Biomedical subjects

Karl-Walter Jauch

Publications and source records attributed to Karl-Walter Jauch.

64 records · Page 4Linked to original sources

PubMed2002

Neorectal reservoir is not the functional principle of the colonic J-pouch: the volume of a short colonic J-pouch does not differ from a straight coloanal anastomosis.

BACKGROUND: Low anterior resection with coloanal anastomosis prevents a definitive stoma in patients with distal rectal cancer. However, imperative stool urge, stool fragmentation, prolonged stooling sessions, and minor problems of incontinence are frequently observed in the postoperative situation and negatively affect quality of life. Therefore, the colonic J-pouch was originally constructed to create a stool reservoir. In a randomized, prospective study, the short (5 cm) colonic J-pouch was tested for function and continence vs. straight coloanal anastomosis. METHODS: Over a period of 30 months, 74 consecutive patients (55 males) with rectal cancer in the lower and middle third of the rectum were included and randomized into two groups. Anastomosis was performed either as a coloanal or a colon-pouch-anal anastomosis. The standardized surgical procedure included mobilization of the left hemicolon, central ligation of the inferior mesenteric artery and vein, preaortal lymph node dissection, autonomic nerve preservation, and total mesorectal excision. The anastomosis was performed at the upper anal canal or at the intersphincteric level. All patients were evaluated preoperatively and six months postoperatively for fecal continence, including sphincter manometry and defecation habits. In addition, quality of life was determined by use of a standardized questionnaire (European Organization for Research and Treatment of Cancer, EORTC-QLQ-C30). RESULTS: Thirty-seven patients were randomized into each group. In general, problems with continence for liquids or gas occurred less frequently in the colonic J-pouch group 6 months after surgery. The frequency of bowel movements was lower in the J-pouch group (2.5 per day) than in the coloanal group (4.7 per day). Importantly, in a manometric study at the same postoperative point, neorectal capacity was decreased to a similar degree in both groups compared with the preoperative rectal volume. Thus, the expected and postulated reservoir effect could not be achieved by forming a 5-cm colonic J-pouch. CONCLUSION: The colonic J-pouch was superior with regard to continence for gas and liquids compared with a straight coloanal anastomosis. Furthermore, stool frequency was significantly lower in the J-pouch group than in the coloanal reconstruction group. However, because neorectal capacity decreased equally in both groups, we speculate that the advantage of the colonic J-pouch is not in the creation of a larger neorectal reservoir but rather may be related to decreased motility.

Adult↗

PubMed2002

Hepatocyte expression of soluble donor MHC class I antigen via gene transfer inhibits multiple aspects of the antidonor immune response in fully sensitized rat transplant recipients.

Sensitized organ transplant recipients face an increased risk of hyperacute rejection (HAR) due to donor major histocompatibility complex (MHC) class I antigen (Ag) preexposure. We recently reported a novel donor-specific strategy to address this problem, whereby soluble donor MHC class I Ag gene therapy prevented HAR of heart allografts in passively sensitized rats. Here, we tested this same approach in presensitized rat recipients with a fully preactivated humoral and cellular immune response. Our gene therapy method involved liposomal transfection of cultured recipient (Lewis-RT1.A(1)) hepatocytes with DNA encoding secretable donor MHC class I Ag, RT1.A(a). Control-transfected or RT1.A(a)-transfected hepatocytes were implanted intrasplenically into Lewis rats presensitized with three skin transplants. Subsequently, antidonor antibody, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) assays were performed. Additionally, the effectiveness of our gene therapy on the prevention of ACI (RT1(a)) heart HAR was evaluated. Results indicated that soluble MHC not only decreased cytotoxic antibody levels, but also suppressed antidonor CTL and HTL responses; furthermore, HAR of heart allografts was prevented in all recipients. Therefore, soluble donor MHC class I gene therapy can inhibit multiple aspects of the primed antidonor immune response in actively presensitized rats. Development of this strategy in presensitized humans could improve organ transplant outcome.

Animals↗

PubMed2002

Use of an adenoviral vector to express soluble donor-major histocompatibility complex molecules capable of suppressing the immune response in rat transplant recipients.

There is an accumulating body of evidence indicating that soluble major histocompatibility complex (sMHC) molecules have donor-specific immunosuppressive properties. One classic, but still unproven, theory is that production of sMHC by liver transplants induces a potent immunosuppressive effect. To mimic this possible effect, we have developed a replication deficient adenovirus (Ad-RQ) to express high levels of donor sMHC class I molecules (sRT1.A(a)) in the liver. Ad-RQ produced sRT1.A(a) was measured by enzyme-linked immunosorbent assay (ELISA) after in vitro infection of Lewis (RT1(l)) hepatocytes, and in vivo following intravenous virus injection into Lewis rats. Results indicated high sRT1.A(a) expression in Lewis hepatocyte cultures and, in vivo, high expression was also demonstrated and maintained for at least 1 week. A strong immunosuppressive potential of sMHC in vivo was revealed by prolongation of cardiac (ACI, RT1(a)) heart allograft survival in high-responder Lewis rat recipients treated with Ad-RQ alone. Furthermore, limiting dilution cytotoxic T-lymphocyte precursor (CTLp) analysis of lymphocytes from Ad-RQ-treated Lewis recipients receiving an ACI heart transplant indicated a marked decrease in antidonor CTLp frequency. In conclusion, our results demonstrate that viral vectors can be used effectively to express high levels of sMHC molecules, and their immunosuppressive effect, without concurrent immunosuppression, is sufficiently potent to prolong heart transplant survival.

Adenoviridae↗

PubMed2002

Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor.

Conventional immunosuppressive drugs have been used effectively to prevent immunologic rejection in organ transplantation. Individuals taking these drugs are at risk, however, for the development and recurrence of cancer. In the present study we show that the new immunosuppressive drug rapamycin (RAPA) may reduce the risk of cancer development while simultaneously providing effective immunosuppression. Experimentally, RAPA inhibited metastatic tumor growth and angiogenesis in in vivo mouse models. In addition, normal immunosuppressive doses of RAPA effectively controlled the growth of established tumors. In contrast, the most widely recognized immunosuppressive drug, cyclosporine, promoted tumor growth. From a mechanistic perspective, RAPA showed antiangiogenic activities linked to a decrease in production of vascular endothelial growth factor (VEGF) and to a markedly inhibited response of vascular endothelial cells to stimulation by VEGF. Thus, the use of RAPA, instead of cyclosporine, may reduce the chance of recurrent or de novo cancer in high-risk transplant patients.

Adenocarcinoma↗

PubMed2002

Heat stress prevents impairment of bile acid transport in endotoxemic rats by a posttranscriptional mechanism.

BACKGROUND & AIMS: Endotoxemia leads to reduction of bile acid transporters in the hepatocyte membrane and impaired bile acid transport. Because heat stress ameliorates other sequelae of endotoxemia, studies were performed to determine whether heat stress would correct deficient bile acid transport caused by endotoxin. METHODS: Body temperature of rats was elevated to 42 degrees C for 10 minutes. Lipopolysaccharide was injected after different time intervals, and maximal transport for cholyltaurine was measured in perfused rat livers. Sodium-dependent and -independent uptake was studied in isolated hepatocytes. Protein expression, messenger RNA levels, and tissue distribution of the bile acid transporters sodium taurocholate cotransporting protein (ntcp) and bile salt export pump (bsep) were also analyzed. RESULTS: In the perfused liver, cholyltaurine transport was reduced by 59% by endotoxin, but transport was not reduced when heat stress was applied 2 hours before injection of lipopolysaccharide. The protective effect coincided with maximal expression of heat shock proteins 70 and 25. Sodium-dependent and -independent transport was preserved by heat stress. Expression of bile acid transporters in plasma membrane fractions was reduced after injection of lipopolysaccharide but not if lipopolysaccharide was preceded by heat stress. In contrast, messenger RNA levels of bile acid transporters were not preserved by heat stress. CONCLUSIONS: Heat stress preserves bile acid transporters during endotoxemia by a posttranscriptional mechanism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Insulin attenuates the systemic inflammatory response to thermal trauma.

BACKGROUND: Insulin has been recently shown to decrease mortality and prevent the incidence of multi-organ failure in critically ill patients. The molecular mechanisms by which insulin improves survival have not been defined. The purpose of the present study was to determine the effect of insulin therapy on the systemic inflammatory response. In vivo we determined the effect of insulin therapy on the inflammatory cascade, which was induced by thermal injury. MATERIALS AND METHODS: Thermally injured rats (30% TBSA) were randomly divided into two groups to receive either saline (n= 28) or insulin (n= 28). Our outcome measures encompassed the effect of insulin on pro- inflammatory cytokines, anti-inflammatory cytokines, and hepatic signal transcription factor mRNA expression. RESULTS: Insulin significantly decreased dose dependently serum pro-inflammatory cytokines IL-1beta at 1, 5, and 7 days, IL-6 at 1 day, MIF at 5 and 7 days, and TNF at 1 and 2 days after injury when compared with controls (p<0.05). Insulin increased anti-inflammatory cytokines IL-2 and IL-4 at 5 and 7 days after trauma, and IL-10 at 2, 5 and 7 days after trauma when compared with controls (p< 0.05). Pro-inflammatory signal transcription factors STAT-5 and C/EBP-beta mRNA were significantly decreased 1 and 2 days posttrauma; insulin increased anti-inflammatory signal transcription factor mRNA expression of SOCS-3 and RANTES 7 days after the injury (p< 0.05). CONCLUSIONS: Our data provide insight that insulin attenuates the inflammatory response by decreasing the pro- inflammatory and increasing the anti-inflammatory cas-cade, thereby restoring systemic homeostasis, which has been shown critical for organ function and survival in critically ill patients.

Animals↗

PubMedDate not supplied

Effect of amino acid infusion on human postoperative colon protein synthesis in situ.

BACKGROUND: Amino acids are an integral part of parenteral nutrition because of their anabolic action helping to conserve body protein after surgical stress. At the gastrointestinal tract, an adequate supply of amino acids may be particularly important because of the gut's high rate of protein turnover, cell division, and proliferation. However, no information is available about the effects of amino acids on human intestinal protein metabolism after surgery. METHODS: Studies were performed in postabsorptive patients 8-10 days after major abdominal surgery. Mass spectrometry techniques (capillary gas chromatography/combustion isotope ratio mass spectrometry) were used to directly determine the incorporation rate of 1-[13C]-leucine into colon mucosal protein. All subjects had a colostomy, which allowed easy access to the colon mucosa, and consecutive sampling from the same tissue was performed during continuous isotope infusion (0.16 micromol/kg min). Isotopic enrichments were determined at baseline and after a 4-hour infusion of amino acids or after infusion of saline (control group). RESULTS: Compared with baseline, infusion of amino acids reduced fractional colon protein synthesis significantly by -29.2 +/- 8.3%. This decrease was also significantly different from the corresponding (insignificant) change during saline infusion (+19.4 +/- 26.9%, p < .05 vs amino acid group). CONCLUSIONS: After surgery, an amino acid infusion acutely reduces postoperative colon protein synthesis. This effect possibly may be attributed to interactions of specific amino acids (glutamine) with an altered intestinal immune system and enterocyte activity.

Amino Acids↗

PubMedDate not supplied

The effect of hyperglycemic hyperinsulinemia on small-intestinal mucosal protein synthesis in patients after surgical stress.

Hyperglycemic hyperinsulinemia cannot stimulate intestinal protein synthesis in healthy individuals but does so in conditions characterized by an altered somatotropic axis such as diabetes. Only in a state of growth hormone resistance (high growth hormone but low insulin like growth factor [IGF-1] concentrations), extra insulin may acutely reverse the impaired, growth-hormone-induced IGF-1 release, thereby exerting anabolic actions at the intestinal tract. Growth hormone resistance can be also found in patients after surgical stress. Therefore, we wanted to test the hypothesis whether hyperglycemic hyperinsulinemia would stimulate ileal protein synthesis in the latter condition. Mass spectrometry techniques (capillary gas chromatography/combustion isotope ratio mass spectrometry) were used to directly determine the incorporation rate of 1-[(13)C]-leucine into ileal mucosal protein. All subjects had an ileostomy, which allowed easy access to the ileal mucosa, and consecutive sampling from the same tissue was performed during continuous isotope infusion (0.16 mumol/kg min). Isotopic enrichments and fractional protein synthesis were determined at baseline (period I) and after a 4-hour glucose infusion (170 mg/kg/h) or after infusion of saline (control group) (period II). In controls, ileal protein synthesis declined significantly during prolonged isotope infusion (period I: 1.11 +/- 0.14%/h, period II: 0.39 +/- 0.13%/h, p < .01). In contrast, ileal protein synthesis remained constant during glucose infusion (period I: 1.32 +/- 0.35%/h, period II: 1.33 +/- 0.21%/h, n.s. vs period I, but p < .005 vs the corresponding value at the end of period II in the control group). Using the continuous tracer infusion technique, ileal protein synthesis seemingly declines over a short time in control subjects. We found evidence that this artificial decline was due to mass effects of a rapidly turning over mucosa protein pool in which an isotopic plateau was reached during the experiment and of which the size amounted to approximately 4% of the total mixed protein pool. Maintenance of ileal protein synthesis during glucose infusion therefore indicates a rise of ileal protein synthesis in a slowly turning over protein pool. This effect in postsurgical patients would be compatible with the concept of intestinal insulin action to depend on the specific clinical state (eg, growth hormone resistance).

Aged↗

PubMedDate not supplied

Endovascular treatment of a symptomatic suture aneurysm caused by an aortic isthmus restenosis.

After operative treatment of aortic isthmus stenoses, late complications, such as aneurysm formation or aortic restenosis, might occur, with relevant morbidity and mortality rates during open surgical reintervention. We report on the endovascular repair of a symptomatic suture aneurysm caused by an aortic isthmus restenosis by thoracic aortic stent graft implantation and additional intraoperative balloon dilatation. Based on our experience, endovascular repair of thoracic aortic aneuryms caused by native aortic isthmus stenosis or postcoarctation restenosis is a valuable treatment option, especially in symptomatic patients with an imminent risk of rupture or a difficult immediate transthoracic surgical approach. Long-term follow-up is required to assess the durability of the stent graft treatment.

Aortic Aneurysm, Thoracic↗

PubMedDate not supplied

Elevated MIA serum levels are predictors of poor prognosis after surgical resection of metastatic malignant melanoma.

The secreted MIA protein is upregulated in melanocytic tumors and expression parallels the progressive malignancy of melanoma cells. Recent reports suggest MIA as a diagnostic tumor marker that may also serve as an indicator of tumor progression. In this study we evaluated the association between pre- and post-treatment serum levels of MIA and survival in 70 patients with advanced melanoma. Elevated (> or = 8.8 ng/ml) pre-treatment levels of MIA predicted a poor prognosis in these patients. Overall median survival in stages III and IV was 13 months in MIA positive patients, compared to 28 months in patients with negative pre-treatment MIA levels. The staging-related analysis showed a median survival of 14 months in MIA positive patients, versus 28 months in MIA negative patients in stage III, and 12, versus 19, months in stage IV melanoma, respectively. In addition, there was a trend towards a poorer survival in patients where MIA serum levels remained high after surgery. Therefore, determination of pre- and post-treatment serum MIA levels could be useful for the management and prognosis of metastatic melanoma patients.

Adult↗