The antiapoptotic effects of blood constituents in patients with chronic lymphocytic leukemia

OBJECTIVE: Clonal B-lymphocytes of chronic lymphocytic leukemia (B-CLL) are characterized by decreased sensitivity to programmed cell death and, therefore, they accumulate in vivo. However, these malignant cells die rapidly in vitro. In the current study we concentrated on the contribution of autologous serum (AS) and lymphocyte subsets to the survival of the malignant cells in vitro. METHODS: Mononuclear cells from the peripheral blood of 26 CLL patients and 24 controls were incubated overnight in the presence or absence of AS and heat-inactivated AS (HI-AS) or fetal calf serum (FCS). Also, isolated B cells were incubated at different concentrations in the presence of AS and/or isolated T cells. The level of apoptosis of CD19+ cells was measured by flow cytometry. RESULTS: Spontaneous apoptosis of unfractionated B-CLL cells incubated with AS, FCS or without serum was significantly lower than the rate of B-cell death in the control group, in similar culture conditions. AS had an antiapoptotic effect on unfractionated B-CLL cells when compared with FCS. The rate of apoptosis of B-CLL cells was directly associated with stage. HI of AS had a variable effect, which was related to the stage of the disease. High concentrations of B cells and the addition of autologous T cells reduced the rate of apoptosis when incubated without serum. The antiapoptotic effect of T cells was most prominent in progressive stages. CONCLUSIONS: B-CLL cells exhibit decreased spontaneous apoptosis, which is partially prevented by humoral (AS) and cellular (T cells and B-CLL cells) factors. The equilibrium between apoptotic and antiapoptotic factors changes with disease progression.     

Reduction of cis,trans,cis-[PtCl2(OCOCH3)2(NH3)2] by aqueous extracts of cancer cells

Pt(IV) complexes must be reduced to kill cancer cells. While reduction rates correlate with reduction potentials, we wanted to check if the rates of reduction depend on the cell line used. The reduction of cis,trans,cis-[PtCl2(OCOCH3)2(NH3)2] by extracts of three cell lines was measured, and the rates follow the order A2780cisR > A2780 > HT-29. The reduction is not carried out by the low molecular weight (MW) antioxidants but primarily by cellular components with MW > 3000.     

Prospective drug utilization evaluation of three broad-spectrum antimicrobials: cefepime, piperacillin-tazobactam and meropenem

BACKGROUND: Cefepime, piperacillin-tazobactam and meropenem are among the broadest-spectrum and most expensive antimicrobials. AIM: To evaluate guidelines for appropriate use of these drugs. METHODS: We developed guidelines for use of these antibiotics, and conducted a two-phase drug utilization evaluation. We included all patients who received one of the study drugs during two 3-month periods, with an educational intervention in the intervening period. Appropriateness was determined for initiation of treatment, and for adaptation or continuation of established treatment. RESULTS: Overall, 205 patients received 271 courses with one of these antibiotics, for a total of 709 defined daily doses (DDD) of cefepime, 543 of piperacillin-tazobactam, and 680 of meropenem (8.3, 6.3 and 7.9 DDD/1000 admission days, respectively). Of these 271 courses, 234 were appropriate (86%). Treatment was continued for > or =5 days in 60%, of which 88% were appropriate (NS). Of the 271 courses, 210 (77%) were empirical (83% appropriate), while 61 (23%) were based on a relevant culture result (97% appropriate) (p < 0.001). Appropriateness differed significantly between departments (p < 0.001), and between the two phases (p < 0.001). The major difference between the two surveys was a decrease in meropenem usage (p < 0.05). DISCUSSION: The vast majority of courses with cefepime, piperacillin-tazobactam and meropenem are empirically selected and continued, underlying the importance of an optimal initial choice. Antibiotic guidelines, in conjunction with formal infectious disease consultation, can contribute to more appropriate use of these drugs.     

Normal levels and function of endothelial progenitor cells in patients with psoriatic arthritis

Endothelial progenitor cells (EPCs) are a population of bone marrow derived cells which have been attributed with the ability to migrate into areas of tissue ischemia and to posses reparative qualities. EPCs have been shown to be decreased in level and function in various inflammatory disorders. Psoriasis and psoriatic arthritis are associated with an increase in cardiovascular morbidity. The aim of the study was to investigate the number of EPCs among patients suffering from psoriasis and psoriatic arthritis. Patients suffering from active psoriasis and psoriatic arthritis were recruited as well as healthy controls. Disease activity was assessed with the DAS-28, BASDAI and PASI scores. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by FACS analysis using the CD34/133 and CD34/KDR. No significant difference was found between numbers of EPCs between healthy controls, patients with psoriasis and psoriatic arthritis. A significant correlation was found between levels of VGEF and the BASDAI score. The results of the current study do not support a significant role for EPCs in the pathogenesis of psoriasis and psoriatic arthritis.     

Role of multisection CT angiography in the evaluation of vertebrobasilar vasospasm in patients with subarachnoid hemorrhage

BACKGROUND AND PURPOSE: Optimal means for assessing cerebral vasospasm, mainly at the vertebrobasilar system, have not been established. The purpose of this study was to evaluate the role of multisection CT angiography (MCTA) in the detection and quantification of vertebrobasilar vasospasm (VBS) indicated on transcranial Doppler (TCD) imaging in patients with subarachnoid hemorrhage (SAH). METHODS: Forty-three MCTA studies of the vertebrobasilar arteries were performed with a multisection spiral CT scanner in 36 patients with SAH. Parameters used were 1-mm collimation, 0.625Q pitch, 120 kV, and 250 mAs. Contrast material was injected (80-100 mL, 3 mL/s) after a 15-20-second delay. Postprocessing of the vertebrobasilar system was performed by using maximum intensity projection and volume-rendering reconstruction. Vessel diameter was measured at different intracranial locations along the vertebral and basilar arteries perpendicular to their long axis by using curved reformatted multiplanar reformation. TCD imaging of the posterior circulation was performed within 24 hours. RESULTS: MCTA demonstrated narrowed arteries compatible with VBS in 13 patients, consistent with TCD findings. Despite TCD recordings of high flow velocity in three other patients, MCTA did not reveal vasospasm but did show wide arteries feeding arteriovenous malformations in two and normal-sized arteries in one. VBS in two patients was identified on MCTA but overlooked during TCD imaging. Twenty patients had normal findings on both TCD and MCTA studies. CONCLUSION: Cerebral MCTA is recommended as a reliable, rapid, and minimally invasive diagnostic method, one complementary to TCD imaging for assessing VBS in patients with SAH.