Search PubMed⌕ Search

Biomedical subjects

M E Clouse

Publications and source records attributed to M E Clouse.

At least 19 recordsLinked to original sources

Percutaneous tumor ablation: increased coagulation by combining radio-frequency ablation and ethanol instillation in a rat breast tumor model.

PURPOSE: To determine if percutaneously applied radio frequency (RF) combined with percutaneous ethanol instillation (PEI) can increase the extent of ablation in rat breast tumors. MATERIALS AND METHODS: R3230 mammary adenocarcinoma was implanted bilaterally in the mammary fat pads of 18 female rats. The tumor nodules measured 1. 2-1.5 cm. Eight tumors each were treated with (a) conventional, monopolar RF (96 mA +/- 28; 70 degrees C for 5 minutes); (b) PEI (250 microL of ethanol infused over 1 minute); (c) combined therapy of PEI immediately followed by RF ablation; or (d) combined therapy of RF ablation immediately followed by PEI. Four tumors were not treated and served as controls. Histopathologic examination included staining for mitochondrial enzyme activity. Resultant coagulation necrosis was compared between treatment groups. RESULTS: Coagulation necrosis was observed only within treated tumors. Tumors treated with RF alone had 6.7 mm +/- 0.6 of coagulation surrounding the electrode, and those treated with PEI alone had 6.4 mm +/- 0.6 of coagulation around the instillation needle (not significant). Significantly increased coagulation of 10.1 mm +/- 0.9 (P: <.001) was observed with the combined therapy of PEI followed by RF. RF followed by PEI did not increase coagulation (6.4 mm +/- 0.8 around the needle; not significant). CONCLUSION: PEI followed by RF ablation therapy increases the extent of induced coagulation necrosis in rat breast tumors, as compared with either therapy alone.

Administration, Cutaneous↗

Biliary complications after orthotopic liver transplantation in rats.

We recently experienced a high frequency of biliary complications after orthotopic liver transplantation in rats (22 of 25 cases (88%): biloma, 20 cases; biliary peritonitis, 2 cases). These complications seemed to be rare in general, but some researchers reported such cases and addressed them mainly through rearterialization. The biliary complications we encountered were found to be associated with necrosis of the donor bile duct and an opportunistic infection of Enterobacteriaceae. After administering appropriate antibiotics, the complications significantly diminished (2 of 25 cases (8%), P = 0.0001). The nonarterialized bile duct, which becomes ischemic soon after liver transplantation, appears to be susceptible to infections. Such opportunistic infections may prevent the development of arterial collaterals, causing bile duct necrosis and the subsequent leakage of bile juice. When biliary complications frequently occur after nonarterialized liver transplantation in rats, the possibility of an opportunistic infection should thus be considered.

Animals↗

Diabetic versus nondiabetic limb-threatening ischemia: outcome of percutaneous iliac intervention.

OBJECTIVE: The purpose of this study was to compare the effectiveness of iliac angioplasty and outcomes in diabetic patients and nondiabetic patients with limb-threatening ischemia. MATERIALS AND METHODS: Records of 91 consecutive patients with limb-threatening ischemia (rest pain, nonhealing ulceration, or gangrene) who, during a 6-year period, underwent iliac angioplasty of hemodynamically significant lesions were reviewed. Stents were placed in patients with suboptimal findings at angioplasty. Sixty-eight (75%) of the 91 patients were diabetic. Life table analysis and log-rank significance tests were used to compare rates of primary iliac artery patency, primary and secondary graft patency, limb salvage, and survival in diabetic patients versus nondiabetic patients. RESULTS: One hundred seven iliac lesions were treated with percutaneous angioplasty. Ten iliac stents were placed because of suboptimal results at angioplasty. The mean time of follow-up was 20 months (range, 2-62 months). Sixty-eight patients (75%) underwent peripheral reconstruction. Outcomes were comparable in both patient groups for primary iliac patencies at 4 years (diabetic patients, 85%; nondiabetic patients, 76%; p = .5), primary and secondary graft patencies at 4 years (diabetic patients, 65% and 73%, respectively; nondiabetic patients, 74% and 100%, respectively; p = .7 and .19, respectively), 4-year limb-salvage rates (diabetic patients, 93%; nondiabetic patients, 79%; p = .07). Major complications of angioplasty occurred in four patients (4.4%). CONCLUSION: Outcomes of iliac angioplasty and limb-salvage rates were comparable for diabetic patients and nondiabetic patients who underwent current methods of iliac angioplasty and infrainguinal reconstruction.

Aged↗

Adeno-associated virus-mediated delivery of antiangiogenic factors as an antitumor strategy.

Antiangiogenic tumor therapies have recently attracted intense interest for their broad-spectrum action, low toxicity, and, in the case of direct endothelial targeting, an absence of drug resistance. To promote tumor regression and to maintain dormancy, antiangiogenic agents need to be chronically administered. Gene therapy offers a potential way to achieve sustained therapeutic release of potent antiangiogenic substances. As a step toward this goal, we have generated recombinant adeno-associated virus (rAAV) vectors that carry genes coding for angiostatin, endostatin, and an antisense mRNA species against vascular endothelial growth factor (VEGF). These rAAVs efficiently transduced three human tumor cell lines tested. Transduction with an rAAV-encoding antisense VEGF mRNA inhibited the production of endogenous tumor cell VEGF. Conditioned media from cells transduced with this rAAV or with rAAV-expressing endostatin or angiostatin inhibited capillary endothelial cell proliferation in vitro. Antiangiogenic rAAVs may offer a novel gene therapy approach to undermining tumor neovascularization and cancer progression.

Angiostatins↗

Liver metastases from colorectal cancer: drug delivery with liposome-encapsulated doxorubicin.

PURPOSE: To evaluate the intratumoral distribution of liposome-encapsulated doxorubicin. MATERIALS AND METHODS: Tumor-bearing livers of 24 mice were studied with in vivo fluorescence and electron microscopy after injection of liposomal doxorubicin in the hepatic artery, portal vein, or tail vein. Distribution and uptake of liposomes and doxorubicin in tumors were compared at 5, 30, and 60 minutes after injection. In vitro evaluation of uptake of doxorubicin in Kupffer cells and in human colorectal cancer cells incubated under normoxic and hypoxic conditions for 5, 30, and 60 minutes was performed with fluorescence microscopy. RESULTS: Doxorubicin autofluorescence was seen in tumors 30 minutes after intraarterial and intraportal injection and was statistically significantly greater at 60 minutes (P < .001). Liposomes were observed in small tumors (diameter < 300 microns) and were trapped in Kupffer cells around larger, hypovascular tumors. Electron microscopy findings confirmed intracytoplasmic, perinuclear uptake of liposomes in tumor cells. In vitro, a higher proportion of doxorubicin was seen in cancer cells (92%) than in Kupffer cells (75%) after 60 minutes incubation. CONCLUSION: Liposomal doxorubicin can be reliably delivered to liver metastases via the hepatic artery, eliminating need for tumor embolization. Further evaluation is warranted, and the drug may be useful for treating patients with unresectable liver metastases.

Animals↗

Thrombolysis of infrapopliteal bypass grafts: efficacy and underlying angiographic pathology.

OBJECTIVE: The purpose of this study was to determine retrospectively the effectiveness of thrombolysis of occluded infrapopliteal bypass grafts and to identify factors affecting success. MATERIALS AND METHODS: The records of 52 consecutive patients (52 grafts) who underwent selective urokinase thrombolysis of grafts to the pedal or tibial arteries were reviewed. The need for subsequent surgery and the influence of diabetes on outcome were analyzed. RESULTS: There were 43 vein and nine Goretex (W-L Gore, Flagstaff, AZ) and vein composite grafts inserting into tibial and peroneal arteries (n = 28) or pedal arteries (n = 24). Mean time of follow-up was 19 months. All grafts were entered, and technical success was achieved in 73% of patients. Twenty-six patients required some form of graft revision. Overall patency at 30 days was 76%. Thirty-day limb-salvage and mortality rates were 82% and 4%, respectively. No significant difference was found in 1-yr outcomes between diabetic and nondiabetic patients or between pedal and tibial grafts. Major complications occurred in eight patients (15%). CONCLUSION: Thrombolysis of occluded grafts that insert into the pedal or tibial vessels was as effective as thrombolysis of more proximal grafts and native arterial thrombolysis, which have reported 30-day limb-salvage rates that range between 80% and 90%. Diabetes and grafting to foot vessels did not adversely affect response to thrombolysis. Surgery was often required to correct an underlying lesion revealed by thrombolysis. Despite the small size of the arteries to which the grafts were anastomosed, selective thrombolysis of occluded infrapopliteal bypass grafts proved to be an effective procedure.

Adult↗

Multimodality treatment of hepatocellular carcinoma in a hepatobiliary specialty center.

OBJECTIVES: To review the experience of the treatment of hepatocellular carcinoma by a single multimodality team during a 6-year period, including all patients who were referred for possible surgical intervention, to evaluate prognostic factors at presentation, and to determine the results of the different modalities of treatment that were used. DESIGN: Retrospective study of 154 patients who were referred to our Hepatobiliary Surgical Unit with the diagnosis of hepatocellular carcinoma from January 1988 through August 1995. SETTING: Tertiary care center. RESULTS: Methods of treatment included surgical resection (n=49), transplantation (n=22), hepatic artery chemoembolization (n=30), systemic chemotherapy (n=25), and no treatment (n=22). Predictive prognostic factors included coexisting cirrhosis, symptoms at presentation, and abnormal liver function test results. Unfavorable tumor characteristics were size (diameter, >5 cm) and multicentricity. For patients who underwent surgical exploration, advanced staging according to the manual of the American Joint Committee on Cancer, vascular invasion, and a margin of less than 1 cm in the group for patients who underwent resection impacted negatively on the prognosis. The median survival (42.4 months) for the group of patients who underwent resection was significantly higher than that for the groups of patients who did not undergo resection. Chemoembolization was associated with significantly better survival results than was systemic chemotherapy. CONCLUSIONS: Hepatic resection offers the best chance at cure for patients with hepatocellular carcinoma. The high association between hepatocellular carcinoma and cirrhotic liver disease makes surgical resection, even in favorable tumor types, a difficult task based on low hepatic reserve whose tumors are considered unresectable can be considered for chemoembolization. Liver transplantation should be reserved for selected patients with cirrhotic liver disease who have tumors (diameter, <5 cm) in the contest of neoadjuvant protocols.

Adolescent↗

TmDOTP5-: a substance for NMR temperature measurements in vivo.

The chemical shifts of 31P and 1H in thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate) (TmDOTP5-) are approximately two orders of magnitude more sensitive to temperature than are water proton and 19F shifts. In the physiologically relevant pH range, the 31P and 1H chemical shifts of TmDOTP5- are linear functions of temperature between 25 and 47 degrees C. The results indicate that using TmDOTP5- can provide measurements of temperature in vivo that are significantly more accurate than methods based on water and fluorocarbon chemical shifts.

Abdomen↗

Severe ascites: efficacy of the transjugular intrahepatic portosystemic shunt in treatment.

PURPOSE: To evaluate the transjugular intrahepatic portosystemic shunt (TIPS) as primary treatment in patients with cirrhosis and severe ascites. MATERIALS AND METHODS: A TIPS placement was attempted in 54 consecutive patients with intractable ascites. Clinical assessment findings, shunt patency, complications, and survival were analyzed. RESULTS: A TIPS was successfully placed in 50 patients (93%). Follow-up for clinical effectiveness in 51 patients was a mean of 285 days (range, 1-981 days). Forty patients (78%) gained clinical benefit from the shunt. Of these, 29 (57%) had a complete response (required no further paracentesis) and 11 patients (22%) had a partial response (required less frequent but additional paracentesis for control of ascites). The absence of preprocedure renal insufficiency (creatinine < 1.5 mg/dL [< 130 mumol/L]) was the only characteristic identified as an indicator of clinical success (P < .05). Eleven patients (22%) required shunt revision during follow-up to gain or prolong control of symptoms. Cumulative survival in the population evaluated for clinical efficacy was 53% at 6 months and 48% at 1 year. A complete response was the only variable that indicated increased survival (P < .05; R2 = 12%) with a 6-month survival rate of 76% and a 1-year rate of 71%. CONCLUSION: TIPS placement appears to be effective as a primary treatment of patients with cirrhosis and severe ascites.

Adult↗

Time-of-flight MR angiography of the portal venous system: value compared with other imaging procedures.

OBJECTIVE: The purpose of this study was to retrospectively compare two-dimensional time-of-flight MR angiography with other imaging procedures in the evaluation of the portal venous system in 152 consecutive patients. MATERIALS AND METHODS: The findings on MR angiography performed on 152 patients to depict breath-hold, two-dimensional time of flight MR angiography. Selective arterial presaturation, bolus tracking, and three-dimensional reconstruction were used routinely. Findings were correlated with findings on sonography (104 patients), CT (8 patients), and conventional digital subtraction angiography (19 patients) as well as surgery (23 patients). RESULTS: Agreement between results of MR angiography and alternative types of imaging was excellent (99%). Agreement with sonography (100 of 104), CT (8 of 8), conventional angiography (18 of 19), and surgery (23 of 23) was good. Visualization of varices and spontaneous shunts by MR angiography was superior to that by other imaging techniques. CONCLUSION: Our experience shows that time-of-flight MR angiography is reliable and accurate for depicting portal venous anatomy. MR angiography shows vessels that are not visible with sonography. Complicated pathology is clearly visualized in a way that is not possible with other techniques.

Angiography, Digital Subtraction↗

In vivo microscopic assessment of hepatic microcirculation during liver allograft rejection in the rat.

The hemodynamic alterations in hepatic microvasculature during acute rejection of rat liver allografts was studied using in vivo fluorescence microscopy. ACI rat livers were transplanted into Lewis (allograft) or ACI (isograft) recipients. Microscopy was performed on days 3 (n = 7) and 6 (n = 7) in allografts, and on day 6 (n = 7) in isografts. Naive ACI livers (n = 7) served as nontransplant controls. Changes in sinusoidal blood perfusion, microvascular structure, and leukocyte-endothelial interactions were observed and quantitated. Six days after transplantation, acinar perfusion was markedly impaired in allografts and was accompanied by a lower percentage of perfused sinusoids (59 +/- 8%, mean +/- SEM, P < 0.01) relative to isografts (89 +/- 3%) and nontransplant controls (100 +/- 0%). The hepatic cord width in allografts was significantly greater than in isografts or in nontransplant controls, indicating swelling of parenchymal and sinusoidal lining cells. Furthermore, the number of leukocytes adhering to the sinusoidal endothelium significantly increased in allografts. Adherence to postsinusoidal venules was more prominent in allograft livers (4025 +/- 1400/mm2 of vascular endothelial surface) compared with that in isografts (574 +/- 77/mm2) and nontransplant controls (185 +/- 28/mm2). These microcirculatory alterations in allografts were significant even on day 3. The results show extensive abnormalities of the microcirculatory hemodynamics in rejecting liver allografts which were associated with increased leukocyte adherence to microvascular endothelium. Our findings may provide strategic information for the prevention and treatment of allograft rejection.

Animals↗

Biliary intervention by means of percutaneous puncture of the antecolic jejunal loop.

PURPOSE: To evaluate the safety and efficacy of biliary intervention performed by means of percutaneous transjejunal access. MATERIALS AND METHODS: In 28 patients with conventional antecolic Roux-en-Y choledochojejunostomy or hepaticojejunostomy loops, 41 attempts were made at direct percutaneous entry into the jejunal loop. Indications for previous surgery included sclerosing cholangitis, orthotopic liver transplantation, cholangiocarcinoma, bypass of benign iatrogenic strictures, and bypass of choledochal cyst. Roux-en-Y loops were directly accessed with single-wall, 19-gauge needles after localization by review of previous cholangiograms or computed tomographic (CT) scans and localization of surgical clips with fluoroscopy. RESULTS: The transjejunal approach was successful in 36 of 41 attempts. In 30 cases, transhepatic puncture was entirely avoided. There were four minor complications and one major complication of biliary sepsis. No procedure-related deaths occurred. CONCLUSION: This transjejunal approach is an effective and safe route for a variety of percutaneous biliary procedures in patients with biliary-enteric anastomoses.

Anastomosis, Roux-en-Y↗

Portal vein: US-guided localization prior to transjugular intrahepatic portosystemic shunt placement.

To mark the portal vein prior to transjugular intrahepatic portosystemic shunt (TIPS) placement, metallic coils adjacent to (n = 18) and a wire within (n = 18) the portal vein were placed with ultrasonographic (US) guidance. The mean number of punctures for successful portal vein entry was 3.0 with coils and 2.9 with a wire, and the mean total procedure time was 127.5 and 110.0 minutes, respectively (differences, not significant), and mean time at US was 20 and 10 minutes, respectively.

Adult↗

31P nuclear magnetic resonance spectroscopic evaluation of liver preservation solutions.

The individual effects of verapamil and 2 antioxidants on perfused rat liver nucleoside triphosphate (NTP) recovery following cold storage in University of Wisconsin (UW) solution was assessed using 31P nuclear magnetic resonance spectroscopy. The pharmacological agents were added to UW solution and were present only during organ storage. NTP recovery was significantly higher for the 24-hr UW + 40 microM verapamil group as compared with the 24-hr UW group. None of the other pharmacological agents caused a significant increase in NTP recovery. These findings suggest that addition of verapamil to UW organ preservation solution may result in better poststorage liver function.

Acetylcysteine↗