Donor-derived acute promyelocytic leukemia in a liver-transplant recipient.
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Bone Marrow Cells↗
Biomedical subjects
M Peters
Publications and source records attributed to M Peters.
Acquired immunoparalysis in paediatric intensive care: prospective observational study.
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Child↗
Effects of amantadine treatment on in vitro production of interleukin-2 in de-novo patients with idiopathic Parkinson's disease.
An involvement of immunological events in the process of neurodegeneration has frequently been reported. We investigated the cytokine producing capacity for interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) in whole blood cultures of de-novo patients with idiopathic Parkinson's disease (PD) at the time of first diagnosis and after oral amantadine treatment. Before treatment, productions of IL-2 and IFN-gamma were markedly decreased in PD patients compared to patients with major depressive disorder and healthy controls. After amantadine treatment, the in vitro IL-2 secretion defect was corrected to normal levels in half of the patients, and the increase in IL-2 production was correlated with an increase in IFN-gamma secretion. Our findings suggest that immunological abnormalities occur in the course of PD and that a formerly unappreciated therapeutic potential of amantadine may arise from its immunomodulatory effects on altered T cell function in patients with PD.
Adult↗
Agriculture sector resource and environmental policy analysis: an economic and biophysical approach.
Agricultural pollution of the environment is jointly determined by economic decisions driving land use, production practices, and stochastic biophysical processes associated with agricultural production, land and climate characteristics. It follows that environmental and economic statistics, traditionally collected independently of each other, offer little insight into non-point pollutant loadings. We argue that effective policy development would be facilitated by integrating environmental and economic data gathering, combined with simulation modelling linking economic and biophysical components. Integrated data collection links economics, land use, production methods and environmental loadings. An integrated economic/biophysical modelling framework facilitates policy analysis because monetary incentives to reduce pollution can be evaluated in the context of market costs and returns that influence land use and production activity. This allows prediction of environmental and economic outcomes from alternative policies to solve environmental problems. We highlight steps taken to merge economic and biophysical modelling for policy analysis within the Economic Research Service of the United States Department of Agriculture. An example analysis of a policy to reduce agricultural nitrogen pollution is presented, with the economic and environmental results illustrating the value of linked economic and biophysical analysis.
Agriculture↗
The effect of finger-movement speed of the dominant and the subdominant hand on cerebellar activation: A functional magnetic resonance imaging study.
We studied the effects of different speeds of unimanual and bimanual movements on functional magnetic resonance signal changes in the cerebellum. Six healthy consistently right-handed subjects were scanned at rest and while executing a sequential finger-to-thumb-opposition task either unimanually (left or right hand) or bimanually. Movement frequency was paced by an auditory signal at rates of either 1 or 3 Hz. Significant frequency-dependent blood oxygen level-dependent signal increases were demonstrated ipsilaterally and contralaterally in the intermediate and lateral portions of the anterior cerebellum for bimanual movements and for unimanual movements with the subdominant hand. There was only a weak frequency-dependent effect for unimanual movements performed with the dominant hand. In addition, signals were stronger on the right intermediate zone of the anterior cerebellum for movements involving the right (dominant) hand while there was stronger activity on the left cerebellar hemisphere for movements involving the left (subdominant) hand. Taken together, these results suggest that rate and movement task effects on cerebellar activation are differentially sensitive to subdominant and dominant hand movements.
Adult↗
[The resources of the social network of single person households during acute illness. Basic data for home care planning in an influenza epidemic].
UNLABELLED: 230 single persons living in the city of Zurich, 60% aged 18-45, 10% 45-65 and 22% older than 64 years; 70% males were subject to an enquiry. The questioned persons mostly live in two-room-apartments, on average for 11 years, they are single for 8.5 years on average. Solely 5.4% have no living relatives but 32% see them only irregularly (same for all age groups) and 4% are not persistently in touch with friends or acquaintances. 36% were needing help in the past because of sickness or accident. They got it from neighbours (38%), friends, acquaintances (36%), family members (17%) and from home care organisations (9%). In case of a heavy wave of influenza only 14% would not help their neighbours, they would help an average of four neighbours but also they would surely not help four neighbours. The answering persons know 23 singles (= 10%) who presumably would not get any help and 20 (= 9%) who would decline help. 90% of the questioned persons believe, that they would get help by family members or friends, even if those live far away, but still 29% expect help from home care organisations, of the questioned over 64 years old even 52%. CONCLUSION: 10-30% of city singles need help in form of home care in case of an acute illness like heavy influenza.
Adolescent↗
Consensus report on quality control of quantitative measurements of renal function obtained from the renogram: International Consensus Committee from the Scientific Committee of Radionuclides in Nephrourology.
Among all the physiological indices that can be quantified using renography, measurement of renal function is the most basic. These measurements are used to make critical clinical management decisions and, as such, their reliability needs to be quality assured. This article seeks to address each aspect of the renography procedure, with particular emphasis on the effect on measurement of relative renal function. Estimation of individual kidney function is mentioned, but only briefly. A consensus approach was adopted, overseen, and directed by a chairman appointed by the Scientific Committee of the International Radionuclides in Nephro-Urology Group. The chairman selected the panel of experts from eight different countries based on their practical experience in the field. Where evidence exists to support the various recommendations it is given. Otherwise, the stated guidance represents the considered opinion of a body of experts, based on long experience and unpublished data. Some necessary compromises were made to account for the fact that renography is seldom performed solely with the purpose of measuring relative renal function. The technicalities of renography have always been a source of debate in nuclear medicine, which is reflected by the fact that a consensus could simply not be reached on a small number of issues. The structure of the report ensures that these are clearly indicated. This should serve to highlight gaps in our current knowledge, thus helping to direct future research. It is envisaged that the recommendations will be revised on a 2-year cycle to ensure that they remain up to date. An "open" process will be used to encourage participation and ownership. It is hoped that promotion of these guidelines, suitably complemented by audit processes, will raise standards in the practice of gamma camera renography.
Adult↗
Acquired protein S deficiency caused by estrogen treatment of tall stature.
OBJECTIVE: To evaluate the potential thrombogenic changes in the coagulation and fibrinolytic system related to treatment with ethinyl estradiol (200 and 300 microg). SUBJECTS AND METHODS: Twenty-five healthy girls with expected final height exceeding 185 cm, as calculated by the method of Bayley and Pinneau, were treated with 200 microg or 300 microg of ethinyl estradiol. Coagulation and fibrinolytic parameters were determined before and during estrogen treatment and 2 and 4 weeks after estrogen withdrawal. RESULTS: No difference in the effects on hemostasis was found between the 2 treatment groups. All 25 patients developed protein S deficiency during estrogen treatment, which in most girls lasted for 4 weeks after cessation of estrogen administration. During therapy, protein C activity increased, whereas antithrombin did not change. Plasminogen and plasmin-alpha(2) antiplasmin complexes significantly increased. Protein S deficiency was accompanied by significantly increased prothrombin fragment 1+2 and fibrinopeptide A. In contrast, thrombin-antithrombin complexes did not change. CONCLUSION: High-dose estrogen treatment to reduce the final height in tall girls is associated with a reversible acquired protein S deficiency with indications of a pre-thrombotic state. Risk of venous thrombo-embolism may be enhanced, especially when additional risk factors for thrombosis are present.
Blood Coagulation↗
Randomised trial of mycophenolate mofetil versus azathioprine for treatment of chronic active Crohn's disease.
BACKGROUND: Crohn's disease is a chronic inflammatory disease of the alimentary tract. Azathioprine is an effective agent in the management of chronic active Crohn's disease leading to long term remission of disease activity. Such treatment leads to limited efficacy or side effects in a small subset of patients. AIMS: To compare efficacy and side effects of treatment with azathioprine plus corticosteroids versus mycophenolate mofetil (MMF) plus corticosteroids in patients with chronic active Crohn's disease. METHODS: Seventy patients with chronic active Crohn's disease (Crohn's disease activity index (CDAI) greater than 150) were randomised for treatment with azathioprine/cortisone or MMF/cortisone. Corticosteroid dosage was tapered according to a standard protocol. Disease activity was monitored by clinical scores after one, two, three, and six months. RESULTS: Treatment of patients with moderately active (CDAI 150-300) Crohn's disease with MMF/cortisone led to a significant reduction in clinical activity scores comparable to treatment with azathioprine/cortisone. Treatment of patients with highly active Crohn's disease (CDAI greater than 300) with MMF/cortisone caused significant suppression of clinical activity earlier than azathioprine/cortisone treatment. Treatment with MMF/cortisone was associated with few adverse effects. CONCLUSION: Treatment of chronic active Crohn's disease with MMF plus cortisone appears to be effective and well tolerated and should be considered in patients allergic to azathioprine or in whom azathioprine has failed.
Anti-Inflammatory Agents↗
Abnormalities in liver function and coagulation profile following the Fontan procedure.
OBJECTIVE: To investigate liver function and coagulation disorders in patients with a Fontan circulation at different time intervals after surgery. DESIGN: Retrospective analysis of clinical data and cross sectional study relating liver function and coagulation profile to time since surgery, in 28 surviving patients after the modified Fontan procedure. PATIENTS: 20 patients (71%) with atriopulmonary anastomosis, seven (25%) with atrioventricular anastomosis, and one (4%) with total cavopulmonary connection. Follow up ranged from 2.0 to 21.8 years (mean 11.1). RESULTS: Abnormal liver function tests, mainly reflecting cholestasis, were present in 21 patients who had a significantly longer follow up (p < 0.01). Protein synthesis was normal in almost all patients. Coagulation profile showed abnormalities in 22 patients. "Procoagulant" abnormalities-that is, decreased plasminogen and protein C activity-were found in 11 and five patients, respectively. The extent of these abnormalities was less in patients with a longer follow up. Anticoagulant abnormalities were factor V deficiency in 16 patients and factor VII deficiency in 17, resulting in a prolonged prothrombin time in 19 patients. Thirteen patients had both pro- and anticoagulant abnormalities. A prethrombotic state was present in five patients, with a significantly longer mean time interval since surgery (p = 0.05). Thus, although the individual procoagulant indices decreased with increasing time intervals since surgery, a prethrombotic state was found particularly in patients with a long term follow up. CONCLUSIONS: Mild cholestasis was mainly present in Fontan patients with a long duration of follow up. Along with laboratory procoagulant abnormalities indicating a prethrombotic state, anticoagulant abnormalities were also present. The coagulation profile varied at different time intervals after surgery. Thus detailed evaluation should be performed regularly, and the use of anticoagulants should be considered in every patient. Long term prospective studies are needed to evaluate the individual fluctuations of coagulation profile over time following a Fontan procedure.
Adolescent↗
Longitudinal analysis of factor VIII inhibitors in a previously untreated mild haemophilia A patient with an Arg593-->Cys substitution.
Recent studies suggest that certain missense mutations associated with mild to moderate haemophilia A predispose to inhibitor development. In this study, we present a longitudinal analysis of the epitope specificity of an inhibitor that developed in a mild haemophiliac with an Arg593-->Cys mutation. Immunoprecipitation studies revealed the presence of antibodies directed towards the light chain and A2 domain of factor VIII. Limited reactivity was observed with metabolically labelled C2 domain. Almost complete inhibitor neutralization was achieved upon addition of A2 domain. Binding of the inhibitor was not affected by the presence of the Arg593-->Cys substitution in the recombinant A2 fragment. Evaluation of the epitope specificity of anti-factor VIII antibodies in plasma samples obtained at different time-points of inhibitor development revealed initial development of a low titre inhibitor directed towards the A2 domain and factor VIII light chain. A second period of factor VIII replacement therapy resulted in a dramatic rise in factor VIII inhibitor titre, which maintained their original epitope specificity. Based on the results of this and previous studies (Fijnvandraat et al., 1997; Thompson et al., 1997) it is argued that inhibitor development in patients with the Arg593-->Cys mutation may proceed via a similar mechanism.
Aged↗
Serological differences in Neospora caninum-associated epidemic and endemic abortions.
A sandwich enzyme-linked immunosorbent assay (ELISA) for the sensitive and specific detection of bovine antibodies to Neospora caninum was developed and evaluated using sera from cattle experimentally infected with N. caninum, Toxoplasma gondii, Sarcocystis cruzi, Sarcocystis hominis, Sarcocystis hirsuta, Eimeria bovis, Cryptosporidium parvum, Babesia divergens, and field sera from naturally exposed animals. Field sera were classified using a gold standard that included the results from an indirect fluorescent antibody test (IFAT) and an immunoblot (IB). Based on these gold standard results, i.e., IFAT-IB results, an equal relative sensitivity and specificity of 94.2%(theta0) was reached when a cutoff of 0.034 (d0) was employed. The analysis of IFAT-IB-positive field sera showed that within groups of aborting and nonaborting dams, the animals from herds with endemic N. caninum-associated abortions had significantly higher ELISA indices than animals from herds with N. caninum-associated epidemic abortions. By contrast, IFAT-IB-positive aborting dams from herds with endemic N. caninum-associated abortions had significantly lower IFAT titers than IFAT-IB-positive aborting dams from herds with epidemic N. caninum-associated abortions. This is the first time that statistically significant serological differences between herds exhibiting epidemic and endemic N. caninum-associated abortions are described.
Abortion, Veterinary↗
The efficiency of vertical transmission of Neospora caninum in dairy cattle analysed by serological techniques.
The association of Neospora caninum infections with cattle families was examined in a dairy cattle herd with sporadic abortions using three different serological tests. Cattle seropositive for N. caninum clustered in six families, three of which encountered abortions. In absence of age-related differences in the N. caninum seroprevalence, the family association of N. caninum infection indicated that congenital infection represented the predominant route of transmission in this herd. Fourteen (93%) out of 15 descendants of 10 seropositive cows were seropositive themselves. Only one female calf of a seropositive cow remained seronegative and gave birth to a calf which was tested seronegative again. Only one seronegative cow that had two seronegative descendants also gave birth to one seropositive calf. This was the only indication for potential postnatal transmission that occurred in the herd. The results of this study suggest that the N. caninum-infection can be maintained over several generations at a nearly constant prevalence level, apparently without a need for dispersion by an definitive host.
Abortion, Veterinary↗
Mycophenolate mofetil for treatment of active inflammatory bowel disease. Clinical and immunological studies.
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CD4-Positive T-Lymphocytes↗
Interleukin-6 and soluble interleukin-6 receptor: direct stimulation of gp130 and hematopoiesis.
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Animals↗
Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver.
Studies with tumor necrosis factor p55 receptor- and interleukin-6 (IL-6)-deficient mice have shown that IL-6 is required for hepatocyte proliferation and reconstitution of the liver mass after partial hepatectomy. The biological activities of IL-6 are potentiated when this cytokine binds soluble forms of its specific receptor subunit (sIL-6R) and the resulting complex interacts with the transmembrane signaling chain gp130. We show here that double transgenic mice expressing high levels of both human IL-6 and sIL-6R under the control of liver-specific promoters spontaneously develop nodules of hepatocellular hyperplasia around periportal spaces and present signs of sustained hepatocyte proliferation. The resulting picture is identical to that of human nodular regenerative hyperplasia, a condition frequently associated with immunological and myeloproliferative disorders. In high expressors, hyperplastic lesions progress with time into discrete liver adenomas. These data strongly suggest that the IL-6/sIL-6R complex is both a primary stimulus to hepatocyte proliferation and a pathogenic factor of hepatocellular transformation.
Adenoma↗
In vivo and in vitro activities of the gp130-stimulating designer cytokine Hyper-IL-6.
IL-6 is a multifactorial cytokine mediating acute inflammatory responses in the liver. When IL-6 binds to a specific receptor (IL-6R), the IL-6/IL-6R complex associates with the signal transducer gp130, initiating intracellular signaling. A soluble form of the IL-6R (sIL-6R) renders target cells sensitive to IL-6 that do not express the IL-6R on their surfaces. A designer cytokine, termed Hyper-IL-6, consisting of IL-6 covalently linked to the sIL-6R was fully active on gp130-expressing cells at 100- to 1000-fold lower concentrations than unlinked IL-6 and IL-6R. Mice were injected i.p. with Hyper-IL-6 or IL-6. Upon injection of Hyper-IL-6 into mice, the acute phase response, as measured by haptoglobin mRNA expression in the liver, was markedly increased and lasted significantly longer compared with that in mice injected with a 10-fold higher dose of IL-6 alone. On human hepatoma cells, Hyper-IL-6 caused similar effects, indicating that the longer lasting response to the fusion protein could not only be explained by the longer plasma half-life of the fusion protein. Experiments using iodinated IL-6 and Hyper-IL-6 revealed that Hyper-IL-6 bound with high affinity to gp130 and was less efficiently internalized. This effect might explain the longer lasting activity of this protein on cells. The highly active IL-6/sIL-6R designer protein might be of significant clinical importance for the stimulation of cells that are more responsive to the IL-6/sIL-6R complex than to IL-6 alone. Such cells include hemopoietic progenitor cells and hepatocytes.
Acute-Phase Reaction↗