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Biomedical subjects

C M Miller

Publications and source records attributed to C M Miller.

At least 127 records · Page 7Linked to original sources
PubMed1995

FK506 (tacrolimus) compared with cyclosporine for primary immunosuppression after pediatric liver transplantation. Results from the U.S. Multicenter Trial.

We report on the efficacy and safety of FK506 (tacrolimus) compared with a cyclosporine (CsA)-based immunosuppressive regimen after 1 year of treatment in pediatric liver allograft recipients (< 12 years) participating in a multicenter U.S. randomized trial. Patients received either FK506 or CsA as primary immunosuppression following a first ABO-compatible liver transplant. Intravenous FK506 was initiated at 0.1 mg/kg per day, followed by oral FK506 beginning at 0.3 mg/kg per day. The dose was adjusted to maintain plasma trough levels of 0.5-2.0 ng/ml. The CsA group was treated according to each center's usual protocol. Both groups received the same initial doses of corticosteroids. All rejection episodes were biopsy-proven and a standardized algorithm was adopted for the treatment of rejection. Thirty patients were randomized to the FK506 group and 20 to the CsA group. After twelve months of follow-up 20 patients remained in the FK506 group and 13 in the CsA group. Patient survivals were 80% and graft survival 70% in the FK506 group compared with 81% and 71% respectively, in the CsA group. 48% of the FK506 group remained rejection-free compared with 21% of the CsA group, and 79% of FK506-treated patients did not require OKT3 compared with 68% of CsA treated patients. The cumulative corticosteroid dose was less at each time point throughout the first year in the FK506 group. The incidence of serious and minor infections was similar in both groups. Nephrotoxicity, neurotoxicity, and gastrointestinal disturbances were the major toxicities reported. Differences did not reach statistical significance between the two groups although major neurologic events, diarrhea and dyspepsia were more often reported in the FK506 group. There was no difference in mean serum creatinine at 12 months between the two groups. There was a tendency toward lower mean serum cholesterol in the FK506 group. There was no hirsuitism in the FK506 group compared with a 30% incidence in the CsA group. In conclusion, compared with CsA, there is a trend toward less rejection in FK506-treated pediatric allograft recipients, while both drugs have a similar spectrum of side effects.

Adrenal Cortex Hormones↗
PubMed1995

N-acetylcysteine ameliorates reperfusion injury after warm hepatic ischemia.

Glutathione is important in cellular defense against oxidative stress. We postulated that administration of N-acetylcysteine (NAC), a glutathione precursor, might help maintain or replenish hepatic glutathione stores, thereby reducing reperfusion injury in liver grafts after warm ischemia. Eighteen pigs were subjected to 2 hr of warm hepatic ischemia and divided into a control group (group A, n = 6), a preischemia treatment group (group B, n = 6: NAC, 150 mg/kg, continuous i.v. infusion 1 hr before ischemia), and a postischemia treatment group (group C, n = 6: NAC, 150 mg/kg continuous i.v., begun 20 min before reperfusion and continued for 1 hr). At initiation of laparotomy, we measured hepatic levels of reduced glutathione (GSH), its oxidized form (GSSG), ATP, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH). Before reperfusion, after 2 hr of warm ischemia, GSH, GSSG, and ATP were measured. One hour after reperfusion, we measured GSH, GSSG, ATP, AST, and LDH. Bile output was recorded every 10 min. Postoperfusion AST and LDH were significantly lower in both treatment groups than in controls. In group B, hepatic glutathione was maintained at significantly higher levels than in controls, even after ischemia (P < 0.05). In group C, although hepatic GSH levels fell until reperfusion, after administration of NAC, hepatic GSH reached the level of the preischemia treatment group. In both treatment groups, GSH 1 hr after reperfusion was significantly higher than in the controls (P < 0.01): regeneration of glutathione was seen in all 6 animals in group C, compared with 2/6 in group B and none in the control group. ATP recovery, bile output, and survival were all better in the treatment groups than in the control group. Pretreatment with NAC helps maintain hepatic glutathione during warm ischemia; given after ischemia, NAC is effective in replenishing depleted glutathione stores. Adjunctive use of NAC was associated with improved glutathione homeostasis, improved bile output and ATP regeneration, and increased survival.

Acetylcysteine↗
PubMed1995

CA19-9 does not predict cholangiocarcinoma in patients with primary sclerosing cholangitis undergoing liver transplantation.

The results of liver transplantation in patients with cholangiocarcinoma have been poor. It has been suggested that elevated serum CA19-9 levels predict cholangiocarcinoma in patients with primary sclerosing cholangitis. We analyzed the predictive value of CA19-9 antigen as a marker of cholangiocarcinoma in patients with primary sclerosing cholangitis evaluated for liver transplantation. We reviewed the charts of 26 patients with primary sclerosing cholangitis (stage IV) in whom preoperative serum CA19-9 levels were determined; 22 of 26 underwent liver transplant. Explant specimens were serially sectioned and examined for tumor. In 3 of the 26 patients, cholangiocarcinoma was diagnosed during pretransplantation evaluation; exploratory laparotomy on the last patient showed no evidence of cholangiocarcinoma, and this patient is awaiting transplantation. Twelve of the 26 patients had CA19-9 levels more than double the laboratory reference range (0-37 U/mL) (mean 183.1 +/- 103 U/mL, range 77-415 U/mL). Two of the 12 patients with elevated CA19-9 levels had cholangiocarcinoma. Of the 14 patients with normal levels, two had cholangiocarcinoma. No correlation between elevated CA19-9 and bile duct dysplasia was noted. Sensitivity for serum CA19-9 levels more than twice the reference range is 50%, specificity is 54.5%, positive predictive value is 16.6%. An elevated serum CA19-9 level in a patient with stage IV primary sclerosing cholangitis does not reliably predict coexisting cholangiocarcinoma. Persistently high or rising serum CA19-9 levels do not indicate more urgent need for liver transplantation.

Adult↗
PubMed1995

Progressive multifocal leukoencephalopathy after orthotopic liver transplantation.

Six weeks after liver transplantation, a 51-year-old man developed a slowly progressive hemiparesis with deteriorating mental status and seizures. Successive computed tomography (CT) scans of the brain revealed unilateral nonenhancing white matter lucencies that gradually coalesced and progressed to both hemispheres. Brain biopsy results were consistent with progressive multifocal leukoencephalopathy (PML). We believe this is the first antemortem description of PML after liver transplantation. Herein, we describe the case and review the literature on PML after solid organ transplantation. Early recognition of this central nervous system disease may be important with new advances in therapy of this viral infection of the immunocompromised patient.

Biopsy↗
PubMed1995

High-dose acyclovir and intravenous immune globulin reduce the incidence of CMV disease after liver transplantation.

We attempted to prevent cytomegalovirus (CMV) disease in liver transplant (LTx) recipients by means of a combined prophylaxis regimen consisting of high-dose acyclovir (HDA) and immune globulin (IVIG). In 259 consecutive patients, HDA was given for 3 months post-LTx; recipients seronegative for CMV also received IVIG. The previous 94 patients comprised our control group; in this group, low dose acyclovir was given to prevent herpes, and prophylaxis of CMV consisted of IVIG given only to seronegative recipients of seropositive donors. The overall incidence of CMV disease was lower in the HDA group (10.8%) than in the control group (27.6%); (P < 0.001). The CMV disease rate associated with primary exposure was 26.3% in the HDA group and 83.3% in the control group (P < 0.001). The incidence of CMV disease occurring after acute rejection was 9.5% in HDA patients and 24.6% in controls (P < 0.005) The HDA protocol was associated with a trend toward a lower incidence of CMV in patients requiring OKT3 therapy (16.7% vs 29%). High-dose acyclovir/IVIG thus reduces the incidence of CMV disease in seronegative recipients after LTx and lowers the risk of CMV disease associated with therapy for rejection.

Acyclovir↗
PubMed1995

Eimeria maxima gametocyte antigens: potential use in a subunit maternal vaccine against coccidiosis in chickens.

Affinity-purified gametocyte antigens (APGA) from Eimeria maxima, emulsified in Freund's adjuvant, were injected intramuscularly into breeding hens on two or three occasions. As a result, progeny of the immunized hens were partially immune to infection with E. maxima, Eimeria tenella and Eimeria acervulina (with a reduction in total oocyst output of 45-63% as compared with progeny of untreated hens). Thus, APGA in Freund's adjuvant appears to have great potential as part of a maternally applied vaccine against coccidiosis. The ability of APGA to induce partial cross-species protection is most probably due to the existence of conserved epitopes in the different species as indicated by comparative Western blots of E. maxima and E. tenella. Surprisingly, Freund's adjuvant by itself also induced significant levels of maternal immunity to coccidiosis (with a 12-35% reduction in oocyst output in the progeny). In contrast to the purified antigens or Freund's alone, crude extracts from gametocytes as well as other developmental stages, induced little if any significant maternal immunity despite provoking the production of large amounts of parasite-specific IgG, including antibodies to APGA. This result indicates that a successful maternal vaccine against coccidiosis requires, in addition to good recognition of protective antigens, the exclusion of irrelevant antigens from the vaccine preparation.

Animals↗
PubMed1995

Decentralized lab testing. A collaborative approach to point of care testing.

What is involved in setting up and managing a decentralized laboratory testing program at a hospital? What elements are involved in making such a program a success? Multidepartmental and multidisciplinary cooperation and communication are the keys to implementing a cost-effective, user-friendly system that assures quality patient care and operator competence.

Blood Glucose↗
PubMed1995

A multidisciplinary approach to hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: A multidisciplinary approach has been developed to evaluate and treat patients with cirrhosis and hepatocellular carcinoma (HCC). STUDY DESIGN: We evaluated 153 patients with cirrhosis and HCC. Fourteen patients with Child's A cirrhosis underwent resection. Transplantation was performed in 40 patients with HCC less than 5 cm (32 incidental, eight recognized preoperatively), in six patients with HCC 5 cm or greater not recognized preoperatively, and in 11 patients with recognized HCC 5 cm or greater; the latter 11 underwent transplantation in a multimodality protocol using pretransplant chemoembolization and intraoperative and postoperative chemotherapy. RESULTS: Among the 14 patients who underwent resection, the three-year survival rate was 39 percent. Among the 40 patients with HCC less than 5 cm who underwent transplantation, no tumor recurrence was observed. Among the six with HCC 5 cm or greater unrecognized preoperatively, three had tumor recurrence. Among the 11 with HCC 5 cm or greater enrolled in the protocol, there were no deaths and one recurrence at a mean of 433 days follow-up. The four-year survival rate for all patients who underwent transplantation with HCC was 56 percent (66 percent excluding the six patients with unrecognized HCC 5 cm or larger). CONCLUSIONS: Hepatocellular carcinoma less than 5 cm in patients with cirrhosis (Child's B or C) is an indication for hepatic transplantation. Hepatocellular carcinoma less than 5 cm in patients with cirrhosis (Child's A), although resectable, may in some cases be better treated by hepatic transplantation. Transplantation for HCC 5 cm or greater within a multimodality protocol has yielded excellent results at two years.

Aged↗
PubMed1995

Severe or multiple rejection episodes are associated with early recurrence of hepatitis C after orthotopic liver transplantation.

Recurrent hepatitis C causes significant morbidity after liver transplantation. Because immunosuppression is associated with enhanced viral replication, we postulated that clinical recurrence of the disease may be associated with augmented immunosuppression for rejection. In 96 patients with hepatitis C who received liver transplants, we recorded the interval from transplantation to recurrence, the episodes of steroid-resistant rejection (SRR) requiring OKT3, the number of rejection episodes, and the use of OKT3 induction. Recurrence was diagnosed based on elevated transaminases and characteristic histology. Hepatitis C recurred in 43 of 96 patients. Fifteen of 21 patients (71.4%) who previously had SRR had recurrence, versus 28 of 75 patients (37.3%) who either had no SRR (72 patients) or had it after recurrence was diagnosed (3 patients) (P < .01). Mean time to recurrence was 127 +/- 31 days in the 15 patients who had had SRR versus 246 +/- 42 days in the other 28 patients (P = .02). Recurrence and number of rejection episodes were clearly associated: 6 of 33 patients (18.2%) with no rejection had recurrence (P < .05), versus 11 of 26 patients (42.3%) with one rejection episode (P < .05) and 26 of 37 (70.2%) with more than 1 episode (P < .05). OKT3 induction was used in 15 patients; 9 of 15 patients had recurrence (ns) at 337 +/- 95 days. Of 72 patients who initially received triple immunosuppression, 30 patients had recurrence at 186 +/- 25 days (P = .05). Nine patients received primary FK506; 4 had recurrence at 68 +/- 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Resistance↗
PubMed1995

A rational approach to the use of hepatic transplantation in the treatment of metastatic neuroendocrine tumors.

BACKGROUND: Gastrointestinal neuroendocrine tumors are slow growing, and metastases are often limited to the liver. Whereas in asymptomatic patients, observation alone may be reasonable, in patients with neuroendocrine tumors and unresectable hepatic metastases, transplantation of the liver may be beneficial. We have developed a protocol in which patients with multiple hepatic metastases are initially treated with chemotherapy and embolization to control symptoms and inhibit tumor growth. Hepatic transplantation is reserved for patients in whom tumor progresses or symptoms of hormone production or mass effect persist. STUDY DESIGN: This is a retrospective review of eight patients with neuroendocrine tumor metastases who were referred to the Mount Sinai Hospital for evaluation for hepatic transplantation. RESULTS: Of the eight patients, three have undergone transplantation; all are alive, with no evidence of tumor recurrence at 12 to 30 months. In two patients, symptoms have been controlled by embolization of the hepatic artery or chemotherapy, or both; another has had massive hepatomegaly as a result of tumor progression, with wasting and portal hypertension, and currently awaits transplantation. Two patients died as a result of progressive disease, soon after referral. CONCLUSION: Transplantation of the liver may be an important treatment modality for a selected group of patients with neuroendocrine tumors unresponsive to conventional therapy.

Adult↗