Search PubMed⌕ Search

Biomedical subjects

R S Markin

Publications and source records attributed to R S Markin.

At least 91 records · Page 5Linked to original sources

Disseminated Trichosporon beigelii infection after orthotopic liver transplantation.

A 25-year-old male, who received an orthotopic liver transplant for fulminant hepatic failure resulting from hepatitis B, had disseminated Trichosporon beigelii infection develop. Of the 55 cases of disseminated T. beigelii that have been reported in the English-language medical literature, most have occurred in patients who were both neutropenic and had compromised cell-mediated immunity. Mortality has ranged from 60 to 78%. Outcome appears to depend significantly on leukocyte recovery. Histologically, Trichosporon can be confused with Candida; however, recognition of the arthroconidia and pleomorphic hyphae and pseudohyphae of Trichosporon should allow their differentiation.

Adult↗

Heterotopic liver of the jejunum. Report of a case and a review.

A case of heterotopic liver of the jejunum confirmed by electron microscopy in a 2-year-old girl is described. We review the literature regarding heterotopic liver and discuss its embryogenesis. We suggest that in our case, there was trapping of hepatocyte-destined mesenchyme prior to biliary tree development.

Child, Preschool↗

Pontine and extrapontine myelinolysis following liver transplantation. Relationship to serum sodium.

The relationship between central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) and serum sodium changes in the setting of orthotopic liver transplantation (OLT) is examined. Postmortem examination of 14 patients with end-stage liver disease who underwent liver transplantation revealed CPM in four, of which three also had EPM. A retrospective review of clinical and laboratory data was performed on all patients. There were marked perioperative rises (21-32 mEq/L) in the serum sodium concentration in all four patients who developed myelinolysis. In contrast, the largest increase in sodium in patients without demyelination was 16 mEq/L. We conclude that perioperative rises in the serum sodium concentration increase the risk of myelinolysis. CPM and EPM should be considered if the patient develops mental status changes or focal neurological deficits several days after OLT.

Adult↗

Computed tomography and magnetic resonance imaging of cervical metastasis.

Thirteen patients with head and neck cancer underwent staging by clinical examination, computed tomography (CT), and magnetic resonance imaging (MRI) in a standardized blinded fashion. All patients subsequently underwent radical neck dissection with subsequent pathologic staging. CT and MRI each predicted 93% of staging results correctly, with clinical examination correct 67% of the time. Staging of primary tumors had an accuracy of 90% by clinical examination, 40% by CT, and 50% by MRI when compared to staging the pathologic specimen. Understaging was seen in 50% of CT scans and 30% of MRI scans. We believe either CT or MRI should be considered for routine staging of the neck in all head and neck malignancies.

Aged↗

Maternal serum and amniotic fluid alpha-fetoprotein testing: our approach to screening, diagnosis and counseling.

Maternal serum and amniotic fluid alpha-fetoprotein testing has increased significantly in our laboratory and throughout the state since 1985. The results of this test are reported in a novel fashion as multiples of the median. The calculation and reporting of the test results are highly dependent upon gestational age, maternal weight, race and presence or absence of maternal diabetes. When properly interpreted alpha-fetoprotein determinations are a good screening test for early detection of neural tube defects and Trisomy 21 (Down Syndrome). Our approach to screening, diagnosis and counseling is discussed.

Adult↗

Cyclosporine concentrations in blood after liver transplantation: correlation of immunoassay results with clinical events.

To investigate the clinical utility of immunoassays for cyclosporine and metabolites in plasma and whole blood, we monitored 25 patients after orthotopic liver transplantation. We compared cyclosporine as measured by TDx fluorescence polarization immunoassay (of both plasma and whole blood) and by two polyclonal radioimmunoassays (from Sandoz and INCSTAR). We found considerable differences in measured cyclosporine concentrations, which were dependent on method, matrix, and clinical condition. Correlation coefficients between results by the various methods for samples from individual patients ranged from 0.825 to 0.996. The three methods used for monitoring cyclosporine in whole blood gave proportional results (Sandoz less than INCSTAR less than TDx) in individual patients, but results for the two methods for plasma sometimes differed by more than 100%. In some cases, ratios of plasma cyclosporine concentration (result by TDx/result by Sandoz) were correlated with disturbances in hepatic excretory function or kidney function. This ratio may be useful in monitoring for nephrotoxicity.

Adolescent↗

Main autopsy findings in liver transplant patients.

The major autopsy findings from 22 patients (6 children, 16 adults) having undergone therapeutic orthotopic liver transplant are summarized. The mean age for children was 4.2 yr (range 4 mo to 9 yr) and 41 yr (range 20 to 57 yr) for adults. The mean posttransplant survival time in these patients was 16.7 d for children and 72.5 d for adults. The changes present in hepatic allograft included graft rejection (13), viral infections (11), massive necrosis due to hepatic arterial thrombosis (6), and recurrent hepatitis B (3). Infectious complications were present in 20 of 22 patients. The extrahepatic organs primarily involved by infection were lungs and brain. Bronchopneumonia and abscess formation were the most common lung findings, whereas cerebral edema and herniation, and infection occurred in the brain. Cardiac findings included acute myocardial infarction, mycotic mural thrombus and cytomegalovirus myocarditis. The gastrointestinal tract, adrenals, and kidneys were virtually spared. No significant changes were found in the pancreas and urogenital tract.

Adult↗

Biochemical and functional effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the heart of female rats.

Biochemical, functional and morphologic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the hearts of female rats were examined. Six days after the treatment of rats with TCDD, the blood pressures and resting heart rates were significantly less than in control animals. Treated animals were also less responsive to the effects of the beta-1 agonist, (-)isoproterenol. No histopathologic changes were observed in the heart although extensive centrilobular necrosis occurred in the liver after TCDD administration. Serum levels of thyroxine were 66% less than in control animals. Marked lipid peroxidation was produced in the liver with small but significant increases occurring in the heart. TCDD administration had no effect on catalase activity in the heart, but produced a 20% decrease in superoxide dismutase activity relative to control animals. The effects of TCDD on cardiac function do not appear to be due to a direct action of the xenobiotic on the heart but possibly to a down-regulation of beta-receptors in the heart as a result of the hypothyroid state.

Animals↗

Induction of hyperplastic liver nodules in Wistar and MRC-Wistar rats by phenobarbital and the liver carcinogens acetoxime, 1-nitroso-5,6-dihydrouracil and 3-nitroso-2-oxazolidinone.

We tested the ability of phenobarbital and two liver carcinogens, acetoxime and 1-nitroso-5,6-dihydrouracil (NDHU), to induce hyperplastic liver nodules (HLN) in MRC-Wistar and Wistar rats, using a system that included a single diethylnitrosamine (DEN) treatment, partial hepatectomy, and administration of the test compound in drinking water for 8 weeks. All three compounds induced significant HLN frequencies (number of HLN/cm2) in both rat strains. When the results for each strain were "normalized" for each compound and then combined, HLN frequency in MRC-Wistar rats was significantly lower (P less than 0.01) than that in Wistar rats. The weak liver carcinogen 3-nitroso-2-oxazolidinone (NOZ) did not induce a significant HLN frequency in MRC-Wistar rats. Acetoxime was highly volatile and was not mutagenic in the Ames test under a variety of conditions. The results for acetoxime are of interest because simple oximes are common constituents of oil paints. HLN induction by nitrosodihydrouracil is of interest because, unlike most liver carcinogens, this compound probably does not require metabolic activation and shows only a mild acute hepatoxicity.

Animals↗

Searching for the endogenous benzodiazepine using the graph theoretical approach.

The graph theoretical indices of several compounds with reported benzodiazepine receptor binding affinities were calculated. Our results demonstrate a structural similarity among diazepam, triazolam, and the beta-carboline nucleus and a structural dissimilarity to the purines and nicotinamide. This result correlates with their respective binding affinities. Using the graph theoretical indices as structural descriptors of the benzodiazepines and the significant ligands of the beta-carbolines, a search for peptide sequences as potential ligands was explored. Single amino acids through pentapeptides with all possible amino acid substitutions and chemical modifications were calculated. The peptides generated were subjected to graph theoretical analysis, and their indices were compared to those of the benzodiazepines. Comparisons resulted in seven dipeptides and six tripeptides that are topologically similar to the benzodiazepines and beta-carbolines. The dipeptides are histidine- or tryptophan-containing compounds with pyroglutamine, phenylalanine, and tyrosine residues in the second position. The tripeptides have two aromatic amino acid residues and a pyroglutamine or glycyl terminal residue. These structures are promising candidates because (1) they are structurally (topologically) similar to the benzodiazepines, represented by diazepam and triazolam, and to the beta-carbolines; and (2) they are sequences that may reasonably form a part of a larger peptide or that may be formed metabolically by proteolysis.

Anti-Anxiety Agents↗

Quantitative structure-activity study on human pharmacokinetic parameters of benzodiazepines using the graph theoretical approach.

The graph theoretical indices for a series of 13 benzodiazepines were calculated using a graph-path topological method. The total molecule, the ring fragments, and combinations of ring fragments were subjected to a quantitative structure-activity analysis using eight pharmacokinetic parameters. The metabolic clearance and the blood-to-plasma concentration ratios were most highly correlated with the graph theoretical indices, with R values of 0.975 and 0.938, respectively. These correlations were found when the diazepine + benzo fragment and phenyl fragment were used to calculate the graph-path indices. Terminal disposition half-life was correlated with the benzo + diazepine fragment, with R = 0.969. Truncating the graph-path codes by eliminating cycles in the total molecule markedly improved the correlation coefficients. When compared to the graph-path indices for the total molecule, the correlation coefficients for the terminal disposition half-life and metabolic clearance data rose from 0.721 to 0.935 and from 0.770 to 0.968, respectively, using the graph-path indices of the truncated molecule. Intrinsic clearance of unbound drug also was poorly correlated with the total molecule (r less than 0.7) but rose significantly using the graph-path indices of the truncated molecule (r = 0.971 and 0.975 for the well-stirred and parallel-tube models, respectively).

Anti-Anxiety Agents↗

Rapid identification of cytomegalovirus in liver allograft biopsies by in situ hybridization.

Identifying the etiology of hepatic dysfunction in liver transplant patients is critical to their clinical management and in maintaining graft survival. While cytomegalovirus (CMV) is a well-known cause of posttransplant hepatitis, the morphologic diagnosis of CMV hepatitis in liver biopsies can be difficult. Because conventional tissue culture for CMV requires days to weeks, the final results often arrive too late to be clinically useful. In this study, 44 liver allograft biopsies from 21 patients with hepatic dysfunction were evaluated for CMV by routine light microscopy, conventional tissue culture, and in situ DNA hybridization (IH) using commercially available biotinylated CMV-specific DNA probes. Whereas 38.6% of the biopsy specimens were positive by IH, 15.9% were culture-positive biopsies and 13.6% were positive by routine light microscopy. Assuming tissue culture to be the standard, IH demonstrated a sensitivity of 100% and a specificity of 73%. In comparison, routine light microscopy showed a sensitivity of 71.4% and specificity of 97.3%. In addition, three biopsy specimens positive only by IH were from three patients who had other liver biopsies positive for CMV by either light microscopy or viral culture. In situ DNA hybridization allows rapid detection (5-6 h) of CMV in paraffin-embedded liver allograft biopsies; it also has a sensitivity that surpasses routine histologic examination and perhaps even tissue culture.

Adolescent↗

Intestinal mucosa diamine oxidase activity reflects intestinal involvement in Crohn's disease.

The activity of diamine oxidase (DAO), an enzyme found in the apical villous cells of the small intestine mucosa, should reflect the status of the intestinal mucosa. Our purpose was to determine whether DAO activity in the intestinal mucosa is diminished in patients with Crohn's disease and correlates with the severity of histological changes. Mucosal DAO activity was determined in 42 tissue specimens from patients with Crohn's enteritis (n = 15), Crohn's colitis (n = 9), and ulcerative colitis (n = 11), and from patients with no intestinal disease (n = 7). DAO activity was estimated by the metabolism of [14C]putrescine. Histologic changes were graded on a scale of 0-4. Normal histology was graded as zero, mild edema, and inflammation in the lamina propria as one, crypt abscess formation and inflammation as two, more severe inflammation plus or minus granulomata as three, and most severe inflammation with active ulceration as four. Tissue DAO activity was significantly less in patients with ileitis (4.8 +/- 3.6) compared with those with Crohn's colitis (15.0 +/- 11.6), ulcerative colitis (16.8 +/- 19.7), and normal intestine (17.6 +/- 14.3 U/mg protein/h, p less than 0.05). Intestinal DAO activity showed a positive correlation with the histologic scores. Recurrence of Crohn's disease developed postoperatively in two patients with low tissue DAO activity (1.4 and 2.9 U/mg protein/h). Intestinal DAO activity is diminished in patients with Crohn's ileitis and correlates with the severity of histologic changes. Tissue DAO activity might prove useful in predicting the risk of recurrence or anastomotic complications after resection for Crohn's disease.

Adult↗

Development of squamous cell carcinoma of the esophagus after endoscopic variceal sclerotherapy.

We describe the case of a 45-yr-old white male with portal hypertension and presumed Laennec's cirrhosis who developed squamous cell carcinoma of the esophagus 8 months after completion of a course of endoscopic variceal sclerotherapy. The epidemiology and natural history of esophageal cancer and their relationship to our patient are analyzed. This report emphasizes that squamous cell carcinoma of the esophagus should be considered in the differential diagnosis of postsclerotherapy dysphagia. Further studies will be required to determine whether or not esophageal variceal sclerotherapy is associated coincidently or causally with the development of squamous cell carcinoma of the esophagus in patients at increased risk for this condition.

Carcinoma, Squamous Cell↗

Hepatocarcinoma in a child with the Alagille syndrome.

A child with the Alagille syndrome of intrahepatic bile duct paucity developed hepatocarcinoma. Disabling cirrhosis had rendered this child a suitable candidate for transplantation before the discovery of carcinoma. However, the extension of the tumor outside the liver precluded the performance of this potentially life-saving operation. Serial monitoring of the serum alpha-fetoprotein concentration may be of value in the early identification of tumors in pediatric candidates for transplantation.

Abnormalities, Multiple↗

Thromboangiitis obliterans (Buerger's disease) and smokeless tobacco.

Thromboangiitis obliterans, a distinct clinical and pathologic entity characterized by segmental inflammatory and proliferative lesions of the tunica media of small arteries and veins, has been reported frequently in men who have a history of heavy cigarette smoking. We report a case of thromboangiitis obliterans in a 38-year-old man that was clearly associated with the use of smokeless (chewing) tobacco. In addition to a physical history and examination and laboratory evaluation, a biopsy of the skin and deep subcutaneous tissue of the patient's left thigh was performed, and this revealed occlusion of 2 large dermal blood vessels by a highly organized thrombus. A regimen of nifedipine and antiplatelet therapy, plus complete abstinence from tobacco, resulted in resolution of the patient's symptoms and pain. Our findings may be of particular importance in view of the increasing popularity of smokeless tobacco and the complications which may result from its use.

Adult↗