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Thomas Kraus

Publications and source records attributed to Thomas Kraus.

30 records · Page 2Linked to original sources

Heidelberg's first experiences in establishing a living-donation liver transplantation programme.

BACKGROUND: Since indications for liver transplantation (LTx) have increased and the shortage of brain dead transplant organs continues, an increase in deaths related to extended waiting periods can be documented. Living-related LTx (LRLTx) is a good alternative that can help compensate the shortness of organs for transplantation and can reduce waiting periods and deaths related to a long waiting list. We started a LRLTx programme at the transplantation centre, Department of Surgery at the University of Heidelberg to increase our transplantation activities. In this article we present our primary experiences and protocol. METHODS: From September 2002 to June 2003, three LRLTx were performed. Indications in recipients were hepatocellular carcinoma in two cases and liver cirrhoses due to hepatitis B in one patient. Two patients received the right liver (segments V-VIII) of their donors. One patient received the complete liver collected as a Domino LTx. All liver transplants were performed without the use of a venous bypass. RESULTS: The peri- and post-operative courses of our donors were without complications, except for an infected intraabdominal bilioma, which was drained interventionally. The donors were fully able to work after the operation. The coordinative and logistical work should not be underestimated. CONCLUSIONS: This therapy should only be offered and performed in centres with excellent expert knowledge in liver and transplantation surgery.

Adult↗

New aspects on reperfusion injury to liver--impact of organ harvest.

The aetiology of primary graft non-function and dysfunction is unknown but most likely involves Kupffer cell-dependent reperfusion injury; however, reasons for transplant failure are complex and involve organ retrieval, preservation and transplantation. Important factors include the donor's condition, cold and warm ischaemic times, operative complications in the recipient, the immune status of the recipient and surgical experience. The donor operation and surgical technique also have an effect on outcome after transplantation. This is important, since surgical organ manipulation of the liver during harvest cannot be prevented completely with standard procedures. This is especially true during organ harvest for living-donor liver transplantation and split-liver transplantation in general. Most recently, an experimental setting has conclusively demonstrated that gentle in situ organ manipulation by touching, retracting and moving liver lobes gently during harvest dramatically reduces survival after transplantation via Kupffer cell-dependent mechanisms. These mechanisms involve disturbances of hepatic microcirculation, a hypermetabolic state of the liver, hypoxia and almost complete denudation of endothelial lining cells. Glycine, a non-essential, non-toxic amino acid, which prevents activation of Kupffer cells, prevented all effects of harvest-related injury to the liver when given before transplantation. Based on these data, intravenous glycine has been administered to patients before reperfusion of their liver transplant. Both serum transaminases and the rate of primary non-function have been dramatically reduced, compared with historic controls. These preliminary clinical results with glycine before reperfusion are promising for further improvement of the overall outcome after liver transplantation.

Animals↗

Results of renal transplantation using kidneys harvested from living donors at the University of Heidelberg.

BACKGROUND: Although a majority of patients undergoing renal transplantation currently receive a cadaver kidney, living donors continue to be an important source of transplanted kidneys. Recipients of living donor kidneys demonstrate improved graft survival. To expand the pool of suitable organ donors an organ procurement programme of living donors has been developed over the past 35 years. We have reviewed our living donor nephrectomy experience over this period to analyse the donor and recipient peri- and postoperative morbidity and mortality rate. METHODS: We reviewed the operative complications and the long-term outcome of 219 living donated kidney transplantations before and after introduction of cyclosporine A. Donor and graft complications as well as recipient complications and survival rate were investigated. Additionally, the findings of 16 laparoscopically operated living donors were compared to a group of 20 patients who underwent a conventional surgery. RESULTS: The overall recipient 3 and 5 year survival rates in the cyclosporine A era were 95 and 94%, respectively. Prior to the introduction of cyclosporine A, the overall recipient survival rates at 3 and 5 years were 84 and 84%, respectively. The overall graft survival rates were 92 and 85% for the cyclosporine A era compared to 68 and 60% before introduction of cyclosporine A, at 3 and 5 years, respectively. The patient and graft survival rate in the cyclosporine group were significantly higher than in the pre-cyclosporine group (log-rank: P = 0.0107 and P = 0.0003, respectively). Donor complications included pain at the incision site (35%), mild hypertension (27%), proteinuria (19%), urinary tract infections (11%), pneumothorax (5%), blood transfusion (3.5%) and wound infection (3%), with no mortalities. Our results showed a longer duration of operation, and longer warm ischaemia and cold ischaemia times in laparoscopically operated living donors than those that were seen in the conventional approach. There was no statistically significant difference in complications between both techniques. However, the hospitalization days and usage of analgesic medication in laparoscopy donors were lower than in the conventional approach. CONCLUSIONS: Similar to previous studies the results of the present analysis confirm an increase in patient and graft survival rates in the cyclosporine era compared to before its usage. Living donor nephrectomy, done through a conventional or laparoscopic approach, remains a valuable source of kidneys for transplantation with low complication rates.

Adolescent↗

Long-term results of paediatric kidney transplantation at the University of Heidelberg: a 35 year single-centre experience.

BACKGROUND: Kidney transplantation remains the most effective treatment for children with end-stage renal disease. We analysed data from the University of Heidelberg transplant programme to present our results on paediatric kidney transplantations over the past 35 years. METHODS: From 1967 to 2003, 354 paediatric kidney transplantations were performed at the University of Heidelberg. Data were obtained from the paediatric kidney transplantation records consisting of 291 (82%) cadaveric and 63 (18%) living donated transplants. Demographic data, family relationship of the living donors, surgical technique, immunosuppressive drugs, graft and patient survival rates were assessed. RESULTS: The mean age of cadaveric and living donors was 32.0+/-17.1 and 37.6+/-7.5 years, respectively. The family relationship of the living donors included the mother in 65% of cases, the father in 31%, and other relatives in 4%. In the last 4 years, the respective mean cold ischaemia time was 1.6+/-0.5 h for living donated and 13.5+/-4.1 h for cadaveric donors. The mean age of children who received kidneys from cadaveric and living donors was 11.3+/-4.5 and 10.4+/-4.5 years, respectively, with a male to female ratio of 57 to 43%. Overall patient survival rates were 95% after 1 year and 89% after 5 years. The patient 5 and 10 year survival rates for living donor renal transplantations were 95 and 95%, respectively. Graft survival rates improved since 1990 compared with the period prior to 1990: 82.5 vs 56.7% graft survival at 1 year and 82.5 vs 50% after 5 years (P = 0.03). Comparing the operating technique in a subgroup of our patients that received the same immunosuppressive regimen, anastomoses with the aorta and vena cava (51%, n = 31) were associated with a graft survival of 86.6 and 83.3% after 1 and 5 years, whereas anastomoses with iliac vessels (49%, n = 30) were associated with a graft survival of 55.8 and 51.6% after 1 and 5 years, respectively (P = 0.01). CONCLUSIONS: There has been a gradual improvement in our paediatric kidney transplantation results over time. Living donor paediatric kidney transplants have higher patient and better graft survival rates than cadaveric donor kidney transplants. Using the aorta and inferior vena cava for graft anastomosis, utilizing newer immunosuppressive drugs and implementing living kidney donation have positively affected the results of our paediatric kidney transplantations.

Adolescent↗

Chronic cholangitis caused by Bordetella hinzii in a liver transplant recipient.

Bordetella hinzii was isolated in four biliary specimens collected over 6 months from a liver transplant recipient with cholangitis. The isolates were resistant to most beta-lactam antibiotics and fluoroquinolones. Molecular typing was performed by pulsed-field gel electrophoresis. These data add cholangitis to the spectrum of disease manifestations caused by B. hinzii.

Adult↗

Lung function among workers in the soft tissue paper-producing industry.

OBJECTIVES: To describe lung function in correlation with information on exposure to dust and fibers in soft tissue paper-producing factories in Germany. METHODS: Ambient monitoring was performed for inhalable, respirable dust and fibers in nine soft tissue paper-producing factories. In a study group of 1,047 workers (189 control subjects, 240 workers with moderate exposure, and 618 workers with high exposure), spirometry (FVC, FEV(1)) was performed. Information on occupational history, duration of exposure, workshop within the company, former occupational exposures, and smoking habits were collected. By employing multiple linear regression modeling, the potentially confounding effects of age, sex, body mass index, smoking habits, and factory were incorporated into the analysis of FVC, FEV(1), and FEV(1) in percent of FVC (FEV(1)%FVC). By employing a logistic regression model, odds ratios were calculated for FVC < 80% predicted in different exposure subgroups. RESULTS: The mean concentrations for inhalable, respirable, and fibrous dusts were 12.4 mg/m(3), 0.28 mg/m(3), and 420,000 fibers per cubic meter. With relation to cumulative dust and fiber exposure, a decrease of FVC from 105.4% predicted to 96.9% predicted (dust) and 97.1% predicted (fibers) in the subgroup with highest cumulative exposure was observed. For FEV(1), a decrease from 107.3% predicted to 103.0% predicted (dust) and 102.8% predicted (fibers) was found. The parameter estimates show dose-response relationships that are more pronounced for FVC compared to FEV(1). FEV(1)%FVC did not change significantly with increasing cumulative exposure, indicating a restrictive pattern of the findings. CONCLUSIONS: Due to high ambient dust concentrations and the observed adverse effects on lung function, a reduction of dust exposure and secondary preventive measures is advised.

Adult↗

Assessment of renal graft function by perioperative monitoring of cortical microcirculation in kidney transplantation.

BACKGROUND: We evaluated the significance of perioperative cortical microperfusion for graft function and long-term prognosis after renal allotransplantation. Thermodiffusion technology was clinically applied for the first time, after previous validation for perfusion monitoring of the renal cortex in pigs. METHODS: A thermodiffusion probe was inserted into the renal cortex in 30 transplant recipients after graft reperfusion. Real-time measurements were recorded until the end of the operation. In 14 patients perfusion was measured daily until postoperative day 7. Microcirculation was correlated to serum creatinine level, scintigraphic findings, and long-term outcome. RESULTS: In primary graft function, intraoperative perfusion was 85+/-7 mL/100 g per min compared with significantly lower values in cases with subsequent graft dysfunction. The best discrimination was defined for a level of 70 mL/100 g per min with a positive predictive value of 88% for detection of good graft function and 86% for nonfunction. Intraoperative perfusion was significantly different in patients with normal grafts, delayed function, and graft loss. Postoperatively, lower perfusion was found in acute tubular necrosis; a significant correlation could be noted between microcirculation and perfusion index measured by nuclear scanning (r=0.78, P<0.01). Living-related grafts were characterized by higher intraoperative perfusion and superior graft quality. CONCLUSION: Thermodiffusion could be clinically applicable for the perioperative monitoring of renal graft perfusion. Intraoperative reduction of cortical microcirculation has a high predictive value with respect to detection of delayed renal function. Postoperatively, impaired renal microperfusion is associated with acute tubular necrosis. Living-related donor grafts show less microcirculatory alteration than cadaveric kidneys.

Adolescent↗

Effects of hemodynamic instability on brain death-induced prepreservation liver damage.

BACKGROUND: Brain death (BD) is an important multifactorial variable contributing to donor-specific liver damage. Our study aimed at assessing the specific effects of hemodynamic instability on systemic and hepatic parameters of perfusion, bowel ischemia, and oxidative stress in a porcine model of BD. METHODS: BD was induced in 16 pigs (German Landrace, 18-28 kg) in two groups (hypotension-BD [HYPO-BD], n=8; normotension-BD [NORM-BD], n=8), which were compared with control animals/living donors (n=6) for a period of 2 hr. We analyzed systemic hemodynamic parameters, bowel ischemia (intramucosal pH in the stomach and colon, plasma endotoxin levels, and endotoxin-neutralizing capacity [ENC]), and oxidative stress (total glutathione levels in erythrocytes) and compared the findings with hepatic parameters of perfusion (hepatic arterial flow, portal venous flow, and microperfusion) and liver oxidative stress (reduced glutathione and oxidized glutathione levels in the liver). RESULTS: Independent of the hemodynamic stability, liver macrocirculation and microcirculation decreased (HYPO-BD, 79+/-6 to 69+/-10 mL/100 g/min; NORM-BD, 81+/-10 to 73+/-7 mL/100 g/min; P<0.05). Hepatocellular damage (aspartate aminotransferase: NORM-BD, 49+/-20 units/L; HYPO-BD, 170+/-140 units/L; P<0.01) and hepatic oxidative stress (reduced glutathione in the liver/oxidized glutathione in the liver: NORM-BD, 29.4+/-2.3 to 13.0+/-1.3; HYPO-BD, 29.4+/-2.3 to 9.05+/-0.81; P<0.001) increased in both BD groups. With dependence on systemic hemodynamic parameters, bowel ischemia increased (intramucosal pH in the colon, 7.22+/-0.01, P<0.01; ENC, 75+/-14 endotoxin-neutralizing units/mL, P<0.01; endotoxin levels, 7+/-2 to 43+/-10 pg/mL, P<0.01) in the HYPO-BD group but not in the NORM-BD group or the living donor group. Furthermore, systemic oxidative stress was increased in the HYPO-BD group only (total glutathione levels in erythrocytes, 2.65+/-0.25 to 0.15+/-0.25 mM; P<0.01). CONCLUSIONS: During BD, liver-specific parameters (portal venous flow, microperfusion, aspartate aminotransferase activity, ENC, and hepatic oxidative stress) were compromised, independent of the hemodynamic status. Therefore, the systemic hemodynamic status does not reflect the functional status of the liver during BD.

Animals↗

Induction of apoptosis by HIV-1-infected monocytic cells.

We have previously described a soluble 6000-Da peptide produced by an HIV-1-infected human macrophage cell line, clone 43(HIV), which induces apoptosis in T and B cells. We have identified this factor as the novel cDNA clone FL14676485 that encodes for the human hypothetical protein, FLJ21908. The FL14676485 cDNA clone was isolated from a 43(HIV) lambda ZAP Escherichia coli expression library and screened with a panel of rabbit and mouse anti-apoptotic Abs. We transfected the FL14676485 clone into Bosc cells and non-HIV-1-infected 43 cells. Western blot analysis of lysates from the FL14676485-transfected 43 cells and Bosc cells using anti-proapoptotic factor Abs revealed a protein with a molecular mass of 66 kDa corresponding to the size of the full-length gene product of the FL14676485 clone, while Western blot of the supernatant demonstrated a doublet of 46-kDa and 6000-Da peptide that corresponds to our previously described proapoptotic factor. Primary HIV-1(BaL)-infected monocytes also produce the FLJ21908 protein. Supernatants from these transfected cells induced apoptosis in PBMC, CD4(+), and CD8(+) T and B cells similar to the activity of our previously described proapoptotic factor. PCR analysis of 43 cells and 43(HIV) cells revealed a base pair fragment of 420 bp corresponding to the FL14676485 gene product in 43(HIV) cells, but not in 43 cells. The FLJ21908 protein induces apoptosis through activation of caspase-9 and caspase-3. We have further demonstrated that the FLJ21908 protein has apoptotic activity in the SH-SY5Y neuronal cell line and can be detected in brain and lymph tissue from HIV-1-infected patients who have AIDS dementia. The FLJ21908 protein may contribute to the apoptosis and dementia observed in AIDS patients.

AIDS Dementia Complex↗

Diurnal variations of interleukin-6 plasma levels are confounded by blood drawing procedures.

Recent findings suggest that inflammatory cytokines are involved in sleep regulation. In part, this idea is based on studies showing that systemic levels of interleukin-6 (IL-6) are affected by sleep and sleep deprivation. However, intravenous (IV) catheters used for repetitive blood sampling were reported to increase local IL-6 production, which might confound sleep-dependent or circadian changes in the plasma concentrations of this cytokine. To further examine the effects of blood drawing procedures on IL-6 plasma levels, 12 healthy young male subjects participated in a 24-h cross-over study protocol involving sleep and sleep deprivation. Blood was collected half-hourly through an IV line and one additional sample was taken by a simple needle stick from the contralateral arm in parallel to the last sample from the catheter. Difficulties in blood sampling, the plasma levels of IL-6, cortisol and subjective sleepiness were quantified. In samples from the IV line there was a linear increase in IL-6 levels in both conditions, whereas the amount of IL-6 detected in the needle stick sample at the end did not differ from baseline. IL-6 levels were significantly higher in samples rated as difficult and those difficulties were more frequent during sleep compared to nocturnal wakefulness. IL-6 levels did not correlate to variations in sleepiness or cortisol levels. We conclude that variations in IL-6 plasma levels measured in samples from an IV catheter are caused, at least in part, by changes in local cytokine production rather than by physiological changes in circulating IL-6 levels.

Adolescent↗

Epidemiology, implications and mechanisms underlying drug-induced weight gain in psychiatric patients.

Body weight gain frequently occurs during drug treatment of psychiatric disorders and is often accompanied by increased appetite or food craving. While occurrence and time course of this side effect are difficult to predict, it ultimately results in obesity and the morbidity associated therewith in a substantial part of patients, often causing them to discontinue treatment even if it is effective. This paper reviews the available epidemiological data on the frequency and extent of weight gain associated with antidepressant, mood-stabilizing, and antipsychotic treatment. Possible underlying pathomechanisms are discussed with special attention to central nervous control of appetite including the role of leptin and the tumor necrosis factor system. Metabolic alterations induced by drug treatment such as type 2 diabetes mellitus and the metabolic syndrome are also considered. Weight gain appears to be most prominent in patients treated with some of the second generation antipsychotic drugs and with some mood stabilizers. Marked weight gain also frequently occurs during treatment with most tricyclic antidepressants, while conventional antipsychotics typically induce only slight to moderate weight gain. Serotonin reuptake inhibitors may induce weight loss during the first few weeks, but some of them induce weight gain during long-term treatment. Several antidepressant and antipsychotic drugs are identified which reliably do not cause weight gain or even reduce weight. Based on these insights, countermeasures to manage drug-induced weight gain are suggested.

Behavior Therapy↗