Colpocystodefecography in obstructed defecation: is it really useful to the surgeon?

Objective Colpocystodefecography images the pelvic floor with the dynamics of defecation, but various authors claim that it overestimates clinical findings. The aim of this study was to evaluate the pre‐ and postoperative consistency between clinical and colpocystodefecographic findings in patients undergoing surgery for obstructed defecation. Method Between June 2001 and September 2003, 20 patients underwent transvaginal posterior colpoperineorrhaphy and rectal mucosal prolapsectomy with one circular stapler for symptomatic rectocele and concomitant anorectal prolapse. They were prospectively evaluated both before surgery by designed questionnaire on constipation and incontinence, proctological, gynaecological and urological examinations, colpocystodefecography and anorectal manometry, and after operation at 6 months by questionnaire and a proctological check‐up. The mean follow‐up was 30 months (24–48 months). Results At 6 months the questionnaire revealed a major response in terms of symptoms. The proctological visit confirmed the absence of rectocele in 19 (95%) patients, while the anorectal prolapse had completely disappeared in 17 (85%) patients. Postoperative colpocystodefecography demonstrated a general reduction in the dimensions of the rectocele, which had completely disappeared in five (25%) patients; 40% of the patients had a persistent anorectal prolapse. Conclusion Preoperative data analysis showed a statistically significant correlation between clinical and radiological findings. Postoperatively the global clinical assessment correlated well with patient satisfaction, while there was evidence of a statistically significant difference between the radiological and clinical findings. Routine postoperative use of colpocystodefecography is unjustified unless there is clinical evidence of surgical failure.     

Expansion of human SCID-repopulating cells under hypoxic conditions

It has been proposed that bone marrow (BM) hematopoietic stem and progenitor cells are distributed along an oxygen (O2) gradient, where stem cells reside in the most hypoxic areas and proliferating progenitors are found in O2-rich areas. However, the effects of hypoxia on human hematopoietic stem cells (HSCs) have not been characterized. Our objective was to evaluate the functional and molecular responses of human BM progenitors and stem cells to hypoxic conditions. BM lineage-negative (Lin-) CD34+CD38- cells were cultured in serum-free medium under 1.5% O2 (hypoxia) or 20% O2 (normoxia) for 4 days. Using limiting dilution analysis, we demonstrate that the absolute number of SCID-repopulating cells (SRCs) increased by 5.8-fold in hypoxic cultures compared with normoxia, and by 4.2-fold compared with freshly isolated Lin-CD34+CD38- cells. The observed increase in BM-repopulating activity was associated with a preferential expansion of Lin-CD34+CD38- cells. We also demonstrate that, in response to hypoxia, hypoxia-inducible factor-1alpha protein was stabilized, surface expression of angiogenic receptors was upregulated, and VEGF secretion increased in BM Lin-CD34+ cultures. The use of low O2 levels to enhance the survival and/or self-renewal of human BM HSCs in vitro represents an important advance and could have valuable clinical implications.     

Chronic lymphocytic leukemia B cells contain anomalous Lyn tyrosine kinase, a putative contribution to defective apoptosis

B cell chronic lymphocytic leukemia (B-CLL) is a neoplastic disorder characterized by accumulation of B lymphocytes due to uncontrolled growth and resistance to apoptosis. Analysis of B cells freshly isolated from 40 patients with chronic lymphocytic leukemia demonstrated that the Src kinase Lyn, the switch molecule that couples the B cell receptor to downstream signaling, displays anomalous properties. Lyn is remarkably overexpressed at the protein level in leukemic cells as compared with normal B lymphocytes, with a substantial aliquot of the kinase anomalously present in the cytosol. Whereas in normal B lymphocytes Lyn activation is dependent on B cell-receptor stimulation, in resting malignant cells, the constitutive activity of the kinase accounts for high basal protein tyrosine phosphorylation and low responsiveness to IgM ligation. Addition of the Lyn inhibitors PP2 and SU6656 to leukemic cell cultures restores cell apoptosis, and treatment of malignant cells with drugs that induce cell apoptosis decreases both activity and amount of the tyrosine kinase. These findings suggest a direct correlation between high basal Lyn activity and defects in the induction of apoptosis in leukemic cells. They also support a critical role for Lyn in B-CLL pathogenesis and identify this tyrosine kinase as a potential therapeutic target.