Biomedical subjects

T Rose

Publications and source records attributed to T Rose.

At least 19 recordsLinked to original sources

PubMed2006

Dietary protein induces endothelin-mediated kidney injury through enhanced intrinsic acid production.

Dietary protein as casein (CAS) augments intrinsic acid production, induces endothelin-mediated kidney acidification, and promotes kidney injury. We tested the hypothesis that dietary CAS induces endothelin-mediated kidney injury through augmented intrinsic acid production. Munich-Wistar rats ate minimum electrolyte diets from age 8 to 96 weeks with 50 or 20% protein as either acid-inducing CAS or non-acid-inducing SOY. Urine net acid excretion and distal nephron net HCO3 reabsorption by in vivo microperfusion (Net J(HCO3)) were higher in 50 than 20% CAS but not 50 and 20% SOY. At 96 weeks, 50% compared the 20% CAS had higher urine endothelin-1 excretion (U(ET-1)V) and a higher index of tubulo-interstitial injury (TII) at pathology (2.25+/-0.21 vs 1.25+/-0.13 U, P<0.03), but each parameter was similar in 50 and 20% SOY. CAS (50%) eating NaHCO3 to reduce intrinsic acid production had lower Net J(HCO3), lower U(ET-1)V, and less TII. By contrast, 50% SOY eating dietary acid as (NH4)2SO4 had higher Net J(HCO3), higher U(ET-1)V, and more TII. Endothelin A/B but not A receptor antagonism reduced Net J(HCO3) in 50% CAS and 50% SOY+(NH4)2SO4 animals. By contrast, endothelin A but not A/B receptor antagonism reduced TII in each group. The data support that increased intake of acid-inducing dietary protein induces endothelin B-receptor-mediated increased Net J(HCO3) and endothelin A-receptor-mediated TII through augmented intrinsic acid production.

Acidosis, Renal Tubular↗

PubMed2006

[Typical injuries seen in football players].

Injuries seen in football players mainly affect the knee and ankle joints and muscles. The causes include chronic overstrain and traumatization usually resulting from physical contact between opponent players. Torsional trauma of the joints results in excessive stressing of the capsular ligaments, potentially leading to rupture of the structures involved. Therapeutic options range from conservative measures to reconstructive or prosthetic surgery. While muscular injuries have a good prognosis with regard to the chances of continuing sports activities, injuries to ligaments often enforce a lengthy pause from sports. Extensive injuries to cartilages can terminate a player's sporting career. However, new procedures that take account of physiological biomechanics, together with the further development of surgical technologies now often allow players to regain their pre-injury level of fitness. Specific rehabilitation is a major therapeutic means of preventing further injury.

Ankle Injuries↗

PubMed2005

KATP-channels in beta-cells in tissue slices are directly modulated by millimolar ATP.

In pancreatic beta-cells, inhibition of K(ATP)-channels plays a pivotal role in signal transduction of glucose-induced insulin release. However, the extreme sensitivity of K(ATP)-channels to its ligand ATP as found in inside-out patches is not directly compatible with modulation of these channels at physiological [ATP](i). We studied K(ATP)-channel sensitivity to ATP in beta-cells in dispersed culture and in fresh pancreatic tissue slices. Physiological [ATP](i) blocks more than 99% of K(ATP)-channels in cultured beta-cells, while only 90% in beta-cells in slices, indicating reduced sensitivity to ATP in the fresh slices. Applying cytosolic factors like ADP, phosphatidylinositol-4,5-bisphosphate (PIP(2)) or oleoyl-CoA did not restore the K(ATP)-channel sensitivity in cultured beta-cells. Our data suggest that interaction between SUR1 and Kir6.2 subunit of the K(ATP)-channel could be a factor in sensitivity modulation. Tissue slices are the first beta-cell preparation to study direct K(ATP)-channel modulation by physiological [ATP](i).

Adenosine Triphosphate↗

PubMed2005

[Ex-vivo gene therapy with BMP-4 for critically sized defects and enhancement of fracture healing in an osteoporotic animal model].

Fractures in osteoporotic bones or segment defects are problematic bone lesions with a reduced biological capability of regeneration. We tested the hypothesis that cell-mediated ex vivo gene therapy to deliver BMP4 can heal critically sized defects and improve bone healing in osteoporotic rats. Primary muscle-derived cells were isolated from the hindlimb muscle of rats and retrovirally transduced to express bone morphogenic protein 4 (BMP4). The bone formation was evaluated following local application of these cells in critically sized defects and in fractures of osteoporotic bones. Radiographic analysis revealed bridging callus formation in a critically sized defect in all specimens using muscle-derived cells expressing BMP4 at 12 weeks. These findings were confirmed by histological evaluation, which revealed callus bone formation with good integration to the distal and proximal bone. Following treatment with muscle-derived cells expressing BMP4, the bone healing process in the osteoporotic bone was improved to the level similar to that of normal bone. The ex vivo gene therapy could be a promising tool for the treatment of osteoporotic fractures and critically sized defects. The reduced number of complications (nonunions, loss of reduction, and fragment dislocation), shortening of hospitalization period, and improvement of bone strength are decisive advocates for this treatment option.

Animals↗

PubMed2004

[The angle stable locking-proximal-humerus-plate (LPHP) for proximal humeral fractures using a small anterior-lateral-deltoid-splitting-approach - technique and first results].

The Locking-Proximal-Humerus-Plate (LPHP) was slided from proximally to distally through a small anterior-lateral-deltoid-splitting-approach following a closed reduction. Additional tension band wiring for the rotator cuff was fixed at the plate after screw insertion. The prospective study included 35 patients (age median: 63 years, range: 33-92; male: 13, female: 22) from 08/01-05/02. The follow-up period was set to 3 months postoperatively, whereas 29 patients were able to attend. The patient-group with 2-part fractures (n = 8) showed an average Constant score of 77.6 points (+/- 10.7, "good"), the patients with 3-part fractures (n = 16) an average score of 75.1 points (+/- 14.4, "good") and the patients with 4-part fractures (n = 5) an average score of 64.8 points (+/- 10. 4, "moderate"). Specific, approach-related problems were not observed. Almost all fractures revealed bony union during the first 3 months and only one loss of reduction was found. A screw loosening in 2 cases and a break of the plate in 3 cases were seen as implant related problems, and furthermore in 5 cases the screws placed in the humeral head were too long. Only one early re-osteosynthesis with the same plate was necessary due to an initial non-correct reposition. As demonstrated by these good short-term results, this technique seems to be a suitable procedure for displaced humeral head fractures.

Adult↗

PubMed2004

Fresh meniscal allograft transplantation and autologous ACL/PCL reconstruction in a patient with complex knee trauma following knee dislocation--a case report.

Instability of the knee joint, particularly in combination with the loss of one meniscus, regularly leads to the early development of arthritis. This paper describes the case of a 19-year-old male with ruptures of the anterior (ACL) and posterior cruciate ligament (PCL) along with the loss of the medial meniscus due to knee dislocation. Combined, time-delayed reconstruction of both the ACL and PCL and the allogenic fresh meniscal transplantation of the medial meniscus without bone plugs were performed. The control arthroscopy performed 6 months post-transplantation revealed good vitality and integration of the grafts as assessed both macroscopically and histologically. A small portion of the posterior horn had to be refixated, and the anterior horn was atrophic. At 24 months after trauma and 13 months following meniscal transplantation, the patient achieved a Lysholm score of 88 points and clinical examination indicated a stable knee. Fresh meniscal allograft transplantation, in combination with autologous ACL and PCL reconstruction, constitutes--in specialized centers--an alternative treatment option for complex trauma of the knee joint with loss of a meniscus.

Accidents, Traffic↗

PubMed2003

[Arthroscopy for anterior joint pathology at the upper ankle joint --pathogenesis, therapy and results].

The conservative treatment of chronic ankle pain and at the so-called "footballer's joint" is of limited success. Arthroscopy is a possibility of operative treatment. 25 arthroscopies were carried out at the upper ankle joint at anterior joint pathology from January 1998 to June 1999. 21 patients could be examined in a median follow-up of 16 months (4-24). The median age was 31 years (17-56; female: 6, male: 15). Synovilitis was found in all cases. In 9 cases exophytes of the tibia, in 10 cases osteochondral lesions and in 7 cases antero-lateral impingement ware seen. The preoperative Score of Mazur of median 63 (21-85) points showed a significant raise (p < 0.05) in follow-up to median 93 (81-100) points. The complete athletic rehabilitation could be restored in 2/3 of the patients. The conservative therapy represents a good method of treatment chronic troubles in the upper ankle joint. Arthroscopy is indicated if no recovery can be attained.

Adolescent↗

PubMed2003

The CardioOP-Data Clas (CDC). Development and application of a thesaurus for content management and multi-user teleteaching in cardiac surgery.

OBJECTIVES: Self-directed and customized medical education programs are gaining importance in health care instruction. We prototypically implemented a repository-driven online computer system (CardioOP) for teleteaching in Heart Surgery. It supports authoring and multiple re-use of multimedia data for different user groups in different instructional applications and therefore requires a process of content management. METHODS: We defined objectives for a terminological system to support semantic, cross-media type annotation and retrieval of learning objects: domain completeness, German (natural) language processing, multi-user concepts, extensibility and maintenance, content based annotation and technical implementation. Existing terminologies (ICD10, READ V3, Snomed III, UMLS 1997, MESH) have been analysed according to these objectives. RESULTS: We found that the analysed terminologies did not meet our criteria sufficiently. Therefore, we developed a domain-specific thesaurus, the CardioOP-DataClas (CDC). The application of the CDC within a database-driven authoring process using specifically developed tools is reported. CONCLUSIONS: Metadata play an important role in the effective discovery and search, access, integration and management of educational multimedia data in medicine but so far, there is no terminology to support content management for instructional multimedia. We prototypically designed and applied a thesaurus for the CardioOP educational system. Additional work is needed to evaluate the system in terms of user-friend-liness, concept coverage and information retrieval performance.

Cardiac Surgical Procedures↗

PubMed2002

Structural basis of inward rectifying potassium channel gating.

The last 10 years have seen rapid advances in the understanding of potassium channel function. Since the first inward rectifying (Kir) channels were cloned in 1994, the structural basis of channel function has been significantly elucidated, and determination of the crystal structure of a bacterial K channel (KcsA) in 1998 provided an atomic resolution of the permeation pathway. This review considers recent experimental studies aimed at uncovering the structural basis of Kir channel activity, and the applicability of comparative models based on KcsA to illuminate Kir channel pore structure and opening and closing processes.

Humans↗

PubMed2001

Molecular mapping of thrombin-receptor interactions.

In addition to its procoagulant and anticoagulant roles in the blood coagulation cascade, thrombin works as a signaling molecule when it interacts with the G-protein coupled receptors PAR1, PAR3, and PAR4. We have mapped the thrombin epitopes responsible for these interactions using enzymatic assays and Ala scanning mutagenesis. The epitopes overlap considerably, and are almost identical to those of fibrinogen and fibrin, but a few unanticipated differences are uncovered that help explain the higher (90-fold) specificity of PAR1 relative to PAR3 and PAR4. The most critical residues for the interaction with the PARs are located around the active site where mutations affect recognition in the order PAR4 > PAR3 > PAR1. Other important residues for PAR binding cluster in a small area of exosite I where mutations affect recognition in the order PAR1 > PAR3 > PAR4. Owing to this hierarchy of effects, the mutation W215A selectively compromises PAR4 cleavage, whereas the mutation R67A abrogates the higher specificity of PAR1 relative to PAR3 and PAR4. 3D models of thrombin complexed with PAR1, PAR3, and PAR4 are constructed and account for the perturbations documented by the mutagenesis studies.

Amino Acid Sequence↗

PubMed2001

Structural basis of the interaction of the pyelonephritic E. coli adhesin to its human kidney receptor.

PapG is the adhesin at the tip of the P pilus that mediates attachment of uropathogenic Escherichia coli to the uroepithelium of the human kidney. The human specific allele of PapG binds to globoside (GbO4), which consists of the tetrasaccharide GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc linked to ceramide. Here, we present the crystal structures of a binary complex of the PapG receptor binding domain bound to GbO4 as well as the unbound form of the adhesin. The biological importance of each of the residues involved in binding was investigated by site-directed mutagenesis. These studies provide a molecular snapshot of a host-pathogen interaction that determines the tropism of uropathogenic E. coli for the human kidney and is critical to the pathogenesis of pyelonephritis.

Adhesins, Escherichia coli↗

PubMed2001

Replacement of thrombin residue G184 with Lys or Arg fails to mimic Na+ binding.

Na+ binding to thrombin enhances the catalytic activity toward numerous synthetic and natural substrates. The bound Na+ is located in a solvent channel 16 A away from the catalytic triad, and connects with D189 in the S1 site through an intervening water molecule. Molecular modeling indicates that the G184K substitution in thrombin positions the protonated epsilon-amino group of the Lys side-chain to replace the bound Na+. Likewise, the G184R substitution positions the guanidinium group of the longer Arg side-chain to replace both the bound Na+ and the connecting water molecule to D189. We explored whether the G184K or G184R substitution would replace the bound Na+ and yield a thrombin derivative stabilized in the highly active fast form. Both the G184K and G184R mutants lost sensitivity to monovalent cations, as expected, but their activity toward a chromogenic substrate was compromised up to 200-fold as a result of impaired diffusion into the S1 site and decreased deacylation rate. Interestingly, both G184K and G184R substitutions compromised cleavage of procoagulant substrates fibrinogen and PAR1 more than that of the anticoagulant substrate protein C. These findings demonstrate that Na+ binding to thrombin is difficult to mimic functionally with residue side-chains, in analogy with results from other systems.

Arginine↗

PubMed2001

Flexibility of the Kir6.2 inward rectifier K(+) channel pore.

Interactions of sulfhydryl reagents with introduced cysteines in the pore-forming (Kir6.2) subunits of the K(ATP) channel were examined. 2-Aminoethyl methanethiosulfonate (MTSEA(+)) failed to modify Cd(2+)-insensitive control-Kir6.2 channels, but rapidly and irreversibly modified Kir6.2[L164C] (L164C) channels. Although a single Cd(2+) ion is coordinated by L164C, four MTSEA(+) "hits" can occur, each sequentially reducing the single-channel current. A dimeric fusion of control-Kir6.2 and L164C subunits generates Cd(2+)-insensitive channels, confirming that at least three cysteines are required for coordination, but MTSEA(+) modification of the dimer occurs in two hits. L164C channels were not modified by bromotrimethyl ammoniumbimane (qBBr(+)), even though qBBr(+) caused voltage-dependent block (as opposed to modification) that was comparable to that of MTSEA(+) or 3-(triethylammonium)propyl methanethiosulfonate (MTSPTrEA(+)), implying that qBBr(+) can also enter the inner cavity but does not modify L164C residues. The Kir channel pore structure was modeled by homology with the KcsA crystal structure. A stable conformation optimally places the four L164C side chains for coordination of a single Cd(2+) ion. Modification of these cysteines by up to four MTSEA(+) (or three MTSPTrEA(+), or two qBBr(+)) does not require widening of the cavity to accommodate the derivatives within it. However, like the KcsA crystal structure, the energy-minimized model shows a narrowing at the inner entrance, and in the Kir6.2 model this narrowing excludes all ions. To allow entry of ions as large as MTSPTrEA(+) or qBBr(+), the entrance must widen to >8 A, but this widening is readily accomplished by minimal M2 helix motion and side-chain rearrangement.

Amino Acid Sequence↗

PubMed2001

Fracture-dislocations of the elbow joint--strategy for treatment and results.

Between January 1993 and December 1996, 41 patients with fracture dislocation of the elbow joint were treated in our department. In 28 patients (median age 46 years, range 15-77 years; 16 male, 12 female), a clinical and radiological follow-up was obtained after median 34 months (range 12-59 months). In addition to the humero-ulnar dislocation, isolated fractures were present in 13 patients and combined fractures in 15 (all with involvement of the radial head). Primary neurological deficits were found in 7 and open fractures in 3 patients. In 7 patients, primary definitive surgical therapy was carried out by open reduction and internal fixation. A two-step surgical management (initial closed reduction and immobilization, 5 patients with external fixator, 7 with plaster; secondary open surgical procedure) was performed in 12 and conservative treatment in 9 patients. According to the Leipzig Elbow Score, taking subjective, clinical and radiological criteria into consideration, 4 patients achieved 'excellent' and 5 patients a 'good' result. Ten patients were scored 'moderate' and 9 'poor'. The rate of secondary complications necessitating revision was 36%. Poor results were primarily caused by extensive initial soft-tissue damage, delayed definitive surgical therapy, and ectopic heterotopic ossification. In contrast, fracture localization and degree of arthrosis were not of significant importance for the final outcome. In fracture dislocations, the goal is a primary definitive surgical treatment aiming for early postoperative physiotherapy.

Adolescent↗

PubMed2001

Arthroscopic-assisted simultaneous reconstruction of the posterior cruciate ligament and the lateral collateral ligament using hamstrings and absorbable screws.

Arthroscopic-assisted simultaneous reconstruction of the posterior cruciate ligament (PCL) and the lateral collateral ligament (LCL) using hamstring tendon grafts is described. The femoral tunnel is drilled through an incision over the medial femoral condyle and the tibial tunnel through the same skin incision used for harvesting the tendon graft. PCL reconstruction is performed using a 4-strand hamstring tendon graft and absorbable screw fixation. The tendon of the semitendinosus muscle of the uninvolved knee is used as a lateral loop for LCL reconstruction. After pulling the transplant through the fibular head, femoral fixation of the loop is made with an absorbable screw.

Absorbable Implants↗

PubMed2001

A relational approach to providing care for a person suffering from dementia.

AIMS OF THE PAPER: This paper examines the care provision for people suffering from dementia and explores the potential benefits associated with an approach to care that emphasizes the importance of relationships. BACKGROUND: Recent research findings have provided an incentive to re-evaluate the established approaches to care for this client group. Two separate studies identified education and intellectual stimulation as important determinants of the onset of Alzheimer's disease (Ott et al. 1995, Snowdon et al. 1996). These findings have encouraged the hypothesis that potential symptomatic benefits may be achieved by providing a more stimulating environment for people with dementia. METHODS: A case study is outlined which illustrates an approach to caring influenced by the Continental philosopher, Emmanuel Levinas. Primacy is given to the relationships that make up caring, and not to a method that sets out to achieve an identified objective. The issue of mutual responsibility within the provision of care is highlighted in the case study. FINDINGS: The hypothesis presented in this paper is that a person has more of an opportunity to develop to the limits of their potential by establishing the importance of relationships in providing care by means of education and training of the people involved. The beneficiaries might be the caregiver or the person in receipt of care. CONCLUSIONS: An environment that attempts to educate people to recognize the importance of relationships will be more effective in achieving the potential benefits of symptom alleviation identified by the research into Alzheimer's disease outlined in this paper.

Aged↗

PubMed2001

Sacrococcygeal teratoma: results of a retrospective multicentric study in Belgium and Luxembourg.

Eighteen patients, operated upon for sacrococcygeal teratoma in 7 different centres in Belgium and Luxembourg between 1992 and 1996, were reviewed. From an epidemiological point of view, this series compares very well to others. Although excellent results were obtained, with all patients surviving, some imperfection in diagnosis, timing of delivery and of operation, and in operative technique was observed. Therefore, it is stated that for optimal treatment of sacrococcygeal teratoma to be achieved, these cases should be treated in just a very few centres of neonatal surgery.

Adult↗

PubMed2001

The Microcystis cyanobacteria bloom in the Swan River--February 2000.

In February 2000 the Swan-Canning estuary in Western Australia experienced a record bloom of the toxic cyanobacteria Microcystis aeruginosa. At its height, concentrations of M. aeruginosa reached integrated water column cell counts of 15,000/ml and formed bright green scums in sheltered bays, where counts of 130 million cells/ml were recorded. Due to public health concerns parts of the river were closed from 10 to 22 February 2000. Two unseasonably large summer rain events in early and late January 2000 created conditions for the bloom. Freshwater runoff, estimated at 270 GL, was enough to fill the Swan-Canning estuary five times over and brought with it high levels of nutrients, mainly nitrogen (> 2.0 mg/L TN) and phosphorus (> 0.15 mg/L TP). A number of methods to reduce bloom accumulations were tried, including an attempt to increase the salinity of the surface water above the critical 10 ppt level for Microcystis; using a bentonite clay and poly-aluminium chloride mixture to flocculate and sink the algae; and sucking up scums using oil spill equipment. Over 900 tonnes of M. aeruginosa were removed and safely disposed using sewage treatment facilities. The bloom collapsed when the freshwater flush subsided and seawater intrusion from the Indian Ocean re-established itself, raising the salinities above the tolerance of Microcystis.

Environmental Monitoring↗