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Biomedical subjects

L D Ferrell

Publications and source records attributed to L D Ferrell.

At least 73 records · Page 4Linked to original sources
PubMed1992

Glutathione monoethyl ester ameliorates caerulein-induced pancreatitis in the mouse.

Studies in animal models suggest that oxygen radicals may be important in the pathogenesis of acute pancreatitis. Because glutathione is an essential component of the defense against radical-mediated cellular injury, we investigated whether pancreatic glutathione content is influenced by inducing acute pancreatitis and whether augmenting the intracellular supply of glutathione would alter the course of pancreatitis. Caerulein, a decapeptide cholecystokinin analogue, induces acute necrotizing pancreatitis in mice when given in high doses (50 micrograms/kg per h) over a period of 6 h. The pancreatic glutathione content (total, GSH + GSSG) in mice treated with high-dose caerulein fell to 17% of normal within 4 h of beginning caerulein and recovered toward normal after discontinuing caerulein treatment. Mice treated with glutathione monoethyl ester (20 mmol/kg 1 h before caerulein, 10 mmol/kg 3 and 7 h after starting caerulein) were found to have blunted depletion of pancreatic glutathione, diminished histologic evidence of pancreatitis (necrosis, inflammation, and vacuolization), and lower serum amylase values compared with mice treated with caerulein alone. These findings suggest that the profound depletion of pancreatic glutathione caused by hyperstimulation of the pancreas with caerulein is critically important in the pathogenesis of acute caerulein-induced pancreatitis.

Amylases↗
PubMed1991

Persistent hepatitis B virus following interferon alfa therapy and liver transplantation.

A 44-year-old man with chronic hepatitis B virus infection and cirrhosis was treated with recombinant human interferon alfa for 67 days immediately before orthotopic liver transplantation and immunoprophylaxis with hyperimmune globulin to hepatitis B virus in the peritransplant period. Dot blots for hepatitis B virus DNA demonstrated marked reduction in viremia after 41 days of interferon alfa treatment. Southern analysis for hepatitis B virus in liver showed a pronounced decrement in actively replicating forms in the explant, although hepatic infection was still detectable. After liver transplantation, tests for serum hepatitis B virus DNA and hepatitis B surface antigen remained negative. The patient died 32 days after transplantation of causes unrelated to hepatitis B virus. DNA isolated from liver and other visceral organs at autopsy showed infection of the engrafted liver and the persistence of monomeric relaxed circular forms of hepatitis B virus DNA in pancreas, kidney, and spleen. Thus, graft reinfection occurred despite aggressive antiviral therapy and immunoprophylaxis combined with liver transplantation. Existing viral serological markers appear insufficiently sensitive to assess residual infectivity.

Adult↗
PubMed1991

Histopathologic study of transjugular intrahepatic portosystemic shunts.

A detailed histopathologic analysis of intrahepatic portosystemic shunts was performed following liver transplantation in five patients. Gross examination revealed that all stents were patent and unchanged in size, shape, and position from initial placement. Histologic examination at 4 days revealed an irregular luminal surface with liver parenchyma protruding between the stent wires and a single, patchy layer of endothelial cells lining the shunt surface. By 3 weeks, the stent wires were covered by a pseudointima of granulation tissue, and the luminal surface was lined with a contiguous layer of endothelial cells. Excessive pseudointimal proliferation resulted in shunt occlusion at 3 months in one patient whose shunt was subsequently reopened percutaneously.

Female↗
PubMed1991

Effects of the seleno-organic substance Ebselen in two different models of acute pancreatitis.

This study evaluated the effects of the seleno-organic substance Ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one] in two models of acute hemorrhagic and acute edematous pancreatitis. Ebselen is known to catalyze glutathione peroxidase-like reactions and to inhibit lipid peroxidation. Hemorrhagic pancreatitis was induced by feeding a choline-deficient, ethionine-supplemented (CDE) diet to mice for 66 h. Edematous pancreatitis was induced by 7-h subcutaneous injections of 50 micrograms/kg of cerulein in mice. Ebselen was given from the beginning of the CDE diet either as a subcutaneous injection of 100 mg/kg at 6-h intervals or was mixed in with the CDE diet to yield a daily dose of 100 mg/kg of Ebselen. In further experiments, Ebselen was given at various time intervals after the beginning of the CDE diet as subcutaneous injections of 100 mg/kg at 6-h intervals. In the cerulein model, Ebselen was given 5 min prior to each cerulein injection at doses from 10-500 mg/kg. Prophylactic administration of Ebselen given orally or subcutaneously significantly improved survival from 38.5% in the control group of saline-injected CDE-fed mice to 61.9 and 65.0%, respectively. Ebselen also reduced increases in serum amylase and pancreatic weight in the diet model. Therapeutic administration of Ebselen significantly increased survival only when injections were started 20 h after the beginning of the CDE diet (64%), but not when started after 40 h (44%). Similarly, increases in serum amylase and pancreatic weight due to the CDE diet were significantly reduced by Ebselen only when injections were started after 20 h but not when started after 40 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Paneth-like cells in an adenoma and adenocarcinoma in the ampulla of Vater.

A case of adenocarcinoma with significant Paneth cell differentiation arising in a villoglandular polyp at the ampulla of Vater is presented. Paneth-like cells, containing distinct fuchsinophilic granules, were a prominent component of the nonglandular invasive adenocarcinoma and were also seen in the associated adenomatous polyp. Lysozyme, trichrome, and periodic acid-Schiff digest stains, and electron microscopy confirmed that the granules were lysosomal in nature. This case confirms that cells with Paneth-like features can be a significant component in invasive neoplasms and can occur at unusual sites such as the ampulla of Vater.

Adenocarcinoma↗
PubMed1990

Pancreatic exocrine secretion in acute experimental pancreatitis.

Little is known about exocrine pancreatic secretory function in patients with acute pancreatitis, in particular during the early phase of the disease. Therefore, this study evaluates basal and stimulated pancreatic secretion in vivo and in vitro in four different models of acute pancreatitis which reflect its clinical spectrum of severity: (a) edematous pancreatitis induced in the rat by seven IP injections of 50 micrograms/kg cerulein at hourly intervals; (b) edematous pancreatitis with cellular necrosis induced in the mouse by seven IP injections of 50 micrograms/kg cerulein at hourly intervals; (c) hemorrhagic pancreatitis induced in the mouse by feeding an ethionine-supplemented, choline-deficient diet for 66 hours; and (d) hemorrhagic pancreatitis induced in the rat by retrograde infusion of 0.6 mL 5% sodium taurocholate into the pancreatic duct. Secretory studies were performed in vivo and in vitro at various times after onset of pancreatitis. The results show that the exocrine pancreas gradually became resistant to cholecystokinin stimulation after the onset of acute pancreatitis in all four animal models. Cholecystokinin-stimulated secretion was almost abolished in vivo and in vitro at the time of maximal histological damage. In vivo basal secretion was also reduced. In vitro there was an increase in basal release of amylase from isolated acini that was not caused by an increase in luminal secretion but by enzyme release from damaged cells. The time course of improvement of secretory function after acute experimental pancreatitis depended on the severity of the pancreatitis. Recovery of secretory capacity took longer after severe necrotizing pancreatitis than after edematous pancreatitis. However, the ultimate resolution of secretory function was remarkable, in particular after severe hemorrhagic pancreatitis. In all four models, secretory capacity became indistinguishable from normal before the morphological alterations had completely resolved. The present experimental data suggest that pancreatic secretion, and particularly pancreatic secretory response to cholecystokinin, may also be reduced in patients early after the onset of acute pancreatitis.

Acute Disease↗
PubMed1990

Effects of long-term CCK stimulation and CCK blockade on pancreatic and intestinal growth, morphology, and function.

This study evaluated the effects of long-term cholecystokinin (CCK) stimulation and blockade on pancreatic and intestinal growth, function, and morphology. CCK release was induced by feeding of the protease inhibitor camostate and CCK blockade by feeding of the CCK antagonist CR 1409. Four groups of NMRI-mice received the following diets for 9 months (each group consisting of 36 mice): (1) chow (control); (2) chow + 100 mg/kg/day camostate; (3) chow + 50 mg/kg/day CR 1409; (4) chow + 100 mg/kg/day camostate + 50 mg/kg/day CR 1409. Long-term feeding of camostate greatly increased pancreatic weight by induction of marked hypertrophy (increase in protein content) and moderate hyperplasia (increase in DNA content). Camostate feeding also increased secretory capacity of the exocrine pancreas. Despite camostate-induced growth neither hyperplastic nor neoplastic nodules developed. The CCK-antagonist CR 1409 markedly inhibited the effects of camostate which are therefore mainly mediated by CCK. Neither long-term CCK stimulation nor CCK blockade altered morphology or composition of duodenal mucosa. Feeding of CR 1409 alone (i.e., without camostate) slightly but significantly decreased pancreatic content of protein and secretory capacity of enzymes when compared to the chow-fed control; pancreatic weight and DNA content remained unchanged after long-term administration of CR 1409. Thus, long-term, continuous and effective blockade of the CCK-receptor only slightly inhibited pancreatic growth and secretory capacity. CCK is, therefore, not an essential growth factor for the pancreas, although increases of endogenous CCK stimulate pancreatic growth and secretory capacity.

Animals↗
PubMed1988

Fine-needle aspiration biopsy of tibial adamantinoma: a case report.

Adamantinoma of long bones is a rare, primary bone tumor of controversial histogenesis, usually arising in the anterior midshaft of the tibia. This slowly growing, radiolucent, expansile tumor eventually causes thinning or destruction of overlying cortical bone. Fine-needle aspiration biopsy (FNAB) is a rapid, safe, and relatively painless means of obtaining diagnostic material from bone tumors, provided the mass has eroded through or markedly attenuated the overlying cortex. A case is presented of primary adamantinoma of the tibia which was sampled first by FNAB and subsequently by surgical biopsy.

Adult↗
PubMed1988

Therapeutic regimens in acute experimental hemorrhagic pancreatitis. Effects of hydration, oxygenation, peritoneal lavage, and a potent protease inhibitor.

In this study we evaluated the effects of hydration, oxygenation, peritoneal lavage, and the protease inhibitor gabexate mesilate in acute hemorrhagic pancreatitis induced by feeding mice a choline-deficient, ethionine-supplemented diet. Different groups of mice were kept at various concentrations of O2 (21%, 35%, and 45% O2), or were treated by either s.c. injections or i.p. injections of electrolyte solution at various doses (0, 4, 6, or 8 ml/day). Further groups were treated either with i.p. lavage, lavage with 1.5 mg/ml of gabexate, or i.p. injections of 100 mg/kg of gabexate without lavage. The potential benefits of the various regimens were assessed by measuring survival, various biochemical and histologic features, and alterations in hematocrit, pH, and blood gases. Increasing O2 concentrations reversed hypoxemia and acidosis, but had no effect on biochemical or morphologic alterations and did not improve survival. However, hydration by s.c. fluid markedly improved survival and normalized the hematocrit without having major effects on biochemical or morphologic alterations. Intraperitoneal fluid did not improve survival. Gabexate injections without lavage had a slight effect on survival and serum amylase concentration and very little effect on histology. Lavage without gabexate had a greater effect on survival, serum amylase, and histology. Addition of gabexate to the lavage fluid increased the beneficial effect of lavage. Increases in amylase and activated trypsin in ascites were markedly reduced by lavage and even more so by lavage with addition of gabexate. We conclude that sufficient hydration appears to be an important factor in supportive care for severe acute pancreatitis, whereas oxygenation without sufficient hydration has no major benefit. Peritoneal lavage with gabexate showed the greatest benefit of the various regimens for acute severe pancreatitis and is worthy of clinical trials.

Acute Disease↗
PubMed1988

Plastic-embedded endoscopic biopsies. Diagnostic advantages.

As the use of endoscopic biopsy has increased in recent years, the pathologists whose job it is to interpret these small specimens have been asked to give more specific diagnoses. Plastic embedding has proved to be a useful diagnostic tool because it provides better morphology than routine paraffin embedding and because enzyme histochemical and immunohistochemical markers can be used. We applied these techniques to endoscopic biopsies hoping to increase the diagnostic yield. Biopsies from 75 patients were fixed in paraformaldehyde, embedded in methacrylate, and sectioned at 2 mu. These sections were then compared with routine sections from the same patient. Additional special stains were used and enzyme histochemistry, or immunohistochemistry was performed on the plastic- or paraffin-embedded tissue as needed. We found that in 26.7% of the cases, plastic sections resulted in more specific diagnoses than was possible with paraffin sections. When distinguishing lymphomas from poorly differentiated carcinomas, this method provided much better morphologic differentiation and better demonstration of leukocyte common antigen than keratin staining. Identification of B- or T-cell antigens was possible on plastics but not on paraffin. Furthermore, lesions such as histiocytosis X and cryptosporidiosis were more accurately identified. Thus, we found that the plastic-embedded tissue provided all the information yielded by routine paraffin embedding and also improved the diagnostic yield on certain types of neoplastic or infectious processes.

Biopsy↗
PubMed1987

Gabexate mesilate (FOY) protects against ceruletide-induced acute pancreatitis in the rat.

Acute pancreatitis (AP) is believed to result from intraparenchymal activation of trypsin and other digestive enzymes within the pancreas followed by autodigestion of the gland. Gabexate mesilate (FOY), a synthetic guanidino acid ester exhibiting potent and versatile inhibitory actions on a number of proteinases (e.g., trypsin, kallikrein, C1-r, C1 esterase, plasmin, thrombin, phospholipase A2), was examined for its ability to protect the rat pancreas against development of AP induced by pharmacological doses of ceruletide (CRT). Rats were i.v. infused for 6 h with either CRT (5 micrograms/kg/h) or CRT + FOY (50 mg/kg/h). In FOY-treated rats the serum amylase and trypsinogen concentrations were reduced by 60 and 80%, respectively, compared to rats infused with CRT alone. Histologically, the extent of acinar cell vacuolization in the pancreas was significantly reduced and interstitial edema, although not assessed by quantitative morphometric techniques, appeared to be qualitatively lessened in the FOY-treated rats. The ability of FOY to inhibit significantly AP produced by supramaximal doses of CRT, coupled with its inhibitory properties on components of the coagulation and complement cascades, stress the importance of continued research on this compound as a potential therapeutic agent for treatment of AP and its systemic sequelae.

Acute Disease↗
PubMed1987

Experimental acute pancreatitis. In vitro magnetic resonance characteristics.

The effect of pancreatitis on magnetic resonance T1 and T2 relaxation times was evaluated in two different models of acute pancreatitis in the rat. Acute edematous pancreatitis was induced by repetitive intraperitoneal injections of the cholecystokinin-analogue caerulein; acute hemorrhage pancreatitis was induced by retrograde infusion of the bile salt sodium taurocholate into the pancreatic duct. T1 and T2 relaxation times were obtained in vitro from fresh pancreatic specimens at 37 degrees C with a 0.25 resistive spectrometer. In both edematous and hemorrhagic pancreatitis, significant prolongation of T1 and T2 was noted as early as 1.5 hours after the initiation of pancreatitis when compared with normal rat pancreas. Maximal prolongation occurred at 7 hours in the caerulein model with T1 of 966 +/- 46 msec (mean +/- SEM) (normal + 278 +/- 12 msec) and T2 of 75.9 +/- 2.9 msec (normal = 32.8 +/- 3.3 msec), and after 6 hours in the bile salt model with T1 of 798 +/- 40 msec and T2 of 92.5 +/- 3.3 msec. After the time point of maximal prolongation, T1 and T2 gradually decreased toward the normal values. The prolongation of T1 and T2 paralleled each other throughout the time course of pancreatitis in both models. The prolongation of both relaxation times correlated closely with pancreatic weight, water content, and amylase concentration in serum and ascites. The present determination of T1 and T2 relaxation times by in vitro spectrometry suggests that magnetic resonance imaging has the potential for detecting early pathologic changes in acute pancreatitis and thus may be helpful for an early clinical diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1987

Cancer-associated alterations of blood group antigen expression in the human pancreas.

Certain alterations of blood group substance (BGS) expression have been observed in gastrointestinal cancer tissues. However, in the pancreas little is known about BGS expression by normal or malignant tissue. The present immunohistochemical study analyzed simultaneously the expression of A, B, H, Lewisa (Lea), and Lewisb (Leb) antigens in specimens of normal pancreas, chronic pancreatitis, and pancreatic carcinoma (primary and metastatic). In normal pancreas all five antigens were expressed in ducts, ductules, and acini, but not in islets. Acinar cells expressed A, B, H, and Leb in supranuclear cytoplasm, whereas Lea was found mainly on centroacinar cells. Only BGSs that were appropriate for the host's blood type were expressed, except for one case of Lea deletion. BGS expression by chronic pancreatitis tissue closely resembled that by normal tissue. In primary pancreatic cancer two cancer-associated alterations were noted that were not found in either normal pancreas or chronic pancreatitis. Deletion of an expected A, B, H, or Leb antigen occurred in approximately 25% of cases, particularly in more poorly differentiated cancers. Incompatible expression of an unexpected A or B antigen occurred in 33% of cases, regardless of degree of differentiation. Metastatic pancreatic cancers also exhibited BGS deletion and incompatibility. In both primary and metastatic cancers the incidence of incompatible A or B expression was higher in cancers from the United States than in cancers from Japan, but the incidence of BGS deletion was similar between the two countries. It was concluded that deletion of A, B, H, or Leb antigens and incompatible expression of A or B antigens are cancer-associated events in the pancreas.

ABO Blood-Group System↗
PubMed1987

Expression of LewisX and sialylated LewisX antigens in human colorectal polyps.

The LewisX (LeX) antigen [characterized by trisaccharide Gal beta 1----4 (Fuc alpha 1----3)N-acetylglucosamine] is an oncodevelopmental antigen in the human colon. Monoclonal antibodies (MoAbs), anti-SSEA-1 and AH8-183, which recognize LeX antigen either on short oligosaccharide side chains or as a terminal immunodeterminant on longer carbohydrate side chains of glycoconjugates, bind to most colon cancer tissues but also to some normal colon mucosae. However, the monoclonal antibodies FH1, FH4, FH6, and IB9, which recognize extended difucosylated and trifucosylated LeX structures or their sialylated derivatives, are more cancer-associated because they rarely bind to normal colon mucosa. In the present study, these MoAbs were used to compare the expression of various LeX-related antigens in premalignant (adenomatous) and nonpremalignant (hyperplastic) colorectal polyps. Antigen expression in polyps was also compared to antigen expressions of normal colon mucosa and colon cancer tissues. The four MoAbs recognizing extended LeX antigens bound to adenomatous polyps (APs) significantly more than to hyperplastic polyps (HPs). In contrast, anti-SSEA-1 and AH8-183 recognizing monofucosyl LeX were less able to distinguish between APs and HPs. In APs, staining with the four MoAbs recognizing extended LeX antigens correlated with the premalignant parameters of larger polyp size, more severe dysplasia, and increased villose component. However, staining with AH8-183 correlated only with polyp size, and anti-SSEA-1 correlated only with polyp size and degree of dysplasia. In general, the staining frequency of HPs was similar to that of normal colon mucosa, although FH6, which did not stain any specimens of normal mucosa, stained a few HPs. The staining frequency of APs was less than that of colon cancer tissues, but these differences were generally not statistically significant. In conclusion, extended LeX antigens and their sialylated derivatives are cancer-associated antigens that are expressed preferentially in premalignant colon polyps, that tend to correlate with malignant potential in these polyps, and that may eventually help to define mechanisms involved in the polyp-to-cancer sequence.

Antibodies, Monoclonal↗
PubMed1987

Toxicity of sevoflurane in rats.

Sevoflurane, an experimental potent volatile anesthetic with a low blood/gas partition coefficient, degrades in the presence of soda lime to products the toxicity of which is unknown. We tested whether toxic products were produced by the passage of sevoflurane through soda lime, and a comparison was made of the toxicity of sevoflurane passed through soda lime with the toxicity of other potent volatile anesthetics in current clinical use. Halothane, isoflurane, sevoflurane (all in 1-MAC concentrations), or no anesthetic (control) were passed through soda lime for 4 hr with 12, 14, or 100% oxygen to groups of rats with hepatic microsomal enzyme induction. Separate groups of 12-13 rats were given 1 MAC of sevoflurane that had not passed through soda lime and either 14 or 100% oxygen. Sevoflurane was no more toxic than isoflurane and both of these anesthetics were less toxic than halothane. Soda lime was not a factor in any toxicity produced. Hepatic injury with all agents varied inversely with the oxygen concentration administered during anesthesia.

Anesthetics↗
PubMed1987

Chronic nonspecific inflammatory bowel disease of the cecum and proximal colon in children with grossly normal-appearing colonic mucosa: diagnosis by colonoscopic biopsies.

The diagnosis of inflammatory bowel disease rests on radiologic, endoscopic, and histologic criteria. Five patients, 2 to 17 years of age, sought medical attention because of chronic abdominal pain, diarrhea, and heme-positive stools. Rectal biopsies, visual inspection of colonic mucosa through the colonoscope, and contrast radiographs of the large and small intestine yielded nonspecific results. Serial endoscopic biopsies demonstrated a gradient of inflammatory changes diminishing in severity distally from the ileocecal valve and cecum. The disease process was most evident in specimens from the cecum, whereas biopsies distal to the transverse colon had a normal histologic appearance in all five patients. Biopsies from the proximal colon may provide evidence of inflammatory bowel disease not detectable using standard techniques. The combination of chronic abdominal pain, diarrhea, and heme-positive stools associated with inflammatory changes in biopsy specimens obtained from the proximal colon, but normal findings on radiologic, colonoscopic, and rectal biopsy examinations, may represent an early stage in the evolution of chronic nonspecific inflammatory bowel disease, including ulcerative colitis or regional enteritis (Crohn disease).

Adolescent↗
PubMed1987

Studies of the toxicity of I-653, halothane, and isoflurane in enzyme-induced, hypoxic rats.

The physical stability and low blood solubility of the new inhaled anesthetic, I-653, imply that this agent produces limited or no toxic effects. To test this possibility, its effects were compared with those of other volatile agents on hepatic, renal, and pulmonary specimens taken from enzyme-induced, hypoxic rats. Male Sprague-Dawley rats were pretreated with phenobarbital and exposed for 1 hr to 12% O2 and no anesthesia (control) or to 1.2 MAC of one of three anesthetics: I-653, isoflurane, or halothane. Liver, kidney, and lung specimens were taken 24 hr after exposure concluded. The livers of all rats given halothane (n = 6) had swelling (20.5 +/- 5.7% of a lobule [mean +/- SD]) and centrilobular necrosis (6.7 +/- 2.1% of a lobule). Isoflurane produced only slight injury (6.7 +/- 3.5% swelling and 1.0 +/- 0.0% necrosis in 3 of 15 rats). No hepatic injury occurred in control rats (n = 20) or in those given I-653 (n = 16). Pulmonary and renal injury were not evident with any agent. Results suggest that I-653 has equivalent or less effect on hepatic, renal, and pulmonary integrity than currently available inhaled anesthetics.

Anesthetics↗