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Biomedical subjects

R M Ferguson

Publications and source records attributed to R M Ferguson.

At least 37 records · Page 2Linked to original sources
PubMed1998

In vivo immunogenicity of purified allogeneic hepatocytes in a murine hepatocyte transplant model.

BACKGROUND: It has been reported previously that liver grafts and liver cells seem to be tolerogenic, based on the high frequency of spontaneous tolerance after orthotopic liver transplantation in rodents and on the phenomenon of portal venous tolerance in other models. The purpose of the current study was to characterize in vivo immune responses to allogeneic hepatocytes transplanted into the portal circulation. METHODS: In this functional model of hepatocyte transplantation, "donor" hepatocytes from mice transgenic for human alpha1-antitrypsin (hA1AT) were transplanted by intrasplenic injection into host mice and the secreted hA1AT protein measured in host serum to determine hepatocellular graft survival. Host immune responses were assessed by measurement of donor-specific alloantibodies and delayed-type hypersensitivity responses. In some experiments, liver nonparenchymal cells (NPCs) were co-transplanted with the allogeneic hepatocyte transplant. RESULTS: Allogeneic hepatocyte transplant into immunocompetent hosts resulted in loss of host serum hA1AT by days 7-10 after transplant, whereas syngeneic hosts maintained long-term hepatocellular graft survival as reflected by persistence of serum hA1AT for > 20 weeks. Allogeneic hepatocyte transplantation resulted in the development of donor-specific alloantibody and delayed-type hypersensitivity responses, as well as a "second set" response of accelerated hepatocellular graft rejection after a second transplant. Pretransplantation or co-transplantation of donor-matched liver NPCs at the time of allogeneic hepatocyte transplantation did not prolong hepatocellular allograft survival. CONCLUSIONS: Allogeneic hepatocytes introduced into the portal circulation via intrasplenic injection are immunogenic not tolerogenic and stimulate a weak humoral and strong cell mediated host immune response in vivo. Co-transplantation or pretransplantation of allogeneic liver NPCs did not protect allogeneic hepatocytes from immunologic rejection.

Animals↗
PubMed1998

A functional model of hepatocyte transplantation for in vivo immunologic studies.

BACKGROUND: Previous studies to determine the significant donor and host factors which contribute to immune responses to allogeneic hepatocytes have been pursued with in vitro and in vivo studies. However, in order to further characterize in vivo host immune responses to transplanted hepatocytes in conjunction with their consequences upon allograft survival, a functional model of hepatocyte transplantation in which the function and survival of transplanted hepatocytes could be serially assessed was pursued. METHODS: A transgenic mouse line expressing the human alpha1-antitrypsin (hA1AT) gene was developed in an FVB/N (H2q) mouse (hA1AT-FVB/N). Hepatocytes from these "donor" transgenic mice were transplanted into host mice by intrasplenic injection, and subsequent survival of the transgenic hepatocytes was determined by assay for the secreted hA1AT protein in host serum by enzyme-linked immunosorbent assay. RESULTS: Transplantation of transgenic "donor" hepatocytes (hA1AT-FVB/N) into (a) syngeneic FVB/N (H2q), (b) allogeneic immunoincompetent C57BL/6.SCID (H2b), or (c) allogeneic T cell-deficient (outbred) hosts resulted in long-term survival (> 16 weeks) of hepatocytes. Transplantation of allogeneic hepatocytes (hA1AT-FVB/N, H2q) into C57BL/6 (H2b), C3H (H2k), or BALB/c (H2d) hosts resulted in loss of hA1AT in host serum by day 10 after transplant. Likewise, transplantation of allogeneic hepatocytes into hosts deficient in B cells, CD8+ T cells, or CD4+ T cells resulted in loss of hA1AT by day 10 after transplant. CONCLUSIONS: This functional model of hepatocyte transplantation is validated for the study of host immune responses to hepatocellular grafts and to assess efficacy of strategies designed to alter these in vivo immune responses. The immunologic rejection of allogeneic hepatocytes appears to be T cell-mediated.

Animals↗
PubMed1998

Function and survival of renal allografts from the same donor transplanted into kidney-only or kidney-pancreas recipients.

BACKGROUND: The aim of this study was to assess whether kidney-pancreas transplantation (KPT) compromises the prognosis of kidney transplantation (KT). METHODS: This study included 368 paired recipients who received grafts from the same donor (184 KPT/184 KT), i.e., renal grafts with the same pretransplant functional and pathologic characteristics. RESULTS: KPT recipients (KPR) were significantly younger and included fewer African-Americans (22% vs. 6%, P=0.0005) than recipients of kidney alone (KR). During year 1 after transplant surgery, KPR were re-admitted more often than KR (4.2+/-2 vs. 2.8+/-2, P < 0.0001). The number of acute rejections (AR) and the serum creatinine were not significantly different in KR and KPR up to 3 years after transplant. After 44+/-29 months, 13% of KR and 17% of KPR died (NS), and 17% of KR and 16% of KPR lost their kidneys (NS). In KPR, reduced renal graft survival did not correlate with AR (P=0.44), but it correlated with: older donors, younger recipients, elevated serum creatinine at 6 months, pancreas loss, and the number of episodes of acute graft dysfunction evaluated by biopsy (multivariate analysis). By Cox, graft and patient survival were not significantly different in KR and KPR. However, the patient survival of KPR < 40 years of age was lower than that of KR (P=0.02). Renal biopsies (n=165) in 40 paired recipients showed no significant differences in AR, interstitial fibrosis, or vascular pathology. CONCLUSIONS: Renal graft function, structure, and survival are not different in KPR and KR, but the correlates of renal graft survival are different in these two groups of recipients.

Adult↗
PubMed1998

Prophylactic cholecystectomy is not indicated following renal transplantation.

BACKGROUND: The appropriate management of gallstones in patients undergoing renal transplantation is controversial. Screening for gallstones and subsequent prophylactic cholecystectomy has been recommended by some authors for kidney transplant candidates. Our program does not practice routine pretransplant screening for gallstones, and we reviewed our data to determine the outcome of our management approach. METHODS: We reviewed the records of the 1,364 currently followed patients who have undergone kidney transplant at our institution since 1985 in order to evaluate the morbidity and mortality of biliary disease in the post-transplant period. We attempted to contact all patients by telephone or mail survey for the presence of biliary tract disease or operations. RESULTS: Six hundred and sixty-two patients were fully evaluated. Fifty-two (7.85%) required cholecystectomy for stone disease. Seven patients underwent incidental cholecystectomy during other operations, 2 patients developed acalculus cholecystitis, and 14 patients with asymptomatic cholelithiasis are being followed up. Surgical indications included 38 biliary colic, 9 acute cholcystitis, 3 gallstone pancreatitis, and 2 patients who were asymptomatic. Fifty-two patients underwent 30 laparoscopic cholecystectomies, 20 open cholecystectomies, and 2 conversions. Surgery occurred from 7 days to 9.6 years following transplantation. Overall, the median hospital stay (no postoperative stay) was 4 days (range 1 to 57). Patients undergoing laparoscopy had a median stay of 2 days compared with 7 days for those undergoing an open procedure. Complications were seen in 6 patients (11.5%) with no morbidity and no graft loss. The 1-, 2-, and 5-year graft survival was 98%, 96%, and 85%, respectively, in patients undergoing cholecystectomy. CONCLUSIONS: Transplant patients are not at an increased risk for developing biliary tract disease compared with nontransplant patients. Gallstone disease does not have a negative impact on graft survival. Treatment of gallstones has a low risk and does not represent an increased risk of complications in patients following renal transplantation.

Adult↗
PubMed1998

Occult herpes family viruses may increase mortality in critically ill surgical patients.

BACKGROUND: Effects of cytomegalovirus (CMV) or herpes simplex virus (HSV) infection on surgical intensive care unit (SICU) patients' hospital outcome are unknown. METHODS: Between July 1, 1994, and September 1, 1995, general SICU patients with persistent sepsis and no bacterial or fungal source identifiable had viral cultures obtained. Patients with positive broncho-alveolar lavage, blood, skin, or sputum cultures for CMV or HSV were studied. RESULTS: Twenty eligible patients had positive viral cultures during the study period, and 85% of these patients developed subsequent bacterial and/or fungal infections. Mortality was significantly higher following viral infection than in chronic SICU patients (65% vs 35%, P <0.006). Patients with thrombocytopenia complicating their viral infection had significantly higher mortality than those without thrombocytopenia (92% vs 25%, P <0.004). CONCLUSIONS: At least 14% of critically ill surgical patients have occult infection or reactivation of herpes family viruses. These viruses have known immunosuppressive effects, which may predispose chronic SICU patients to subsequent bacterial and fungal infection, and subsequent organ system failure and death.

Aged↗
PubMed1998

Patient survival after renal transplantation: I. The impact of dialysis pre-transplant.

Patients on dialysis and recipients of renal transplants have higher mortality than individuals without kidney disease. In this study we evaluated the possible impact of dialysis therapy before transplantation on patient survival after the transplant. This analysis includes all of the patients who received a cadaveric renal transplant at The Ohio State University from 1984 to 1991 and who remained alive with functioning grafts for at least six months after the transplant (N = 523). After a follow-up of 84 +/- 14 months, 28% of the patients died and 23% lost their grafts. By multivariate analysis, reduced patient survival (censored at the time of graft loss) correlated with these pre-transplant variables: Older age (P < 0.0001), the presence of diabetes (P = 0.0002), smoking (P = 0.009), and the length of time on dialysis (P = 0.0002). Thus, 7% of patients who were never dialyzed, 23% of those dialyzed for less than three years, and 44% of patients dialyzed for > or = three years died post-transplant. By Cox regression, patient survival months correlated with time on dialysis pre-transplant (P = 0.0003). The type of dialysis (CAPD vs. hemodialysis) did not correlate with patient survival. Graft survival, censored for patient death, did not correlate with any of these pre-transplant variables. The relationship between time on dialysis and patient mortality is due to at least two factors: (1) transplant recipients who had dialysis for > or = 3 years had higher mortality due to infections (22%) than those who had dialysis for < 3 years (3%, P = 0.01 by X2); and (2) increasing time on dialysis increases the prevalence of both left ventricular hypertrophy (P = 0.008) and cardiomegaly (P = 0.004), and these relationships are statistically independent of other factors that also correlate with the prevalence of cardiovascular disease. In conclusion, increased time on dialysis prior to renal transplantation is associated with decreased survival of transplant recipients.

Adult↗
PubMed1998

Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate Alamar Blue assay.

A colorimetric, microplate-based Alamar Blue assay (MABA) method was used to determine the MICs of isoniazid (INH), rifampin, streptomycin (SM), and ethambutol (EMB) for 34 Peruvian Mycobacterium tuberculosis isolates (including both pansensitive and multidrug-resistant strains) and the H37Rv strain by using bacterial suspensions prepared directly from solid media. Results for all isolates were available within 8 days. Discordant results were observed on initial tests for 3 of 16 INH-susceptible isolates, 5 of 31 EMB-susceptible isolates, and 2 of 4 SM-resistant isolates (by the BACTEC 460 system). The overall agreements between the MICs obtained by MABA and the results obtained with the BACTEC 460 system were 87.9% for initial results and 93.6% after retesting 12 of 17 samples with discrepant results. Interpretation of MABA endpoints improved with technical experience. The MABA is a simple, rapid, low-cost, appropriate technology which does not require expensive instrumentation and which makes use of a nontoxic, temperature-stable reagent.

Antibiotics, Antitubercular↗
PubMed1998

Acute rejection following renal transplantation. Evidence that severity is the best predictor of subsequent graft survival time.

UNLABELLED: Timely recognition of risk factors influencing graft survival time following kidney transplantation could facilitate the development of clinical interventions that would increase the longevity of graft survival. To identify these risk factors, we performed a retrospective analysis of the clinical outcome of 1949 renal transplants performed at The Ohio State University Transplant Program between 22 September 1982 and 14 June 1996. The number of acute rejection (AR) episodes was most predictive of shorter graft survival time. The first AR episode severity (indexed using the difference between post-treatment serum creatinine (RxCr) and baseline serum creatinine (BCr), or DeltaCr = RxCr - BCr) was the best predictor of graft survival time (r = 0.27, p < 0.0001) in patients experiencing AR. Subsequent AR episodes occurred more frequently in patients with a higher DeltaCr. However, DeltaCr was the best predictor of graft survival time (r = 0.44, p < 0.0001) in patients who had only one AR episode. The severity of the first AR episode (DeltaCr) correlated with the risk of subsequent AR episodes, the severity of a second AR episode and the average of mean blood pressures obtained after, but not before, the first AR episode. Therefore, we conclude that the severity of the first AR episode was the best predictor of renal allograft survival time in all patients experiencing AR, independent of subsequent AR episodes and correlated with subsequent clinical events which also influence renal allograft survival time. Thus, early diagnosis and aggressive treatment of the first AR episode are warranted to minimize AR severity and thereby maximize subsequent graft survival time. CONCLUSIONS: The severity of the first acute rejection episode following renal transplantation is the best determinant of graft survival time and correlates with subsequent clinical events which could further reduce graft survival time.

Acute Disease↗
PubMed1997

Impact of acute rejection and early allograft function on renal allograft survival.

Both acute rejection and the function of a renal allograft early after transplantation correlate with long-term graft survival. In this study we assessed the relationship between these two factors in 843 adult recipients of first cadaveric renal grafts, transplanted at a single institution and followed for a minimum of 3.5 years. Patients were divided into four groups according to (1) history of acute rejection (AR) during the first 6 months after transplantation, and (2) concentration of serum creatinine at 6 months after transplantation (SCr(6mo) < or > or = 2 mg/dl). Death censored allograft survival was not significantly different among patients without AR and with low SCr(6mo) (group 1, n=376), patients without AR but with an elevated SCr(6mo) (group 2, n=117), and patients with AR but low SCr(6mo) (group 3, n=185). In contrast, graft survival was significantly worse in patients with AR and an elevated SCr(6mo) (group 4, n=165) compared with patients in the other three groups (Cox, P<0.0001). The elevated SCr(6mo) in group 4 patients was not necessarily the consequence of AR, as 32% of patients in group 4 had a SCr at 10 days after transplantation (SCr(10d)), before they had AR, that was equal to or higher than the SCr(6mo). Based on this observation we investigated the implications of the SCr(10d) concentration for graft prognosis. The SCr(10d) correlated weakly with graft survival (Cox, P=0.05). However, an elevated SCr(10d) correlated with other potential risk factors for graft survival including: Older donors (P<0.0001), male recipients (P<0.0001), and heavier recipients (P<0.0001, all by multivariate regression); and posttransplant factors such as, increasing numbers of AR (P<0.0001), higher posttransplant blood pressure (P<0.0001), and lower doses of cyclosporine (P<0.0001, all by multivariate regression). In conclusion, graft dysfunction predicts poor graft survival only when associated with AR. Similarly, AR predicts a poor renal allograft survival only when associated with graft dysfunction. The SCr(10d) is an indicator of risk factors from both the donor and recipient, and an elevated SCr(10d) predicts a higher risk of acquiring additional risk factors early after transplantation.

Acute Disease↗
PubMed1997

Clinical and economic impact of flow cytometry crossmatching in primary cadaveric kidney and simultaneous pancreas-kidney transplant recipients.

We retrospectively compared the clinical and financial impact of a final cross-match by T cell flow cytometry (FXM) versus conventional complement-dependent cytotoxicity (CXM) in consecutive primary cadaveric kidney (K) and primary simultaneous cadaveric pancreas-kidney (SPK) transplant recipients. Mean follow-up was 14 months for both the K (range, 5-22 months) and SPK (range, 5-22 months) recipients. There were no instances of a positive CXM result if the FXM result was negative. However, 18 of the 102 (18%) K recipients and 11 of the 66 (17%) SPK recipients were FXM positive, CXM negative, but no grafts lost to hyperacute rejection in this group. In addition, patient survival, graft survival, incidence of acute rejection, and kidney and pancreas function (immediate and late) were not different in the FXM-positive versus the FXM-negative groups. Charges for the CXM and FXM methods were compared over a 6-month period. During that period, the FXM charges averaged $583 less per recipient than the CXM charges (58% reduction in charges), and the time required to perform the FXM method was 50% of that required for the CXM method. These results demonstrate that a clinical pathway for primary transplantation that utilizes the FXM rather than the CXM final cross-match is clinically safe, with no adverse effect on posttransplant outcome, reduces organ preservation time by shortening the waiting period for the final cross-match results, and significantly reduces the tissue typing charges. However, about 9% of all primary K and SPK recipients will be FXM positive, CXM negative on final cross-match and will be unnecessarily denied a transplant. In this study, we describe a method to identify these patients so that they can be tested by traditional CXM to avoid being denied access to donor organs.

Adult↗
PubMed1997

The laparoscopic management of post-transplant lymphocele. A critical review.

BACKGROUND: The managements of lymphocele in patients following kidney (KT) and pancreas (KPT) transplantation is evolving. Open surgery has been the traditional treatment, but some authors have advocated laparoscopic drainage in selected patients. METHODS: We retrospectively reviewed our results in lymphocele treatment since developing a laparoscopic program at our institution. RESULTS: Between May 1994 and June 1995, 186 KTs and 48 KPTs were performed, and 1,354 patients are currently being followed. Eight patients developed symptomatic lymphoceles an average of 26 months (range 4-59) following 6 KTs and 2 KPTs. All patients diagnosed were successfully drained laparoscopically, with no conversions to open surgery. Laparoscopic ultrasound was used to help with localization of the fluid collection. Operative time averaged 59 min, median hospital stay was 1 day (range 1-4), and there were no perioperative complications. Follow-up imaging was obtained on six patients, 3-16 months following their procedures, and no recurrences were noted. A review of the literature demonstrates a 5.3% rate of major complications and a 7% incidence of lymphocele recurrence. CONCLUSIONS: Intraoperative laparoscopic ultrasound can help to localize fluid collections and prevent organ injuries. Laparoscopic drainage of lymphocele following transplantation results in minimal disability and an acceptable complication rate, although it is higher than with open drainage. Therefore, laparoscopic drainage should be considered as primary treatment for all patients with symptomatic post-transplant lymphocele.

Drainage↗
PubMed1997

Liver transplantation in Ohio.

BACKGROUND: Since its inception in 1984, the Ohio Solid Organ Transplantation Consortium has tracked liver transplantation outcomes for its five member institutions. Presented herein is a 12-year summary of this data analyzed to determine whether, with increasing experience, outcomes have improved in a cost-effective manner. METHODS: Between July 1984 and June 1996, 1,063 liver transplants were performed in Ohio in 943 patients (772 adults and 171 children), of which 943 were primary and 120 were retransplants (13%). Outcome comparisons were made for three eras: 1984-1988, 1988-1992, and 1992-1996. RESULTS: The percentage of urgent (United Network for Organ Sharing status 1 and 2) transplants has decreased (62% to 41%), whereas that of homebound patients has increased (38% to 59%). Average time on the waiting list has increased from 39 to 165 days, and the average length of stay has decreased from 44 to 27 days. Patient survival at 1-year increased in each era (64%, 80%, and 82%, respectively). Although actual hospital charges have remained relatively constant, they have decreased substantially when compared in 1985 dollars as corrected for inflation. CONCLUSIONS: Patients undergoing liver transplantation in Ohio are now listed earlier in the course of their disease and wait longer for their transplant, but enjoy a better chance of survival, have a shorter hospital stay, and a relatively less expensive operation. These data indicate that with increased experience, the Ohio Solid Organ Transplantation Consortium liver transplantation teams perform liver transplantation in a more cost-effective manner.

Adolescent↗
PubMed1997

Relationships between arterial hypertension and renal allograft survival in African-American patients.

In previous studies, we showed that in African-American patients arterial hypertension during the first 6 months after transplantation is associated with a high risk of renal allograft loss. In this study, we sought to examine the relationships between pretransplant blood pressure (preBP), blood pressure early after transplantation (postBP), and allograft function and survival. The study included 116 African-American recipients of first cadaveric renal allografts followed for 64 +/- 40 months. Prior to transplantation, 78% of the patients required antihypertensive medications and 59% had poorly controlled BP (average mean arterial pressure, > or =107 mm Hg). Blood pressure levels increased significantly during the first month posttransplant, particularly in patients with poorly controlled preBP. During the first 6 months posttransplant, 95% of patients required antihypertensive drugs; after the transplant, patients required significantly more and higher doses of antihypertensives compared with pretransplant. In 38% of the patients, postBP remained high despite therapy. The level of postBP correlated with the patient's weight pretransplant and with the level of preBP. Pretransplant BP correlated with postBP 1 month after transplantation (r = 0.4, P < 0.0001), and 70% of the patients with poorly controlled postBP had uncontrolled preBP. Patients with poorly controlled preBP had worse graft survival than patients with well-controlled preBP (P = 0.03 by Cox regression). Furthermore, compared with patients with well-controlled postBP, patients with high postBP had higher serum creatinine at 10 days (P = 0.04) and at 6 months (P = 0.0004) posttransplant; these patients had reduced graft survival (P = 0.0006 by Cox). We found no objective evidence of differences in patient compliance between individuals with high postBP and those with well-controlled postBP. This study confirms the association between high postBP and reduced renal allograft survival in African-American patients. In addition, these results show that the level of preBP can be used to identify patients at high risk of developing severe hypertension immediately after transplantation and those at risk for renal allograft failure.

Adult↗
PubMed1997

Rescuing Prometheus: a policy proposal to alleviate excess demand for liver transplantation.

A growing demand for liver transplantation coupled with a static supply of organs results in an excess demand crisis. Excess demand for liver transplantation equals the number of patients left on the UNOS waiting list at the end of the year who have not expired, undergone transplant, or been withdrawn. Only in the arena of transplantation doses the United States medical community confront a true rationing dilemma stemming from a scarcity of livers available for transplantation. An excess demand crisis intensifies debate in policy areas such as allocation and patient listing criteria. A cohesive rationing policy should manage both the demand for transplantation and the supply of transplantable organs. Demand-side management as applied to liver transplantation could decrease the incidence of critically ill patients waiting for transplants, the number of retransplants performed and the total cost of transplantation to the health care system.

Health Care Rationing↗