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Biomedical subjects

F Dahm

Publications and source records attributed to F Dahm.

7 recordsLinked to original sources
PubMed2006

Distribution and dynamic changes of sphingolipids in blood in response to platelet activation.

BACKGROUND: Sphingolipids are signaling molecules in a range of biological processes. While sphingosine-1-phosphate (S1P) is thought to be abundantly stored in platelets and released upon stimulation, knowledge about the distribution and function of other sphingolipids in blood is lacking. OBJECTIVES: To analyze the sphingolipid content of blood components with special emphasis on dynamic changes in platelets. METHODS: Blood components from mice and humans were prepared by gradient centrifugation and analyzed by liquid chromatography-mass spectrometry. Additionally, murine platelets were activated in vitro and in vivo. RESULTS: Isolated non-activated platelets of mice were devoid of S1P, but instead contained dihydrosphingosine-1-phosphate (dhS1P), along with a high concentration of ceramide. Activation of platelets in vitro led to a loss of dhS1P and an increase in sphingosine, accompanied by a reduction of ceramide content. Platelet activation in vivo led to an immediate and continuous rise of dhS1P in plasma, while S1P remained stable. The sphingolipid distribution of human blood was markedly different from mice. Human platelets contained dhS1P in addition to S1P. CONCLUSIONS: Mouse platelets contain dhS1P instead of S1P. Platelet activation causes loss of dhS1P and breakdown of ceramide, implying ceramidase activation. Release of dhS1P from activated platelets might be a novel signaling pathway. Finally, the sphingolipid composition of mouse and human blood shows large differences, which must be considered when studying sphingolipid biology.

Animals↗
PubMed2006

Cholestasis protects the liver from ischaemic injury and post-ischaemic inflammation in the mouse.

BACKGROUND AND HYPOTHESIS: Cholestasis is associated with high morbidity and mortality in patients undergoing major liver surgery, but the mechanisms responsible remain elusive. Increased ischaemic liver injury and inflammation may contribute to the poor outcome. METHODS: Common bile duct ligation (biliary obstruction with hyperbilirubinaemia) or selective ligation of the left hepatic duct (biliary obstruction without hyperbilirubinaemia) was performed in C57BL/6 mice before 1 h of hepatic ischaemia and 1, 4 or 24 h of reperfusion. Infection with the intracellular hepatic pathogen Listeria monocytogenes for 12 and 48 h was used to study ischaemia-independent hepatic inflammation. RESULTS: Cholestatic mice showed considerable protection from ischaemic liver injury as determined by transaminase release, histological liver injury and neutrophil infiltration. In cholestatic mice, reduced injury correlated with a failure to activate nuclear factor kappaB (NFkappaB) and tumour necrosis factor alpha (TNFalpha) mRNA synthesis, two key mediators of post-ischaemic liver inflammation. After selective bile duct ligation, both the ligated and the non-ligated lobes showed blocked activation of NFkappaB as well as reduced induction of TNFalpha mRNA synthesis and neutrophil infiltration. By contrast, infection with L monocytogenes showed comparable activation of NFkappaB and hepatic recruitment of neutrophils 12 h after infection. CONCLUSION: Cholestasis does not increase but rather dramatically protects the liver from ischaemic injury and inflammation. This effect is mediated by a systemic factor, but not bilirubin, and is associated with a preserved capacity to trigger an inflammatory response to other stimuli such as a bacterial pathogen.

Animals↗
PubMed2006

Blocking the path to death: anti-apoptotic molecules in ischemia/reperfusion injury of the liver.

This review highlights recent advances in our understanding of intracellular mechanisms underlying programmed cell death in hepatic ischemia/reperfusion injury. A range of molecules have been tested with the intention to block the pathways of programmed cell death at different levels and to thereby enhance viability of the liver in surgical procedures including liver transplantation. Cellular death receptors, the mitochondrial pathway of apoptosis, p53, mitogen-activated protein kinases (MAPKs) and intracellular proteases all present potential targets for pharmaceutical agents to prevent ischemia induced cell death in the liver. Although evidence has been provided for effective inhibition of injury and improvement of survival by such agents, an optimal treatment strategy remains to be developed.

Animals↗
PubMed2003

[Vasectomy today: a review of 1,275 vasectomies in 10 years].

We report on a large series of 1,275 patients who underwent outpatient vasectomy performed by a single urological surgeon within a 10-year period. In addition, the results of a prospective questionnaire-based study on 217 patients regarding their opinions and motivation, and the financial aspects of the vasectomy are discussed. The mean age was 37.0+/-5.9 years. A total of 98.4% of the patients had an uneventful postoperative course. The average duration of sick leave was 2.2+/-0.21 days. During the study period, the length of sick leave dropped significantly from 2.63 (1990/91) to 1.1 days (1998/99; P=0.001). Efficacy was documented with azoospermia rates of 96.6% and 98.5% in patients who presented for two and three sperm examinations, respectively. A vast majority of patients (94.6%) felt that the procedure should be covered by their health insurance, although 88.1% stated they would also pay by themselves. A minority of patients (0.7%: 9/1,275) subsequently considered vasectomy reversal. The wish to reverse the vasectomy was significantly associated with a younger patient age. In conclusion, outpatient vasectomy provides a safe and reliable form of contraception at low cost. Overall satisfaction in appropriately counselled patients is very high. Based on these findings, further attempts to propagate vasectomy as a timely form of contraception are medically and socioeconomically recommended.

Adolescent↗
PubMed2003

Kidney transplantation--new developments.

The standard of care for patients with end-stage renal disease is kidney transplantation, which not only confers a survival benefit compared to hemodialysis, but is also cost-effective. The indications, contraindications as well as the preoperative assessment of recipients are discussed. The recurrence rate of the underlying renal disease has to be taken into account, especially in living donation. Growing organ shortage has lead transplant surgeons to accept older, less healthy, and even non-heart-beating donors, with generally good results. Living-donation is safe for the donor, outcome is excellent and plays an increasing role today. It has surpassed the number of cadaveric kidney transplantations in some countries. Many centres now apply laparoscopic donor nephrectomy with low morbidity. Matching for ABO blood group and HLA is routinely performed, as well as pre-transplant crossmatching. The surgical procedure has been standardized and the complication rate is low. Immunosuppressive protocols have evolved over time, and while the optimal regimen has not been defined, the availability of numerous agents allows the regimen to be individualized. New agents are being introduced into clinical practice. With increasing long-term graft survival and thus life-long immunosuppression, cardiovascular disease, de-novo malignancies and infectious complications are major causes of morbidity and mortality of transplant recipients. Effective prophylactic measures are often available, and surveillance protocols are warranted in these patients. Overall, the outcome of renal transplantation is excellent and has improved over time. Future prospects include induction of allograft tolerance, tissue engineering and xenotransplantation.

Forecasting↗
PubMed2001

Current indication of a modified Sugiura procedure in the management of variceal bleeding.

BACKGROUND: The role of gastroesophageal devascularization (Sugiura-rype procedures) for the treatment of variceal bleeding remains controversial. Although Japanese series reported favorable longterm results, the technique has nor been widely accepted in the Western Hemisphere because of a high postoperative morbidity and mortality. The reasons for the different outcomes are unclear. In a multidisciplinary team approach we developed a therapeutic algorithm for patients with recurrent variceal bleeding. STUDY DESIGN: The Sugiura procedure was offered only to patients with well-preserved liver function (Child A or Child B cirrhosis without chronic ascites) who were not candidates for distal splenorenal shunt, transhepatic porto-systemic shunt, or liver transplantation. RESULTS: Fifteen patients with recurrent variceal bleeding underwent a modified Sugiura procedure between September 1994 and September 1997. All but one patient (operative mortality 7%) are alive after a median followup of 4 years. Recurrent variceal bleeding developed in one patient; esophageal strictures, which were successfully treated by endoscopic dilatation, developed in three patients; and one patient experienced mild encephalopathy. Major complications were noted only in patients with impaired liver function (Child B cirrhosis) or when the modified Sugiura was performed in an emergency setting. The presence of cirrhosis or the cause of portal hypertension had no significant impact on the complication rate. CONCLUSIONS: This series was performed during the last decade when all modern therapeutic options for variceal bleeding were available. Our results indicate that the modified Sugiura procedure is an effective rescue therapy in patients who are not candidates for selective shunts, transhepatic porto-systemic shunt, or transplantation. Emergency settings and decreased liver function are associated with an increased morbidity.

Adolescent↗