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Biomedical subjects

R Cameron

Publications and source records attributed to R Cameron.

At least 19 recordsLinked to original sources
PubMed1994

Prostaglandin E in the treatment of recurrent hepatitis B infection after orthotopic liver transplantation.

While orthotopic liver transplantation (OLT) has become the treatment of choice for most irreversible end-stage liver diseases, its role in patients with hepatitis B (HBV) infection is controversial. A high risk of reinfection of the transplanted graft, associated with significant morbidity and mortality, has been reported. Although passive and active immunization can delay reappearance of the virus in the allograft, there is not yet an effective therapy for recurrent HBV infection in liver transplant recipients. Between October 1985 and March 25, 1991, 28 OLT in 25 patients with acute and chronic HBV infections were performed. Twelve of the patients were HBV DNA-negative, six were HBV DNA-positive, and seven were not tested prior to transplantation. Only the 19 patients surviving more than 100 days after transplantation were considered to have sufficient duration of follow-up (mean 734 days; range 500-1545) to include in analysis of recurrence. Five (26%) were free of recurrent disease at the time of last follow-up (mean 1031 days, range 526 to 1770 days. Recurrent HBV in the allograft, as defined by positive immunoperoxidase stains of biopsy sections for viral antigens, was detected in 74% (13 male, 1 female; 7 Asian, 7 white) at a mean of 134 days posttransplantation. Histological changes of viral hepatitis, first appearing an average of 157 days (range 95-326) posttransplantation, were evident in 13 of 14 with positive immunostaining. Twelve of the 14 patients were treated, on an open trial basis, with intravenous and oral prostaglandin E (PGE) because of deteriorating clinical condition. Eleven of the twelve responded to PGE with an initial drop in serum transaminases, improvement in coagulopathy and resolution of encephalopathy. One patient failed to respond and died of a myocardial infarction within 9 days of institution of therapy. Three of the eleven patients with an initial response relapsed and died in liver failure as a direct result of recurrent HBV after 13, 16, and 37 days of treatment in association with generalized sepsis. Eight of the 12 patients (67%) had a sustained favorable response to PGE therapy (mean follow-up 737 days, range 403-1545). All patients with a sustained response had accompanying improvement in histology and reduction in viral antigen staining in hepatocytes. Treatment with PGE appeared to be of benefit in recurrent HBV infection of the transplanted liver with an initial response rate of 92% and a sustained response rate of 67%.

Administration, Oral↗
PubMed1994

Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathologic features.

BACKGROUND: Bronchioloalveolar lung carcinoma (BAC) is a unique type of lung cancer with distinguishing pathologic, biologic, epidemiologic, demographic, and perhaps etiologic features. METHODS: The authors investigated and analyzed all of the cases of pathologically confirmed BAC seen at our institution in the hope of discovering new or confirming known features of this disease. RESULTS: When cases of BAC expressed as a percentage of total lung cancers were analyzed in successive 5-year periods from 1955 to 1990, BAC rose from less than 5% to 24.0% (P < 0.001). Much of the increase in BAC occurred in women, as evidenced by a male-to-female ratio that wavered around unity. The mean age of BAC adenocarcinoma patients was 59.2 +/- 11.5 years, compared to 64.1 +/- 13.5 years for non-BAC adenocarcinoma (P < 0.05). BAC also contrasted with other forms of lung cancer by exhibiting a relatively high incidence of multifocality (25% versus 5%) (P < 0.001). There was an association between histologic subtype of BAC and pattern of pulmonic involvement. The mucinous subtype was more strongly associated with diffuse pulmonic involvement, and the sclerotic subtype was more strongly associated with multifocal involvement (P < 0.001). Furthermore, BAC cases exhibited a 20% incidence of dedifferentiation into patterns of poorly differentiated adenocarcinoma, a feature that was more associated with the mucinous and sclerotic subtypes (P < 0.05). CONCLUSIONS: The emergence of BAC as a prominent type of lung cancer should stimulate new basic laboratory and case-control studies to elucidate further the natural history and etiology of this unique disease.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1994

Liver transplantation for hepatocellular carcinoma.

Twenty-nine patients with hepatocellular carcinoma (HCC) underwent orthotopic liver transplantation (OLTx) at the University of Toronto. Four patients did not have cirrhosis. Of the 25 patients with cirrhosis, 19 had known or suspected HCC before OLTx. Eleven patients tested positive for the hepatitis B surface antigen (HBsAg). No patients received adjuvant chemotherapy. None of the patients have developed recurrent HCC in a follow-up of 9 to 87 months (mean: 33 months). The actuarial post-transplant survival of all patients at 3 months, 1 year and 3 years was 75%, 61%, and 46%, respectively. The survival of HBsAg-negative patients was 69% at 3 years, whereas HBsAg-negative patients had a 3-year survival of 18% (p = 0.045). These results suggest that OLTx for carefully selected patients with otherwise unresectable HCC is associated with a low risk of recurrence. HBsAg-positive patients with HCC have a high mortality, suggesting that they make poor candidates for OLTx.

Adult↗
PubMed1994

Neurons and astroglia express distinct subsets of Na,K-ATPase alpha and beta subunits.

We have analyzed the expression pattern of Na,K-ATPase alpha and beta subunit isoforms within the rodent and primate central nervous system. Membrane fractions prepared from rat cerebral cortical type-1 astrocytes and rat cerebellar granule and hippocampal neurons were characterized by immunoblot analyses using a panel of alpha and beta subunit isoform-specific antisera. Each cell type was found to express the alpha 1 isoform but showed differences in the expression of other subunits. Cortical astrocytes displayed alpha 2 and beta 2 subunits, whereas cerebellar granule neurons showed expression of alpha 3 and beta 1 subunits. All three alpha subunit isotypes were detected in hippocampal neurons. A survey of the immunofluorescent staining pattern of the alpha 3 subunit in rat and monkey brain confirmed that expression of this Na,K-ATPase alpha subunit isoform was restricted exclusively to neurons. These results suggest that both neurons and astrocytes express multiple, yet distinct, Na,K-ATPase isoenzymes. The identification of cell types expressing limited combinations of alpha and beta subunits should provide a framework for understanding the physiological significance of Na,K-ATPase isoenzyme diversity and may provide useful tools for the analysis of cell lineage in the mammalian central nervous system.

Animals↗
PubMed1993

The vascular pathology of human hepatic allografts.

Studies of hepatic transplant vasculopathy (TV) have described arterial lesions in selected cases but have not sought to establish the relative prevalence of various arterial and venous lesions. We examined 20 unselected liver allografts and 12 controls to establish the spectrum and distribution of transplant-related arterial and venous lesions. Sections of 1,175 arteries and 936 portal and hepatic veins were reviewed and several histologic parameters were tabulated. Fibrotic (18 cases: 184 arteries and 17 veins) and cellular (10 cases: 353 arteries and 33 veins) lesions were seen. Three allografts had evidence of severe TV with abundant foam cell, myointimal, and mixed fibrocellular lesions in the intima of arteries. These three grafts also had foam cells in portal veins. Allografts with TV had more stenotic arteries (P < .05) and more intimal cellular proliferation (P < .05) compared with non-TV allografts and with controls. Foam cells often demonstrated immunoperoxidase staining for actin, lysozyme, or UCHL-1. Two of the TV cases had marked paucity of bile ducts and required retransplantation.

Adult↗
PubMed1993

The role of transjugular liver biopsy in fulminant liver failure: relation to other prognostic indicators.

Early and accurate diagnosis and prognosis of patients with fulminant liver failure is of critical importance for optimum management. We investigated the role of transjugular liver biopsy in the management of patients with fulminant liver failure and assessed its value in comparison with the recently proposed King's College criteria. Sixty-one patients with fulminant liver failure, ages 2 to 82 yr, were retrospectively analyzed. The main outcome measures were survival vs. death or progression to orthotopic liver transplantation. Transjugular liver biopsy was successful in 60 of 61 patients, with a mean core tissue length of 2.1 cm. There were eight minor complications, all of which were managed conservatively. Biopsy specimens were evaluated for degree of fibrosis, percentage of hepatocellular necrosis and presence of bile duct proliferation, hepatocellular mitotic figures and binucleate hepatocytes for each of the 54 specimens available for analysis. In 34 of 54 patients (63%), the presumed clinical diagnosis was confirmed by transjugular liver biopsy. In 11 patients the procedure served to clarify clinical uncertainty, whereas in 9 of 54 (16.7%) the diagnosis was altered after transjugular liver biopsy. The percentage of necrosis was the only histological parameter that appeared to have significant discriminatory prognostic value, with only 2 of 19 survivors having greater than 70% necrosis. Twenty-one of these biopsy specimens were reviewed by two pathologists, and their degree of correlation for the various features was assessed. Almost perfect concordance was found between the two pathologists on the percentage of hepatocellular necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1993

Oral iron chelation with 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in iron loaded thalassemia patients.

Despite the successes of deferoxamine (DFO) in the treatment and prevention of iron overload, an effective orally available iron chelating drug is needed, since erratic compliance with irritating, cumbersome parenteral infusions still results in fatal iron accumulation in many patients. Disorders of increased iron absorption should also benefit from the development of safe and effective iron chelating agents. Individuals with non-transfusion-dependent thalassemia (thalassemia "intermedia"), exhibit excessive dietary iron absorption that can lead to serious iron loading by the second or third decade of life. An orally effective iron-chelating drug would have major therapeutic advantages for all these patients.

Administration, Oral↗
PubMed1993

Podocytic cytoskeletal disaggregation and basement-membrane detachment in puromycin aminonucleoside nephrosis.

Puromycin aminonucleoside--(PAN) treated rats develop acute nephrotic syndrome, mimicking human minimal lesion disease. In PAN nephrosis, podocyte detachment from the glomerular basement membrane (GBM) is the most likely cause of massive proteinuria in this model. To elucidate further the mechanisms of PAN-induced cellular dysfunction, new methods were employed to visualize podocyte cytoskeletal aggregation and to measure fibrillar attachment to the GBM. Adult Sprague-Dawley rats (n = 4/group) received a single tail-vein injection of PAN (75 mg/kg). On days 1, 2, 3, and 5 following injection, 24-hour urine collections were obtained for creatinine clearance, albuminuria, and total proteinuria. Then kidneys from each group were fixed by perfusion. Podocytic cytoskeleton was visualized by scanning electron microscopy. Subepithelial GBM staining and attachment fiber number, observed on digitized images of transmission electron micrographs, were quantitated with computer-based density analysis. A significant reduction in attachment fiber number in the GBM lamina rara externa occurred by day 5. On scanning electron micrographs, the secondary and tertiary podocytic processes were observed to be formed by highly aggregated cytoskeleton, which became partially disaggregated by day 3, was totally absent by day 5, and normalized by day 20. Immunogold staining revealed that actin and vinculin localized to the tertiary podocytic processes in the normal state were dispersed into the cell body following PAN. Podocyte cytoskeletal disaggregation precedes, and detachment from the GBM occurs simultaneously with, the onset of massive proteinuria in the PAN model.

Actins↗
PubMed1992

Development of glutathione S-transferase placental form (GST-P) stained foci during hamster buccal pouch mucosa carcinogenesis.

The expression of the placental form of glutathione S-transferase (GST-P) using anti-rat liver GST-P antibody was investigated in hamster buccal pouch mucosa (HBPM) treated with 0.5% dimethylbenz[a]anthracene (DMBA) biweekly for 12 weeks. This preliminary study showed that the anti-rat liver GST-P antibody is applicable to the HBPM model and that DMBA treatment induced GST-P positive foci. These foci are randomly distributed and frequently involved the hyperplastic and dysplastic segments of the epithelium, as well as squamous cell carcinoma. Further study is needed to explore the kinetics of these GST-P positive foci.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Reduction of tissue iron stores and normalization of serum ferritin during treatment with the oral iron chelator L1 in thalassemia intermedia.

In patients with thalassemia intermedia in whom hyperabsorption of iron may result in serious organ dysfunction, an orally effective iron-chelating drug would have major therapeutic advantages, especially for the many patients with thalassemia intermedia in the Third World. We report reduction in tissue iron stores and normalization of serum ferritin concentration after 9-month therapy with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in a 29-year-old man with thalassemia intermedia and clinically significant iron overload (SF 2,174 micrograms/L, transferrin saturation 100%; elevated AST and ALT, abnormal cardiac radionuclide angiogram) who was enrolled in the study with L1 75 mg/kg/day after he refused deferoxamine therapy. L1-Induced 24-hour urinary iron excretion during the first 6 months of therapy was (mean +/- SD, range) 53 +/- 30 (11 to 109) mg (0.77 mg/kg), declining during the last 3 months of L1 to 24 +/- 14 (13-40) mg (0.36 mg/kg), as serum ferritin decreased steadily to normal range (present value, 251 micrograms/L). Dramatic improvement in signal intensity of the liver and mild improvement in that of the heart was shown by comparison of T1-weighted spin echo magnetic resonance imaging with images obtained immediately before L1 administration was observed after 9 months of L1 therapy. Hepatic iron concentration decreased from 14.6 mg/g dry weight of liver before L1 therapy to 1.9 mg/g liver after 9 months of therapy. This constitutes the first report of normalization of serum ferritin concentration in parallel with demonstrated reduction in tissue iron stores as a result of treatment with L1. Use of L1 as a therapeutic option in patients with thalassemia intermedia and iron overload appears warranted.

Adult↗
PubMed1992

ras transformation of simian virus 40-immortalized rat hepatocytes: an in vitro model of hepatocarcinogenesis.

Primary rat hepatocytes were transfected with simian virus 40 DNA and cultured in a chemically defined medium. Proliferating colonies developed after 2-3 weeks. Three cell lines were established by cloning albumin-secreting colonies, as identified by an immunooverlay assay. Two of the cell lines, ALB-6 and ALB-8, expressed all five liver-specific mRNAs studied, albumin, alpha-1-antitrypsin, fibrinogen, alpha-1-acid glycoprotein, and histidase. ALB-6 cells were nontumorigenic in nude mice while ALB-8 cells were weakly tumorigenic with only one of four injected nude mice developing a slowly growing tumor. Further transfection of ALB-6 and ALB-8 cells with an activated c-Ha-ras or N-ras oncogene resulted in strongly tumorigenic cells. The tumors induced by ras-transformed ALB-6 cells were moderately differentiated hepatocellular carcinomas. The tumors derived from ras-transformed ALB-8 cells were poorly differentiated, while the slowly growing tumors induced by untransfected or control DNA-transfected ALB-8 cells were well-differentiated trabecular hepatocellular carcinomas, suggesting histological dedifferentiation of cells following ras transformation. However, the synthetic capabilities of the cells were not lost in that the ras-transfected cultures and the tumors induced by ras-transformed cells retained the ability to synthesize the five liver-specific mRNAs. Thus we have developed an in vitro model of carcinogenesis in which, by sequential exposure to SV40 DNA and a ras oncogene, primary rat hepatocytes are transformed.

Animals↗
PubMed1992

Rat glomerular epithelial cells in culture express characteristics of parietal, not visceral, epithelium.

Glomerular epithelial cells (GEC) in culture are derived from intact isolated glomeruli. Although there is general agreement about distinguishing GEC from mesangial and endothelial cells, there is still uncertainty regarding the visceral versus parietal origin of cultured GEC. If these cells are to provide a useful model system, it is necessary to establish well-defined cell populations. The purpose of this study was to evaluate this important issue by comparing the characteristics of cultured GEC with glomerular epithelium from rat kidney sections. By electron microscopy, GEC were polygonal, with cilia and desmosomes between cells, similar to parietal cells in situ. Because intermediate filaments are specifically expressed in differentiated cells in the kidney, the expression of intermediate filaments in cultured GEC were compared with those of intact glomeruli. Cultured GEC are positive for cytokeratin and negative for vimentin and desmin, identical to parietal cells in situ. In contrast, podocytes are positive for vimentin and desmin and negative for cytokeratin. In vivo, podocytes express gp330 and puromycin-aminonucleoside (PAN) susceptibility, which are used as markers for cultured GEC. Immunoperoxidase staining of rat kidney sections with monoclonal anti-gp330 demonstrated gp330 localization to the cell surface and coated pits of the parietal cells, similar to its localization in podocytes. The presence of gp330 in cultured GEC was confirmed by immunoblot. PAN administration to rats induced vacuolization and detachment from the basement membrane in the parietal cells of Bowman's capsule, similar to the cytotoxicity observed in podocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Post-transplant recurrent hepatitis B viral liver disease. Viral-burden, steatoviral, and fibroviral hepatitis B.

Recurrence of hepatitis is a well-documented complication of hepatitis B liver disease, post-transplantation. It is well established also that the earliest hepatocellular change is the appearance of hepatitis B viral (HBV) markers and that the disease is rapidly progressive. In this article on 17 liver transplants in 16 HBV positive patients with long-term follow-ups (100-1234 days), the distinctive pathologic features of this disease are emphasized: the extreme viral load, the steatosis, and/or fibrosis. An attempt to quantitate the magnitude of the viral burden was made and the result was a staggering figure. In one patient, an estimated 10(18) HBV core particles were present in the liver. One of two patterns of progression were noted. In four patients in addition to the massive nuclear hepatitis B core antigen (HBcAg) and cytoplasmic hepatitis B surface antigen (HBsAg) positivity, superimposed hepatitic changes led to diffuse hepatic fibrosis (fibroviral hepatitis B); and in another six patients, extraordinary hepatocellular viral marker positivity and steatosis were the hallmarks (steatoviral hepatitis B). Steatosis is not usually considered a feature of HBV liver pathology. These results suggest that more than one type of posttransfusion recurrent hepatitis B liver disease exists pathologically.

Fatty Liver↗
PubMed1991

Syncytial giant-cell hepatitis. Sporadic hepatitis with distinctive pathological features, a severe clinical course, and paramyxoviral features.

BACKGROUND AND METHODS: We describe a new form of hepatitis, occurring in 10 patients over a period of six years, characterized clinically by manifestations of severe hepatitis, histologically by large syncytial giant hepatocytes, and ultrastructurally by intracytoplasmic structures consistent with paramyxoviral nucleocapsids. RESULTS: The patients ranged in age from 5 months to 41 years. The tentative clinical diagnosis before biopsy was non-A, non-B hepatitis in five patients and autoimmune chronic active hepatitis in the others. Five patients underwent liver transplantation; the others died. The diagnosis of syncytial giant-cell hepatitis was established pathologically. The liver cords were replaced in all 10 patients by syncytial giant cells with up to 30 nuclei. In 8 of the 10 the cytoplasm contained pleomorphic particles of 150 to 250 microns, filamentous strands, and particles of 14 to 17 nm with peripherally disposed spikes resembling paramyxoviral nucleocapsids. Structures resembling degenerated forms were found in the other two patients. One of two chimpanzees injected with a liver homogenate from the index patient had an increase in the titer of paramyxoviral antibodies, probably an anamnestic reaction to previous paramyxoviral infection, suggesting that a paramyxoviral antigen but not viable virus was present in the liver homogenate. CONCLUSIONS: Although further virologic studies will be required for precise classification, we believe that paramyxoviruses should be considered in patients with severe sporadic hepatitis.

Acute Disease↗
PubMed1991

Effects of treadmill exercise on weight cycling in female mice.

Weight cycling increases food efficiency and rate of weight regain. This study induced weight loss in adult female B6D2F1 mice via dietary energy restriction and exercise to determine whether the weight loss regimen influenced rate of weight regain. Four groups of animals were studied: RES, restricted (food restricted); EX, exercised (treadmill exercised); SC, sham control (treadmill exposure, not exercised); LC, lab chow control (appropriately aged control). Both EX and SC voluntarily reduced food intake to the level of the RES animals. The RES group showed increased food efficiency and rate of weight regain relative to the LC group; this effect was attenuated in both the EX and SC groups. These findings demonstrate that a) the cycling phenomenon occurs in mice, and b) stressors such as forced exercise or exposure to a novel environment can modify the pattern of food efficiency and rate of weight regain engendered by dietary restriction.

Animals↗