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Biomedical subjects

A Studer

Publications and source records attributed to A Studer.

At least 19 recordsLinked to original sources

Feasibility and safety of norepinephrine-induced arterial hypertension in acute ischemic stroke.

The feasibility and safety of induced arterial hypertension (10 to 20% of the initial value) in the acute phase of ischemic stroke were retrospectively evaluated in 34 patients treated with norepinephrine (NE) for a median of 26 hours. Maximal variability of systolic blood pressure during NE application was within 15% of the target values. Cardiac arrhythmia occurred in one patient, and intracerebral hemorrhage occurred in two patients (fatal in one and asymptomatic in the other). The authors conclude that induced arterial hypertension is feasible and safe in patients with acute stroke.

Acute Disease↗

Mechanism of ischemic infarct in spontaneous carotid dissection.

BACKGROUND AND PURPOSE: It is unclear whether stroke in patients with spontaneous dissection of the cervical internal carotid artery (ICAD) is due to thromboembolism or impaired hemodynamics. This study investigated the mechanism of stroke in ICAD by examining brain imaging and cerebrovascular findings of such patients. METHODS: We retrospectively evaluated the prospectively collected brain CT, MR, and ultrasound findings of 141 consecutive patients with 143 ICADs causing ischemic stroke. Eleven patients were not included because they had an inappropriate temporal bone window (n=6) or were treated with thrombolysis (n=5). Thus, the data of 130 patients (76 men, 54 women) with 131 ICADs were analyzed. RESULTS: All patients had territorial infarcts; 6 patients (5%) also had border-zone infarct patterns. Territorial infarcts affected the middle cerebral artery (MCA) in 130 of 131 cases (99%) and the anterior cerebral artery (ACA) in 1 case (1%). Additional vascular territories were affected in 8 patients with MCA infarcts (ACA, n=5 [4%]; posterior cerebral artery, n=3 [2%]). The pattern (hemodynamic versus thromboembolic) and extent of infarction were not influenced by vascular findings (MCA stenosis or occlusion, ACA occlusion, degree of obstruction in the dissected ICA, pattern of cross-flow in 115 patients with >80% ICA stenosis or occlusion). CONCLUSIONS: This study suggests that thromboembolism, not hemodynamic infarction, is the essential stroke mechanism in ICAD.

Brain Ischemia↗

Ischemic infarct involving all arterial territories of the thalamus.

Ischemic infarcts of the thalamus involve one or two of its four arterial territories that are usually supplied by the posterior cerebral (PCA) and the posterior communicating (PCoA) arteries. We report a patient who suffered ischemic infarcts in all arterial territories of the right thalamus. Magnetic resonance (MR) angiography showed an occlusion of the right PCA and failed to visualize a PCoA. We assume that the absence of a relevant thalamic blood supply deriving from the PCoA enabled PCA occlusion to cause infarcts in all thalamic territories.

Arteries↗

Recanalisation of cerebral venous thrombosis.

OBJECTIVE: To investigate recanalisation in the first 12 months after cerebral venous thrombosis. METHODS: 33 consecutive patients presenting with cerebral venous thrombosis were enrolled in the study. Diagnosis was made by magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) or catheter angiography. Patients were initially treated with intravenous heparin. Warfarin was given for at least four months. Cerebral MRI and MRV were done at four months and repeated after 12 months if venous thrombosis persisted. Outcome was evaluated by the Rankin scale at 12 months. RESULTS: Outcome at 12 months was good, with a median modified Rankin scale score of 0 (range 0 to 2); 27 patients (82%) had no residual deficits. No patient suffered recurrent cerebral venous thrombosis, deep vein thrombosis, or pulmonary embolism during follow up. After four months, all deep cerebral veins and cavernous sinuses, 94% of superior sagittal sinuses, 80% of straight sinuses, 73% of jugular veins, 58% of transverse sinuses, and 41% of sigmoid sinuses had recanalised. No further recanalisation was observed thereafter. CONCLUSIONS: The results suggest that recanalisation only occurs within the first four months following cerebral venous thrombosis and not thereafter, irrespective of oral anticoagulation.

Adult↗

Carotid dissection with and without ischemic events: local symptoms and cerebral artery findings.

OBJECTIVE: To study whether spontaneous dissections of the cervical internal carotid artery dissection (ICAD) with and without ischemia of the brain or retina differ in the prevalence of vascular risk factors, local neurologic signs and symptoms, and stenoses and occlusions of the cerebral arteries. METHODS: The authors prospectively studied 181 consecutive patients with 200 ICAD. Diagnosis was based on ultrasonography and MRI or catheter angiography. Vascular risk factors, presenting local (headache, neck pain, Horner syndrome, pulsatile tinnitus, cranial nerve palsy on the side of the ICAD) and ischemic signs and symptoms, and ultrasonographic findings in the carotid and basal cerebral arteries were evaluated. RESULTS: ICAD with ischemic events (n = 145) had a higher prevalence of hypercholesterolemia (p < 0.05), >80% stenoses and occlusions of the ICA (p < 0.0001), and intracranial obstructions (p < 0.001). ICAD without ischemic events (n = 55) had a higher prevalence of Horner syndrome (p < 0.001), cranial nerve palsy (p < 0.01), and normal ICA findings (p < 0.0001). CONCLUSIONS: These data suggest that ICAD causing high-grade stenosis and occlusion are more likely to lead to intracranial obstructions and cerebral or retinal ischemic events. Conversely, ICAD without luminal narrowing cause more local signs and symptoms.

Adolescent↗

Radical transfer hydrosilylation/cyclization using silylated cyclohexadienes.

[reaction: see text] A new method for mild metal-free hydrosilylation is described. Silylated cyclohexadienes are used as radical transfer hydrosilylating reagents for various double and triple bonds. A trialkylsilane is transferred from a cyclohexadiene moiety to an alkene. The hydrosilylation can be combined with a C-C bond formation as shown for the preparation of silylated cycloalkanes from the corresponding dienes.

Journal Article↗

The persistent radical effect in organic synthesis.

The persistent radical effect (PRE) is a principle that explains the highly selective cross-coupling between a persistent and a transient radical when both species are formed at equal rates. In this paper, the concept of the PRE is briefly discussed. Applications of the PRE in different reactions such as Co-mediated radical addition and cyclization reactions, Kharasch reactions catalyzed by transition metals, the Barton reaction, and our nitroxide-mediated tin-free radical cyclizations are presented. Some future perspectives for the PRE in organic synthesis are also provided.

Journal Article↗

Factors influencing the C-O bond homolysis of alkoxyamines: effects of H-bonding and polar substituents.

The synthesis of various new trialkylhydroxylamines is described. The rate constant of the C-O bond cleavage of these new alkoxyamines has been measured. For example, C-O bond homolysis rates in a series of para-substituted TEMPO-styryl compounds TEMPO-CH(CH3)C6H5X 1a (p-MeO), 1b (p-Me), 1d (p-H), 1e (p-Br), and 1f (p-MeO2C) are presented. Furthermore, rate constants for the C-O bond cleavage of alpha-heteroaryl-substituted secondary alkoxyamines are discussed. A correlation by which the rate constant for the C-O bond cleavage of TEMPO-derived alkoxyamines can be predicted from the C-H BDEs of the corresponding alkanes is presented. Solvent effects as well as the effect of camphorsulfonic acid on the rate of the C-O bond homolysis are discussed. Finally, EPR and kinetic evidence show that alkoxyamines derived from nitroxides which are capable of intramolecular H-bonding undergo C-O bond cleavage faster than the corresponding non-H-bond-forming analogues.

Journal Article↗

Chloromethane: tetrahydrofolate methyl transfer by two proteins from Methylobacterium chloromethanicum strain CM4.

The cmuA and cmuB genes are required for growth of Methylobacterium chloromethanicum strain CM4 with chloromethane as the sole carbon source. While CmuB was previously shown to possess methylcobalamin:tetrahydrofolate methyltransferase activity, sequence analysis indicated that CmuA represented a novel and so far unique two-domain methyltransferase/corrinoid-binding protein involved in methyl transfer from chloromethane to a corrin moiety. CmuA was purified from wild-type M. chloromethanicum strain CM4 and characterized as a monomeric, cobalt-containing and zinc-containing enzyme of molecular mass 67 kDa with a bound vitamin B12 cofactor. In combination, CmuA and CmuB proteins catalyze the in vitro transfer of the methyl group of chloromethane to tetrahydrofolate, thus affording a direct link between chloromethane dehalogenation and core C1 metabolism of Methylobacterium. Chloromethane dehalogenase activity in vitro is limited by CmuB, as formation of methyltetrahydrofolate from chloromethane displays apparent Michaelis-Menten kinetics with respect to methylated CmuA, with an apparent Km of 0.27 microM and a Vmax of 0.45 U x mg(-1). This contrasts with sequence-related systems for methyl transfer from methanogens, which involve methyltransferase and corrinoid protein components in well-defined stoichiometric ratios.

Bacterial Proteins↗

Chloromethane utilization gene cluster from Hyphomicrobium chloromethanicum strain CM2(T) and development of functional gene probes to detect halomethane-degrading bacteria.

Hyphomicrobium chloromethanicum CM2(T), an aerobic methylotrophic member of the alpha subclass of the class proteobacteria, can grow with chloromethane as the sole carbon and energy source. H. chloromethanicum possesses an inducible enzyme system for utilization of chloromethane, in which two polypeptides (67-kDa CmuA and 35-kDa CmuB) are expressed. Previously, four genes, cmuA, cmuB, cmuC, and purU, were shown to be essential for growth of Methylobacterium chloromethanicum on chloromethane. The cmuA and cmuB genes were used as probes to identify homologs in H. chloromethanicum. A cmu gene cluster (9.5 kb) in H. chloromethanicum contained 10 open reading frames: folD (partial), pduX, orf153, orf207, orf225, cmuB, cmuC, cmuA, fmdB, and paaE (partial). CmuA from H. chloromethanicum (67 kDa) showed high identity to CmuA from M. chloromethanicum and contains an N-terminal methyltransferase domain and a C-terminal corrinoid-binding domain. CmuB from H. chloromethanicum is related to a family of methyl transfer proteins and to the CmuB methyltransferase from M. chloromethanicum. CmuC from H. chloromethanicum shows identity to CmuC from M. chloromethanicum and is a putative methyltransferase. folD codes for a methylene-tetrahydrofolate cyclohydrolase, which may be involved in the C(1) transfer pathway for carbon assimilation and CO(2) production, and paaE codes for a putative redox active protein. Molecular analyses and some preliminary biochemical data indicated that the chloromethane utilization pathway in H. chloromethanicum is similar to the corrinoid-dependent methyl transfer system in M. chloromethanicum. PCR primers were developed for successful amplification of cmuA genes from newly isolated chloromethane utilizers and enrichment cultures.

Amino Acid Sequence↗

Stereoselective radical aryl migration from silicon to carbon.

Highly diastereoselective radical 1,5 phenyl migration reactions from silicon in diarylsilyl ethers to various C-centered radicals to form the corresponding 3-phenylated alcohols are described. Functionalized aryl groups can also be transferred. The effect of the variation of the attacking radical on the aryl transfer reaction is discussed. Best results are obtained for the phenyl migration to nucleophilic secondary alkyl radicals, where high yields (up to 81%) and high selectivities (up to 95% ds) have been obtained. The mechanism of the process is discussed and a model to explain the stereochemical outcome of the reaction is presented. Finally, stereoselective 1,4 aryl migration reactions from Si to C, including a new method for the alpha-arylation of esters, are presented.

Alcohols↗

Synthesis of biaryls by intramolecular radical aryl migration from silicon to carbon

A new method for the preparation of biaryls via intramolecular 1,5 aryl migration reaction from silicon in silyl ethers to aryl radicals is presented. Various readily available diphenylsilyl ethers can be used as substrates in this reaction. Functionalized aryl groups can also be transferred. The analogous 1,4 aryl migration reaction is less efficient.

Journal Article↗

[Guideline for the diagnosis of postmenopausal bleeding. PMPB Working Group of the SGGG].

2.1. History and clinical-gynecological investigation including a Pap smear are the first step in the clarification. The history should make sure if there is in fact bleeding from the genital and not from the urological or the intestinal region. Drug intake should be recorded, and risk factors for the development of endometrial carcinoma should be considered. This will not affect further investigation. The clinical-gynecological investigation should prove the source of postmenopausal bleeding according to the anatomical site--uterine, infra-, or suprauterine. The causes of infrauterine bleeding may easily be diagnosed by means of inspection of the external genitalia and further by using a speculum. The causes of uterine bleeding are of major importance. Cytology and colposcopy, supported by bimanual investigation, exclude cervical carcinoma as a cause of bleeding. Atypical endometrial cells on the cytological smear arouse suspicion of endometrial carcinoma. 2.2. Transvaginal sonography (TVS) is the next step if the above-mentioned investigations are negative. Both adnexa should always be investigated and the findings sonographically documented, so that solid cystic masses in the adnexal area can be better identified as suprauterine causes of postmenopausal bleeding. Then the uterus should be investigated. Further procedures are decided from the results of measurement of the longitudinal section of the endometrium at the level of maximum endometrial thickness. If the endometrial thickness is _<4 mm, an observant attitude can be assumed. After 3 months the patient should be controlled against using TVS. If bleeding recurs or the endometrial thickness is >4 mm on TVS, the procedure given in subparagraph 2.3 should be followed. In case the endometrial thickness is >4mm or not measurable, a histomorphological investigation according to subparagraph 2.3 should be performed. In such cases, saline infusion sonohysterography(SIS) is useful as a simple method to supplement TVS. It can aid in the decision making as to which further, more invasive measures should be taken (endometrial biopsy/hysteroscopic resection). Computerized tomography or magnetic resonance imaging are, as a rule, not indicated in patients with postmenopausal bleeding. 2.3. A definite diagnosis is possible only on the basis of a histological investigation. If TVS or SS show evidence of a polypoid state, removal under hysteroscopic control is the diagnostic method of choice. In cases of symmetrical or asymmetrical thickening of the endometrium on SIS, a less invasive biopsy may be sufficient. If the biopsy specimen does not yield representative diagnostic material, one should proceed as described above. A fractionated curettage should as a rule not be performed solely, but in combination with hysteroscopy.

Adult↗

A corrinoid-dependent catabolic pathway for growth of a Methylobacterium strain with chloromethane.

Methylobacterium sp. strain CM4, an aerobic methylotrophic alpha-proteobacterium, is able to grow with chloromethane as a carbon and energy source. Mutants of this strain that still grew with methanol, methylamine, or formate, but were unable to grow with chloromethane, were previously obtained by miniTn5 mutagenesis. The transposon insertion sites in six of these mutants mapped to two distinct DNA fragments. The sequences of these fragments, which extended over more than 17 kb, were determined. Sequence analysis, mutant properties, and measurements of enzyme activity in cell-free extracts allowed the definition of a multistep pathway for the conversion of chloromethane to formate. The methyl group of chloromethane is first transferred by the protein CmuA (cmu: chloromethane utilization) to a corrinoid protein, from where it is transferred to H4folate by CmuB. Both CmuA and CmuB display sequence similarity to methyltransferases of methanogenic archaea. In its C-terminal part, CmuA is also very similar to corrinoid-binding proteins, indicating that it is a bifunctional protein consisting of two domains that are expressed as separate polypeptides in methyl transfer systems of methanogens. The methyl group derived from chloromethane is then processed by means of pterine-linked intermediates to formate by a pathway that appears to be distinct from those already described in Methylobacterium. Remarkable features of this pathway for the catabolism of chloromethane thus include the involvement of a corrinoid-dependent methyltransferase system for dehalogenation in an aerobe and a set of enzymes specifically involved in funneling the C1 moiety derived from chloromethane into central metabolism.

Amino Acid Sequence↗