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Biomedical subjects

R S Markin

Publications and source records attributed to R S Markin.

At least 37 records · Page 2Linked to original sources

Epstein-Barr virus hepatitis after liver transplantation.

OBJECTIVES: The purpose of this study was to review our experience with Epstein-Barr virus (EBV) hepatitis after liver transplantation. METHODS: During a 68-month period, we performed 668 liver transplants and 585 patients. We identified 11 patients (2 percent), including 5 adults and 6 children with EBV hepatitis after liver transplantation. The diagnosis of EBV hepatitis was established by evaluating allograft biopsies. The histology was confirmed by the use of polymerase chain reaction technology. RESULTS: The average time of diagnosis after liver transplantation was 45 days. Eight of eleven cases occurred within the first six months after transplantation. After the diagnosis of EBV hepatitis, treatment consisted of a decrease in immunosuppression plus antiviral therapy and intravenous immunoglobulin. The one-year actuarial survival for patients with EBV hepatitis, was 73 percent (8 of 11). Two patients died of progressive multi-organ EBV involvement. To determine the risk of developing EBV hepatitis, we reviewed our experience with the administration of antilymphocyte preparations in 585 patients. The patients found to have a significantly greater risk of developing EBV hepatitis included those receiving more than one course of antilymphocyte therapy or greater than a total dose of 70 milligrams of OKT3 in a single course. CONCLUSIONS: EBV hepatitis after liver transplantation is an infrequent event, which may be treated successfully. The occurrence of EBV hepatitis appears closely linked to the use of antilymphocyte preparations.

Adult↗

Cholangiocarcinoma following orthotopic liver transplantation. A unique pattern of recurrence diagnosed using immunohistochemical stains.

Tumor recurrence is an important complication following liver resection or transplantation for primary liver malignancy. We describe and immunohistochemically characterize a unique pattern of recurrent cholangiocarcinoma in a 45-year-old woman after orthotopic liver transplantation. In routine histologic sections, cytologically malignant cells infiltrated sinusoidal channels and occasionally simulated atypical Kupffer cells. Immunoperoxidase markers for low-molecular-weight cytokeratins highlighted these malignant cells and established their epithelial character. The presence of malignant cells within sinusoids may be subtle and requires careful evaluation of biopsy material. In appropriately selected cases, immunoperoxidase stains for cytokeratins may help in the detection of recurrent primary tumors of the liver.

Bile Duct Neoplasms↗

Glomerular injury in end-stage liver disease--role of circulating IgG and IgM immune complexes.

The relationship of IgG- and IgM-bound circulating immune complexes and immune dysfunction to glomerular injury was evaluated in 15 children with end-stage liver disease (ESLD) awaiting liver transplantation. Compared with age-matched controls, children with ESLD had significantly (P < 0.01) increased serum IgG, IgA, and IgM levels, as well as IgG- and IgM-bound circulating immune complexes. Furthermore, they showed a significant (P < 0.05) depression of C3 and C4 levels compared with controls. Hematuria occurred in 66% of children with ESLD, and the urinary protein/creatinine ratio was also significantly (P < 0.01) increased compared with controls (4.65 +/- 2.56 vs. 0.16 +/- 0.04 mg/mg). Light microscopy of renal biopsy tissue obtained from 6 children with ESLD at the time of transplantation demonstrated mesangial proliferation and expansion with basement membrane splitting. This was associated with subendothelial deposits on electron-microscopic examination, compatible with a diagnosis of membranoproliferative glomerulonephritis. By immunofluorescence, deposition of IgG, IgA, and IgM occurred in various combinations with co-deposition of complement fragments. We conclude that membranoproliferative glomerulonephritis is a common finding in children with ESLD, probably due to entrapment of circulating IgG- and IgM-bound immune complexes.

Antigen-Antibody Complex↗

Hepatobiliary complications of total parenteral nutrition.

The relationships between various hepatobiliary disorders and the administration of total parenteral nutrition (TPN) were reviewed and, in particular, the role of TPN in their pathogenesis was critically evaluated. Several clinical and pathological entities including steatosis, steatohepatitis, cholestasis, and cholelithiasis have been commonly linked to TPN, and instances of chronic decompensated liver disease have been reported. However, it is concluded that it is often difficult to extricate the effects of TPN on hepatobiliary function from many other hepatotoxic factors that may be operative in these patients. Thus, whereas considerable evidence exists to support a role fro carbohydrate or calorie excess in TPN solutions in the pathogenesis of steatosis, a loss of enteric stimulation and not TPN per se may be the primary factor in the development of cholestasis, biliary sludge, and gallstones. The apparent predilection of infants to TPN-related cholestasis may be based on the relative immaturity of the neonatal biliary excretory system.

Adult↗

Treatment of mammalian bite wounds of the maxillofacial region.

Infected human bites may result in devastating consequences. Failure to recognize the destructive potential of infections of bone, tendons, joints, and soft tissue caused by oral microorganisms can lead to serious loss of intrinsic functions. Rapid prevention or resolution of infection by appropriate use of antibiotics and surgical treatment continues to be a therapeutic challenge.

Animals↗

Fulminant hepatic failure with massive necrosis as a result of hepatitis A infection.

Fulminant hepatic failure as a result of hepatitis A is a rarely diagnosed complication entity in developed countries. With the advent of specific serologic markers for acute hepatitis A virus infection, the incidence and pathology of fulminant hepatitis A can be more clearly defined. We describe four patients (one adult, three children; two males and two females, ages 2 1/2-58 years) referred to our institution for orthotopic liver transplantation subsequent to fulminant hepatic failure following hepatitis A infection. All of these patients had a history of residence in or travel to hepatitis A endemic areas. Hepatitis A infection was documented by the presence of serum IgM against hepatitis A virus prior to transplantation. Infection with hepatitis B virus, cytomegalovirus, Epstein-Barr virus, and herpes simplex virus was excluded by clinical and specific serologic examinations. All patients presented with varying degrees of encephalopathy, progressing to coma. Coagulopathy in the form of prolonged prothrombin time and partial thromboplastin time was present in all patients. Peak liver parenchymal enzymes increased to greater than ten times the upper limit of the normal range. Total and direct bilirubin levels increased to > 20 and 10 mg/dl, respectively. Histologic evaluation of the explanted livers showed a spectrum of changes ranging from periportal hepatocellular necrosis with focal parenchymal collapse and prominent bile duct proliferation to massive necrosis with complete loss of hepatic architecture.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

Fulminant hepatic failure after methotrexate and PUVA therapy for psoriasis.

Acute hepatic failure developed after 8-methoxypsoralen and ultraviolet irradiation for psoriasis in a patient with prior methotrexate-induced cirrhosis. Review of the literature and the temporal relationship between 8-methoxypsoralen and hepatic injury in our patient suggests it may be a direct hepatotoxin. In our report, submassive necrosis superimposed on cirrhosis appears to have produced hepatic failure.

Hepatic Encephalopathy↗

Frozen section evaluation of donor livers before transplantation.

Frozen section examination was performed on 385 donor livers before transplantation. Exclusion criteria were applied to the donor livers examined to exclude potentially dysfunctional livers. The exclusion criteria included the following: severe macrovesicular steatosis, ischemic necrosis, prominent chronic portal inflammation, prominent periductular fibrosis, granulomatous inflammation, bridging fibrosis, and malignancy. Twenty-seven of the 385 donor livers examined were excluded before transplantation. The following histologic features were present in the excluded livers: severe steatosis (22), ischemic necrosis (2), portal inflammation (1), and periductular fibrosis (2). Steatosis was present in 51 of the 385 (13.25%) organs examined, including 22 of the donor organs excluded before transplantation. Twenty-nine livers with mild to moderate steatosis were implanted into size and blood type-matched recipients. Indicators of allograft function (prothrombin time and bilirubin) and damage (aspartate aminotransferase and alanine aminotransferase) were measured daily for the first 10 days after transplant. There was no statistically significant difference between the group of nonfat livers and donor livers containing mild steatosis. Statistically significant higher posttransplant serum alanine aminotransferase and prothrombin time levels were present in the patients with livers implanted with mild versus moderate steatosis. The 1-year survival rate for patients receiving fatty versus nonfatty donor livers was not statistically different (Kaplan-Meier, P = 0.592). No significant differences were found in the clinical and laboratory characteristics of donors whose organs were implanted compared with the clinical and laboratory characteristics of donors whose organs were excluded. The primary nonfunction rate after applying the exclusion criteria was 1.4%, which is a significant decrease compared with our primary nonfunction rate of 8.5% before using frozen section examination. Frozen section examination is useful in excluding donor organs which may become dysfunctional after transplantation.

Adenosine↗

Successful application of extracorporeal liver perfusion: a technology whose time has come.

We have used extracorporeal liver perfusion (ECLP) to aid in the management of three patients with fulminant hepatic failure (FHF). Organs were used for ECLP only if they would have gone otherwise unused through United Network for Organ Sharing. In all three patients treated, serial serum bilirubin and arterial ammonia values trended toward the normal range. The neurologic examinations improved dramatically in two patients, and metabolic function of the extracorporeally perfused livers was unequivocally demonstrated by the clearance of theophylline in the last two patients. Two patients ultimately had successful liver transplants, whereas the third patient failed to improve neurologically despite evidence of metabolic function by the extracorporeally perfused liver, and died 7 days after ECLP was discontinued, from pulmonary and renal failure. These studies suggest that, 30 yr after initial clinical trials, ECLP can be applied safely without the need for arterial access 1) as a bridge to transplantation, 2) to assess whether patients in FHF will benefit from improved hepatic function and therefore transplantation, and 3) potentially, to evaluate the "usability" of questionable donor organs.

Adolescent↗

The immunopathology and clinical relevance of lymphocyte cultures in liver transplantation.

Lymphocytes infiltrating human liver allograft biopsies were expanded in vitro for 3 to 5 days in recombinant IL-2 and then uniformly quantified and phenotypically characterized. The extent of proliferation was correlated with the degree and pattern of lymphocyte infiltration of the source biopsy as well as with the subsequent clinical outcome. Each of the 117 cases was assigned to one of three primary clinical outcome groups based on a retrospective evaluation of the clinical course before and after biopsy. The groups consisted of cases involving viral infection (n = 21), rejection (n = 40), or nonrejection-related allograft dysfunction (n = 56). The rejection group showed significantly greater in vitro expansion of lymphocytes (4201 +/- 685) compared to the nonrejection group (2720 +/- 408, P < 0.05). However, cases from the viral infection group showed the highest overall average lymphocyte growth (6655 +/- 2595, P < 0.05). Immunohistologic evaluation of the source liver transplant biopsy demonstrated increased T-cell infiltration of portal triads primarily by CD8+ T-cells in rejection compared to nonrejection cases (semiquantitative grade 1.3 +/- 0.1 versus 1.0 +/- 0.1, P < 0.05). The viral infection group demonstrated more significant T-cell infiltration (again predominantly CD8+) of the lobules compared to cases without viral infection (1.9 +/- 0.3 versus 1.3 +/- 0.1, P < 0.05). Immunohistologic evaluation of the cultured lymphocytes from the biopsies demonstrated a marked predominance (75% of cultures) of CD8+ T-cells compared to CD4+ T-cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

A randomized prospective trial of acyclovir and immune globulin prophylaxis in liver transplant recipients receiving OKT3 therapy.

The use of OKT3 therapy is a major risk factor for opportunistic infections in liver transplant recipients. In the last 2 years, we prospectively randomized 100 patients receiving OKT3 therapy into either a control group (n = 50) or a prophylaxis group (n = 50). Prophylaxis consisted of six doses of intravenous immune globulin over 4 weeks and oral acyclovir for 3 months after OKT3 therapy. The two groups were comparable with respect to demographic, immunologic, and clinical characteristics. The regimen of prophylaxis resulted in (1) a significant reduction in the incidence of herpetic and Epstein-Barr viral infections; (2) no change in the incidence of cytomegalovirus infections; (3) a significant decrease in the incidence of fungal infections; and (4) fewer deaths due to sepsis. The incidence of viral and fungal infections was higher after OKT3 induction than after rescue therapy. Our conclusion is that opportunistic infections are frequent after OKT3 therapy in hepatic allograft recipients. Treatment with intravenous immune globulin and oral acyclovir is safe and effective in preventing non-cytomegaloviral and fungal infections in this setting, thus conferring a survival advantage with fewer deaths due to sepsis.

Acyclovir↗

Cost justification of a laboratory information system: an analysis of projected tangible and intangible benefits.

A pre- and postimplementation comparison of tangible and intangible benefits of the laboratory information system are presented. The key activities projected to save costs through work reduction were evaluated as a basis for procuring a laboratory information system. Following implementation and four years of LIS operation the individual activities used for justification were resurveyed. The tangible benefits which were measured prior to LIS justification totaled $153,471.84 per year based upon fiscal year 1985-86 dollars. The objective re-evaluation of these activities four years after implementation and operation resulted in a measured $115,326.93 per year savings. The loss of projected savings is directly related to over estimates in the original justification evaluation and personnel behavior. The intangible benefits projected were all realized including a number of intangible benefits which made a significant impact on several departmental and clinical services at our institution.

Academic Medical Centers↗

Cytomegalovirus infection and disease after liver transplantation. An overview.

Cytomegalovirus is the single most important pathogen in clinical transplantation. Although much progress has been made in our understanding of the molecular biology and epidemiology of CMV infection and in our ability to diagnosis and treat CMV disease, it remains a major cause of morbidity but is no longer a major cause of mortality after liver transplantation. Risk factors for CMV disease after liver transplantation include donor and recipient serologic status, the use of antilymphocyte therapy, and retransplantation. CMV disease occurs early after transplantation, and the most frequent site of disease is the hepatic allograft. We have treated 79 patients with intravenous ganciclovir, with ultimate control of disease achieved in 69 patients (87.3%). Preliminary results using intravenous immunoglobulin and oral acyclovir for CMV prophylaxis in high-risk patients have been encouraging. In addition to producing clinical syndromes. CMV may have direct immunologic effects and is a marker of the net state of immunosuppression.

Cytomegalovirus↗

An unusual case of choledochal cyst causing hepatic failure requiring orthotopic liver transplantation.

The authors describe a case of orthotopic liver transplantation (OLT) in a patient with an infantile form of choledochal cyst that progressed to severe hepatic failure. Choledochal cyst must be included in the differential diagnosis of extrahepatic biliary obstruction in infants; it represents an additional reason to consider early exploratory laparotomy, both for diagnosis and to perform definitive excision. In the event that end-stage liver disease develops, OLT should be considered.

Choledochal Cyst↗

Esophageal ulceration following doxycycline ingestion.

Esophageal ulceration occasionally occurs in patients taking doxycycline capsules or tablets. In the case described here, examination of biopsy specimens obtained at endoscopy showed polarizable matrix material in the ulcer bed, thus confirming the diagnosis.

Adult↗

Bile duct hemorrhage: a biopsy finding after cholangiography or biliary tree manipulation.

We report on 13 patients with a distinctive bile duct lesion that presented histologically as erythrocyte engorgement of the epithelium of the small bile ducts, resulting in a red-beaded appearance. In ten of our cases, the lesion was associated with a recent history of cholangiography, and in two of our cases with vigorous manipulation of the distal biliary tree, raising the possibility that the hemorrhage might have been caused by increased pressure within the ducts during cholangiography or as a result of mechanical trauma to the biliary system.

Bile Duct Diseases↗

Treatment of valproic acid-associated hepatic failure with orthotopic liver transplantation.

OBJECTIVE: To report a case of valproic acid (VPA)-induced hepatotoxicity and to discuss the incidence rates, risk factors, possible etiologies, preventive measures, and treatment courses for this severe reaction. DATA SOURCES: Case reports, review articles, and relevant laboratory studies identified by MEDLINE. DATA EXTRACTION: Data were abstracted from pertinent published sources by one author and reviewed by the remaining authors. DATA SYNTHESIS: The case of a 23-year-old woman with VPA-associated hepatic failure was successfully treated with orthotopic liver transplantation. Hepatic failure is a rare, often fatal, adverse effect of VPA. Most cases of VPA-associated hepatic failure have occurred within several months of initiation of therapy. Initial symptoms of presentation often include nausea and vomiting, lethargy, or loss of seizure control. Laboratory values to be monitored include serum concentrations of hepatic enzymes, and, in some patients, tests indicative of the liver's synthetic capabilities. The exact mechanism of VPA-associated hepatic failure has not been clearly established; however, it is postulated to involve the formation of toxic metabolites. Major risk factors include age less than two years and concomitant treatment with more than one anticonvulsant. Other significant risk factors include underlying metabolic or serious neurologic disorders. CONCLUSIONS: Caution should be taken when initiating VPA therapy and clinicians should be familiar with the risk factors and clinical presentation of this reaction.

Adult↗