The FLT3 ligand is a direct and potent stimulator of the growth of primitive and committed human CD34+ bone marrow progenitor cells in vitro

The present studies investigated the effects of the recently cloned flt3 ligand (FL) on the in vitro growth and differentiation of primitive and committed subsets of human CD34+ bone marrow (BM) progenitor cells. FL alone was a weak growth stimulator of CD34+ BM cells, but synergistically and directly enhanced colony formation in combination with interleukin (IL) 3, granulocyte colony-stimulating factor (G-CSF), CSF-1, granulocyte macrophage (GM) CSF stem cell factor (SCF), and IL-6. FL and SCF were equally effective in stimulating colony formation in combination with IL-3. However, the tri-factor combination of FL + IL-3 + SCF stimulated 2.3-fold and 2.5-fold more colonies than FL + IL-3 and SCF + IL-3, respectively. These additional recruited progenitors appeared to be predominantly located in a primitive (CD71-) subset of the CD34+ progenitors, as 4.5-fold more colonies were formed by CD34+CD71- cells in response to FL + IL-3 + SCF than to FL + IL-3 or SCF + IL-3. Similar findings were observed in serum-containing and serum-deprived cultures. Whereas FL did not enhance burst-forming unit-erythroid (BFU-E) colony formation of CD34+ BM cells in the presence of serum, a low number of BFU-E colonies were formed in response to FL plus erythropoietin (Epo) under serum-deprived conditions. In addition, FL both in serum-containing and serum-deprived cultures stimulated colony formation of more committed myeloid progenitors in CD34+CD71+ BM cells. Thus, FL potently stimulates the growth of primitive and more committed human BM progenitor cells.     

Relapse of Wegener's granulomatosis in the first trimester of pregnancy: a case report

The association of Wegener's granulomatosis and pregnancy is rare and poses unique therapeutic challenges, particularly when active disease presents in early pregnancy. We describe a 22-yr-old woman who recovered successfully from her initial episode of Wegener's granulomatosis with a standard course of treatment with prednisolone and cyclophosphamide. Two and a half years later, she presented with relapse during the first trimester of pregnancy (primigravida). Since the clinical features suggested mild disease, she was started on prednisolone at a dose of 1 mg/kg/day, to which she seemed to respond very well for 3 months. Unfortunately, she had a spontaneous abortion at 5 months of gestation while on 25 mg/day of prednisolone. At this time, her disease flared further, with clinically manifest lung disease which was not part of her initial presentation. She was treated with another course of oral cyclophosphamide and prednisolone, and a remission was achieved in 4 months. There are no agreed guidelines on the treatment of Wegener's granulomatosis during pregnancy. In this report, the therapeutic issues are discussed against the background of the available literature.      

Ligase chain reaction in detection of Chlamydia DNA in synovial fluid cells

Synovial fluid cells from 12 patients with reactive arthritis (ReA) triggered by Chlamydia trachomatis were studied for the presence of Chlamydia DNA using the ligase chain reaction (LCR) LCx (Abbott) and the polymerase chain reaction (PCR) Amplicor (Roche). In addition, peripheral blood leucocytes from 11 of these patients were analysed by LCR. As controls, seven patients with newly diagnosed rheumatoid arthritis (RA) were included. Chlamydia trachomatis DNA was detectable by LCR in samples of synovial fluid cells from 4/12 patients with C. trachomatis-triggered ReA, and in none by PCR. Chlamydia trachomatis DNA was not detectable in the synovial fluid cells of the seven RA patients by either method, neither was C. trachomatis DNA detectable in the peripheral blood leucocytes of the ReA patients (0/11) or controls (0/6) by LCR. The LCR technique may be useful in the demonstration of Chlamydia DNA in synovial fluid cells.      

Exuberant pigmented conjunctivitis epidemiology, immunology, histopathology, and treatment with mitomycin-C

We describe a unique form of ocular disease called “exuberant pigmented conjunctivitis” and demonstrate the allergic response to environmental particles combined with high altitude, dust, concentrated ultraviolet rays, and extreme dryness. A nonsteroid treatment with mitomycin-C was studied to avoid known topical steroid side effects. The authors have stated that they does not have a significant financial interest or other relationship with any product manufacturer or provider of services discussed in this article. The authors also do not discuss the use of off-label products, which include unlabeled, unapproved, or investigative products or devices.     

Association of biomarkers of inflammation and oxidative stress with the risk of chronic kidney disease in Type 2 diabetes mellitus in North Indian population

Chronic kidney disease (CKD) is a major cause of morbidity and mortality worldwide. It results from diverse etiologies, diabetes being a frontrunner amongst them. Type 2 diabetes mellitus (DM) is being increasingly recognized as a proinflammatory state with increased oxidative stress which enormously increases the risk of micro and macro vascular diseases. This study was planned to explore the possible association between tumor necrosis factor-alpha (TNF-α), urinary monocyte chemoattractant protein-1 (uMCP-1), high-sensitivity C-reactive protein (hsCRP) and parameters of oxidative stress in patients with Type 2 diabetes mellitus (DM) and diabetic chronic kidney disease (DM–CKD). Fifty patients each were recruited in DM, DM–CKD and healthy control groups. Plasma TNF-α, hsCRP and uMCP-1 levels as inflammatory mediators were measured by ELISA, reduced glutathione (GSH), ferric reducing ability of plasma (FRAP) as parameters of antioxidant activity and malondialdehyde (MDA) as marker of oxidative stress, were measured spectrophotometrically. Plasma TNF-α, hsCRP and uMCP-1 were significantly higher in DM–CKD compared to DM and healthy controls. Lipid peroxidation, measured as MDA was significantly higher in patients with DM–CKD as compared to patients with DM and healthy controls. Further, antioxidant capacity of blood measured as FRAP and GSH was found to be significantly lower in patients with DM and DM–CKD as compared to healthy controls (p < 0.001). Plasma TNF-α and uMCP-1 showed a significant positive correlation with HbA_1c (r = 0.441, 0.643), hsCRP (r = 0.400, 0.584) and MDA (r = 0.423, 0.759) and significant negative correlation with GSH (R = ? 0.370, ? 0.800) and FRAP (r = ? 0.344, ? 0.684) Increased inflammatory markers viz. TNF-α, hsCRP and uMCP-1 and markers of oxidative stress i.e. increased MDA and decreased GSH and FRAP in DM–CKD suggest an important role of inflammation and oxidative stress in the pathogenesis of renal damage in diabetic patients.     

Bullous mastocytosis: report of a patient and a brief review of the literature

We report a 6-month-old male infant who presented to the pediatric dermatology clinic at Wake Forest University Baptist Medical Center with a generalized bullous eruption since 3 months of age. A sepsis work up was performed at an outside hospital before presentation and did not reveal any evidence of systemic infection. Clinical presentation revealed a well-nourished, appropriate-for-age, 6-month-old boy with multiple tense bullae, some in a "string of pearls" arrangement, on the bilateral upper extremities and trunk. Multiple erosions were also noted. Laboratory evaluation revealed a normal complete blood count. Polymerase chain reaction was negative for herpes simplex virus types I and II. Histologic sections demonstrated a large space of separation between the epidermis and dermis which was filled by a monomorphous infiltrate composed of round to oval cells with centrally placed nuclei, consistent with mast cells. Leder and C-Kit stains were strongly positive, confirming the diagnosis of bullous mastocytosis. Treatment included fluocinonide 0.05% cream and tacrolimus 0.1% ointment to active lesions and silver sulfadiazine 1% cream to erosions. Improvement was noted during follow-up examination.