PubMed Health⌕ Search

Biomedical subjects

A Königsrainer

Publications and source records attributed to A Königsrainer.

At least 19 recordsLinked to original sources
PubMed2007

Lactate down-regulates cellular poly(ADP-ribose) formation in cultured human skin fibroblasts.

BACKGROUND: Polyadenosine diphosphate-ribose (poly(ADP-ribose)) is a nuclear polymer which is derived from nicotinamide adenine dinucleotide (NAD(+)) catalysed by poly(ADP-ribose) polymerase 1 (PARP-1). Aside from the well known role of poly(ADP-ribosyl)ation (pADPR) in DNA repair, pADPR is also involved in other cellular processes such as apoptosis and gene expression. However, the factors that regulate the level of pADPR are not fully elucidated. In view of the fact that healing wounds contain high concentrations of lactate (10-15 mM) and exogenous lactate reduce the NAD(+) pool in cultured fibroblasts, we propose that high lactate lowers the level of nuclear pADPR. MATERIALS AND METHODS: Neonatal human dermal fibroblasts (NHDF) were plated to subconfluence and allowed to adhere. Cells were treated with 15 mM l-lactate and pADPR production was assessed by immunofluorescence analysis using 10H antibody. Difference in pADPR production was determined by calculation of positively stained cells compared to total cell numbers. Inhibition of PARP activity was tested by treatment with 100 microM 3-aminobenzamide (3-AB). Specificity of the lactate effect on pADPR synthesis was verified by using the analogue d-lactate. The contents of nicotinamide adenine dinucleotide (NAD(+)) and its reduced form (NADH) in lactated and non-lactated cell cultures were quantified by the enzymatic cyclic assay. RESULTS: We found that exogenous l-lactate (15 mM) can significantly depress pADPR content in cultured fibroblasts. PARP-1 activity was inhibited by 3-AB and analogue d-lactate showed no effect on pADPR synthesis. NAD(+)/NADH ratio was significantly lowered in lactated compared to non-lactated cell culture. CONCLUSIONS: Exogenous l-lactate (15 mM) can depress pADPR content in cultured fibroblasts. In view of the fact that healing wounds contain such high concentrations of lactate, we propose that down regulation of pADPR is associated with elevated tissue repair via pADPR dependent gene expression. This observation is important in understanding the stimulation of lactate-mediated protein expression during wound healing.

Cells, Cultured↗
PubMed2007

The lower esophageal sphincter strength in patients with gastroesophageal reflux before and after laparoscopic Nissen fundoplication.

Lower esophageal sphincter pressure (LESP) and sphincter strength (LESS) were measured before and after short and floppy laparoscopic Nissen fundoplication (LNF) in 38 patients with severe gastro-esophageal reflux disease (GERD). These patients were compared with a control group of 23 healthy volunteers. GERD was assessed by stationary manometry, 24-h pH recordings and endoscopy. LESS was verified by motorized pull-back of an air-filled balloon catheter from the stomach into the esophagus. The catheter assembly was well tolerated by all study participants. LESP increased significantly after operation from 8 mmHg to 14 mmHg (75% of normal values; P < 0.0001), but compared to the control group, LESP (22 mmHg) decreased significantly (P < 0.002). In the control group and in patients with GERD, LESP and LESS showed excellent correlation (r = 0.97, r = 0.94, respectively). After LNF, LESS increased significantly from 0.6 to 1.6 N (P < 0.0001), about 166%. We conclude that the measurement of LESS is able to explain the discrepancy between satisfactory NF operation and the distinct increase of postoperative LESP. The evaluation of LESS is a helpful tool in assessing functional understanding of laparoscopic Nissen fundoplication with a short and floppy wrap.

Adult↗
PubMed2006

[Klatskin tumor surgical treatment].

Due to the difficulties of diagnosis of central bile duct carcinoma an experienced surgeon should be involved in the decision-making process at an early stage. This is true in particular with regard to the fact that currently the only curative treatment option is an extended bile duct resection with up to 80% five-year survival rates. In case of a too small liver volume, contralateral selective percutaneous embolization of the portal vein can be performed. Liver transplantation is reserved to a selected group of patients with local inoperability, but it is becoming more and more important due to the possibility of living donor liver transplantation associated with multimodal treatment strategies.

Bile Duct Neoplasms↗
PubMed2005

Prevalence of vertebral alterations and the effects of calcium and vitamin D supplementation on calcium metabolism and bone mineral density after gastrectomy.

BACKGROUND: Bone disease is common after gastrectomy, resulting in decreased bone mass and an increased risk of fracture. No proven therapy is currently available. METHODS: Serum markers of calcium metabolism in 98 patients after partial or total gastrectomy were compared with those in 30 age- and sex-matched healthy controls. Patients with disorders of calcium metabolism were investigated by conventional radiography and single-energy computed tomography of the spine. Forty patients participated in a 1-year follow-up study to investigate the effects of vitamin D and calcium supplementation on calcium metabolism and bone mineral density. RESULTS: Altered serum markers of calcium and phosphate metabolism were observed in 77 (79 per cent) of 98 patients. Sixty (79 per cent) of these had vertebral alterations. Vertebral fractures were detected in 22 patients, grade I vertebral deformities in 50 patients, grade II deformities in 22 patients and osteopenia (Z-score less than - 1) in 30 patients. Calcium and vitamin D supplementation resulted in an increase in 25-hydroxy-vitamin D (P < 0.001), 1,25-dihydroxy-vitamin D (P = 0.048) and osteocalcin (P = 0.045), whereas levels of parathyroid hormone were decreased (P = 0.007). Bone mineral density did not change over time. CONCLUSION: Disturbances of calcium and bone metabolism are common after gastrectomy. Calcium and vitamin D supplementation normalized levels of markers of calcium metabolism and might have prevented age-related bone mass loss, although it did not increase bone mineral density after 1 year.

Biomarkers↗
PubMed2005

Progression of macrovascular diseases is reduced in type 1 diabetic patients after more than 5 years successful combined pancreas-kidney transplantation in comparison to kidney transplantation alone.

Recent reports have demonstrated an improved cardiovascular outcome after simultaneous pancreas-kidney transplantation (SPKT) compared with kidney transplantation alone (KTA) in type 1 diabetic patients with end-stage renal disease. The purpose of this study was to determine the impact of SKPT and KTA on the progression of cerebrovascular disease (CVD), coronary heart disease (CHD) and peripheral vascular disease (PVD) 5 and 10 years after transplantation. Only patients with graft survival more than 5 years, were included in this study. In summary, 12 type 1 diabetic patients with SPKT and 10 diabetic subjects with KTA were evaluated. The immunosuppressive therapy was similar in both patient groups. The mean observation period was 124 (72-184) months in the SPKT group and 122 (64-216) months in the group with KTA. To investigate the vascular risk profile we examined mean HbA1c, blood pressure and lipid levels in both patient groups during the first 5 years (period I) and the second 5 years (period II) after transplantation (measurements at least at 3-month intervals). Additionally, we evaluated the prevalence of moderate (stage I-II) and severe (stage III-IV) macrovascular diseases prior as well as 5 and 10 years after transplantation. During period I the mean HbA1c-value was 5.7+/-0.4% in the group with SPKT versus 7.4+/-0.8% in the KTA group, and in period II 5.8+/-0.4% in the SPKT group versus 7.6+/-0.9% (P<0.001) in the patients with KTA. The cholesterol levels were approximately the same in both groups, the triglycerides were lower in the patients with SPKT than in the subjects with KTA with 1.3+/-0.4 vs. 2.2+/-0.9 mmol/l in period I, and 1.4+/-0.5 vs. 2.3+/-0.6 mmol/l in period II (P<0.05). The BP-values were similar in both groups. Five years after transplantation the prevalence of vascular diseases was not significantly different between both groups. During the following 5 years the prevalence of macrovascular diseases increased more in the KTA than in the SKPT group. After a mean observation period of 10 years the SKPT group showed a lower prevalence of vascular diseases (stage I-IV) with 41% CVD, 50% CHD and 50% PAV in comparison to the KTA group with a prevalence of 80% CVD, 90% CHD and 80% PAV), the difference was not statistically significant because of the small patient groups. The frequency of the vascular complications myocardial infarction (16% vs. 50%), stroke (16% vs. 40%) and amputations (16% vs. 30%) was in summary significant lower in the patients with SPKT than in the patients with KTA (P<0.05). In conclusion, while for the first 5 years after transplantation the progression of macroangiopathy in patients with SPKT and KTA was not significantly different, after a mean 10-year observation period the progression of macrovascular diseases was significantly lower in recipients with a functioning SPKT compared to patients with a KTA; this can be explained by a better vascular risk profile after SPKT. The 10-year patient survival was 83% in the SPKT group and 70% in patients with KTA.

Adult↗
PubMed2004

[Pathology of small intestine transplantation].

Small bowel transplantation is being increasingly performed to treat patients with irreversible intestinal failure or short bowel syndrome. Worldwide approximately 100 transplantations are currently performed per year. Technical advances and new immunosuppressive strategies adopted during the last 10 years have significantly improved the quality of live and survival rate of the patients. The 5-year survival rate is currently around 60%. However, the procedure still bears significant live threatening risks. Mayor problems include surgical complications like anastomotic leakage or peritonitis, acute allograft rejection, systemic infection and in later stages loss of graft function due to chronic rejection. Acute rejection is common after intestinal transplantation. It may occur any time after transplantation and is seen in 50%-80% of the patients. The characteristic changes are enterocyte apoptosis in the crypts, cryptitis and mononuclear cell infiltration with activated lymphocytes. Severe cases may reveal ulcerations or even sloughing and widespread exfoliation of the epithelium and are almost invariably associated with graft loss. The histopathological abnormalities may be patchy and occur in grossly normal mucosa. Therefore, multiple biopsies should be generally sampled for histology. Acute rejection must be distinguished from infections in particular opportunistic viral infections caused by Cytomegalovirus (CMV) or Adenovirus as well as from Epstein-Barr virus-related B-lymphocyte proliferations. Differential diagnosis also includes preservation injury and ischemia resulting in damage of the mucosal surface epithelium. Long-term graft function and survival are now increasingly determined by chronic rejection. The hallmarks of chronic rejection are obliterative arteriopathy of mesenterial vessels and progressive fibrosis of the transplant including its mesentery.

Graft Rejection↗
PubMed2003

Percutaneous portal vein embolisation in preparation for extended hepatic resection of primary nonresectable liver tumours.

BACKGROUND: In patients with malignant primary and secondary liver tumours or proximal bile duct carcinoma radical surgery is superior to all other therapeutic modalities in terms of survival and quality of life. Radical resection, however, often requires the removal of a large amount of liver parenchyma, resulting in a marked reduction of functional liver tissue with the risk of liver failure. AIM: Preoperative partial portal vein embolisation induces hypertrophy of the controlateral liver and thereby increases the safety of extended liver resections. PATIENTS AND METHODS: Between January 1997 and February 2001 we applied this strategy in 19 patients with primary and secondary nonresectable hepatobiliary malignancies, in whom the estimated amount of the remnant liver was < or =25% of the liver volume. RESULTS: The increase in volume ranged between 7 and 245%. Radical extended liver resection was performed in 13 patients (68%) without mortality. After a mean observation time of 22 months patient survival was 19 months with six tumour-related deaths during the second year after surgery. The remaining seven patients are alive and well with tumour recurrence in one. CONCLUSION: Preoperative partial portal vein embolisation allows more patients with previously unresectable liver tumours to benefit from a potentially curative resection.

Biliary Tract Neoplasms↗
PubMed2003

Haemolytic uraemic syndrome and mutations of the factor H gene: a registry-based study of German speaking countries.

BACKGROUND: The aetiology of atypical haemolytic uraemic syndrome (aHUS) is, in contrast to classical, Shiga-like toxin induced HUS in children, largely unknown. Deficiency of human complement factor H and familial occurrence led to identification of the factor H gene (FH1) as the susceptibility gene, but the frequency and relevance of FH1 mutations are unknown. METHODS: We established a German registry for aHUS and analysed in all patients and 100 controls the complete FH1 gene by single strand confirmational polymorphism and DNA sequencing. In addition, complement C3 and factor H serum levels were assayed. Demographic data at onset of aHUS and follow up were compared for the mutation positive and negative groups. RESULTS: Of 111 patients with aHUS (68 female, 43 male, mean age 33 years) 14% had FH1 germline mutations, including two of eight patients with familial aHUS. For each of these eight patients, both parents were tested, and we were able to trace the mutation for five cases. In the other three cases (one with the mutation 3749 C/T, one with 3200 T/C, and one with 3566+1 G/A), we could not detect the mutation in either parent, although paternity was proven by genetic fingerprinting, suggesting that these subjects have new mutations. C3 was decreased in five mutation carriers but also in two non-carriers, and factor H was decreased in none of the carriers, but elevated in six carriers and 15 non-carriers. Clinical parameters including associated medications and diseases, and outcome of aHUS and of post-aHUS kidney transplantation were similar in the mutation positive and negative groups. CONCLUSION: FH1 germline mutations occur with considerable frequency in patients with aHUS. Hypocomplementaemia is not regularly associated with a germline mutation, and factor H serum levels can even be elevated. Screening for FH1 mutations contributes to the classification of aHUS.

Adult↗
PubMed2002

Organ tolerance following cadaveric liver transplantation for chronic graft-versus-host disease after allogeneic bone marrow transplantation.

A paediatric patient was treated with orthotopic liver transplantation after he developed cirrhosis of the liver due to chronic graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation. His pre-existing chronic GVHD of the skin disappeared and immunosuppressive therapy could be gradually tapered and finally withdrawn 71 months after liver transplantation. Two and a half years after discontinuation of all immunosuppressive therapy, the patient is in excellent condition with neither signs of chronic GVHD nor rejection of the liver graft.

Anemia, Sideroblastic↗
PubMed2002

Experience with ATG short course high dose induction therapy in a series of 112 enteric drained pancreatic transplants.

BACKGROUND: New immunosuppressive protocols and advanced surgical technique resulted in a major improvement in the outcome of pancreatic transplantation. PATIENTS AND METHODS: 112 enteric drained whole pancreas transplants (PTx) performed at the Innsbruck University Hospital between 3.1997 and 10.2001 were retrospectively analysed. Prophylactic immunosuppression consisted of FK506, MMF and steroids. A short course of high dose ATG induction was given additionally. Perioperative antimicrobial prophylaxis consisted of Amoxicillin/Clavulanic (32 PTx), Pipercillin/Tazobactam (68 PTx), quinolones (10 PTx) or macrolide (2 PTx). 64 patients additionally received fluconazole. RESULTS: Actuarial patient, pancreas and kidney graft survival at one year were 96.4%, 86.7% and 95.3%, surgical complication rate was 28%, rejection rate 40%. Eight grafts were lost due to intraabdominal infection, seven due to rejection. Median perioperative observation days (OD) were 29 (range 14-125), patients were on antibiotics for 68% of OD, and developed fever on 33% of OD. Incidence of CMV infection was 42% (but only five patients developed CMV disease), HSV 24%, intraabdominal infection 22%, UTI 11%, wound infection 9% and pneumonia: 5%. CONCLUSION: ATG short course induction is well tolerated after enteric drained PTx. Infection represents a frequent and at least for IA sepsis serious complication after PTx with enteric drainage.

Adult↗
PubMed2001

Increased tacrolimus levels during diarrhea.

While it is well known that diarrhea results in decreased trough levels of cyclosporin A, experience with levels of tacrolimus (FK506) and diarrhea is limited. We have therefore measured the tacrolimus trough levels of four male and two female recipients of solid organs before, during, and after gastroenteritis. The average age of these six patients was 31 (1-60) years. Four patients had received a kidney transplant, one patient had undergone simultaneous kidney-pancreas transplantation, and another patient had received a liver transplant. Rotavirus was identified in the feces specimen of a 1-year-old child that had undergone liver transplantation. All patients showed an elevated tacrolimus trough level (peak 20-60 ng/ml) after onset of gastroenteritis. Under symptomatic therapy and adequate adjustment of tacrolimus dose, the gastroenteritis stopped and tacrolimus levels returned to the therapeutic range. We recommend that FK506 levels be carefully monitored during diarrhea in order to prevent intoxication.

Adolescent↗
PubMed2001

Rotavirus infection as cause of tacrolimus elevation in solid-organ-transplanted children.

Rotavirus (RV) is the most common cause of diarrheal illness in children. We report three solid-organ-transplanted patients in whom RV infection caused increased trough levels of the immunosuppressive macrolide tacrolimus (TAC) by mechanisms that are still under investigation. The virus was detected for longer in the feces of these patients than in infants not receiving immunosuppressive therapy. In association with short-term monitoring of blood trough levels of TAC, the dosage should be reduced early if symptoms of an acute gastroenteritis are present.

Adult↗
PubMed2001

Renal allograft rupture is associated with rejection or acute tubular necrosis, but not with renal vein thrombosis.

BACKGROUND: Whereas rejection was reported to be the most common cause of renal allograft rupture (RAR) in the pre-cyclosporin era, renal vein thrombosis (RVT) is purported to be the main cause of RAR in patients taking cyclosporin. The extremely low incidence of RVT in our series (0.11%) prompted us to analyse our collective with regard to RAR. METHOD: Between 1974 and 1999, 1811 renal transplants were performed. Patients with RAR, defined as a tear of the renal capsule and parenchyma, were identified and possible underlying factors studied. RESULTS: RAR was diagnosed in nine male and five female recipients (0.8%) with a median age of 36 years. Immunosuppression consisted of azathioprine and prednisolone in seven patients and of cyclosporin-based therapy in the seven others. At exploration five grafts were removed immediately: three because of irreversible rejection, one because of deep wound infection, and one with a twisted renal vein. Six of the nine salvaged kidneys have been functioning after a mean observation time of 45 months. In the pre-cyclosporin era RAR was associated with acute rejection in five out of seven cases as compared with only three of the seven on cyclosporin treatment. Core biopsies might have been the cause in three cases. CONCLUSION: RAR is a rare complication after renal transplantation. Acute rejection still represents the most frequent cause of RAR in the cyclosporin era.

Adult↗
PubMed2001

Massive progression of diffuse hepatic lymphangiomatosis after liver resection and rapid deterioration after liver transplantation.

Hepatic involvement is an exceptional presentation of lymphangiomatosis. In this case report we describe a patient who underwent liver transplantation secondary to progressive hepatic involvement, which occurred 2 yr after partial hepatectomy. Within 1 yr after liver transplantation the disease condition deteriorated, with rapid progression of pre-existing skeletal lesions and development of pulmonary disease. We conclude that liver transplantation may be a treatment option for hepatic lymphangiomatosis. In the presence of pre-existing extrahepatic lesions, however, liver transplantation seems to be contraindicated.

Adult↗
PubMed2000

Successful stem cell transplantation following orthotopic liver transplantation from the same haploidentical family donor in a girl with hemophagocytic lymphohistiocytosis.

The case of a 4-month-old girl with familial hemophagocytic lymphohistiocytosis is described. The patient underwent stem cell transplantation from her haploidentical mother 2 months after receiving a living-related liver transplant from the same donor for acute hepatic failure. Conditioning regimen consisted of 16 mg/kg busulfan, 200 mg/kg cyclophosphamide, 10 mg/kg thiothepa, and antithymocyte globulin. Myeloid engraftment occurred on day +10, but CD3(+) cells of recipient origin remained. To convert the T-cell chimerism, the patient received donor lymphocyte infusion on day +43, and subsequently the allelic pattern changed to complete donor genotype on day +57. Four months after stem cell transplantation the patient is disease free, with complete donor chimerism in bone marrow and stable hepatic graft function without any immunosuppressive therapy. (Blood. 2000;96:3997-3999)

Behavior Therapy↗