Spatial and temporal contrasts in the distribution of crops and pastures across Amazonia: A new agricultural land use data set from census data since 1950.

Amazonia holds the largest continuous area of tropical forests with intense land use change dynamics inducing water, carbon, and energy feedbacks with regional and global impacts. Much of our knowledge of land use change in Amazonia comes from studies of the Brazilian Amazon, which accounts for two thirds of the region. Amazonia outside of Brazil has received less attention because of the difficulty of acquiring consistent data across countries. We present here an agricultural statistics database of the entire Amazonia region, with a harmonized description of crops and pastures in geospatial format, based on administrative boundary data at the municipality level. The spatial coverage includes countries within Amazonia and spans censuses and surveys from 1950 to 2012. Harmonized crop and pasture types are explored by grouping annual and perennial cropping systems, C3 and C4 photosynthetic pathways, planted and natural pastures, and main crops. Our analysis examined the spatial pattern of ratios between classes of the groups and their correlation with the agricultural extent of crops and pastures within administrative units of the Amazon, by country, and census/survey dates. Significant correlations were found between all ratios and the fraction of agricultural lands of each administrative unit, with the exception of planted to natural pastures ratio and pasture lands extent. Brazil and Peru in most cases have significant correlations for all ratios analyzed even for specific census and survey dates. Results suggested improvements, and potential applications of the database for carbon, water, climate, and land use change studies are discussed. The database presented here provides an Amazon-wide improved data set on agricultural dynamics with expanded temporal and spatial coverage. KEY POINTS: Agricultural census database covers Amazon basin municipalities from 1950 to 2012Harmonized database groups crops and pastures by cropping system, C3/C4, and main cropsWe explored correlations between groups and the extent of agricultural lands.

Management of children and adolescents with primary immune thrombocytopenia: controversies and solutions.

The management including diagnostic procedures, prophylaxis, treatment and follow-up of patients with primary immune thrombocytopenia (ITP) in childhood is controversial due to limited clinical data, difficulties in the estimation of individual bleeding risk and heterogeneity of pathophysiology potentially causing various treatment responses. Advances in the management of children include increased international collaborations, improved quality of diagnosis and treatment, increased clinical data, refinement of consensus statements where clinical evidence is absent, new drugs and last but not least establishment of watch-and-wait strategies. The Intercontinental Cooperative ITP Study Group promotes international collaboration since more than 10 years based on a worldwide network and experience in registries. Future considerations include concentration of available resources, strengthening international collaboration, focusing on most important scientific and clinical questions, such as identification of the subgroup of patients that benefits most from prophylactic platelet-enhancing treatments and investigation of treatment endpoints other than concepts solely based on the platelet count, including bleeding symptoms, health-related quality of life and economical aspects of treatments.

Intravenous immunoglobulins induce potentially synergistic immunomodulations in autoimmune disorders.

The increase in platelets in patients with immune thrombocytopenia (ITP) by intravenous administration of human immunoglobulin concentrates (IVIG) reflects a therapeutic immunomodulatory intervention targeted at the disturbed immune response in many inflammatory and autoimmune disorders. These immunoglobulin concentrates contain large numbers of antibodies as well as trace levels of various other immunologically active molecules. Clinical and laboratory studies have documented various mechanisms of action of IVIG. The complex network of immunological reactions resulting from the infusion of IVIG includes changes in several cytokines, interactions with dendritic cells, T- and B- lymphocyte effects, macrophage effects, mediated by distinct Fc-gamma receptors. In addition, effects on complement components and apoptosis have also been observed. Synergism between the different elements of the immune response characterizes the beneficial effects of IVIG in inflammatory and autoimmune disorders. They have immunopathogeneses and clinical manifestations which are difficult to define and therefore IVIG treatment indications remain heterogeneous. Dose finding studies are missing for most of the indications of the drug. In future research, defining the appropriate subgroups of patients should be undertaken. This may be accomplished by prospective registries collecting data on large numbers of patients with long-term follow-up. Controlled clinical and laboratory studies may follow based on new, validated patient selection criteria and focused on mechanisms of action, leading to more evidence-based indications.

Reactivity of acute lymphoblastic leukemia and normal bone marrow cells with the monoclonal anti-B-lymphocyte antibody, anti-Y 29/55.

Malignant lymphocyte populations in peripheral blood of patients with B-cell chronic lymphocytic leukemia, leukemic variant of B-cell non-Hodgkin's lymphoma, and hairy cell leukemia can be characterized by the use of a monoclonal murine antibody (anti-Y 29/55) which is directed against a cell membrane component normally confined to the sessile nonrecirculating cells of the B-lymphocyte population in lymphoid tissues. The present report describes the reactivity of the anti-Y 29/55 antibody with bone marrow cells obtained from children with acute lymphoblastic leukemia using an indirect immunofluorescence method in combination with morphological and cytokinetic studies. In 25 patients (acute lymphoblastic leukemia subtype: 14 common; 4 pre-B-cell; 4 null; and 3 T-cell), a maximum of 2% of cells (small lymphocytes) were stained. One patient presented with blasts exhibiting cytoplasmic and surface immunoglobulin M (IgM) (pre-B-B-cell acute lymphoblastic leukemia). About 11% of this patient's blast cells showed a positive reaction with anti-Y 29/55. They could not be differentiated by morphological criteria from the anti-Y 29/55-negative blast cell population. In another patient with pre-B-B-cell acute lymphoblastic leukemia, only 1% of anti-Y 29/55-positive cells was found. In bone marrow of children with relative lymphocytosis, 1.4 to 8.7% of mononuclear cells reacted with anti-Y 29/55. Morphologically, these cells were small lymphocytes and predominantly expressed surface IgM. In two of these children, a further subdivision of bone marrow cells could be achieved by combining anti-Y 29/55 and cytoplasmic IgM reactivity with [3H]thymidine pulse labeling. These studies revealed that the actively proliferating, normal pre-B-cell population was anti-Y 29/55-nonreactive, whereas a nonproliferating population of anti-Y 29/55-reactive, cytoplasmic IgM-positive cells probably represented B-cells with surface immunoglobulin M reacting when cytoplasmic IgM was assessed. We conclude that the reactivity of the monoclonal anti-B-cell antibody (anti-Y 29/55) is restricted to surface immunoglobulin-positive bone marrow cells and that neither leukemic or normal pre-B-cells nor common, null-cell, or T-cell acute lymphoblastic leukemia blasts react.

Proliferation of lymphoid precursor cells in the bone marrow of patients with various disorders of the immune system.

In the human bone marrow the nuclear enzyme terminal deoxynucleotidyl transferase (TdT) is expressed by cells during early stages of lymphocyte differentiation. In order to investigate a possible regulation of lymphopoiesis at this level of differentiation, the relative frequency and the in vitro 3H-thymidine labeling index (3HdT-LI) of TdT-positive bone marrow cells were assessed in patients with different functional activities of the immune system. TdT-positive lymphoid precursor cells could be detected in the bone marrow of all children investigated, including six patients with various forms of immunodeficiency. Neither a transient hyperfunction of the immune system during the immunological rebound after cessation of long-term chemotherapy for acute lymphoblastic leukemia, nor a congenital or acquired hypofunction of the immune system had any detectable influence on the invariably high in vitro 3HdT-LI of TdT-positive bone marrow cells, a phenomenon possibly related to an autonomous and high turnover of this precursor cell compartment in the human bone marrow.

Intellectual outcome in children and adolescents with acute lymphoblastic leukaemia treated with chemotherapy alone: age- and sex-related differences.

One of the most relevant concerns in long-term survivors of paediatric acute lymphoblastic leukaemia (ALL) is the development of neuropsychological sequelae. The majority of the published studies report on patients treated with chemotherapy and prophylactic central nervous system (CNS) irradiation, little is known about the outcome of patients treated with chemotherapy-only regimens. Using the standardised clinical and neuropsychological instruments of the SPOG Late Effects Study, the intellectual performance of 132 paediatric ALL patients treated with chemotherapy only was compared to that of 100 control patients surviving from diverse non-CNS solid tumours. As a group, ALL and solid tumour survivors showed normal and comparable intellectual performances (mean global IQ 104.6 in both groups). The percentage of patients in the borderline range (global IQ between 70 and 85) was comparable and not higher as expected (10% cases and 13% controls, expected 16%). Only 2 (2%) of the former ALL and 1 (1%) of the solid tumour patients were in the range of mental retardation (global IQ<70). Former known risk factors described in children treated with prophylactic CNS irradiation, like a younger age at diagnosis of ALL and female gender, remained valid in chemotherapy-only treated patients. The abandonment of prophylactic CNS irradiation and its replacement by a more intensive systemic and intrathecal chemotherapy led to a reduction, but not the disappearance of late neuropsychological sequelae.

Antihyperglycemic activities of cryptolepine analogues: an ethnobotanical lead structure isolated from Cryptolepis sanguinolenta.

Cryptolepine (1) is a rare example of a natural product whose synthesis was reported prior to its isolation from nature. In the previous paper we reported the discovery of cryptolepine's antihyperglycemic properties. As part of a medicinal chemistry program designed to optimize natural product lead structures originating from our ethnobotanical and ethnomedical field research, a series of substituted and heterosubstituted cryptolepine analogues was synthesized. Antihyperglycemic activity was measured in vitro and in an NIDDM mouse model to generate the first structure-bioactivity study about the cryptolepine nucleus.

Ethnobotanical-directed discovery of the antihyperglycemic properties of cryptolepine: its isolation from Cryptolepis sanguinolenta, synthesis, and in vitro and in vivo activities.

Using an ethnobotanical approach in combination with in vivo-guided fractionation as a means for lead discovery, cryptolepine was isolated as an antihyperglycemic component of Cryptolepis sanguinolenta. Two syntheses of cryptolepine, including an unambiguous synthesis, are reported. The hydroiodide, hydrochloride, and hydrotrifluoromethanesulfonate (hydrotriflate) salts of cryptolepine were synthesized, and a comparison of their spectral properties and their in vitro activities in a 3T3-L1 glucose transport assay is made. Cryptolepine and its salt forms lower blood glucose in rodent models of type II diabetes. While a number of bioactivities have been reported for cryptolepine, this is the first report that cryptolepine possesses antihyperglycemic properties.

Evidence for HLA-linked susceptibility factors in childhood leukemia.

To test the hypothesis that susceptibility to leukemia can be governed by (a) recessive gene(s) associated with the major histocompatibility complex (MHC) in man, we performed an analysis of the inheritance of HLA antigens in 55 families in which one of the children developed ALL. We found among the parents of affected children a highly significant increased compatibility at the DR locus (p = 0.003). A similar increase was observed in sharing HLA antigens of the B locus (p = 0.02). The observed number of homozygotes among the patients was twice the expected value in families where the parents shared a B and a DR antigen. In segregation analysis, heterozygotes for the shared parental HLA antigen were significantly more prevalent among the healthy siblings. Our genetical analysis indicates that mating of certain shared alleles of the HLA system (especially of the DR locus) is associated with the risk for the offspring to develop ALL in childhood. This situation favors the expression of recessive genes associated with the MHC, and presumably those involved in the susceptibility to acute leukemia. Because familial leukemia is a rare event, the susceptibility to childhood ALL must also implicate genes outside the MHC and important environmental factors.

Idiopathic thrombocytopenic purpura (ITP): immunomodulation by intravenous immunoglobulin (IVIg).

ITP is a destructive thrombocytopenia. Platelets are coated with antibodies and these opsonized platelets are rapidly removed by phagocytes. On the other hand, therapeutic application of antibody concentrates (IVIg) rapidly raise platelet counts, and in some patients, sustained platelet recovery has been observed. The mechanism of action of IVIg is far from being clear. Several possible mechanism of action of IVIg treatment have been described. The immediate effect of IVIg seems to be a decrease in (unspecific) Fc mediated mononuclear phagocytosis, the long term effect might be a change in the complex network of the regulatory function of the immune response. Both types of interactions seem to play a keyrole in the immunomodulation. The various possible modes of actions evoke investigation of IVIg in a wide range of diseases with similar ineffective immune response. Controlled clinical studies have to be done to prove or disapprove the use of IVIg in other indications.

Intravenous immunoglobulin therapy for idiopathic thrombocytopenic purpura and other immune-related disorders: review and update of our experiences.

Idiopathic thrombocytopenic purpura (ITP) is a disorder characterized by a destructive thrombocytopenia. Since the demonstration of a humoral antiplatelet factor which causes a transient ITP when given to healthy volunteers, ITP has been thought of as an autoimmune disease. The target antigen seems to be heterogeneous; it is either a primary platelet membrane autoantigen or a secondary autoantigen absorbed on the platelet. The former was recently confirmed by the observation that serum and platelet eluates of patients with ITP bind to normal platelets, but not to Glanzmann's thrombasthenic platelets which are deficient in glycoproteins IIb and IIIa. The heterogeneity of ITP is also reflected in the difference in response to immunoglobulin prepared for intravenous administration (IVIG) treatment. In our multicenter studies for severe ITP (less than 30 X 10(9)/liter platelet count) in children, we observed the existence of at least two subgroups of ITP, namely rapid responders (greater than or equal to 30 X 10(9)/liter platelet at 72 hours after the start of IVIG) and slow responders (less than 30 X 10(9)/liter platelet counts at 72 hours). Rapid responders mostly showed a permanent increase of their platelet counts while slow responders often had a transient platelet increase. Slow responding children were therefore comparable with adults with ITP. Because the adult type of ITP occurs often in young women, fetal risk must frequently be addressed. The situation of neonatal ITP reflects both the antigenic and therapeutic heterogeneity of ITP. The severity of the disease probably depends on the character of the antigen and its related autoantibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Childhood leukaemia in Switzerland: comparison of different sources of data.

Since 1976 the Swiss Paediatric Oncology Groups (SPOG) has registered leukaemia cases occurring in Switzerland. The registration was set up for clinical research; however, since 1985 efforts have been made to complete the registers with cases not taking part in a clinical trial. The data of the SPOG register between 1976 and 1989 are compared to data from cancer registers and the mortality statistics of the Federal Office of Statistics. Between 1985 and 1988 the SPOG register included 91% of the cases recorded by the six cantonal registries. Compared to mortality data, registration was 100% in 1989. The SPOG data file can therefore be assumed to be complete enough to be used for epidemiological studies on incidence of leukaemias and on time trends of leukaemias in Switzerland.

[High-dose immunoglobulin infusions in idiopathic thrombopenic purpura]. / Perfusions d'immunoglobulines à forte dose dans les purpuras thrombopéniques idiopathiques.

In childhood approximately 90% of all idiopathic thrombocytopenic purpuras (ITP) are acute while in adults the majority is chronic (6 months duration). 0,5 - 1% of the children with ITP die. Conventional treatment comprises corticosteroids and, for chronic ITP, splenectomy and/or cytostatic immunosuppression. Inspired by the disappearance, during substitution, of concomitant ITP in 2 agammaglobulinemic boys, 13 children with ITP (3 chronic, 4 intermittent, 6 acute) were treated with high-dose intravenous immunoglobulin SRK. All responded favorably but one boy with chronic ITP became resistant after 11 months of infusions. F(ab')2 fragments are inactive. High doses of immunoglobulin could block Fc receptors of macrophages. They could also facilitate the formation and elimination of immune complexes and, indirectly, prevent the accumulation of platelet-associated immunoglobulin.

[Idiopathic thrombocytopenic purpura in children]. / Idiopathische thrombozytopenische Purpura beim Kind.

In children the rate of acute, transient ITP is much higher than the chronic form of ITP. Often acute childhood ITP is a para- or postinfectious event. Pathophysiologically bleeding symptoms mainly depend on the ratio between normal or increased platelet production and early destruction of platelets. The management of ITP has to be focused on the individual bleeding symptoms rather than to the platelet count (see staging system). Today's treatments are directed against the disturbed immune response. As recent guidelines and surveys demonstrate opinion based recommendations have to be challenged by evidence based clinical research in ITP (see www.unibas.ch/itpbasel).

[Livedo racemosa, skin necrosis at the basal toe joint]. / Livedo racemosa, Hautnekrose am Zehengrundgelenk.

An 81 year old male patient treated by sulfonylurea and diet was known to have type II diabetes for three years. Because of pulmonary embolism phenprocoumon had been administered for four months. Painful livedo racemosa developed acutely on both lateral sides of the feet and the left knee. A necrosis of the skin over the base of the left small toe developed within a few days. On the basis of the clinical picture cholesterol-embolism was diagnosed. Since anticoagulation is known to promote cholesterol-embolism it was discontinued. Prostaglandin E1 infusions into both legs were administered. Within 3 months the cutaneous lesions healed completely.

Childhood ITP: 12 months follow-up data from the prospective registry I of the Intercontinental Childhood ITP Study Group (ICIS).

BACKGROUND: Acute and chronic idiopathic thrombocytopenic purpura (ITP) is traditionally based on the duration of thrombocytopenia at the cut-off point of 6 months after diagnosis. Registry I evaluated the diagnosis, definition, management, and follow-up of childhood ITP. This report focuses on children with thrombocytopenia persisting more than 6 months. PROCEDURE: Data were collected by questionnaires to the physicians caring for children with ITP, at diagnosis, 6, and 12 months later. Data were compared regarding initial features and follow-up with emphasis on children with persistent thrombocytopenia, and those with ITP who recovered their platelet counts between 7 and 12 months from diagnosis. RESULTS: At 12 months from diagnosis, 79 of 308 (25.6%) evaluable children recovered from ITP and 229 had ongoing ITP. Children with recovered ITP were younger than children with ongoing ITP (P = 0.043) and exhibited a lower frequency of bleeding symptoms during the first 6 months after diagnosis (P = 0.018). Frequency of hospitalization, bone marrow aspiration, and drug treatment differed regionally. CONCLUSIONS: The high rate of recovery from ITP between 7 to 12 months demonstrates, that the cut-off point of 6 months for the definition of chronic ITP does not adequately differentiate chronic from acute ITP. The majority of children with ITP have variable time to recovery with gradual improvement of platelet counts and disappearance of bleeding signs. ITP is a heterogeneous disorder with a diverse natural history and diverse pattern of treatment response.

Immune thrombocytopenic purpura and intravenous immunoglobulin.

The observation, in 1980, of a rapid increase in platelet counts as a result of administration of intravenous immunoglobulin (IVIG) in a patient with immune thrombocytopenic purpura (ITP) was followed by clinical studies confirming the efficacy of this new treatment alternative in ITP. Simultaneously, new sensitive assays using monoclonal antibodies against platelet glycoproteins showed that chronic ITP in adults and children is often an autoimmune disorder. There seem to be both immediate and long-term effects of IVIG in ITP which may be explained by mechanisms of action other than immunoglobulin G substitution. The mode of action of IVIG could correspond to interference with Fc receptors on phagocytes or be a result of antiidiotypic antibodies in IVIG that may induce secondary changes in the complex immunologic network. These immunomodulatory effects were the basis for the use of IVIG in the treatment of patients with other immune-related disorders. New aspects regarding definition and treatment of ITP, the possible mechanisms of action of IVIG, and the implications thereof are discussed and updated.

Immune thrombocytopenia in children: the immune character of destructive thrombocytopenia and the treatment of bleeding.

It is now recognized that different forms of destructive thrombocytopenia due to antibody binding to platelets exist, which can be differentiated by sensitive new assays. Thus, the name has been changed from idiopathic to immune thrombocytopenic purpura (ITP). The immune character of ITP has been further supported by the success of treatment with human antibody concentrate-immunoglobulin treatment. During different studies of ITP in children, it has been recognized that only patients with bleeding in addition to a platelet count less than 20 x 10(9)/L need to be treated. The various forms of treatment are reviewed.