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Biomedical subjects

M Golling

Publications and source records attributed to M Golling.

At least 37 records · Page 2Linked to original sources
PubMed2002

[Development of primary malignancies after liver and kidney transplantation and the treatment approach].

Primary malignancy after solid organ transplantation has a more than three-fold incidence compared to the normal population. Causes are intensity and duration of immunosuppression, pre-operatively undetected, occult malignancy or pre-cancerous lesions in the recipient, direct or indirect tumor transmission via the transplant and environmental factors. Measures for prevention comprise antiviral treatment of individuals at risk for primary EBV-infection and prevention of sun exposure. Early detection follows general medical guidelines and, in addition, selective screening of certain risk groups of patients. Treatment of solid tumors follows established guidelines of professional working parties. Post-transplant lymphoproliferative disorders can often be treated with anti-CD antibody (rituximab). Antiproliferative immunosuppressants like rapamycin may seem promising with regard to a possibly reduced incidence of de-novo malignancy in the future.

Humans↗
PubMed2002

[Intensive care treatment of post-traumatic liver failure].

Liver failure following trauma or surgery is associated with a mortality of between 15-->50%, depending on the extent of the operation, pre-operative functional impairment of the liver as well as the occurrence of concomitant infectious disease. The liver can be the source as well as the target of posttraumatic liver failure (PLF). PLF can be caused by a reduction of liver perfusion due to hypotension, catecholamines or increased intraabdominal pressure. Further contributing factors include prolonged parenteral nutrition, endotoxemia, and potentially hepatotoxic drugs (sedatives, anticonvulsive drugs, antibiotics etc.). PLF is mostly associated with MOF. The Child classification and the APACHE score may predict prognosis before surgery and serum bilirubin levels thereafter. Prevention and therapy is based on treatment of shock and tissue hypoxia. It should be accompanied by appropriate diagnostic measures and followed by an aggressive medical and surgical approach.

APACHE↗
PubMed2001

[Posterior pelvic exenteration in locoregional recurrence of rectal carcinoma--indications, technique and outcome].

Despite a potentially curative operation in over 70% of rectal carcinomas, local recurrence is observed in up to 55%. The most common location is at or around the anastomosis and the presacral region. Locoregional recurrence is--apart from distant metastases--the most important factor determining prognosis and survival. If an R0 resection can be performed, a 5-year survival rate of 20-30% can be achieved. Whether patients will benefit from a palliative operation is still a matter of debate. Morbidity is estimated to exceed 60% and perioperative mortality always below 10%. In this article, we review the indication, preoperative diagnostic and therapeutic procedures as well as results of the posterior pelvic exenteration with sacral resection. Taking all aspects into account, posterior pelvic exenteration seems to be justified due to the lack of alternatives and the potential benefit of palliative and curative resection. With respect to the effort in time, personnel, surgical expertise and logistics, this operation should be preferably performed in specialized and well-equipped medical institutions.

Humans↗
PubMed2001

[Definition of surgical degree of freedom by functional anatomy in liver resection surgery].

Liver resections have developed to very complex and differentiated operations, clearly adapted to individual anatomical and physiological conditions. In parallel, perioperative morbidity has been dramatically reduced. Intraoperative strict consideration of various details of hepatic anatomy, particularly of functional liver anatomy, has proved to be of particular importance when liver surgery reaches indication and technical limits. The term "functional anatomy" stands for a form of hepatic substructurization, which is primarily based on the existence of hemodynamically independent regions of liver parenchyma. A selection of some of the most important details and facts of functional liver anatomy and secondary derived guidelines for surgical strategy and technique is presented in an overview, with special focus on liver resection.

Hepatectomy↗
PubMed2001

[Indications and outcome of liver metastases resection].

Liver resection with curative intent for metastastic disease can be performed at low operative morbidity and mortality (< 3%). Most data relate to colorectal metastases. Five year survival following primary and repeat liver resection is consistently reported as 25-30% and has not been improved by adjuvant chemotherapy. Options for improvement of prognosis by purely technical means appear limited. Instead, future strategies should aim at increasing the number of patients amenable to potentially curative liver resection. This could be achieved by earlier diagnosis, by combination of surgical resection with neoadjuvant treatment or thermoablation, by selective portal embolisation as well as further surgical specialisation. The search for effective adjuvant therapy should continue.

Colorectal Neoplasms↗
PubMed2001

Characterization of renal parenchymal perfusion during experimental infrarenal aortic clamping and declamping with enhanced thermodiffusion electrodes.

Despite multiple previous experimental and clinical investigations, it has not been fully clarified until now whether infrarenal aortic cross-clamping (IRAC) induces a significant disturbance of renal parenchymal perfusion. Most renal cortical flow data collected thus far have been heterogenous because of inherent limitations of available measurement technology. The enhanced thermal diffusion (TD) electrode is a newly developed and previously validated prototype device that allows continuous quantification of parenchymal kidney perfusion after local probe implantation. We monitored renal perfusion during experimental IRAC with TD for the first time, thereby also evaluating the potential applicability of the method in clinical aortic surgery. IRAC (20 min) followed by sudden declamping was performed in pigs under general anesthesia (n = 14). Renal cortical blood flow (RCBF) was continuously quantified by TD, total aortic flow (TABF) and renal artery flow (RABF) were measured by ultrasonic flow probes, and parameters of systemic circulation were determined by Swan-Ganz catheter. Our results showed that kidney perfusion can be continuously quantified using TD electrodes during experimental aortic surgery in a porcine model. IRAC does not lead to a significant impairment of RCBF in young pigs as measured by TD. Renal perfusion appears to be predominantly pressure driven. Consequently, abrubt aortic declamping can bring about prolonged renal ischemia. Transfer of the TD method to RCBF monitoring during clinical aortic surgery appears to be feasible and should be investigated in selected cases.

Animals↗
PubMed2001

Immunogenicity of two accelerated hepatitis B vaccination protocols in liver transplant candidates.

OBJECTIVE: It is common practice to immunize patients against hepatitis B virus infection prior to orthotopic liver transplantation (OLT). We compared the seroprotection rates of two accelerated schedules with a recombinant hepatitis B vaccine in patients awaiting OLT. DESIGN AND METHODS: Patients were prospectively recruited and vaccinated with either 20 micrograms (group 1, n = 14) or 40 micrograms (group 2, n = 20) hepatitis B surface antigen per dosage. Thirty-nine healthy volunteers served as a historical control group. Patients in all groups were vaccinated with an accelerated schedule (0, 7 and 21 days). All patients underwent clinical and laboratory examinations (HBs antibodies, CD4/CD8 ratio, transaminases). RESULTS: The accelerated hepatitis B vaccination schedules were well tolerated. Eight weeks after the third injection, no significant differences in seroprotection rates were observed between group 1 (31%) and group 2 (26%). There was no correlation with respect to seroconversion rates and gender, smoking habits or CD4/CD8 ratio. CONCLUSION: These data suggest that accelerated vaccination schedules with a recombinant hepatitis B vaccine are safe and well-tolerated, but only achieve poor seroconversion rates in OLT candidates. Increasing the vaccine dose to 40 micrograms hepatitis B surface antigen per injection did not result in a higher response rate. Because of the low risk of acquiring de novo hepatitis B infection after transplantation, it should be questioned whether routine hepatitis B vaccination with standard recombinant vaccines prior to liver transplantation should be recommended any longer.

Adult↗
PubMed2001

Endothelin-1 and big-endothelin concentrations are elevated in liver graft tissue during cold storage and reperfusion.

Endothelin (ET) and its precursor big-ET were synchronously analyzed by RIA in liver biopsies and systemic plasma during porcine orthotopic liver transplantation (OLT) before graft harvesting (phase A), after cold storage (phase B), and early (phase C) and late reperfusion (phase D). Tissue and plasma concentrations were correlated with length of survival and reperfusion. Increased tissue ET/big-ET levels were already detected during phase B (ET: 46 +/- 20; big-ET: 245 +/- 119 pg/mg cytosolic protein) and remained elevated in phase C (ET: 49 +/- 16; big-ET: 306 +/- 144 pg/mg) compared to baseline (ET: 32 +/- 13; big-ET: 185 +/- 164 pg/mg; p < 0.05). In phase D, a rapid concentration decline was detected (ET: 36 +/- 26; big-ET: 163 +/- 138 pg/mg). Systemic ET levels were elevated in phase B (3.4 +/- 3.0 pg/ml), C, (2.8 +/- 1.2 pg/ml) and D (2.6 +/- 2.0 pg/ml), compared to baseline (1.7 +/- 1.1 pg/ml; p < 0.05). ET/big-ET kinetics in liver tissue and systemic plasma showed analogous characteristics. Intrahepatic ET accumulation during storage and early reperfusion could be of relevance for harvest-related disturbances of hepatic microcirculation.

Animals↗
PubMed2000

Microchimerism in bone marrow-derived CD34(+) cells of patients after liver transplantation.

Lymphoid and dendritic cells of donor origin can be detected in the recipient several years after a solid organ transplantation. This phenomenon is termed microchimerism and could play a role in the induction of tolerance. The fate of other hematopoietic cells transferred by liver transplantation, in particular of stem and progenitor cells, is unknown. For this reason, we studied peripheral blood and bone marrow samples of 12 patients who had received a liver transplant from an HLA-DR mismatched donor. Eight patients were long-term survivors between 2.8 and 10.1 years after allografting. CD34(+) cells from bone marrow were highly enriched with the use of a 2-step method, and a nested polymerase chain reaction was applied to detect donor cells on the basis of allelic differences of the HLA-DRB1 gene. Rigorous controls with DRB1 specificities equal to the donor and host were included. In 5 of 8 long-term liver recipients, donor-specific CD34(+) cells could be detected in bone marrow. Microchimerism in the CD34(+) cell fraction did not correlate to the chimeric status in peripheral blood. In conclusion, our results demonstrate a frequent microchimerism among bone marrow-derived CD34(+) cells after liver transplantation. The functional role of this phenomenon still needs to be defined. (Blood. 2000;96:763-767)

Adolescent↗
PubMed2000

Effects of exogenous endothelin-1 application on liver perfusion in native and transplanted porcine livers.

PURPOSE: This study was designed to assess and differentiate the impact of progressivly increasing portal venous endothelin-1 (ET) plasma concentrations on hepatic micro- and macroperfusion of native porcine livers (Group A) and liver grafts after experimental transplantation (Group B). METHODS: A standardized gradual increment in systemic ET plasma concentration (0-58 pg/ml) was induced by continuous ET-1 infusion into the portal vein in both groups (A: n = 10, B: n = 10). Control animals received only saline (n = 5, each group). Hepatic microcirculation (HMC) was quantified by thermodiffusion electrodes, hepatic artery flow (HAF), and portal venous flow (PVF) by Doppler flowmetry. RESULTS: No changes in ET or perfusion parameters were observed in controls. The mean ET level after orthotopic liver transplantation (OLT) in Group B was elevated (baseline: 3.8 +/- 2.4 pg/ml) compared with Group A (2.8 +/- 1.9 pg/ml). With rising ET levels HAF decreased progressively in Group A from 205 +/- 97 (baseline) to 160 +/- 72 ml/min, and in Group B from 161 +/- 87 to 146 +/- 68 ml/min. PVF decreased in Group A from 722 +/- 253 to 370 +/- 198 ml/min, and in Group B from 846 +/- 263 to 417 +/- 203 ml/min. Baseline HMC in Group A was 86 +/- 15 and decreased significantly to 29 +/- 9 ml/100 g/min, and baseline MC in Group B was 90 +/- 22 and decreased to 44 +/- 32 ml/100 g/min. No significant alteration in systemic circulation was noted at the ET concentrations investigated. CONCLUSIONS: Significant impairment of hepatic micro- and macrocirculation was detected after induction of systemic ET levels above 9.4 pg/ml both in native and in transplanted livers. Disturbance of HMC was caused predominantly by reduction of portal venous flow, while the effect of ET on HAF was less pronounced. Characteristics of flow impairment in transplanted and native livers were analogous after short cold ischemic graft storage (6 h).

Animals↗
PubMed2000

Intramucosal pH and liver endotoxin clearance during experimental liver transplantation.

The study was designed to assess the gastrointestinal ischaemia and the influence of the specific Kupffer cell toxin gadolinium chloride (GdCl3) on the hepatic and extrahepatic endotoxin [lipopolysaccharide (LPS)] clearance during experimental orthotopic liver transplantation (OLT) in pigs. In eight pig liver transplantations, the donors received 20 mg/kg of GdCl3 24 h before explantation, while controls (n = 8) received normal saline. Gastric and sigmoid intramucosal pH (pHi), LPS and endotoxin-neutralising capacity (ENC) levels were measured in the portal vein and superior vena cava after laparatomy, at the end of the anhepatic phase and 1 h after reperfusion. During the anhepatic phase, the sigmoid pHi decreased significantly from 7.32 +/- 0.02 to 7.29 +/- 0.03 (P < 0.001) and was associated with a substantial increase of portal LPS. Following reperfusion, the systemic LPS concentrations were significantly lower in the pretreated group [39 +/- 23 pg/ml (Control); 14 +/- 7 (GdCl3); P < 0.05] suggesting an improved liver LPS clearance [86% (GdCl3); 58.2% (Control); P < 0.05]. This corresponded to an increased ENC in the pretreated group [118 +/- 52 ENU/ml (GdCl3) vs 81 +/- 45 ENU/ml (Control); P < 0.05]. The anhepatic phase induced splanchnic ischaemia which correlated with portal endotoxaemia. Donor preconditioning with GdCl3 leads to lower systemic LPS concentrations in the recipient and increases ENC values in the early phase after OLT. An improved hepatocellular LPS extraction and/or an activation of the extrahepatic reticulo-endothelial system as a result of GdCl3 treatment is discussed.

Animals↗
PubMed2000

Sequential (domino) transplantation of the liver in a transthyretin-50 familial amyloid polyneuropathy. Special reference to cardiological diagnosis and complications.

BACKGROUND: General shortage of cadaveric organs has led to a search for alternative methods to expand the donor pool. Sequential (domino) transplantation is yet another attempt to compensate for the declining consent to organ donation. PATIENTS AND METHODS: To qualify for a domino liver transplantation, the following preconditions must be fulfilled: (1) extrahepatic disease must exist, (2) liver must be fully functional, and (3) the genetic defect in the host should recur within a sufficient latency period. Familial amyloid polyneuropathy (FAP) is an autosomal dominant disease which involves a genetic defect for transthyretin (TTR), which is predominantly produced in the liver. RESULTS: In this report, we describe a rare case of a FAP TTR-50 variant undergoing domino liver transplantation. Since myocardial symptoms precede peripheral polyneuropathy, special emphasis should be placed on arrhythmias and the restrictive cardiomyopathy necessitating a veno-venous bypass or a cardiac pacemaker in order to improve cardiac contractility. The type of anastomosis of the suprahepatic inferior vena cava and possible alternatives are discussed. CONCLUSION: Despite ethical problems, the advantages of the domino procedure are obvious: (1) expansion of the donor pool, (2) ability to use living donors, and (3) presence of very short ischemic time and thus excellent liver function. Due to the kinetics of TTR production and deposition, donors and recipients of FAP livers should be followed up using an extensive neurological and cardiological protocol.

Adult↗
PubMed2000

Evidence for impaired glucose effectiveness in cirrhotic patients after liver transplantation.

To evaluate the impact of acute and chronic liver disease and single immunosuppression (cyclosporine A [CSA] or FK506) on insulin sensitivity and glucose effectiveness in liver-grafted patients, we performed a frequently sampled intravenous glucose tolerance test (FSIGTT) in nondiabetic patients after orthotopic liver transplantation (OLT) with acute liver failure ([ALF] group, n = 9, with CSA therapy), in patients after OLT with chronic liver disease (CSA group, n = 8; FK506 group, n = 8), and in 9 healthy control subjects. Insulin sensitivity and glucose effectiveness were determined by analyzing glucose and insulin data from the FSIGTT with Bergman's minimal model technique for glucose. The intravenous glucose tolerance index ([KG] ie, the slope of the regression of the logarithm of blood glucose concentration) was not different between the ALF group (2.17 +/- 0.16 min(-1)) and controls (2.29 +/- 0.13 min(-1)), but was lower (P < .05) in both groups with chronic liver disease (CSA group, 1.46 +/- 0.1; FK506 group, 1.61 +/- 0.11 min(-1)) compared with the ALF group (P < .05). A positive relation for the KG and glucose effectiveness was found in all liver-grafted patients and controls. Insulin sensitivity was not different between all liver-grafted patients and controls. The body mass index (BMI) was the overall determinant of insulin sensitivity in all groups. Single immunosuppressive therapy does not impair insulin sensitivity in liver-grafted patients. The lower glucose effectiveness in liver-grafted patients with chronic liver disease but not in patients after ALF points to a defect in the regulation of glucose-mediated glucose uptake in peripheral tissue.

Adult↗
PubMed1999

[The VCS clip--experimental experiences with a new vascular suture stapling device].

Despite improvements in technique and suture material, vascular anastomosis is still associated with a significant rate of early (stenosis, thrombosis) and late (intimal hyperplasia) complications. Although automatic mechanical staplers were practical und comparatively safe to use, they did not play a major role in vascular surgery, probably due to the complexity and difficult handling. In an experimental study with the VCS clip system, we found a significant improvement in performing a hepatic artery anastomosis [9.2 +/- 1.5 min (VCS) vs 20.6 +/- 2.7 min (suture), P < 0.001], early patency and flow rate [150 +/- 29.1 ml/min (1.0 h)-->79.9 +/- 24.0 ml/min (24 h) (suture) vs 186 +/- 45 ml/min (1.0 h)-->162 +/- 48 ml/min (VCS), P < 0.005]. Besides easy handling, the VCS clip system allows for a fast, standardized vascular anastomosis without intimal penetration.

Anastomosis, Surgical↗