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Biomedical subjects

U Bolder

Publications and source records attributed to U Bolder.

At least 19 recordsLinked to original sources

[Nutritional therapy. Indication and approaches].

Appropriate nutritional therapy of surgical patients intends to supply calories for the maintenance of essential body functions. Beyond this goal, nutritional support may also significantly reduce nosocomial morbidity if applied properly and to the right patients. In surgical patients, nutritional therapy should start preoperatively by identifying and treating malnutrition and be continued postoperatively as a patient-tailored supportive measure. Oral/enteral nutrition is feasible in the majority of patients. Rare exceptions are patients with intestinal leakage, overt ileus, and circulatory shock. If the upper gastrointestinal tract is not functioning (as in swallowing disorders or after construction of surgical anastomoses), tube systems may be used. They can be placed endoscopically or at the time of surgery (needle catheter jejunostomy) to allow continuous enteral nutrition. If oral/enteral nutrition cannot completely meet caloric requirements of the patient, additional parenteral supply is indispensable to reach the intended caloric goal.

Energy Intake↗

Use of anticoagulation during wireless capsule endoscopy for the investigation of recurrent obscure gastrointestinal bleeding.

Detecting the source of obscure gastrointestinal bleeding can be difficult. Capsule endoscopy is a promising diagnostic tool for investigating patients with this condition, although identifying the source of intermittent or low-grade bleeding remains a diagnostic challenge. We present case reports of two patients with obscure gastrointestinal bleeding, in whom the source of recurrent bleeding episodes was diagnosed by capsule endoscopy while they were on anticoagulation therapy. The first patient, an 81-year-old white woman, was on long-term oral anticoagulation because she had chronic atrial fibrillation. Capsule endoscopy demonstrated a bleeding tumor in the region of the terminal ileum. The second patient, a 59-year-old white man, underwent an initial capsule endoscopy, which was negative. After initiation of anticoagulation with heparin, a second capsule endoscopy procedure in this patient revealed several small bleeding lesions in the proximal small bowel. In both cases a gastrointestinal stromal tumor was identified as the bleeding source and was resected. These two cases demonstrate that provocation of bleeding during capsule endoscopy may increase its sensitivity.

Aged, 80 and over↗

["Fast-Track" for laparoscopic-assisted rectum resection--what can be achieved? First results of a feasibility study].

AIM: "Fast-track" multimodal rehabilitation is increasingly entering the perioperative management strategies in colon surgery aiming at minimized perioperative morbidity and accelerated recovery. So far little is known about the complementary effects of minimally invasive surgery along with "fast-track" rehabilitation in the treatment of rectal cancer. The aim of this pilot study was to investigate the influence of "fast-track" perioperative management on morbidity, recovery and length of hospital stay in laparoscopically-assisted rectum resections and to compare those data to earlier results. METHODS: An interdiciplinary "fast-track" multimodal rehabilitation strategy with avoidance of mechanical bowel cleansing, with a restrictive intravenous intra- and postoperative fluid regimen, forced mobilisation, and early enteral nutrition was introduced into clinical practice and applied in 16 laparoscopically-assisted rectum resections. Data were collected in the course af a prospective analysis. The mean patient age was 62 (42-79) years. RESULTS: Mean time of surgery was 245 (SD 46) min, and the mean intraoperative infusion rate was 11.2 (SD 2.6) ml/kg/BW. On day 2, 14 of the 16 patients tolerated solid food and 12 patients had had bowel movements. All patients returned to their initial body weight by day 4. The median postoperative hospital stay was 7.5 days (6-20), 12 patients were discharged between day 6 and 8. Two patients were readmitted for intestinal atony, one patient developed an anastomotic leakage. CONCLUSIONS: "Fast-track" rehabilitation is feasible in rectum surgery and seems to complement the beneficial effects of minimally invasive surgery without increasing the complication rate.

Adult↗

A multimodal treatment approach including high-dose chemotherapy in very advanced gastric cancer: evidence for control of metastatic disease.

The present multimodal treatment approach was designed to achieve prolonged tumor control in advanced gastric cancer. A total of 26 patients with stage IV gastric cancer (metastatic disease n=25), ECOG performance status 0-3 and laparoscopically evaluated peritoneal status received a modified EAP schedule to prove chemosensitivity and to mobilize autologous peripheral blood stem cells (aPBSC). Patients without progressive disease proceeded to tandem high-dose chemotherapy (HD-CT) and aPBSCT. Patients with >50% reduction of the target lesion received a second cycle of HD-CT. Responders were selected for local R0 resections (D2 resection) according clinical criteria. Of 26 patients, 20(77%) achieved partial remission after dose-intensive chemotherapy: local R0 resection was achieved in 12 out of 14 patients selected for surgery (46% of all patients). Eight of these R0-resected patients initially had peritoneal carcinomatosis. With a median follow-up of 3.2 years, four patients are still alive. The median overall survival was 8.4 months (CI 2.5-14.4 months), for histologic regression grade 3 (seven out of 25 patients, 28%) 29 months (CI 12-46 months). The combined treatment approach is tolerable and feasible in advanced disease and opens a therapeutic window for a significant proportion of patients, even in cases with histologically proven peritoneal carcinomatosis.

Adult↗

[Synovial sarcoma in clinical practice--description of selected cases].

UNLABELLED: Clinically, synovial sarcoma becomes apparent as a growing mass. Initial presentation and the course may be variable. We discuss 4 characteristic patients. CASE 1: A 37 year-old female patient presented with a mass in her thigh after two consecutive resections of a malignant hemangioendothelioma. HISTOLOGY: Biphasic synovial sarcoma (G II). CASE 2: A tumor was enucleated in the adductors of a 42 year-old female patient. HISTOLOGY: Biphasic synovial sarcoma (G I). 2 years later local tumor recurrence (G I) occurred. Treatment was provided by wide resection and radiotherapy. CASE 3: Resection of a suspected neurinoma in the thigh of a 34 year-old male patient. HISTOLOGY: Biphasic synovial sarcoma, positive margins. CASE 4: A 74 year- old female patient receiving anticoagulants was symptomatic due to intracranial tumor hemorrhage of a metastasis of a previously unknown synovial sarcoma of her popliteal fossa. The primary tumor was initially misdiagnosed as Baker's cyst, causing a deep vein thrombosis. HISTOLOGY: Angioinvasive synovial sarcoma (G II). Survival: 11 months. THERAPY: Wide resection and postoperative irradiation in cases 1-3. Indication for the irradiation in case 2 and 3 was due to the inadequate operation. An amputation was performed in case 4 because of infiltration of the neurovascular structures. CONCLUSION: The presentation of synovial sarcoma does not differ from other soft tissue sarcomas. Patients should be treated in specialized centers to reduce inadequate operations. Outcome and rate of metastatic disease suggest the need for improved adjuvant treatment modalities.

Adult↗

Zonal down-regulation and redistribution of the multidrug resistance protein 2 during bile duct ligation in rat liver.

We have studied regulation of the multidrug resistance protein 2 (mrp2) during bile duct ligation (BDL) in the rat. In hepatocytes isolated after 16, 48, and 72 hours of BDL, mrp2-mediated dinitrophenyl-glutathione (DNP-GS) transport was decreased to 65%, 33%, and 33% of control values, respectively. The impaired mrp2-mediated transport coincided with strongly decreased mrp2 protein levels, without any significant changes in mrp2 RNA levels. Restoration of bile flow after a 48-hour BDL period resulted in a slow recovery of mrp2-mediated transport and protein levels. Immunohistochemical detection of the protein in livers of rats undergoing BDL showed strongly reduced mrp2 staining after 48 hours, which was initiated in the periportal areas of the liver lobule and progressed toward the pericentral areas after 96 hours. Immunofluorescent detection of mrp2 in livers of rats undergoing 48 hours of BDL revealed decreased staining accompanied by intracellular localization of the protein in pericanalicular vesicular structures. Within this intracellular compartment, mrp2 colocalized with the bile salt transporter (bsep) and was still active as shown by vesicular accumulation of the fluorescent organic anion glutathione-bimane (GS-B). We conclude that down-regulation of mrp2 during BDL-induced obstructive cholestasis is mainly posttranscriptionally regulated. We propose that this down-regulation is caused by endocytosis of apical transporters followed up by increased breakdown of mrp2, probably in lysosomes. This breakdown of mrp2 is more severe in the periportal areas of the liver lobule.

ATP Binding Cassette Transporter, Subfamily B↗

Preoperative assessment of mortality risk in hepatic resection by clinical variables: a multivariate analysis.

Hepatic resection is a chance for cure for primary and secondary liver tumors and a variety of benign diseases. Despite advances in surgical technique and patient care, preoperative and postoperative morbidity in patients undergoing liver resection remains high. Because a high morbidity represents a risk factor contributing to a fatal outcome of the surgical procedure, our study aimed to investigate the contribution of different risk factors to a fatal outcome and if mortality can be predicted by the presence of certain risk factors. Two hundred fifty-seven patients undergoing hepatic resection (curative and palliative) were analyzed preoperatively, immediately after surgery, and 10 days after surgery for 60 potential risk factors. Survivors (n = 238) and nonsurvivors (n = 19) were compared univariately. The analysis identified 14 variables to differentiate between groups. These variables were processed by multivariate logistic regression analysis. Three models to estimate 30-day mortality were identified, tested for statistical accuracy, and assessed for their receiver-operated characteristics (ROCs). The variables in the multivariate models were as follows: preoperatively, age, number of comorbid factors, and presence of cirrhosis; immediately after surgery, age, number of comorbid factors, and percentage of resected liver; and 10 days after surgery, age, hours of ventilation, and number of adverse events. Goodness of fit was 0. 863, 0.912, and 0.966, respectively. Areas under the ROC curves were 83.6%, 85.7%, and 98.0%. The specificity (probability to identify survivors correctly) was greater than 90% for all models, although sensitivity (probability to identify nonsurvivors correctly) was greater than 90% only for 10 days after surgery. We conclude that logistic regression is appropriate to assess the importance of risk factors in the course of hepatic resection and to identify patient groups at high risk.

Female↗

Sulindac is excreted into bile by a canalicular bile salt pump and undergoes a cholehepatic circulation in rats.

BACKGROUND & AIMS: Dihydroxy bile acids induce a bicarbonate-rich hypercholeresis when secreted into canalicular bile in unconjugated form; the mechanism is cholehepatic shunting. The aim of this study was to identify a xenobiotic that induces hypercholeresis by a similar mechanism. METHODS: Five organic acids (sulindac, ibuprofen, ketoprofen, diclofenac, and norfloxacin) were infused into rats with biliary fistulas. Biliary recovery, bile flow, and biliary bicarbonate were analyzed. Sulindac transport was further characterized using Tr(-) rats (deficient in mrp2, a canalicular transporter for organic anions), the isolated perfused rat liver, and hepatocyte membrane fractions. RESULTS: In biliary fistula rats, sulindac was recovered in bile in unconjugated form and induced hypercholeresis of canalicular origin. Other compounds underwent glucuronidation and were not hypercholeretic. In the isolated liver, sulindac had delayed biliary recovery and induced prolonged choleresis, consistent with a cholehepatic circulation. Sulindac was secreted normally in Tr(-) rats, indicating that its canalicular transport did not require mrp2. In the perfused liver, sulindac inhibited cholyltaurine uptake, and when coinfused with cholyltaurine, induced acute cholestasis. With both basolateral and canalicular membrane fractions, sulindac inhibited cholyltaurine transport competitively. CONCLUSIONS: Sulindac is secreted into bile in unconjugated form by a canalicular bile acid transporter and is absorbed by cholangiocytes, inducing hypercholeresis. At high flux rates, sulindac competitively inhibits canalicular bile salt transport; such inhibition may contribute to the propensity of sulindac to induce cholestasis in patients.

Animals↗

[Hepatocellular transport of bile acids and organic anions in infection and SIRS--evidence for different mechanisms for regulating membrane transport proteins].

The alteration of proinflammatory mediators during sepsis and SIRS results in a large variety of adaptive changes of metabolic and physiologic variables. This study investigated the alterations of hepatocellular transport in a rat sepsis model (LPS i.p.) as well as in a model inducing SIRS by sterile abscess formation (turpentine i.m.). Two bile acids (Cholyltaurine and Chemodeoxycholyltaurine) and one organic anion (Sulfolithocholyltaurine) were used as marker substrates to investigate the time course of hepatocellular transport function. Experiments were performed in isolated perfused rat livers and plasma membrane vesicles. During sepsis, both, the transport of bile acids and that of the organic anion was markedly reduced. In contrast no alteration of transport was detected during SIRS. However, biliary secretion of glutathione (+90%) and bile acid independent bile flow (%) were increased. mRNA levels of bile acid and organic anion transport proteins were reduced. The lowest values were noted 12 h after injection of LPS or turpentine. Almost unchanged kinetic parameters during SIRS pointed to a normal population of transporters with regard to quantity and substrate affinity. Therefore it seems that transcriptional regulation plays an important role for the expression of transport proteins during sepsis, whereas posttranscriptional regulation may be of importance during SIRS. The clinical phenomenon of septic cholestasis including jaundice implies endotoxemia and differenciates against SIRS.

Animals↗

[Optimal postoperative nutrition: pro and contra enteral and parenteral feeding].

Malnutrition is correlated with an increased incidence of postoperative complications. As a consequence, preoperative hyperalimentation results in a decrease of postoperative complications in patients with malnutrition. In contrast, the beneficial effects of postoperative nutritional support are still to be proven. The majority of prospective trials have shown limited advantageous effects for patients with delayed nutritional intake after the surgical procedure. In these patients enteral nutrition has been shown to reduce the rate of infectious complications. If enteral nutrition cannot be applied, the addition of glutamine as a dipeptide is beneficial with regard to intestinal barrier function.

Enteral Nutrition↗

Intestinal absorption and enterohepatic cycling of biliary iron originating from plasma non-transferrin-bound iron in rats.

In iron overload, non-transferrin-bound iron (NTBI) is found in plasma and is rapidly removed by hepatocytes. Some of this NTBI is excreted into bile. Biliary excretion of NTBI, in the form of an iron-deferiprone chelate, is greatly increased by deferiprone, an iron chelator. The aim of this study was to test whether biliary iron as such or as an iron-deferiprone chelate (both originating from plasma NTBI) is absorbed from the intestine and re-secreted into bile. In healthy biliary fistula (donor) rats, biliary 55Fe originating from plasma NTBI was obtained by injecting Fe citrate (to saturate transferrin) followed by 55Fe. This biliary 55Fe was infused into the duodenum of (recipient) rats whose transferrin was saturated or unsaturated. Similar experiments were performed using iron-overloaded (donor) rats given deferiprone, followed by infusion of the biliary 55Fe-deferiprone chelate into iron-overloaded (recipient) rats. The results show that in healthy (recipient) rats, duodenal infusion of 55Fe from NTBI was followed by increased plasma 55Fe when transferrin was unsaturated, or by biliary excretion of 55Fe when transferrin was saturated, indicating intestinal absorption of 55Fe. In iron-overloaded rats, neither plasma nor bile became radioactive, indicating no intestinal absorption of iron from the deferiprone chelate. We conclude that biliary iron, originating from NTBI, is absorbed from the intestine, and undergoes enterohepatic circulation if transferrin is saturated. In iron-overloaded rats, biliary iron originating from plasma NTBI and present as an iron-deferiprone chelate in bile is not absorbed.

Animals↗

Effect of side chain length on biotransformation, hepatic transport, and choleretic properties of chenodeoxycholyl homologues in the rodent: studies with dinorchenodeoxycholic acid, norchenodeoxycholic acid, and chenodeoxycholic acid.

To assess the effect of side chain length on the metabolism and physiological effects of homologues of chenodeoxycholic acid (CDCA), dinorCDCA, the C22 homologue, was synthesized and its hepatic biotransformation, transport kinetics, and choleretic properties were defined in rat and hamster biliary fistula and in isolated perfused rat liver. Results were compared with those of norCDCA, the C23 homologue, and of CDCA, the natural C24 homologue. In the rat, dinorCDCA was secreted mostly in unconjugated form (the majority as dinor-alpha-muricholic acid); the remainder was glucuronidated. In the hamster, glucuronidation was greater, and the unconjugated fraction contained equal parts of dinorCDCA and 5beta-hydroxy-dinorCDCA. NorCDCA was glucuronidated extensively (70%, rat; 40%, hamster). CDCA, in contrast, was efficiently amidated with taurine or glycine. In the perfused liver, the initial uptake rate of all three homologues was identical; later, regurgitation and/or cholehepatic shunting of dinorCDCA and norCDCA, but not of CDCA, occurred. In rats and hamsters with biliary fistulas, dinorCDCA and norCDCA, but not CDCA, induced a bicarbonate-rich hypercholeresis of canalicular origin. Hypercholeresis was not induced by the taurine conjugate of dinorCDCA. Hepatobiliary retention of both dinorCDCA and norCDCA occurred, consistent with efficient ductular absorption (calculated to be 94%) and cholehepatic cycling of the unmetabolized bile acids. It is concluded that dinorCDCA, as norCDCA, is inefficiently amidated, is metabolized as a xenobiotic, and induces hypercholeresis. DinorCDCA is the first dihydroxy bile acid to be identified that is secreted largely in unconjugated form in bile.

Animals↗

Hepatocyte transport of bile acids and organic anions in endotoxemic rats: impaired uptake and secretion.

BACKGROUND & AIMS: In sepsis, intrahepatic cholestasis occurs frequently, suggesting impaired hepatocyte transport of bile acids and organic anions. The aim of the study was to define the magnitude, time course, and the site of impaired biliary secretion in a rat sepsis model. METHODS: Maximal transport for two bile acids (cholyltaurine and chenodeoxycholyltaurine) and two organic anions (sulfobromophthalein and sulfolithocholyltaurine) was measured in isolated perfused livers at various times after lipopolysaccharide injection. Basolateral and canalicular liver plasma membrane vesicles were used to characterize the impairment in hepatocyte transport. RESULTS: Maximal hepatocyte transport was reduced for all compounds by 60%-81% compared with controls. Bile acid-independent bile flow was reduced by 51%. Impairment was maximal 12 hours after endotoxin injection and recovered thereafter. In basolateral plasma membrane vesicles, sodium-dependent transport for bile acids was reduced by 36%-47%. Sodium-independent transport of organic anions was reduced by 40%-55%. Adenosine triphosphate-stimulated transport was greatly decreased in canalicular vesicles prepared from endotoxemic animals for all four compounds probably because of a reduced number of transport molecules, based on kinetic studies. CONCLUSIONS: Basolateral and canalicular bile acid and organic anion transport are markedly impaired in endotoxemia. These mechanisms may contribute to the cholestasis of sepsis.

Adenosine Triphosphate↗

Repeated administration of recombinant human insulin-like growth factor-I in patients after gastric surgery. Effect on metabolic and hormonal patterns.

OBJECTIVE: The primary objective of this investigation was to evaluate the anticatabolic effects of repeated subcutaneous administration of recombinant human insulin-like growth factor-I (rhlGF-I) in patients after gastric surgery. SUMMARY BACKGROUND DATA: The anabolic and protein-sparing effects of growth hormone are primarily mediated by IGF-I. Malnutrition and catabolic states result in increasing blood levels of growth hormone and decreasing levels of IGF-I. Experimental data showed that exogenous IGF-I could attenuate or reverse catabolism. METHODS: After giving their written informed consent, 38 male and female patients undergoing gastrectomy (age 40-75 years, body mass index 17-30 kg/m2) were treated with 80 micrograms/kg body weight rhlGF-I or placebo in a prospective, randomized, double-blind study for 5 consecutive days. Patients received a standardized total parenteral nutritional regimen with 3 g/kg body weight glucose and 0.1 g/kg body weight nitrogen. Nitrogen balance and 3-methylhistidine excretion were measured daily. Hormone profiles (IGF-I, IGFBP1, IGFBP3, cortisol, insulin, glucagon, triiodothyronine [T3], levothyroxine [T4], and thyroxine-binding globulin) were taken.

Adult↗

Improved cumulated nitrogen balance after administration of recombinant human growth hormone in patients undergoing gastrointestinal surgery.

OBJECTIVE: To examine the effect of recombinant human growth hormone (rhGH) on the catabolic state following major gastrointestinal surgery. DESIGN: The study was designed as a prospective controlled randomized clinical trial. SETTING: Intensive care unit and the surgical ward of the Department of Surgery, Städtische Kliniken Dortmund, FRG. PATIENTS: 39 patients were studied postoperatively following gastrectomy or resection of the rectum. The patients were 40-75 years old. INTERVENTION: 0.075 (n = 11), 0.15 (n = 9) or 0.30 IU rhGH/kg/day (n = 9) or placebo (n = 10) were given subcutaneously at 8:00 a.m. during 5 postoperative days. Resting energy expenditure (REE) on the 1st postoperative day was 2,042 +/- 82 kcal/24 h (REE/BEE 1.44 +/- 0.04). Isocaloric, isonitrogenous total parenteral nutrition provided the energy requirements (4 g carbohydrates/kg, 0.9 g fat/kg, 1.25 g amino acids/kg). RESULTS: After 5 days of treatment, cumulated nitrogen balance (CNB) was improved dose-relatedly. In controls, net nitrogen losses (-20.47 +/- 3.86 g) were significantly higher than after 0.15 (-12.14 +/- 3.5 g) and 0.30 IU rhGH/kg (-10.0 +/- 2.61 g). 0.075 IU rhGH/kg showed no significant effect on CNB (-18.07 +/- 5.73 g). The modulation of protein metabolism by GH may be mediated by insulin-like growth factor-I (IGF-I). Postoperatively serum (S)-IGF-I was decreased in all groups. rhGH caused a significant dose-related increase in S-IGF-I levels on day 6, whereas in controls it remained unchanged during the study period. Besides significant elevations in serum glucose in some cases of both larger dosage groups no side effects were detected. CONCLUSIONS: The protein-sparing effect of rhGH after major gastrointestinal surgery is dose related but not linear. A threshold value for a significant improvement in the CNB seems to be at least at 0.15 IU rhGH/kg/day.

Adult↗