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R Hoffmann

Publications and source records attributed to R Hoffmann.

At least 19 recordsLinked to original sources
PubMed2002

[Impairment of ventilatory parameters and exercise capacity in patients with pulmonary hypertension and chronic heart insufficiency].

BACKGROUND AND OBJECTIVE: Chronic heart failure often coincides with secondary pulmonary hypertension. In this study the influence of pulmonary hypertension on exercise capacity and ventilatory parameters in patients with chronic heart failure was examined. PATIENTS AND METHODS: 21 patients with chronic heart failure (six women, 15 men, mean age 55 +/- 10 years) and a left ventricular ejection fraction of 25 % +/- 5 % were studied by right heart catheterization, bodyplethysmography including carbonmonoxide diffusion testing and spiroergometry. Seven patients suffered from ischemic and 14 patients from dilative cardiomyopathy. Pulmonary hypertension (defined as pulmonary artery mean pressure > 25 mmHg) was found in ten patients. RESULTS: Patients with pulmonary hypertension showed a reduced vital capacity (75 % +/- 20 % of normal values vs. 93 % +/- 14 % of normal values, p < 0.001), a lower forced expiratory volume in one second (FEV1 68 % +/- 21 % of normal values vs. 91 % +/- 15 % of normal values, p < 0.001), and a reduced carbonmonoxide-diffusing capacity (58 % +/- 21 % vs. 77 % +/- 21 %, p < 0.001) compared to patients without pulmonary hypertension. Mean expiratory flow at 25 % and 75 % of the exspiration time was lower in patients with pulmonary hypertension (30 % +/- 13 % vs. 50 % +/- 29 % and 62 % +/- 25 % vs. 81 % +/- 20 %, each p < 0.05). In patients with pulmonary hypertension, the flow-volume diagram characteristically showed signs of "small airway disease". Spiroergometry revealed a significantly lower maximum oxygen-uptake (12.5 +/- 2.1 vs. 15.2 +/- 4.1 ml/min/kg, p < 0.05), oxygen-uptake at the anaerobic threshold (9.7 +/- 1.6 vs. 12.0 +/- 3.0 ml/min/kg, p < 0.05), carbon dioxide ventilatory efficiency (EqCO2 38 +/- 9 vs. 31 +/- 3, p < 0.05) and ventilatory reserve (39 % +/- 22 % vs 51 % +/- 21 %, p < 0.05) in patients with pulmonary hypertension. CONCLUSION: In patients with chronic heart failure the presence of pulmonary hypertension leads to a reduction of exercise capacity and impaired ventilatory parameters. Lung functional testing reveals bronchial obstruction, "small airway disease" and a reduced ventilatory efficiency.

Cardiac Catheterization↗
PubMed2002

Identification of the crayfish plague fungus Aphanomyces astaci by polymerase chain reaction and restriction enzyme analysis.

To characterise the DNA of the crayfish plague fungus Aphanomyces astaci, Saprolegniales (Oomycetes), primers were developed to amplify a 1050bp segment of the 28S rDNA region. Restriction enzymes were applied to the amplicon obtained, to distinguish A. astaci from 12 fungal species belonging also to the Saprolegniales and five more distantly related fungi. Most of the fungal species included in the study are either known parasites of freshwater crayfish cuticle or can be found in their natural environment. A. astaci DNA was distinguishable from the DNA of other fungal species tested by using the primers developed plus restriction enzymes AluI, HindIII and AvaI. Prior to this study, methods for A. astaci-species determination, e.g. spore production and infection experiments, required a protracted period to yield results; the method described in this study is quicker.

Animals↗
PubMed2002

Concordance between telepathologic diagnosis and conventional histopathologic diagnosis: a multiobserver store-and-forward study on 20 skin specimens.

OBJECTIVE: To study the validity and feasibility of transferring images of cutaneous biopsy specimens via e-mail to remote physicians active in dermatopathology for teleconsultation. DESIGN: Twenty skin specimens previously diagnosed at the Department of Dermatology, University of Graz, Austria, were subsequently sent for teleconsultation using the store-and-forward method. For each case, 3 or 4 images at different magnifications were sent by e-mail to 16 colleagues (11 dermatopathologists and 5 pathologists) in 15 centers in 6 different countries. Six weeks later each observer received the hematoxylin-eosin-stained specimens to render a conventional diagnosis. SETTING: Dermatopathology and pathology units within institutional and private settings. MATERIAL: Twenty small skin biopsy specimens of cutaneous diseases were selected randomly from a study set of 80. MAIN OUTCOME MEASURE: Concordance between telepathologic diagnoses and conventional histopathologic diagnoses of 20 skin specimens. RESULTS: On average, 78% of the telediagnoses were correct (range, 60%-95%), whereas 85% of the conventional diagnoses were correct (range, 60%-95%). A perfect diagnostic concordance was obtained in 7 (35%) of 20 cases, and a significant difference was identified in only 1 case. CONCLUSIONS: Results suggest that telepathology performed by physicians active in dermatopathology may serve as a reliable technique for the diagnosis of cutaneous diseases when experts in dermatopathology are not available locally. Furthermore, teledermatopathology is attractive because it provides an opportunity to obtain timely consultation on difficult cases.

Adult↗
PubMed2002

Expression and distribution of calcitonin receptor-like receptor in human hairy skin.

Calcitonin gene-related peptide and adrenomedullin exert potent effects in skin but their cellular targets are unknown. This study aimed to identify the cellular location of calcitonin receptor-like receptor (CRLR) which is pharmacologically identical to CGRP receptor-1, a putative molecular target of CGRP and adrenomedullin. RT-PCR analysis of human hairy skin revealed the presence of CRLR mRNA and immunohistochemical analysis, employing a previously characterized polyclonal antibody raised to CRLR, provided novel evidence of the cellular distribution of CRLR. Extensive and specific CRLR-immunostaining was detected in arteriolar smooth muscle and venular endothelium and is consistent with CGRP's putative role in neurogenic inflammation. Novel targets for CGRP and/or adrenomedullin were identified, including capillary endothelium, hair follicles and sweat glands.

Adrenomedullin↗
PubMed2002

High-throughput peptide synthesis and peptide purification strategy at the low micromol-scale using the 96-well format.

The increasing demand for short- and medium-sized peptides in many fields of biological, medical and pharmaceutical research requires optimized and universally applicable high-throughput synthesis and purification techniques at the low-micromol scale. Here, we describe a continuous peptide synthesis/purification approach using the 96-well format. First, a micromol scale peptide synthesis on resin beads was optimized on a novel miniaturized 96-reaction vessel block employing standard Fmoc/tBu-chemistry. Almost 90% of the synthesized peptides contained the target sequence as the main component, as judged from matrix-assisted laser desorption/ionization (MALDI) mass spectra. Impurities were mostly related to partially protected peptides. Second, we tested the applicability of ion pair reversed-phase solid-phase extraction (IP-RP-SPE) to purify individual peptides. Depending on the length and predicted hydrophobicity of the peptides, elution was performed with 25 or 35% aqueous acetonitrile in the presence of 0.1% trifluoroacetic acid (TFA). Thus, scavengers used during TFA cleavage and partially protected peptides carrying very hydrophobic protecting groups were effectively removed. Using a narrow step gradient, the target peptides were even separated from deleted sequences and protected peptides with similar hydrophobicities. Third, we combined the micromol-scale synthesis in the 96-well format with purification by IP-RP-SPE on a 96-well micro-extraction plate format. This simple, fast and parallel approach was tested on 12-mer and 15-mer peptides to map epitopes of T- and B-cell clones, respectively. Approximately 80% of all peptides were obtained at purities > 90% without purification by RP-HPLC. In summary, this novel approach has several advantages: (i) the micromol-scale reduced the cost of peptide synthesis, (ii) large numbers of peptides were purified faster, (iii) the volumes of eluents and waste were significantly reduced, and (iv) the RP-HPLC column was not contaminated with hydrophobic impurities.

Acetonitriles↗
PubMed2002

17alpha-estradiol induces aromatase activity in intact human anagen hair follicles ex vivo.

For topical treatment of androgenetic alopecia (AGA) in women, solutions containing either estradiol benzoate, estradiol valerate, 17beta- or 17alpha-estradiol are commercially available in Europe and some studies show an increased anagen and decreased telogen rate after treatment as compared with placebo. At present it is not precisely known how estrogens mediate their beneficial effect on AGA-affected hair follicles. We have shown recently that 17alpha-estradiol is able to diminish the amount of dihydrotestosterone (DHT) formed by human hair follicles after incubation with testosterone, while increasing the concentration of weaker steroids such as estrogens. Because aromatase is involved in the conversion of testosterone to estrogens and because there is some clinical evidence that aromatase activity may be involved in the pathogenesis of AGA, we addressed the question whether aromatase is expressed in human hair follicles and whether 17alpha-estradiol is able to modify the aromatase activity. Herewith we were able to demonstrate that intact, microdissected hair follicles from female donors express considerably more aromatase activity than hair follicles from male donors. Using immunohistochemistry, we detected the aromatase mainly in the epithelial parts of the hair follicle and not in the dermal papilla. Furthermore, we show that in comparison to the controls, we noticed in 17alpha-estradiol-incubated (1 nM) female hair follicles a concentration- and time-dependent increase of aromatase activity (at 24 h: 1 nM = +18%, 100 nM = +25%, 1 micro M = +57%; 24 h: 1 nM = +18%, 48 h: 1 nM = +25%). In conclusion, our ex vivo experiments suggest that under the influence of 17alpha-estradiol an increased conversion of testosterone to 17beta-estradiol and androstendione to estrone takes place, which might explain the beneficial effects of estrogen treatment of AGA.

Adult↗
PubMed2002

Alopecia areata - animal models.

Several rodent models with spontaneous and induced alopecia areata (AA), a nonscarring inflammatory hair loss disease with suspected autoimmune elements, have been identified. Of these, the C3H/HeJ mouse and DEBR rat have been most extensively used in examining AA development. Flow cytometry and micro array characterization, manipulation of inflammatory cells by in vivo cell depletion or cell receptor blockade, lymph node cell transfer between affected and unaffected rodents, and the recent use of transgenic knockout mice have given important insights into the development of AA. From our current understanding of rodent models, the development of AA relies upon a general genetic susceptibility where major susceptibility genes may be supplemented by minor disease severity modifying genes. However, the actual onset of AA, its duration, extent, and persistence in individual rodents may be modified by epigenetic factors. Rodent AA seems to be fundamentally, but not exclusively, Th1 cell mediated. Onset of disease may be dependent on several factors including the break down of the putative anagen stage hair follicle immune privilege, appropriate antigen presentation with costimulation of lymphocytes, presence of autoreactive lymphocytes, and a deficiency of functional immune system regulatory cells. Rodents have already been used in examining a variety of current AA treatments and developing new therapies with some success. With a greater understanding of AA disease mechanisms through rodent model research, improved and more specific treatment interventions may be defined.

Alopecia Areata↗
PubMed2002

Male androgenetic alopecia.

Androgenetic alopecia (AGA) is the most common type of hair loss in men. The relative strong concordance of the degree of baldness in fathers and sons is not consistent with a smiple Mendelian trait and a polygenic basis is considered to be most likely. So far the predisposing genes for AGA are unknown and we do not understand the molecular steps involved in androgen-dependent beard growth versus androgen-dependent hair loss, but AGA can be defined as a DHT-dependent process with continuous miniaturization of sensitive hair follicles. The type 2 5aR plays a central role by the intrafollicular conversion of T to DHT. Due to the inceasing knowledge in this field, this article shall privide an critical overwiew of recent discoveries.

Alopecia↗
PubMed2002

Refinements in stress echocardiographic techniques improve inter-institutional agreement in interpretation of dobutamine stress echocardiograms.

AIMS: To determine the degree of inter-institutional agreement in the assessment of dobutamine stress echocardiograms using modern stress echocardiographic technology in combination with standardized data acquisition and assessment criteria. METHOD AND RESULTS: Among six experienced institutions, 150 dobutamine stress echocardiograms (dobutamine up to 40 microg x kg(-1) min(-1) and atropine up to 1 mg) were performed on patients with suspected coronary artery disease using fundamental and harmonic imaging following a consistent digital acquisition protocol. Each dobutamine stress echocardiogram was assessed at every institution regarding endocardial visibility and left ventricular wall motion without knowledge of any other data using standardized reading criteria. No patients were excluded due to poor image quality or inadequate stress level. Coronary angiography was performed within 4 weeks. Coronary angiography demonstrated significant coronary artery disease (> or = 50% diameter stenosis) in 87 patients. Using harmonic imaging an average of 5.2+/-0.9 institutions agreed on dobutamine stress echocardiogram results as being normal or abnormal (mean kappa 0.55; 95% CI 0.50-0.60). Agreement was higher in patients with no (equal assessment of dobutamine stress echocardiogram results by 5.5+/-0.8 institutions) or three-vessel coronary artery disease (5.4+/- 0.8 institutions) and lower in one- or two- vessel disease (5.0+/-0.9 and 5.2+/-1.0 institutions, respectively; P=0.041). Disagreement on test results was greater in only minor wall motion abnormalities. Agreement on dobutamine stress echocardiogram results was lower using fundamental imaging (mean kappa 0.49; 95% CI 0.44-0.54; P<0.01 vs harmonic imaging). CONCLUSION: Modern echocardiographic technology in combination with standardized digital image processing and uniform reading criteria results in a higher inter-institutional agreement in the interpretation of dobutamine stress echocardiogram compared to historic reports.

Adrenergic beta-Agonists↗
PubMed2002

Treatment of complex acetabular fractures through a modified extended iliofemoral approach.

OBJECTIVES: To assess the rate of anatomic reconstructions as well as approach-related morbidity and complications in the treatment of complex acetabular fractures through a modified extended iliofemoral approach. DESIGN: Prospective clinical study. SETTING: Level I trauma center, University Hospital. PATIENTS: Inclusion criteria were as follows: (a) associated acetabular fracture or transverse fracture with comminuted roof area stated as not sufficiently reconstructable through a single approach, and (b) age between sixteen and sixty-five years. A total of forty-nine patients with fifty complex acetabular fractures could be included out of the series of ninety-six acetabular fractures treated operatively from August 1992 to February 1996. Open reduction and internal fixation of complex acetabular fractures through the modified extended iliofemoral approach were performed. RESULTS: In 80 percent of the fifty fractures the reduction was anatomic with a remaining displacement of less than or equal to one millimeter, in eight cases there was a persistent displacement of two millimeters, and two fractures had a poor result with a three-millimeter displacement. Complications included 8 percent loss of reduction, 13 percent heterotopic ossification grade 3, and 4 percent avascular femoral head necrosis. At the two-year follow-up there were 74 percent good or excellent radiographic and clinical results. Two patients had already been reoperated with total hip replacement, and the two patients with femoral head necrosis are currently scheduled for arthroplasty. CONCLUSIONS: The modified extended iliofemoral approach proved to be appropriate to achieve anatomic reduction in complex acetabular fractures. The high rate of approach-related morbidity has to be considered carefully and may lead to a decreased incidence of extended approaches.

Acetabulum↗
PubMed2002

[Hormonal interaction and hair growth].

Androgenetic alopecia (AGA) is the most common form of hair loss in men and women. This continuous process results in a form of alopecia that follows a definite pattern in those individuals who are genetically predisposed. Although clinically different, the pathogenetic pathways leading to this type of hair loss are thought to be similar in both sexes. A genetic predisposition is a feature of AGA, but the predisposing genes are still unknown. Our understanding, however, of the hormonal effects on hair growth is far more advanced. AGA can be defined as a dihydrotestosterone (DHT)-dependent process with continuous miniaturization of sensitive hair follicles. So far, we do not understand the molecular steps involved in androgen-dependent beard growth versus androgen-dependent hair loss. However, the local androgen metabolism plays a central role in the intrafollicular conversion of weak androgens, such as DHEAS, to more potent androgens such as T or DHT within the hair follicle. The dermal papilla plays a central role by exhibiting an array of important steroidogenic isoenzymes. Provided that the dermal papilla (DP) cell triggers and regulates the growth of hair follicles, this physiological role may be reflected by metabolic differences, which could account for differences in androgen sensitivity as observed in hair follicles from different body sites, and in conditions such as male pattern baldness. The observation of STS, 17beta-HSD, 3beta-HSD, 3alpha-HSD and type 2 5alpha-R-activity within the DP could be a clue to understanding the regulation of androgen action in the human hair follicle by local androgen modification on target cell level. Hence, some of the intrafollicular steroidogenic enzymes would be potential pharmaceutical targets for the treatment of AGA or hirsutism.

Alopecia↗
PubMed2001

Predictive value of markers of myocardial reperfusion in acute myocardial infarction for follow-up left ventricular function.

This study evaluated recently suggested invasive and noninvasive parameters of myocardial reperfusion after acute myocardial infarction (AMI), assessing their predictive value for left ventricular function 4 weeks after AMI and reperfusion defined by myocardial contrast echocardiography (MCE). In 38 patients, angiographic myocardial blush grade, corrected Thrombolysis In Myocardial Infarction frame count, ST-segment elevation index, and coronary flow reserve (n = 25) were determined immediately after primary percutaneous transluminal coronary angioplasty (PTCA) for first AMI, and intravenous MCE was determined before, and at 1 and 24 hours after PTCA to evaluate myocardial reperfusion. Results were related to global wall motion index (GWMI) at 4 weeks. MCE 1 hour after PTCA showed good correlation with GWMI at 4 weeks (r = 0.684, p <0.001) and was in an analysis of variance the best parameter to predict GWMI 4 weeks after AMI. The ST-segment elevation index was close in its predictive value. Considering only invasive parameters of reperfusion myocardial blush grade was the best predictor of GWMI at 4 weeks (R(2) = 0.3107, p <0.001). A MCE perfusion defect size at 24 hours of > or =50% of the MCE perfusion defect size before PTCA was used to define myocardial nonreperfusion. In a multivariate analysis, low myocardial blush grade class was the best predictor of nonreperfusion defined by MCE. Thus, intravenous MCE allows better prediction of left ventricular function 4 weeks after AMI than other evaluated parameters of myocardial reperfusion. Myocardial blush grade is the best predictor of nonreperfusion defined by MCE and is the invasive parameter with the greatest predictive value for left ventricular function after AMI. Coronary flow parameters are less predictive.

Aged↗
PubMed2001

Neutral loss analysis in MALDI-MS using an ion-gate scanning mode.

Matrix-assisted laser desorption/ionization reflector time-of-flight (MALDI-reTOF) and electrospray ionization (ESI) mass spectrometry (MS) have become essential tools for the characterization of peptides and proteins. Whereas ESI in combination with a triple quadrupole analyzer allows product ion, precursor ion, and neutral loss analyses, MALDI-reTOF instruments can only be used to record product ion spectra based on the in-source or postsource decay (PSD). We describe a new method to perform neutral loss analyses in MALDI-reTOF instruments in a manner that identifies posttranslationally modified peptides and furthermore retrieves sequence information from peptides. The method is based on the selection of ions in a small time interval to record only signals within the corresponding mass interval. By stepping the time interval through the complete mass range, we obtained a spectrum of stable ions by combining the signals of all individually recorded time intervals. This method furthermore permits PSD fragment ions to be identified, since they reach the detector earlier than the stable ions transmitted in the chosen time interval. The neutral loss analysis were calculated by correlating the PSD fragment ions to the corresponding parent ion detected in this time interval. Moreover, this MALDI-MS mode increased the number of detectable signals in complex peptide mixtures and the signal-to-noise ratio.

Amino Acid Sequence↗
PubMed2001

Complicated goings-on in the metal-manipulated ring-opening of cyclobutene.

Most reported examples of transition metal-mediated pericyclic reactions have been shown to proceed by nonpericyclic mechanisms. However, the conversion of Fe(CO)(4)-cyclobutenes to Fe(CO)(3)-butadienes and CO is thought to proceed through a mechanism involving an electrocyclic ring-opening step. We have examined this and possible alternative mechanisms for the parent Fe(CO)(4)-cyclobutene complex using hybrid HF-DFT calculations. In this system there is an inherent preference for a pathway that avoids metal-templated electrocyclic ring-opening, but the pericyclic pathway is predicted to dominate for more elaborate substrates and under certain experimental conditions.

Journal Article↗
PubMed2001

Characterisation of humic substances using atmospheric pressure chemical ionisation and electrospray ionisation mass spectrometry combined with size-exclusion chromatography.

Humic substances were analysed by atmospheric pressure chemical ionisation (APCI) and electrospray ionisation (ESI) mass spectrometry in positive and negative modes. Using APCI the average m/z range of humic substances was reduced 5-fold compared to ESI. High-resolution time-of-flight mass spectrometry revealed the formation of multiply charged molecules in the ESI mode. Moreover, it was possible to obtain daughter ion mass spectra of humic substances by nanospray tandem mass spectrometry. The size-exclusion chromatography elution profile of humic substances was highly influenced by the pH of the analyte solution. By contrast, the pH had no significant influence on the observed mass spectra of humic substances.

Atmospheric Pressure↗
PubMed2001

Electron-rich rods as building blocks for Sb strips and Te sheets.

We analyze the bonding in a number of networks of heavy main group elements comprised of finite-length linear chains fused at right angles. Isolated linear chain building blocks may be understood easily by analogy with three-orbital four-electron "hypervalent" bonding picture in such molecules as I(3)(-) and XeF(2). After deriving the appropriate electron-counting rules for such linear units, we proceed in an aufbau to fuse these chains into simple (and not so simple) infinite networks. It is proposed that (a) infinite Sb(3) ribbons of vertex sharing squares are stable for an electron count of 20 electrons per three atoms (i.e., ); (b) sidewise fused Sb double ribbons are stable for an electron count of 38 electrons per six atoms (i.e., ); (c) Sb(4) strips cut from a square lattice are stable at the electron count of 24 electrons per four atoms (i.e., ); (d) Te(6) defect square sheets are stable at the electron count of 40 electrons per six atoms (i.e., ). The electronic structures of the solid-state compounds containing these networks, namely La(12)Mn(2)Sb(30), alpha-ZrSb(2), beta-ZrSb(2), Cs(3)Te(22), and Cs(4)Te(28), are elaborated. We propose preferred electron counts for two hypothetical Sb ribbons derived from the Sb(3) ribbon in La(12)Mn(2)Sb(30). A possibility of geometry distortion modulation by excess charge in lattices comprised of even-membered linear units is suggested.

Journal Article↗
PubMed2001

Quantitative measurement of short-range chemical bonding forces.

We report direct force measurements of the formation of a chemical bond. The experiments were performed using a low-temperature atomic force microscope, a silicon tip, and a silicon (111) 7x7 surface. The measured site-dependent attractive short-range force, which attains a maximum value of 2.1 nanonewtons, is in good agreement with first-principles calculations of an incipient covalent bond in an analogous model system. The resolution was sufficient to distinguish differences in the interaction potential between inequivalent adatoms, demonstrating the ability of atomic force microscopy to provide quantitative, atomic-scale information on surface chemical reactivity.

Journal Article↗