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Biomedical subjects

R Hermann

Publications and source records attributed to R Hermann.

At least 91 records · Page 5Linked to original sources

Physicians' attitudes regarding Down syndrome.

We conducted a representative survey to obtain current information about attitudes of pediatricians, child neurologists, and pediatric surgeons in Hungary regarding Down syndrome. The findings are compared to those of a similar study from Canada. In the treatment of mentally handicapped newborns, none of the Hungarian doctors would choose active euthanasia; only a few percent would perform passive euthanasia. Hungarian doctors give priority to the hospital-based ethical committee in the decision-making process regarding the treatment versus nontreatment of a newborn with major congenital anomalies. In contrast to the Canadians, only a few doctors would discuss this question with parents and nurses. Most Hungarian physicians are not aware of legal regulations in this field. These attitudes can be explained by religious and cultural traditions different from the Canadian and Western European standards. The Hungarian medical community, like other Eastern European countries, is much more authoritative than the Canadian system. Furthermore, the appropriate legal regulations are not yet properly codified.

Adult↗

Synthesis and antibacterial activity of derivatives of the glycopeptide antibiotic A-40926 and its aglycone.

Starting from the antibiotic A-40926 and the aglycone of A-40926 a series of compounds were prepared by modifying the free functionalities. Their antimicrobial activity was determined, particularly against Neisseria gonorrhoeae, against which A-40926, unlike other natural glycopeptides, is active. Improved in vivo activity was displayed by the monomethyl ester of A-40926 esterified at the carboxyl group of the N-acylamino-glucuronyl moiety.

Animals↗

Preserved merosin M-chain (or laminin-alpha 2) expression in skeletal muscle distinguishes Walker-Warburg syndrome from Fukuyama muscular dystrophy and merosin-deficient congenital muscular dystrophy.

The merosin M-chain (or laminin-alpha 2) is one of three subunits of laminin-2 which is highly expressed in striated muscle and peripheral nerve. Complete lack of laminin-alpha 2 expression in skeletal muscle is the hallmark of one form of congenital muscular dystrophy which is characterized by dysmyelination of the central nervous system (CNS), links to chromosome 6q2 and is common among Caucasians. Laminin-alpha 2 expression was also found to be significantly reduced in Fukuyama congenital muscular dystrophy which links to chromosome 9q3. We report consistently preserved laminin-2 expression, including laminin-alpha 2, as detected by immunofluorescence in skeletal muscle from five patients with Walker-Warburg syndrome which is characterized by congenital muscular dystrophy and, in addition, type II lissencephaly or pachygyria, defective CNS myelination, and ocular dysgenesis. These findings show that in spite of partial phenotypic overlap between Fukuyama CMD and Walker-Warburg syndrome the two disorders are nosologically separate disease entities. They also exclude that Walker-Warburg syndrome is allelic to the common form of congenital muscular dystrophy with laminin-alpha 2 deficiency.

Antibodies↗

Double-layer coating for high-resolution low-temperature scanning electron microscopy.

Specimen damage caused by mass loss due to electron beam irradiation is a major limitation in low-temperature scanning electron microscopy of bulk specimens. At high primary magnifications (e.g., 100,000 x) a hydrated sample is usually severely damaged after one slow scan (about 3000 e-nm-2). The consequences of this beam damage are significantly reduced by coating the frozen-hydrated sample with a 5-10-nm-thick carbon layer. Since this layer covers up surface details, the sample is first unidirectionally shadowed with a thin heavy metal layer (e.g., 2 nm of platinum) that is in close contact with the biological surface (double layer coating). This heavy metal layer can be visualized in field-emission scanning electron microscopy with the material-dependent backscattered electron signal. The method allows for routine observation of large frozen-hydrated samples. By use of an in-lens field-emission SEM and a sensitive backscattered electron detector, structural information comparable to that obtained with the transmission electron microscopy freeze-fracture replica technique can be achieved.

Carbon↗

The imperative of outcome assessment in psychiatry.

This report describes the current conceptualization of outcome assessment in psychiatry and focuses on how assessment instruments can be built into psychiatric facility-based practice. First, the domains of clinical assessment are outlined, with an emphasis on three elements: level of psychiatric symptoms, clinical functioning, and patient satisfaction. Examples of outcome instruments then are provided as well as the elements of their successful implementation. Finally, the value of linking outcome assessment to data on patient characteristics and service utilization are discussed in order to gain insight into the relationship between treatment and outcome. The clinical, fiscal, and regulatory imperatives emerging for outcome assessment call for its demystification and widespread application.

Hospitals, Psychiatric↗

Immuno-gold-labelling of CUT-1, CUT-2 and cuticlin epitopes in Caenorhabditis elegans and Heterorhabditis sp. processed by high pressure freezing and freeze-substitution.

CUT-1 and CUT-2 are two distinct protein components of cuticlin, the insoluble residue of the cuticles of nematodes. In previous experiments of gold-immuno-labelling on sections of chemically fixed Caenorhabditis elegans, CUT-1 and CUT-2 epitopes were specifically lost. Cryo-immobilization of C. elegans under high pressure followed by freeze-substitution, however, resulted in a good preservation of these antigenic sites and of the ultrastructure of the worms. The entomopathogenic nematode Heterorhabditis sp. processed by the same cryopreparation protocol has shown a strong reactivity with anti-sera raised against CUT-1, CUT-2 and against the whole cuticlin residue of C. elegans. The localization of these epitopes was conserved across the two species.

Animals↗

Pyogenic hepatic abscess: results of current management.

From 1980 to 1991, 56 cases of pyogenic liver abscess were treated at the Cleveland Clinic. The most frequently used treatment was percutaneous catheter drainage of the abscess under computed tomography (CT) guidance (39 patients), followed by CT-guided aspiration without catheter drainage (10 patients). Six patients were initially treated by open operative drainage; another five were operated upon after CT guided drainage had failed. One patient with advanced pancreatic cancer was treated with antibiotics only. The overall mortality rate was 12.5% (7/56). It is clear that the preferred method of treatment for pyogenic hepatic abscess is now CT guided catheter drainage. Operative drainage is reserved for patients who fail to respond to percutaneous drainage or in whom surgery is indicated for other purposes. Aspiration without catheter drainage is a modality that needs further evaluation to define its indications.

Adult↗

[Dealing with adverse effects in phase I trials].

A questionnaire was completed by members of the Association for Applied Human Pharmacology (AGAH) in Germany with the aim of assessing the present situation regarding management of adverse events (AEs). A recommendation for documentation and evaluation of AEs was to be presented after discussion within the AGAH. The questionnaire referred to general questions, documentation of AEs, intensity and causality, coding and serious adverse events (SAE). Percentage return of answered questionnaires was 54.5%. Of the people contacted, 9.1% said they did not carry out phase I trials, and 36.4% did not reply. The survey in the 24 institutes convers an estimated 11200 volunteers who are included in clinical trials each year. The discussion about commencement of AEs documentation and its duration was contentious. Of the respondents, 38.5% AEs only after application of the trial substance, while 61.5% also make a documentation during the pre-trial phase (recruitment, pre-examination, supervision before application). 13.6% document only up to the post-examination and half of those questioned until AE symptoms have disappeared. 22.7% document until disappearance of symptoms only when AEs are definitely associated with the trial substance. A 3-point scale is used by most people questioned for evaluation of the intensity of an AE. Evaluation of causality, mostly undertaken by the examining physician and the director of the clinical trial, is not carried out homogeneously. There are several categories, but four classifications are most commonly used. 62.5% of codings of AEs are carried out according to the WHO Adverse Reaction Terminology.(ABSTRACT TRUNCATED AT 250 WORDS)

Adverse Drug Reaction Reporting Systems↗

[Diffuse thymus hyperplasia following chemotherapy for nodular sclerosing Hodgkin lymphoma].

A persistent or new mass in the anterior mediastinum after chemotherapy for mediastinal lymphoma poses a major differential diagnostic problem. Misinterpretation as a persistent or recurrent tumor may lead to additional unnecessary and potentially harmful therapy. Benign mediastinal tumors, albeit very rare, need confirmation by biopsy since they cannot be distinguished by radiological methods from persistence or relapse of lymphoma. We present a case report of a patient with diffuse thymic hyperplasia following successful chemotherapy for nodular sclerosing Hodgkin's disease, with a review of the literature.

Adult↗

Microbes, enzymes and genes involved in dichloromethane utilization.

Dichloromethane (DCM) is efficiently utilized as a carbon and energy source by aerobic, Gram-negative, facultative methylotrophic bacteria. It also serves as a sole carbon and energy source for a nitrate-respiring Hyphomicrobium sp. and for a strictly anaerobic co-culture of a DCM-fermenting bacterium and an acetogen. The first step of DCM utilization by methylotrophs is catalyzed by DCM dehalogenase which, in a glutathione-dependent substitution reaction, forms inorganic chloride and S-chloromethyl glutathione. This unstable intermediate decomposes to glutathione, inorganic chloride and formaldehyde, a central metabolite of methylotrophic growth. Genetic studies on DCM utilization are beginning to shed some light on questions pertaining to the evolution of DCM dehalogenases and on the regulation of DCM dehalogenase expression. DCM dehalogenase belongs to the glutathione S-transferase supergene family. Analysis of the amino acid sequences of two bacterial DCM dehalogenases reveals 56% identity, and comparison of these sequences to those of glutathione S-transferases indicates a closer relationship to class Theta eukaryotic glutathione S-transferases than to a number of bacterial glutathione S-transferases whose sequences have recently become available. dcmA, the structural gene of the highly substrate-inducible DCM dehalogenase, is carried in most DCM utilizing methylotrophs on large plasmids. In Methylobacterium sp. DM4 its expression is governed by dcmR, a regulatory gene located upstream of dcmA, dcmR encodes a trans-acting factor which negatively controls DCM dehalogenase formation at the transcriptional level. Our working model thus assumes that the dcmR product is a repressor which, in the absence of DCM, binds to the promoter region of dcmA and thereby inhibits initiation of transcription.

Amino Acid Sequence↗

Pharmacokinetics of naftopidil, a novel anti-hypertensive drug, in patients with hepatic dysfunction.

The pharmacokinetics of naftopidil, a novel alpha-1 adrenoceptor-blocking antihypertensive, were investigated in ten patients (9M/1F) with hepatic dysfunction after oral administration (50 mg, tablet) and after an intravenous infusion of 5.0 mg over 2 minutes. Results were compared to a control group of 12 healthy subjects (6M/6F) of a previous investigation, which was carried out according to the identical study protocol. The pharmacokinetic parameters obtained for the i.v. administration were comparable in both groups (half life 3.6 +/- 3.4 hours in liver-impaired subjects versus 3.3 +/- 2.1 hours in controls; clearance 11.9 +/- 4.7 ml/minute/kg versus 11.0 +/- 1.6 ml/minute/kg). Following oral administration the plasma levels and half-life times of naftopidil were significantly increased in liver impairment (t1/2 16.6 +/- 19.3 hours versus 5.4 +/- 3.2 hours in controls; P = 0.012). Mean values for the absolute bioavailability in patients with hepatic dysfunction were significantly higher (mean 75%, median 53%, range 13.4-211.0%) compared to healthy subjects (mean 17%, median 16%, range 6.7-29.6%, P = 0.001). Reduction of functional hepatic blood flow in chronic liver disease or, as evidenced in one case as a consequence of shunt surgery, is the probable cause of the observed alteration in naftopidil kinetics. This phenomenon occurred only following the oral 50 mg dose whereas the intravenous 5 mg dose obviously still could be normally handled. Naftopidil demethylation and hydroxylation were both less and non-uniformly affected. The pharmacokinetic findings suggest that in patients with severe hepatic impairment or evidence for marked changes in hepatic blood flow the dose of naftopidil may require adjustment to the lower end of the therapeutic range and/or may be limited to once daily. However, before definite conclusions can be drawn, further steady-state studies are required. Despite the pharmacokinetic discrepancies no difference in drug tolerability was seen between patients and healthy subjects.

Administration, Oral↗

Effects of flupirtine coadministration on phenprocoumon plasma concentrations and prothrombin time.

The influence of flupirtine, a non-opioid, centrally acting analgesic agent on phenprocoumon plasma levels and protein binding as well as prolongation of prothrombin time has been investigated in 12 healthy male volunteers. Subjects received phenprocoumon 1.5 mg od over 28 days. From day 15 to 28 oral flupirtine 100mg tid was added. Phenprocoumon plasma levels and prothrombin time (Quick time), measured at trough before the morning drug intake, were chosen as primary pharmacokinetic and pharmacodynamic variables. In addition, phenprocoumon protein binding and the eudismic ratio of phenprocoumon were determined. The mean values from data obtained on day 12 to 15 (i.e. measurements under phenprocoumon alone) and the mean values from those data obtained from day 25 to 28 (i.e. under comedication with flupirtine) were subject to subsequent statistical procedures. Phenprocoumon plasma concentrations came to 1.38 +/- 0.28 micrograms/ml on day 12 to 15 and were not significantly altered under flupirtine coadministration with 1.48 +/- 0.36 micrograms/ml on day 25 to 28 (95% confidence interval: 1.02-1.11, point estimator: 1.06). The average Quick time came to 68 +/- 10% on day 12-15 and 73 +/- 15% on day 25-28. The nonparametric 95%-confidence interval for the ratio ranged between 0.96 and 1.14, the point estimator was determined to 1.04. Protein binding of phenprocoumon was determined to 88.8% +/- 0.5 on day 14 and to 88.9 +/- 0.5% on day 28. The ratio of S/R-phenprocoumon was 1:0.84 on day 14 and 1:0.84 on day 28. These results do not provide any evidence for a pharmacokinetic and/or pharmacodynamic interaction between flupirtine and phenprocoumon.

Administration, Oral↗

Dichloromethane as the sole carbon source for an acetogenic mixed culture and isolation of a fermentative, dichloromethane-degrading bacterium.

Dichloromethane (DCM) is utilized by the strictly anaerobic, acetogenic mixed culture DM as a sole source of carbon and energy for growth. Growth with DCM was linear, and cell suspensions of the culture degraded DCM with a specific activity of 0.47 mkat/kg of protein. A mass balance of 2 mol of chloride and 0.42 mol of acetate per mol of DCM was observed. The dehalogenation reaction showed similar specific activities under both anaerobic and aerobic conditions. Radioactivity from [14C]DCM in cell suspensions was recovered largely as 14CO2 (58%), [14C]acetate (23%), and [14C]formate (11%), which subsequently disappeared. This suggested that formate is a major intermediate in the pathway from DCM to acetate. Efforts to isolate from culture DM a pure culture capable of anaerobic growth with DCM were unsuccessful, although overall acetogenesis and the partial reactions are thermodynamically favorable. We then isolated bacterial strains DMA, a strictly anaerobic, gram-positive, endospore-forming rod, and DMB, a strictly anaerobic, gram-negative, endospore-forming homoacetogen, from culture DM. Both strain DMB and Methanospirillum hungatei utilized formate as a source of carbon and energy. Coculture of strain DMA with either M. hungatei or strain DMB in solid medium with DCM as the sole added source of carbon and energy was observed. These data support a tentative scheme for the acetogenic fermentation of DCM involving interspecies formate transfer from strain DMA to the acetogenic bacterium DMB or to the methanogen M. hungatei.

Bacteria, Anaerobic↗

Progress in scanning electron microscopy of frozen-hydrated biological specimens.

Modern scanning electron microscopy yields structural information down to 2 to 5 nm from thin, beam transparent biological specimens. This paper examines the possibilities of garnering this level of structural information from bulk, frozen-hydrated samples. Freeze-fractured, frozen-hydrated yeast cells, frequently taken as a yardstick to monitor progress in low-temperature scanning electron microscopy, have been used to optimize both metal shadowing methods and observation parameters (e.g. accelerating voltage, electron beam irradiation of the specimen). Uncoated frozen-hydrated yeast cells do not change electrically at an accelerating voltage of 30 kV. Increasing charging effects are however observed with decreasing accelerating voltages. Very thin metal films are therefore used for specimen coating to localize and enhance the specific secondary electron signal. Planar-magnetron sputtering of a 1 nm metal layer provides high resolution secondary electron images, at 30 kV, of freeze-fractured, frozen-hydrated yeast cells in an in-lens field-emission scanning electron microscope. Structural information comparable to that of transmission electron microscopy of freeze-fractures is attained. Planar-magnetron sputtering of either chromium, tungsten or platinum results in essentially the same information density (smallest visible significant structural detail). Frozen-hydrated samples are very beam sensitive and have to be observed under minimum dose conditions.

Cryopreservation↗

Towards high resolution SEM of biological objects.

The major task of biological high resolution SEM and TEM is to provide structural information for correlating structure and function. It is the only methodology with the inherent power needed to observe structures down to molecular dimensions within the context of complex biological systems. Specimen preparation and imaging techniques should therefore be directed towards the preservation and imaging of the smallest significant details in order to fully exploit this unique, integrating feature of biological electron microscopy, complementing the progress of the techniques used in cell biology, biochemistry, and molecular biology.

Animals↗

Interference with protein binding at AP2 sites by sequence-specific methylation in the late E2A promoter of adenovirus type 2 DNA.

The in vitro methylation of the +6, +24, and -215 located 5'-CCGG-3' sequences in the late E2A promoter of adenovirus type 2 (Ad2) DNA abrogates promoter function. 5-Methyldeoxycytidine (5-mC) at positions +6 and +24 in both or either of the two DNA complements in the late E2A promoter abolishes the formation of a high-molecular-mass DNA-protein complex that is essential for promoter function. The formation of this complex can be competed for by an oligodeoxyribonucleotide with a consensus AP2 sequence, but not by AP1, AP3, or CREB sequences. The AP2 sites comprise the +6 and +24 located 5'-CCGG-3' sequences in the late E2A promoter; the AP1, AP3 and CREB sequences are in their immediate vicinity. Methylation of either the +6 or the +24 5' -CCGG-3' sequence also compromises formation of the DNA-protein complex. A 40 nucleotide pair oligodeoxyribonucleotide encompassing the -215 5' -CCGG-3' site in the late E2A promoter can also form DNA-protein complexes which is not affected by the introduction of a 5-mC residue in the -215 position. The data suggest that the AP2 protein together with other proteins is involved in the generation of a transcription-activating complex with the late E2A promoter of Ad2 DNA, and the formation of this complex is completely abolished when both the +6 and +24 5'-CCGG-3' sequences are methylated.

Adenovirus Early Proteins↗