Reversed Holocene temperature-moisture relationship in the Horn of Africa.

Anthropogenic climate change is predicted to severely impact the global hydrological cycle1, particularly in tropical regions where agriculture-based economies depend on monsoon rainfall2. In the Horn of Africa, more frequent drought conditions in recent decades3,4 contrast with climate models projecting precipitation to increase with rising temperature5. Here we use organic geochemical climate-proxy data from the sediment record of Lake Chala (Kenya and Tanzania) to probe the stability of the link between hydroclimate and temperature over approximately the past 75,000 years, hence encompassing a sufficiently wide range of temperatures to test the 'dry gets drier, wet gets wetter' paradigm6 of anthropogenic climate change in the time domain. We show that the positive relationship between effective moisture and temperature in easternmost Africa during the cooler last glacial period shifted to negative around the onset of the Holocene 11,700 years ago, when the atmospheric carbon dioxide concentration exceeded 250 parts per million and mean annual temperature approached modern-day values. Thus, at that time, the budget between monsoonal precipitation and continental evaporation7 crossed a tipping point such that the positive influence of temperature on evaporation became greater than its positive influence on precipitation. Our results imply that under continued anthropogenic warming, the Horn of Africa will probably experience further drying, and they highlight the need for improved simulation of both dynamic and thermodynamic processes in the tropical hydrological cycle.

Exponentially fitted open Newton-Cotes differential methods as multilayer symplectic integrators.

Classical open and closed Newton-Cotes differential methods possessing the characteristics of multilayer symplectic structures have been constructed in the past. In this paper, we study the exponentially fitted open Newton-Cotes differential methods of order two, four, and six. It is shown that these integrators, just as their classical counterparts, preserve the volume in the phase space of a Hamiltonian system. They can be converted into a multilayer symplectic structure so that volume-preserving integrators of a Hamiltonian system are obtained. A numerical example has been carried out to show the effectiveness of the present differential method.

Reye syndrome revisited: a descriptive term covering a group of heterogeneous disorders.

UNLABELLED: Reye syndrome, characterised by the combination of liver disease and noninflammatory encephalopathy, is a non-specific clinicopathological entity and a descriptive term covering a group of heterogeneous disorders. Nowadays, some of these patients are diagnosed more correctly as having infectious, metabolic, toxic or other disease. The non-specific case definition implies that the epidemiological studies suggesting a link with acetylsalicylic acid have been performed on a heterogeneous group of children, whereby the value of these studies and their ensuing hypothesis is weakened. Moreover, a detailed analysis of the epidemiological surveys of the Centers for Disease Control, the Yale study and of the British risk factor study provides evidence that not only the use of acetylsalicylic acid but also that of phenothiazines and other anti-emetics is significantly greater in Reye syndrome cases than in controls. As to the decline of Reye syndrome, recent literature data reveal that this is related to more accurate modern diagnosis of infectious, metabolic or toxic disease, reducing the percentage of idiopathic or true cases of Reye syndrome. CONCLUSION: Reye syndrome is a non-specific descriptive term covering a group of heterogeneous disorders. Moreover, not only the use of acetylsalicylic acid but also of antiemetics is statistically significant in Reye syndrome cases. Both facts weaken the validity of the epidemiological surveys suggesting a link with acetylsalicylic acid.

Meningoradiculitis due to borreliosis presenting as low back pain only.

We report a child with Borrelia burgdorferi meningoradiculitis. This entity, also known as Bannwarth syndrome, is rare and its presentation with low back pain only is even more unusual. The MRI findings can suggest the diagnosis.

[Sudden death in young persons caused by arrhythmogenic right ventricular dysplasia]. / Plotselinge dood bij jonge mensen door aritmogene rechterventrikeldysplasie.

A previously healthy boy aged 14 developed persistent ventricular tachycardia while engaged in sports; ultrasonography revealed arrhythmogenic right ventricular dysplasia (ARVD). He was treated with a class III antiarrhythmic drug but nevertheless died 4 years later during recreational activities. An uncle of the boy was found to have died suddenly on a playing field, 25 years previously at the age of 20. In ARVD, fibrolipomatous areas in the right ventricle lead to dilations of the wall where (sometimes fatal) re-entrant tachycardias may develop. An autosomal dominant heredity with variable expression and penetrance is considered probable, while the genetic defect was located recently. Examination and, if necessary, pharmacotherapy of relatives of an ARVD patient may reduce the risk of a fatal arrhythmia.

Treatment of patients with myelodysplastic syndromes with allogeneic bone marrow transplantation from genotypically HLA-identical sibling and alternative donors.

Between December 1981 and March 1994, 24 patients with a myelodysplastic syndrome (MDS) underwent allogeneic bone marrow transplantation (BMT) for RA with trilineage dysplasia (n = 4), CMML (n = 1), RAEB (n = 4), RAEBt (n = 9) and AML following MDS (n = 6). Fifteen patients (two RAEB, seven RAEBt and six sAML) received chemotherapy before BMT resulting in complete remission in 10 patients (six RAEBt and four sAML) at the time of BMT. Sixteen marrow donors were genotypically HLA-identical siblings. Remaining donors were other family members (five) or unrelated donors (three). The status of the underlying disease at the time of conditioning was the major factor determining long-term survival. The disease-freed survival of RA patients and patients presenting with RAEB, RAEBt and AML but transplanted in complete remission, was respectively 50 and 60%. On the contrary, none of the nine high-risk MDS patients transplanted with persistent disease, survived. Outcome after transplantation with alternative donors was inferior with one long-term survivor, mainly related to the high incidence of severe acute GVHD and its accompanying infectious complications. Six patients relapsed resulting in an actuarial probability of relapse of 28%. Twelve patients died of transplant-related complications leading to a non-relapse mortality at 5 years of 50%. At present eight patients are alive and disease-free 20 to 132 months post-transplantation resulting in an actuarial 5-year disease-free survival of 40.7%. Our results suggest that allogeneic bone marrow transplantation is a feasible treatment option for patients with MDS. However, improvement in GVHD prophylaxis and supportive care to reduce transplant-treated mortality and improved relapse prevention are imperative.

Production of granulocyte-macrophage colony-stimulating factor by T cells is regulated by B7 and IL-1 beta.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has proliferation- and differentiation-inducing effects on immature myeloid cells in the bone marrow, and it can modulate the function of several types of mature myeloid cells. We have stimulated purified human T cells with immobilized anti-CD3 or mitogenic anti-CD2 (a combination of monoclonal antibodies 9-1 and 9.6) which could induce GM-CSF production. The cytokines interleukin-1 beta (IL-1 beta) and IL-2 strongly enhanced GM-CSF production, while IL-4, IL-6, GM-CSF, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) had no effect. Activation of protein kinase C by phorbol myristate acetate or triggering of CD28 on T cells by monoclonal antibody 9.3 provided accessory signals for enhanced GM-CSF production in activated T cells. Most important, the addition of mouse cells transfected with human B7-1 (CD80), a natural ligand for CD28, provided a potent accessory signal for GM-CSF production by activated T cells, which could not be blocked by cyclosporin A. The effect of IL-1 beta was in fact indirect, and resulted from enhanced IL-2 production, while the effect of B7 resulted from both IL-2-dependent and IL-2-independent pathways. We conclude that antigen-presenting cells (APC) can up-regulate GM-CSF production through IL-1 beta and through CD28 triggering by B7 molecules. As GM-CSF itself up-regulates B7 expression and IL-1 beta production by APC, a bidirectional regulatory feedback pathway between APC and T cells seems to modulate GM-CSF production.

Cutaneous pathology in primary erythermalgia.

Primary or idiopathic erythermalgia is characterized by recurrent, red, warm, and painful lower extremities. It arises at young age and persists throughout life because no treatment is available. We report the cutaneous pathology of affected skin lesions of three patients with primary erythermalgia. Biopsy specimens showed a mild perivascular mononuclear infiltrate, thickened blood vessel basement membranes, abundant perivascular edema, and moderate endothelial swelling. The thickened basal membrane of the blood vessels showed a laminar structure, and abundant perivascular edema and moderate endothelial cell swelling were evident. These histopathologic findings in primary erythermalgia appear to be nonspecific but allow diagnostic differentiation from erythromelalgia in which fibromuscular intimal proliferation and occlusive thrombi in the endarteriolar capillaries are apparent and from erythermalgia secondary to vasculitis. Histopathologic examination of affected skin lesions in patients with red, congested, warm, and painful burning extremities is a valuable tool in the diagnostic process.

Juvenile fibrosarcoma of the temporal bone.

A case of juvenile fibrosarcoma arising from the head and neck region is described. This type of tumour should be considered as a separate entity different from the fibrosarcoma in adults because of the different clinical behaviour. The symptomatology, the radiographic features and the literature data are reviewed.

Cytogenetic and immunohistochemical evidence that giant cell fibroblastoma is related to dermatofibrosarcoma protuberans.

From cytogenetic and immunohistochemical findings in a primary giant cell fibrosarcoma and its recurrence, it is further demonstrated that a close relationship exists between this tumor and dermatofibrosarcoma protuberans. Both tumors express CD34 and show rearrangements of chromosomes 17 and 22.

Granulocyte-macrophage colony-stimulating factor antagonizes the transforming growth factor-beta-induced expression of Fc gamma RIII (CD16) on human monocytes.

Fc-gamma receptor III (Fc gamma RIII, CD16) type A is expressed on natural killer cells, on a small subset of peripheral blood monocytes and on mature macrophages. Along with differentiation into macrophages, monocytes will express Fc gamma RIII when cultured with transforming growth factor-beta (TGF-beta). In view of the involvement of granulocyte-macrophage colony-stimulating factor (GM-CSF) in myeloid cell differentiation, we investigated the effect of this cytokine on Fc gamma RIII expression in cultures of peripheral blood monocytes. GM-CSF antagonized TGF-beta-induced expression of Fc gamma RIII on monocytes in vitro in a dose-dependent way. The effect of GM-CSF persisted in cultures until at least day 7. The suppression was at the mRNA level, as shown by Northern analyses with a CD16 specific probe, and the signalling pathway involved tyrosine kinase activity. Interferon-gamma and interleukin-2 had no effect on the induced expression of Fc gamma RIII by TGF-beta, while interleukin-4, similar to GM-CSF, antagonized this induction. Our findings suggest that regulatory cytokine networks can drive monocytes into different effector functions and differentiation pathways.

[Transient erythroblastopenia in 4 children]. / Voorbijgaande erytroblastopenie bij 4 kinderen.

In four patients, all girls, aged 2, 3.5, 4 and 5 years, transient erythroblastopenia was diagnosed. The children were presented because of acute pallor. The haemoglobin levels were 2.8 to 5.0 mmol/l. After 3 weeks all patients had recovered or were recovering with increasing haemoglobin values. Three of the four patients needed one blood transfusion. In two patients there was evidence of a parvovirus B19 infection. Transient erythroblastopenia is mostly seen in patients aged 1-4 years. Most cases are postinfectious and there is evidence that human parvovirus B19 is responsible for many cases. In the very young child the differential diagnosis from Blackfan-Diamond anaemia may be very difficult.

5q- syndrome in a child.

A boy aged 8 years, 10 months presented with refractory anemia. Bone marrow investigation revealed monolobular megakaryocytes. Cytogenetic analysis showed a clonal abnormality: 46, XY, del(5)(q14q32). This is the youngest individual ever reported with this disorder. A year after diagnosis, while on treatment with human recombinant erythropoietin, the bone marrow showed an excess of blasts. No bone marrow donor could be found. Transformation to acute myelomonocytic leukemia occurred 3 months later. In spite of intensive chemotherapy, the child died of progressive disease with massive splenomegaly and jaundice. The case illustrates that the 5q- syndrome can occur de novo in children. The outcome in this child was poor, which may reflect a difference from the adult 5q- syndrome or may possibly be related to the erythropoietin the child received.

Consecutive glioblastoma and B cell non-Hodgkin's lymphoma in a young child with von Recklinghausen's Neurofibromatosis.

A young child with neurofibromatosis type 1 (NF1) is reported who developed two primary malignancies: a glioblastoma, followed 6 months later by an abdominal B cell non-Hodgkin's lymphoma. The child is now 4.5 years off treatment and disease free, but has developed progressive and severe psychomotor retardation as sequelae. The NF1 gene is known to act as a tumor suppressor gene. The possible mechanisms leading to the occurrence of a second primary tumor in this child are discussed.