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Biomedical subjects

B Hoffmann

Publications and source records attributed to B Hoffmann.

At least 73 records · Page 4Linked to original sources

Role of RgpA, RgpB, and Kgp proteinases in virulence of Porphyromonas gingivalis W50 in a murine lesion model.

Extracellular Arg-x- and Lys-x-specific cysteine proteinases are considered important virulence factors and pathogenic markers for Porphyromonas gingivalis, a bacterium implicated as a major etiological agent of chronic periodontitis. Three genes. rgpA, rgpB, and kgp, encode an Arg-x-specific proteinase and adhesins (RgpA), an Arg-x-specific proteinase (RgpB), and a Lys-x-specific proteinase and adhesins (Kgp), respectively. The contribution to pathogenicity of each of the proteinase genes of P. gingivalis W50 was investigated in a murine lesion model using isogenic mutants lacking RgpA, RgpB, and Kgp. Whole-cell Arg-x-specific proteolytic activity of both the RgpA(-) and RgpB(-) isogenic mutants was significantly reduced (3- to 4-fold) relative to that of the wild-type W50. However, for the Kgp(-) isogenic mutant, whole-cell Arg-x activity was similar to that of the wild-type strain. Whole-cell Lys-x proteolytic activity of the RgpA(-) and RgpB(-) mutants was not significantly different from that of wild-type W50, whereas the Kgp(-) mutant was devoid of Lys-x whole-cell proteolytic activity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis using proteinase-specific antibodies of cell sonicates of the wild-type and mutant strains showed that the proteinase catalytic domain of each of the mutants was not expressed. This analysis further showed that RgpB appeared as 72- and 80-kDa bands, and the catalytic domains of RgpA and Kgp appeared as processed 45-kDa and 48-kDa bands, respectively. In the murine lesion model, mice were challenged with three doses of each mutant and wild-type strain. At the lower dose (3.0 x 10(9) viable-cells), no lesions were recorded for each of the mutants, whereas wild-type W50 induced large ulcerative lesions. At a dose of 6.0 x 10(9) viable-cells, all the mice challenged with the wild-type strain died, whereas mice challenged with the RgpA(-) and RgpB(-) isogenic mutants did not die but developed lesions. Mice challenged with the Kgp(-) isogenic mutant at this dose did not develop lesions. At a 1.2 x 10(10) viable-cell dose, only 40% of mice challenged with the Kgp(-) mutant developed lesions, and these lesions were significantly smaller than lesions induced by the wild-type strain at the 3.0 x 10(9) viable-cell dose. All the mice challenged with the RgpA(-) mutant died at the 1.2 x 10(10) viable-cell dose, whereas only 20% died when challenged with the RgpB(-) mutant at this dose. Wild-type phenotype was restored to the RgpB(-) mutant by complementation with plasmid pNJR12::rgpB containing the rgpB gene. There was no difference between the pNJR12::rgpB-complemented RgpB(-) mutant and the wild-type W50 strain in whole-cell Arg-x activity, protein profile, or virulence in the murine lesion model. These results show that the three proteinases, RgpA, RgpB, and Kgp, all contributed to virulence of P. gingivalis W50 in the murine lesion model and that the order in which they contributed was Kgp >> RgpB > or = RgpA.

Adhesins, Bacterial↗

Can a decline in the population means of cardiovascular risk factors reduce the number of people at risk?

OBJECTIVE: To prove the possibility of shifting distribution of cardiovascular risk factors for a whole population over time and thereby to influence the prevalence of the corresponding disease states, according to the theory stated by Geoffrey Rose in 1985. DESIGN: Examination of standardised data from the German Cardiovascular Prevention Study (GCP), a seven year long, population-based, multicentre intervention trial, concerned with decreasing risk factors for cardiovascular disease. SETTING AND SUBJECTS: three cross sectional surveys of a population 25 to 69 years old in six study regions, and three nationwide cross sectional surveys in the former West Germany in 1984, 1988 and 1991. MAIN OUTCOME MEASURES: The relation between the population mean for systolic and diastolic blood pressure, total serum cholesterol, body mass index, and alcohol intake, and the prevalence of the corresponding disease states, as are systolic (> or =140 and > or =160 mm Hg) and diastolic hypertension (> or =90 and > or =95 mm Hg), hypercholesterolaemia (> or =250 and > or =300 mg/dl), overweight (body mass index > or =30 kg/m2), and heavy drinking (weekly alcohol intake > or =300 g/week). Results are expressed as linear regression equations and Pearson correlation coefficients. RESULTS: The correlation between the mean population values and prevalence of disease was close for blood pressures and body mass index. The Pearson coefficients, corrected for the influence of values increased above borderlines, were 0.86 and 0.81 respectively for systolic blood pressure, 0.88 and 0.91 for diastolic blood pressure, 0.28 and 0.52 for cholesterol, and 0.86 for the body mass index. The coefficient for alcohol intake was 0.55. CONCLUSIONS: It seems possible to shift the risk distribution of a population for some physiological parameters over time with the effect of changing the disease prevalence. This strategy can be used successfully for specific preventive measures, as was strongly advocated by Geoffrey Rose.

Adult↗

Cobalt-specific T lymphocytes in synovial tissue after an allergic reaction to a cobalt alloy joint prosthesis.

Metals such as cobalt and nickel are common contact allergens. We studied the mechanisms underlying an allergic reaction with marked synovial inflammation in a patient with a cobalt alloy arthroplasty. After removing the joint prosthesis the adjacent synovial tissue was examined for cobalt-specific T lymphocytes. Synovial membrane mononuclear cells were expanded in interleukin 2 and cloned using a representative cloning protocol. T cell clones were tested for their proliferative response to cobalt and further characterized with regard to cytokine secretion, phenotype, and HLA restriction. Additionally, synovial fibroblasts were tested for their function as antigen presenting cells (APC). Almost 30% of the T cell clones reacted to cobalt, but not to the control nickel. All these T cell clones were CD4 positive. The cobalt induced proliferative response could be blocked by anticlass II antibodies. Also, synovial fibroblasts expressing class II molecules induced by interferon-gamma were able to serve as APC. However, when testing a panel of APC of HLA class II mismatched donors, no requirement for a certain HLA class II molecule could be defined. Further studies are necessary to determine mechanisms of presentation and recognition of cobalt by T lymphocytes, a prerequisite for improved prevention and treatment of metal induced allergic reactions.

Antigen Presentation↗

Correction of congenital heart defects and mitral valve operations using limited anterolateral thoracotomy.

PURPOSE: Median sternotomy, which generally is used as a standard access for atrial septal defect (ASD) and mitral valve operations, has a significant risk of postoperative instability/osteomyelitis of the sternum. Moreover, especially in young women, the resulting large scar is a poor cosmetic result that may have adverse psychological consequences. Our presentation suggests that these difficulties may be avoided by the use of a less invasive approach consisting of a limited anterolateral thoracotomy with standard cannulation. MATERIAL AND METHODS: From June 1997 until December 1999, 13 women, mean age 31.9 +/- 9.2 years, with atrial septum defect (n = 8), sinus venosus defect with partial anomalous pulmonary venous connection (n = 1), left atrial myxoma (n =1) or mitral valve regurgitation (n = 3), were scheduled for less invasive operation. In all cases a double lumen tube was used for ventilation. After a submammarian skin incision of about 10 cm a limited anterolateral thoracotomy was performed in the fifth right intercostal space. For cannulation of the ascending aorta a trochar cannula was used. Both caval veins were cannulated by angled vena cava catheters. Standard cardiopulmonary bypass was established using normothermia in all patients undergoing operations with correction of congenital heart defects and mild hypothermia (32 degrees C) in the three patients undergoing mitral valve operation. Surgery was performed in cardioplegic arrest using Bretschneider's solution. All corrections of congenital heart defects were performed by Goretex patches. Mitral valve reconstruction was carried out in two patients, and one patient underwent mitral valve replacement. RESULTS: No complications occurred in any of the 13 patients peri- or postoperatively. Total time of operation was 211.9 +/- 36.0 minutes, the perfusion time was 77.0 +/- 25.8 minutes, and the aortic cross-clamp time was 51.8 +/- 21.9 minutes. Mean stay in ICU was 1.2 +/- 0.4 days (total hospital stay: 7.8 +/- 2.2 days). Postoperative thoracic x-ray and cardiac echocardiography/dopplersonography revealed no pathological findings in any patients. CONCLUSION: Atrial septal defect operations, including partial anomalous pulmonary venous connection, left atrial myxoma and mitral valve operations, can be performed safely and effectively using a limited anterolateral thoracotomy and standard cannulation technique with excellent cosmetic results.

Adolescent↗

Isolation of a new insertion element of Yersinia intermedia closely related to remnants of mobile genetic elements present on Yersinia plasmids harboring the Yop virulon.

A new insertion element present in two alleles, designated IS1635.1 and IS1635.2, was identified on a plasmid of a Yersinia intermedia strain by hybridization with the Yersinia enterocolitica pYV virulence plasmid. IS1635.1 and IS1635.2 are 861 bp long, carry imperfect inverted terminal repeats and possess a single open reading frame encoding a putative transposase of the IS6 family. A truncated IS1635 element is present immediately downstream of element IS1635.2. The capacity of the IS1635 elements to mediate transposition in Yersinia was demonstrated with a R6K-derived suicide vector, where a kanamycin resistance gene had been inserted between IS1635.1 and IS1635.2. Hybridization and sequence alignments showed that remnants of IS1635-like insertion elements harboring large deletions and point mutations are present on the Yop virulon harboring plasmids of pathogenic Yersinia strains. In a few cases, the IS1635 element has also been found on plasmids of apathogenic Yersinia strains.

Bacterial Outer Membrane Proteins↗

Dual epitope recognition by the VASP EVH1 domain modulates polyproline ligand specificity and binding affinity.

The Ena-VASP family of proteins act as molecular adaptors linking the cytoskeletal system to signal transduction pathways. Their N-terminal EVH1 domains use groups of exposed aromatic residues to specifically recognize 'FPPPP' motifs found in the mammalian zyxin and vinculin proteins, and ActA protein of the intracellular bacterium Listeria monocytogenes. Here, evidence is provided that the affinities of these EVH1-peptide interactions are strongly dependent on the recognition of residues flanking the core FPPPP motifs. Determination of the VASP EVH1 domain solution structure, together with peptide library screening, measurement of individual K(d)s by fluorescence titration, and NMR chemical shift mapping, revealed a second affinity-determining epitope present in all four ActA EVH1-binding motifs. The epitope was shown to interact with a complementary hydrophobic site on the EVH1 surface and to increase strongly the affinity of ActA for EVH1 domains. We propose that this epitope, which is absent in the sequences of the native EVH1-interaction partners zyxin and vinculin, may provide the pathogen with an advantage when competing for the recruitment of the host VASP and Mena proteins in the infected cell.

Amino Acid Motifs↗

Receptor blockers - general aspects with respect to their use in domestic animal reproduction.

Receptor blockers compete with the respective agonist for binding to a given receptor without inducing complete signal transduction. In recent years, major interest has focused on sex-steroid hormone receptor blockers (antagonists). Indications have been obtained that inadequate changes in receptor conformation and subsequent failure of transcriptional activation are major events preventing hormonal activity. However, various subtypes and variants of receptors and receptor mutations have also been identified. Expression of antihormonal effects may vary depending on the type of receptor the blocker is bound to. Hence, receptor blockers may also have an inherent agonistic activity. Aglepristone is the first antiprogestin registered for veterinary use with the indication "interruption or prevention of pregnancy"; similarly, these types of compounds were successfully used for induction of parturition in the dog and cat and for conservative treatment of pyometra in the dog. Moreover, application of antiprogestins has clearly demonstrated the role of progesterone as a major factor controlling overt pseudopregnancy in dogs. With respect to farm animals, parturition was induced in cows without an increased incidence of retained fetal membranes. Other than antiprogestins, antioestrogens and antiandrogens are still in a more experimental phase. In particular for use in humans, high-affinity blockers binding to the oxytocin/vasopressin receptor are in development; they exert distinct tocolytic activities. Also, the release of GnRH can be inhibited by respective antagonists; however, their use in reproduction is still hampered by the high dose requirement and the side effects observed.

Animal Husbandry↗

A consensus Porphyromonas gingivalis promoter sequence.

We have determined the transcription start points (tsp) for recently identified Porphyromonas gingivalis W50 genes, kgp, rgpA, rgpB (formerly designated prtK, prtR, and prtRII respectively), fetB and the mcmAB operon. Alignment of the DNA upstream of these tsp and those from the literature has enabled us to identify consensus sequences that may represent a P. gingivalis promoter. There is a potential -10 hexamer sequence, 5'-TATATT-3' centred on average at -10/11 nt which is repeated at -19/20 nt and an upstream consensus, 5'-CAGAT(A/G)-3' which is centred at -39/40 nt.

Bacterial Outer Membrane Proteins↗

MRP8/MRP14, CD11b and HLA-DR expression of alveolar macrophages in pneumonia.

Activation of alveolar macrophages is characterised by specific alterations to the expression pattern of surface markers under certain pathological conditions. MRP8/MRP14 and CD11b are involved in the regulation of macrophage migration and adhesion. HLA-DR regulates the antigen presentation by alveolar macrophages. The aim of this study was to investigate the phenotype of alveolar macrophages in pneumonia particularly in relationship to the changes in concentrations of TGF-beta1 and IL-8. Using cytofluorimetry, we analysed the surface expression of MRP8/MRP14, CD11b, and HLA-DR on alveolar macrophages of 42 pneumonia (PN) patients, 14 patients with interstitial lung diseases (ILD), five patients with chronic obstructive lung disease (COPD), and 58 patients without lung disease. Phenotypic characteristics were correlated to the concentration of TGF-beta1 and IL-8 in the bronchoalveolar lavage fluid (BALF) of the same patients. The direct influence of TGF-beta1 and IL-8 on expression of MRP8/MRP14, CD11b and HLA-DR of cultured monocytes and MonoMac cells was analysed. Significantly more MRP8/MRP14 and CD11b positive macrophages and less HLA-DR-positive macrophages were found in PN but not in ILD or COPD. The percentage of CD11b-positive macrophages correlated with the TGF-beta1 as well as the IL-8 concentrations. The amount of HLA-DR-positive macrophages correlated negatively to the concentration of TGF-beta1 and IL-8. These findings document a significant activation of alveolar macrophages during pneumonia. TGF-beta1 led to a modulation of HLA-DR and MRP8/MRP14-antigen expression in vitro. In conclusion, it was shown that in pneumonia but not in ILD or COPD alveolar macrophages were characterised by an increased MRP8/MRP14 and CD11b expression and a diminished HLA-DR expression. The characterisation of subpopulations within the alveolar macrophages may be a useful tool for the monitoring of disease progression.

Antigens, Differentiation↗

Crystal structures and thermotropic properties of alkyl alpha-D-glucopyranosides and their hydrates.

Thermotropic properties and crystal structures of alkyl alpha-D-glucopyranosides and their hydrates were estimated by X-ray, DSC and thermogravimetric measurements (TGA). Monohydrates rapidly lose their crystal water several degrees below the melting point of the anhydrous glucopyranosides. The melting points of the monohydrates measured in DSC pressure cells (chain length longer than seven) are lower, and the clearing points higher than those of the anhydrous glucosides. Layer distances of smectic and crystalline phases of anhydrous compounds were established. Melting points, densities and layer distances of the crystalline anhydrous glucopyranosides display strong even-odd effects. The strong decrease of these effects in the case of the monohydrates can be elucidated by the results of X-ray crystal structure analysis.

Calorimetry, Differential Scanning↗

Developmental and metabolic regulation of the phosphoglucomutase-encoding gene, pgmB, of Aspergillus nidulans.

We have isolated the pgmB gene from Aspergillus nidulans, which encodes a phosphoglucomutase, one of the key enzymes in carbohydrate metabolism. The pgmB gene is located on chromosome VII and its ORF encodes 557 amino acids. Mutant phenotypes were analysed by expression of high levels of pgmB antisense RNA, which lead to a loss of detectable levels of sense RNA. Under conditions of antisense RNA expression, a 30% reduction in the growth rate was observed in comparison to wild-type. On the enzyme level, expression of pgmB antisense RNA resulted in a 35% reduction in total phosphoglucomutase activity. Two pgmB mRNAs were observed under all conditions tested and differ with respect to the location of the poly(A) site. Expression of pgmB driven by the GAL1 promoter in Saccharomyces cerevisiae complemented the growth phenotype of a pgm2delta mutant strain and suppressed the sensitivity of a gcn4delta mutant strain to amino acid starvation in the presence of galactose. Cultivation of A. nidulans in the presence of glucose or galactose as carbon source did not affect transcription of pgmB. However, amino acid starvation conditions resulted in a six-fold reduction in the level of pgmB mRNA, while genes for amino acid biosynthesis showed increased transcription. Transcription of pgmB was low during hyphal growth and in the sexual phase of development, but was significantly increased during the asexual stage of the A. nidulans life cycle.

Amino Acid Sequence↗

Angiotensin II formation and endothelin clearance in ARDS patients in supine and prone positions.

OBJECTIVE: In patients with acute respiratory distress syndrome (ARDS), the prone position may enhance oxygenation by changing ventilation/perfusion ratio. In this study, we investigated whether the prone position affects the net balance between pulmonary endothelin (ET-1) and angiotensin II (Ang II) production and clearance, two metabolic functions of lung endothelial cells. SETTING: Anaesthesiological intensive care unit of a university hospital. PATIENTS: Ten ARDS patients (Murray score > 2.5) were studied in both the supine position (SP) and the prone position (PP). MEASUREMENTS AND DESIGN: Blood samples were taken simultaneously from the patient in SP for assessment of mixed venous and arterial ET-1 and Ang II concentrations, and plasma renin concentration (PRC). This was repeated after 60 min in SP, immediately after turning the patient into PP, and 60 min thereafter. Net arterial/mixed venous ET-1 clearances and net Ang II formations were calculated. RESULTS: arterial oxygen tension increased from SP to PP by an average of 60 mmHg, about 20%. Arterial ET-1 concentrations of ARDS patients were 1.57 +/- 1.1 pg/ml (mean +/- SD) and within the range of healthy persons. Net ET-1 clearances were negative in SP, indicating pulmonary release of ET-1, and did not change in PP. Arterial Ang II concentrations (73 +/- 56 pg/ml) as well as PRC (126 +/- 85 pg/ml) were markedly elevated. Net transpulmonary Ang II formation did not change. CONCLUSION: Acute changes of oxygenation in ARDS patients by positioning do not induce any short-term effects on pulmonary ET-1 net clearance or Ang II net formation.

Adult↗

There is no disease-specific role for streptococci-responsive synovial T lymphocytes in the pathogenesis of psoriatic arthritis.

The initiation or exacerbation of psoriasis vulgaris is associated with infections by group A streptococci. T lymphocytes specific for streptococcal antigens or expressing a restricted, for streptococcal superantigens typical T cell receptor Vbeta chain repertoire have been described in psoriatic skin lesions. The aim of our study was, therefore, to clarify whether streptococci-reactive T lymphocytes played a role in the pathogenesis of psoriatic arthritis (PsA), and by which antigens they might be stimulated. Synovial membrane mononuclear cells from patients with PsA and other arthropathies, separated by collagenase digestion, were expanded in interleukin-2-supplemented medium and subsequently cloned in a representative cloning procedure. The T cell lines and about 30% of the T cell clones proliferated in response to preparations of group A streptococci but not to other bacteria as tested by [3H]thymidine incorporation assays. Interestingly, they did not proliferate in response to exotoxin-negative streptococci, but did so in response to the streptococcal pyrogenic exotoxins A and C, which are known to be superantigens. Accordingly, no HLA-DR restriction was seen for the proliferative response. The remaining 70% of the established T cell clones did not react to an antigen of group A streptococci. Our results show that in patients with PsA, osteoarthritis or rheumatoid arthritis a significant number of synovial T lymphocytes were responsive to streptococcal superantigens, but not to conventional streptococcal antigens. A disease-specific role of streptococci-reactive T lymphocytes in the pathogenesis of PsA is, therefore, unlikely.

Adult↗

The tryptophan synthase-encoding trpB gene of Aspergillus nidulans is regulated by the cross-pathway control system.

The tryptophan synthase-encoding gene, trpB, of Aspergillus nidulans was cloned and characterized. It was mapped to chromosome I, between the gene medA, which is required for sexual and asexual development, and an ORF encoding a protein with significant similarity to subunit B of vacuolar ATP synthases. The 5' untranslated region was found to be at least 142 nucleotides (nt) long, the poly(A) addition site was localized at position + 216 relative to the stop codon by sequencing of several independent cDNA clones. The trpB gene contains two exons separated by an intron of 105 nt, which is located close to the 5' end of the ORF. Directly upstream of the transcriptional start site, one well conserved potential binding site for the cross-pathway control transcriptional activator CPCA was found. The level of trpB transcript was shown to be regulated by cross-pathway control. A knockout mutant for trpB displays tryptophan auxotrophy, no trpB transcript is detectable, and development is perturbed to an extent that is dependent on the amount of tryptophan added to the medium. The trpB gene encodes a protein of 723 amino acids, with a calculated molecular weight of 77.6 kDa. The deduced amino acid sequence shows 72.6% similarity to the tryptophan synthase of Neurospora crassa. Most amino acid residues essential for catalytic activity in the tryptophan synthase of Salmonella typhimurium are conserved. The linker region joining the two domains of the enzyme is 13 residues longer than the longest connector found so far in tryptophan synthases from fungi.

Amino Acid Sequence↗

c-Jun and RACK1 homologues regulate a control point for sexual development in Aspergillus nidulans.

Amino acid limitation results in impaired sexual fruit body formation in filamentous fungi such as Aspergillus nidulans. The starvation signal is perceived by the cross-pathway regulatory network controlling the biosynthesis of translational precursors and results in increased expression of a transcriptional activator encoded by a c-Jun homologue. In the presence of amino acids, the gene product of the mammalian RACK1 homologue cpcB is required to repress the network. Growth under amino acid starvation conditions permits the initiation of the sexual developmental programme of the fungus, but blocks fruit body formation before completion of meiosis. Accordingly, arrest at this defined control point results in microcleistothecia filled with hyphae. Addition of amino acids results in release of the block and completion of development to mature ascospores. The same developmental block is induced by either overexpression of c-Jun homologues or deletion of the RACK1 homologue cpcB of A. nidulans in the presence of amino acids. Therefore, the amino acid starvation signal regulates sexual development through the network that also controls the amino acid biosynthetic genes. Expression of the RACK1 gene suppresses the block in development caused by a deletion of cpcB. These data illuminate a connection between metabolism and sexual development in filamentous fungi.

Amino Acids↗

Native corrinoids from Clostridium cochlearium are adeninylcobamides: spectroscopic analysis and identification of pseudovitamin B(12) and factor A.

The corrinoids from the obligate anaerobe Clostridium cochlearium were extracted as a mixture of Co(beta)-cyano derivatives. From 50 g of frozen cells, approximately 2 mg (1.5 micromol) of B(12) derivatives was obtained as a crystalline sample. Analysis of the corrinoid sample of C. cochlearium by a combination of high-pressure liquid chromatography and UV-Vis absorbance spectroscopy revealed the presence of three cyano corrinoids in a ratio of about 3:1:1. The spectroscopic data acquired for the sample indicated the main components to be pseudovitamin B(12) (Co(beta)-cyano-7"-adeninylcobamide) (60%) and factor A (Co(beta)-cyano-7"-[2-methyl]adeninylcobamide) (20%). Authentic pseudovitamin B(12) was prepared by guided biosynthesis from cobinamide and adenine. Both pseudovitamin B(12) and its homologue, factor A, were subjected to complete spectroscopic analysis by UV-Vis, circular dichroism, mass spectrometry, and by one- and two-dimensional (1)H, (13)C-, and (15)N nuclear magnetic resonance (NMR) spectroscopy. The third component was indicated by the mass spectra to be an isomer of factor A and is likely (according to NMR) to be 7"-[N(6)-methyl]-adeninylcobamide, a previously unknown corrinoid. C. cochlearium thus biosynthesizes as its native "complete" B(12) cofactors the 7"-adeninylcobamides and two homologous corrinoids, in which the nucleotide base is a methylated adenine.

Circular Dichroism↗

Complications and neurosurgical interventions during early rehabilitation in head injured patients.

Guidelines for the treatment of traumatic brain injury (TBI) are subject of actual efforts in neurosurgery, anaesthesiology and traumatology as well as in the basic sciences. International collaborations such as European Brain Injury Consortium (EBIC), Pan-European-Advisory Board (PAB) and Euroacademy of Multidisciplinary Neurotraumatology (EMN) are working on pathophysiological understanding and evaluation of clinical outcomes to establish standards for a holistic concept from resuscitation to rehabilitation. We reviewed the courses of 252 brain injured patients, treated over a four year period in our department including surgery, intensive care and early rehabilitation. Our special interest was focussed on complications during the early rehabilitation period and the neurological outcomes to define quantity and quality of monitoring as well as the need for invasive interventions at the interface between acute and rehabilitative medicine.

Brain Diseases↗