Rituximab: an emerging treatment for recurrent diffuse alveolar hemorrhage in systemic lupus erythematosus.

Diffuse alveolar hemorrhage (DAH) is a rare manifestation of systemic lupus erythematosus (SLE) and is associated with high mortality rates. Treatment typically consists of aggressive immunosuppression with pulse-dose steroids, cyclophosphamide, and plasma exchange therapy. Mortality rates remain high despite use of multiple medical therapies. We present a case of recurrent DAH in a 52-year-old female with SLE after a deceased donor renal transplant who was successfully treated with rituximab. Our report highlights the pathophysiologic importance of B-cell-mediated immunosuppression in SLE-associated DAH and suggests that rituximab may represent a viable alternative to cyclophosphamide in the treatment of this disease. We also review eight other reported cases of rituximab use in SLE-associated DAH.

Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis.

The pathogenesis of early-onset endometriosis has recently been revisited, sparked by the discovery of endometrial stem/progenitor cells and their possible role in endometriosis, and because maternal pregnancy hormone withdrawal following delivery induces uterine bleeding in the neonate. The neonatal uterus has a large cervix to corpus ratio which is functionally blocked with mucous, supporting the concept of retrograde shedding of neonatal endometrium. Only 5% show overt bleeding. Furthermore, the presence of endometriosis in pre-menarcheal girls and even in severe stage in adolescents supports the theory that early-onset endometriosis may originate from retrograde uterine bleeding soon after birth. Endometrial stem/progenitor cells have been identified in menstrual blood suggesting that they may also be shed during neonatal uterine bleeding. Thus, we hypothesized that stem/progenitor cells present in shedding endometrium may have a role in the pathogenesis of early-onset endometriosis through retrograde neonatal uterine bleeding. During the neonatal and pre-pubertal period, shed endometrial stem/progenitor cells are postulated to survive in the pelvic cavity in the absence of circulating estrogens supported by niche cells also shed during neonatal uterine bleeding. According to this hypothesis, during thelarche, under the influence of rising estrogen levels, endometrial stem/progenitor cells proliferate and establish ectopic endometrial lesions characteristic of endometriosis. This New Research Horizon review builds on recent discussions on the pathogenesis of early-onset endometriosis and raises new avenues for research into this costly condition.

The uptake of laparoscopic colorectal surgery in Great Britain and Ireland: a questionnaire survey of consultant members of the ACPGBI.

OBJECTIVE: The National Institute for Clinical Excellence (NICE) has recommended laparoscopic resection as an alternative to open surgery for patients with colorectal cancer. The aim of this study was to evaluate the current uptake of laparoscopic colorectal surgery in Great Britain and Ireland. METHOD: A questionnaire was distributed to members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) regarding their current surgical practice. Results were analysed individually, by region, and nationwide. RESULTS: Information was received on 436 consultants (in 155 replies), of whom 233 (53%) perform laparoscopic colorectal procedures. During the previous year, 25% of colorectal resections were performed laparoscopically by the respondents. However, of those surgeons who were performing laparoscopic resections, only 30% performed more than half of all their resections laparoscopically. Right hemicolectomy, left-sided resections, and rectopexy were the most frequently performed laparoscopic resections. There was an even distribution throughout the country of consultants performing laparoscopic resections (regional IQR 48-60%). The main reason for consultants not performing laparoscopic procedures was a lack of training or funding. CONCLUSION: Laparoscopic colorectal surgery is being performed by more than half (53%) of colorectal consultants nationwide, although only a quarter of all procedures are being undertaken laparoscopically.

Identification of surface markers for prospective isolation of human endometrial stromal colony-forming cells.

BACKGROUND: Human endometrium is a highly regenerative tissue. We hypothesized that the source of endometrial stromal and vascular regeneration is a resident stromal stem/progenitor cell population. Putative human endometrial stromal stem/progenitor cells have been identified using clonal assays, a retrospective functional stem cell assay. Therefore, the aim of this study was to screen potential stem cell markers for the prospective isolation of human endometrial stromal stem/progenitor cells and to determine their capacity to identify colony-forming stromal cells. METHODS: Single-cell suspensions of human endometrial stromal cells were sorted using fluorescence-activated cell sorting into positive and negative populations based on STRO-1, CD133, CD90 or CD146 expression for clonal assays. All markers were immunolocalized in human endometrium. RESULTS: Small populations (2-9%) of human endometrial stromal cells expressed each of the markers. Only CD146(+) cells were enriched for colony-forming cells, and CD90(hi) cells showed a trend for greater enrichment compared with CD90(lo) cells. STRO-1 and CD146 were localized to perivascular cells of the endometrium. CD90 was strongly expressed by functionalis stroma and perivascular cells, but only weakly expressed in the basalis stroma. CD133 was expressed by epithelial cells of the endometrium, rather than by stroma or perivascular cells. CONCLUSIONS: This study identified CD146 as a marker of colony-forming human endometrial stromal cells supporting the concept that human endometrium contains a population of candidate stromal stem/progenitor cells.

Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium.

BACKGROUND: Human endometrium has immense regenerative capacity, growing ~5 mm in 7 days every month. We have previously identified a small population of colony-forming endometrial stromal cells which we hypothesize are mesenchymal stem cells (MSC). The aim of this study was to determine if the co-expression of two perivascular cell markers, CD146 and platelet-derived growth factor-receptor beta (PDGF-Rbeta), will prospectively isolate endometrial stromal cells which exhibit MSC properties, and determine their location in human endometrium. METHODS: Single cell suspensions of human endometrial stromal cells were fluorescence activated cell sorting (FACS) sorted into CD146(+)PDGF-Rbeta(+) and CD146(-)PDGF-Rbeta(-) populations and analysed for colony-forming ability, in vitro differentiation and expression of typical MSC markers. Full thickness human endometrial sections were co-stained for CD146 and PDGF-Rbeta. RESULTS: FACS stromal CD146(+)PDGF-Rbeta(+) stromal cells (1.5% of sorted population) were enriched for colony-forming cells compared with CD146(-)PDGF-Rbeta(-) cells (7.7 +/- 1.7 versus 0.7 +/- 0.2% P <0.0001), and also underwent differentiation into adipogenic, osteogenic, myogenic and chondrogenic lineages. They expressed MSC phenotypic surface markers and were located near blood vessels. CONCLUSION: This study shows that human endometrium contains a small population of MSC-like cells that may be responsible for its cyclical growth, and may provide a readily available source of MSC for tissue engineering applications.