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Biomedical subjects

B Hofmann

Publications and source records attributed to B Hofmann.

At least 19 recordsLinked to original sources
PubMed2001

[Physician as a body technician].

"The physician as a technician" is a metaphor for a significant critique of modern medicine. This article approaches some of these critiques. The notion of medicine as an art is sometimes used to remind us of and in praise of the non-technical aspects of medicine. After indicating some difficulties with modern conceptions of medicine as art, I bring in the ancient concept of art, "téchnê", arguing that it avoids some of the difficulties of the modern art concept. Téchnê actually integrates the scientific, technical and normative aspects of medicine and gives a positive interpretation of the claim that the physician has become a technician. The concept provides medicine with a fruitful framework for understanding both technology and philosophy.

Concept Formation↗
PubMed2001

Early experience with a quadrileaflet stentless mitral valve.

BACKGROUND: Presently no ideal prosthesis for mitral valve replacement exists. The quadrileaflet mitral valve (SJM-Quattro-MV; St. Jude Medical, Inc, St. Paul, MN) is a chordally supported stentless bioprosthesis. Due to its specific geometry it seems to be particularly suited for mitral valve replacement. METHODS: From March 1999 to October 2000, 12 patients (ages 71+/-2 years) received the SJM-Quattro-MV. Six patients suffered from valvular stenosis and 6 patients from incompetence. Preoperatively, all patients were in New York Heart Association functional class III, with left ventricular ejection fraction amounts of 54%+/-17%. RESULTS: Eleven patients received a medium size SJM-Quattro-MV and one patient received a large size SJM-Quattro-MV. Cross-clamp time was 99.8+/-4.9 minutes. Additional procedures were coronary artery bypass grafting (n = 3) and left atrial microwave ablation (n = 2). Postoperative mortality (n = 1) was procedure related. At follow-up of 11.6+/-5.4 months, all patients were well, the transvalvular pressure gradient was 5.0+/-1.4 mm Hg, and the effective orifice area 2.7+/-0.2 cm2. CONCLUSIONS: Our preliminary experiences with the SJM-Quattro-MV presented good clinical results and promoted an optimistic way of thinking about the further development of these valve prostheses.

Aged↗
PubMed2001

Structure of fibroblast growth factor 9 shows a symmetric dimer with unique receptor- and heparin-binding interfaces.

Fibroblast growth factors (FGFs) constitute a family of at least 20 structurally related heparin-binding polypeptides active in regulating cell growth, survival, differentiation and migration. FGF9, originally discovered as a glia-activating factor, shares 30% sequence identity with other FGFs and has a unique spectrum of target-cell specificity. FGF9 crystallized in the tetragonal space group I4(1), with unit-cell parameters a = b = 151.9, c = 117.2 A. The structure of the glycosylated protein has been refined to an R value of 21.0% with R(free) = 24.8%) at 2.6 A resolution. The four molecules in the asymmetric unit are arranged in two non-crystallographic dimers, with the dimer interface composed partly of residues from N- and C-terminal extensions from the FGF core structure. Most of the receptor-binding residues identified in FGF1- and FGF2-receptor complexes are buried in the dimer interface, with the beta8-beta9 loop stabilized in a particular conformation by an intramolecular hydrogen-bonding network. The potential heparin-binding sites are in a pattern distinct from FGF1 and FGF2. The carbohydrate moiety attached at Asn79 has no structural influence.

Amino Acid Sequence↗
PubMed2001

Structures of tryparedoxins revealing interaction with trypanothione.

Tryparedoxins (TXNs) catalyse the reduction of peroxiredoxin-type peroxidases by the bis-glutathionyl derivative of spermidine, trypanothione, and are relevant to hydroperoxide detoxification and virulence of trypanosomes. The 3D-structures of the following tryparedoxins are presented: authentic tryparedoxin1 of Crithidia fasciculata, CfTXN1; the his-tagged recombinant protein, CfTXN1H6; reduced and oxidised CfTXN2, and an alternative substrate derivative of the mutein CfTXN2H6-Cys44Ser. Cys41 (Cys40 in TXN1) of the active site motif 40-WCPPCR-45 proved to be the only solvent-exposed redox active residue in CfTXN2. In reduced TXNs, its nucleophilicity is increased by a network of hydrogen bonds. In oxidised TXNs it can be attacked by the thiol of the 1N-glutathionyl residue of trypanothione, as evidenced by the structure of 1N-glutathionylspermidine-derivatised CfTXN2H6-Cys44Ser. Modelling suggests Arg45 (44), Glu73 (72), the Ile110 (109) cis-Pro111 (110)-bond and Arg129 (128) to be involved in the binding of trypanothione to CfTXN2 (CfTXN1). The model of TXN-substrate interaction is consistent with functional characteristics of known and newly designed muteins (CfTXN2H6-Arg129Asp and Glu73Arg) and the 1N-glutathionyl-spermidine binding in the CfTXN2H6-Cys44Ser structure.

Amino Acid Sequence↗
PubMed2000

Linkage and LOH studies in 19 cylindromatosis families show no evidence of genetic heterogeneity and refine the CYLD locus on chromosome 16q12-q13.

Familial cylindromatosis is an autosomal dominant predisposition to multiple neoplasms of the skin appendages. The susceptibility gene has previously been mapped to chromosome 16q12-q13 and has features of a recessive oncogene/tumour suppressor gene. We have now evaluated 19 families with this disease by a combination of genetic linkage analysis and loss of heterozygosity in cylindromas from affected individuals. All 15 informative families show linkage to this locus, providing no evidence for genetic heterogeneity. Recombinant mapping has placed the gene in an interval of approximately 1 Mb. There is no evidence, between families, of haplotype sharing that might be indicative of common founder mutations.

Carcinoma, Adenoid Cystic↗
PubMed2000

Imaging of tumour neovasculature by targeting the TGF-beta binding receptor endoglin.

In vivo imaging of endothelial markers in intact tumour neovasculature would have applications in assessing the efficacy of anti-angiogenic agents in clinical trials. Although a variety of different endothelial markers have been described, few have been evaluated as imaging markers. The transforming growth factor-beta (TGF-beta) binding receptor endoglin is a proliferation-associated endothelial marker. We hypothesised that endoglin would be an ideal target for imaging since it is strongly upregulated in proliferating endothelial cells of the tumour neovasculature. We used a radiolabelled monoclonal anti-endoglin antibody and compared its neovascular binding, accumulation and in vivo behaviour to an isotype-matched control IgG(2a). Our data show that the probe binds specifically and rapidly within minutes in vivo and that correlative autoradiography and immunohistology support the in vivo imaging findings. Imaging of abundantly expressed endothelial targets circumvents delivery barriers normally associated with other tumour targeting strategies, and can potentially be used to quantitate molecular angiogenic markers.

Antigens, CD↗
PubMed2000

Identification of the familial cylindromatosis tumour-suppressor gene.

Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).

Amino Acid Sequence↗
PubMed1999

[The development of artificial kidney--from sausage casing to capillary fibers].

In 1994, Willem Kolff published his results on haemodialysis on humans. His achievements were based on 19th century medicine. Richard Bright had contributed to the knowledge of kidney diseases and Graham and Fick had described diffusion through semipermeable membranes. Some initial tests of haemodialysis had been performed by Abel and Haas in the beginning of the 20th century. But it was Kolff's publication that initiated three innovative decades of development of artificial kidneys: the development from sausage casing to the hollow fiber kidneys.

Animals↗
PubMed1999

Mechanism of gadophrin-2 accumulation in tumor necrosis.

The molecular mechanism by which gadophrin-2 targets necrotic tumor tissue was investigated. Biodistribution studies and magnetic resonance imaging (MRI) and histologic/autoradiographic correlation were performed in xenograft mouse models bearing human tumors (HT 29, WiDr, LX 1). Binding of gadophrin-2 to DNA, lipids, or proteins was determined by fluorescence spectrophotometry. Protein binding was determined by dialysis and gel electrophoresis. Accumulation of gadophrin-2 was low (<0.7% injected dose/g tissue at 24 hours after injection) in viable tumor but higher in necrotic tumor regions and was readily detectable by MRI. Within a given tumor, the agent preferentially localized in the periphery of necrotic areas. Within these regions gadophrin-2 was bound to interstitial albumin and not other proteins, lipids, or DNA. Tumoral accumulation of gadophrin-2 most likely occurs through its binding to plasma albumin and subsequent slow extravasation into the tumor interstitium.

Animals↗
PubMed1999

[Psycho-neurogenic factors as a cause of life-threatening arrhythmias].

Tachyarrhytmias often occur during increased emotional arousal or mental excitation. The implantable cardioverter defibrillator (ICD) allows the exact documentation of arrhythmic episodes and their time of onset. Therefore, the type of arrhythmia can be differentiated as well as the circumstances surrounding the event. These features allow the assessment of possible psychic arrhythmogenic factors in the natural environment. We analyzed the ICD-protocols of three male patients (in ages between 60 and 68), whose devices had successfully terminated a ventricular tachycardia and compared the onset of the episodes with the patients' detailed descriptions of the corresponding life situations. The analysis of the circumstances at the time of arrhythmia-onset revealed a relationship between the occurrence of life-threatening arrhythmias in natural environment and emotional stress. The stressors could be defined as situations of increased vulnerability leading to sympathetic excitation. The induction of tachyarrhythmia was promoted in case 1 by acute psychic distress (public speaking), by the increasing panic-attack-like vicious circle of the cognitive anticipation of an unfavorable outcome (case 2), and an adverse anger reaction superimposed on persistent feelings of help- and hopelessness (case 3). These findings are in line with several experimental and epidemiological studies providing evidence for a relationship between psychic arousal and the induction of tachyarrhythmias. The knowledge of emotional and mental factors that function as a trigger for arrhythmias may lead to new therapeutic approaches in the prevention of sudden cardiac death.

Aged↗
PubMed1999

Effect of topical tazarotene in the treatment of congenital ichthyoses.

The clinical efficacy and tolerability of the topical receptor-selective retinoid tazarotene in the treatment of congenital ichthyoses was investigated. Twelve consecutive patients with different forms of congenital ichthyosis were enrolled in an open, non-randomized, intraindividually controlled, half-side pilot study. Diagnoses were X-linked recessive ichthyosis, non-erythrodermic autosomal recessive lamellar ichthyosis, autosomal dominant ichthyosis vulgaris and ichthyosis bullosa of Siemens (IBS). Tazarotene 0.05% gel was applied unilaterally daily on a defined body area measuring 10% of the body surface area. The contralateral side was treated with an ointment containing 10% urea. After 14 days, application frequency was reduced to three times a week, and stopped after another 2 weeks. The follow-up period was 3 months. Reduction in scaling and roughness was used to assess the clinical response in the tazarotene-treated area compared with the control area. Clinical and laboratory assessments were performed every 14 days during the trial. Unilateral improvement in favour of the tazarotene-treated side was observed in nine of 12 patients (75%). Four patients (33%) achieved an excellent response and four (33%) achieved a good response. No therapeutic effect was seen in patients with IBS. The remission persisted during the reduction phase and after discontinuation for up to 2 months. Local irritation in three patients was the only side-effect detectable. Short-term topical application of tazarotene 0.05% gel is a very effective and well-tolerated treatment modality in different forms of congenital ichthyoses and may be an alternative to systemic retinoid therapy.

Administration, Cutaneous↗
PubMed1999

Gadolinium neutron capture therapy (GdNCT) of melanoma cells and solid tumors with the magnetic resonance imaging contrast agent Gadobutrol.

RATIONALE AND OBJECTIVES: The therapeutic gain of neutron capture therapy with a neutral macrocyclic gadolinium (Gd) complex (Gadobutrol) was evaluated through in vitro and in vivo studies in a beam of low-energy neutrons. METHODS: Neutron irradiation for both the in vitro and in vivo studies was performed in a beam of low-energy neutrons produced by the research reactor of the Hahn-Meitner-Institut, Berlin. Malignant melanoma cells of human origin were irradiated in the presence or absence of Gadobutrol. In vivo irradiation was performed on tumor-bearing nude mice. The tumor site was irradiated subsequent to intratumoral injection of Gadobutrol and compared with irradiation in the absence of the Gd complex. RESULTS: In vitro studies showed a Gd-dependent delay of cell proliferation as a consequence of neutron irradiation. In animals, intratumoral administration of the Gd complex at a dose of 1.2 mmol Gd/kg before neutron irradiation results in a significant delay in tumor growth with respect to the control groups. CONCLUSIONS: In vitro and in vivo studies showed a therapeutic benefit with the neutral Gd complex and suggest Gd-containing magnetic resonance contrast media are potential candidates for neutron capture therapy. The Gd dose used in the irradiation experiments was four times the presently accepted high dose in clinical magnetic resonance imaging.

Animals↗
PubMed1999

Crystallization and preliminary X-ray analysis of tryparedoxin I from Crithidia fasciculata.

The thioredoxin-related protein tryparedoxin I from Crithidia fasciculata has been crystallized using PEG 4000 as a precipitant. The enzyme forms long needle-shaped crystals which diffract to at least 1.7 A. A native data set has been collected at the DESY synchrotron from a flash-frozen crystal at 90 K to 1.7 A resolution. The data set shows that the crystals belong to the orthorhombic space group P212121 and have unit-cell parameters a = 37.94, b = 51. 39, c = 71.46 A. Tryparedoxin I is involved in a trypanothione-dependent peroxide metabolic pathway specific for trypanosomatids and may therefore be a suitable candidate for the design of drugs for the specific treatment of a variety of important tropical diseases caused by these parasites.

Animals↗
PubMed1998

[Medical equipment--old, of poor quality and hazardous?].

In the public debate on Norwegian health care it is claimed that hospitals use old and hazardous medical equipment. A survey carried out on 2,031 pieces of equipment at Lillehammer hospital showed an average age of 7.35 years and a mean life span of 14.91 years. The survey showed that the failure rate was highest for newer equipment. It also showed that the operator error rate was higher for newer devices, older equipment being less complex and therefore easier to use. The results did not support the claim that hospitals use old and hazardous medical equipment.

Equipment Failure↗