Microphase separation of living cells.

Self-organization of cells is central to a variety of biological systems and physical concepts of condensed matter have proven instrumental in deciphering some of their properties. Here we show that microphase separation, long studied in polymeric materials and other inert systems, has a natural counterpart in living cells. When placed below a millimetric film of liquid nutritive medium, a quasi two-dimensional, high-density population of Dictyostelium discoideum cells spontaneously assembles into compact domains. Their typical size of 100 µm is governed by a balance between competing interactions: an adhesion acting as a short-range attraction and promoting aggregation, and an effective long-range repulsion stemming from aerotaxis in near anoxic condition. Experimental data, a simple model and cell-based simulations all support this scenario. Our findings establish a generic mechanism for self-organization of living cells and highlight oxygen regulation as an emergent organizing principle for biological matter.

Hematopoietic stem cell transplantation in severe congenital neutropenia: experience of the French SCN register.

Our objective was to study the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with severe congenital neutropenia (SCN). Among 101 cases of SCN included in the French Severe Chronic Neutropenia Registry, nine patients received HSCT between 1993 and 2003, in seven institutions. The indications were nonresponse to G-CSF therapy in four cases, bone marrow failure in one case, and myelodysplastic syndrome or leukemia in four cases. The conditioning regimen consisted of total body irradiation in two cases and chemotherapy alone in the other seven cases. Seven patients received stem cells from unrelated donors and two from identical siblings. Engraftment occurred in all but one of the patients. Three patients died. The respective causes of death were graft-versus-host disease, infection, and EBV post-transplant lymphoproliferative disease. Six patients are alive and in complete remission, with a median follow-up of 3.1 years. These results indicate that HSCT is feasible for patients with SCN who do not respond to G-CSF, who have malignant transformation, or who are at a high risk of malignant transformation, even if an HLA-identical sibling donor is not available.

Plateletpheresis concentrates produced with the COMTEC cell separator: the French experience.

The latest generation of cell separators such as Trima (Gambro), Amicus (Baxter) and AS-TEC 204 (Fresenius), allow the collection of leucocyte-reduced platelet concentrates without secondary filtration. Fresenius has recently developed the COMTEC cell separator whose performance has been evaluated by several teams in France. This new cell separator is an improved version of the Fresenius AS-TEC 204 cell separator, designed to allow more efficient platelet collections. This study reports on the experience of six French teams (from Bordeaux, Clermont-Ferrand, Creteil, Dijon, Lille and Nancy) who obtained 696 leucocyte-reduced plateletpheresis concentrates in the course of collection using the new Fresenius COMTEC cell separator. All healthy volunteer donors fulfilled French selection criteria for platelet apheresis. Donors were eligible if they had suitable venous accesses, if their bodyweight was *50 kg and if their pre-apheresis platelet count was >150 x 10(9) l(-1). Between 4606 and 5229 ml of blood were processed. The mean volume of the platelet concentrates was between 439 and 493 ml (mean 460 +/- 63 ml). The platelet yield was of the order of 5.18 +/- 1.02 x 10(11) with only one platelet concentrate below the norm of 2 x 10(11) platelets (0.91 x 10(11)). No plausible explanation for this was found. The residual leucocyte levels conform to current norms. The platelet concentrates contained less than 1 x 10(6) leucocytes per concentrate (mean 0.233 +/- 0.150 x 10(6) leucocytes) in more than 97% of the components produced with >95% statistical confidence. The efficacy of the cell separator (52.44 +/- 7.35%) is comparable to that of other separators. The Fresenius COMTEC cell separator makes it possible to obtain leucocyte-reduced platelet concentrates which comply with current standards both in terms of platelet content and residual leucocyte level.

[(P)FAPA syndrome: value of cimetidine]. / (P)FAPA syndrome: intérêt de la cimétidine.

UNLABELLED: The (P)FAPA syndrome (periodic fever, adenitidis, pharyngitis, aphthous stomatitis) was described in 1987. The etiology of this periodic syndrome remains unknown. We report three new cases. CASE REPORTS: Three girls, aged from 23 months to eight years, developed (P)FAPA. The other causes of periodic fevers were eliminated and the various treatments (antibiotics, antipyretics, nonsteroidal anti-inflammatory agents) proved ineffective. The repetition of the periodic bouts resulted in depressive disorders, absenteeism from school and a drop in weight in the youngest patient. Two of them suffered a sinusal involvement (chronic sinusitis, polyp) and had an increase in the level of immunoglobulin A. In all three cases, cimetidine at a dose of 20 mg/kg/d was well tolerated and resulted in a disappearance of the periodic fevers. CONCLUSION: Cimetidine, as an immunomodulating agent, appears to be beneficial in the in-depth treatment of (P)FAPA syndrome.

Oesophageal atresia, VACTERL association: Fanconi's anaemia related spectrum of anomalies.

Oesophageal atresia usually occurs without any genetic background. Three cases associated with Fanconi's anaemia are reported. One neonate had growth retardation and numerous malformations including oesophageal atresia and four other components of the VACTERL association. In the two others, oesophageal atresia was isolated. In patients with such malformations an early diagnosis of Fanconi's anaemia may have important genetic and therapeutic implications.

Second thyroid neoplasms after prophylactic cranial irradiation for acute lymphoblastic leukemia.

An understanding of the pathogenesis of second cancers may help in their prevention. We report on two children who were treated for acute lymphoblastic leukemia (ALL), with an exclusively cranial prophylactic irradiation (18 Gy) and who presented with a thyroid carcinoma (TC) 12 and 13 years later. From a thorough review of the literature of TC after ALL and of radiation-induced TC, a strong case can be made that these tumors are caused by late effects of scattered radiation. The risk is at its highest in small children. After cranial irradiation, patients require clinical monitoring of the thyroid and cervical area for nodules, continued indefinitely. We suggest that, in most cases, an alternative form of neuromeningeal prophylaxis should be offered in small children with ALL.

Portal vein thrombosis after splenectomy for hereditary stomatocytosis in childhood.

UNLABELLED: Portal vein thrombosis is a rare but potentially lethal complication in children requiring splenectomy. We report on a 15-year-old boy with a dehydrated hereditary stomatocytosis, who underwent splenectomy and presented a postoperative partial portal vein thrombosis. With prompt heparin therapy, neither propagation of the thrombus nor further cavernous transformation in the following occurred 6 years. CONCLUSION: Recent data suggest that hereditary stomatocytosis carries a high risk of thrombotic complications, especially after splenectomy. This procedure, the benefit of which is limited in this condition, should therefore be strongly avoided.

Response at three months is a good predictive factor for newly diagnosed chronic myeloid leukemia patients treated by recombinant interferon-alpha.

In a single institution, we have used recombinant interferon- (IFN-) to treat 116 newly diagnosed Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) patients and analyzed the predictive factors for response and survival. The patients whose median age was 50.3 years (range, 9 to 70) were administered IFN- (5 million units/m2/d) subcutaneously. The IFN- dose was subsequently adjusted to maintain the white blood cell and platelet counts between 1.5 and 5 x 10(9)/L, 50 and 100 x 10(9)/L, respectively. At diagnosis, the Sokal score was used to classify the patients into three groups: low (n = 57), intermediate (n = 42), and high risk (n = 16). A complete hematological response (CHR) was achieved in 93 cases (80.2%). Of the 116 patients, 113 were available for cytogenetic evaluation. Fifty patients (43%) achieved a major cytogenetic response (MCR) (=65% marrow Ph- cells), 37 of them having a complete cytogenetic response (CCR). The estimated 5-year survival of the 116 patients was 68% +/- 11% (95% confidence interval [CI]) with a median follow-up of 42 months (range, 3 to 114) and 85% +/- 11% (95% CI) with a median follow-up of 30.9 (range, 3 to 111) when patients were censored at the time of transplantation. Event-free survival at 5 years (adding death and transplant as event) was 46% +/- 11% (95% CI). Using proportional hazards regression to study time-dependent variables, we confirmed that the most significant factor associated with survival was the cytogenetic response (MCR or CCR) (P <.0001). This factor was independent compared with the Sokal score and baseline variables used to calculate the Sokal score. Moreover, using either univariate or multivariate analysis, the achievement of CHR within 3 months was strongly correlated with MCR (P <.0001). Minimum cytogenetic response (mCR, ie, at least 5% of Ph- metaphases) at 3 months was also a significant predictive factor for MCR (P <.0001). These results show that IFN- can induce a high rate of hematological and cytogenetic response when administered in doses leading to myelosuppression. Factors such as the achievement of CHR and mCR within 3 months could be useful to identify early those patients who will not respond to IFN- and who need alternative treatments such as stem cell transplantation.