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B G Ericzon

Publications and source records attributed to B G Ericzon.

At least 73 records · Page 4Linked to original sources
PubMed1993

Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosis.

Familial amyloid polyneuropathy (FAP) is a fatal autosomal dominant disorder. Progressive peripheral and autonomic neuropathy are associated with neural and visceral deposition of amyloid, derived most commonly from the Met-30 variant of the plasma protein transthyretin. We have reported previously that orthotopic liver transplantation causes prompt replacement of variant transthyretin by the donor wild-type in the plasma. We now report clinical outcome 1-2 years after transplantation. Three of the first four patients have improved general wellbeing, walking ability, and bowel function, and one of them has regained normal bladder and bowel function. There has been little objective improvement in peripheral neuropathy. The fourth patient, who had the most severe neurological deficits and a complicated postoperative course, has not improved but there has been no further deterioration in contrast to the inexorable progression before transplantation. Quantitative scintigraphy with radiolabelled serum amyloid P component showed visceral amyloid deposits in all three patients studied; in two who were followed serially the deposits regressed after transplantation in association with the clinical improvement. Another FAP patient who was also monitored prospectively for 2 years but who did not undergo transplantation, showed, as expected, progression of neuropathy and increased visceral amyloid deposition. Liver transplantation does therefore have important benefits in FAP during the first 2 years after surgery. Neurological decline is halted and amyloid deposits can be mobilised. The best timing and long-term results of the procedure must now be established.

Adult↗
PubMed1993

Infections in human liver recipients: different patterns early and late after transplantation.

The first 49 consecutive patients who underwent orthotopic liver transplantation between 1984 and 1989 in our department were studied with regard to symptomatic and asymptomatic post-transplantation infections. The major infections carrying a risk of fatal outcome are presented. During the first 4 weeks, fungal and bacterial infections predominated, the percentages of patients affected being 27% and 35%, respectively. Eight patients (17%) suffered from bacterial septicemia, which in six cases was due to gram-negative micro-organisms. The bacterial septicemia was often associated with severe ischemic damage to the graft, rejection, or cholangitis. In addition, a concomitant invasive fungal infection supervened in seven out of eight septic patients, further aggravating the patients' condition. Seventeen of the 49 patients (35%) died after transplantation within 3.3 years. Infection was the cause of death in nine patients (18%), with bacterial septicemia and/or fungemia in eight of these. Cytomegalovirus (CMV) disease was the dominant cause of illness after the 1st month. While only 5 of the 49 patients developed CMV disease during the 1st month (10%), as many as 16 of the 40 recipients who survived beyond that time suffered from symptomatic CMV viremia (40%). CMV mismatching, i.e., the donation of a CMV-positive organ to a CMV-seronegative recipient, entailed the highest risk for CMV disease. Pneumocystis carinii pneumonia occurred within 4 months in 10% of the patients. The four liver recipients affected were among the 20 patients not receiving trimethoprim-sulfamethoxazole prophylaxis. None of the 28 patients who received this prophylaxis over a 12-month period developed this complication (P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Toxicology of FK506 in the cynomolgus monkey: a clinical, biochemical, and histopathological study.

We investigated clinical, biochemical, and histopathological parameters in FK506-treated cynomolgus monkeys. Eight monkeys given oral FK506, 1 (n = 4) or 10 (n = 4) mg/kg daily, survived the 90 days of treatment apparently in good health and without significant changes in biochemical and histopathological parameters, as did 2 control monkeys except one monkey on 10 mg/kg/day FK506 orally, who was found to have a malignant lymphoma. In contrast, monkeys given intramuscular FK506 1 mg/kg daily (n = 4) had to be sacrificed at day 20, 25, 32, and 47 because of severe illness. They showed abnormal biochemical parameters (increased serum urea and aspartate aminotransferase activity) and major histopathological changes in the kidney (mesangial cell proliferation and acute tubular necrosis), pancreas (depletion of beta cells), liver (steatosis), and heart (cardiomyopathy). Intramuscular administration of 1 mg/kg daily resulted in serum levels ranging from 10 to 15 ng/ml, while oral administration at a dose of 1 or 10 mg/kg daily resulted in equal or even higher serum levels (range 2-70 ng/ml). Thus, the height of the serum trough level of FK506 using the enzyme immunoassay is not related to the toxicity of FK506 in cynomolgus monkeys.

Administration, Oral↗
PubMed1992

Seroprevalence and outcome of hepatitis C in liver transplantation.

A recombinant enzyme-linked immunosorbent assay (ELISA) followed by a neutralization test (NT) and recombinant immunoblot assay (RIBA) were used for the detection of antibody to hepatitis C virus (anti-HCV) in 71 patients receiving 84 orthotopic liver grafts between 1984 and 1990. Before the liver transplantation (LTX) anti-HCV was present in six of the 71 recipients (8.5%) who were accepted for LTX because of acute or chronic liver failure. After LTX anti-HCV could not be detected in one of the patients, but it was continuously present in the others for more than 12 months. Detectable HCV antibodies were not present in the three patients who underwent LTX because of clinical evidence of fulminant NANB hepatitis. Two of 48 (4.2%) previously HCV seronegative recipients, who survived more than 3 months, seroconverted 9 and 16 months, respectively, after transplantation. The postoperative seroconversion was probably due to the transfer of virus via perioperative blood transfusions. Thus, these liver recipients may be able to respond by producing anti-HCV despite immunosuppressive therapy. None of the seven post-transplant HCV-seropositive patients developed symptoms such as icterus or fatigue, which would suggest the presence of liver insufficiency due to HCV infection. However, two of them had increased transaminase levels and histological signs of mild hepatitis. No significant difference was found in 1-year survival, prothrombin complex, albumin levels or the risk for retransplantation in post-transplant anti-HCV-seropositive patients, compared with those without detectable HCV antibodies (71% vs 69%, respectively). Thus, during the study period of 1-5 years, the clinical course of HCV infection was milder than that reported for hepatitis B infection in liver recipients.

Acute Disease↗
PubMed1992

The correlation between cytological patterns in bile and histological findings in liver transplantation.

The cytological patterns in bile were compared with the histological findings in concomitant specimens from liver transplants. In cases where cytology showed a moderate (n = 10) or high cell density (n = 8), histology demonstrated rejection in 14 of 18 specimens and cholangitis in 4. When the cell density was low (n = 22), histology was nearly normal in 3 specimens and showed cholangitis in 9, while rejection was observed in 10 specimens. Cell density in bile did not correlate quantitatively with the severity of cellular infiltration in the portal triads or with the percentage of bile ducts attacked by inflammatory cells. The results of the present study support our hypothesis that an increased concentration of cells in bile is indicative of liver transplant rejection (sensitivity 58%), while normal cytology does not rule out the possibility of rejection (specificity 75%).

Adult↗
PubMed1992

The effect of FK506 treatment on pancreaticoduodenal allotransplantation in the primate.

The effect of FK506 monotherapy on pancreaticoduodenal allotransplantation was studied in a primate model. The recipients were made diabetic by total pancreatectomy, thus glycemic control depended on the graft. In control animals hyperglycemia occurred after 14 +/- 3 days and the animals died after 36 +/- 15 days. For FK506-treated animals, the time until development of hyperglycemia was 60 +/- 12 days (P less than 0.05). The animals were then sacrificed by day 90 (P less than 0.05). All three control animals lost their graft function because of severe rejection, as verified by postmortem examination. Only one of the five treated animals showed evidence of a moderate-to-severe rejection at 90 days, one animal having a mild rejection as judged by the histological findings. The drug was clinically well tolerated in all except one animal that became apathetic and refused to eat. Hyperglycemia and an elevated serum creatinine level, which were probably related to the FK506 treatment, occurred in one animal each. Both of these side-effects were reversed by reducing the dose. Thus the use of FK506 permits successful single pancreatic transplantation in primates.

Amylases↗
PubMed1992

FK506-induced impairment of glucose metabolism in the primate--studies in pancreatic transplant recipients and in nontransplanted animals.

The effect of FK506 on glucose metabolism was studied in five cynomolgus monkeys after pancreatic transplantation and in 10 nontransplanted cynomolgus monkeys. We have clearly demonstrated that FK506 can induce hyperglycemia in these animals. In the orally treated nontransplanted animals the hyperglycemia was usually very mild (4.5-6.0 mmol/L). In one of the five transplanted animals, hyperglycemia was induced by the FK506 treatment, since histological signs of rejection were absent and since plasma glucose levels normalized on dose reduction. The glucose disappearance rates, as indicated by the K-values, decreased from a mean of 3.0 +/- 0.5%/min before FK506 treatment to 2.4 +/- 0.6%/min at one month and 1.5 +/- 0.4%/min at three months in the nontransplanted animals. In the transplant group, the K values decreased significantly from 4.2 +/- 0.6%/min in the donor animals to 1.4 +/- 0.4%/min at day 10 posttransplantation (P < 0.02). At one and three months postoperatively, the mean K-values were 1.4 +/- 0.2%/min and 1.2 +/- 0.6%/min, respectively. We conclude that FK506 is diabetogenic in the cynomolgus monkey. This side effect, however, was found to be reversible on dose reduction.

Animals↗
PubMed1991

Relevance of a positive crossmatch in liver transplantation.

We studied 27 liver transplants in 24 patients performed between November 1984 and January 1988. We investigated retrospectively the importance of donor reactive HLA class I and class II and of non-HLA antibodies for graft survival in these patients. In order to determine the specificity and class of the antibodies, we used monoclonal antibodies to HLA-A, -B, -C and DR and DQ antigens to block cytotoxicity of sera and the reagent dithiothreitol to characterize the immunoglobulin class. We found that humoral immunity to HLA antigens in liver-grafted patients, demonstrable as the presence of cytotoxic antibodies reactive with donor splenic T and/or B cells in the pretransplantation period, is associated with significantly lower graft survival as compared with patients without demonstrable preformed HLA antibodies (P = 0.01). In addition we found that a substantial proportion of patients had donor-reactive cytotoxic antibodies which were not HLA specific. Thus, our study shows that HLA immunity can influence liver allograft survival, and that it is useful to have patient cytotoxic antibodies characterized with regard to HLA reactivity prior to transplantation.

Adolescent↗
PubMed1991

Diabetes induction and pancreatic transplantation in the cynomolgus monkey: methodological considerations.

The aim of this study was to develop a model for pancreatic transplantation in the primate in order to test a new immunosuppressive drug. Initially, streptozotocin was used to induce insulin-dependent diabetes mellitus, but it was found to be ineffective and associated with a high morbidity. Furthermore, streptozotocin-induced insulin-dependent diabetes mellitus did not always persist, thus invalidating the evaluation of pancreatic graft function. Therefore, total pancreatectomy was introduced and combined with the pancreatic allotransplantation as a single procedure. Enteric diversion of the pancreatic juice was chosen since this avoids exocrine pancreatic insufficiency and facilitates the oral administration of the test drug. Intra-arterial monitoring of blood pressure and blood gases during the operation and avoidance of hypothermia in the animal were found to be the most important factors contributing to a successful outcome from the operative procedure.

Animals↗
PubMed1991

Comparison of fine-needle aspiration biopsy and histology in human liver transplants.

The findings in 50 fine-needle aspiration biopsies obtained from 27 liver transplants in 24 patients were compared with concomitant histologic findings. When histology showed rejection, rejection was diagnosed in 20 out of 29 FNAB specimens; when rejection was absent histologically, FNAB was negative in 20 out of 21 specimens (sensitivity 69%, specificity 95%). There was a statistically significant correlation between the degree of immunoactivation as reflected by total corrected increment (TCI) in FNAB specimens and the portal triad cell density during rejection, while no correlation existed between the 2 parameters in situations other than rejection. When cholestasis was demonstrated histologically, FNAB showed cholestasis in 30 out of 31 specimens. Furthermore, FNAB showed fatty change in the hepatocytes in 29 out of 43 specimens from livers with histologically evident steatosis. Histology showed necrotic areas in 40 specimens; however, only in 12 concomitant FNAB specimens were necrotic clumps observed. In conclusion, FNAB is a good method for diagnosing acute liver transplant rejection as well as for evaluating intracellular cholestasis or fatty change. Furthermore, TCI seems to reflect the severity of cellular infiltration in the portal triads during rejection.

Adolescent↗
PubMed1991

Biochemical effect of liver transplantation in two Swedish patients with familial amyloidotic polyneuropathy (FAP-met30).

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disorder characterized by progressive peripheral and autonomic neuropathy, associated with neural and systemic amyloid deposits. The amyloid fibrils contain a variant transthyretin (TTR) molecule (TTR met30), over 90% of which is produced in the liver. After liver transplantation in two patients with severe symptomatic FAP, only normal TTR was detectable in circulation. The two patients are being monitored at regular intervals, and, although in one patient there was no evidence of reduction in the quantity of amyloid present at 6 months, there had been no further progression of the neuropathy.

Adult↗