Short-column liquid chromatographic assay for caffeine and chloramphenicol in serum.
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1-Propanol↗
Biomedical subjects
R S Markin
Publications and source records attributed to R S Markin.
Assay methods for cyclosporine monitoring following liver transplantation.
This article reviews therapeutic drug monitoring for cyclosporine in liver transplantation. Brief descriptions of various immunoassay methods include sample matrix selection, assay reagents, and metabolite cross-reactivity information. Multiple comparisons of the various methods are outlined. Examples of the method-dependent relationship between clinical events and changes in cyclosporine concentration are presented. Other potential predictors of liver allograft function are listed.
Chromatography, High Pressure Liquid↗
A macro-driven Lotus 1-2-3 template for calculating and plotting receiver-operator characteristic curves for clinical laboratory tests.
Receiver-operator characteristic (ROC) curve analysis has become an accepted method of evaluating the efficiency of clinical laboratory tests. The calculations necessary to plot such curves are not difficult, but are repetitive and time consuming. Such calculations are easily done by computers. The availability, ease of use and graphics capabilities of spreadsheet programs such as Lotus 1-2-3 lend themselves to these applications. In this article, we describe such an application.
Clinical Laboratory Techniques↗
Orthotopic liver transplantation for graft-versus-host disease following bone marrow transplantation.
Chronic graft-vs.-host disease occurs in 30%-50% of long-term survivors of allogeneic bone marrow grafts, and may eventuate in cirrhosis. In this study, a young woman, originally diagnosed as having acute myelogenous leukemia, underwent successful bone marrow transplantation but later developed graft-vs.-host disease-induced cirrhosis and recurrent variceal hemorrhage. She underwent successful orthotopic liver transplant. Her postoperative course was uncomplicated, with no evidence of rejection or recurrence of graft-vs.-host disease. As bone marrow transplantation is more widely used and survival improves, the number of patients with graft-vs.-host disease or venoocclusive disease resulting in cirrhosis is likely to increase. Hepatic transplantation should be considered for bone marrow transplant patients who develop end-stage liver disease.
Adult↗
Hepatic lipid peroxidation, sulfhydryl status, and toxicity of the blue-green algal toxin microcystin-LR in mice.
Microcystin-LR (MCLR), a cyclic heptapeptide produced by the blue-green algae Microcystis aeruginosa, produces death in female mice treated with 100 micrograms MCLR/kg. Kupffer-cell hyperplasia was observed histologically after treatment with 50 or 100 micrograms MCLR/kg. No other changes or lethality were observed with the 50 micrograms MCLR/kg, while 100% lethality occurred in less than 2 h in mice treated with 100 micrograms/kg. In these animals liver weights increased by 45% and hepatic hemoglobin content increased 106% at 60 min posttreatment. Liver histology showed loss of hepatic architecture and necrosis 30 min after treatment, and congestion with blood became evident at 45 min after treatment. Serum enzymes were significantly increased 45 min posttreatment. Hepatic nonprotein sulfhydryl content decreased 19% when calculated on the basis of cytosolic protein and 39% when based upon the total protein content, respectively. The sulfhydryl content of the liver cytoskeletal fraction decreased 26% by 30 min after treatment. Decreased enzyme-mediated and increased non-enzyme-mediated lipid peroxidation were observed in hepatic microsomes following both in vivo and in vitro exposure of hepatic microsomes to MCLR. The toxicity of MCLR may be related to alterations in the sulfhydryl content of the cytoskeletal protein. Furthermore, MCLR may either directly or indirectly affect microsomes, suggesting alterations in structure and function of smooth endoplasmic reticulum.
Alanine Transaminase↗
Filtration of platelet-poor plasma specimens yields platelet-free plasma. Application for batch analysis of beta-thromboglobulin and platelet factor 4.
The authors investigated filtration of platelet-poor plasma through a 0.2-micron filter for the analysis of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) in frozen specimens. Platelets were detected by electron micrograph in the platelet-poor plasma preparation without filtration. No platelets or platelet fragments were seen after filtration. Freezing the unfiltered specimens resulted in a significant increase in the beta-TG and PF4 concentrations, presumably because of release of these proteins from the platelet alpha-granules during freezing and thawing. There was no change in the PF4 levels and only a slight decrease in beta-TG levels after freezing of the filtered specimens. The filtered samples could be frozen for later batch analysis, resulting in considerable cost savings to the laboratory.
Blood Platelets↗
Reduction in mammary tumorigenesis in the rat by cabbage and cabbage residue.
Mammary cancer was induced in female Sprague-Dawley rats by a single injection of N-methyl-N-nitrosourea (MNU) and rats were randomized to control fat (5%) and high fat (24.6%) diets. In addition, dried cabbage (5 and 10%) and collards (5%) were included in the diets of some animals. No statistically significant differences were observed in food consumption, body wt gain and caloric intake between the MNU-treated and control groups in the rats fed the low-fat diet. However, the groups fed the high-fat diet consumed more than the rats maintained on the control diet. The rats on the control fat diet containing cabbage exhibited a significantly lower incidence of mammary cancer than rats that were fed the control-fat diet without cabbage. This effect was not observed in comparable rats on the high-fat diet. The inhibitory effect on mammary tumorigenesis was demonstrated using a residue obtained from cabbage by exhaustive extraction with methanol, methylene chloride and petroleum ether. These studies reinforce the efficacy of cabbage as a 'suppressor' of cancer in experimental model systems under control-fat dietary conditions.
Animals↗
Epstein-Barr virus-associated syndromes in immunosuppressed liver transplant recipients. Clinical profile and recognition on routine allograft biopsy.
The clinical profile and histopathologic changes in needle biopsies of the liver were studied in 10 cases of acute Epstein-Barr virus infection occurring in liver transplant recipients. The systemic viral syndrome in four cases resembled that seen in infectious mononucleosis, whereas in six others it was characterized by atypical signs and symptoms in the form of jaw pain, arthralgias, joint space effusions, diarrhea, encephalitis, pneumonitis, mediastinal lymphodenopathy, and ascites. Laboratory investigation showed marked elevations in hepatocellular enzymes and circulating atypical lymphocytes in the peripheral blood. Pancytopenia was noted in eight cases. A range of histopathologic changes was noted in the allografts ranging from alterations typically observed in infectious mononucleosis to a distinctive constellation characterized by (a) mixed mononuclear portal and sinusoidal infiltrates containing atypical large noncleaved cells and immunoblasts; (b) associated lobular activity indicative of a hepatitic process, and (c) relatively mild duct damage not in proportion to the severity of the inflammatory infiltrates. The patients responded to reduced immunosuppression, but recurrent viral syndromes occurred in four instances and one patient died of systemic lymphoproliferative disease.
Acyclovir↗
The impact of extended preservation on clinical liver transplantation.
The introduction of UW solution into clinical transplantation has permitted extended cold storage preservation of the liver. Over a 46-month period, we have performed 308 orthotopic liver transplants (266 primary, 42 retransplants) in 266 recipients. Our experience is divided into cold-storage preservation in Eurocollins (163 transplants in 140 recipients) and UW (145 transplants in 131 recipients) solutions. Donor and recipient factors were comparable between the two groups. The use of UW solution has permitted an increase in the mean preservation time from 5.2 +/- 1.0 [EC] to 12.8 +/- 4.3 [UW] hr (P less than 0.001). The mean total operating time was reduced but intraoperative blood loss was unchanged with UW preservation. The number of transplants performed during the daytime hours has increased dramatically (21.5% [EC] vs. 71% [UW], P less than 0.001). The incidence of primary nonfunction, hepatic artery thrombosis, 1-month graft survival, and early retransplantation were similar in the 2 groups. Initial allograft function as determined by bile production, histology, and clinical assessment were likewise similar. Mean serum bilirubin, transaminase, and prothrombin levels were virtually identical by 5 days posttransplant. The enhanced margin of safety afforded by extended preservation has increased the capability for distant organ procurement and sharing, minimized organ wastage, and improved the efficiency of organ retrieval. With the relaxation of logistical constraints, our rate of liver import has nearly doubled (20.9% [EC] vs. 39.3% [UW], P less than 0.001). Extended preservation has permitted the development of reduced-size liver grafting (n = 12), resulting in a significant reduction in the number of deaths occurring while awaiting transplantation. Therefore, we advocate the use of UW solution with selective extension of preservation based not only on donor and recipient factors but also on manpower, resource, and logistical considerations.
Adenosine↗
Donor selection for orthotopic liver transplantation: lack of an effect of gender or cytomegalovirus (CMV) status.
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Adult↗
Immunohistologic identification of Epstein-Barr virus-induced hepatitis reactivation after OKT-3 therapy following orthotopic liver transplant.
Reactivated Epstein-Barr virus infection associated with hepatitis appeared in a liver transplant patient receiving monoclonal OKT-3 antibody for rejection. The histologic findings in liver biopsy specimens characteristic of allograft rejection were observed prior to and during the initial phase of antirejection therapy. However, failure of a complete response to antirejection therapy promoted rebiopsy. The specimen showed portal infiltrates composed predominantly of plasma cells and immunoblasts. The presumptive diagnosis of Epstein-Barr virus hepatitis was confirmed by staining frozen liver tissue for Epstein-Barr virus nuclear-associated antigen. OKT-3 therapy was discontinued, and cyclosporine and steroid doses were reduced. Gradually, clinical features, serum aminotransferase and bilirubin levels, and the portal lymphoid infiltrate resolved. Epstein-Barr virus serology showed an increase in convalescent titers IgG-antiviral capsid antigen, and Epstein-Barr virus nuclear-associated antigen. The histologic, clinical, and laboratory features supporting the diagnosis of Epstein-Barr virus hepatitis in a liver transplant patient are presented and discussed. This diagnosis guided appropriate therapy.
Antibodies, Monoclonal↗
Primary sclerosing cholangitis: the emerging role for liver transplantation.
Primary sclerosing cholangitis is a progressive liver disease for which orthotopic liver transplantation is the only curative procedure. Questions exist regarding the role of temporizing procedures and the timing of transplantation. During the past 4 yr, we have performed liver transplants in 177 adult recipients. Twenty-six patients (14.6%) with primary sclerosing cholangitis received 30 transplants including 12 men and 14 women. The recipients were examined for a number of preoperative and postoperative variables. The 4-yr actuarial survival in patients with primary sclerosing cholangitis after transplantation was 88%. Patients were segregated according to preoperative risk variables. Twenty patients were low and medium risk, with one death (95% survival). Three patients were high risk, with two deaths (33% survival). In conclusion, orthotopic liver transplantation is safe and effective therapy for primary sclerosing cholangitis. Early referral for transplantation is recommended to reduce the mortality associated with this procedure in those with advanced hepatic failure.
Actuarial Analysis↗
Infection after liver transplantation.
Infections occurring in liver transplant recipients result in significant morbidity and mortality. Factors influencing the frequency of posttransplant infections include pretransplant nutritional status, latent viral infections, and the degree of immunosuppression used to modulate the immune response to the allograft. Infectious agents may be introduced into the patient via the allograft, through infusion of blood products, and through intravenous lines, catheters, and drains. Infections also develop as a result of reactivation of latent viruses or by overgrowth or invasion by endogenous organisms. The intensity of the immunosuppressive regimen directly affects the frequency of infection. Infection may be categorized as bacterial, viral, fungal, or protozoal. The most frequent organisms include bacterial--enterobacteriaceae; viral--cytomegalovirus; fungal--Candida species and Aspergillus species; and protozoal--Pneumocystis carinii. Diagnosing infection requires the use of many different methods in combination, including routine bacterial culture, viral culture, and fungal culture. Histologic and cytologic examination may lead to rapid identification of some organisms. Specialized collection procedures such as bronchoalveolar lavage provide rapid access to material for culture and cytologic examination. Serum serology in conjunction with histotopic or cytologic evaluation is useful in diagnosing some infections, such as Epstein-Barr virus. New technology such as polymerase chain reaction allows detection of all types of infection at or before the onset of clinical symptoms. Rapid and early diagnosis of infection in this patient population can reduce infection-related morbidity and mortality.
Bacterial Infections↗
Neural patterns in inflammatory bowel disease: an immunohistochemical survey.
The differential diagnosis of inflammatory bowel disease remains a significant diagnostic problem for surgical pathologists. Neural abnormalities, such as hypertrophy of nerve plexi, hyperplasia of ganglion cells, and ultrastructural axonal degeneration have been described in patients with regional enteritis. We performed an immunohistochemical survey of forty cases of regional enteritis, ulcerative colitis, nonspecific colitis, and normal colon. A panel of antibodies, directed against neuron-specific enolase, S-100 protein, synaptophysin, neurofilament protein, and nerve growth factor receptor, was utilized to evaluate the distribution of nerve fibers in paraffin-embedded tissue. Anti-synaptophysin and anti-nerve growth factor receptor highlighted small, arborizing nerve fibers in the mucosa, not apparent in the routinely stained sections. Intense staining of these fibers was observed in regional enteritis with antinerve growth factor receptor. This antibody may aid the discrimination of inflammatory bowel disease from other causes of colonic inflammation and facilitate the identification of regional enteritis in endoscopic biopsies.
Colitis, Ulcerative↗
Hepatic failure associated with imipramine therapy.
Imipramine, a widely used antidepressant, has rarely been associated with hepatic abnormalities. In the majority of reported cases, hepatic effects have been transient and readily reversible on discontinuation of the drug. We cared for an 11-year-old boy with hepatic failure and massive cell necrosis which followed treatment with imipramine for enuresis. This therapy led to fulminant hepatic failure and subsequent liver transplantation.
Child↗
Predictive value of intraoperative liver biopsies of donor organs in patients undergoing orthotopic liver transplantation.
The evaluation of prerevascularization and postrevascularization biopsies in comparison with clinical and laboratory data has revealed a direct correlation between elevated PT and AST levels and pericentral and panlobular individual hepatocyte necrosis. No other significant correlations were determined when comparing selected histologic features to selected clinical laboratory values. In conclusion, these biopsies are of limited use in predicting subsequent allograft function in the absence of prominent individual hepatocyte or pericentral necrosis.
Adult↗
Tracheal invasion by thyroid carcinoma.
Tracheal invasion may occur by direct extension of thyroid carcinoma. Follicular, papillary, mixed follicular and papillary, and poorly differentiated cell types have all been found to cause tracheal invasion. Two cases of tracheal invasion by thyroid carcinomas prompted us to review the literature, although our review revealed little current data on tracheal invasion. We reviewed the records of all patients surgically treated for thyroid carcinoma at the University of Nebraska Medical Center from 1976 through 1987. The results of this review and our review of the literature on tracheal invasion are reported here. We conclude that thyroid carcinomas behave most aggressively in men and older patients. The more poorly differentiated follicular thyroid carcinomas have also been found to behave aggressively. Our findings show that en bloc resections are indicated in certain patients with tracheal invasion.
Adenocarcinoma↗
Clinical patterns of cytomegalovirus disease after liver transplantation.
During a 43-month period, we performed 248 liver transplantations in 211 patients (127 adults and 84 children). Cytomegalovirus (CMV) disease was documented in 73 recipients (34.6%). Risk factors for CMV disease included donor CMV seropositivity, antilymphocyte therapy, and retransplantation. The mean time of occurrence of CMV disease was 38.3 days after transplantation, and the most frequent site of disease was the hepatic allograft. A total of 69 patients were treated with intravenous ganciclovir, with a prompt and lasting response documented in 51 (73.9%). The remaining 18 (26.1%) developed recurrent CMV disease, which was more common after primary CMV exposure. Cytomegalovirus disease was ultimately controlled by ganciclovir in 94.2% of cases. This disease occurs early after transplantation and can be related to well-defined risk factors. Although ganciclovir therapy is effective, preliminary experience with prophylaxis shows promise in reducing the incidence of CMV disease.
Adolescent↗