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Martin Weber

Publications and source records attributed to Martin Weber.

33 records · Page 2Linked to original sources

[Can communication with terminally ill patients be taught? Evaluation of a course model].

BACKGROUND AND PURPOSE: Communication with terminally ill patients is a main responsibility of physicians. However, many physicians feel insufficiently prepared for this task. Models of courses resulting in improvements of communicative skills of participants have been published mainly in the Anglo-American literature. This study describes the realization of a 2-day course model based on the experiences of the first three courses of this kind in Rhineland-Palatinate, and analyzes changes of participants' communication behavior. METHODS: After each seminary, an evaluation form concerning participants' satisfaction with the course was filled in. Furthermore, all course participants received a questionnaire at the beginning and at the end of the course, as well as 3 months afterwards. The participants were asked to assess their own sense of security in seven different communication settings on a visual analog scale, and to specify perceived changes in their communication behavior 3 months after the course. RESULTS: The first three courses were attended by 31 participants. Course evaluation revealed high satisfaction scores with methods as well as with clarity and relevance of the contents. Self-assessment of participants showed a growing sense of security in different communication settings. Important increases could be demonstrated for communicating a diagnosis of cancer with good or less good prognosis, recurrence of cancer or a far progressive cancer disease without curative approach. 3 months after the course, participants described multiple changes indicating increased sensibility and professionalism in communication behavior. CONCLUSION: The realized communication skills courses resulted in relevant changes in communication behaviour and self-confidence of participants. Communication with terminally ill patients can be taught.

Communication↗

Opioid switching.

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Analgesics, Opioid↗

Minor histocompatibility antigens on canine hemopoietic progenitor cells.

Adoptive immunotherapy with CTL against minor histocompatibility Ags (mHA) provides a promising way to treat leukemia relapse in allogeneic chimeras. Here we describe the in vitro generation of CTL against mHA in the dog. We tested their inhibitory effect on the growth of hemopoietic progenitor cells stimulated by hemopoietic growth factors in a 4-day suspension culture. CTL were produced by coculture of donor PBMC with bone marrow-derived dendritic cells (DCs). These DCs were characterized by morphology, high expression of MHC class II and CD1a, and the absence of the monocyte-specific marker CD14. Characteristically these cells stimulated allogeneic lymphocytes (MLR) and, after pulsing with a foreign Ag (keyhole limpet hemocyanin), autologous T cells. CTL were generated either ex vivo by coculture with DCs of DLA-identical littermates or in vivo by immunization of the responder with DCs obtained from a DLA-identical littermate. In suspension culture assays the growth of hemopoietic progenitor cells was inhibited in 53% of DLA-identical littermate combinations. In canine families mHA segregated with DLA as restriction elements. One-way reactivity against mHA was found in five littermate combinations. In two cases mHA might be Y chromosome associated, in three cases autosomally inherited alleles were detected. We conclude that CTL can be produced in vitro and in vivo against mHA on canine hemopoietic progenitor cells using bone marrow-derived DCs.

Animals↗

Muscarinic and nicotinic ACh receptor activation differentially mobilize Ca2+ in rat intracardiac ganglion neurons.

The origin of intracellular Ca2+ concentration ([Ca2+]i) transients stimulated by nicotinic (nAChR) and muscarinic (mAChR) receptor activation was investigated in fura-2-loaded neonatal rat intracardiac neurons. ACh evoked [Ca2+]i increases that were reduced to approximately 60% of control in the presence of either atropine (1 microM) or mecamylamine (3 microM) and to <20% in the presence of both antagonists. Removal of external Ca2+ reduced ACh-induced responses to 58% of control, which was unchanged in the presence of mecamylamine but reduced to 5% of control by atropine. The nAChR-induced [Ca2+]i response was reduced to 50% by 10 microM ryanodine, whereas the mAChR-induced response was unaffected by ryanodine, suggesting that Ca2+ release from ryanodine-sensitive Ca2+ stores may only contribute to the nAChR-induced [Ca2+]i responses. Perforated-patch whole cell recording at -60 mV shows that the rise in [Ca2+]i is concomitant with slow outward currents on mAChR activation and with rapid inward currents after nAChR activation. In conclusion, different signaling pathways mediate the rise in [Ca2+]i and membrane currents evoked by ACh binding to nicotinic and muscarinic receptors in rat intracardiac neurons.

Animals↗

The C terminus (amino acids 75-94) and the linker region (amino acids 42-54) of the Ca2+-binding protein S100A1 differentially enhance sarcoplasmic Ca2+ release in murine skinned skeletal muscle fibers.

S100A1, a Ca2+-binding protein of the EF-hand type, is most highly expressed in striated muscle and has previously been shown to interact with the skeletal muscle sarcoplasmic reticulum (SR) Ca2+ release channel/ryanodine receptor (RyR1) isoform. However, it was unclear whether S100A1/RyR1 interaction could modulate SR Ca2+ handling and contractile properties in skeletal muscle fibers. Since S100A1 protein is differentially expressed in fast- and slow-twitch skeletal muscle, we used saponin-skinned murine Musculus extensor digitorum longus (EDL) and Musculus soleus (Soleus) fibers to assess the impact of S100A1 protein on SR Ca2+ release and isometric twitch force in functionally intact permeabilized muscle fibers. S100A1 equally enhanced caffeine-induced SR Ca2+ release and Ca2+-induced isometric force transients in both muscle preparations in a dose-dependent manner. Introducing a synthetic S100A1 peptide model (devoid of EF-hand Ca2+-binding sites) allowed identification of the S100A1 C terminus (amino acids 75-94) and hinge region (amino acids 42-54) to differentially enhance SR Ca2+ release with a nearly 3-fold higher activity of the C terminus. These effects were exclusively based on enhanced SR Ca2+ release as S100A1 influenced neither SR Ca2+ uptake nor myofilament Ca2+ sensitivity/cooperativity in our experimental setting. In conclusion, our study shows for the first time that S100A1 augments contractile performance both of fast- and slow-twitch skeletal muscle fibers based on enhanced SR Ca2+ efflux at least mediated by the C terminus of S100A1 protein. Thus, our data suggest that S100A1 may serve as an endogenous enhancer of SR Ca2+ release and might therefore be of physiological relevance in the process of excitation-contraction coupling in skeletal muscle.

Amino Acid Sequence↗

Antibodies present in normal human serum inhibit invasion of human brain microvascular endothelial cells by Listeria monocytogenes.

Listeria monocytogenes causes meningitis and encephalitis in humans and crosses the blood-brain barrier by yet unknown mechanisms. The interaction of the bacteria with different types of endothelial cells was recently analyzed, and it was shown that invasion into, but not adhesion to, human brain microvascular endothelial cells (HBMEC) depends on the product of the inlB gene, the surface molecule InlB, which is a member of the internalin multigene family. In the present study we analyzed the role of the medium composition in the interaction of L. monocytogenes with HBMEC, and we show that invasion of HBMEC is strongly inhibited in the presence of adult human serum. The strong inhibitory activity, which is not present in fetal calf serum, does not inhibit uptake by macrophage-like J774 cells but does also inhibit invasion of Caco-2 epithelial cells. The inhibitory component of human serum was identified as being associated with L. monocytogenes-specific antibodies present in the human serum. Human newborn serum (cord serum) shows only a weak inhibitory activity on the invasion of HBMEC by L. monocytogenes.

Animals↗

Adoptive immunotherapy in chimeras with donor lymphocytes.

Allogeneic stem cell transplantation has a well-defined indication in the treatment of hematological malignancies. The beneficial immune effect of allogeneic marrow transplantation has long been known, but only recently have methods been developed to separate the graft-versus-leukemia (GVL) effect from graft-versus-host disease (GVHD). Animal experiments have shown that lymphocytes from the marrow donor can be transfused without causing severe GVHD if stable chimerism and tolerance is established. First clinical studies have been preformed in patients with recurrent chronic myelogenous leukemia. In these patients complete molecular remissions were induced that persist without further maintenance treatment. These results have been confirmed in larger multicenter studies in Europe and the USA. The best results were obtained in chronic myelogenous leukemia (CML); repeated successes have been reported in relapsing acute myeloid leukemia (AML), myelodysplastic syndromes and multiple myeloma (MMY), and rare responses were reported for acute lymphoid leukemia. Contrary to animal experiments GVHD has been observed in human patients although to a lesser extent than expected in transplants not given immunosuppression. Secondly myelosuppression has been observed in patients treated with relapsing CML. In CML the incidence of GVHD could be reduced by depleting CD8+ T cells from the donor lymphocyte concentrate. Alternatively only small numbers of T lymphocytes can be transfused and in the case of failing responses, the numbers of donor lymphocytes may be increased. Results in recurrent AML have been improved by the use of low-dose cytosine arabinoside, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor mobilized blood cells as compared to lymphocytes only. In MMY the response rate is higher than in AML, but the remissions are of limited duration in most patients. Several protocols have been designed to include preemptive donor lymphocyte transfusion in patients with a high relapse risk after transplantation. Problems remain to avoid chronic GVHD and to circumvent the immune escape mechanisms of leukemia.

Adoptive Transfer↗

Malunion following trimalleolar fracture with posterolateral subluxation of the talus--reconstruction including the posterior malleolus.

Malunion after a malleolar fracture can include a displaced posterior malleolus with associated posterolateral subluxation of the talus. Corrective osteotomy including the posterior malleolus was performed in four patients. Joint congruity was obtained in every case. The patients were followed for 46 to 80 months postoperatively. They all experienced an improvement in pain and three of four patients were unlimited in their walking capacity. Mild to moderate residual symptoms were frequent. The symptoms were attributed to the damage of the cartilage and soft-tissues both from the initial injury and from weightbearing on the incongruous joint. Discrete, non-progressive osteophytes were seen in all patients. Delay in reconstruction did not preclude a good result, although early reoperation is felt to be preferable.

Adult↗

The active site of cellobiohydrolase Cel6A from Trichoderma reesei: the roles of aspartic acids D221 and D175.

Trichoderma reesei cellobiohydrolase Cel6A is an inverting glycosidase. Structural studies have established that the tunnel-shaped active site of Cel6A contains two aspartic acids, D221 and D175, that are close to the glycosidic oxygen of the scissile bond and at hydrogen-bonding distance from each other. Here, site-directed mutagenesis, X-ray crystallography, and enzyme kinetic studies have been used to confirm the role of residue D221 as the catalytic acid. D175 is shown to affect protonation of D221 and to contribute to the electrostatic stabilization of the partial positive charge in the transition state. Structural and modeling studies suggest that the single-displacement mechanism of Cel6A may not directly involve a catalytic base. The value of (D2O)(V) of 1.16 +/- 0.14 for hydrolysis of cellotriose suggests that the large direct effect expected for proton transfer from the nucleophilic water through a water chain (Grotthus mechanism) is offset by an inverse effect arising from reversibly breaking the short, tight hydrogen bond between D221 and D175 before catalysis.

Aspartic Acid↗

Total hip replacement in patients with Parkinson's disease.

From 1970 to 1994, 107 total hip arthroplasties (THAs) were performed in 98 patients with Parkinson's disease. The average age of the patients was 72 years. Preoperative diagnoses were osteoarthrosis in 58 hips, failed endoprosthesis in 19, aseptic loosening in ten, femoral neck fracture in 18, and other diagnoses in two. Milder neurological stages I-III were assigned to 96 patients, and tendon release for contracture was performed in eight patients. Of the 38 complications eight were urinary tract infections and six dislocations. Of these 15 occurred in the 58 primary THAs and 23 in the 49 nonprimary THAs. In patients with primary THAs there were no dislocations; however, one of the four postoperative deaths occurred following primary THA. We followed 75 hips for 7 (2-21) years; 51 patients had died by the time of the study. Neurological status deteriorated over time with 57% of patients progressing to functional stages IV or V, although consistent improvement was noted for pain relief. Function was directly related to the stage of the neurological disease.

Aged↗

Reconstruction of the cuboid in compression fractures: short to midterm results in 12 patients.

Cuboid compression fractures are rare injuries, usually occurring in combination with medial midfoot fractures or dislocations. During a three year period 12 patients with cuboid fractures were operatively treated at our institution. Eleven patients had involvement of the tarsometatarsal 4 and 5 joints, four of the calcaneocuboid joint, and three of both the proximal and distal joints. The lateral column was shortened in five patients. Open reduction was facilitated using a distracting external fixator. Iliac crest corticocancellous grafts were necessary in seven patients. Single or double plate fixation was performed in eight, screw fixation alone in four patients. Follow-up ranged from 12 to 47 months. Results were good with respect to restoration of length, reconstruction of the joint facets and overall return to function. Minor residual symptoms were noted in one (of four) injured calcaneocuboid joints, in none (of 11) of the tarsometatarsal joints 4 and in two (of 11) of the tarsometatarsal joints 5. More frequently and to a greater extent symptoms arose from the associated midfoot injuries. Deformity and disability from cuboid compression fractures can effectively be prevented by immediate aggressive treatment consisting of open reduction and internal fixation.

Adult↗

Gaps in policy-relevant information on burden of disease in children: a systematic review.

BACKGROUND: Valid information about cause-specific child mortality and morbidity is an essential foundation for national and international health policy. We undertook a systematic review to investigate the geographical dispersion of and time trends in publication for policy-relevant information about children's health and to assess associations between the availability of reliable data and poverty. METHODS: We identified data available on Jan 1, 2001, and published since 1980, for the major causes of morbidity and mortality in young children. Studies with relevant data were assessed against a set of inclusion criteria to identify those likely to provide unbiased estimates of the burden of childhood disease in the community. FINDINGS: Only 308 information units from more than 17,000 papers identified were regarded as possible unbiased sources for estimates of childhood disease burden. The geographical distribution of these information units revealed a pattern of small well-researched populations surrounded by large areas with little available information. No reliable population-based data were identified from many of the world's poorest countries, which account for about a third of all deaths of children worldwide. The number of new studies diminished over the last 10 years investigated. INTERPRETATION: The number of population-based studies yielding estimates of burden of childhood disease from less developed countries was low. The decreasing trend over time suggests reductions in research investment in this sphere. Data are especially sparse from the world's least developed countries with the highest child mortality. Guidelines are needed for the conduct of burden-of-disease studies together with an international research policy that gives increased emphasis to global equity and coverage so that knowledge can be generated from all regions of the world.

Acute Disease↗

Elimination of Haemophilus influenzae type b (Hib) disease from The Gambia after the introduction of routine immunisation with a Hib conjugate vaccine: a prospective study.

BACKGROUND: Routine immunisation of infants in The Gambia with a Haemophilus influenzae type b (Hib) polysaccharide-tetanus toxoid conjugate vaccine began in May, 1997. We investigated the effectiveness of the vaccine when delivered through the expanded programme on immunisation and the effect of national immunisation on incidence of Hib disease. METHODS: Surveillance for Hib disease was maintained in the western half of The Gambia using standard methods with an emphasis on meningitis. We estimated vaccine efficacy using the case control method, and vaccine coverage and population denominators for incidence rates using a cluster sample survey. Prevalence of Hib carriage in a sample of 1-2-year old children attending health centres for vaccination was ascertained with oropharyngeal swabs plated onto antiserum agar. FINDINGS: Between May, 1997, and April, 2002, a total of 5984 children were examined for possible Hib infections. 49 children had Hib disease, 36 of whom had meningitis. The annual incidence rates of Hib meningitis before any use of the vaccine (1990-93) dropped from over 200 per 100,000 children aged younger than 1 year to none per 100,000 in 2002, and from 60 to no cases per 100,000 in children younger than 5 years. The prevalence of Hib carriage decreased from 12% to 0.25% (p<0.0001). Two doses of vaccine were needed for direct protection from Hib disease (vaccine efficacy 94%, 95% CI 62-99). Since most children received a protective dose after the age of greatest disease risk, indirect effects were important in reducing disease incidence. INTERPRETATION: The Gambian Hib immunisation programme reduced the occurrence of Hib disease despite irregular vaccine supply. The effect of the programme in The Gambia has important implications for the introduction of the vaccine into routine immunisation programmes of other developing countries.

Child, Preschool↗

Nonoperative treatment of acute rupture of the achilles tendon: results of a new protocol and comparison with operative treatment.

BACKGROUND: Excellent results are reported from both nonoperative and operative treatment of Achilles tendon rupture. PURPOSE: To describe a new nonoperative treatment protocol for Achilles tendon ruptures and compare outcomes with operative treatment. STUDY DESIGN: Retrospective cohort study. METHODS: We treated 23 patients nonoperatively with an equinus ankle cast and boot and compared their outcome with that of a group of 24 patients previously treated operatively. Muscle strengthening and walking with full weightbearing were started as soon as tolerated in both groups. Follow-up examinations were performed for 18 nonoperatively treated patients after 23 months and for 15 operatively treated patients after 49 months. RESULTS: Subsidence of pain, return to unaided walking, and return to work was faster in the nonoperatively treated group. Patient satisfaction, return to sports, and ultimate strength was the same for both groups. The complication rate was similar, except for reruptures: four early in the nonoperative group and one late in the operative group. Two types of reruptures occurred in the nonoperative group: 1). normally healing tendon subjected to new trauma, rerupturing in the healing zone, and achieving a good result with continued nonoperative treatment; and 2). tendon failing proximal to the initial rupture at the muscle-tendon junction, without trauma, requiring operative repair and augmentation. CONCLUSIONS: Results of operative and nonoperative treatment were equivalent.

Achilles Tendon↗