[Arachnoiditis following spinal anesthesia-Case report and review of the literature]. / Arachnoiditis nach Spinalanästhesie ­ Fallbericht und Literaturübersicht.

A 61-year-old woman underwent a tension-free vaginal tape (TVT) operation due to stress incontinence. After technically difficult spinal anesthesia with two attempts the patient developed symptoms of nerve irritation, complained about neckache and headache and showed signs of agitation. The regimen was shifted to general anesthesia and surgery was performed. Because of postoperatively persistent headache and sensory disturbances an MRI scan of the lumbar spine was performed on the first postoperative day without pathological findings. The patient was able to leave the hospital after 1 week with significant relief of symptoms but 3 weeks later she developed neurocognitive impairment with memory deficits. A second MRI scan of the head now showed signs of disturbance of CSF circulation with hydrocephalus. Treatment was performed with drainage and ventriculoperitoneal shunt. Further evaluation showed a severe, multisegmental arachnoiditis and the patient developed a progressive paraparesis. The patient presented her case for assessment to a commission on medical malpractice 13 months after anesthesia. The commission detected no treatment errors. In connection to the case report a literature review of characteristics and etiologies of chronic adhesive arachnoiditis is given, which is a known but very rare complication of spinal anesthesia or similar procedures.

[A protestant pastor as the pioneer of emergency medicine : Sebastianus Albinus published the first emergency manual 400 years ago]. / Ein evangelischer Pfarrer als Pionier der Notfallmedizin : Vor 400 Jahren ließ Sebastianus Albinus die erste Notfallfibel drucken.

In 1588 Sebastian Weiß, the son of a miller, became the first Lutheran pastor of Dittersbach in Saxony. At home he had repeatedly witnessed successful resuscitation of drowned persons by means of simple measures by his parents. Missing appropriate recommendations in the medical literature, in 1620 as "Sebastianus Albinus" he published a booklet with measures for reviving apparently drowned persons. This Kurtze Bericht und Handgrieff (Brief report and handgrip) attracted great attention amongst physicians, especially the reprint of 1675 of which a few copies still exist. The first printed edition from 1620 was lost until, some years ago, the apparently only still existing copy was rediscovered in the Herzog August Library in Wolfenbüttel.

[Hans Franz Edmund Killian - nestor of German anesthesia : Critical appraisal on the 125th anniversary of his birth]. / Hans Franz Edmund Killian ­ Nestor der deutschen Anästhesie : Kritische Würdigung zum 125. Geburtstag.

The surgeon Hans Killian was born on 5 August 1892 in Freiburg im Breisgau, Germany. Together with the pharmacologist Hellmut Weese and the surgeon Helmut Schmidt he was one of the nestors of modern German anesthesia. Early on during his scientific and clinical career, he addressed problems of surgical anesthesia and in 1928 he became one of the editors of the first German journal of anesthesia Narcosis and Anesthesia ("Narkose und Anästhesie"). In 1934 he published the textbook Anesthesia for Surgical Purposes ("Narkose zu operativen Zwecken"). Between World Wars I and II, he campaigned for anesthesia to become an independent medical discipline comparable to the situation in the Anglo-Saxon countries at that time. Because of his merits in the foundation of the German Society of Anesthesia on 10 April 1953 he became its first honorary member. Killian died on 7 March 1982 in Freiburg, Germany. Excerpts of his autobiography which he wrote a few years before his death and which were part of his inheritance are published here for the first time.

[Victory over surgical pain : 170 years ago the era of modern anesthesia began - but what happened in the operating theater in the time before?] / Sieg über den Operationsschmerz : Vor 170 Jahren begann die Ära der modernen Anästhesie ­ aber was geschah in der Zeit davor im Operationssaal?

170 years ago, on 6 October 1846, the dentist William Thomas Green Morton, sucessfully demonstrated ether anesthesia in a patient undergoing surgery in the operating theater of the Massachusetts General Hospital in Boston. He thereby put an end to the unthinkable suffering of patients who had to undergo surgery when fully conscious. Before this "discovery" surgical procedures resembled a battle for life and death. Only a few documents exist illustrating the attitude of surgeons concerning their actions and which tortures patients had to tolerate. One of the first German standard operating procedures for the perioperative period was formulated in 1812 by Christian Bonifacius Zang. In her diaries and letters, the english novelist Frances Burney described her mastectomy without anesthesia on 30 September 1811. The Scottish physician and novelist John Brown, in his story of "Rab and his friends", painted a picture of the mastectomy of Ailie Noble by the famous Scottish surgeon James Syme in 1833, also without anesthesia. Finally, in his letters the Scottish scientist George Wilson described the amputation of his left foot at the ankle in January 1843, again by James Syme and again without the use of anesthesia.

Effect of smoking cessation counseling within a randomised study on early detection of lung cancer in Germany.

INTRODUCTION: In the German lung cancer screening trial LUSI, smoking cessation counseling (SCC) was offered to all participants at time of randomization, and smoking habits were asked for within annual questionnaire inquiries. We analyzed the smoking habits of the participants within the first 2 years of follow-up and especially the potential effect of the SCC on these habits. MATERIALS AND METHODS: We used the smoking data of the initial inquiry on which the decision on invitation to the study was based, the socio-economic data of the questionnaire filled-in at time of randomization, the psycho-social data obtained during the SCC, and the annual questionnaire data of the first two annual follow-up screening rounds. RESULTS: Smoking prevalence decreased in the entire cohort significantly by 4 %, whereby the decrease was with 4.5 % statistically not significantly higher in the control arm than in the screening arm with 3.4 %. The decline was much stronger in the subgroup of attendees to stop-smoking counseling and mounted up therein to 10 %. In some participants, an increase of readiness to quit smoking was observed during the counseling hour, but did not show effects on smoking status 2 years later. DISCUSSION: We did not see a tendency to increased smoking among participants of the intervention arm or the entire study. The decline of smoking prevalence among the attendees of the counseling might be due to self-selection. Since the issue of effectiveness of smoking cessation counseling is important, further research with randomization into offering counseling or no intervention should be taken into consideration.

[Partial anomalous pulmonary venous connection as incidental finding: Explanation for apparently paradoxical central venous blood gas analysis results]. / Fehlmündende Lungenvene als Zufallsbefund: Erklärung für paradox erscheinende zentralvenöse Blutgasanalysen.

A partial anomalous pulmonary venous connection (PAPVC) is a congenital abnormality of the great thoracic vessels the incidence of which is underestimated and is associated with a left-right shunt. It rarely develops into a right-sided cardiac insufficiency. Because of the mostly low left-right shunt volume, a PAPVC is often asymptomatic and mostly incidentally detected in advanced age. Incorrect positioning of a central venous catheter or paradoxical blood gas parameters can serve to indicate the presence of a PAPVC. This article presents the case a 50-year-old patient with a PAPVC of the left upper lobe pulmonary vein draining into the left innominate vein without prior clinical symptoms. Blood gas analyses from the superior vena cava, where the catheter placement was confirmed by computed tomography angiography, showed unexplainable arterial values. The anatomical abnormality was confirmed by computed tomography.

Superoxide production by cytochrome bc1 complex: a mathematical model.

Reactive oxygen species (ROS) are involved in the pathophysiology of several diseases (e.g. Alzheimer or atherosclerosis) and also in the aging process. The main source of ROS in aerobic organisms is the electron transport chain (ETC) in the inner mitochondrial membrane. Superoxide is produced at complexes I and III of the ETC, starting a complex network of ROS reactions. To achieve a deeper mechanistic understanding of how ROS are generated by complex III, we developed a mathematical model that successfully describes experimental data of complex III activity in various rat tissues, the production of ROS with and without antimycin and ROS generation depending on different values of the membrane potential ∆Ψ. The model also reinforces the idea of ubiquinone acting as a redox mediator between heme bL and oxygen, as proposed earlier.

The structure of eukaryotic and prokaryotic complex I.

The structures of the NADH dehydrogenases from Bos taurus and Aquifex aeolicus have been determined by 3D electron microscopy, and have been analyzed in comparison with the previously determined structure of Complex I from Yarrowia lipolytica. The results show a clearly preserved domain structure in the peripheral arm of complex I, which is similar in the bacterial and eukaryotic complex. The membrane arms of both eukaryotic complexes show a similar shape but also significant differences in distinctive domains. One of the major protuberances observed in Y. lipolytica complex I appears missing in the bovine complex, while a protuberance not found in Y. lipolytica connects in bovine complex I a domain of the peripheral arm to the membrane arm. The structural similarities of the peripheral arm agree with the common functional principle of all complex Is. The differences seen in the membrane arm may indicate differences in the regulatory mechanism of the enzyme in different species.

Regulatory demands on data quality for the environmental risk assessment of pharmaceuticals.

The evaluation of the quality of data and their use within the review of environmental risk assessment of human as well as veterinary pharmaceuticals is described from a regulatory point of view. A definition and differentiation in three categories for the reliability of data are given. Existing criteria relating to international testing standards for categorising reliability are adopted for their use within the environmental risk assessment of pharmaceuticals. A systematic documentation of evaluating reliability for literature data as well as for experimental studies (effect and environmental fate studies) is proposed. The data quality criteria are defined in order to increase the transparency of the evaluation process in Germany and thus the quality of the environmental risk assessment of pharmaceuticals.

Hypoxic reoxygenation during initial reperfusion attenuates cardiac dysfunction and limits ischemia-reperfusion injury after cardioplegic arrest in a porcine model.

OBJECTIVE: In clinical practice, reperfusion of ischemic myocardium usually occurs under high arterial oxygen levels. However, this might aggravate cardiac ischemia-reperfusion injury caused by excessive oxidative stress. In an experimental in vivo study, the cardioprotective role of hypoxic reoxygenation during initial reperfusion was assessed. METHODS: Twenty-one adult pigs were started on cardiopulmonary bypass with aortic crossclamping (90 minutes) and cardioplegic arrest. During initial reperfusion, 10 pigs underwent standard hypoxic reoxygenation (Pa(O(2)), 250-350 mm Hg), whereas gradual reoxygenation (Pa(O(2)), 40-90 mm Hg) was performed in 11 pigs. Cardiac function was analyzed by means of the thermodilution method and conductance catheter technique. RESULTS: In both groups cardiac index was decreased 10 minutes after cardiopulmonary bypass compared with preoperative values. Sixty minutes after cardiopulmonary bypass, cardiac index improved significantly after gradual reoxygenation compared with that after hypoxic reoxygenation (3.2 +/- 0.6 vs 2.5 +/- 0.5 L min(-1) m(-2), P = .04). Correspondingly, end-systolic pressure-volume relationship and peak left ventricular pressure increase were significantly less decreased in the gradual reoxygenation group. During and after reperfusion, malondialdehyde and troponin T values within the coronary sinus were significantly lower after gradual reoxygenation (60 minutes after declamping: malondialdehyde, 7.6 +/- 0.8 vs 4.6 +/- 0.5 micromol/L [P = .007]; troponin, 0.12 +/- 0.02 vs 0.41 +/- 0.12 ng/mL [P = .02]). CONCLUSION: Hypoxic reoxygenation at the onset of reperfusion attenuates myocardial ischemia-reperfusion injury and helps to preserve cardiac performance after myocardial ischemia in a pig model.

Mitochondrial dysfunction: an early event in Alzheimer pathology accumulates with age in AD transgenic mice.

Recent evidence suggests mitochondrial dysfunction as a common early pathomechanism in Alzheimer's disease integrating genetic factors related to enhanced amyloid-beta (Ass) production and tau-hyperphosphorylation with aging, as the most relevant sporadic risk factor. To further clarify the synergistic effects of aging and Ass pathology, we used isolated mitochondria of double Swedish and London mutant APP transgenic mice and of non-tg littermates. Pronounced mitochondrial dysfunction in adult Thy-1 APP mice, such as a drop of mitochondrial membrane potential and reduced ATP-levels already appeared at 3 months when elevated intracellular but not extracellular Ass deposits are present. Mitochondrial dysfunction was associated with higher levels of reactive oxygen species, an altered Bcl-xL/Bax ratio and reduction of COX IV activity. We observed significant decreases in state 3 respiration and FCCP-uncoupled respiration in non-tg mice after treatment with extracellular Ass. Similar deficits were seen only in aged Thy-1 APP mice, probably due to compensation within the respiratory chain in young animals. We conclude that Ass dependent mitochondrial dysfunction starts already at 3 months in this AD model before extracellular deposition of Ass and progression accelerates substantially with aging.

The three-dimensional structure of complex I from Yarrowia lipolytica: a highly dynamic enzyme.

The structure of complex I from Yarrowia lipolytica was determined by three-dimensional electron microscopy. A random conical data set was collected from deep stain embedded particles. More than 14000 image pairs were analyzed. Through extensive classification combined with three-dimensional reconstruction, it was possible for the first time to show a much more detailed substructure of the complex. The peripheral arm is subdivided in at least six domains. The membrane arm shows two major protrusions on its matrix facing side and exhibits a channel like feature on the side facing the cytoplasm. Structures resembling a tether connecting the subunits near the catalytic center with the protrusions of the membrane arm provide a second connection between matrix and membrane domain.

Expression of the chemokine receptor CXCR1 in human glomerular diseases.

Leukocyte infiltration, a hallmark of renal diseases, is orchestrated in part by the actions of chemokines. The chemokine CXCL8/interleukin (IL)-8 is expressed during renal diseases and allograft rejection, whereas the corresponding receptor CXCR1 has not been described previously. Expression of CXCR1 was characterized in peripheral blood using multicolor fluorescence-activated cell sorter analysis (FACS). CXCR1 was localized in 81 formalin-fixed, paraffin-embedded renal specimens by immunohistochemistry using a monoclonal antibody against human CXCR1. Included were biopsies with crescentic glomerulonephritis (CGN, n = 22), immunoglobulin (Ig) A nephropathy (n = 15), membranoproliferative glomerulonephritis (MPGN, n = 17), lupus nephritis (n = 12), membranous nephropathy (n = 11), and non-involved parts of tumor nephrectomies (n = 4). Consecutive tissue sections of human tonsils, allograft explants, and renal biopsies were stained for CD15- and CD68-positive cells. Expression of CXCR1 and CXCL8/IL-8 mRNA was quantified by real-time reverse transcriptase-polymerse chain reaction of microdissected renal biopsies (n = 35) of the same disease entities. By FACS CXCR1 expression was found on polymorphonuclear CXCR1 expression by polymorphonuclear leukocytes (PMNs), natural killer cells, and a subpopulation of monocytes. By immunohistochemistry, CXCR1 expression was found on infiltrating inflammatory cells (predominantly PMNs), as well as on intrinsic renal cells (arterial smooth muscle cells, endothelial cells of peritubular capillaries). The distribution pattern of CXCR1 differed between disease entities. The highest numbers of glomerular CXCR1-positive cells were present in biopsies with MPGN, followed by lupus nephritis, and CGN. CXCR1 might be involved in the recruitment of PMNs to the glomerular tuft, which could be targeted by CXCR1-blocking agents.

Cluster N1 of complex I from Yarrowia lipolytica studied by pulsed EPR spectroscopy.

After reduction with nicotinamide adenine dinucleotide (NADH), NADH:ubiquinone oxidoreductase (complex I) of the strictly aerobic yeast Yarrowia lipolytica shows clear signals from five different paramagnetic iron-sulfur (FeS) clusters (N1-N5) which can be detected using electron paramagnetic resonance (EPR) spectroscopy. The ligand environment and the assignment of several FeS clusters to specific binding motifs found in several subunits of the complex are still under debate. In order to characterize the hyperfine interaction of the surrounding nuclei with FeS cluster N1, one- and two-dimensional electron spin echo envelope modulation experiments were performed at a temperature of 30 K. At this temperature only cluster N1 contributes to the overall signal in a pulsed EPR experiment. The hyperfine and quadrupole tensors of a nitrogen nucleus and the isotropic and dipolar hyperfine couplings of two sets of protons could be determined by numerical simulation of the one- and two-dimensional spectra. The values obtained are in perfect agreement with a ferredoxin-like binding structure by four cysteine amino acid residues and allow the assignment of the nitrogen couplings to a backbone nitrogen nucleus and the proton couplings to the beta-protons of the bound cysteine residues.

Risk of congenital anomalies in the vicinity of waste landfills in Denmark; an epidemiological study using GIS.

Waste landfills are a potential hazard to health. Public concern exists about this potential hazard and researchers agree that further research is required on this field. The objective of the study was to investigate the association between waste landfill location and congenital anomalies risk in Denmark. The study was a multisided epidemiological geographical comparison study of risk of congenital anomalies combined and congenital anomalies of the cardiovascular and nervous systems with maternal residence in the vicinity of 48 Danish waste landfills compared with those living further away in the years 1997 to 2001. We used routine health and population data in Geographical Information System (GIS) to investigate the risk. The subjects were 2,477 live birth with congenital anomalies. All relative risks in the proximal zones of 0-2 km were set to 1 for comparison. For all anomalies combined relative risk in the middle zones of 2-4 km joint was 0.991 and in the distal zones of 4-6 km joint the relative risk was 1.013. For congenital anomalies of the nervous system, the relative risk in the middle zones was 1.226 and in the distal zones 1.113. For congenital anomalies of the cardiovascular system, the relative risk in the middle zones was 0.926 and in the distal zones 0.854. This result was not supported by the aggregated risk ratio mean. We found no association between waste landfill location and congenital anomalies combined or of the nervous system. However, we found small excess risk for congenital anomalies of the cardiovascular system. No causal mechanisms are available to explain these findings, but alternative explanations include approximated birth rates and residual confounding. It is our recommendation that more comprehensive multisided studies will be executed to examine the safety of waste landfills.

Structure-function relationships in mitochondrial complex I of the strictly aerobic yeast Yarrowia lipolytica.

The obligate aerobic yeast Yarrowia lipolytica has been established as a powerful model system for the analysis of mitochondrial complex I. Using a combination of genomic and proteomic approaches, a total of 37 subunits was identified. Several of the accessory subunits are predicted to be STMD (single transmembrane domain) proteins. Site-directed mutagenesis of Y. lipolytica complex I has provided strong evidence that a significant part of the ubiquinone reducing catalytic core resides in the 49 kDa and PSST subunits and can be modelled using X-ray structures of distantly related enzymes, i.e. water-soluble [NiFe] hydrogenases from Desulfovibrio spp. Iron-sulphur cluster N2, which is related to the hydrogenase proximal cluster, is directly involved in quinone reduction. Mutagenesis of His226 and Arg141 of the 49 kDa subunit provided detailed insight into the structure-function relationships around cluster N2. Overall, our findings suggest that proton pumping by complex I employs long-range conformational interactions and ubiquinone intermediates play a critical role in this mechanism.

[The gap1 operon of the cyanobacterium Synechococcus PCC 7942 carries a gene encoding glycogen phosphorylase and is induced under anaerobic conditions]. / GAP1-operon tsianobakterii Synechococcus PCC 7942 kodiruet glikogenfosforilazu i indutsiruetsia v anaéusloviiakh.

The cloning and sequencing of the gap1 operon, which encodes the glycolytic NAD-specific glyceraldehyde-3-phosphate dehydrogenase in the cyanobacterium Synechococcus PCC 7942, showed that the gap1 gene is closely linked to the glgP gene encoding glycogen phosphorylase (an enzyme that catalyzes the first step of glycogen degradation). Northern blotting experiments showed that the gap1 and glgP genes are co-expressed and organized in a bicistronic operon, whose expression is enhanced under anaerobic conditions. The nucleotide sequence of the operon has been submitted to GenBank under accession number AF428099.

Exploring the catalytic core of complex I by Yarrowia lipolytica yeast genetics.

We have developed Yarrowia lipolytica as a model system to study mitochondrial complex I that combines the application of fast and convenient yeast genetics with efficient structural and functional analysis of its very stable complex I isolated by his-tag affinity purification with high yield. Guided by a structural model based on homologies between complex I and [NiFe] hydrogenases mutational analysis revealed that the 49 kDa subunit plays a central functional role in complex I. We propose that critical parts of the catalytic core of complex I have evolved from the hydrogen reactive site of [NiFe] hydrogenases and that iron-sulfur cluster N2 resides at the interface between the 49 kDa and PSST subunits. These findings are in full agreement with the "semiquinone switch" mechanism according to which coupling of electron and proton transfer in complex I is achieved by a single integrated pump comprising cluster N2, the binding site for substrate ubiquinone, and a tightly bound quinone or quinoid group.

External alternative NADH:ubiquinone oxidoreductase redirected to the internal face of the mitochondrial inner membrane rescues complex I deficiency in Yarrowia lipolytica.

Alternative NADH:ubiquinone oxidoreductases are single subunit enzymes capable of transferring electrons from NADH to ubiquinone without contributing to the proton gradient across the respiratory membrane. The obligately aerobic yeast Yarrowia lipolytica has only one such enzyme, encoded by the NDH2 gene and located on the external face of the mitochondrial inner membrane. In sharp contrast to ndh2 deletions, deficiencies in nuclear genes for central subunits of proton pumping NADH:ubiquinone oxidoreductases (complex I) are lethal. We have redirected NDH2 to the internal face of the mitochondrial inner membrane by N-terminally attaching the mitochondrial targeting sequence of NUAM, the largest subunit of complex I. Lethality of complex I mutations was rescued by the internal, but not the external version of alternative NADH:ubiquinone oxidoreductase. Internal NDH2 also permitted growth in the presence of complex I inhibitors such as 2-decyl-4-quinazolinyl amine (DQA). Functional expression of NDH2 on both sides of the mitochondrial inner membrane indicates that alternative NADH:ubiquinone oxidoreductase requires no additional components for catalytic activity. Our findings also demonstrate that shuttle mechanisms for the transfer of redox equivalents from the matrix to the cytosolic side of the mitochondrial inner membrane are insufficient in Y. lipolytica.