Biomedical subjects

P Huber

Publications and source records attributed to P Huber.

At least 19 recordsLinked to original sources

PubMed2006

Structural transformations of even-numbered n-alkanes confined in mesopores.

The n-alkanes C12H26, C14H30, and C16H34 have been imbibed and solidified in mesoporous Vycor glass with a mean pore diameter of 10 nm. The samples have been investigated by x-ray diffractometry and calorimetric measurements. The structures and phase sequences have been determined. Apart from a reduction and the hysteresis of the melting-freezing transition, pore-confined C12 reproduces the liquid-triclinic phase sequence of the bulk material, but for C16 an orthorhombic rotator mesophase appears that in the bulk state is absent for C16 but well known from odd-numbered alkanes of similar length. In pore-confined C14 this phase shows up on cooling but not on heating.

Journal Article↗

PubMed2006

Src kinase phosphorylates vascular endothelial-cadherin in response to vascular endothelial growth factor: identification of tyrosine 685 as the unique target site.

Src-family tyrosine kinases are regulatory proteins that play a pivotal role in the disorganization of cadherin-dependent cell-cell contacts. We previously showed that Src was associated with vascular endothelial (VE)-cadherin and that tyrosine phosphorylation level of VE-cadherin was dramatically increased in angiogenic tissues as compared to quiescent tissues. Here, we examined whether VE-cadherin was a direct substrate for Src in vascular endothelial growth factor (VEGF)-induced VE-cadherin phosphorylation, and we identified the target tyrosine sites. Co-transfections of Chinese hamster ovary cells (CHO) cells with VE-cadherin and constitutively active Src (Y530F) resulted in a robust tyrosine phosphorylation of VE-cadherin that was not detected with kinase-dead Src (K298M). In an in vitro Src assay, the VE-cadherin cytoplasmic domain is directly phosphorylated by purified Src as well as the tyrosine residue 685 (Tyr)685-containing peptide RPSLY(685)AQVQ. VE-cadherin peptide mapping from human umbilical vein endothelial cells stimulated by VEGF and VE-cadherin-CHO cells transfected with active Src revealed that Y685 was the unique phosphorylated site. The presence of PhosphoY685 was confirmed by its ability to bind to C-terminal Src kinase-SH2 domain in a pull-down assay. Finally, we found that in a VEGF-induced wound-healing assay, cadherin adhesive activity was impaired by Src kinase inhibitors. These data identify that VEGF-induced-VE-cadherin tyrosine phosphorylation is mediated by Src on Y685, a process that appears to be critical for VEGF-induced endothelial cell migration.

Animals↗

PubMed2006

Assessing clinical competence: a pilot project to evaluate the feasibility of a standardized patient -- based practical examination as a component of the Swiss certification process.

PURPOSE: advances in the assessment of clinical competence have prompted medical schools and licensing authorities to complement written and oral tests with practical ones. The purposes of this project were to (1) determine how clinical competencies not effectively addressed on the present Swiss federal examinations can be assessed adequately on a standardised patient-based practical examination (SCE) and (2) evaluate the SCE validity, reliability and feasibility. METHOD: a bilingual, three-hour standardised patient-based clinical examination was pilot tested in 2003 with 48 volunteered fifth and sixth-year students from the five Swiss medical schools. All students took the same eight 15-minute patient cases. To ensure the test content validity, test cases were selected by a multi-disciplinary and -institutional committee of clinical faculty on the basis of predefined exam blueprint criteria and in reference to the Swiss catalogue of learning objectives. RESULTS: moderate correlations between the SCE and the existing Federal final written examinations (0.46) and the newly pilot-tested structured oral examination or SOE (0.56) [3] suggested that they were complementary to one another and that each might emphasise aspects of the clinical competence which others might not. The reliability (a coefficient) of the SCE scores ranged from 0.73 to 0.77. CONCLUSIONS: limited experiences gathered throughout the SCE pilot project demonstrated its feasibility. Preliminary results suggested that SCE scores had a good level of construct validity and reliability and seemed to complement scores obtained on the final certification written examinations and the newly tested SOE. These results, however, need to be further confirmed with larger samples studies.

Certification↗

PubMed2006

Inverse planned stereotactic intensity modulated radiotherapy (IMRT) in the treatment of incompletely and completely resected adenoid cystic carcinomas of the head and neck: initial clinical results and toxicity of treatment.

BACKGROUND: Presenting the initial clinical results in the treatment of complex shaped adenoid cystic carcinomas (ACC) of the head and neck region by inverse planned stereotactic IMRT. MATERIALS: 25 patients with huge ACC in different areas of the head and neck were treated. At the time of radiotherapy two patients already suffered from distant metastases. A complete resection of the tumor was possible in only 4 patients. The remaining patients were incompletely resected (R2: 20; R1: 1). 21 patients received an integrated boost IMRT (IBRT), which allow the use of different single doses for different target volumes in one fraction. All patients were treated after inverse treatment planning and stereotactic target point localization. RESULTS: The mean follow-up was 22.8 months (91-1490 days). According to Kaplan Meier the three year overall survival rate was 72%. 4 patients died caused by a systemic progression of the disease. The three-year recurrence free survival was according to Kaplan Meier in this group of patients 38%. 3 patients developed an in-field recurrence and 3 patient showed a metastasis in an adjacent lymph node of the head and neck region. One patient with an in-field recurrence and a patient with the lymph node recurrence could be re-treated by radiotherapy. Both patients are now controlled. Acute side effects >Grade II did only appear so far in a small number of patients. CONCLUSION: The inverse planned stereotactic IMRT is feasible in the treatment of ACC. By using IMRT, high control rates and low side effects could by achieved. Further evaluation concerning the long term follow-up is needed. Due to the technical advantage of IMRT this treatment modality should be used if a particle therapy is not available.

Adult↗

PubMed2006

Benefits of a programme taking advantage of patient-instructors to teach and assess musculoskeletal skills in medical students.

AIM: To evaluate a rheumatoid arthritis patient-instructor-based formation-assessment programme for its ability to improve and assess musculoskeletal knowledge and skills in third-year medical students. METHODS: (1) The quality of our musculoskeletal teaching was assessed before patient-instructor intervention through an open-questions test (pre-test) and performance record forms (PRFs) filled in by the patient-instructors. (2) The improvement afforded by patient-instructors was evaluated through a second (identical) open-questions test (post-test). (3) The resulting skills in the students were further assessed by an individual patient-instructors physical status record form (PSRF), filled in by the students. RESULTS: Pre-tests and post-tests showed an improvement in correct answers from a mean score of 39% to 47%. The history-taking questions that obtained <50% scores in the pre-test mostly dealt with the consequences of a chronic illness. Intervention of patient-instructors especially improved knowledge of the psychosocial aspects and side effects of drugs. With regard to physical examination, patient-instructors makedly improved the identification of assessment of signs of active and chronic inflammation. PRF analysis showed that 10 of 28 questions answered by <50% of the students were related to disease characteristics of rheumatoid arthritis, extra-articular signs, side effects of drugs and psychosocial aspects. Analysis of the PSRF indicated that the weakness of our students' physical examination abilities in particular is related to recognising the types of swelling and differentiating tenderness from pain on motion. CONCLUSION: This study proves the considerable benefits of the involvement of patient-instructors in the teaching and assessment of clinical skills in students.

Arthritis, Rheumatoid↗

PubMed2006

Kilovoltage CT using a linac-CT scanner combination.

Modern radiotherapy techniques such as intensity modulation are capable of generating complex dose distributions whose high dose areas tightly conform to the tumour target volume, sparing critical organs even when they are located in close proximity. This potential can only be exploited to its full extent when the accumulated dose actually delivered over the complete treatment course is sufficiently close to the dose computed on the initial CT scan used for treatment planning. Exact patient repositioning is mandatory, but also other sources of error, e.g. changes of the patient's anatomy under therapy, should be taken into account. At the German Cancer Research Center, we use a combination of a linear accelerator and a CT scanner installed in one room and sharing the same couch. It allows the quantification and correction of interfractional variations between planning and treatment delivery. In this paper, we describe treatments of prostate, paraspinal and head and neck tumours. All patients were immobilized by customized fixation devices and treated in a stereotactic setup. For each patient, frequent CT scans were taken during the treatment course. Each scan was compared with the original planning CT using manual checks and automatic rigid matching algorithms. Depending on the individual case, the adaptation to variations was carried out offline after several fractions or in real-time between the CT scan and linac irradiation. We discuss the techniques for detecting and correcting interfractional errors and outline the procedural steps of a linac-CT scanner-supported radiation treatment course.

Humans↗

PubMed2005

Tracing the glycogen cells with protocadherin 12 during mouse placenta development.

Among the different trophoblast subtypes of the mouse placenta, the glycogen cells (GC) are one of the trophoblast subtypes that invade the decidua. We previously established that GC specifically expressed protocadherin 12 (PCDH12). In this paper, we investigated the origin of the PCDH12-positive cells and we characterized their fate in the maternal tissues. Our data indicate that they directly originate from the central part of the ectoplacental cone at embryonic day (E) 7.5. PCDH12-positive cells start to accumulate glycogen from E10.5 and the first migrating cells could be observed from this age. Unlike other placental and decidual cells, GC do not express P-cadherin, which may explain their migration properties in this organ. In the decidua, GC settle in the vicinity of the maternal vascular sinuses but do not incorporate in the endothelium. By the end of gestation (E17.5), most GC islets of the decidua enter into a lytic phase and form large lacunae. These lacunae, filled with glycogen, may provide a substantial source of energy at the end of gestation or during delivery. Our data suggest that spongiotrophoblasts and GC are two independent lineages and we bring insights into GC migration and fate.

Animals↗

PubMed2005

Faraday instability in a surface-frozen liquid.

Faraday surface instability measurements of the critical acceleration, a(c), and wave number, k(c), for standing surface waves on a tetracosanol (C24H50) melt exhibit abrupt changes at T(s)=54 degrees C, approximately 4 degrees C above the bulk freezing temperature. The measured variations of a(c) and k(c) vs temperature and driving frequency are accounted for quantitatively by a hydrodynamic model, revealing a change from a free-slip surface flow, generic for a free liquid surface (T>T(s)), to a surface-pinned, no-slip flow, characteristic of a flow near a wetted solid wall (T<T(s)). The change at T(s) is traced to the onset of surface freezing, where the steep velocity gradient in the surface-pinned flow significantly increases the viscous dissipation near the surface.

Journal Article↗

PubMed2005

Stereotactically guided fractionated re-irradiation in recurrent glioblastoma multiforme.

PURPOSE: To assess the feasibility, efficacy and toxicity of fractionated stereotactic radiotherapy in the treatment of recurrent glioblastoma multiforme. PATIENTS AND METHODS: From January 1995 to July 2003, 53 patients with histologically proven glioblastoma multiforme were treated at recurrence with fractionated stereotactic radiation therapy. A median dose of 36 Gy using a median fractionation of 5 x 2 Gy/week was applied. RESULTS: Median overall survival was 21 months, and median overall survival from the time point of re-irradiation was 8 months. The median time interval between primary and secondary radiation therapy was 10 months. In this patient population, no variables predicting longer overall survival could be determined. However, neurosurgical resection at relapse was associated with increased survival after re-irradiation (p=0.04), but left progression-free survival unaltered. Treatment was well-tolerated and no severe toxicities developed. CONCLUSION: Stereotactically guided fractionated re-irradiation is a safe and effective treatment modality in selected cases of recurring glioblastoma multiforme. Since this is not a randomized study, further evaluation in larger patient collectives is warranted. Also, based on recent results of radiochemotherapy in the treatment of primary glioblastoma multiforme, concomitant chemotherapy at relapse might be considered in the future.

Brain Neoplasms↗

PubMed2005

Dynamics of serum procalcitonin in patients after major neurosurgery.

Classical markers of infection cannot differentiate reliably between inflammation and infection after neurosurgery. This study investigated the dynamics of serum procalcitonin (PCT) in patients following major neurosurgery. PCT concentrations remained < 0.2 ng/mL during the post-operative course. In contrast, leukocyte and neutrophil counts, as well as C-reactive protein (CRP) levels, increased significantly post-operatively (leukocytes, range 7.1-23.7 x 10(9)/L, p < 0.001; neutrophils, range 70.8-94.5%, p < 0.001; CRP, median 14 mg/L, range 3-95 mg/L, p < 0.001). Analysis of PCT levels using assays with improved sensitivity may be useful in the diagnosis of neurosurgical patients with post-operative fever of unknown origin.

Adult↗

PubMed2005

The biomechanical effect of radial shortening on the radiocapitellar articulation.

Repeated trauma to the radial head may be one of the causative factors in the genesis of osteochondritis dissecans of the capitellum. We measured the force, contact area and pressure across the radiocapitellar articulation of the elbow before and after radial shortening osteotomy in five fresh-frozen cadaver upper limbs with loads of 45, 90 and 135 N, respectively. Measurements were made on pressure-sensitive film placed in the radiocapitellar articulation with the forearm in the supinated, neutral and pronated positions before and after radial shortening. Radial shortening significantly reduced the mean force and contact area across the radiocapitellar articulation in all positions of the forearm.

Biomechanical Phenomena↗

PubMed2004

Comparison of different methods for the measurement of serum testosterone in the aging male.

BACKGROUND: Circulating testosterone (T) levels, mainly non-SHBG bound fractions, decline with advancing age. Free (FT) and bioavailable (BT) testosterone levels have been suggested to represent more reliably the bioactive hormone at the tissue level as compared to total testosterone (TT) levels. However, there is an ongoing controversy as to which T assay is most appropriate in defining T deficiency in the aging male. METHODS: In a prospective observational study, TT, FT and BT levels were measured in 51 elderly men (55 to 70 years). TT levels were determined on two different days using 2 different assays. FT was calculated using TT, albumin and SHBG levels as well as measured directly by radioimmunoassay. The free androgen index (FAI) was calculated using the formula 100 x TT/SHBG. BT was obtained by precipitation of SHBG-bound T with ammonium sulphate. RESULTS: We found good correlations within different assays for TT (r = 0.87 to 0.91, p <0.001) and between TT and calculated FT (r = 0.66 to 0.84, p <0.001). In contrast, the correlation between TT and BT was poor (r = 0.17 to 0.19, p = ns). TT was equivalent to calcFT and was better in mirroring clinical sings of androgen deficiency in elderly men as compared to BT. The intra-individual day-to-day variance of TT levels was 14.8% (range 0.1-79%) with a coefficient of variance of 12.6%. CONCLUSION: Serum TT and the calculated FT fraction correlated well with each other and were superior in defining a group of elderly men with suspected androgen deficiency. In contrast, FT measured by direct RIA and BT reflected gonadal function poorly. Our data favour the repetitive use of TT when screening for androgen deficiency in elderly men.

Aged↗

PubMed2004

Isolation and partial characterization of a calcium-dependent lectin (chiletin) from the haemolymph of the flat oyster, Ostrea chilensis.

A calcium-dependent lectin (chiletin) was isolated from oyster haemolymph by mannose elution from Sepharose CL-6B followed by anion exchange chromatography. Chiletin was predominantly composed of 12 and 24 kDa bands when examined with SDS-PAGE under reducing and non-reducing conditions, respectively. Larger molecular weight bands of 36 and 50 kDa were also variably present under reducing conditions. The NH2-terminal sequence of the 24 kDa band was determined and was not homologous to any known protein from the databases searched. Isolated chiletin was composed of multiple isomers approximately 12 kDa in size and ranging in pI from 5.2 to 6.0. Rabbit antiserum was raised to a synthetic peptide coupled to keyhole limpet hemocyanin and the size of the chiletin subunits was confirmed by Western blot. Two and five different conformational aggregates of chiletin were resolved in oyster haemolymph using size exclusion chromatography in 8 M urea and PBS, respectively. The largest aggregate obtained from size exclusion in 8 M urea was estimated to be greater than 640 kDa. The ability of whole haemolymph and isolated chiletin to agglutinate sheep red blood cells was inhibited by galactose and mannose. Chiletin was identified by immunohistochemistry to be most consistently present in the auricle, followed by the digestive gland, however staining was seen sporadically in haemocytes, gastrointestinal epithelium and interstitial connective tissue cells.

Agglutination Tests↗

PubMed2003

Expression of thymidine kinase driven by an endothelial-specific promoter inhibits tumor growth of Lewis lung carcinoma cells in transgenic mice.

The possibility of inhibiting tumor growth by limiting angiogenesis has raised considerable interest. In this study, we examined the feasibility of inhibiting tumor growth by targeting a suicide gene in the endothelium. Toxicity must be directed solely to angiogenic cells. Therefore, we used the herpes simplex virus-thymidine kinase (TK) gene, in combination with the prodrug ganciclovir (GCV), which affects replicative cells. To test this strategy, we produced transgenic mice carrying the TK gene driven by the vascular endothelial (VE)-cadherin promoter. Lewis lung carcinoma cells were injected subcutaneously to establish tumors and to test the effect of GCV on tumor growth. In two independent transgenic lines, GCV treatment (75 mg/kg/day) resulted in a 66-71% reduction of tumor volume at day 20 postimplantation compared to wild-type mice (650 and 550 versus 1930 mm(3), P<0.02 and 0.01, respectively), whereas no significant difference was observed when vehicle alone was injected. Tumor growth inhibition was accompanied by a marked reduction in tumor vascular density (151 versus 276 vessels/mm(2), P<0.05) and an increase in tumor cell death, suggesting that tumor growth inhibition was caused by a reduction in tumor angiogenesis. Our data support the potential utility of endothelial targeting of suicide genes in cancer therapy.

Animals↗

PubMed2003

Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay: a prospective randomized comparison of two hundred unselected patients undergoing off-pump versus conventional coronary artery bypass grafting.

OBJECTIVE: Retrospective comparisons of selected patients undergoing off-pump versus conventional on-pump coronary artery bypass grafting have yielded inconsistent results and raised concerns about completeness of revascularization in off-pump coronary artery bypass grafting. METHODS: Two hundred unselected patients referred for elective primary coronary artery bypass grafting were randomly assigned to undergo off-pump coronary artery bypass grafting with an Octopus tissue stabilizer (Medtronic, Inc, Minneapolis, Minn) or conventional coronary artery bypass grafting with cardiopulmonary bypass by a single surgeon. Revascularization intent determined before random assignment was compared with the revascularization performed. All management followed strict, unbiased, criteria-driven protocols. Patients and nonoperative care providers were blinded to surgical group. RESULTS: Baseline characteristics were similar. The number of grafts performed per patient (mean +/- SD 3.39 +/- 1.04 for off-pump coronary artery bypass grafting, 3.40 +/- 1.08 for conventional coronary artery bypass grafting) and the index of completeness of revascularization (number of grafts performed/number of grafts intended, 1.00 +/- 0.18 for off-pump coronary artery bypass grafting, 1.01 +/- 0.09 for conventional coronary artery bypass grafting) were similar. Likewise, the index of completeness of revascularization was similar between groups for the lateral wall. Combined hospital and 30-day mortalities and stroke rates were similar. Postoperative myocardial serum enzyme measures were significantly lower after off-pump coronary artery bypass grafting, suggesting less myocardial injury. Adjusted postoperative thromboelastogram indices, fibrinogen, international normalized ratio, and platelet levels all showed significantly less coagulopathy after off-pump coronary artery bypass grafting. Patients undergoing off-pump coronary artery bypass grafting received fewer units of blood, were more likely to avoid transfusion altogether, and had a higher hematocrit at discharge. Cardiopulmonary bypass was an independent predictor of transfusion (odds ratio 2.42, P =.0073) by multivariate analysis. More patients undergoing off-pump coronary artery bypass grafting were extubated in the operating room and within 4 hours. Postoperative length of stay (in days) was shorter for off-pump coronary artery bypass grafting (5.1 +/- 6.5 for off-pump coronary artery bypass grafting, 6.1 +/- 8.2 for conventional coronary artery bypass grafting, P =.005 by Wilcoxon test). One patient (in the conventional coronary artery bypass grafting group) required angioplasty for graft closure within 30 days. CONCLUSIONS: When compared with conventional coronary artery bypass grafting with cardiopulmonary bypass, off-pump coronary artery bypass grafting achieved similar completeness of revascularization, similar in-hospital and 30-day outcomes, shorter length of stay, reduced transfusion requirement, and less myocardial injury.

Blood Transfusion↗

PubMed2003

Are solidified fillings of mesopores basically bulk-like except for the geometric confinement?

A short review of our thermodynamic and structural work on Ar, N(2), CO, O(2), and the n-alkane C(19)H(40) in mesoporous glasses is presented. The experimental information comes from X-ray diffraction, vapour pressure isotherms, optical transmission, heat capacity, and dielectric measurements. The filling in the pore centre formed by capillary condensation is distinguished from the adsorbed layers on the pore walls and is compared to the bulk state. Special attention is paid to metastable states and to the rearrangement of partial fillings that show up as a consequence of phase transitions.

Journal Article↗

PubMed2003

A comparison of biomechanical mechanisms of whiplash injury from rear impacts.

Several hypotheses have been proposed to explain the mechanism of injury in whiplash including, pressure on nerve root ganglia, stretching of facet capsules, or damage to facet articular cartilage. These injury mechanisms have not been directly compared in the same study. A comparison could provide insight into the most likely mechanism of whiplash injury. Twenty eight volunteers underwent rear impacts with head and chest acceleration data collected. The same apparatus was used to test 11 cervico-thoracic human cadaveric spines with an instrumented headform attached. Head acceleration, individual vertebral kinematics from high speed video, local nerve root pressure, and facet joint contact pressures were collected during impacts. Each specimen was tested first at an impact acceleration similar to that of volunteers, who reported minimal or no symptoms after the test, then at double the acceleration. Head X (forward) and Z (upward) accelerations of cadaveric specimens were very similar in time sequence and magnitude to those of unprepared volunteers. Pressure around the lower cervical nerve roots ranged from 2.7kPa to 10kPa, and occurred generally after chest but before peak head acceleration. Facets at C4-5 and C5-6 had the highest probability (64% and 71% respectively) of pinching. Neither pressure rise nor pinching changed significantly with increased acceleration. Vertebral intersegmental extension rotations (4 ( o ) -9.5 ( o ) ) and posterior translations (3.7-8.9 mm) peaked near maximum head excursion into the head restraint, at the time of peak head acceleration. Vertebral shear translations showed the largest (and only significant) increases with increased impact acceleration. This data implies that facet shearing was most sensitive to the increased acceleration in this experiment and may be a primary mechanism of cervical spine injury in rear impacts.

Acceleration↗

PubMed2003

Nitrogen removal from digester supernatant via nitrite--SBR or SHARON?

Separate biological elimination of nitrogen from the digester supernatant of a municipal wastewater treatment plant (WWTP) was investigated in pilot and full-scale plants. Denitrification mainly via nitrite was achieved in a sequencing batch reactor (SBR) and a continuous flow reactor (CSTR or SHARON). Suppression of nitrite oxidation in the SBR was feasible at short aerobic/anaerobic intervals allowing for immediate denitrification of the produced nitrite. Nitrate production could also be stopped by exposing the biomass to anaerobic conditions for 11 days. Temporarily high concentrations (up to 80 gNH3-Nm(-3)) of free ammonia could not be considered as the major reason for inhibiting nitrite oxidation. In a full-scale SBR plant 90% of the nitrogen load was denitrified in a total hydraulic retention time (HRT) of 1.6 days and with a sludge age between 15 and 20 days. Ethanol and methanol were used for denitrification. The specific average substrate consumption was 2.2 gCOD(dosed) g(-1)N(removed) with an effective biomass yield of 0.2 gCOD(biomass) g(-1)COD(dosed). No dosing with base was required. In the SHARON process full nitrogen elimination was achieved only with a total HRT greater than 4 days at 29 degrees C. The overall costs were estimated at 1.4 euros kg(-1)N(removed) for the SBR and 1.63 euros kg(-1)N(removed) in SHARON mode, respectively. The SHARON process is simple in operation (CSTR) but the tank volume has to be significantly greater than in SBR.

Bacteria, Aerobic↗