Biomedical subjects

Matthias Glanemann

Publications and source records attributed to Matthias Glanemann.

15 recordsLinked to original sources

PubMed2006

Validation of cardiovascular risk scores in a liver transplant population.

Increased prevalence of cardiovascular risk factors has been acknowledged in liver transplant recipients, and an increased incidence of cardiovascular events has been suspected. Individual risk determination, however, has not yet been established. Outpatient charts of 438 primary liver transplants have been reviewed, and suspected cardiovascular risk factors were correlated with cardiovascular events observed during a follow-up period of 10 yr. Receiver operation characteristics curve (ROC) analysis was performed to validate established cardiovascular risk scores. For calibration, the Hosmer-Lemeshow test was performed. A total of 303 of 438 patients were available for risk factor analysis at 6 months and demonstrated complete follow-up data (175 male, 128 female). A total of 40 of those 303 patients experienced fatal or nonfatal cardiovascular events (13.2%). In univariate analysis, age (P < 0.001), gender (P = 0.002), body mass index (P = 0.018), cholesterol (P = 0.044), creatinine (P = 0.006), diabetes mellitus (P = 0.017), glucose (0.006), and systolic blood pressure (P = 0.043), but not cyclosporine A (P = 0.743), tacrolimus (P = 0.870), or steroid medication (P = 0.991), were significantly associated with cardiovascular events. Multivariate analysis, however, identified only age, gender, and cholesterol as independent predictors. In ROC analysis, corresponding areas under the curve for Systematic Coronary Risk Evaluation Project (SCORE), Prospective Cardiovascular Münster Study (PROCAM), and Framingham risk scores (FRSs) were calculated with 0.800, 0.778, and 0.707, respectively. Calibration demonstrated an improved goodness of fit for PROCAM compared to SCORE risk calculations. In conclusion, SCORE and PROCAM proved to be valuable in discriminating our liver transplant recipients for their individual risk of cardiovascular events. Furthermore, calibrated PROCAM risk estimates are required to calculate the number of patients needed to treat in the setup of prospective intervention trials.

Adult↗

PubMed2005

Prospective randomized comparison between a new mattress technique and Cattell (duct-to-mucosa) pancreaticojejunostomy for pancreatic resection.

The majority of lethal complications after pancreatic head resection are due to septic complications after leakage from the pancreatojejunostomy. Especially the smooth pancreatic remnant is prone to develop parenchymal leaks from shear forces applied during tying of the sutures. We developed a new mattress technique that avoids such shear forces, and we compared this method to the standard Cattell (duct-to-mucosa) technique. A total of 113 patients undergoing standard pancreatic head resection were prospectively randomized to receive either the standard Cattell anastomosis (n = 56) or the new mattress technique (n = 57). All patients were evaluated for surgical and medical complications until discharge. Primary diagnosis and further demographic data compared well between the groups. The time to perform the mattress anastomosis was significantly shorter (15 vs. 22 minutes; p < 0.0001). The incidence of complications at the pancreatojejunostomy, and the length of hospital stay and survival were not significantly different between the two groups; however, a trend toward more reoperations was noted in the Cattell group (10 vs. 5; p < 0.097). The new mattress technique is simple, and our data show that the two techniques yield similar incidences of complications. Therefore the mattress technique for pancreatojejunostomy seems to be safe and is, in our opinion, well suitable for training schedules in pancreatic surgery.

Adult↗

PubMed2005

Ischemic preconditioning impairs liver regeneration in extended reduced-size livers.

OBJECTIVE: To evaluate the effect of ischemic preconditioning (IPC) in an experimental setting of extended liver resection with 30 minutes of inflow occlusion in rats. SUMMARY BACKGROUND DATA: IPC has been proven an effective strategy against hepatic ischemia-reperfusion injury in both animal and human studies. However, decreased protective effects in terms of transaminase levels were found in patients with larger resection volume, questioning the benefit of IPC in case of small liver remnants. METHODS: Rats undergoing 90% hepatectomy under strict inflow occlusion for 30 minutes were subjected to either receive or not receive an IPC period (5 minutes of ischemia followed by 30 minutes of reperfusion). In addition to 10-day survival rate, laser Doppler flowmetry of hepatic blood flow and fluorescence microscopic analysis of the hepatic microcirculation were performed to assess the effect of IPC on initial microvascular reperfusion of liver remnants after 90% resection. Moreover, regeneration capacity of livers undergoing IPC and 70% resection was studied over 7 days by means of histology and immunohistochemistry. RESULTS: Ten-day survival of rats which underwent IPC and 90% hepatectomy was 0 out of 10 animals versus 1 out of 10 animals without IPC. Hemodynamic and microcirculatory analysis revealed signs of hyperperfusion during initial reperfusion of preconditioned liver remnants in 90% hepatectomized animals. In addition to increased transaminase levels, IPC impaired hepatic proliferative response after 70% organ resection, as indicated by both a significant reduction in mitotic figures and Ki-67 nuclear staining of hepatocytes, as well as a decrease in restitution of liver mass. CONCLUSIONS: Though portal hypertension reflecting shear stress has been reported to trigger liver regeneration, remnant liver tissue after major hepatectomy may not benefit from hyperperfusion-induced trigger for cell cycle entry but is rather dominated from hyperperfusion-induced local organ injury. Further studies are required to finally judge on the harmfulness of IPC in extended liver resection.

Animals↗

PubMed2005

Older liver graft transplantation, cholestasis and synthetic graft function.

Older liver grafts are often discarded because of conservative selection criteria. We report on our clinical experience with graft-age related outcome. Patients transplanted with livers older than 70 years (70.2-80.2 years, n = 38) were compared with controls transplanted with livers younger than 70 years. Pairs were matched for age, gender, indication and cold ischemic time. Mean donor age was 73.4 +/- 2 vs. 39 +/- 16 years. Patient and graft survival did not differ between both groups after 1-year follow-up (P = 0.19 and P = 0.24 respectively). Retransplantation rate was 10.5% vs. 5.3% (P = 0.40). Initial poor function occurred in two patients in the study group versus four patients in the control group (P = 0.69). The incidence of rejection episodes was comparable. Parameters of cholestasis and protein synthesis showed no difference 1-year post-transplant. Mean age of donor organs in matched pairs group B was near by half of that in the older donor group A (39.0 vs. 73.4 years). Post-transplant outcome as indicated by patient and graft survival was comparable between both groups. Donor organ age had no impact on postoperative organ function. We recommend to accept liver grafts from organ donors older than 70 years to expand the donor pool.

Adult↗

PubMed2005

Coronary event rates in liver transplant recipients reflect the increased prevalence of cardiovascular risk-factors.

Increased prevalence of cardiovascular risk-factors in liver transplant recipients compared with pretransplant and standard population data has been acknowledged. The impact of risk-profiles on cardiovascular event rates or death, however, has not yet been established. Here we evaluate the development of risk-factors during a prospective follow-up of 10 years in 302 patients and compare numbers of coronary events with data from the German Prospective Cardiovascular Münster (PROCAM)-Score population. Prevalence of overweight (17% vs. 27%), hypertension (70% vs. 80%), and diabetes (21% vs. 25%) increased from early to late after transplantation, while elevated serum cholesterol (64% vs. 37%) and triglycerides (40% vs. 21%) became less frequent. Cardiovascular risk-profiles favoring tacrolimus over ciclosporin A based immunosuppression early after transplantation converged over time. Increased risk-scores in liver transplant recipients matched with score standardized event rates in the PROCAM population (ratio: 1.11, 95% CI: 0.53-2.03), nine events were predicted for the transplant population and oppose 10 events observed. Thus, indicating a reflection of increased cardiovascular risk-profiles in corresponding numbers of cardiovascular events.

Adult↗

PubMed2005

Hepatic resection in liver transplant recipients: single center experience and review of the literature.

Biliary complications such as ischemic (type) biliary lesions frequently develop following liver transplantation, requiring costly medical and endoscopic treatment. If conservative approaches fail, re-transplantation is most often an inevitable sequel. Because of an increasing donor organ shortage and unfavorable outcomes in hepatic re-transplantation, efforts to prolong graft survival become of particular interest. From a series of 1685 liver transplants, we herein report on three patients who underwent partial hepatic graft resection for (ischemic type) biliary lesions. In all cases, left hepatectomy (Couinaud's segments II, III and IV) was performed without Pringle maneuver or mobilization of the right liver. All patients fully recovered postoperatively, but biliary leakage required surgical revision twice in one patient. At last follow-up, two patients presented alive and well. The other patient with persistent hepatic artery thrombosis (HAT), however, demonstrated progression of disease in the right liver remnant and required re-transplantation 13 months after hepatic graft resection. Including our own patients, review of the literature identified 24 adult patients who underwent hepatic graft resection. In conclusion, partial graft hepatectomy can be considered a safe and beneficial procedure in selected liver transplant recipients with anatomical limited biliary injury, thereby, preserving scarce donor organs.

Adult↗

PubMed2004

Steroid administration before partial hepatectomy with temporary inflow occlusion does not influence cyclin D1 and Ki-67 related liver regeneration.

BACKGROUND AND AIMS: If temporary inflow occlusion is required during liver resection, the postoperative course might be complicated by ischaemia-reperfusion injury. Steroids protect against ischaemia-reperfusion injury; however, due to its anti-proliferative character concerns exist on its use on liver regeneration after resection. We investigated the effects of methylprednisolone on hepatocyte proliferation after partial hepatectomy with temporary inflow occlusion. PATIENTS AND METHODS: Prior to surgery, one group of Wistar rats received methylprednisolone, while a second group served as non-treated controls. Ischaemia-reperfusion injury was indicated by AST, ALT, and GLDH at 6 h after surgery. Immunohistochemistry tools were used to determine the mitotic index and Ki-67 expression, while cyclin D1 expression characterized the proliferative activity on days 1, 4, 7, and 10. RESULTS: The post-ischaemic liver enzyme release had significantly decreased in the methylprednisolone group, while expression of cyclin D1, percentage of Ki-67-positive cells, and mitotic cell index were comparable in both groups. Similar results were found for bilirubin and albumin and for weight of proliferating liver. CONCLUSION: Although steroid administration significantly reduced ischaemia-reperfusion-associated tissue injury, it has no apparent effects on hepatic regeneration. Thus, steroids could be recommended if a temporary liver ischaemia is required during surgery, in order to reduce complications caused by severe ischaemia-related organ dysfunction.

Animals↗

PubMed2004

Heme oxygenase-1 protects human hepatocytes in vitro against warm and cold hypoxia.

BACKGROUND/AIMS: Hepatic injury induced by ischemia/reperfusion following surgery, transplantation, or circulatory shock combined with resuscitation is a major clinical problem. METHODS: In this study, hypoxic and inflammatory conditions were mimicked by exposing human hepatocytes to N(2) (at 4 and 37 degrees C) or to cytokines/endotoxin to investigate the potential protective effects of heme oxygenase-1 (HO-1). Incubation of human hepatocytes with single cytokines (IFN-gamma, IL-1beta, TNF-alpha) or LPS, as well as a combination of all four stimuli (CM, cytomix) caused a time-dependent HO-1 mRNA expression over 12h and a decline by 24 h. In parallel, we observed a time-dependent membrane leakage for LDH and AST and a maximum HO-1 protein expression between 3-24 h. RESULTS: Warm and cold hypoxia showed similar results in HO-1 mRNA and protein expression and the release of LDH and AST. CoPP, a potent HO-1 inducer, and bilirubin, a co-product of the HO-pathway, protected human hepatocytes from warm and cold hypoxia. HO-1 enzyme activity was highest during warm hypoxia, followed by cold hypoxia and CM which was confirmed by intracellular Fe(2+) formation. CONCLUSIONS: Taken together, we demonstrated, that HO-1 induction protected human hepatocytes against warm and cold hypoxia. Our results also suggest that HO-1 induction may have therapeutic potential against inflammatory insults.

Aspartate Aminotransferases↗

PubMed2004

Ischemic preconditioning and methylprednisolone both equally reduce hepatic ischemia/reperfusion injury.

BACKGROUND: Ischemic preconditioning (I/P) and methylprednisolone (MP) have been suggested to protect against ischemia-reperfusion (IR) injury, which results in an increased tolerance against organ hypoxia. METHODS: Before 45 minutes of hepatic ischemia, male Wistar rats were pretreated with either I/P (5/30 minutes) or MP (30 mg/kg BW). The degree of IR injury and the postischemic inflammatory (leukocyte infiltration, myeloperoxidase, intercellular adhesion molecule-1) and apoptotic (TUNEL, caspase 3, cytochrome C) activity was measured in both groups and compared with non-pretreated (ischemic) animals. RESULTS: Histology and enzyme release revealed that I/P and MP treatment provided significant protection as compared with ischemic controls. TUNEL-positive cells, as well as caspase 3 and cytochrome C expression, were clearly reduced in hepatic tissue of MP-treated animals and partially reduced in I/P-treated animals when compared with ischemic animals. The inflammatory response was considerably reduced in MP- and I/P-treated animals, especially in the early period after ischemia. NF-kappaB/Rel-binding activity was increased after I/P and decreased in MP-treated animals, whereas ischemic controls showed a constant binding activity. CONCLUSIONS: MP (probably by downregulation of NF-kappaB-binding activity) and I/P attenuated the postischemic apoptotic and inflammatory response. Both treatments equally reduced IR-related hepatocellular damage, and, thus, may also be applied equally in surgery involving warm organ hypoxia.

Animals↗

PubMed2003

Primary permanent arterialization of the portal vein in liver transplantation.

Permanent total arterialization of the portal vein in liver transplantation has been described as a method of providing portal inflow after insufficient thrombectomy due to chronic occlusion of the portal-vein system. A specific problem is the restriction of the arterial inflow and its long-term adaptation after transplantation. We describe here the surgical techniques and clinical course of three patients who underwent portal-vein arterialization for liver transplantation. Two patients had an uneventful course. In one patient, a flow reduction by means of coil embolization of one arterial inflow branch was performed; thereafter, the patient recuperated well. Analysing the microcirculation of an arterialized graft in comparison with liver grafts with normal non-arterialized portal-vein inflow, we observed an increase in inter-sinusoidal distance and a decrease in sinusoidal red blood cell velocity. From a technical point of view, we recommend permanent portal-vein arterialization by an iliac artery graft interposition from the subdiaphragmatic aorta. The inflow to the portal vein can easily be reduced by the banding of the arterial graft interposition.

Adult↗

PubMed2003

Ischemic preconditioning protects from hepatic ischemia/reperfusion-injury by preservation of microcirculation and mitochondrial redox-state.

BACKGROUND/AIMS: Ischemic preconditioning (IP) is known to protect hepatic tissue from ischemia-reperfusion injury. However, the mechanisms involved are not fully understood yet. METHODS: Using intravital multifluorescence microscopy in the rat liver, we studied whether IP exerts its beneficial effect by modulating postischemic Kupffer cell activation, leukocyte-endothelial cell interaction, microvascular no-reflow, mitochondrial redox state, and, thus, tissue oxygenation. RESULTS: Portal triad cross-clamping (45 min) followed by reperfusion induced Kupffer cell activation, microvascular leukocyte adherence, sinusoidal perfusion failure (no-reflow) and alteration of mitochondrial redox state (tissue hypoxia) (P<0.05). This resulted in liver dysfunction and parenchymal injury, as indicated by decreased bile flow and increased serum glutamate dehydrogenase (GLDH) levels (P<0.05). IP (5 min ischemia and 30 min intermittent reperfusion) was capable to significantly reduce Kupffer cell activation (P<0.05), which was associated with a slight attenuation of leukocyte adherence. Further, IP markedly ameliorated sinusoidal perfusion failure (P<0.05), and, thereby, preserved adequate mitochondrial redox state (P<0.05). As a consequence, IP prevented the decrease of bile flow (P<0.05) and the increase in serum GLDH levels (P<0.05). CONCLUSIONS: IP may exert its beneficial effects on hepatic ischemia-reperfusion injury by preserving mitochondrial redox state, which is guaranteed by the prevention of reperfusion-associated Kupffer cell activation and sinusoidal perfusion failure.

Animals↗

PubMed2003

Clinical implications of hepatic preservation injury after adult liver transplantation.

Several advances in organ preservation have allowed for improved results after liver transplantation; however, little information is available regarding the clinical impact of preservation injury on the postoperative course. The medical records of 889 liver transplants were retrospectively reviewed. Preservation injury was classified according to postoperative aspartate aminotransferase values as minor (<1000 U/L), moderate (1000-5000 U/L), or severe (>5000 U/L). The following criteria were analyzed and compared according to the extent of preservation injury: patient and graft survival, retransplantation rate, duration of hospitalization and postoperative ventilation, as well as incidence of rejection, infection, and hemodialysis. The majority of patients received a liver with minor preservation injury (75.9%), whereas 22.7% and 1.3% of grafts showed moderate or severe injury. Graft survival was significantly lower in patients with severe preservation injury, when compared to minor or moderate injury. The relative risk for initial nonfunction was 39.36-fold increased (95% confidence interval (ci): 10.3-150.2), as it was increased for duration of postoperative ventilation (6.92-fold; 95%ci: 2.1-22.3) and hemodialysis (6.13-fold; 95%ci: 1.9-19.3). Since the incidence of retransplantation was significantly increased (50%), patient survival remained comparable between all groups. Severe preservation injury had a tremendous impact on the postoperative clinical course, requiring the maximum medical effort to achieve adequate patient survival.

Adult↗

PubMed2003

Hepatic artery thrombosis after adult liver transplantation.

The incidence, clinical presentation, therapeutic options, and outcome of hepatic artery thrombosis (HAT) were analyzed in a series of 1,192 consecutive adult orthotopic liver transplantations (OLTs). HAT after OLT was observed in 30 cases, resulting in an incidence of 2.5%. The incidence of HAT increased 5.76-fold when the donor hepatic artery was reconstructed with an interposition graft to the supraceliac aorta (P <.05). Early HAT (within the first 30 days after OLT) occurred in 14 of these patients (46.7%), whereas in 16 patients (53.3%), HAT occurred beyond 30 days post-OLT. Clinical presentation of HAT ranged from an increase in serum transaminase levels with or without cholestasis to liver abscess and biliary complications, including cholangitis, bile duct stenosis or necrosis, to liver dysfunction and failure. Impairment of graft function was observed in patients with early HAT, whereas biliary tract destruction was seen more often in patients with late HAT. In only 1 patient was HAT clinically asymptomatic. Therapy consisted of recombinant plasminogen lysis with hepaticojejunostomy, liver abscess drainage, endoscopy or surveillance, and surgical thrombectomy. In 14 of 30 patients (46.7%), the occurrence of HAT required re-OLT. Nine patients with HAT died during follow-up; however, only 4 of these deaths were related to HAT, resulting in a mortality rate of 13.3%. Our results indicate that HAT is a rare but serious complication after OLT, requiring re-OLT in almost 50% of patients. In particular, conservative treatment modalities may significantly prolong graft survival, thus postponing re-OLT.

Adolescent↗

PubMed2002

Results of end-to-end cavocavostomy during adult liver transplantation.

The results of end-to-end cavocavostomy during adult liver transplantation were analyzed with special regard to caval complications. In a series of 1000 liver transplants, we observed 17 patients who suffered from postoperative caval obstruction (6 patients) or caval stenosis (11 patients), for an incidence of 1.7%. Surgical therapy was performed in 10 patients (58.8%), and 5 patients required retransplantation (29.4%). Four patients died during the later postoperative course. Two fatalities were related to caval complications, resulting in a mortality rate of 11.8%. Our results indicate that end-to-end cavocavostomy is a safe technique for cavocaval anastomosis. For only a few exceptions, such as pediatric transplantation, reduced size livers, or size mismatch between donor and recipient, should alternative techniques such as end-to-side or side-to-side cavocavostomy be performed.

Adult↗

PubMedDate not supplied

Long-term results of mycophenolate mofetil as part of immunosuppressive induction therapy after liver transplantation.

BACKGROUND: The addition of mycophenolate mofetil (MMF) to the induction protocol resulted in a lower incidence of rejection episodes. However, the question whether MMF should be administered in combination with tacrolimus or cyclosporine has not been answered yet. In our study, we report on the long-term results of triple induction therapy after orthotopic liver transplantation (OLT), consisting of MMF and low-dose corticosteroids, in combination with either tacrolimus or cyclosporine. METHODS: Between March 1996 and April 1997, 120 consecutive patients, who underwent OLT at our institution, were enrolled in this study. Of these patients, 80 received triple induction therapy consisting of cyclosporine and MMF (40) or tacrolimus and MMF (40), in combination with low-dose corticosteroids, whereas the remaining 40 patients served as 'MMF-free' control group receiving dual induction therapy with tacrolimus and corticosteroids. Besides the eight-yr follow-up of patient and graft survival, clinical data were also reviewed for episodes of rejection and infection. Additionally, the early post-operative pharmacokinetics of mycophenolic acid (MPA, immunological active metabolite of MMF) were evaluated. RESULTS: Long-term results provided higher patient and graft survival after tacrolimus/MMF-based induction therapy than after cyclosporine/MMF-based induction therapy. However, the tacrolimus-based control protocol yielded similar results and, therefore, no significantly superior effect was observed when MMF was added. The same observation was made for incidence of rejection and infection episodes. AUC and C(max) of MPA increased in combination with tacrolimus compared with cyclosporine. CONCLUSIONS: Although pharmacological synergy between tacrolimus and MMF was observed, MMF showed no significant beneficial effects in the immunosuppressive induction protocol, neither in combination with tacrolimus nor with cyclosporine.

Cyclosporine↗