Eric M. Walser

Hyperglycemia-induced inhibition of splanchnic fatty acid oxidation increases hepatic triacylglycerol secretion

The effect of hyperglycemia (∼8 mmol/l) on splanchnic fatty acid oxidation and triacylglycerol (TG) secretion rates was investigated in five healthy men. U-13C-labeled fatty acids were infused to estimate fatty acid kinetics and oxidation across the splanchnic region, and in vivo labeled very low density lipoprotein (VLDL)-TG was infused to estimate TG secretion rate. Plasma fatty acid carbon enrichment and concentration were maintained constant by infusion of lipids and heparin in the hyperglycemia experiments. Fatty acid uptake by the splanchnic region was 1.4 ± 0.2 and 2.2 ± 0.9 μmol ⋅ kg-1 ⋅ min-1in the basal and clamp experiments, respectively, whereas fatty acid oxidation decreased from 0.4 ± 0.04 to 0.2 ± 0.05 μmol ⋅ kg-1 ⋅ min-1( P < 0.05). Hepatic TG secretion increased from 0.35 ± 0.07 μmol ⋅ kg-1 ⋅ min-1in the basal state to 0.53 ± 0.11 μmol ⋅ kg-1 ⋅ min-1after 15 h of hyperglycemia ( P< 0.05). Similarly, plasma VLDL-TG concentration increased from 0.28 ± 0.06 to 0.43 ± 0.05 mmol/l during the clamp ( P < 0.05). In summary, hyperglycemia attenuates fatty acid oxidation in the splanchnic region in human volunteers, even when fatty acid availability is constant. This adaptation results in a significant increase in the VLDL-TG secretion rate and concentration in plasma.The effect of hyperglycemia ( approximately 8 mmol/l) on splanchnic fatty acid oxidation and triacylglycerol (TG) secretion rates was investigated in five healthy men. U-13C-labeled fatty acids were infused to estimate fatty acid kinetics and oxidation across the splanchnic region, and in vivo labeled very low density lipoprotein (VLDL)-TG was infused to estimate TG secretion rate. Plasma fatty acid carbon enrichment and concentration were maintained constant by infusion of lipids and heparin in the hyperglycemia experiments. Fatty acid uptake by the splanchnic region was 1.4 +/- 0.2 and 2.2 +/- 0.9 micromol. kg-1. min-1 in the basal and clamp experiments, respectively, whereas fatty acid oxidation decreased from 0.4 +/- 0. 04 to 0.2 +/- 0.05 micromol. kg-1. min-1 (P < 0.05). Hepatic TG secretion increased from 0.35 +/- 0.07 micromol. kg-1. min-1 in the basal state to 0.53 +/- 0.11 micromol. kg-1. min-1 after 15 h of hyperglycemia (P < 0.05). Similarly, plasma VLDL-TG concentration increased from 0.28 +/- 0.06 to 0.43 +/- 0.05 mmol/l during the clamp (P < 0.05). In summary, hyperglycemia attenuates fatty acid oxidation in the splanchnic region in human volunteers, even when fatty acid availability is constant. This adaptation results in a significant increase in the VLDL-TG secretion rate and concentration in plasma.

Portal Venous Thrombosis: Percutaneous Therapy and Outcome

PURPOSEnTo study the efficacy of percutaneous treatment for portal vein thrombosis (PVT).nnnMATERIALS AND METHODSnOf 20 patients who were evaluated for symptomatic portal occlusion, 14 were successfully treated with use of percutaneous techniques. In patients with noncavernomatous PVT (n = 15), the initial treatment was to increase portal output by creating a transjugular intrahepatic portosystemic shunt (TIPS), which was successful in 12 cases. Methods to decrease arterial input to the portal system (hepatosplenic arterial embolization) were used as primary therapy in two patients and in an additional two patients with continued symptoms, despite a functioning TIPS.nnnRESULTSnAll TIPS survivors had patent shunts, although patients with complete PVT required more frequent revisions compared to patients with nonocclusive PVT. Hepatosplenic arterial embolization controlled symptoms in the four patients who were treated, but both patients with patent TIPS died of liver failure after embolization. Of the 14 patients treated, eight died at a mean of 6.2 months (six from hepatoma).nnnCONCLUSIONnTIPS is effective in patients with noncavernomatous PVT, although patients with complete thrombosis experience recurrent shunt occlusions and also may develop hepatoma. If TIPS fails, or if symptoms recur, hepatosplenic arterial embolization may be an option.

Regional acetate kinetics and oxidation in human volunteers

We have used a 3-h primed continuous infusion of [1,2-13C]acetate in five fasted (24 h) volunteers to quantify splanchnic and leg acetate metabolism (protocol 1). Fractional extraction of acetate by both tissues was high ( approximately 70%), and simultaneous uptake and release of acetate were observed. Labeled carbon recovery in CO2 was 37.9 +/- 2.3% at the whole body level, 37.7 +/- 1.5% across the splanchnic bed, and 37.3 +/- 2.9% across the leg. Furthermore, we calculated whole body labeled carbon recovery during 15 h of [1, 2-13C]acetate infusion in three volunteers (protocol 2). Whole body acetate carbon recovery in CO2 was significantly higher (66.7 +/- 4. 5%) after 15 h of tracer infusion than after 3 h. We conclude that acetate is rapidly taken up by the leg and splanchnic tissues and that the percent recovery of CO2 from the oxidation of acetate is heavily dependent on the length of acetate tracer infusion. In the postabsorptive state, labeled carbon recovery from acetate across the leg and the splanchnic region is similar to the whole body CO2 recovery.

Effect of hyperglycemia-hyperinsulinemia on whole body and regional fatty acid metabolism

The effects of combined hyperglycemia-hyperinsulinemia on whole body, splanchnic, and leg fatty acid metabolism were determined in five volunteers. Catheters were placed in a femoral artery and vein and a hepatic vein. U-13C-labeled fatty acids were infused, once in the basal state and, on a different occasion, during infusion of dextrose (clamp; arterial glucose 8.8 +/- 0.5 mmol/l). Lipids and heparin were infused together with the dextrose to maintain plasma fatty acid concentrations at basal levels. Fatty acid availability in plasma and fatty acid uptake across the splanchnic region and the leg were similar during the basal and clamp experiments. Dextrose infusion decreased fatty acid oxidation by 51.8% (whole body), 47.4% (splanchnic), and 64.3% (leg). Similarly, the percent fatty acid uptake oxidized decreased at the whole body level (53 to 29%), across the splanchnic region (30 to 13%), and in the leg (48 to 22%) during the clamp. We conclude that, in healthy men, combined hyperglycemia-hyperinsulinemia inhibits fatty acid oxidation to a similar extent at the whole body level, across the leg, and across the splanchnic region, even when fatty acid availability is constant.The effects of combined hyperglycemia-hyperinsulinemia on whole body, splanchnic, and leg fatty acid metabolism were determined in five volunteers. Catheters were placed in a femoral artery and vein and a hepatic vein. U-13C-labeled fatty acids were infused, once in the basal state and, on a different occasion, during infusion of dextrose (clamp; arterial glucose 8.8 ± 0.5 mmol/l). Lipids and heparin were infused together with the dextrose to maintain plasma fatty acid concentrations at basal levels. Fatty acid availability in plasma and fatty acid uptake across the splanchnic region and the leg were similar during the basal and clamp experiments. Dextrose infusion decreased fatty acid oxidation by 51.8% (whole body), 47.4% (splanchnic), and 64.3% (leg). Similarly, the percent fatty acid uptake oxidized decreased at the whole body level (53 to 29%), across the splanchnic region (30 to 13%), and in the leg (48 to 22%) during the clamp. We conclude that, in healthy men, combined hyperglycemia-hyperinsulinemia inhibits fatty acid oxidation to a similar extent at the whole body level, across the leg, and across the splanchnic region, even when fatty acid availability is constant.

Hepatic Perfusion before and after the Transjugular Intrahepatic Portosystemic Shunt Procedure: Impact on Survival

PURPOSEnThis study correlates transjugular intrahepatic portosystemic shunt (TIPS) mortality with flow patterns in the cirrhotic liver.nnnMATERIALS AND METHODSnTwenty-seven TIPS patients and 10 control subjects were used for this study. The authors evaluated hepatic perfusion with venous injections of Tc-99m pertechnetate before and after TIPS. Hepatic time-activity curves were analyzed for type and amount of liver perfusion. These parameters were correlated with survival for a mean follow-up of 18 months.nnnRESULTSnThe mean arterial contribution to liver blood flow was 25.4% in the normal control patients, 39.9% in patients prior to TIPS, and increased to 48.3% after TIPS. Although the proportion of arterial supply to the cirrhotic liver varied widely, TIPS mortality did not correlate with the preprocedure hepatic artery/portal venous perfusion ratio. However, patients with both an arterialized flow pattern and low total hepatic perfusion had higher mortality, with a mean survival of 2 months compared to patients with a more favorable perfusion profile (mean survival, 28.4 months).nnnCONCLUSIONSnThe proportion of arterial perfusion to the liver before TIPS did not affect survival. However, patients with a combination of reduced total hepatic perfusion and an arterial flow pattern had poorer survival, suggesting that both the quantity and quality of hepatic perfusion predicts TIPS outcome.

Percutaneous Transpedicular Management of Discitis

PURPOSEnTo present the technique of percutaneous transpedicular biopsy and debridement of discs in diagnosis and management of discitis.nnnMATERIALS AND METHODSnFifteen patients underwent disc biopsy through a transpedicular approach with local anesthesia and fluoroscopic guidance. An attempt was made to debride the disc as much as possible. A surgical vacuum drain was deployed through the transpedicular tract when there was persistent drainage.nnnRESULTSnFifteen patients underwent percutaneous transpedicular disc biopsy and debridement of disc for suspected discitis. Three patients underwent biopsy only and 12 underwent percutaneous discectomy. Six patients had at least one positive culture. Eight patients who underwent discectomy had immediate improvement of pain or neurologic symptoms, obviating emergency surgical debridement of the disc. Four patients did not improve and underwent surgical debridement and fusion.nnnCONCLUSIONSnTranspedicular biopsy of the disc is an effective technique for adequate tissue retrieval and diagnosis of discitis. Adequate debridement in selected patients with antibiotic therapy may be definitive. Epidural extension of discitis and massive vertebral destruction precludes percutaneous treatment.

Quantification of Intrahepatic Portosystemic Shunting after Placement of a Transjugular Intrahepatic Portosystemic Shunt

PURPOSEnTo quantify portosystemic shunting and hepatic portal perfusion after placement of a transjugular intrahepatic portosystemic shunt (TIPS).nnnMATERIALS AND METHODSnTechnetium-99m macroaggregated albumin (MAA) was injected directly into the portal veins of nine asymptomatic patients 3 months after TIPS placement. Portosystemic shunting was quantified by comparing counts in the lungs with those in the liver. One cirrhotic patient and one healthy patient who received portal MAA injections were used as controls.nnnRESULTSnNo portosystemic shunting was found in the healthy patient. In the cirrhotic control patient, 77% of the injected activity was in the lungs. Patients with portosystemic shunts had even more activity in the lungs. Even stenotic shunts diverted greater than 80% of portal blood flow systemically. Flow through the TIPS ranged from 84% to 100% (average, 93%); these fractions of flow correlated inversely with portosystemic pressure gradients.nnnCONCLUSIONnCirrhotic livers may divert much of the portal blood systemically before TIPS placement. Afterward, this proportion rises, and most portal flow is diverted into the pulmonary circulation.

Handbook of Angioplasty and Stenting Procedures

Handbook of angioplasty and stenting procedure , Handbook of angioplasty and stenting procedure , کتابخانه دیجیتال جندی شاپور اهواز

Tc-99m sestamibi imaging of a pancreatic VIPoma and parathyroid adenoma in a patient with multiple type I endocrine neoplasia

Technetium-99m sestamibi is known to localize in primary malignant and metastatic tumors. Specifically, brain, breast, thyroid, parathyroid, lung, and kidney tumors have been imaged. The Verner Morrison syndrome, which is caused by excessive vasoactive intestinal peptide (VIP), consists of watery diarrhea, hypokalemia, and achlorhydria. This condition is rarely associated with multiple endocrine neoplasia. The authors present a case of multiple endocrine neoplasia type I with visualization of a pancreatic VIPoma and parathyroid adenoma with Tc-99m MIBI.

Regional disposal of intravenously infused glucose during prolonged hyperglycemia-hyperinsulinemia.

We measured splanchnic and leg glucose uptake during prolonged (i.e., 15 hours), moderate hyperglycemia-hyperinsulinemia (clamp). Plasma free fatty acid (FFA) concentration was maintained at basal concentration during the clamp via infusion of exogenous lipids and heparin in healthy volunteers to create a metabolic profile similar to glucose intolerance (i.e., hyperglycemia-hyperinsulinemia with elevated FFA concentration). During the clamp, glucose was infused at an average rate of 49 +/- 4 micromol/kg/min, which resulted in a plasma glucose concentration of 8.8 +/- 0.5 mmol/L compared with a concentration of 4.4 +/- 0.2 mmol/L in the basal state (P < 0.05). Insulin concentration increased from 5.5 +/- 1.1 microU/mL (basal) to 31.3 +/- 12.7 microU/mL (clamp; P < 0.05), whereas plasma FFA concentration was similar in the two conditions (3.9 +/- 0.5 mmol/L and 4.1 +/- 0.5 mmol/L, basal and clamp, respectively). Glucose balance across the splanchnic region switched from net release (-5.8 +/- 0.7 micromol/kg/min) in the basal state to net uptake in the clamp (19.8 +/- 3.7 micromol/kg/min; P < 0.05) and accounted for approximately 40% of the infused glucose. Glucose uptake across the leg was 0.7 +/- 0.2 micromol/kg/min (basal) and 5.5 +/- 2.2 micromol/kg/min (clamp; P < 0.05). In summary, tissues in the splanchnic region (i.e., liver) are important for disposal of intravenously infused glucose during prolonged, moderate hyperglycemia-hyperinsulinemia. Accelerated hepatic glucose uptake may disrupt normal liver metabolism, with potentially dangerous consequences for the patient. Measures to control systemic glucose concentration may be necessary to prevent excessive glucose disposal in the liver.