Classical Kaposi's: A rare cause of gastrointestinal haemorrhage

Classical Kaposi's sarcoma (KS) is an indolent neoplasm involving mucocutaneous sites predominantly in elderly Mediterranean or Jewish persons. Whilst gastrointestinal involvement is common, it is usually asymptomatic. This case report presents a case of massive gastrointestinal haemorrhage in a patient with stable cutaneous disease and outlines options for the investigation and management of this rare complication.     

Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18

Platelets bound to thrombogenic surfaces have been shown to support activation-dependent firm adhesion of neutrophils in flow following selectin-mediated tethering and rolling. The specific receptor(s) responsible for mediating adhesion-strengthening interactions between neutrophils and platelets has not previously been identified. Furthermore, the ability of adherent platelets to support the migration of bound neutrophils has not been tested. We studied neutrophil interactions with activated, surface-adherent platelets as a model for leukocyte binding in vascular shear flow and emigration at thrombogenic sites. Our results demonstrate that the beta 2-integrin Mac-1 (CD11b/CD18) is required for both firm attachment to and transmigration of neutrophils across surface-adherent platelets. In flow assays, neutrophils from patients with leukocyte adhesion deficiency-1 (LAD-I), which lack beta 2-integrin receptors, formed P-selectin-mediated rolling interactions, but were unable to develop firm adhesion to activated platelets, in contrast to healthy neutrophils, which developed firm adhesion within 5 to 30 seconds after initiation of rolling. Furthermore, the adhesion-strengthening interaction observed for healthy neutrophils could be specifically inhibited by monoclonal antibodies (mAbs) to Mac-1, but not to lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) or intercellular adhesion molecule-2 (ICAM-2; CD102). Further evidence for a beta 2-integrin-dependent neutrophil/platelet interaction is demonstrated by the complete inhibition of interleukin (IL)-8-induced neutrophil transmigration across platelets bound to fibronectin-coated polycarbonate filters by mAbs to Mac-1. Thus, Mac-1 is required for firm adhesion of neutrophils to activated, adherent platelets and may play an important role in promoting neutrophil accumulation on and migration across platelets deposited at sites of vascular injury.     

Circulating Anti-neutrophil Cytoplasmic Autoantibodies in Subglottic Stenosis: a Useful Aid in Diagnosing Vasculitis in This Condition?

Five patients with subglottic stenosis, occurring either asa presenting symptom or as a manifestation in the course ofa systemic disease, are described. Indirect immunofluorescencerevealed the presence of circulating autoantibodies againstboth cytoplasmic and perinuclear constituents of neutrophilsin all five. Antibodies directed against a 29 kDa antigen ofthe azurophilic granules (two patients), against myeloperoxidase(one patient), and against both the 29 kDa antigen and myeloperoxidase(one patient) were found by enzyme-linked immunosorbent assay.These autoantibodies have previously been found in patientswith Wegener's granulomatosis, microscopic polyarteritis, (idiopathic)glomerulonephritis and Churg-Strauss syndrome. However, onlyone of these five patients fulfilled the criteria for theseconditions. Since these autoantibodies are seldom observed inother conditions, and other diseases had been excluded by carefulevaluation, we suggest that their presence places subglotticstenosis within the spectrum of necrotizing (granulomatous)vasculitis. Whether immunosuppressive therapy is always warrantedin patients with subglottic stenosis and circulating anti-neutrophilcytoplasmic antibodies is a matter of debate.     

Sonographic appearance of the endometrium: the predictive value for the outcome of in-vitro fertilization in stimulated cycles.

We evaluated the predictive value for pregnancy of the endometrial thickness and pattern assessed by vaginal sonography on the day of human chorionic gonadotrophin (HCG) injection and the day of embryo transfer in 74 stimulated cycles for in-vitro fertilization (IVF) which were analysed prospectively. Thickness was measured from the echogenic interface of the endometrial-myometrium junction in transverse fundal sections. The distribution of endometrial pattern on the day of HCG was 19 A (poor quality) cases (25.7%) and 55 B (good quality) cases (74.3%). On the day of embryo transfer, 16 out of the 19 A cases (84%) remained as A pattern, while the remaining three cases (16%) had changed to B pattern; of the 55 B cases, 29 (53%) remained the same, while 26 cases (47%) changed to A pattern. There was no significant correlation between the endometrial pattern on the day of HCG and/or on the day of embryo transfer and the peak serum oestradiol levels, the number of preovulatory oocytes aspirated, the serum progesterone levels and oestradiol: progesterone ratio on the day of transfer. In contrast, on the day of HCG, endometrial thickness correlated with serum oestradiol levels on that day (P = 0.02). The presence of pattern A on the day of HCG was associated with a lower pregnancy rate [three out of 19 cases, (15.8%)], compared to pattern B [16 out of 55 cases, (29.1%)], although this was not statistically significant (P greater than 0.05). On the day of embryo transfer, comparable pregnancy rates between A pattern [11 out of 42 cases, (26.1%)] and B pattern [eight out of 32 cases, (25%)] were found.(ABSTRACT TRUNCATED AT 250 WORDS)     

Significance of basal follicle-stimulating hormone levels in women with one ovary in a program of in vitro fertilization.

OBJECTIVE: To understand the impact of having a single ovary on basal follicle-stimulating hormone (FSH) level and its diagnostic and prognostic usefulness in in vitro fertilization (IVF). DESIGN: All IVF cases from July 1987 to June 1990 with known basal FSH (n = 1,272) were divided into those with one and those with two ovaries to compare outcomes based on basal FSH levels. SETTING: Tertiary care academic center with a large IVF practice. MAIN OUTCOME MEASURES: Basal FSH, age, and IVF outcomes including peak estradiol, numbers of follicles aspirated, oocytes retrieved, fertilized, and transferred, and pregnancies (clinical and ongoing). RESULTS: In women with only one ovary, basal FSH was increased, and IVF outcomes were poorer. The rise in FSH was able, in large part, to account for the diminished performance in the single ovary cases. CONCLUSIONS: Women with only one ovary have higher basal FSH levels than those with two ovaries, and this rise can be used to predict their IVF performance.     

Integration of adeno-associated virus vectors in CD34+ human hematopoietic progenitor cells after transduction

Gene transfer vectors based on adeno-associated virus (AAV) appear promising because of their high transduction frequencies regardless of cell cycle status and ability to integrate into chromosomal DNA. We tested AAV-mediated gene transfer into a panel of human bone marrow or umbilical cord-derived CD34+ hematopoietic progenitor cells, using vectors encoding several transgenes under the control of viral and cellular promoters. Gene transfer was evaluated by (1) chromosomal integration of vector sequences and (2) analysis of transgene expression. Southern hybridization and fluorescence in situ hybridization analysis of transduced CD34 genomic DNA showed the presence of integrated vector sequences in chromosomal DNA in a portion of transduced cells and showed that integrated vector sequences were replicated along with cellular DNA during mitosis. Transgene expression in transduced CD34 cells in suspension cultures and in myeloid colonies differentiating in vitro from transduced CD34 cells approximated that predicted by the multiplicity of transduction. This was true in CD34 cells from different donors, regardless of the transgene or selective pressure. Comparisons of CD34 cell transduction either before or after cytokine stimulation showed similar gene transfer frequencies. Our findings suggest that AAV transduction of CD34+ hematopoietic progenitor cells is efficient, can lead to stable integration in a population of transduced cells, and may therefore provide the basis for safe and efficient ex vivo gene therapy of the hematopoietic system.