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Biomedical subjects

G Fischer

Publications and source records attributed to G Fischer.

At least 73 records · Page 4Linked to original sources
PubMed2001

Dissociation of LPS-induced monocytic ex vivo production of granulocyte colony-stimulating factor (G-CSF) and TNF-alpha in patients with septic shock.

Over a 6 month period, in 192 patients admitted to the intensive care unit (ICU), a longitudinal analysis of whole blood lipopolysaccharide (LPS)-induced ex vivo cytokine production was performed on a daily basis until discharge from the ICU or death. Twenty-one patients with proven infections were in septic shock for the first time and for at least 3 days' duration. Ex vivo LPS-inducible release of granulocyte colony-stimulating factor (G-CSF) was upregulated and that of TNF-alpha was downregulated in patients with septic shock, regardless whether they survived or died. In conclusion, LPS-induced ex vivo TNF-alpha and G-CSF cytokine release by monocytes is regulated differentially in patients with septic shock. Since upregulation of LPS-induced production of G-CSF occurred earlier in survivors than in non-survivors, rapidly elevated and sustained G-CSF responsiveness may contribute to survival in septic shock.

Adult↗
PubMed2001

Entrapment of the lingual nerve due to an ossified pterygospinous ligament.

During a routine dissection course at the University of Muenster (Germany) an unusual course of the lingual nerve was found with entrapment of the nerve between a widely ossified pterygospinous ligament and the medial pterygoid muscle. Furthermore, the nerve's mobility was restricted by a more distal anastomosis with the inferior alveolar nerve. Although incomplete or complete ossification of the pterygospinous ligament is not uncommon, the combination with a medial course of the lingual nerve has not been described before. Besides practical importance for surgeons and anesthetists, the entrapment of the lingual nerve may lead to lingual numbness and pain associated with speech impairment.

Aged↗
PubMed2001

An iterative algorithm for myocardial activation time imaging.

An iterative algorithm based on a general regularization scheme for nonlinear ill-posed problems in Hilbert scales (method A) is applied to the magnetocardiographic inverse problem imaging the surface myocardial activation time map. This approach is compared to an algorithm using an optimization routine for nonlinear ill-posed problems based on Tikhonov's approach of second order (method B). Method A showed good computational performance and the scheme for determining the proper regularization parameter lambda was found to be easier than in case of method B. The formulation is applied to magnetocardiographic recordings from a patient suffering from idiopathic ventricular tachycardia in which a sinus rhythm sequence was followed by a ventricular extrasystolic beat.

Algorithms↗
PubMed2001

Nonprolyl cis peptide bonds in unfolded proteins cause complex folding kinetics.

Folding of tendamistat, an inhibitor of alpha-amylase, is a fast two-state process accompanied by two minor slow reactions, which were assigned to prolyl isomerization. In a proline-free variant, 5% of the molecules still fold slowly with a rate constant of 2.5 s(-1). This reaction is caused by a slow equilibrium between two populations of unfolded molecules. The time constant for this equilibration process, its sensitivity to LiCl and its temperature dependence identify it as a cis-trans isomerization of nonprolyl peptide bonds. Although nonprolyl peptide bonds have the cis conformation populating only approximately 0.15% in unfolded proteins, their large number generates a significant fraction of slow-folding molecules. This emphasizes that heterogeneous populations in an unfolded protein can induce complex folding kinetics on various time scales.

Amino Acid Substitution↗
PubMed2001

Crystal structure of Mip, a prolylisomerase from Legionella pneumophila.

The human pathogen Legionella pneumophila, the etiological agent of the severe and often fatal Legionnaires' disease, produces a major virulence factor, termed 'macrophage infectivity potentiator protein' (Mip), that is necessary for optimal multiplication of the bacteria within human alveolar macrophages. Mip exhibits a peptidyl prolyl cis-trans isomerase (PPIase) activity, which appears to be important for infection. Here we report the 2.4 A crystal structure of the Mip protein from L. pneumophila Philadelphia 1 and the 3.2 A crystal structure of its complex with the drug FK506. Each monomer of the homodimeric protein consists of an N-terminal dimerization module, a long (65 A) connecting alpha-helix and a C-terminal PPIase domain exhibiting similarity to human FK506-binding protein. In view of the recent significant increase in the number of reported cases of Legionnaires' disease and other intracellular infections, these structural results are of prime interest for the design of new drugs directed against Mip proteins of intracellular pathogens.

Anti-Bacterial Agents↗
PubMed2001

Long-term clinical and molecular remission after allogeneic stem cell transplantation (SCT) in patients with poor prognosis non-Hodgkin's lymphoma.

From 1987 to 1999 35 patients with poor prognosis non-Hodgkin's lymphoma (NHL) underwent allogeneic stem cell transplantation (SCT) at the University Hospitals of Vienna and Graz. Initial biopsy specimens were reclassified according to the Revised European-American Classification of Lymphoid Neoplasms (REAL). All patients surviving 28 days engrafted. Twenty-eight of them (93%) attained clinical remission. At the last follow-up 14 patients were alive and disease-free at a median of 5.0 (range, 2.3-12.9) years after allogeneic SCT. The actuarial overall survival is 35%. Five patients relapsed 1.8 to 27.6 months after transplant, the probability of relapse is 23%. Of the 21 deaths following SCT, seven were due to relapse/refractory disease and 14 due to transplant-related causes. The probability of treatment-related mortality is 48%. After SCT, minimal residual disease (MRD) was monitored by polymerase chain reaction (PCR) in seven patients with a BCL-2/IgH translocation and in 13 with a clonal immunoglobulin heavy chain (IgH) rearrangement. All 20 patients attained clinical remission rapidly and converted to PCR negativity. In the follow-up nine of these patients are in long-term clinical and molecular remission, six PCR-negative patients died of transplant-related causes and five patients relapsed. In summary, allogeneic stem cell transplantation has a curative potential for patients with refractory and recurrent non-Hodgkin's lymphoma. In our series long-term disease-free survival was associated with molecular disease eradication after SCT. Treatment-related mortality rate was high, thus earlier referral of selected patients to allogeneic SCT should be considered.

Adult↗
PubMed2001

Cervical nerve injury after carotid endarterectomy.

OBJECTIVE: to determine the extent and direct significance of cervical nerve injury after carotid endarterectomy. MATERIAL AND METHODS: fifty-two patients (61 operations) were followed by means of patient history and neurological examination between 3 and 55 months following carotid endarterectomy. RESULTS: sixteen operated sites showed normal sensitivity. Patients assessed 3-6 months after surgery showed on average a neurological loss of 3.4 points (scale from 0-4). Patients assessed after 7-12 months had on average a deficit of 2.1 points. After 13-24 months the score was at 1.4 and after the second postoperative year the score yielded only 0.4 points. CONCLUSION: loss of cervical nerve sensation is always present after carotid endarterectomy but tends to improve with time. However, the timing and extent of this improvement is unpredictable. Patients are usually not disturbed by these changes.

Aged↗
PubMed2001

Long-term results of infrainguinal arterial reconstruction with spliced veins are equal to results with non-spliced veins.

OBJECTIVES: to determine the long term patency of spliced and non-spliced infrainguinal vein grafts. METHODS: a prospective registry of all patients undergoing infrainguinal arterial reconstruction with autogenous vein material was retrospectively interrogated. RESULTS: between October 1988 and August 2000, 515 infrainguinal arterial reconstructions were performed on 472 patients. A total of 429 bypasses were performed with uninterrupted greater saphenous vein, 86 reconstructions using spliced vein segments. There was no significant difference in primary (63% vs 57%) and primary assisted patency (81% vs 81%) of limb salvage (88% vs 91%) at 5 years. Limb salvage was not different (88% and 91% respectively). CONCLUSION the splicing of vein grafts does not compromise patency of limb salvage.

Aged↗
PubMed2001

Viral reduction techniques: types and purpose.

Viral reduction techniques help assure the highest level of plasma-product safety that is possible using today's technology. However, worldwide travel and changing demographics could bring new pathogens into focus and thus require plasma-product manufacturers to be continually vigilant in their efforts to refine current reduction techniques and develop and apply new methods. This review focuses on all the currently used viral reduction techniques, why viral reduction continues to be important (even with the use of polymerase chain reaction techniques to improve plasma screening), and possible future directions for viral reduction. When exploring current approaches, including heat treatment (especially pasteurization), solvent/detergent, pH changes, and ultrafiltration, this review also includes (where applicable) the negative impact of these techniques on product integrity and/or viruses not destroyed. Other techniques (eg, chromatography) and the fractionation steps relevant in the production of selected plasma products may also impart viral reduction and are briefly assessed. Relying on an extensive review of current online and printed literature, this article also discusses the current US and European guidelines and regulations that impact viral reduction techniques. This information includes emphasis on the recommendation to use at least 2 reduction techniques (each with a different mode of action) for each plasma product so as to substantially reduce both enveloped and nonenveloped viruses. The approach to validation studies and results from specific studies are reviewed, and future approaches for viral reduction are described.

Guidelines as Topic↗
PubMed2001

Trans-sinusal frontal approach for olfactory groove meningiomas.

The authors report on their experience with the trans-sinusal frontal approach in removing olfactory groove meningiomas. Six tumors were operated on by the trans-sinusal frontal approach, using a bicoronal incision; two tumors developed on one side, and there were four bilateral olfactosellar tumors. Osteotomy of the anterior wall of the frontal sinus was performed with an oscillating saw without any burr hole. The posterior wall of the sinus was resected and the tumor was attacked through a real subfrontal route along the plane of the anterior skull base. Ethmoidal blood supply was controlled at the initial stages of the operation, allowing avascular tumor debulking. Olfactory nerves, invaded by the tumor, were removed along with the tumor. Tumor extensions toward the sella and the optic canals were removed without brain retraction, opening of the Sylvian fissure, or dissection of the carotid arteries. All patients made a good neurologic recovery; intellectual impairment disappeared within 1 month, and visual acuity normalized within 2 weeks. Olfactory nets were preserved on the contralateral side in unilateral tumors. The trans-sinusal frontal approach is technically easy and safe to achieve. Osteotomy and replacement of the anterior wall of the frontal sinus are rapidly performed. When the frontal sinus is small, imageguided surgery allows precise deliniation of its limits and the free bone flap, including the calvarial outer layer, tangentially cut from one supraorbital canal to the other. The cosmetic result is perfect, as the normal contour of the forehead is maintained without any scar or visible burr hole. The trans-sinusal frontal approach gives access to the orbital roofs and to the central anterior skull base from the crista galli to the tuberculum sellae and the anterior clinoid processes. The trans-sinusal frontal approach represents an alternative to conventional craniotomies for tumors developed in the central anterior skull base, especially for olfactory groove meningiomas, whatever their size.

Journal Article↗
PubMed2001

[Pregnancy and substance dependency].

Substance dependency in pregnancy leads to severe health risks for the expecting mother and for the foetus and the new-born. The problem of substance dependent pregnant women lies not only in the use of illegal substances but also to a high degree in the use of legal substances such as alcohol and nicotine. In contrast to most other substances of abuse, opioids do not show cytotoxic or teratogenic characteristics. The primary goal should be the stabilisation of the patient and a reduction of additional illicit consumption. The ideal goal of abstinence is difficult to reach and often puts the women under enhanced risks. Detoxification after week 32 should not be undertaken in order to avoid preterm delivery. It should be standardised that a multiprofessional and interdisciplinary therapeutical care leads to a stabilisation in opioid dependent pregnant addicts and therefore improves the outcome for neonates. Special awareness needs to be addressed towards the diversification of opioid maintenance therapy. Based on the positive results in opioid maintenance therapy in pregnant opioid dependent women, it will be required to establish standards. Furthermore there is a need to establish consistent guidelines for the treatment of the neonatal abstinence syndrome.

Abnormalities, Drug-Induced↗
PubMed2001

[Buprenorphine in pregnancy].

The treatment of opioid dependence during pregnancy is a major challenge for doctors, social workers and gynaecologists. Continuous drug abuse during pregnancy can lead to a variety of complications in the mother, fetus and neonate. lt is recommended practice to maintain pregnant opioid-dependent women with synthetic opioids and according to international guidelines, methadone is the recommended substance so far. However, a neonatal abstinence syndrome (NAS) of varying severity is observed in 60 - 80 % of the neonates with even a longer course of duration in comparison to the NAS after heroin consumption during pregnancy. NAS is characterised by tremor, irritability, hypertonicity, vomiting, sneezing, fever, poor suckling, and sometimes convulsions. Recent studies have investigated the safety and efficacy of other synthetic opioids like sublingual buprenorphine for the treatment of pregnant patients. We present a 22 year old opioid-dependent woman, who has been maintained continuously on buprenorphine for 3 years. During the treatment episode she delivered two healthy newborns and both did not show any symptoms of NAS. The maintenance therapy with buprenorphine proved safety and efficacy during pregnancy, the mother was free of continuous heroin abuse, verified through supervised urine-toxicology. The quantitative and qualitative difference in NAS may be explained by the partial mu-receptor agonist and kappa-antagonist receptor profile of buprenorphine compared to pure mu-agonist action of methadone or heroin.

Adult↗
PubMed2001

Pyeloureteral junction stenosis and ureteral valve causing hydronephrosis.

A young female patient underwent ureteral resection and Hynes-Anderson pyeloureteroplasty because of pyeloureteral junction stenosis and a ureteral valve (UV), which caused hydronephrosis. Despite using ultrasonography and intravenous urography the ureteral valve was observed only on exploration. UV should be considered as a possible cause of upper urinary tract obstruction; retrograde urography can be essential.

Adult↗
PubMed2001

Evolution of gene order in the genomes of two related yeast species.

Changes in gene order between the genomes of two related yeast species, Saccharomyces cerevisiae and Saccharomyces bayanus var. uvarum were studied. From the dataset of a previous low coverage sequencing of the S. bayanus var. uvarum genome, 35 different synteny breakpoints between neighboring genes and two cases of local gene inversion were characterized in detail. The number and the type of the chromosomal rearrangements that have led to these differences were identified. We show that evolution of gene order in the genomes of these two yeast species is driven mainly by gene duplication onto different chromosomes followed by differential loss of the repeated copies. In addition, local gene inversions also would result from a mechanism of gene duplication, but in an inverted orientation, followed by loss of the original copy. The identification of traces of anciently duplicated genes, called relics, show that the loss of duplicates is more frequently caused by the accumulation of numerous mutations in one of the two copies than by DNA deletion. Surprisingly, gross chromosomal rearrangements such as translocations have only a minor effect on gene order reshuffling as they account for <10% of the synteny breakpoints.

Chromosome Inversion↗
PubMed2001

Transcatheter closure of persistent ductus arteriosus in infants using the Amplatzer duct occluder.

AIM: To evaluate whether transcatheter closure with the Amplatzer duct occluder offers an alternative to surgical treatment in infants with a persistent ductus arteriosus. METHODS: 12 patients under 1 year of age (age 1-11 months, body weight 2.6-8.7 kg) with clinical and echocardiographic findings of a significant duct were considered for transcatheter closure with the Amplatzer occluder. The device is made of a Nitinol and polyester fabric mesh and provides occlusion by stenting the duct. Measured angiographically, the narrowest diameter of the ducts ranged from 1.5-5 mm; in six patients pulmonary hypertension was also present. RESULTS: The devices were implanted and complete duct occlusion was demonstrated during follow up in 10 patients. Procedure related difficulties occurred in nine of the 12 cases and led to relatively long procedure and fluoroscopy times (procedure time 50-180 minutes, median 80 minutes; fluoroscopy time 4.9-49 minutes, median 16 minutes). In two infants transcatheter closure could not be achieved and surgical duct ligation had to be carried out. CONCLUSIONS: In small infants with a persistent ductus arteriosus the Amplatzer duct occluder offers an alternative to surgical treatment, but further improvement of the implantation system is necessary before the procedure can be recommended as the treatment of choice.

Alloys↗
PubMed2001

FKBP ligands as novel therapeutics for neurological disorders.

Given their clinical importance for the treatment of acute and chronic neurodegenerative diseases in humans including nerve injuries (e.g. Alzheimer's disease, Parkinson's disease, diabetic neuropathy) a number of different approaches were pursued to obtain selectively acting FK506-binding protein (FKBP) ligands: computational methods and target-oriented screening of natural compound and synthetic product libraries. The resulting monofunctional ligands, which inhibit the peptidyl prolyl cis/trans isomerase activity of FKBPs, highlight the role of these enzymes in neuronal signaling. The exploration of the mechanisms of neuroregenerative and neuroprotective action of some of these compounds is the main focus of ongoing neuropharmaceutical research.

Animals↗