BACKGROUND: Endodontics as a discipline has offered patients the opportunity to maintain their natural teeth. As the population expands and ages, the demand for endodontic therapy can be expected to increase as patients seek dental options to keep their teeth for a lifetime. CLINICAL IMPLICATIONS: New materials, techniques and instruments are entering the market-place to assist dentists in providing patients with more predictable and reliable endodontic treatment. In addition, these new systems make the delivery of endodontic services more efficient. This article describes these advances in endodontic treatment for dentists interested in incorporating these advances into their clinical practice. (+info)
Leukocytosis and the retinoic acid syndrome in patients with acute promyelocytic leukemia treated with arsenic trioxide.
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PURPOSE: Arsenic trioxide, like all-trans-retinoic acid (RA), induces differentiation of acute promyelocytic leukemia (APL) cells in vivo. Treatment of APL patients with all-trans RA is commonly associated with leukocytosis, and approximately 50% of patients develop the RA syndrome. We reviewed our clinical experience with arsenic trioxide to determine the incidence of these two phenomena. PATIENTS AND METHODS: Twenty-six patients with relapsed or refractory APL were treated with arsenic trioxide for remission induction at daily doses that ranged from 0.06 to 0.17 mg/kg. RESULTS: Twenty-three patients (88%) achieved complete remission. Leukocytosis was observed in 15 patients (58%). The median baseline leukocyte count for patients with leukocytosis was 3,900 cells/microL (range, 1,200 to 72,300 cells/microL), which was higher than that for patients who did not develop leukocytosis (2,100 cells/microL; range, 500 to 5,400 cells/microL; P =.01). No other cytotoxic therapy was administered, and the leukocytosis resolved in all cases. The RA syndrome was observed in eight patients (31%). Patients who developed leukocytosis were significantly more likely to develop the RA syndrome (P <.001), and no patient without a peak leukocyte count greater than 10,000 cells/microL developed the syndrome. Among the patients with leukocytosis, there was no observed relation between the leukocyte peak and the probability of developing the syndrome (P =.37). CONCLUSION: Induction therapy of APL with all-trans RA and arsenic trioxide is associated with leukocytosis and the RA syndrome. These clinical effects seem to be intrinsically related to the biologic responsiveness and the differentiation process induced by these new agents. (+info)
BCR-ABL mediates arsenic trioxide-induced apoptosis independently of its aberrant kinase activity.
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In the prechemotherapy era arsenic derivatives were used for treatment of chronic myelogenous leukemia, a myeloproliferative disorder characterized by the t(9;22) translocation, the Philadelphia chromosome (Ph+). In acute promyelocytic leukemia response to arsenic trioxide (As2O3) has been shown to be genetically determined by the acute promyelocytic leukemia-specific t(15;17) translocation product PML/RARalpha. Hence, we reasoned that As2O3 might have a selective inhibitory effect on proliferation of BCR-ABL-expressing cells. Here, we report that: (a) As2O3 induced apoptosis in Ph+ but not in Ph- lymphoblasts; (b) enforced expression of BCR-ABL in U937 cells dramatically increased the sensitivity to As2O3; (c) the effect of As2O3 was independent of BCR-ABL kinase activity; and (d) As2O3 reduced proliferation of chronic myelogenous leukemia blasts but not of peripheral CD34+ progenitors. In summary, these data establish As2O3 as a tumor cell-specific agent, making its clinical application in Ph+ leukemia feasible. (+info)
Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis.
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Arsenic trioxide (As(2)O(3)) has recently been used successfully in the treatment of acute promyelocytic leukemia and has been shown to induce partial differentiation and apoptosis of leukemic cells in vitro. However, the mechanism by which As(2)O(3) exerts its antileukemic effect remains uncertain. Emerging data suggest that the endothelium and angiogenesis play a seminal role in the proliferation of liquid tumors, such as leukemia. We have shown that activated endothelial cells release cytokines that may stimulate leukemic cell growth. Leukemic cells, in turn, can release endothelial growth factors, such as vascular endothelial growth factor (VEGF). On the basis of these observations, we hypothesized that As(2)O(3) may interrupt a reciprocal loop between leukemic cells and the endothelium by direct action on both cell types. We have shown that treatment of proliferating layers of human umbilical vein endothelial cells (HUVECs) with a variety of concentrations of As(2)O(3) results in a reproducible dose- and time-dependent sequence of events marked by change to an activated morphology, up-regulation of endothelial cell adhesion markers, and apoptosis. Also, treatment with As(2)O(3) caused inhibition of VEGF production in the leukemic cell line HEL. Finally, incubation of HUVECs with As(2)O(3) prevented capillary tubule and branch formation in an in vitro endothelial cell-differentiation assay. In conclusion, we believe that As(2)O(3 )interrupts a reciprocal stimulatory loop between leukemic cells and endothelial cells by causing apoptosis of both cell types and by inhibiting leukemic cell VEGF production. (Blood. 2000;96:1525-1530) (+info)
Gray scale second harmonic imaging of acoustic emission signals improves detection of liver tumors in rabbits.
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This study evaluates a new reticuloendothelium specific sonographic contrast agent NC100100 (Sonazoid) for detection of liver VX-2 tumors in rabbits. Gray scale imaging of five groups of three rabbits, with hepatic VX-2 tumors implanted 7, 10, 12, 14, and 18 days previously, was performed prior to injection of Sonazoid (dosages, 0.01-0.5 ml/kg). Sonazoid produces induced acoustic emission after uptake in the liver. Therefore, harmonic gray scale images were obtained immediately after injection as well as delayed (by up to 2(1/2) h). Five rabbits (one from each group) also had angiography performed, while all animals were evaluated by pathologic examination. Non-contrast enhanced sonography detected 17 of 61 tumors (29%), as well as three false-positives, while the addition of Sonazoid detected 57 tumors (93%) and one false-positive (P<0.001). Acoustic emission made 2 x 2 mm tumors (invisible in conventional B-mode sonography) clearly perceivable in harmonic gray scale. In the subgroup that received angiography, 12 of 36 tumors (33%) were detected with conventional sonography compared to 22 tumors (61%) seen with angiography (P = 0.002). After injection of Sonazoid the ultrasonographic detection rate increased to 97% (35 of 36 tumors), which was a significant improvement over angiography (P = 0.00024). Improved detection of hepatic VX-2 tumors with second harmonic gray scale imaging of Sonazoid is possible because of this agent's acoustic emission capabilities. (+info)
Antimicrobial evaluation of N-alkyl betaines and N-alkyl-N, N-dimethylamine oxides with variations in chain length.
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Alkyl betaines and alkyl dimethylamine oxides have been shown to have pronounced antimicrobial activity when used individually or in combination. Although several studies have been conducted with these compounds in combinations, only equimolar concentrations of the C(12)/C(12) and C(16)/C(14) chain lengths for the betaine and the amine oxide, respectively, have been investigated. This study investigates the antimicrobial activity of a wide range of chain lengths (C(8) to C(18)) for both the betaine and amine oxide and attempts to correlate their micelle-forming capabilities with their biological activity. A broth microdilution method was used to determine the MICs of these compounds singly and in various molar ratio combinations. Activity against both Staphylococcus aureus and Escherichia coli was investigated. Antimicrobial activity was found to increase with increasing chain length for both homologous series up to a point, exhibiting a cutoff effect at chain lengths of approximately 16 for betaine and 14 for amine oxide. Additionally, the C(18) oleyl derivative of both compounds exhibited activity in the same range as the peak alkyl compounds. Critical micelle concentrations were correlated with MICs, inferring that micellar activity may contribute to the cutoff effect in biological activity. (+info)
Retinoic acid (RA) and As2O3 treatment in transgenic models of acute promyelocytic leukemia (APL) unravel the distinct nature of the leukemogenic process induced by the PML-RARalpha and PLZF-RARalpha oncoproteins.
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Acute promyelocytic leukemia (APL) is associated with chromosomal translocations always involving the RARalpha gene, which variably fuses to one of several distinct loci, including PML or PLZF (X genes) in t(15;17) or t(11;17), respectively. APL in patients harboring t(15;17) responds well to retinoic acid (RA) treatment and chemotherapy, whereas t(11;17) APL responds poorly to both treatments, thus defining a distinct syndrome. Here, we show that RA, As(2)O(3), and RA + As(2)O(3) prolonged survival in either leukemic PML-RARalpha transgenic mice or nude mice transplanted with PML-RARalpha leukemic cells. RA + As(2)O(3) prolonged survival compared with treatment with either drug alone. In contrast, neither in PLZF-RARalpha transgenic mice nor in nude mice transplanted with PLZF-RARalpha cells did any of the three regimens induce complete disease remission. Unexpectedly, therapeutic doses of RA and RA + As(2)O(3) can induce, both in vivo and in vitro, the degradation of either PML-RARalpha or PLZF-RARalpha proteins, suggesting that the maintenance of the leukemic phenotype depends on the continuous presence of the former, but not the latter. Our findings lead to three major conclusions with relevant therapeutic implications: (i) the X-RARalpha oncoprotein directly determines response to treatment and plays a distinct role in the maintenance of the malignant phenotype; (ii) As(2)O(3) and/or As(2)O(3) + RA combination may be beneficial for the treatment of t(15;17) APL but not for t(11;17) APL; and (iii) therapeutic strategies aimed solely at degrading the X-RARalpha oncoprotein may not be effective in t(11;17) APL. (+info)
Water vapour in a closed anaesthesia circuit reduces degradation/adsorption of halothane by dried soda lime.
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Dry lime causes a loss of volatile anaesthetics by degrading and adsorbing them. Degradation produces toxic substances and heat. Rehydration of lime stops degradation. If humidified breathing gases rehydrate lime, closed anaesthesia-circuits may reduce the loss of anaesthetics. To test this hypothesis we ventilated a reservoir bag with PhysioFlex-devices using fresh (F) and dried (D) soda lime both in the presence (+H) and absence (-H) of halothane. We measured halothane delivery, humidity, temperature, and lime weight. Halothane was lost for 13 min in D + H. Humidity increased steeper with fresh lime, whereas absorbent weight increased more with dried lime; halothane increased both variables (F + H: 99%, 8 g; F - H: 93%, 6 g; D + H: 58%, 17 g; D - H: 24%, 15 g). Surprisingly, temperature remained constant, probably because of the high gas flow (70 litres min-1) generated inside the Physioflex. These findings indicate rehydration of dried lime by humid gases and a rapid cessation of the loss of halothane in the PhysioFlex. (+info)