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Biomedical subjects

M E Clouse

Publications and source records attributed to M E Clouse.

At least 37 records · Page 2Linked to original sources

31P NMR assessment of orthotopic liver rejection in a rat model.

31P NMR spectroscopy was used serially to study rejecting (ACl-->LEW) and nonrejecting (ACl-->ACl) orthotopic liver transplants in rats. Recipients were evaluated on post-transplant days 1, 3, 5, 7, 9, and 11. The relative changes in phosphomonoester (PME), inorganic phosphate (Pi), high-energy phosphates and pH were studied. The earliest significant difference between the rejecting and nonrejecting groups was a decrease in the alpha-NTP peak area on Day 5. This was followed by significant decreases in beta-NTP and pH, and increases in PME and Pi on Day 7. High-resolution 31P NMR spectra of perchloric acid extracts demonstrated the PME increase to be due mainly to elevated phosphoethanolamine. Using the parameter (Pi + PME)/(alpha + beta + gamma-NTP), rejecting livers were distinguished from nonrejecting livers at a moderate stage of rejection.

Animals↗

Hepatic arterial chemoembolization for metastatic neuroendocrine tumors.

PURPOSE OF THE STUDY: To evaluate the effectiveness of chemoembolization of the liver with doxorubicin and iopamidol emulsified in ethiodized oil for the treatment of metastatic neuroendocrine tumors. PATIENTS AND METHODS: Twenty patients with hepatic islet cell or carcinoid metastases were treated with selected hepatic arterial embolization consisting of an emulsion of doxorubicin and iopamidol emulsified in ethiodol followed by Gelfoam powder embolization. Fifteen patients had failed intravenous chemotherapy. Two of the patients with carcinoid tumors had three embolizations over 4 and one 6 years earlier with gelatin sponge only. RESULTS: In 14 patients with hormonally active tumors, hormones secretion decreased 90% (range 69-98%) in 10 days with relief of symptoms in all patients. Average tumor size decrease was 84%. Average hospital stay was 8 days. Six patients are alive and asymptomatic at 14-33 months postembolization. Fourteen patients have died 2-16 months postembolization. Ten patients died 2-37 months postembolization from progressive liver disease. One of these patients was 103 months post-Gelfoam embolization and 13 months postchemoembolization. In 8 patients, the pancreas was the primary site: 5 were nonfunctioning islet cell carcinomas, 1 glucagonoma, 1 gastrinoma and 1 carcinoid. The primary site in 1 patient with carcinoid was the bronchus, and the primary site was unknown in 1 patient with gastrinoma. The remaining 4 patients died with liver disease under control from renal failure, peritonitis, carcinoid heart failure and generalized bone metastases. The response rate was 95% with median duration of response 8.5 months. The median survival was 24 months. CONCLUSION: Chemoembolization with doxorubicin and iopamidol emulsified in ethiodized oil is less morbid than embolization with particulate matter alone, is more convenient and less costly, and it is less morbid than the effects of systemic chemotherapy. The median survival, duration and response compare favorably with other reported therapies.

Adenoma, Islet Cell↗

Hepatic arterial chemoembolization for metastatic neuroendocrine tumors.

BACKGROUND: Patients with neuroendocrine neoplasma, even with metastases to the liver, often have indolent disease and are treated conservatively. However, when debilitating symptoms from hormonal syndromes or mass effect arise, more aggressive treatment may be warranted. METHODS: Thirty-nine chemoembolization procedures were performed in 30 patients with significant symptoms, with carcinoids and islet cell tumors. An emulsification of intraarterial doxorubicin, iodized oil, and water-soluble contrast was followed by embolization with absorbable gelatin powder or pledgets. RESULTS: Twenty-seven patients exhibited subjective improvement in clinical symptoms. Hormonal markers and/or tumor size decreased by at least 50% in 79% of patients. Inclusion of minor responses raises this to 92%. Seven complications were noted, and no procedure-related deaths occurred. Median survival was 24 months after chemoembolization or 53 months after diagnosis. Computed tomographic features of tumor vascularity, distribution of metastatic lesions, and distribution of ethiodized oil were not clearly correlated with outcome. Presence of a nonresected primary tumor had a negative effect on survival. CONCLUSIONS: Compared with previously described treatments for neuroendocrine liver metastases, this technique appears to be more effective and to be associated with less morbidity, and is recommended for patients with significant symptoms who have failed to respond to more conservative therapy and who are not surgical candidates.

Adult↗

Hepatic utilization of exogenous nucleotide precursors for restoration of ATP after cold ischemia in rats.

The study objective was to assess hepatic utilization of exogenous adenosine or adenine to enhance ATP recovery in rat liver after cold ischemia. ATP was measured noninvasively by 31P nuclear magnetic resonance (NMR) in perfused livers before and after 18 h of cold ischemia. The hepatocellular concentration of ATP during the initial postischemic reperfusion without adenosine or adenine coinfusion was 60% of that in fresh liver. The ATP increased significantly (P < 0.001) to 139% and 82% of baseline in postischemic livers coinfused for 90 min with adenosine or adenine (final concentration, 1 mmol/L), respectively. Less than 0.5% of the excess adenosine was catabolized to uric acid. In conclusion, adenosine and, to a lesser extent, adenine are salvaged by liver after extended cold ischemia to enhance ATP restoration. Provision of these ATP precursors, as components of an enteral formulation may facilitate the repletion of liver ATP and foster early resumption of liver function after an ischemic insult.

Adenine↗

A rat fatty liver transplant model.

A rat model of fatty liver transplantation has been developed to study primary nonfunction in fatty liver grafts. ACI rats were fed with a diet deficient in choline and methionine for 7, 14, 28, and 42 days. Fat content in the pretransplant livers was examined by gas chromatography and histology. The main constituent of the fatty droplets was determined to be triglyceride. The triglyceride concentration reached a maximum by day 14 and remained constant for an additional 28 days. Histology revealed an absence of necrosis in 14- and 28-day fatty livers but scattered hepatocytic necrosis and inflammation in 42-day fatty livers. After being given cold (UW stored, 4 degrees C) or warm (37 degrees C) ischemia, the fatty liver was orthotopically transplanted into normal ACI rats. The one-week survival of fatty liver grafts after 6, 12, 18, and 24 hr cold preservation was 5/5, 5/6, 3/8, 0/6 for 14-day fatty liver and 5/5, 4/6, 0/8, 0/6 for 42-day fatty livers. The survival of normal liver grafts was 5/5, 6/6, 5/9, 2/8, respectively. Increased survival rate was correlated with the absence of hepatocytic necrosis. The survival after 15 and 30 min warm ischemia prior to transplant was 5/5, 2/6 for normal liver grafts and 4/7, 0/6 for 28-day fatty liver graft, respectively. Fatty livers were less resistant to damage induced by cold or warm ischemia.

Animals↗

Hepatic microcirculatory changes after reperfusion in fatty and normal liver transplantation in the rat.

The hepatic microcirculation in fatty and normal liver grafts in ACI rats was investigated using in vivo microscopy. Six groups were studied. They were: normal and fatty control livers (sham operated), 6-hr cold University of Wisconsin solution (UW)-preserved fatty and normal liver grafts (survival conditions, fatty and normal liver grafts), 18-hr cold UW-preserved fatty livers (nonsurvival conditions, fatty liver graft), and 24-hr cold UW-preserved normal livers (nonsurvival conditions, normal liver grafts). Fatty livers in all groups were found to have narrow and irregular sinusoids with blood cell adhesions to endothelial cells. The number of adhesions increased as the preservation time increased. Sinusoidal blood flow area decreased as the preservation time increased and was correlated with survival in both normal and fatty liver grafts. The phagocytic activity of Kupffer cells (corrected for flow) increased as the preservation time increased. The phagocytic Kupffer cell activity of the 18-hr preserved fatty liver group was greater than the activity of any other group. These features may cause liver cell death and contribute to primary graft nonfunction after transplantation of a fatty liver.

Animals↗

31P NMR assessment of orthotopic rat liver transplant viability. The effect of warm ischemia.

The relationship between NMR visible high energy phosphates and transplant outcome for the case of liver damage by warm ischemia was investigated. In vivo 31P nuclear magnetic resonance (NMR) spectroscopy of rat liver was performed before the induction of warm ischemia in the donor and 20 min after reestablishment of portal blood flow in the recipient. Pretransplant damage was varied by subjecting the livers to 0, 15, 30, or 60 min of warm ischemia prior to harvesting. In the controls (0 min warm ischemia), 4 of 4 rats survived transplantation (one week survival end-point) and the mean NTP recovery was 94 +/- 8%; 3 of 6 rats survived in the 15 min warm ischemia group. Mean NTP recovery was 77 +/- 20% in the 15 min survival subgroup and 32 +/- 20% in the nonsurvival subgroup. Of 6 rats, 1 survived in the 30 min group. NTP recovery was 44% for the 30 min survivor and 37 +/- 5% in the nonsurvival subgroup. Of 4 rats, 1 survived in the 60 min warm ischemia group. NTP recovery was 56% for the 60 min survivor and 28 +/- 7% in the nonsurvival subgroup. Overall, there was a significant difference between the mean NTP recovery of the survival and nonsurvival subgroups (78 +/- 21% versus 31 +/- 18%, P < 0.001). The dividing line between the survival and nonsurvival groups was approximately 50% NTP recovery. Of 9 rats with liver NTP recovery greater than 50%, 8 survived while 10 of 11 rats with less than 50% recovery died. NMR visible NTP recovery 20 min after the reestablishment of portal blood flow was a good indicator of transplant outcome in the case of rat liver damage by warm ischemia.

Animals↗

23Na- and 31P-NMR studies of perfused mouse liver during nitrogen hypoxia.

The effects of nitrogen hypoxia on isolated perfused mouse livers from fed mice were studied at 37 degrees C using 23Na and 31P nuclear magnetic resonance (NMR) spectroscopy. The paramagnetic shift reagent, dysprosium-triethylenetetraminehexaacetic acid, was used to distinguish intracellular from extracellular sodium. The area of the intracellular sodium resonance remained relatively constant over the first 30 min of hypoxia and then increased by a factor of approximately 2 relative to controls over the next 30 min. High-energy phosphate metabolites were measured using 31P-NMR. The beta-ATP resonance decreased to zero, and the intracellular pH decreased from 7.3 to 6.9 during 60 min of hypoxia. Liver enzyme activity in the effluent exiting the liver increased in direct proportion to the length of hypoxia up to 56 min. The sodium, ATP, and enzyme changes during hypoxia were correlated with histological and electron-microscopic findings. The morphology of liver specimens exposed to 30 min of hypoxia was close to normal, whereas extensive centrilobular and midlobular necrosis was seen in specimens subjected to 60 and 90 min of hypoxia. The effect of 30 min of reoxygenation after 15, 30, 45, 60, and 90 min of hypoxia was also studied. The level of beta-ATP recovery depended on the duration of hypoxia. For 60 min of hypoxia followed by reoxygenation, beta-ATP recovered to only 20% of control values. The morphology of hypoxic livers after 30 min of reoxygenation was similar to livers subjected to hypoxia alone.

Animals↗

Liver transplantation: MR angiography with surgical validation.

Thirty patients (mean age, 45 years) were evaluated with magnetic resonance (MR) angiography before liver transplantation to assess the accuracy of MR angiography. A series of breath-hold, two-dimensional images were acquired and subsequently processed to form three-dimensional projection angiograms. Graphic information on blood flow in the portal vein was acquired by using presaturation bolus tracking. Correlative duplex ultrasound (US) was performed in 28 patients, and surgical or autopsy correlation was available in all cases. MR angiography demonstrated patency of the portal vein in 26 (96%) of 27 patients, made possible the diagnosis of portal venous occlusion in three of three patients, depicted reversed portal flow in one patient, and provided clear delineation of the extent of varices and specific portosystemic collateral vessels. When duplex US was successful, there was full agreement with MR angiographic results in assessing portal vein patency and flow direction. All of the MR findings were corroborated at surgical exploration or autopsy. The authors conclude that MR angiography is very accurate in the portal system and is valuable in preoperative assessment for liver transplantation.

Abdomen↗

Hepatic arterial embolization for metastatic hormone-secreting tumors. Technique, effectiveness, and complications.

Ten patients with hepatic metastases from islet cell tumors or carcinoid tumors had clinical symptoms from hormonal secretion and/or pain related to the mass effect of neoplastic liver involvement. Hepatic arterial embolization (HAE) using radiographically guided catheters to inject thrombogenic material was applied to the right and/or left hepatic arteries separately 5 to 7 days apart. All ten patients improved within days of the procedure as confirmed by a decrease in measurable hormone levels (gastrin, adrenocorticotropin, and 5-hydroxy indole acetic acid) or by a decrease in tumor size and improved symptoms. Three patients underwent repeated reembolization from two to four times over nine to 50-month intervals for symptom control. Complications of and indications for HAE in these patients are discussed. It appears to be an effective treatment for dealing with the hormonal syndromes and local symptoms related to the hepatic metastases of hormone-secreting tumors.

Adenoma, Islet Cell↗

Five-year results of iliac and femoropopliteal angioplasty in diabetic patients.

Results of 127 iliac and femoropopliteal transluminal angioplasties in 97 diabetic patients are presented. Patients who had undergone iliac (n = 70), femoral (n = 41), and popliteal (n = 16) angioplasties for stenoses up to 15 cm long were followed up for 6-60 months. In diabetic patients presenting with only claudication or adequate runoff, the 5-year iliac patency rate was 76% and the femoral patency rate was 60%; these results were comparable with those found in nondiabetic patients. For limb salvage, 3-year patency rates were 66% for iliac, 37% for femoral, and 37% for popliteal angioplasties, and 5-year patency rates were 29% for iliac, 7% for femoral, and 0% for popliteal angioplasties. Severe peripheral ischemia, poor runoff, and diffuse stenoses all had negative effects on angioplasty results.

Actuarial Analysis↗

Current diagnostic imaging modalities of the liver.

Although there are many complementary and supplementary types of diagnostic imaging of the liver, a logical sequence for most liver pathology begins with high-quality ultrasound. It is noninvasive and inexpensive but very operator dependent. In other settings, CT may be the preferable screening modality, as it gives an excellent picture of the global anatomy and is easily reproducible. Frequently, the two modalities are complementary and indicated; on other occasions, one method will suffice. Radionuclide evaluation of the liver is usually reserved for hepatobiliary imaging for biliary obstruction or the question of acute cholecystitis and tagged-red cell scanning for hemangioma. It is also frequently used for gallium scanning in hepatoma, but lymphoma and inflammatory diseases are also gallium avid. The invasive imaging tests of the liver--angiography and transhepatic and endoscopic retrograde cholangiography--are performed when insufficient information is obtained by the other methods (as in diagnostic transhepatic cholangiography) or when the procedure offers therapy (as for biliary drainage, percutaneous transhepatic removal of common bile duct stones, percutaneous cholecystosis with gallstone dissolution and liver embolization, or the angiographic evaluation for portal shunting or liver resection). The impact of magnetic resonance imaging and fourth-generation raid angiotomography CT scanning has yet to be felt. The use of intraoperative ultrasound is to be encouraged prior to liver resection because it can demonstrate lesions as small as 3 mm in diameter.

Angiography↗

Hepatic artery embolization for bleeding and tumors.

Hepatic artery embolization has become a standard treatment for liver hemorrhage from a variety of lesions, including trauma, pseudoaneurysms, hematobilia, and arteriovenous fistulas. Embolization is also useful in properly selected cases of bleeding secondary to portal hypertension. It is valuable for many primary and secondary neoplasms when the lesion is unresectable and either there is no other effective treatment or other treatment has failed. Hypovascular tumor deposits have poor response rates, and the author no longer embolizes such lesions, whereas the benefits can be dramatic in the case of a hormone-secreting tumor. Hemorrhage from a tumor can also be controlled.

Embolization, Therapeutic↗

Chemical dissolution of gallstones: in vitro studies.

Groups of human cholesterol gallstones were subjected to monooctanoin with and without agitation, methyl-tert-butyl ether (MTBE) with and without agitation, and monooctanoin and MTBE used in succession with agitation. In this in vitro study, agitation greatly expedited the rate of dissolution with MTBE, by far the more potent of the two solvents. An additive effect was suggested when the solvents were used sequentially, monooctanoin followed by MTBE. Cholesterol-calcium stones were also dissolved by MTBE but at a slower rate, depending on the amount and distribution of calcium. Computed tomographic (CT) scans and mammographic images clearly delineated the amount and distribution of calcification, but plain radiographs did not. On the basis of these findings, the authors instituted two changes in their clinical protocol: All patients with gallstones are now examined by means of CT before chemical dissolution begins, and monooctanoin is instilled overnight before the MTBE procedure.

Caprylates↗