Cellular signalling pathways in immune aging and regeneration.

The thymus is one of the cornerstones of an effective immune system. It produces new T-cells for the naïve T-cell pool, thus refreshing the peripheral repertoire. As we age, the thymus atrophies and there is a decrease in the area of active T-cell production. A decline in the output of the thymus eventually leads to changes in the peripheral T-cell pool which includes increases in the number of cells at or near their replicative limit and contraction of the repertoire. Debate about the age-associated changes in the thymus leading to functional decline centres on whether this is due to problems with the environment provided by the thymus or with defects in the progenitor cell compartment. In mice, the evidence points towards problems in the epithelial component of the thymus and the production of IL-7 (interleukin 7). But there are discussions about how appropriate mouse models are for human aging. We have developed a simple system that utilizes both human keratinocyte and fibroblast cell lines arrayed on a synthetic tantalum-coated matrix to provide a permissive environment for the maturation of human CD34+ haemopoietic progenitor cells into mature CD4+ or CD8+ T-lymphocytes. We have characterized the requirements for differentiation within these cultures and used this system to compare the ability of CD34+ cells derived from different sources to produce mature thymocytes. The TREC (T-cell receptor excision circle) assay was used as a means of identifying newly produced thymocytes.

Acute abdomen secondary to rare yolk sac tumour.

A 36-year-old woman presented unwell, with abdominal pain. A pelvic mass was found and being investigated but when she deteriorated and became peritonitic. An emergency laparotomy was performed and she required a pelvic clearance for a Stage IIB ovarian tumour, later confirmed as a yolk sac tumour. Accurate staging and tumour-reductive surgery strongly affects the prognosis of yolk sac tumours. Thus ability to perform a meticulous surgical clearance may well positively impact on the outcome for these young patients. This case describes the challenges that generalists will be faced with when highly suspicious cancer patients present as an emergency.

Successful use of uterine artery embolisation to treat placenta increta in the first trimester.

A 39-year-old Asian woman was admitted to hospital with persistent, heavy vaginal bleeding following an uncomplicated first trimester surgical termination of pregnancy (STOP). Her heavy bleeding continued after the STOP and she had recurrent hospital admissions which included two procedures to evacuate presumed retained products of conception. She eventually had a MRI scan performed which suggested placental tissue in the fundal region, extended into the uterine wall. The findings were consistent with placenta increta and the patient had a bilateral uterine artery embolisation (UAE), following which her symptoms rapidly subsided. We describe the first successfully managed case of persistent vaginal bleeding secondary to abnormal placentation. It would seem to substantiate the efficacy of UAE as a therapeutic modality for the conservative management of invasive placentation in the first trimester of pregnancy.

Technical description of the B-Lynch brace suture for treatment of massive postpartum hemorrhage and review of published cases.

Massive uncontrolled hemorrhage after childbirth is a leading cause of the pregnancy-related death and resulting morbidity. Uterine atony is the most common cause (75-90%) of primary postpartum hemorrhage. When simple massage of the uterus and uterotonics such as oxytocins, syntometrine and prostaglandins failed to manage this condition, various surgical solutions have been sought, including uterine artery ligation, more complicated stepwise devascularization of the uterus, internal iliac artery ligation and, ultimately, hysterectomy. All these procedures require above average surgical skill. In contrast, the B-Lynch suturing technique (brace suture) is particularly useful because of its simplicity of application, life saving potential, relative safety and capacity for preserving the uterus and subsequent fertility. The adequacy of haemostasis can be assessed both before and immediately after application of the suture. Only if it fails need other more radical surgical methods be considered. The special advantage of this innovative technique is that it presents an alternative to major surgical procedures for controlling pelvic arterial pulse pressure or hysterectomy. To date, this suturing technique, when applied correctly, has been successful with no problems and no apparent complications. This review provides an update on the B-Lynch brace suturing technique, including choice of suture material, use of the technique in early and late gestation, and comparison with other uterine compression surgical techniques. It also includes a comprehensive review and analysis of all published cases and their postoperative follow-up.

A simple model system enabling human CD34(+) cells to undertake differentiation towards T cells.

BACKGROUND: Channelling the development of haematopoietic progenitor cells into T lymphocytes is dependent upon a series of extrinsic prompts whose temporal and spatial sequence is critical for a productive outcome. Simple models of human progenitor cells development depend in the main on the use of xenogeneic systems which may provide some limitations to development. METHODS AND FINDINGS: Here we provide evidence that a simple model system which utilises both human keratinocyte and fibroblast cell lines arrayed on a synthetic tantalum coated matrix provides a permissive environment for the development of human CD34⁺ haematopoietic cells into mature CD4⁺ or CD8⁺ T lymphocytes in the presence of Interleukin 7 (IL-7), Interleukin 15 (IL-15) and the Fms-like tyrosine kinase 3 ligand (Flt-3L). This system was used to compare the ability of CD34(+) cells to produce mature thymocytes and showed that whilst these cells derived from cord blood were able to productively differentiate into thymocytes the system was not permissive for the development of CD34(+) cells from adult peripheral blood. CONCLUSIONS/SIGNIFICANCE: Our study provides direct evidence for the capacity of human cord blood CD34(+) cells to differentiate along the T lineage in a simple human model system. Productive commitment of the CD34⁺ cells to generate T cells was found to be dependent on a three-dimensional matrix which induced the up-regulation of the Notch delta-like ligand 4 (Dll-4) by epithelial cells.