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Biomedical subjects

D Koch

Publications and source records attributed to D Koch.

At least 19 recordsLinked to original sources

Cell motility and local viscoelasticity of fibroblasts.

Viscoelastic changes of the lamellipodial actin cytoskeleton are a fundamental element of cell motility. Thus, the correlation between the local viscoelastic properties of the lamellipodium (including the transitional region to the cell body) and the speed of lamellipodial extension is studied for normal and malignantly transformed fibroblasts. Using our atomic force microscopy-based microrheology technique, we found different mechanical properties between the lamellipodia of malignantly transformed fibroblasts (H-ras transformed and SV-T2 fibroblasts) and normal fibroblasts (BALB 3T3 fibroblasts). The average elastic constants, K, in the leading edge of SV-T2 fibroblasts (0.48 +/- 0.51 kPa) and of H-ras transformed fibroblasts (0.42 +/- 0.35 kPa) are significantly lower than that of BALB 3T3 fibroblasts (1.01 +/- 0.40 kPa). The analysis of time-lapse phase contrast images shows that the decrease in the elastic constant, K, for malignantly transformed fibroblasts is correlated with the enhanced motility of the lamellipodium. The measured mean speeds are 6.1 +/- 4.5 microm/h for BALB 3T3 fibroblasts, 13.1 +/- 5.2 microm/h for SV-T2 fibroblasts, and 26.2 +/- 11.5 microm/h for H-ras fibroblasts. Furthermore, the elastic constant, K, increases toward the cell body in many instances which coincide with an increase in actin filament density toward the cell body. The correlation between the enhanced motility and the decrease in viscoelastic moduli supports the Elastic Brownian Ratchet model for driving lamellipodia extension.

Animals↗

Towards smaller and faster gas chromatography-mass spectrometry systems for field chemical detection.

Gas chromatography-mass spectrometry (GC-MS) is already an important laboratory method, but new sampling techniques and column heating approaches will expand and improve its usefulness for detection and identification of unknown chemicals in field settings. In order to demonstrate commercially-available technical advances for both sampling and column heating, we used solid phase microextraction (SPME) sampling of both water and air systems, followed by immediate analysis with a resistively heated analytical column and mass spectrometric detection. High-concern compounds ranging from 140 to 466 amu were analyzed to show the applicability of these techniques to emergency situations impacting public health. A field portable (about 35 kg) GC-MS system was used for analysis of water samples with a resistively heated analytical column externally mounted as a retrofit using the air bath oven of the original instrument design to heat transfer lines. The system used to analyze air samples included a laboratory mass spectrometer with a dedicated resistive column heating arrangement (no legacy air bath column oven). The combined sampling and analysis time was less than 10 min for both air and water sample types. By combining dedicated resistive column heating with smaller mass spectrometry systems designed specificallyfor use in the field, substantially smaller high performance field-portable instrumentation will be possible.

Gas Chromatography-Mass Spectrometry↗

Climatic conditions as a risk factor in canine gastric dilatation-volvulus.

Canine acute gastric dilatation-volvulus (GDV) is a life-threatening condition of multifactorial origin. The risk of developing GDV is influenced by a variety of factors, including breed, age, gender, temperament, diet and management. A relationship between seasonal variations and the frequency of GDV has been previously documented although no association was found with any specific climatic event. Variables in weather conditions within a defined geographic region were investigated in a retrospective study of 287 client-owned dogs diagnosed with GDV between 1992 and 1999. Monthly incidences were evaluated and differences in atmospheric temperature, humidity and pressure between days in which GDV cases were observed and days in which no case was presented were examined. Although temperature was significantly associated with the occurrence of GDV, the difference in temperatures between days with and days without GDV cases was so small that it is unlikely to be of clinical relevance. Moreover, no significant association was found between GDV occurrence and atmospheric pressure or humidity, and a seasonal variation in GDV incidence was not observed.

Animals↗

[Epidemiology of tick-borne encephalitis (TBE) in Switzerland 1984 to 2004].

From 1984 to 2004 a total of 1370 TBE cases have been reported to the Federal Office of Public Health through the notification system. A significant increase of cases was observed in the nineties. Since 1999 the yearly average of reported cases was 101, corresponding to a yearly incidence of 1.4/10(5) inhabitants for all of Switzerland or to an incidence of approximately 6/10(5) if only the population living in endemic regions is taken into account. Male cases were twice as frequent as female ones. The age distribution showed two peaks in the age ranges of 6 to 14 and 60 to 69 years. Cases in children under 6 years of age were very rare with a yearly average of two hospitalised children. The severity of the disease increased with age. In 86% of the patients CNS involvement was present while 14% showed only flu-like symptoms. Ninety percent of patient with CNS involvement were hospitalised, 1,3% died (on average one death per year since 1999). Cases in fully vaccinated persons were very rare. The majority of patients had most probably been infected at their place of residence or in the nearer surroundings. The incidence in the large cities was low (< or = 1/10(5)/year). In smaller towns located directly in an endemic region, the incidence rose to as much as 18/10(5)/year. During the 21 years of observation, the endemic regions in four cantons known in the early eighties had clearly expanded and new infected regions appeared in seven other cantons. A frequent recreational or occupational exposure in wooded areas was mentioned by 85% of the patients. Although 80% of these concerned leisure time activities (mainly walking), the incidence is most probably still higher in occupationally exposed persons. This indicates that not only persons with leisure time exposure but also occupationally exposed persons are still insufficiently vaccinated to achieve an optimal control of this disease in Switzerland.

Adolescent↗

Fixation of a proximal femoral physeal fracture in a dog using a ventral approach and two Kirschner wires.

A Salter-Harris type I proximal femoral physeal fracture was diagnosed in a six-month-old Norfolk Terrier. The fracture was reduced using a ventromedial approach to the hip joint and fixation with two small Kirschner wires applied from the joint surface and countersunk below the cartilage. The ventromedial approach minimizes soft-tissue and vascular damage and affords direct visualization of the fracture, facilitating reduction and fixation. The two-year postoperative outcome was considered satisfactory in this case.

Accidents, Traffic↗

Extracorporeal shockwave therapy in a dog with chronic bicipital tenosynovitis.

A 15-month-old, spayed female, Bernese mountain dog was presented to the Institute of Small Animal Surgery at the University of Zurich because of chronic left forelimb lameness. The referring veterinarian diagnosed pain in the left shoulder region and had treated the dog with systemic non-steroidal anti-inflammatory drugs and restricted exercise for a two-week period. The follow-up examination revealed only minimal improvement and therefore, the dog was referred for further diagnostic evaluation. Chronic bicipital tenosynovitis and tendinitis of the infraspinatus muscle was diagnosed based on survey radiographs, arthrography, ultrasound, computed tomography (CT), and synovial fluid cytology. The dog underwent three sessions of extracorporeal shockwave therapy and substantial clinical improvement was observed. On follow-up examinations, only mild left forelimb lameness was evident following exercise, and changes in the intertubercular groove and at the supraglenoid tuberosity appeared less active on radiographs and CT. However, six months following treatment, mild degenerative joint disease was apparent.

Animals↗

Coping strategies and the request for a consultation on complementary and alternative medicine -- a cross-sectional survey of patients in a psychosomatic and three medical departments of a german university hospital.

OBJECTIVE: To identify factors, predicting which patients of a large German university hospital request for a consultation on complementary and alternative medicine (CAM). PATIENTS AND METHODS: 350 patients of 3 medical and a psychosomatic department of the University Hospital Freiburg were consecutively surveyed with respect to their coping strategies, health locus of control, anxiety, depression, and the request for a consultation on CAM. Predicting factors were identified via logistic regression models. RESULTS: The request for a CAM consultation was primarily determined by an active coping strategy (odds ratio 1.66, 95% confidence interval 1.27-2.17, p = 0.0002) and a low Karnofsky index (odds ratio 0.79, 95% confidence interval 0.62-0.99, p = 0.0417). Anxiety, depression or internal health locus of control correlated with each other but could not be proved as independent factors for the request for a CAM consultation. CONCLUSION: Patients of a university hospital with an active disease coping have a need for information about CAM.

Adaptation, Psychological↗

Guiding neuronal growth with light.

Control over neuronal growth is a fundamental objective in neuroscience, cell biology, developmental biology, biophysics, and biomedicine and is particularly important for the formation of neural circuits in vitro, as well as nerve regeneration in vivo [Zeck, G. & Fromherz, P. (2001) Proc. Natl. Acad. Sci. USA 98, 10457-10462]. We have shown experimentally that we can use weak optical forces to guide the direction taken by the leading edge, or growth cone, of a nerve cell. In actively extending growth cones, a laser spot is placed in front of a specific area of the nerve's leading edge, enhancing growth into the beam focus and resulting in guided neuronal turns as well as enhanced growth. The power of our laser is chosen so that the resulting gradient forces are sufficiently powerful to bias the actin polymerization-driven lamellipodia extension, but too weak to hold and move the growth cone. We are therefore using light to control a natural biological process, in sharp contrast to the established technique of optical tweezers [Ashkin, A. (1970) Phys. Rev. Lett. 24, 156-159; Ashkin, A. & Dziedzic, J. M. (1987) Science 235, 1517-1520], which uses large optical forces to manipulate entire structures. Our results therefore open an avenue to controlling neuronal growth in vitro and in vivo with a simple, noncontact technique.

Actin Cytoskeleton↗

Re-ventriculostomy for treatment of obstructive hydrocephalus in cases of stoma dysfunction.

In this article, 12 re-ventriculostomies in the treatment for obstructive hydrocephalus are described. The etiology of the hydrocephalus was a benign aqueductal stenosis in 9 patients, a tumor around the aqueduct in 2 patients and intraventricular bleeding in one patient. In all cases the initial ventriculostomy was successful, but after a time interval of 2 weeks to 6 years the patients developed similar clinical symptoms as preoperatively. In all except one case the radiological findings spoke in favour of stoma closure. Intraoperatively the stoma was completely closed in 9 patients and in 3 patients a subtotal closure was observed. In all cases a re-ventriculostomy was performed bluntly with a Fogarty catheter in loco typico at the floor of the third ventricle. Of the 12 patients 6 had an excellent outcome postoperatively, one patient improved and one had a benefit from the re-ventriculostomy although he died of cardiac problems. In the remaining 4 patients the re-ventriculostomy was not successful and the patients needed a shunt operation. In conclusion, after initially successful endoscopic third ventriculostomy, re-ventriculostomy should be considered as a sufficient treatment option in case of suspected stoma dysfunction.

Adolescent↗

Olefin metathesis in supercritical carbon dioxide.

Liquid or supercritical carbon dioxide (scCO(2)) is a versatile reaction medium for ring-opening metathesis polymerization (ROMP) and ring-closing olefin metathesis (RCM) reactions using well-defined metal catalysts. The molybdenum alkylidene complex 1 and ruthenium carbenes 2 and 3 bearing PCy(3) or N-heterocyclic carbene ligands, respectively, can be used and are found to exhibit efficiency similar to that in chlorinated organic solvents. While compound 1 is readily soluble in scCO(2), complexes 2 and 3 behave like heterogeneous catalysts in this reaction medium. Importantly, however, the unique properties of scCO(2) provide significant advantages beyond simple solvent replacement. This pertains to highly convenient workup procedures both for polymeric and low molecular weight products, to catalyst immobilization, to reaction tuning by density control (RCM versus acyclic diene metathesis polymerization), and to applications of scCO(2) as a protective medium for basic amine functions. The latter phenomenon is explained by the reversible formation of the corresponding carbamic acid as evidenced by (1)H NMR data obtained in compressed CO(2). Together with its environmentally and toxicologically benign character, these unique physicochemical features sum up to a very attractive solvent profile of carbon dioxide for sustainable synthesis and production.

Journal Article↗

T-cell activation by recombinant receptors: CD28 costimulation is required for interleukin 2 secretion and receptor-mediated T-cell proliferation but does not affect receptor-mediated target cell lysis.

Recombinant T-cell receptors with antibody-like specificity are successfully used to direct CTLs toward a MHC-independent immune response against target cells. Here we monitored the specific activation of receptor grafted CTLs in the context of CD28 costimulation. Peripheral blood T cells were retrovirally engrafted with recombinant anti-CD30 and anti-carcinoembryonic antigen receptors, respectively, that harbor either the Fc epsilonRI-gamma or the CD3-zeta intracellular signaling domain. Cross-linking of recombinant receptors by solid-phase bound ligand, i.e., CD30 and a carcinoembryonic antigen receptor-specific anti-idiotypic antibody, respectively, induces IFN-gamma secretion that is further enhanced by CD28 costimulation of grafted T cells. Induction of interleukin (IL)-2 secretion, in contrast, requires CD28 costimulation in addition to receptor cross-linking, irrespective of T-cell preactivation by anti-CD3 monoclonal antibody plus IL-2 or by anti-CD3 monoclonal antibody plus anti-CD28 monoclonal antibody. Accordingly, induction of IL-2 secretion upon receptor cross-linking by membrane-bound antigen requires CD28/B7 costimulation whereas IFN-gamma secretion and cell proliferation does not. The efficiency of cytolysis by receptor-grafted CTLs does not depend on and is not affected by CD28 costimulation. The data demonstrate that CTL proliferation, cytokine secretion, and cytolysis upon receptor cross-linking are differentially modulated by CD28 costimulation and that cytolysis does not require B7 expression on target cells.

Animals↗

Atypical teratoid/rhabdoid tumors in adult patients: case report and review of the literature.

Atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system are rare and extremely aggressive malignancies of early childhood. We report a case of AT/RT in an adult patient. A 30-year-old woman presented with headache, vomiting and ataxia during the second trimester of pregnancy. Magnetic resonance imaging revealed a posterior fossa mass. A gross total resection was performed. Pathological examination revealed an AT/RT. Despite the dismal prognosis the patient decided not to undergo an abortion. For this reason postoperative accelerated hyperfractionated radiotherapy was limited to the tumor region. Six months later the woman delivered a healthy baby. One week postpartum, a central nervous system recurrence localized apart from the primary lesion was treated with radiosurgery. Two months later a diffuse progression was noted. Despite a 6 week course of oral temozolomide, the tumor progressed and the patient died 11 months after diagnosis. Although survival was short, surgery and involved field radiotherapy yielded a progression-free interval of 9 months. This allowed the patient to carry pregnancy to term. Radiosurgery resulted in a complete remission of the first recurrence. Oral chemotherapy was not effective in controlling diffuse tumor spread.

Adult↗

Recurrent cubital tunnel syndrome. Etiology and treatment.

Controversy surrounds the treatment of recurrent cubital tunnel syndrome after previous surgery. Irrespective of the surgical technique, namely pure decompression in the ulnar groove and the cubital tunnel distal of the medial epicondyle, and the different methods of volar transposition (subcutaneous, intramuscular, and submuscular), the results of surgical therapy of cubital tunnel syndrome are often not favorable, especially in cases of long-standing symptoms and severe deficits. Twenty-two patients who had previously undergone surgical treatment for ulnar nerve entrapment at the elbow were evaluated because of persistent or recurrent pain, paresthesia, numbness, and motor weakness. Ten patients had undergone a nerve transposition, 5 patients underwent a simple decompression of the ulnar nerve, and 7 patients experienced two previous operations with different surgical techniques. Two patients underwent surgery at our hospital, whereas 20 patients underwent their primary surgery at other institutions. Various surgical techniques were used during the subsequent surgery, such as external neurolysis, subcutaneous anterior transposition, and subsequent transfer of the nerve back into the sulcus. The causes of continued or recurrent symptoms after initial surgery included dense perineural fibrosis of the nerve after subcutaneous transposition, adhesions of the nerve to the medial epicondyle and retention of the medial intermuscular septum. The average follow-up after the last procedure was 7 months (2 - 20 months). All 7 patients with subsequent transfer of the ulnar nerve back into the sulcus became pain-free, whereas only 11 of 15 patients who had external neurolysis or subcutaneous transposition became free of pain or experienced reduced pain. The recovery of motor function and return of sensibility were variable and unpredictable. In summary, reoperation after primary surgery of cubital tunnel syndrome gave satisfactory results in 18 of 22 cases. Subsequent transfer of the ulnar nerve back into the sulcus promises to be useful in cases in which subcutaneous transposition had not been successful.

Adult↗

Adult cochlear implant patient performance with evolving electrode technology.

OBJECTIVE: In 1998, clinical trials were initiated to evaluate the CLARION Multi-Strategy Cochlear Implant (Advanced Bionics Corp., Sylmar, CA, U.S.A.), a precurved electrode with an electrode positioning system (EPS) in adults with severe to profound hearing impairments. In 1999, clinical trials were initiated to assess the CLARION HiFocus electrode with EPS in a similar group of adults. The purpose of this retrospective study was to evaluate and compare the preoperative and 1-, 3-, and 6-month postoperative speech perception scores obtained by the first 56 patients implanted with the precurved electrode with EPS and the first 56 patients implanted with the HiFocus electrode with EPS. Speech strategy preferences were additionally noted and compared at each test interval for each group. STUDY DESIGN: All subjects participated in preoperative testing with hearing aids and postoperative (1, 3 and 6 months) testing with either the precurved electrode with EPS or the HiFocus electrode with EPS. Demographic characteristics and preoperative and postoperative speech perception results were compared within and between the 2 groups. SETTING: Data presented here were collected at cochlear implant programs affiliated with tertiary medical centers located in the United States and Canada that participated in the clinical trials. PATIENTS: Patients were postlinguistically deafened adults who received a CLARION cochlear implant. RESULTS AND CONCLUSION: Within-group evaluations revealed that both groups demonstrated significant improvements on all speech perception measures when 1-month postoperative scores were compared with scores obtained preoperatively with hearing aids. Between-group comparison of demographic data showed that the HiFocus group had a significantly higher mean age at implant and a significantly longer mean duration of deafness than the precurved electrode with EPS group. Statistical comparison of mean speech perception scores showed no significant difference between subjects using the precurved electrode with EPS versus the HiFocus electrode with EPS at the preoperative, 1-, and 3-month test intervals. At the 6-month test interval, the mean CNC Monosyllabic Word Test score obtained by the HiFocus with EPS group was significantly better than the mean score obtained by the group with the precurved electrode with EPS (p < 0.05).

Audiometry↗

Reduced red cell 2,3-diphosphoglycerate concentrations in critical illness without decreased in vivo P50.

We investigated whether red cell 2,3-diphosphoglycerate (2,3-DPG) concentrations are reduced in critical illness, whether acidaemia, hypophosphataemia or anaemia influence 2,3-DPG, and whether there is any net effect on in vivo P50. Twenty healthy, non-smoking, male volunteers were compared with 20 male intensive care patients with APACHE 2 scores >20 on the preceding day. Those transfused in this time were excluded. Venous red cell 2,3-DPG concentrations were measured in both groups. In the patient group, routine multichannel biochemical profile and arterial blood gas analysis were also performed and in vivo P50 calculated. The mean 2,3-DPG concentration was significantly lower in the patient group than in the controls (4.2+/-1.3 mmol/l vs 4.9+/-0.5 mmol/l, P=0.016). The patients were well oxygenated (lowest arterial PO2=75 mm Hg) and showed a tendency to acidaemia (median pH 7.37, range 7.06 to 7.48) and anaemia (median haemoglobin concentration 113 g/l, range 89 to 154 g/l). By linear regression of patient data, pH had a significant effect on 2,3-DPG concentrations (r=0.6, P=0.011). Haemoglobin and phosphate concentrations did not, but there were few abnormal phosphate values. There was no correlation between 2,3-DPG concentrations and in vivo P50 (r2 < or = 0.08). We conclude that 2,3-DPG concentrations were reduced in a broad group of critically ill patients. Although this would normally reduce the P50, the reduction was primarily linked with acidaemia, which increases the P50. Overall, there was no net effect on the P50 and thus no affinity-related decrease in tissue oxygenation.

2,3-Diphosphoglycerate↗