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M Schäfer

Publications and source records attributed to M Schäfer.

At least 19 recordsLinked to original sources
PubMed2003

Incidence and management of Mirizzi syndrome during laparoscopic cholecystectomy.

BACKGROUND: Benign extrinsic obstruction of the hepatic duct, known as "Mirizzi syndrome" (MS), is an uncommon complication of longstanding cholelithiasis. Since laparoscopic cholecystectomy (LC) replaced the open approach, Mirizzi syndrome has regained the interest of biliary surgeons. METHODS: The Swiss Association for Laparoscopic and Thoracoscopic Surgery (SALTS) prospectively collected the data on 13,023 patients undergoing LC between 1995 and 1999. This database was investigated with special regard to patients with Mirizzi syndrome. RESULTS: There were 39 patients (14 men and 25 women; mean age, 61 years) with MS (incidence, 0.3%). Thirty-four patients had type 1 MS and five had type 2. A gallbladder carcinoma was found in four patients (incidence, 11%). In the type 1 group, 23 patients underwent cholecystectomy only, 10 patients had a bile duct exploration and T-tube insertion, and one patient had a Roux-en-Y reconstruction. In three patients with type 2, a hepaticojejunostomy was performed; two others underwent simple closure and drainage (via T-tube) of the biliary fistula. The conversion rate was 74% (24 of 34 patients) in the type 1 group and 100% (five of five patients) for type 2. The overall complication rate was 18%. There were no deaths. CONCLUSIONS: Although MS is rarely encountered during LC, it must be recognized intraoperatively. Conversion to an open approach is often needed, and prior to any surgical intervention, gallbladder cancer must be excluded.

Aged↗
PubMed2003

Role of redox signaling in the autonomous proliferative response of endothelial cells to hypoxia.

Endothelial cells exhibit an autonomous proliferative response to hypoxia, independent of paracrine effectors. In cultured endothelial cells of porcine aorta, we analyzed the signaling of this response, with a focus on the roles of redox signaling and the MEK/ERK pathway. Transient hypoxia (1 hour) stimulated proliferation by 61+/-4% (n=16; P<0.05 versus control), quantified after 24 hours normoxic postincubation. Hypoxia induced an activation of ERK2 and of NAD(P)H oxidase and a burst of reactive oxygen species (ROS), determined by DCF fluorescence. To inhibit the MEK/ERK pathway, we used PD 98059 (PD, 20 micromol/L); to downregulate NAD(P)H oxidase, we applied p22phox antisense oligonucleotides; and to inhibit mitochondrial ROS generation, we used the ubiquinone derivate mitoQ (MQ, 10 micromol/L). All three inhibitions suppressed the proliferative response: PD inhibited NAD(P)H oxidase activation; p22phox antisense transfection did not inhibit ERK2 activation, but suppressed ROS production; and MQ inhibited ERK2 activation and ROS production. The autonomous proliferative response depends on the MEK/ERK pathway and redox signaling steps upstream and downstream of ERK. Located upstream is ROS generation by mitochondria, downstream is NAD(P)H oxidase.

Animals↗
PubMed2003

Inhibition of contractile activation reduces reoxygenation-induced endothelial gap formation.

OBJECTIVE: Barrier function of coronary endothelium becomes disturbed by ischemia-reperfusion. We investigated the mechanism of reperfusion-induced endothelial gap formation in monolayers of cultured endothelial cells (CEC) of the rat, exposed to simulated ischemia (40 min anoxia, pH(o) 6.4) and reperfusion (30 min reoxygenation, pH(o) 7.4). METHODS: Cytosolic Ca(2+) (fura-2) and intercellular gap formation (planimetrical analysis) were determined. Reoxygenation conditions were varied: (a) continuing perfusion at pH(o) 6.4, (b) with or without glucose (2.5 mM), (c) in presence of NaCN (2 mM), (d) with Ca(2+) (10 mM) or BAPTA/AM (25 microM), (e) in the presence of myosin light chain kinase inhibitors ML-7 (5 microM) or wortmannin (1 microM). RESULTS: During anoxia, CEC developed cytosolic Ca(2+) overload which was not reversed during 30 min reoxygenation. Intercellular gap formation started during anoxia, but was increased during reoxygenation. Reoxygenation-related gap formation was largest in presence of glucose, lower when glucose was withdrawn or NaCN was added. Presence of ML-7 or wortmannin also reduced gap formation during reoxygenation. CONCLUSIONS: Reoxygenation induces gap formation. This is dependent on (i) Ca(2+) overload during reoxygenation, (ii) energy production and (iii) activation of myosin light chain kinase. Together these results indicate that activation of the endothelial contractile machinery is the underlying cause.

Androstadienes↗
PubMed2003

Signaling of hypoxia-induced autonomous proliferation of endothelial cells.

Endothelial cells exhibit an autonomous proliferative response to hypoxia, independent of paracrine effectors. In cultured endothelial cells of porcine aorta, we analyzed the signaling and compared hypoxia with mitochondrial inhibition by rotenone. Particularly, roles of the mitogen-activated protein kinase (MAPK) kinase (MEK)/MAPK pathway and cytosolic Ca2+ were studied. Hypoxia resulted in increased proliferation by 65+/-2%. Hypoxia induced transient activation of p42 MAPK (phosphorylation rose from 11+/-5 to 51+/-7%), followed by translocation of p42 MAPK into the nucleus. The proliferative response was diminished after inhibition of the MEK/MAPK pathway by PD 98059 (20 microM) or UO 126 (10 microM) but not sensitive to 8-phenyl-theophillin (10 microM), an adenosine receptor blocker, nor to a neutralizing antibody for vascular endothelial growth factor (VEGF). Inhibition of intracellular Ca2+ release, capacitive Ca2+ influx, or removal of extracellular Ca2+ prevented hypoxic Ca2+ overload and the proliferative response. Suppression of cytosolic Ca2+ rise did not interfere with activation of p42 MAPK but abolished its nuclear translocation. Effects of hypoxia were mimicked by rotenone (10 microM. Transient hypoxic inhibition of mitochondria induces a proliferative endothelial response mediated through Ca2+-independent activation and Ca2+-dependent nuclear translocation of p42 MAPK. This proliferative response is independent of adenosine or VEGF.

Active Transport, Cell Nucleus↗
PubMed2003

Estrogen-induced cell signalling in a cellular model of Alzheimer's disease.

Alzheimer's disease (AD) is characterised by deposition of a 4 kDa amyloid-beta peptide (Abeta) into senile plaques of the affected brain. Abeta is a proteolytic product of the membrane protein, amyloid precursor protein (APP). An alternative cleavage pathway involves alpha-secretase activity and results in secretion of a 100 kDa non-amyloidogenic APP (sAPPalpha) and therefore a potential reduction in Abeta secretion. We have shown that estrogen induces alpha-cleavage and therefore results in the secretion of sAPPalpha. This secretion is signalled via MAP-kinase and PI-3 kinase signal-transduction pathways. These pathways also have the potential to inhibit the activation of glycogen synthase kinase 3beta (GSK), a protein involved in cell death. Therefore, the aim of this work was to further elucidate the estrogen-mediated signaling pathways involved in APP processing, with particular emphasis on GSK activity. By stimulating rat hypothalamic neuronal GT1-7 cells with estradiol, we found that estrogen decreases the activation state of GSK via the MAP kinase pathway. Moreover, the inhibition of GSK activity by LiCl causes enhanced sAPPalpha secretion in a pattern similar to that seen in response to estrogen, suggesting a pivotal role for this deactivation in APP processing. Further, inactivation of GSK by estrogen can be confirmed in an in vivo model. Elucidation of the signaling pathways involved in APP processing may help to understand the pathology of AD and may also prove beneficial in developing therapeutic strategies to combat AD.

Alzheimer Disease↗
PubMed2003

[Incidence, pathoetiology and treatment of interferon-alpha induced neuro-psychiatric side effects].

Interferon alpha (IFN-alpha), an immunomodulatory cytokine, is used for the treatment of several disorders including chronic hepatitis or malignant melanoma. During the therapy IFN-alpha may cause severe neuropsychiatric syndromes including depression with suicidal ideation, paranoid psychoses or confusional states. The reasons and management of these side effects are widely unknown. The underlying pathogenetic mechanisms include various effects on neuroendocrine, cytokine and neurotransmitter systems. This review summarizes therapeutic strategies against IFN-alpha associated psychiatric syndromes. Zolpidem or Zopiclon can be used for the treatment of sleeping disturbances. Serotonin-reuptake-inhibitors including citalopram or paroxetine were shown to be effective for acute treatment of IFN-alpha associated depression. The efficacy of prophylactic treatment for prevention of IFN-alpha induced depression has to be proven in future trials. In an interdisciplinary setting, psychiatric disorders and drug addiction should not prevent patients from interferon-alpha treatment. Furthermore, interdisciplinary care should improve quality of life, adherence and therapeutic outcome of interferon-alpha treated patients.

Humans↗
PubMed2002

The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.

Base Sequence↗
PubMed2002

[Prospective assessment of the learning curve and safety of stapler hemorrhoidectomy].

INTRODUCTION: Stapled haemorrhoidectomy (SH) is a recently introduced procedure for the surgical excision of haemorrhoids. Actually, there is only limited information concerning the impact of the learning curve, complication rates and long-term results. Therefore, a prospective single-center study was performed with special regard to the learning curve and clinical safety of SH. METHODS: The data of 61 SH performed between March 1999 and May 2001 were analyzed. Operating times, complication rates and outcome results were prospectively recorded and then correlated to the surgical experience of the operating team. Postoperative pain was measured using the visual analogue scale (VAS). Sphincter lesions represented by the patient's incontinence and muscle defects were analyzed by using Williams incontinence score and histological examination of the resected specimen. Clinical follow-up studies were performed three and twelve weeks postoperatively. RESULTS: There were 18 patients with grade II haemorrhoids, 38 patients with grade III haemorrhoids, and five patients with grade IV haemorrhoids. Both, operating times and complication rates decreased with more surgical experience. The mean pain score during the first four postoperative days was 1.9 (range 0-8). Mean hospital stay and mean convalescence time were 1.7 days (range 1-5 days) and 10 days (range 1-31 days), respectively. Incontinence scores revealed only minor differences between pre- and postoperative values. CONCLUSIONS: SH represents a safe and effective new treatment modality for symptomatic haemorrhoids. Meticulous surgical technique and experience are mandatory to achieve excellent clinical results, e.g., reduced postoperative pain, shortened hospital stay and convalescence. We adopted SH to our surgical armamentarium for the treatment of haemorrhoids grade III and recurrent haemorrhoids.

Adolescent↗
PubMed2002

Does Switzerland train tomorrow's surgeons today? Today's reflections on tomorrow's surgeons.

Various factors are influencing the Swiss health care system, and therefore, surgeons' actual and future profession. Initiated by the current president of the Swiss Society of Surgery, a group of eight young Swiss surgeons constituted the ad hoc committee "Chirurgie 2020". The goal was to develop several scenarios of the surgeon's professional situation in 20 years. The future direction of surgery will be markedly influenced by medical innovation, political and economic relationships between Switzerland and Europe. However, the development of health care costs represents the most powerful factor predicting all further changes. The current situation of today's surgeons is best characterised as "hamsters in the treadmill" who try to fulfill a multitude of diverging tasks causing major demotivation. In order to retain a leading role in the health care system, surgeons must take part in social and political activities. To provide an excellent curriculum, university and county hospitals must join together to form clinical and educational networks. A clearly defined and structured curriculum must be introduced by the Swiss Society of Surgery. From our current point of view, only everyone's strong personal commitment will help to find solutions and to improve the current and future situation. In particular, today's surgical residents must actively take part in the development of tomorrow's surgery.

Curriculum↗
PubMed2002

Disruption of the RanBP17/Hox11L2 region by recombination with the TCRdelta locus in acute lymphoblastic leukemias with t(5;14)(q34;q11).

The t(5;14)(q33-34;q11) translocation constitutes a recurrent rearrangement in acute lymphoblastic leukemia involving the T cell receptor (TCR) delta locus on chromosome 14. Breakpoint sequences of the derivative chromosome 5 were isolated by application of a ligation-mediated PCR technique using TCR delta-specific primers to amplify genomic DNA from the leukemic cells of a patient with t(5;14). Through exon trap analysis, we identified various putative exons of the chromosome 5 target gene of the translocation; compilation of sequence information of trapped exons and available expressed sequence tags (ESTs) from the GenBank database allowed us to assemble 1.2 kb of the cDNA. Full-length cDNAs were isolated from a human testis cDNA library and sequence analysis predicted a putative Ran binding protein, a novel member of the importin-beta superfamily of nuclear transport receptors, called RanBP17. The t(5;14) breakpoint maps to the 3' coding region of the gene. The breakpoint of a second t(5;14) positive patient was mapped about 8 kb downstream of the most 3' RanBP17 exon and 2 kb upstream of the first exon of the orphan homeobox gene, Hox11L2. In both cases TCR delta enhancer sequences are juxtaposed downstream of the truncated or intact RanBP17 gene, respectively on the derivative chromosome.

Acute Disease↗
PubMed2002

Technique and value of staging laparoscopy.

Despite significant improvements in preoperative tumor staging due to sophisticated new imaging and interventional techniques, peritoneal tumor spread and occult liver and lymph node metastases are only detected during surgery in some patients. Newer treatment modalities using neoadjuvant regimens are only given if occult tumor spread is excluded. Diagnostic laparoscopy has therefore been introduced to prevent patients with advanced tumor disease from unnecessary laparotomy and as a diagnostic tool in neoadjuvant treatment protocols. Laparoscopic ultrasound represents an important technical improvement in diagnostic laparoscopy. The main indication for diagnostic laparoscopy is therefore exact tumor staging, especially in terms of peritoneal, liver, and lymphatic tumor spread, whereas determination of local tumor resectability is not the main issue. The aim of the current review is to summarize the technique of staging laparoscopy and to discuss its clinical value for a variety of gastrointestinal malignancies.

Biliary Tract Neoplasms↗
PubMed2002

["Saar Stroke Teleservice--pilot study for stroke after care with a home care platform].

In the German region Saarland a pilot trial has been conducted for the post-clinical telecare and rehabilitation of stroke patients in there homes by a cooperative network of local healthcare providers. For that purpose an e-home care platform has been developed by a combine of Fraunhofer institutes under the leadership of the Fraunhofer Institute for Biomedical Engineering. A network formed by a clinic, 2 general practitioners and an advice centre cared for 18 patients using the so-called PHS Homecare Platform for telemonitoring and virtual visits by videophone. (PHS: Personal Health Service--A research initiative of the Fraunhofer Society in the years 1996-2001). In the underlying feasibility study the telecare of stroke patients in the context of the German healthcare system has been tested and the e-home care platform has been evaluated.

Computer Communication Networks↗
PubMed2001

"Flexiball" toolkit: a modular approach to self-assembling capsules.

We report the synthesis and characterization of new, self-assembling molecular capsules. The modular strategy makes use of glycoluril building blocks available in multigram amounts combined with aromatic spacer elements. The lengthy syntheses encountered with earlier generations of capsules are avoided, and several capsules of nanometer dimensions are now accessible. Single bond attachments between spacers and glycoluril modules result in monomers as dimeric capsules that are less rigid than their earlier counterparts. The host-guest properties of the homo- and heterodimeric capsules were studied using a combination of NMR and ESI-mass spectrometry. They show a less pronounced selectivity for guests of different sizes, and their increased flexibility prevents self-assembly when no rigidifying elements are present on the central spacer unit. Some of the new capsules bear inwardly directed, secondary amide N-H protons. These can be further functionalized, as shown by their methylation to give tertiary analogues. The structures hold broader implications for the placement of functional groups on concave molecular surfaces.

Alkynes↗
PubMed2001

Role of the reverse mode of the Na+/Ca2+ exchanger in reoxygenation-induced cardiomyocyte injury.

OBJECTIVE: We have recently shown that spontaneous Ca2+ oscillations elicit irreversible hypercontracture of cardiomyocytes during reoxygenation. The aim of this study was to investigate whether influx of exterior Ca2+ through the reverse mode of the Na+/Ca2+ exchanger (NCE) contributes to the development of these oscillations and, therefore, to reoxygenation-induced hypercontracture. METHODS: Isolated cardiomyocytes and hearts from rats were used as models. Cardiomyocytes were exposed to 60 min simulated ischemia (pH(o) 6.4) and 10 min reoxygenation (pH(o) 7.4). During reoxygenation cardiomyocytes were superfused with medium containing 1 mmol/l Ca2+ (control), with nominally Ca2+-free medium or with medium containing 10 micromol/l KB-R 7943 (KB), a selective inhibitor of the reverse mode of the NCE. RESULTS: In reoxygenated cardiomyocytes rapid Ca2+ oscillations occurred which were reduced under Ca2+-free conditions or in presence of KB. Hypercontracture was also significantly reduced under Ca2+-free conditions or in presence of KB. After 30 min of normoxic perfusion isolated rat hearts were subjected to 60 min global ischemia and reperfusion. KB (10 micromol/l) was present during the first 10 min of reperfusion. LVEDP, LVdevP and lactate dehydrogenase (LDH) release were measured. Presence of KB reduced post-ischemic LVEDP and improved left ventricular function (LVdevP). In KB treated hearts the reperfusion induced release of LDH was markedly reduced from 81.1 +/- 9.9 (control) to 49.3 +/- 8.8 U/60 min/g dry weight. CONCLUSION: Our study shows that inhibition of the reverse mode of the NCE, during reperfusion only, protects cardiomyocytes and whole hearts against reperfusion injury.

Analysis of Variance↗
PubMed2001

Alterations in hemodynamics and hepatic and splanchnic circulation during laparoscopy in rats.

BACKGROUND: There is growing evidence that a pneumoperitoneum with increased intraabdominal pressure exerts adverse cardiovascular and splanchnic circulatory effects, whereby portal blood flow, in particular, is disturbed. METHODS: Cardiovascular hemodynamics and the blood flow of hollow viscus and solid organs were evaluated in rats undergoing laparotomy, followed by diagnostic carbon dioxide (CO2) laparoscopy with an intraabdominal pressure of either 4 or 10 mmHg and rapid desufflation of the abdominal cavity. The method we employed used g-labeled microspheres and conventional hemodynamic measurements. RESULTS: During CO2 laparoscopy, cardiac output and mean arterial pressure were significantly reduced to between 20.5% and 25% and 14.8% and 18% respectively. After rapid desufflation, cardiovascular hemodynamics normalized to baseline values. During laparoscopy, blood flow in the hollow viscus organs was less disturbed than that in the solid organs. Although small and large bowel blood flow was reduced significantly (26.6% and 23.9%, respectively), gastric blood flow remained unchanged. The decreases in the liver, spleen, pancreas, and kidney circulation were 29-37.2%, 37.6-64.6%, 51.2-57.5%, and 34.8-40.6%, respectively. Total hepatic blood flow was influenced predominantly by portal blood flow, which was particularly decreased; hepatic arterial flow remained stable. CONCLUSIONS: Severe alterations in cardiovascular hemodynamics, and to hepatic and splanchnic circulation occur rapidly during CO2 laparoscopy. It can be presumed that both increased intraabdominal pressure and hypercapnia are the main factors underlying these disturbances.

Animals↗
PubMed2001

Gas-phase structures of acetyl peroxynitrate and trifluoroacetyl peroxynitrate.

The molecular structures and conformational properties of acetyl peroxynitrate (PAN, CH3C(O)OONO2) and trifluoroacetyl peroxynitrate (FPAN, CF3C(O)OONO2) were investigated in the gas phase by electron diffraction (GED), microwave spectroscopy (MW), and quantum chemical methods (HF/3-21G, HF/6-31G*, MP2/6-31G*, B3PW91/6-31G*, and B3PW91/6-311+G*). All experimental and theoretical methods show the syn conformer (C=O bond of acetyl group syn to O-O bond) to be strongly predominant relative to the anti conformer. The O-NO2 bonds are extremely long, 1.492(7) A in PAN and 1.526(10) A in FPAN, which correlates with their low bond energy and the easy formation of CX3C(O)OO* and *NO2 radicals in the atmosphere. The O-O bonds (1.418(12) A in PAN and 1.408(8) A in FPAN) are shorter than that in hydrogen peroxide (1.464 A). In both compounds the C-O-O-N dihedral angle is close to 85 degrees.

Journal Article↗
PubMed2001

Facial-selective allylation of methyl ketones for the asymmetric synthesis of alpha-substituted tertiary homoallylic ethers.

The asymmetric synthesis of enantiomerically pure a-substituted tertiary homoallylic ethers 4a, 11 and 12a-c by the allylation of ethyl methyl ketone (la) with gamma-substituted allylsilanes 9a-h is described. The allylsilanes were obtained by a nickel-catalysed Grignard cross-coupling reaction of (E)- and (Z)-(3-iodoallyl)trimethylsilane with various Grignard reagents. The reaction of the allylsilanes with la in the presence of the trimethylsilyl ether of N-trifluoroacetylnorpseudoephedrine (3), and catalytic amounts of a mixture of trimethylsilyl triflate and trifluoromethanesulfonic acid led to the homoallylic ethers 4a, 11 and 12a-c with two new stereogenic centres, with a selectivity of 1:9 to >20:1 for the homoallylic and of 1:99 to >60:1 for the allylic centre. The facial selectivity does not depend on the configuration of the allylsilane, and in all reactions the anti product is preferentially formed. Interestingly, a pronounced switch of facial selectivity takes place with increasing length of the alkyl group of the allylsilane.

Journal Article↗