Facial vein terminating in the superficial temporal vein: a case report.
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Aged↗
Biomedical subjects
G Fischer
Publications and source records attributed to G Fischer.
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↗
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↗
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↗
[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↗
[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↗
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↗
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↗
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↗
Immunostains after glutaraldehyde-based tissue fixation.
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Antigens↗
Functional replacement of the essential ESS1 in yeast by the plant parvulin DlPar13.
A functionally Pin1-like peptidyl-prolyl cis/trans isomerase (PPIase(1)) was isolated from proembryogenic masses (PEMs) of Digitalis lanata according to its enzymatic activity. Partial sequence analysis of the purified enzyme (DlPar13) revealed sequence homology to members of the parvulin family of PPIases. Similar to human Pin1 and yeast Ess1, it exhibits catalytic activity toward substrates containing (Thr(P)/Ser(P))-Pro peptide bonds and comparable inhibition kinetics with juglone. Unlike Pin1-type enzymes it lacks the phosphoserine or phosphothreonine binding WW domain. Western blotting with anti-DlPar13 serum recognized the endogenous form in nucleic and cytosolic fractions of the plant cells. Since the PIN1 homologue ESS1 is an essential gene, complementation experiments in yeast were performed. When overexpressed in Saccharomyces cerevisiae DlPar13 is almost as effective as hPin1 in rescuing the temperature-sensitive phenotype caused by a mutation in ESS1. In contrast, the human parvulin hPar14 is not able to rescue the lethal phenotype of this yeast strain at nonpermissive temperatures. These results suggest a function for DlPar13 rather similar to parvulins of the Pin1-type.
Amino Acid Sequence↗
Simultaneous determination of bosentan and its three major metabolites in various biological matrices and species using narrow bore liquid chromatography with ion spray tandem mass spectrometric detection.
An analytical method was developed for the determination of bosentan and its three main metabolites in various matrices and species with focus on robustness. The drug assay involved protein precipitation, followed by liquid-liquid extraction and column switching in combination with narrow bore HPLC-MS-MS. Deuterated analogues of the analytes were used as internal standards. The sample preparation procedure was optimised with respect to minimise the suppression effects from different matrices. The drug and its metabolites could be analysed in plasma, serum, bile, and liver samples from man, dog, and rat with a run cycle time of 10 min. The method used always calibration samples made up in human plasma, whereas quality control samples were prepared in human plasma as well as in the identical matrix as the unknown samples. Calibration graphs for the drug and for the metabolites were linear in the range from 1 or 2 to 2000 or 10,000 ng/ml using a sample volume of 0.25 ml. Mean inter-assay precision and accuracy were 3.0% and 98.4%, respectively. Two additional methods were derived from the main method for the analysis of plasma samples only with focus on reduced manual effort and instrumental run cycle time. The modified methods showed a mean inter-assay precision and accuracy of 5.0% and 99.9% for the method using column-switching, and 3.5% and 98.8% for the method using off-line SPE, respectively. All methods proved to be robust, sensitive, and selective during the analysis of several thousand samples.
Animals↗
Extracorporeal photochemotherapy in the treatment of severe steroid-refractory acute graft-versus-host disease: a pilot study.
Extracorporeal exposure of peripheral blood mononuclear cells to the photosensitizing agent 8-methoxypsoralen and UV-A radiation has been shown to be effective in the treatment of selected diseases mediated by T cells, rejection after solid organ transplantation, and chronic graft-versus-host disease (GVHD). We present 21 patients with a median age of 38 years who developed steroid-refractory acute GVHD grades II to IV after stem cell grafting from sibling or unrelated donors and were referred to extracorporeal photochemotherapy (ECP). Three months after initiation of ECP 60% of patients achieved a complete resolution of GVHD manifestations. Complete responses were obtained in 100% of patients with grade II, 67% of patients with grade III, and 12% of patients with grade IV acute GVHD. Three months after start of ECP complete responses were achieved in 60% of patients with cutaneous, 67% with liver, and none with gut involvement. Adverse events observed during ECP included a decrease in peripheral blood cell counts in the early phase after stem cell transplantation (SCT). Currently, 57% of patients are alive at a median observation time of 25 months after SCT. Probability of survival at 4 years after SCT is 91% in patients with complete response to ECP compared to 11% in patients not responding completely. Our findings suggest that ECP is an effective adjunct therapy for acute steroid-refractory GVHD with cutaneous and liver involvement. However, in patients with acute GVHD grade IV or gut involvement other therapeutic options are warranted.
Acute Disease↗
NMR solution structure of hPar14 reveals similarity to the peptidyl prolyl cis/trans isomerase domain of the mitotic regulator hPin1 but indicates a different functionality of the protein.
The 131-amino acid residue parvulin-like human peptidyl-prolyl cis/trans isomerase (PPIase) hPar14 was shown to exhibit sequence similarity to the regulator enzyme for cell cycle transitions human hPin1, but specificity for catalyzing pSer(Thr)-Pro cis/trans isomerizations was lacking. To determine the solution structure of hPar14 the (1)H, (13)C, and (15)N chemical shifts of this protein have been assigned using heteronuclear two and three-dimensional NMR experiments on unlabeled and uniformly (15)N/(13)C-labeled recombinant protein isolated from Escherichia coli cells that overexpress the protein. The chemical shift assignments were used to interpret the NOE data, which resulted in a total of 1042 NOE restraints. The NOE restraints were used along with 71 dihedral angle restraints and 38 hydrogen bonding restraints to produce 50 low-energy structures. The hPar14 folds into a betaalpha(3)betaalphabeta(2) structure, and contains an unstructured 35-amino acid basic tail N-terminal to the catalytic core that replaces the WW domain of hPin1 homologs. The three-dimensional structures of hPar14 and the PPIase domain of human hPin1 reveal a high degree of conservation. The root-mean-square deviations of the mean atomic coordinates of the heavy atoms of the backbone between residues 38 to 45, 50 to 58, 64 to 70, 81 to 86, 115 to 119 and 122 to 128 of hPar14 were 0.81(+/-0.07) A. The hPar14 model structure provides insight into how this class of PPIases may select preferential secondary catalytic sites, and also allows identification of a putative DNA-binding motif in parvulin-like PPIases.
Amino Acid Sequence↗
Evidence that the substrate backbone conformation is critical to phosphorylation by p42 MAP kinase.
The effect of prolyl bond isomers on the substrate recognition capabilities of various endoproteases may be investigated in a reaction where both cis/trans isomers co-exist. Here we address the question of whether enzyme reactions at the side chain of an amino acid preceding proline proceed through an isomer specific pathway. The proline-directed p42 mitogen-activated protein kinase (ERK2) was used to phosphorylate the serine side chain in Pro-Arg-Ser-Pro-Phe-4-nitroanilide under conditions where different amounts of cis prolyl isomer of the substrate were present. Initial phosphorylation rates were calculated ranging between zero at 100% cis isomer and around 60 pM/min at the equilibrium content of 83.5% trans isomer. In the presence of the peptidyl-prolyl cis/trans isomerase human hFKBP12 (500 nM), cis/trans isomerization proceeds rapidly, permitting the maximal phosphorylation rate to be observed in the dead time of the experiment. Results show that correct signature sequences are not sufficient to render potential substrates reactive to proline-directed enzymatic phosphorylations, but that the conformational state of the peptide bond following serine (threonine) is a critical determinant. Therefore, catalysis by peptidyl-prolyl cis/trans isomerases may add a new level of control to intracellular protein phosphorylations.
Amino Acid Motifs↗
Functional consequences of reduction in NMDA receptor glycine affinity in mice carrying targeted point mutations in the glycine binding site.
We have used site-directed mutagenesis in conjunction with homologous recombination to generate two mouse lines carrying point mutations in the glycine binding site of the NMDAR1 subunit (Grin1). Glycine concentration-response curves from acutely dissociated hippocampal neurons revealed a 5- and 86-fold reduction in receptor glycine affinity in mice carrying Grin1(D481N) and Grin1(K483Q) mutations, respectively, whereas receptor glutamate affinity remained unaffected. Homozygous mutant Grin1(D481N) animals are viable and fertile and appear to develop normally. However, homozygous mutant Grin1(K483Q) animals are significantly lighter at birth, do not feed, and die within a few days. No gross abnormalities in CNS anatomy were detected in either Grin1(D481N) or Grin1(K483Q) mice. Interestingly, in situ hybridization and Western blot analysis revealed changes in the expression levels of NMDA receptor subunits in Grin1(D481N) mice relative to wild type that may represent a compensatory response to the reduction in receptor glycine affinity. Grin1(D481N) mice exhibited deficits in hippocampal theta burst-induced long-term potentiation (LTP) and spatial learning and also a reduction in sensitivity to NMDA-induced seizures relative to wild-type controls, consistent with a reduced activation of NMDA receptors. Mutant mice exhibited normal prepulse inhibition but showed increased startle reactivity. Preliminary analysis indicated that the mice exhibit a decreased natural aversion to an exposed environment. The lethal phenotype of Grin1(K483Q) animals confirms the critical role of NMDA receptor activation in neonatal survival. A milder reduction in receptor glycine affinity results in an impairment of LTP and spatial learning and alterations in anxiety-related behavior, providing further evidence for the role of NMDA receptor activation in these processes.
Animals↗
Chromosomal evolution in Saccharomyces.
The chromosomal speciation model invokes chromosomal rearrangements as the primary cause of reproductive isolation. In a heterozygous carrier, chromosomes bearing reciprocal translocations mis-segregate at meiosis, resulting in reduced fertility or complete sterility. Thus, chromosomal rearrangements act as a post-zygotic isolating mechanism. Reproductive isolation in yeast is due to post-zygotic barriers, as many species mate successfully but the hybrids are sterile. Reciprocal translocations are thought to be the main form of large-scale rearrangement since the hypothesized duplication of the whole yeast genome 10(8) years ago. To test the chromosomal speciation model in yeast, we have characterized chromosomal translocations among the genomes of six closely related species in the Saccharomyces 'sensu stricto' complex. Here we show that rearrangements have occurred between closely related species, whereas more distant ones have colinear genomes. Thus, chromosomal rearrangements are not a prerequisite for speciation in yeast and the rate of formation of translocations is not constant. These rearrangements appear to result from ectopic recombination between Ty elements or other repeated sequences.
Chromosomes, Fungal↗
Platelet glycoprotein Ia gene dimorphism alpha2-807 in malignant arrhythmia in coronary artery disease.
It has been shown recently that the variable expression of the platelet collagen receptor integrin alpha2beta1 predisposes to thrombotic risk on the one hand and hemorrhagic risk on the other hand. The level of expression of the integrin alpha2beta1 is genetically controlled and associated with the alpha2-807 dimorphism. The expression level of this platelet collagen receptor may play a central role in the rapidly evolving coronary artery lesions that lead to malignant arrhythmia and sudden cardiac death. We studied allelic frequencies of the alpha2-807 dimorphism for their relation as a risk factor for malignant arrhythmia in a well-defined subgroup of patients with coronary artery disease. We compared allelic frequencies (by sequence specific primer polymerase chain reaction) of the dimorphism that is associated with integrin alpha2beta1 levels in 94 Caucasoid survivors of sudden cardiac death with a matched group of 106 patients with coronary artery disease without sudden cardiac death. Gene frequencies in the patient groups did not differ and were similar to those in the general population represented by 217 healthy individuals. There was no overrepresentation of an allele in any group. The inherited dimorphism that is associated with the levels of platelet integrin alpha2beta1 is not associated with malignant arrhythmia in coronary artery disease patients.
Adult↗