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D Heim

Publications and source records attributed to D Heim.

At least 19 recordsLinked to original sources
PubMed2006

[TSE surveillance in small ruminants and pigs: a pilot study].

Switzerland is controlling Transmissible Spongiform Encephalopathies (TSE) in cattle (BSE) and small ruminants (scrapie). Since BSE is potentially transmissible to sheep, goats or pigs through feeding of contaminated meat and bone meal, implementation of an active surveillance programme for TSE in these species is discussed. The aim of this pilot study was to obtain preliminary data on the prevalence ofTSE and other neurological disorders in these populations. For that purpose, a total of 398 perished and 825 slaughtered adult small ruminants and pigs was examined for the presence of neuropathological changes. None of these animals revealed positive for TSE. However, the investigations demonstrated that perished sheep and goats exhibited a higher prevalence of relevant neuropathological changes when compared with slaughtered animals. From these results, it is concluded that perished small ruminants are probably a risk population for TSE and should be considered as target populations for an active surveillance programme.

Animals↗
PubMed2006

[Tyrosine kinase inhibitors for the treatment of CML].

Chronic myelogenous leukemia is characterized by the Philadelphia-chromosome, a shortened chromosome 22 which is the result of a reciprocal translocation between chromosome 9 and 22. The fusion gene is called BCR-ABL. After transcription and translation the constitutively activated p210 BCR-ABL oncoprotein is formed. This leads to uncontrolled activation of the ABL tyrosin kinase. Deregulated cellular proliferation and diminished apoptosis of BCR-ABL transformed cells is the result. Expression of the BCR-ABL oncoprotein is sufficient and necessary for the development of a CML phenotype. Imatinib mesylate (Glivec) is a small molecule that binds to the ATP pocket of ABL and blocks downstream signalling events. Imatinib is very effective in the treatment of CML in all stages of the disease. Patients with newly diagnosed chronic phase CML were randomized to imatinib or to interferon plus cytarabine in the IRIS trial. Imatinib showed significantly superior tolerability, hematologic and cytogenetic resposes and increased time to progression. In patients with advanced phase CML, imatinib is less effective and response duration is short. Median overall survival of blast crisis patients is 6.9 months only. Additional BCR-ABL independent chromosomal abnormalities are common in advanced phase CML and result in resistance to imatinib. BCR-ABL kinase-domaine mutations are frequently found in imatinib resistant patients and confer diminished sensitivity to imatinib. Second generation, more powerful ABL kinase inhibitors, which are effective against most of the known mutations are currently tested in clinical trials.

Animals↗
PubMed2005

Transplant-associated microangiopathy (TAM) in recipients of allogeneic hematopoietic stem cell transplants.

We studied occurrence, risk factors and outcome of patients with transplant-associated microangiopathy (TAM) after allogeneic stem cell transplantation (HSCT). A total of 221 consecutive patients were transplanted between 1995 and 2002. TAM is defined as evidence of hemolysis and schistocytes in the first 100 days. Outcomes analyzed included TAM and overall survival. Of 221 patients, 68 had TAM. The cumulative incidence was 31 (25-38)% at 100 days. Patients with TAM had higher LDH, higher bilirubin, higher creatinine and more often neurologic symptoms. TAM was not associated with stem cell source, cyclosporine levels and was not more frequent in recent years. In multivariate analysis, risk factors for TAM included donor type, age, gender, ABO-incompatibility and acute graft-versus-host disease (aGvHD). In patients with TAM, 1-year survival was lower than in patients without TAM (27 +/- 18% for TAM with high schistocyte counts; 53 +/- 15% for TAM with low schistocyte counts; vs 78 +/- 7% in patients without TAM; P<0.0001). TAM was independently associated with mortality adjusting for donor type, age and aGvHD occurrence and severity. TAM is frequent after HSCT and is associated with mortality even after adjustment for aGvHD grade. Risk factors of TAM are similar to aGvHD. TAM may represent endothelial damage driven by donor-host interactions.

Adolescent↗
PubMed2004

High-dose chemotherapy using BEAM for tumor debulking without stem cell support followed by early allogeneic reduced intensity conditioning transplantation to induce a graft-versus-lymphoma effect in patients with high risk or refractory lymphoma.

In patients with refractory lymphoma, we tested the hypothesis that high-dose chemotherapy (BEAM) without stem cell support followed by a reduced intensity (RIC) allogeneic transplant with fludarabine and 2 Gy TBI 28 days later results in tumor debulking and establishment of a graft vs lymphoma effect, with acceptable toxicity. In a pilot protocol we treated 10 patients, 22-62 (median 47) years of age with high-risk or refractory Hodgkin's or non-Hodgkin's lymphoma. Donors were HLA identical siblings (eight) or unrelated volunteers. None died during the neutropenic phase after BEAM which lasted up to the RIC HSCT. The duration of neutropenia was 31-43 (median 36) days. All patients engrafted and nine achieved CR. All developed acute GvHD (median grade III) and all patients at risk developed chronic GvHD. Three patients died of GvHD. One relapsed and six patients are in continuous CR 10-32 (median 15) months after HSCT. This approach appears feasible and results in a high response rate. Neutropenia duration is of concern. It remains to be tested whether separation of debulking chemotherapy and induction of allogeneic effects confers an advantage.

Adolescent↗
PubMed2004

Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation.

This pilot study tested feasibility of natural killer cell purification and infusion (NK-DLI) in patients after haploidentical hematopoietic stem cell transplantation (HSCT). The aim was to obtain >or=1.0 x 10(7)/kg CD56+/CD3- NK cells and <1.0 x 10(5)/kg CD3+ T cells. Mononuclear cells were collected by 10 l leukapheresis. A two-step ex vivo procedure was used to purify NK cells, using an immunomagnetic T-cell depletion, followed by NK-cell enrichment. Five patients with high-risk myeloid malignancies were included, presenting 3-12 months after a haploidentical HSCT with mixed chimerism (3), impending graft failure (1) or early relapse (1). The purified product contained a median of 1.61 x 10(7)/kg (range 0.21-2.2) NK cells and 0.29 x 10(5)/kg (0.11-1.1) T cells. A purity of NK cells of 97% (78-99), a recovery of 35.5% (13-75), and a T-cell depletion of 3.55 log (2.9-4.5) was achieved. Infusions were well tolerated and none of the patients developed graft-versus-host disease. We observed an increase in donor chimerism in 2/5, stable mixed chimerism, decreasing chimerism and relapse of AML in one patient each. Selection of NK-DLI is technically feasible. NK cells are well tolerated when used as adoptive immunotherapy in recipients of haploidentical HSCT.

Adolescent↗
PubMed2003

[The value of ultrasound diagnosis in "acute appendicitis" patient admission].

UNLABELLED: The rate of unnecessary appendectomy is frequently criticized. Today, sonography and CT-scan are helpful tools to minimize this rate. Which value has the ultrasonography in the decision making today? METHODS: Retrospective analysis of 132 patients undergoing appendectomy in respect of sonography and rate of histologically confirmed appendicitis from 1.1.95-31.12.98. Prospective analysis of 99 patients admitted for acute appendicitis in respect of pre- and posttest-probability (after sonography) by the responsible surgeon from 1.1.99-31.12.00. RESULTS: Retrospective part: 122/132 patients had an acute appendicitis (92%). Sonography was performed in 64% of the patients. There was only one wrongly positive sonography. Prospective part: 76/99 patients were operated on. 70/76 had an acute appendicitis (92%). Sonography was performed in 87%. Six patients presented a histologically normal appendix: In two of them no increase of the probability after sonography was noted, in three of them an slight increase of only 20%, and in one of them a decrease of 20% even. CONCLUSION: Sonography with a pre- and posttest-probability is recommended in clinically doubtful cases. In our experience the physician performing the sonography is almost always right. But the diagnosis of an acute appendicitis remains a combination of clinical and sonographic evaluation.

Acute Disease↗
PubMed2003

Risk management of transmissible spongiform encephalopathies in Europe.

Bovine spongiform encephalopathy (BSE) was first described in the United Kingdom (UK) in November 1986. After the introduction of an active surveillance system, most countries in Europe have reported BSE cases in the cattle population. This indicates that the use of active surveillance in addition to passive surveillance is important to assess the true BSE status in a country. Scrapie, a transmissible spongiform encephalopathy (TSE) in sheep and goats, has been reported in countries throughout the world with a few notable exceptions. Concern was expressed that BSE could have been introduced into sheep and goats. Currently, distinguishing between scrapie and BSE in small ruminants is only possible through lengthy experiments in mice. Preliminary results of active surveillance, introduced in 2002, show that significant under-reporting occurred. The history of BSE in cattle shows that risk assessments concerning the risk in a given country were often ignored and subsequent risk management decisions were inaccurate, i.e. although the risk was probable, no measures were taken in terms of either animal or human health. Furthermore, the effect of the measures taken was often overestimated and these had to be amended several times. The most important action to prevent new cases of TSEs occurring is by banning the feeding meat-and-bone meal (MBM) to ruminants. Further measures to be considered are the exclusion of specified risk material and carcasses from rendering, the process parameters for rendering of animal waste and the prevention of cross-contamination of feed with MBM. The most important measures to protect the consumer are the ban on specified risk material, such as brain and spinal cord, which may contain particularly high concentrations of the BSE agent, and the ban on mechanically recovered meat. The most important measures taken in Europe and the scientific background thereof are described and discussed.

Animal Feed↗
PubMed2002

Geographical clustering of cases of bovine spongiform encephalopathy (BSE) born in Switzerland after the feed ban.

Over one-third of the cases of BSE in Switzerland have been born after the feed ban of December 1, 1990. Evidence for the geographical clustering of these cases emerged in two distinct regions. All the 354 BSE cases recorded until June 30, 2000 (set A), and the 376 cases recorded up to May 14, 2001 (set B), were georeferenced to the centres of the communities in which the herds of origin were located, and control populations were georeferenced to the centres of the communities in which these herds were located at the time of the census. The latitudes and longitudes of these centres were used in the statistical analysis of the spatial clustering. The Cuzick-Edwards test and the spatial scan statistics were applied to assess the significance of the clusters, while controlling for the spatial distribution of the underlying cattle population. There was global clustering of the cases born after the ban, and distinct and significant (P<0.05) spatial clusters were repeatedly identified in the two case datasets, and in several control populations (all cases born before the feed ban on a random sample of control farms) in terms of cattle density by region or cow density by region. Differential reporting was excluded as the underlying reason for the observed clusters.

Animals↗
PubMed2002

Do type B malleolar fractures need a positioning screw?

UNLABELLED: Type B malleolar fractures (AO/ASIF classification) are usually stable ankle joint fractures. Nonetheless, some show a residual instability after internal fixation requiring further stabilization. How often does such a situation occur and can these unstable fractures be recognized beforehand?From 1995 to 1997, 111 malleolar fractures (three type A, 90 type B, 18 type C) were operated on. Seventeen out of 90 patients (19%) with a type B fracture showed residual instability after internal fixation (one unilateral, four bimalleolar and 12 trimalleolar fractures). Five of these patients showed a dislocation in the sagittal plane (anteroposterior) clinically or on the radiographs, five a dislocation in the coronal plane with dislocation of the tibia on the medial aspect of the ankle joint, and four an incongruency on the medial aspect of the joint. In three cases, no preoperative abnormality indicating instability was found. The fractures were all fixed using an additional positioning screw. In 11 patients, the positioning screw was removed after 8-12 weeks, in six patients removal was performed after 1 year along with removal of the plate. All 17 patients were reviewed 1 year after internal fixation, 16/17 showed a good or excellent result with identical or only minor impairment of range of motion of the ankle joint. CONCLUSION: Unstable ankle joints after internal fixation of type B malleolar fractures exist. Residual instability most often occurs after trimalleolar fractures with initial joint dislocation. Treatment with an additional positioning screw generally produced a satisfactory result.

Adult↗
PubMed2002

[A method to identify BSE suspects in emergency slaughtered cattle during ante mortem examination].

A method is presented by which a maximal number of BSE-infected cattle that had escaped the filter of clinical examination are identified during ante mortem examination. This approach might prove to be an efficient and cost-effective method for veterinary and non-veterinary meat inspectors to remove infected animals prior to slaughter. In a case-control study, the clinical signs of 224 randomly selected sick slaughtered animals were compared with the clinical signs of 26 sick slaughtered animals in which BSE infection was diagnosed using a rapid test post mortem. In addition, the clinical signs of the sick slaughtered BSE-positive animals were compared with the clinical signs of a group of BSE suspects identified during the same time period and in which BSE infection could be confirmed. As a result of this study a mathematical model was developed to identify BSE suspects. This model contains a total of 7 variables (clinical signs) that proved to be of importance. These signs were aggressive behaviour, grinding of teeth, protruding eyeballs, reduced rumination, inability to stand, overexcitability, and difficulty in standing up. The presented model has a sensitivity of 61.5% (16 out of 26 BSE-positive animals slaughtered while sick were identified) and a specificity of 99.6% when compared to a rapid test conducted post mortem.

Animals↗
PubMed2002

[Beyond BSE: Transmissible spongiform encephalopathies in other animal species].

There are several other diseases besides BSE which belong to the group of transmissible spongiform encephalopathies (TSE). Although most mammals can be experimentally infected with the agent of these diseases, generally only single representatives of the orders Artiodactyla (cloven-hoofed animals), Carnivora (carnivores) and Primates (humans and monkeys) are naturally infected in the field. An overview of the current state of knowledge on TSE in several species like exotic ruminants, deer, mink and cats is presented. Etiological, clinical, anatomic-pathological and epidemiological aspects are described.

Animals↗
PubMed2002

[Transmissible spongiform encephalopathies in sheep and goats].

Scrapie has been known to occur in sheep and goats for over 250 years. Sheep and goats can be experimentally infected orally with BSE, however BSE infection can only be distinguished from scrapie using costly and extensive laboratory procedures. An overview of both the current state of knowledge on Transmissible Spongiform Encephalopathies (TSE) in small ruminants as well as the TSE monitoring and control strategies in place in Switzerland is presented.

Animals↗
PubMed2002

[Geographic distribution of BSE in Switzerland].

Visual evaluation of the occurrence of BAB (born after ban) cases pointed towards spatial clustering. Therefore a statistical analysis of spatial case clustering was conducted using GIS technology. In the initial analysis, all 376 cases (135 BAB, 241 BBB/born before ban) diagnosed through mid of March 2001 were investigated using the spatial scan statistic. Two clusters of BBB cases were identified in the western part of Switzerland, and two clusters of BAB cases in the eastern part. Epidemiological investigations performed within the BAB clusters showed an increased pig density in these cluster regions. Pig density is considered an indicator for the probability of contamination of cattle feed with feed containing meat-and-bone meal that is intended for other species (cross-contamination). In an updated cluster analysis including all cases reported until end of June 2002 (data set B), clusters were identified in the same regions as previously. It was shown that the BAB clusters occurred in different time periods. The small scale differences in cluster size and location are discussed, with an emphasis on the implications for following epidemiological investigations.

Animal Feed↗
PubMed2002

[Risk assessment as an indicator for the distribution of BSE in the world].

For a long time, BSE was considered a problem of the UK exclusively. Even after the detection of BSE cases in countries outside the UK, the risk of having BSE was categorically denied by many other countries. Only after the introduction of active surveillance did several "BSE free" countries detect BSE in their country. However, before the detection of the first cases in several of these countries, a risk assessment (GBR) conducted by the Scientific Steering Committee of the EU showed that a risk could be present. There remain many countries with an unknown BSE risk. In order to minimise import risks from these countries, further risk assessment is needed to evaluate the real BSE distribution worldwide.

Animals↗