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Biomedical subjects

L D Ferrell

Publications and source records attributed to L D Ferrell.

At least 91 records · Page 5Linked to original sources
PubMed1987

Comparison of the toxicity of I-653 and isoflurane in rats: a test of the effect of repeated anesthesia and use of dry soda lime.

The low solubility and high stability of the new volatile anesthetic, I-653, suggest that this agent should have little or no toxic effect. This hypothesis was tested using repeated exposures to I-653, to isoflurane, or to no anesthetic. For 2 consecutive weeks, groups of 16 rats each were subjected to a total of six 2-hr exposures to 100% oxygen and 1.6 MAC I-653, isoflurane, or no anesthetic. Twenty-four hours after the last exposure, the rats were killed by administration of 100% carbon dioxide and then autopsied. Specimens were taken from brain, pituitary, lung, heart, duodenum, pancreas, kidney, and liver. No tissue damage attributable to either anesthetic was found nor was weight gain affected.

Anesthetics↗
PubMed1986

Ultrasound monitored hepatic cryosurgery: longevity study on an animal model.

Ultrasound imaging has been proposed to monitor the amount of frozen tissue during hepatic cryosurgery of primary and metastatic tumors. In this follow-up study, a cryolesion was produced in an adult pig under ultrasound monitoring. The animal was allowed to recuperate for 3 days before being sacrificed. Pathologic and histologic evaluation showed extremely close correlation with the ultrasound image. The necrotic region was clearly observable in the sonogram after 3 days. Ultrasonography can accurately represent the extent of the cryolesion both during as well as following cryosurgery.

Animals↗
PubMed1986

Enzyme histochemistry of hepatocellular neoplasms.

We examined a series of hepatocellular neoplasms, including 4 adenomas, 7 hepatoblastomas, and 18 hepatocellular carcinomas (HCC) with enzyme histochemistry in plastic-embedded sections. Our most striking observation was that there was a distinct difference in the staining pattern for alkaline phosphatase (Alk0) in benign and malignant tumors. Non-neoplastic controls (normal liver, reactive lesions) and benign neoplasms showed a distinctive canalicular pattern of staining with Alk0. Malignant neoplasms, however, showed a virtual absence of Alk0 staining; 6 of 7 hepatoblastomas and 17 of 18 HCCs were practically devoid of staining, while the two positive cases showed a pattern easily discernible from normal. The sensitivity of the observed Alk0 staining pattern in detecting malignant hepatocellular neoplasms was 92% and the specificity was 100%. Cytoplasmic gamma-glutamyl-transferase (GGT) was present in a minority of HCCs, but faint staining was also seen in normal liver or in adenomas. It appears that these nonmorphologic techniques may aid the surgical pathologist in the differential diagnosis of primary hepatocellular neoplasms.

5'-Nucleotidase↗
PubMed1986

Middle aortic syndrome. Effectiveness and durability of complex arterial revascularization techniques.

Middle aortic syndrome typically occurs as severe hypertension in young patients who have weak or absent femoral pulses and an abdominal bruit. It results from a diffuse narrowing of the distal thoracic and abdominal aorta, commonly involving the visceral and renal arteries. The clinical presentation, angiographic assessment, and surgical outcome of 10 patients (mean age: 19.5 years) who underwent one-stage revascularization for middle aortic syndrome were reviewed to determine the effectiveness and durability of one-stage revascularization techniques to relieve these complications. All patients were hypertensive (mean blood pressure: 176 mmHg); six (60%) had severe, poorly controlled hypertension, two of whom had previous failed operations for renovascular hypertension and one who presented with malignant hypertension and acute renal failure. Five patients had disabling myocardial insufficiency, only one of whom had documented coronary artery disease. Four patients had intermittent claudication. Aortography showed variable length high-grade midaortic stenosis, nine had visceral artery involvement, and eight had renal artery involvement. All patients underwent one-stage revascularization by a variety of autogenous and prosthetic techniques. The postoperative recovery was uncomplicated in eight of nine patients and was often associated with dramatic reduction in blood pressure. There was a single death from disruption of the thoracic anastomosis in a patient who had diffuse cystic medial necrosis of the aorta. Arterial biopsy in nine patients indicated evidence for both acquired and congenital origins of the midaortic stenosis. Late follow-up evaluation (mean: 4.1 years) showed normal growth and development, preservation of renal function, and relief of myocardial insufficiency in all patients. Seven patients (77%) are cured of their hypertension, and two (23%) have only mild hypertension. These results indicate that one-stage revascularization of patients with middle aortic syndrome can result in effective and durable relief of these severe life-threatening complications.

Adolescent↗
PubMed1986

Beneficial effects of cholecystokinin-receptor blockade and inhibition of proteolytic enzyme activity in experimental acute hemorrhagic pancreatitis in mice. Evidence for cholecystokinin as a major factor in the development of acute pancreatitis.

The effects of the cholecystokinin (CCK)-receptor antagonist proglumide, the protease inhibitor gabexate, and the hormones secretin and cholecystokinin-octapeptide (CCK-8) were studied in a model of acute hemorrhagic pancreatitis induced by feeding mice a choline-deficient, ethionine-supplemented (CDE) diet. Injections of gabexate and proglumide from initiation of CDE diet (before induction of pancreatitis) increased survival from 37% (diet alone) to 85 and 75%, respectively, and also ameliorated histological alterations and increases in serum amylase concentration and pancreatic activated trypsin. Secretin had no major beneficial effect. When proglumide or gabexate were given after induction of pancreatitis, proglumide still increased survival to 75%, whereas gabexate no longer did. Injection of nontoxic doses of CCK-8 before proglumide or gabexate injections completely abolished all beneficial effects and also increased the severity of pancreatitis due to CDE diet alone. Blockade of CCK receptors and early inhibition of protease activity may be beneficial in severe acute pancreatitis. Cholecystokinin appears to play a contributory role in the development of pancreatitis.

Acute Disease↗
PubMed1986

Sclerosing cholangitis associated with hepatic arterial FUDR chemotherapy: radiographic-histologic correlation.

During a 2-year period, cholangiography was performed on 17 patients with clinical evidence of cholestasis who were receiving hepatic intraarterial floxuridine (IA-FUDR) infusions for treatment of metastatic colorectal adenocarcinoma. The development of cholestasis was associated with persistently elevated alkaline phosphatase, but serial CT examinations of the liver showed no progression of the tumor. All patients had cholangiographic abnormalities (by endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography, or operative cholangiography) of the biliary ductal system similar to those in idiopathic sclerosing cholangitis. Certain features, however, appear specific to IA-FUDR-induced cholestasis. All patients studied had segmental involvement at the common hepatic duct bifurcation. The cystic duct and gallbladder were often involved, but the distal common bile duct was spared. Histologic features of periportal and periductal fibrosis were present in specimens obtained from percutaneous liver biopsy in three patients, cholecystectomy in four patients, and autopsy in two patients. When clinical signs of hepatic dysfunction occur in the absence of tumor progression, biliary sclerosis must be suspected.

Cholangiography↗
PubMed1986

Cancer-associated alterations of blood group antigen expression in human colorectal polyps.

Human colorectal carcinoma tissues may exhibit several patterns of altered blood group substance (BGS) expression: reappearance of A, B, H, or Lewisb antigens in distal colon; deletion of BGS in the proximal colon with or without precursor substance accumulation; and incompatible BGS expression in proximal or distal colon. The present study evaluated these cancer-associated alterations in colorectal polyps with different malignant potential. With respect to ABH antigens, hyperplastic polyps (HPs), considered to have no malignant potential, did not exhibit incompatibility and only a few cases demonstrated BGS reappearance or deletion. Adenomatous polyps (APs) however, frequently reexpressed ABH antigens or expressed incompatible BG-A or B in 27% of polyps; one specimen demonstrated BG-B deletion. Precursor expression was not found in HPs but was frequently observed in APs. Reappearance of ABH in distal polyps was significantly correlated with increasing grade of dysplasia, but was not significantly correlated with polyp size or histological type. With respect to Lewis antigen expression, Lewisb reappearance occurred in almost every distal polyp, and Lewisa-Lewisb coexpression was also quite common. Lea deletion was frequently noted, especially in HP, but the significance of this finding is unclear. This study indicates that several antigenic alterations that occur in colorectal cancer tissues also appear in premalignant polyps, and often in early stages of the neoplastic process. The observation that incompatible expression of BG-A or B occurs only in AP and cancer tissues (as well as mucosa adjacent to cancer) but not in fetal colonic mucosa, adult normal colonic mucosa, or HP, suggests that this may be a cancer-specific phenomenon.

ABO Blood-Group System↗
PubMed1986

Is enflurane hepatotoxic?

We evaluated 88 cases of hepatic injury that followed, and were attributed to, enflurane anesthesia. In 30 of the cases, data were insufficient to assess the role of enflurane vs other variables as causal factors. In 43 ("unlikely") patients, factors known to produce hepatic injury were clearly present; in the remaining 15 ("possible"), such factors were not evident. No consistent pathologic change was found in liver specimens from either the unlikely or the possible group of cases. A syndrome suggested to be associated with enflurane-induced hepatic injury was present in both groups and did not differ between groups. We conclude that the data do not demonstrate a causal relationship between enflurane anesthesia and subsequent liver injury and that if severe injury is caused by enflurane anesthesia, it is an extremely rare event.

Adult↗
PubMed1985

Caerulein-induced acute necrotizing pancreatitis in mice: protective effects of proglumide, benzotript, and secretin.

The onset, course, and regression of the biochemical and structural alterations associated with pancreatitis induced by various doses of caerulein were studied in the mouse. In addition, the protective effect of secretin was compared with that of the cholecystokinin-receptor antagonists proglumide and benzotript. Subcutaneous or intraperitoneal injections of caerulein induced increases in serum amylase concentration and pancreatic weight and histologic evidence of acute pancreatitis, all effects being dose-related. Cytoplasmic vacuoles were the earliest histologic alterations. As the pancreatitis progressed these vacuoles increased to an enormous size. Interstitial inflammation and acinar cell necrosis were prominent after 6 h, reached a maximum after 12 h, and mostly disappeared after 4 days. During the course of pancreatitis approximately 40% of the acinar cells showed signs of severe degeneration or necrosis at the most effective doses of caerulein. Electron microscopy showed both intact and degenerating granules inside the vacuoles. Signs of basolateral exocytosis of zymogen granules were not observed. During the regression of pancreatitis, focal atrophy was a remarkable histologic finding. Repetitive initiation of pancreatitis (six courses of caerulein injections over 5 wk) produced marked focal atrophy and early fibrosis. High doses of proglumide or benzotript markedly ameliorated both the biochemical and structural alterations induced by caerulein. Secretin, even at very high doses, had only minor protective effects. This study presents a model of acute necrotizing pancreatitis in which the severity of the induced pancreatitis ranges dose-dependently from mild interstitial inflammation to severe necrosis. The ultrastructural alterations described herein support the hypothesis that the trigger mechanism of acute pancreatitis appears to be a primary intracellular event rather than an interstitial event that secondarily damages the acinar cells.

Acute Disease↗
PubMed1985

Prostacyclin production in regions of arterial stenosis.

The effect of abnormal flow dynamics on prostacyclin (PGI2) production by intact endothelium is unknown. To investigate this we studied the effects of graded stenoses on vessel wall PGI2 production in dogs (n = 8) whose femoral and carotid arteries (n = 32) were narrowed by machine-milled clips, producing 1.0 cm segmental stenoses of 25%, 50%, 75%, and 90% diameter reduction. Three dogs were injected with Indium 111-labeled platelets and 12 vessels were scanned for platelet deposition. All stenotic vessels were excised at 6 weeks for histologic study (hematoxylin-eosin section and immunohistochemistry for factor VIII) and PGI2 radioimmunoassay (as the metabolite 6-keto PGF1 alpha). All vessels remained patent with no thrombus formation in any segment. Vessel imaging in platelet-labeled animals showed no significant deposition. Histologic analysis demonstrated an intact endothelial surface in the stenotic segments, confirmed by the demonstration of factor VIII production by these cells. PGI2 production (per unit surface area) by the arterial segments with greater than or equal to 50% stenosis markedly exceeded the PGI2 production by the normal proximal and distal segments (p less than 0.0002) and showed further significantly increased production with increasing degrees of stenosis (p less than 0.00001). The data indicate increased PGI2 production by normal endothelium in regions of arterial stenosis. The mechanism of this increase is unknown, but this endothelial "turn on" effect may serve to inhibit deposition of platelets and thrombus formation in the presence of disordered flow patterns.

Animals↗
PubMed1985

Nitrous oxide does not hinder the repair of halothane-induced hepatic injury in the rat.

Nitrous oxide administration may limit DNA synthesis by inactivating methionine synthetase, and may thus hamper the repair of an injured organ such as the liver. To test this possibility, we pretreated rats with phenobarbital and exposed them to 0.3 MAC halothane in 9% oxygen for 46 min, followed immediately and again 24 hr later by 70% nitrous oxide (0.25 MAC) at an FIO2 of 0.30 for 2 hr. The results from this group were compared with an anesthetic control group in which 0.35% isoflurane (0.25 MAC) was substituted for the nitrous oxide. Additional groups were given a third exposure to nitrous oxide or isoflurane 48 hr after the halothane exposure. All rats were killed 24 hr after their last anesthetic exposure. A second (nonanesthetic) control group of phenobarbital-pretreated rats received 0.3 MAC halothane in 9% oxygen for 46 min and no anesthetic thereafter. They were killed 24, 48, or 72 hr later. Histologic changes in the livers of rats did not differ among the groups given nitrous oxide, isoflurane, or no additional anesthetic after exposure to halothane alone. Thus neither nitrous oxide nor isoflurane appears to hinder the repair of hepatic injury produced by halothane in the hypoxic rat model.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1984

Increased nucleoside triphosphatase activity of rat liver nuclear envelope is associated with hepatocarcinogen exposure.

Altered transport of nuclear RNA sequences is an early response to carcinogens. Nuclear envelopes (NE) were isolated and assayed for nucleoside triphosphatase activity (NTPase), on the premise that this enzymatic activity participates in RNA transport. A common feature of the action of five different carcinogens (thioacetamide, 2-acetylaminofluorene, 3'-methyl-4-dimethylaminoazobenzene, dimethylnitrosamine, and aflatoxin B1), at low doses without significant toxicity, was to increase NE NTPase activity and to increase RNA transport, as assessed by the appearance of rapidly labeled RNA in the cytoplasm and by in vitro assay. The increases in NTPase were specific for the NE fraction, and early toxic effects of higher doses initially masked the increases. The induced increases in NE NTPase were long-lived. In contrast, increases in NE NTPase were observed only during the regenerative phase of CCl4 intoxication; the CCl4-induced increase was short-lived and returned promptly to control levels. These changes in NTPase activity were not associated with parallel changes in phosphorylation/dephosphorylation of NE proteins. Increases in NE NTPase and alterations in RNA transport, without attendant nuclear replication, may relate to altered nuclear RNA restriction. This change in a regulatory phenomenon may make these cells more susceptible to further modification, potentially playing a role in the initiation phase of carcinogenesis.

2-Acetylaminofluorene↗
PubMed1984

Brief periods of hypoxia can produce hepatic injury in rats.

To determine whether brief periods of hypoxia could produce hepatic injury, we pretreated Sprague-Dawley rats with phenobarbital, deprived them of food for 24 hr, and then exposed them to various hypoxic mixtures of nitrogen and oxygen for various lengths of time. Rats exposed to 6% oxygen for 15 or more minutes had centrilobular injury, the severity of which was directly related to the length of exposure (r = 0.71). Extrapolation of these data indicated that no injury would occur if exposures were less than 5 min. Experiments using lower concentrations of oxygen did not reveal hepatic injury, probably because death of the animals occurred before the appearance of detectable injury of the liver. Feeding animals before imposition of hypoxia markedly decreased the risk of hepatic injury. Whether patients who are deprived of food preoperatively and whose liver enzymes are induced incur an increased risk of hepatic injury from brief periods of hypoxia remains to be determined.

Animals↗
PubMed1984

Isoflurane does not prevent hepatic injury produced by halothane in rats.

We speculated that the inhibitory effect of isoflurane on the metabolism of halothane might reduce hepatic injury produced by halothane. To test this hypothesis we pretreated male rats with phenobarbital and 24 hr later exposed them to one of three types of anesthesia. One group of rats was anesthetized with 0.6 MAC isoflurane in 21-25% oxygen for 20 min, followed by exposure to 0.3 MAC isoflurane and 0.3 MAC halothane either in 9% oxygen for 46 min (n = 5) or in 12% oxygen for 60 min (n = 11). A second group of rats received 0.3 MAC halothane in 9% oxygen for either 46 min (n = 12) or in 12% oxygen for 60 min (n = 10). The third group received 0.3 MAC isoflurane in 9% oxygen for either 46 min (n = 12) or for 120 min (n = 8). The rats were killed 24 hr after the exposures and liver slides prepared. Histologic examination revealed that rats treated with isoflurane plus halothane, or with halothane alone showed a significant hepatic injury (P less than 0.005) when compared with those treated with isoflurane. Thus isoflurane failed to protect the liver from halothane-induced injury.

Animals↗
PubMed1984

Nitrous oxide, too, is hepatotoxic in rats.

Anesthetic hepatotoxicity was tested under various conditions of hypoxia in rats pretreated with phenobarbital. Administration of 0.3 MAC halothane or fentanyl in 9% oxygen (fractional concentration of inspired oxygen = 0.09) for 46 min produced centrilobular hepatic injury in all rats (P less than 0.001 vs all other groups). Isoflurane, nitrous oxide, and thiopental at 0.3 MAC did not produce hepatic injury greater than that produced in control rats given 9% oxygen, nor was significant injury produced in control phenobarbital-pretreated rats who breathed 6 or 7.5% oxygen for 46 min. With an inspired oxygen concentration of 7.5%, hepatic injury occurred after exposure to 92.5% nitrous oxide (P less than 0.05), but not after enflurane, isoflurane, or thiopental. When hypoxia associated with 9% oxygen was extended to 2 hr, 91% nitrous oxide produced significant injury (P less than 0.001 compared with the controls), while enflurane, isoflurane, and thiopental did not. These and previous results suggest that all anesthetics can produce liver injury in the hypoxic rat model and that the ranking of hepatotoxicity (most to least) may be halothane, fentanyl, nitrous oxide, enflurane = isoflurane = thiopental.

Animals↗
PubMed1983

Hereditary chondrocalcinosis in a Mexican-American family.

In a study of 45 adults in a family of Mexican-Indian ancestry, it was found that 22 (49%) had joint symptoms resembling those of degenerative joint disease. Eleven family members had radiographic evidence of chondrocalcinosis, and 1 adult and 3 adolescents had clinical histories and examinations consistent with the familial arthropathy, but no radiographic evidence of disease. The cause of the arthritis in the affected family members is calcium pyrophosphate crystal deposition. The mode of inheritance appears to be autosomal dominant with a high degree of penetrance. The disease is characterized by onset in the second to fifth decades of either episodes of acute inflammatory arthritis or degenerative joint disease. A unique finding of this study was a "halo" surrounding chondrocytes in 1 patient's cartilage, demonstrating loss of the proteoglycans.

Adult↗
PubMed1983

Carotid plaque histology using real-time ultrasonography. Clinical and therapeutic implications.

To evaluate the ability of ultrasonographic imaging to detect plaque hemorrhage in carotid atheroma, a study was undertaken that compared pathologic findings to preoperative ultrasonographic findings. Ultrasonography identified two plaque categories based on the heterogeneous and homogeneous echo patterns of the lesions studied. Heterogeneous lesions accounted for 91 percent of intraplaque hemorrhages (30 of 33) and 100 percent of ulcerated lesions (15 of 15). In 41 of 50 specimens (82 percent), ultrasonography correctly identified the presence or absence of plaque hemorrhage. False-negative studies (3 of 50) were due to the minute foci of remote hemorrhages. False-positive studies (6 of 50) resulted from plaques that contained large amounts of lipid or cholesterol. Preoperative ultrasound carotid imaging can be used to detect the histologic characteristics of plaque. Since recent clinicopathologic studies have implicated intraplaque hemorrhage and ulceration in symptomatic carotid disease, this information may be of value in choosing therapy, especially for the asymptomatic patient.

Aged↗