Van der Woude syndrome: dentofacial features and implications for clinical practice

Background:  Van der Woude syndrome (VWS) is the most common clefting syndrome in humans. It is characterized by the association of congenital lower lip fistulae with cleft lip and/or cleft palate. VWS individuals have a high prevalence of hypodontia. Although caused by a single gene mutation, VWS has variable phenotypic expression. This study aimed to describe the range of clinical presentations in 22 individuals with VWS to facilitate its diagnosis.
Methods:  A retrospective study of 22 patients with a diagnosis of VWS was undertaken at the Australian Craniofacial Unit (ACFU) in Adelaide. Three extended families with affected members were included in the study cohort.
Results:  The overall prevalence of lip pits in this study cohort was 86%. Cleft phenotypes included bilateral cleft lip and palate (32%); unilateral cleft lip and palate (32%); submucous cleft palate (23%); and isolated cleft hard and soft palate (9%). Missing permanent teeth were reported in 86% of affected individuals.
Conclusions:  Submucous cleft palate in VWS may go undiagnosed if the lower lip pits are not detected. Associated hypodontia and resultant malocclusions will also require management by a dental team.     

Italian healthcare workers' views on mandatory vaccination

Background  

Mandatory vaccination has contributed to the success of immunisation programmes but voluntary vaccination allows people to be responsible for their own health. There are benefits from both policies and the arguments between them remain subject to debate within and without the scientific community, both nationally and internationally. The aim of this study is to assess the opinions of those who actually work in the Vaccination Service.     

Defective and normal haematopoietic stem cells in paroxysmal nocturnal haemoglobinuria

Summary. The expression of decay-accelerating factor (DAF or CD55) and CD59 during haematopoietic cell development in bone marrow aspirates of two patients with paroxysmal nocturnal haemoglobulinuria (PNH) was compared with that in normal bone marrow by five-dimensional flow cytometry. In contrast to early uncommitted haematopoietic progenitor cells (CD34+, CD38-) in normal bone marrow which uniformly express DAF and CD59, the majority of CD34+, CD38- cells in both patients' marrow exhibited the absence of the two proteins. In both specimens, however, subpopulations of CD34+, CD38- cells expressing DAF and CD59 were detectable, indicative of the presence of two lines of haematopoiesis, one abnormal and the other normal. Concurrent abnormal and normal haematopoietic development was further evident by the presence of subpopulations of DAF-, CD59- and DAF+, CD59+ cells along the differentiation and maturation pathways of the myeloid (CD33+, CD15- → CD33+→++, CD15+), the erythroid (CD45^dim, CD71^dim→ CD45-, CD71++), and the B-lymphoid cell lineages (CD10++, CD20- → CD10-, CD20++). While the majority of cells differentiating into and maturing along each cell lineage lacked DAF and CD59, the majority of mature B (CD20++, CD10-) and T-lymphocytes (CD3+) expressed both proteins suggestive of the presence of lymphocytes with a long life span which were generated from normal haematopoietic progenitors before the onset of the disease. The detection of distinct sets of CD34+, CD38- →+ progenitor cells which are DAF+, CD59+ or DAF-, CD59- in marrow of PNH patients has relevance for the treatment of PNH. Cells with the phenotype CD34+, CD38-, DAF+, CD59+ are capable of self renewal and represent potential candidates for autologous bone marrow transplantation following depletion of CD34+, CD38-, DAF-, CD59- cells.     

Quantitative comparison of myeloid antigens on five lineages of mature peripheral blood cells

Five-dimensional flow cytometry was used to identify the 5 lineages of peripheral blood leukocytes simultaneously in a single cell preparation. This technique was then used to compare quantitatively the distribution of cell surface antigens on each of these lineages of cells. Neutrophils, eosinophils, basophils, lymphocytes, and monocytes were uniquely identified by correlating their forward and orthogonal light scattering signals with the amount of cell surface-bound IgE. These three cellular characteristics were combined with two additional immunofluorescence labels to create a 5-dimensional space in which each leukocyte population occupied a unique position. The relative quantities of antigens on each cell type were determined for the monoclonal antibodies CD11b, CD13, CD14, CD15, CD16, CD33, CD38, CD45, CD45R, anti-HLA-DR, and anti-Leu-8 labeled with either fluorescein or phycoerythrin. The amount of antigen was described by the mean fluorescence intensity in comparison with the background fluorescence of each cell type. The distribution of the different cell surface antigens on the 5 major leukocyte populations as well as their interdonor variation were then correlated for 10 normal donors. Since none of the antigens studied was lineage specific, it was shown that the different lineages of blood cells could clearly be identified by quantitative comparison of the antigens. This study provides the basis for discrimination between mature cells and immature stages of differentiation of leukocytes and for distinction between normal and leukemic cells.     

Cytotoxic lymphocytes in B-cell chronic lymphocytic leukemia

Summary The occurrence of cytotoxic lymphocyte subpopulations (i.e., CD 16⁺, CD57⁺ and cytotoxic CD 8⁺) was studied in the peripheral blood of 18 B-cell chronic lymphocytic leukemia (B-CLL) patients. The absolute numbers of CD 57⁺, CD 16⁺ and cytotoxic CD 8⁺ lymphocytes were increased in the peripheral blood of untreated patients as compared with healthy donors, suggesting a causal relation with the accumulation of malignant B-cells. For 5 B-CLL patients and 5 hematological normal donors, the lymphocyte subpopulations in peripheral blood, lymph nodes and bone marrow were determined. A significant immune response was observed in the lymph nodes of the patients, as reflected by the CD 3⁺ lymphocytes, which were 1.7–27 times larger in the patients lymph nodes than in their peripheral blood and bone marrow. In contrast, with peripheral blood this was mainly caused by an increase in CD 4⁺ lymphocytes. The CD 57 lymphocytes in the lymph nodes of the patients had abnormal orthogonal light-scattering signals and an abnormal density of CD 57⁺ receptors in comparison with their peripheral blood CD 57⁺ lymphocytes or the CD57⁺ lymphocytes in the peripheral blood, bone marrow and tonsils of the hematological normal donors. This study shows that although a significant increase of cytotoxic lymphocytes in the peripheral blood of B-CLL patients is observed, the actual distributions of the non-malignant lymphocytes can be quite different at the actual tumor sites, i.e., bone marrow and lymph nodes.     

Flow cytometric characterization of acute myeloid leukemia: IV. Comparison to the differentiation pathway of normal hematopoietic progenitor cells.

Gradual increase of CD38 on cells expressing CD34 characterizes the early cell differentiation pathway of normal human hematopoietic progenitors. In this study the coordinated expression pattern of CD34 and CD38 was assessed on leukemic blasts from bone marrow aspirates of 95 patients with newly diagnosed acute myeloid leukemia (AML). Expression was divided into six categories analogous to the differentiation pathway of normal bone marrow. The CD38 antigen was expressed on the leukemic cells of all patients and CD34+ leukemic cells were found in 79 patients (83%). In 93 patients, the leukemic cells were found along the differentiation pathway defined by CD34 and CD38. In 33 of the 93 patients, a part of the CD34+ cells did not express the CD38 antigen (categories 1 and 2). In another 33 patients, all CD34+ cells expressed CD38 (categories 3 and 4). In the remaining 27 patients, only cells were found which dimly expressed CD34 or did not express CD34 (categories 5 and 6). Of the 93 patients, 88 were treated with intensive chemotherapy according to the protocol of the German AML Cooperative Group. Of these, 21 died early and were not evaluable for treatment response. Complete remission was achieved in 14 of 22 patients (64%) in categories 1 and 2, in 19 of 26 patients (73%) in categories 3 and 4, and in 18 of 19 patients (95%) in categories 5 and 6. The event-free survival was significantly longer in patients of categories 5 and 6 compared to patients in categories 1 and 2 (p less than 0.01) and categories 3 and 4 (p less than 0.05), respectively. We conclude that in the majority of AML patients the immunophenotype of leukemic cells follows the early cell differentiation pathways defined by coordinated expression of CD34 and CD38 similar to that of normal hematopoietic progenitors. The presence of cells in the late cell differentiation stages (CD34+/-, CD38 /+) identifies patients with a higher complete remission rate and longer complete remission duration.     

Health impacts of family planning

Among the many effects of family planning is the influence ithas on mortality and morbidity in women and children throughthe mechanism of changing the number and spacing of children.There is a complex set of relationships between mother's age,parity, birth spacing and infant and child mortality and morbidity.Much effort has been put into untangling this web in the hopeof identifying clear causal connections, but for the most parton the basis of inadequate data. Rather than attempt to establishthe relative importance of child spacing as a cause of decreasesin mortality, this paper takes as its starting point that thereis a connection, and presents some possible causal mechanismswhich explain how short birth intervals and child mortalitycould be related. In addition the most frequently cited hypotheses-maternaldepletion and sibling competition-a third is examined-birthcrowding which, it is suggested, influences the pattern of thetransmission of infectious diseases and, in turn, mortality. In the field of maternal mortality, the data which could beused to quantify the benefits of family planning are in evenshorter supply; however, the causal connections are rather moreeasily identified. The final section combines parity-specificdata on maternal mortality with evidence of changes in fertilitypatterns brought about by family planning to assess how successfulwe can hope to be in reducing through birth control the numberof women who die in childbirth.