TAC have lower serum cholesterol levels and a lower incidence of hypertension than CsA-treated patients.     

Hearing loss from combined exposures among petroleum refinery workers

Seventy-three consecutive cases of childhood acute lymphoblastic leukemia (ALL) diagnosed and managed in Queen Mary Hospital over a 10-year period from 1985 to 1994 were retrospectively analysed for their presenting features and treatment outcome. The 48 boys and 25 girls ranged in age from 0.4 to 14.2 years (median: 4.3 years). Bone and joint pain was a relatively common presenting feature besides fever, hepatosplenomegaly and lymphadenopathy. Immunophenotyping of blast cells showed: 51 B-cell precursor ALL, one B-ALL, 10 T-ALL and three myeloid-antigen positive ALL. Eight cases were unclassified since immunophenotyping had not been performed. Out of the 73 patients, treatment outcome was analysed in 20 cases treated with UKALL-VIII regimen and 28 cases treated with either the UKALL-XI regimen or the Hong Kong Children Cancer Study Group (HKCCSG) protocol which was modelled upon UKALL-XI. Although complete remission rates were similar between the two groups, patients treated with the former regimen that was less intensified suffered more relapses than the latter (56 per cent versus 21 per cent, P = 0.04). There were, however, no significant differences both in event-free survival (38.2 +/- 11.2 per cent versus 71.3 +/- 9.3 per cent, P = 0.12) and overall survival (70.0 +/- 10.2 per cent versus 79.6 +/- 8.3 per cent, P = 0.41) between the two groups at 3 years by long-rank test. With the use of risk-directed therapy and improved supportive care, two-thirds of our patients are able to enjoy long-term event-free survival.     

Cardiac transplantation in perspective for the future. Survival, complications, rehabilitation, and cost

Two hundred twenty-seven cardiac transplant procedures have been performed in 206 patients from January, 1968, to April, 1981. Postoperative survival rates, calculated by the actuarial method for program years 1968 to 1973 (66 patients), are 44%, 33%, 27%, 21%, and 18% at 1, 2, 3, 4, and 5 years after transplantation, respectively. Postoperative survival rates for program years 1974 to 1981 (140 patients) are 63%, 55%, 51, 44%, and 39% at 1, 2, 3, 4, and 5 years after transplantation, respectively. This increase results primarily from improvement in survival achieved in the first 3 postoperative months (59% +/- 7%, 1968 to 1973, versus 80% +/- 40%, 1974 to 1980), reflecting improved patient management. Infection remains the primary cause of death following transplantation (76/131 patients, 58%), followed by acute rejection (24/181, 18.3%), graft arteriosclerosis (14/131, 10.7%), and malignancy (6/131, 4.6%). The development of graft arteriosclerosis has been examined in 85 one-year survivors studied by annual coronary arteriograms. Coronary lesions of varying severity have developed in 21 patients. HLA-A2 incompatibility was associated with a higher incidence of graft arteriosclerosis than was apparent for all other A locus incompatibilities (p less than 0.0003). Lymphoma has been shown to be associated with younger recipient age, a primary disease diagnosis of idiopathic cardiomyopathy, and retransplantation. One hundred six patients have survived at least 1 year after transplantation; 97% were in NYHA Class 1 at that time interval and 82% returned to employment or activity of choice. The longest survival time is new 11 years, 3 months. Cardiac transplantation can be considered "reasonable and therapeutic treatment to extend life" in selected individuals.     

Long-term outcome of kidney-pancreas transplant recipients with good graft function at one year

To assess the long-term outcome of kidney/pancreas transplantation, patients were identified who had good graft function at one year posttransplant and a minimum of 3 years' follow-up. Fifty recipients from 1987-92 met these criteria. Records were reviewed for graft survival, graft function, readmissions, and medical complications. Psychosocial adjustment and quality of life were assessed using the SCL-90-R and SIP surveys, respectively. Patient, kidney, and pancreas survivals were 94%, 86%, and 85% at five years (Kaplan-Meier), with a mean follow-up of 4.3 years. The 3 deaths were due to 2 sudden arrests at home (presumed to be cardiac events) and 1 episode of sepsis. Other graft losses were due to rejection, except for one case of sepsis. The remaining patients are normoglycemic (glucose 92 +/- 23 mg/dl) and have a creatinine of 1.8 +/- 0.6 mg/dl. Mortality after the first year was 0.9%/year. Estimated kidney and pancreas half-lives were 15 +/- 2 and 23 +/- 7 years, respectively. Hospitalization, acute rejection, graft pancreatitis, dehydration, and severe infections all decreased dramatically after the first year. While CMV was the most common infection in the first year, foot infections predominated thereafter. Retinal hemorrhage was infrequent. Sudden death (presumably cardiac) was the chief cause of mortality, while peripheral vascular disease resulted in several amputations. Fractures were common, suggesting the need for increased attention to bone demineralization. Psychosocial and quality of life evaluations were within normal limits. In conclusion, most complications specifically related to transplantation occur in the first year, but underlying disease renders these patients susceptible to a variety of cardiovascular, bone, and other disorders.     

A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group

BACKGROUND: Tacrolimus (FK506), a macrolide molecule that potently inhibits the expression of interleukin 2 by T lymphocytes, represents a potential major advance in the management of rejection following solid-organ transplantation. This randomized, open-label study compared the efficacy and safety of tacrolimus-based versus cyclosporine-based immunosuppression in patients receiving cadaveric kidney transplants. METHODS: A total of 412 patients were randomized to tacrolimus (n=205) or cyclosporine (n=207) after cadaveric renal transplantation and were followed for 1 year for patient and graft survival and the incidence of acute rejection. RESULTS: One-year patient survival rates were 95.6% for tacrolimus and 96.6% for cyclosporine (P=0.576). Corresponding 1-year graft survival rates were 91.2% and 87.9% (P=0.289). There was a significant reduction in the incidence of biopsy-confirmed acute rejection in the tacrolimus group (30.7%) compared with the cyclosporine group (46.4%, P=0.001), which was confirmed by blinded review, and in the use of antilymphocyte therapy for rejection (10.7% and 25.1%, respectively; P<0.001). Impaired renal function, gastrointestinal disorders, and neurological complications were commonly reported in both treatment groups, but tremor and paresthesia were more frequent in the tacrolimus group. The incidence of posttransplant diabetes mellitus was 19.9% in the tacrolimus group and 4.0% in the cyclosporine group (P<0.001), and was reversible in some patients. CONCLUSIONS: Tacrolimus is more effective than cyclosporine in preventing acute rejection in cadaveric renal allograft recipients, and significantly reduces the use of antilymphocyte antibody preparations. Tacrolimus was associated with a higher incidence of neurologic events, which were rarely treatment limiting, and with posttransplant diabetes mellitus, which was reversible in some patients.