Clonal evolution in atypical chronic granulocytic leukemia: a non- Philadelphia translocation

Hemopoietic cells in chronic granulocytic leukemia (CGL) frequently contain a chromosome translocation involving chromosome 22 and another autosome, usually number 9. The translocated chromosome 22 is known as the Philadelphia (Ph) chromosome. The appearance of a second Ph chromosome is the most common cytogenetic abnormality in CGL signaling the blastic phase. For 6 yr we serially studied a man with atypical CGL whose marrow cells were marked by a translocation from chromosome 18 to chromosome 11 [46XY,t(11;18)(q23;q12)]. Three months prior to blast transformation there appeared an extra copy of the marker chromosome 18: 47XY,t(11;18)(q23;q12),+(18p11 leads to 18q12). This man presents a new cytogenetic pattern of clonal evolution in CGL. The pattern is analogous to that of the Ph chromosome and is characterized by a balanced chromosomal rearrangement and the subsequent acquisition of an extra copy of the small translocation chromosome immediately prior to blast transformation.     

Granulocyte macrophage colony-stimulating activity production by cultured human thymic nonlymphoid cells is regulated by endogenous interleukin-1

Supernatants of cultured human thymic nonlymphoid cells were assayed for granulopoietic factors using cultures of low density bone marrow mononuclear cells (LD-BMMC). Thymic nonlymphoid cell-conditioned medium (TNLC-CM) supported vigorous myeloid colony growth of LD-BMMC, and of LD-BMMC depleted of T lymphocytes and/or monocytes. Colony stimulating activity (CSA) in TNLC-CM was abrogated by a highly specific neutralizing antiserum against recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). TNLC-CM also enhanced colony growth in LD-BMMC stimulated by colony stimulating activity from a giant cell tumor culture (GCT). The enhancing activity of TNLC-CM, unlike its CSA activity, required the presence of adherent cells in the marrow cell culture. The addition of anti-interleukin-1 (anti-IL-1) antibody to TNLC-CM inhibited the GCT-enhancing activity, but not the CSA. When the anti-IL-1 immunoglobulin was added directly to cultures of thymic nonlymphoid cells, GM-CSF production was completely inhibited, and the GCT enhancing activity was neutralized. We conclude that an intercellular regulatory network exists in cultured thymic explants in which GM-CSF expression is induced by IL-1. In this system, the granulopoietic effect of IL-1 derives not from a direct effect on myeloid progenitors, but from its ability to recruit CSA production by other cells.     

Application of paclitaxel-eluting metal stents in renal artery of pig model

BACKGROUND AND PURPOSE: Recent reports concerning coronary, carotid, and femoral vasculature have proposed the use of drug-eluting metal stents (MS) to improve clinical and angiographic outcomes. Based on these reports, we used paclitaxel-eluting MS within an animal renal artery lumen and compared the results with those using a bare-metal stent. MATERIALS AND METHODS: The experimental model in this study was the female pig renal artery. Ten pigs with weights ranging from 25 to 30 kg were used. Twenty stents were placed, two in each animal. The MS placement was randomly performed in either the right or left renal artery of each animal. In 10 arteries, a 3.5 x 18 mm R-stent (group A) was placed; in the remaining 10 arteries, a 3 x 32 mm paclitaxel-eluting coronary stent (T-stent, group B) was inserted. Patency was estimated with the use of digital subtraction angiography, CT angiography, and virtual endoscopy at 24 hours and 1 month poststent placement. RESULTS: The positioning of the MS was successful in all cases. The initial angiographic result was maintained 24 hours after the intervention. No stent migration was seen, except for one paclitaxel stent that was acutely occluded. The one-month patency rate, as demonstrated by angiography, CT angiography, and virtual endoscopy, was 70% (8 arteries) in group A and 90% (9 arteries) in group B. The thickness of the endothelium and of the muscular coat was statistically significantly less in group B compared with group A (P = 0.0352 and P = 0.0046, respectively). CONCLUSION: These preliminary experimental study results suggest that the paclitaxel-eluting MS is more efficient than the bare-metal stent when used within the pig renal artery. Further experimental and clinical studies are necessary to validate our preliminary encouraging results.     

Application of paclitaxel-eluting metal mesh stents within the pig ureter: an experimental study

OBJECTIVE: The purpose of the present study is to compare the standard bare metal stents (BMS) with the Paclitaxel-Drug Eluting Stent (DES) in the ureter of a pig model. MATERIALS AND METHODS: We report on an experimental study with ten female pigs weighing between 25 and 30 kg. The stents were randomly placed in either the right or left ureter in each of 10 study animals, for a total of 20 stented ureters. Ten ureters were stented with an R-Stent (Orbus Medical Technologies, Hoevelaken Netherlands), and ten with a Paclitaxel-Eluting Coronary Stent (Boston Scientific, Natick, MA, USA). Patency was measured by radiograph of the nephrostomy tract, intravenous urography and virtual endoscopy at 24 hours and 21 days after the initial procedure, respectively. RESULTS: Free flow of urine through the stents into the bladder was documented in all stented ureters 24 hours after stent insertion by radiograph of the nephrostomy tract. At the 21 day follow-up examination, 5 R-Stents were found to be completely occluded and two partially stenosed, whereas no occluded stent was detected in the Paclitaxel-DES group. Pathology examination of the stents at 21 days follow-up showed that the obstructed R-Stents generated severe inflammation with metaplasia of the urothelium. The Paclitaxel-Eluting MS generated a mild inflammatory response within the ureteral lumen at the site of the stent, without hindering ureteral patency. R-stents proved to develop more hyperplasia compared to the Paclitaxel-Eluting MS. CONCLUSIONS: Paclitaxel-DES, when compared with the standard R- Stent BMS, generated less inflammation and/or hyperplasia of the surrounding tissues, thus maintaining ureteral patency. Long-term animal trials are required to further validate our results.     

The NO donor DETA-NONOate reversibly activates an inward current in neurones and is not mediated by the released nitric oxide

Background and purpose:

It has been previously shown that high levels of nitric oxide (NO), from NO donors, kill neurones, but the mechanisms are unclear.

Experimental approach:

The effects of NO donors on the electrical properties of rat cultured cerebellar granule cells (CGC neurones) were investigated using the whole-cell patch-clamp technique.

Key results:

The NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate or NOC-18) caused a rapid, persistent, but fully reversible inward current that was associated with an increase in baseline noise and was concentration dependent (100 µM–10 mM). The response to 3 mM DETA-NONOate was completely inhibited by 1 mM gadolinium, but not by NO scavengers (1 mM haemoglobin or 1 mM PTIO) or glutamate receptor antagonists (10 µM MK-801 or 60 µM CNQX). Application of decomposed 3 mM DETA-NONOate or 3 mM nitrite had no effect. In contrast, the NO donor S-nitrosoglutathione (GSNO) caused a rapid, persistent, but fully reversible outward current that was also concentration dependent (1–10 mM). The 3 mM GSNO response was unaltered by NO scavengers, glutamate antagonists or gadolinium, but was mimicked by decomposed 3 mM GSNO and 3 mM oxidized glutathione.

Conclusions and implications:

These results suggest that DETA-NONOate directly activates cation-selective channels, causing an inward current in CGCs. In contrast, GSNO causes an outward current in these cells. Some of the effects of these NO donors are independent of NO, and thus caution is required in interpreting results when using high concentrations of these compounds.     

Infrapopliteal application of paclitaxel-eluting stents for critical limb ischemia: midterm angiographic and clinical results

PURPOSE: To report the midterm (30%, or flow-limiting dissection). Patients were followed up with regular clinical evaluation, and digital subtraction angiography was scheduled at 6 months and 1 year. Life-table analysis and Kaplan-Meier plotting of angiographic and clinical variables were performed. Cox proportional-hazards regression analysis was employed to adjust for various covariates and search for independent adverse predictors of angiographic and clinical outcome. RESULTS: Infrapopliteal procedures were performed in 29 patients with 32 limbs with CLI; 79.3% of the patients had diabetes and 34.5% had renal disease. A total of 62 coronary PES were deployed in 50 below-knee lesions (mean stent-implanted length, 25.51 mm+/-12.16). Technical success rate was 100%. The 1-year mortality rate was 16.9%, and the limb salvage rate was 88.5%. The 1-year angiographic in-stent primary patency rate was 30.0%, whereas the incidence of in-stent binary (>50%) restenosis was 77.4%. The 1-year incidence of clinically driven repeat interventions was 30.5%. The Cox model calculated renal disease as the only independent predictor of decreased primary patency and increased repeat intervention events. Initial occlusions also adversely affected primary patency. CONCLUSIONS: Infrapopliteal PES achieved acceptable clinical results in CLI, even though they failed to inhibit vascular restenosis and decrease the need for repeat interventions. Renal disease and initial occlusions are adverse prognostic factors for infrapopliteal endovascular procedures.     

Using an Open-Source PACS Virtual Machine for a Digital Angiography Unit: Methods and Initial Impressions

The productivity gains, diagnostic benefit, and enhanced data availability to clinicians enabled by picture archiving and communication systems (PACS) are no longer in doubt. However, commercial PACS offerings are often extremely expensive initially and require ongoing support contracts with vendors to maintain them. Recently, several open-source offerings have become available that put PACS within reach of more users. However, they can be resource-intensive to install and assure that they have room for future growth—both for computational and storage capacity. An alternate approach, which we describe herein, is to use PACS built on virtual machines which can be moved from smaller to larger hardware as needed in a just-in-time manner. This leverages the cost benefits of Moore's Law for both storage and compute costs. We describe the approach and current results in this paper.