Identification of both myeloid CD11c+ and lymphoid CD11c- dendritic cell subsets in cord blood.

Dendritic cells (DCs) are the most potent antigen-presenting cells described to date. In human peripheral blood, both myeloid and lymphoid subsets of DCs have been identified. In contrast, cord blood (CB) DCs have recently been described as being exclusively of the immature CD11c- lymphoid DC subset. Using an alternative method of enrichment, based on a negative selection system, both lymphoid (HLA-DR+ CD123+++ CD11c- CD33-) and myeloid (HLA-DR++ CD123+ CD11c+ CD33+) DCs were identified in CB. Although the majority of CB DCs showed a lymphoid phenotype, a significant number of CD11c+ myeloid DCs (25.6% +/- 14.5%, n = 13) were also present. Other markers, such as CD80 and CD83, were negative in both subsets. Analyses of the allostimulatory capacity of both subsets showed that freshly isolated CB lymphoid DCs failed to induce a potent allostimulation of naive CB T cells. These features are therefore consistent with previous work reporting an immature phenotype for lymphoid DCs in adult blood. The significance of the inverted CD11c+/CD11c- ratio observed in CB DCs (1:3) with respect to adult blood DCs (3:1) remains to be explained.

Dendritic cells can be successfully generated from CD34+ cord blood cells in the presence of autologous cord blood plasma.

Dendritic cells (DCs) are currently being considered as adjuvants in immunotherapy. Depending on their source and culture conditions, they show different features and maturation states. Dendritic cells can be generated from monocytes and CD34+ haematopoietic stem cells, from both adult and cord blood. Here, we report the generation of mature DCs from enriched CD34+ cord blood (CB) cells using autologous cord blood plasma (ACBP) as a source of serum proteins and factors. In the presence of ACBP, CD34+ cells proliferated and differentiated resulting in a population of cells with a dendritic phenotype as assessed by morphology and flow cytometry analyses. The DC population obtained using ACBP showed higher levels of HLA class II molecules, co-stimulatory molecules including CD40, CD80 or CD86, and the dendritic cell marker CD83, compared with those generated in adult blood serum (ABS). Furthermore, the DCs generated in the presence of ACBP were more potent stimulatory cells in the mixed lymphocyte:dendritic cell reactions (MLDCR), compared to cells generated in ABS. Similar results were obtained using homologous cord blood plasma (HCBP). These results show that ACBP can support the generation of DCs from CD34+ progenitor cells when only GM-CSF and TNFalpha are used as differentiating cytokines.

Sustained expression of CD154 (CD40L) and proinflammatory cytokine production by alloantigen-stimulated umbilical cord blood T cells.

Recent data suggests that graft-versus-host disease (GVHD) is initiated by host APCs. Blockade of CD40:CD154 interactions between APCs and T cells in vivo induces T cell tolerance to host alloantigen and dramatically reduces GVHD. Because allogeneic cord blood (CB) transplantation results in a lower incidence and severity of acute GVHD compared with bone marrow transplantation, we have investigated whether CB T cells can express CD154 in response to stimulation by allogeneic monocyte-derived dendritic cells (MDDC) and have used 5- (and 6-)carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling in combination with intracellular cytokine analysis to assess the proliferation and cytokine profiles of alloantigen-responsive cells. CB T cells stimulated with allogeneic MDDC showed stronger proliferation than adult blood T cells. Surface CD154 expression was detected in the actively dividing CFSElow populations of both the CD4+ and CD4- subsets and was brightest in cells that had divided the most. Assessment of supernatants from MDDC-stimulated CB and adult blood T cells showed no significant difference in the levels of either IFN-gamma or TNF-alpha, but CB T cell supernatants did show a significant lack of detectable IL-2. Intracellular cytokine analysis revealed that dividing CB T cells had been primed to produce IFN-gamma, TNF-alpha, and IL-2 on restimulation. Further phenotype analysis showed that 75% of CB T cells producing IFN-gamma were CD8+. These data suggest that MDDC-stimulated CB T cells express functional CD154 and provide enough costimulation for dendritic cells to prime naive CD8+ CB T cells and induce type 1 cytokine production.

Embolism during caesarean section.

We investigated the occurrence of gas embolism during Caesarean section using a Doppler ultrasound probe and found that it occurs between uterine incision and delivery. Embolism is less common during general anaesthesia than has been reported during regional anaesthesia. Both ruptured membranes and a protracted uterine incision to delivery interval predispose to embolism.

Anaesthesia in an infant with Joubert's syndrome.

The presentation and management of a child with Joubert's syndrome is outlined with specific reference to the problems of opioid sensitivity and abnormal control of respiration.

Epidural fentanyl for shaking in obstetrics.

This study assesses the efficacy of epidural fentanyl in the relief of shaking associated with epidural analgesia. Fifty mothers whose shaking was sufficient to cause distress were divided randomly to receive either fentanyl 25 micrograms in 5 ml sterile normal saline or 5 ml of saline through their in-situ epidural. Shaking stopped within 15 minutes in 18 out of 25 (72%) of those given fentanyl but in only 4 out of 25 (16%) of the saline group and this is statistically significant (p less than 0.01). Fentanyl can be recommended in this context.

Meptazinol versus pethidine for postoperative pain relief in children.

A double-blind, randomised, clinical trial was undertaken comparing intramuscular meptazinol (1 mg/kg) with intramuscular pethidine (1 mg/kg) for the relief of post-tonsillectomy pain, in 100 children under 15 years of age. Pethidine provided better analgesia in those patients who were awake after 30 minutes, but thereafter no statistically significant differences between the degree of pain relief could be detected. Meptazinol caused less sedation than pethidine, in that significantly more patients were awake after 40 minutes in the meptazinol group. The incidence of nausea and vomiting was similar in patients of both groups.