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Comparison of the slow-release polymer-based paclitaxel-eluting Taxus-Express stent with the bare-metal Express stent for saphenous vein graft interventions.

BACKGROUND: The paclitaxel-eluting Taxus-Express stent is superior regarding angiographic and clinical outcome compared with its bare-metal platform for lesions in native coronary arteries. We studied the potential impact of the Taxus-Express stent in comparison with its bare-metal counterpart for treatment of lesions in saphenous vein grafts (SVGs). Furthermore, a meta-analysis was performed regarding use of drug-eluting (DES) vs bare-metal stents (BMS) in SVG lesions. METHODS: We analyzed 13 consecutive patients who underwent percutaneous revascularization in SVG lesions using the slow-release, paclitaxel-eluting Taxus-Express stent. These lesions were balanced with 26 patients with SVG lesions treated with the bare-metal Express stent (BMS) in the preceding period. Angiographic follow-up was performed after 6 months, clinical follow-up after 6 and 12 months. RESULTS: There were no statistically significant differences regarding clinical, procedural and angiographic parameters pre and post intervention. Binary restenoses occurred significantly less in the Taxus group compared with the BMS group (0% vs 34.6%; p=0.016). This translated into a significantly lower occurrence of major adverse cardiac events (death, Q-wave myocardial infarction, repeat target vessel revascularization) in the Taxus group compared with the BMS group at the 6-month (0% vs 26.9%, p=0.039) and 12-month follow-up (7.7% vs 38.5%, p=0.045). Multivariate predictors for freedom of binary restenosis were the reference diameter pre intervention and treatment with Taxus stents. Meta-analysis including 280 DES and 256 BMS patients revealed an odds ratio of 0.34 (95% confidence interval 0.21-0.54) for MACE and 0.26 (95% confidence interval 0.16-0.44) for target vessel revascularizations, both favoring DES. CONCLUSIONS: We conclude that the use of the slow-release Taxus-Express stent has the potential to be superior regarding angiographic and clinical outcome compared with its bare-metal counterpart for treatment of SVG lesions within a 12-month follow-up. A large, randomized trial including a long follow-up period is now required to prove the results of the meta-analysis.

Aged↗

Diagnosis of Taxus (yew) poisoning in a horse.

A 2-year-old bay Thoroughbred colt was found dead overnight in its stall without a known history of any illness, existing disease, or toxicant exposure. No information on the clinical signs before this animal's death was reported. A full necropsy was performed the next morning and revealed a mild to moderate degree of endocardial hemorrhages in both ventricles. Microscopic examination of the heart showed an acute mild multifocal necrosis of papillary muscles and ventricles. The stomach content contained approximately 2% Taxus alkaloids as determined by gas chromatography/mass spectrometry. In the past, diagnosis of Taxus poisoning has been mainly based on history of exposure and the presence of plant parts in the gastrointestinal tract. Pathological lesions associated with Taxus poisoning have not been published for horses. Therefore, this is the first report of cardiac lesions in a horse after lethal exposure to Taxus. On the basis of these findings, it is suggested that Taxus exposure needs to be considered in the differential diagnosis of horses that die suddenly or have cardiac lesions suggestive of Taxus exposure, even if intact plant parts are not identified in the stomach by the naked eye.

Alkaloids↗

Cell lines of Taxus species as source of the anticancer drug taxol.

Callus culture of Taxus baccata and Taxus x Media were induced using explants of young stems and female gametophyte. Culture conditions have been established for the cell suspension of the different callus cell lines. Callus were induced from Taxus baccata and Taxus x Media using Murashige and Skoog (MS) medium supplemented with different concentrations of 2,4 D (2,4-dichlorophenoxyacetic) and benzylaminopurine (BA). All the cultures grew slowly following the first subculture and the majority turned brown and ceased growth. The fast growing callus lines constituted a habituated callus lines (CFGTB; CFGTM; CSTB and CSTB). These callus lines were used to induce cell suspension in the best nutritional medium (1 mg/l 2,4-D and 0.1 mg/l BA). The callus exhibited levels of taxol ranging from 0.1 to 15 mg/Kg on a dry weight basis. Suspension cultures of Taxus baccata (CSTB and CFGTB) and Taxus x Media (CSTM and CFGTM) were maintained at 25 degrees C on a MS medium with two weeks transfers. The maximum taxol production for suspension cell was within the range 5 to 6 mg/l.

Antineoplastic Agents↗

[Effects of aspect on distribution pattern of Taxus chinensis population in Yele, Sichuan Province: an analysis based on patches information].

Employing GIS method and based on patches information, this paper studied the effects of aspect on the distribution pattern of Taxus chinensis population in Yele, Sichuan Province. The results showed that Taxus chinensis population mainly distributed on the aspects of northwest, northeast, east and north. These aspect patches were absolutely dominant on area, mean size, mean edge and the number of Taxus chinensis. There existed a significant correlation between aspect and Taxus chinensis distribution. Taxus chinensis distributed preferentially on north, northeast, northwest and east patches, then on west and southwest patches, and finally on flat and southeast patches. The distribution patterns of Taxus chinensis in Yele were clustering, except on south aspect patches. The intensity of clustering on north aspect patches was the highest, with the value of Clark-Evans (CE) index being 0.906. The intensity of clustering on northeast and northwest aspect patches was lower than that on north aspect patches, with the CE value 0.797 and 0.563, respectively. The CE values on the rest aspect patches were all not larger than 0.5. There existed a significant positive correlation between the intensity of clustering index, number of patches, total patch edge, and the number of Tarus chinensis distributed on the patches, with the value of correlation coefficient 0. 936, 0.735 and 0.802, respectively. There were no significant correlations among the intensity of clustering, patch area, mean patch size, mean patch edge, and mean shape index of aspect patches.

Biomass↗

Sudden unexpected death due to Taxus poisoning. A report of five cases, with review of the literature.

The toxicity of yew (Taxus) has been known since antiquity. However, in the past 31 years, to our knowledge only six cases of Taxus poisoning have been reported in the literature. In the present paper we add five cases. From a forensic point of view, intoxication with Taxus has three important aspects: (i) the clinical presentation, which among other causes should suggest Taxus intoxication; (ii) the fact that the diagnosis may often be easily made by examination of the contents of stomach, duodenum and small bowel and (iii) the widespread availability in the near future of Taxol, an anti-neoplastic drug which is an alkaloid extracted from Taxus. The clinical and autopsy findings are summarized, the diagnostic aspects are discussed and the literature concerning Taxus is reviewed.

Adult↗

Methyl jasmonate-induced overproduction of paclitaxel and baccatin III in Taxus cell suspension cultures.

Taxus cell culture may be an alternative source of paclitaxel and related taxane production. Significantly increased amounts of paclitaxel and baccatin III were observed in cultured cells of Taxus species after exposure to methyl jasmonate. Among the three species of Taxus tested, Taxus media showed the highest paclitaxel content while Taxus baccata showed the highest baccatin III content when 100 microM of methyl jasmonate was added to the culture media. Furthermore, the activities of methyl jasmonate and related substances for inducing paclitaxel production were compared in cell suspension cultures of T. media. Methyl jasmonate and its free acid showed the strongest promoting activity. Reduction of the keto group at the C-3 position greatly reduced this activity. cis-Jasmone, which does not have a carboxyl group at the C-1 position, had almost no activity. These results suggest that these two regions of methyl jasmonate are important for promoting the production of paclitaxel and related taxanes in Taxus cell cultures.

Acetates↗

[Economic impact of the taxus coronary stent: implications for the Spanish healthcare system].

INTRODUCTION AND OBJECTIVES: This article examines the cost impact associated with the utilization of the Taxus drug eluting stent versus a conventional bare-metal stent for percutaneous coronary interventions in a Spanish hospital setting. METHODS: A decision analysis model has been developed to compare the intervention and re-hospitalization costs at 12 and 24 months post-intervention. The analysis considers the general patient population and a high-risk subpopulation (diabetes, small vessel, long lesion). The analysis simulates the results of the TAXUS-IV clinical trial, in a population with similar risks, with appropriate costs, and including budget impact analyses with alternative utilization scenarios. RESULTS: The expected average per patient hospital cost at 12 months was 6934 euros with Taxus and 6756 euros with bare-metal stent (and increase of 2.6%). At 24 months, per patient hospital cost was 6,991 euros for Taxus and 6887 euros for bare-metal stent (an increase of 1.5%). In the high-risk subpopulation, Taxus was overall cost saving as compared to bare-metal stent both at 12 months (decrease of 3.0%) and 24 months (decrease of 4.7%). CONCLUSIONS: Use of Taxus in the overall population slightly raises treatment costs, while in patients with greater risk of restenosis the treatment cost is reduced. Given the decrease in the number of repeat revascularizations with this stent, the cost-effectiveness relationship could be acceptable in the general patient population and is dominant in the high-risk subpopulation.

Coronary Disease↗

Influence of water extracts from the surface of two yew (Taxus) species on mites (Tetranychus urticae).

Taxus cuspidata and Taxus media var. Hicksii contain paclitaxel, among other taxoids, on the surface of the needles. These compounds were removed by 5-s dipping of the needles in water just below its boiling point at 96 degrees C and at 60 degrees C and 40 degrees C. Taxus cuspidata contained a fourfold higher concentration of paclitaxel than Taxus media var. Hicksii. The extract with the higher concentration of paclitaxel was more harmful to the mites Tetranychus urticae Koch, increasing their mortality 150%, prolonging development by ca. 20% and lowering the average fecundity from 112 in the control to 16.13 after treatment with Taxus cuspidata; also, the net reproductive rate dropped from 70.24 to 6.70, which is more than a tenfold reduction.

Animals↗

LC-MS determination of Taxus alkaloids in biological specimens.

A semi-quantitative LC-MS method was developed for the detection of the pseudo alkaloids of Taxus baccata (yew) from human body fluids and tissue samples. This method was used to examine the cause of death of a 43-year-old man who died several hours after he drank a decoction of taxus leaves. Autopsy and histology demonstrated early signs of myocardial hypoxia. Since investigation of the stomach content did not yield evidence of taxus ingestion, the taxus alkaloids were determined in blood, stomach content and tissue samples of the deceased by LC-MS. The samples were prepared by solid phase extraction on RP-18 columns. Chromatographic separation was achieved by HPLC on a RP-8 column, coupled to an ion trap mass spectrometer (Finnigan LCQ). An atmospheric pressure electrospray ionisation was performed. Spectra of the alkaloids were recorded in the single MS mode and in the MS-MS mode and compared with reference spectra obtained from an extract of yew leaves. In the stomach content, the kidneys, the liver and a heart blood sample of the deceased, alkaloids of Taxus baccata, predominantly taxine B and iso-taxine B, were identified. The semi-quantitative evaluation of the heart blood revealed a taxine concentration of 11 micro g taxine/g. As far as we know this is the first case in which a semi-quantitative analysis of taxine alkaloids has been performed.

Adult↗

A comparative study of five fatal cases of Taxus poisoning.

The study presents five fatal cases of poisoning with Taxus spp., all of which were suicides of young people aged between 16 and 26 years. Yew leaves were consumed in four fatalities, whereas a mash from Taxus was ingested in one case. No relevant concentrations of alcohol, narcotic drugs, and pharmaceuticals were determined in postmortem toxicological screening. At forensic autopsy, a widely dilated pupil was found in two decedents. Furthermore, autopsy showed unspecific findings of intoxication in all cases: acute blood congestion of lungs, liver, kidney, and brain as well as dilated cardiac ventricles. No signs of violence could be found in any of the fatalities. Yew leaves were identified in four cases in the stomach and duodenum. 3,5-Dimethoxyphenol, the aglycon of the Taxus ingredient taxicatine, was determined as toxicological evidence for the absorption of yew ingredients. Taxus intoxication could be confirmed by 3,5-dimethoxyphenol concentrations in cardiac blood between 31 and 528 ng/ml for all cases. 3,5-Dimethoxyphenol was also detected in stomach contents as well as in urine, liver, kidneys, and brain samples. Based on the different concentrations of 3,5-dimethoxyphenol determined in the cardiac blood samples, it was concluded that the form of ingestion plays a decisive role in the process of poisoning. Finally, a toxic range for Taxus poisoning based on 3,5-dimethoxyphenol as marker substance is proposed as orientation.

Adolescent↗

Hypertonic sodium bicarbonate for Taxus media-induced cardiac toxicity in swine.

OBJECTIVE: To determine whether intravenous (IV) hypertonic sodium bicarbonate is effective in the reversal of QRS widening associated with severe Taxus intoxication. METHODS: Seventeen anesthetized and instrumented swine were poisoned with an IV extract of Taxus media until doubling of the QRS interval on electrocardiography was achieved. After poisoning (time zero), the animals received either 4 mL/kg IV 8.4% sodium bicarbonate (experimental group; 6 animals), a similar volume of 0.7% NaCl in 10% mannitol (mannitol group; 6 animals), or nothing (control group; 5 animals). The main outcome parameter was QRS duration. Secondary outcome parameters were mean arterial pressure (MAP), heart rate (HR), and cardiac index (CI = cardiac output/kg). Additionally, arterial pH, partial pressure of carbon dioxide (pCO(2)), and plasma-ionized calcium, sodium, and potassium were monitored. RESULTS: Taxus toxicity, defined as a 100% increase in QRS duration, was produced in all animals. The animals were similar in regard to baseline and time 0 physiologic parameters as well as amount of Taxus media extract administered. From times 5 through 30 minutes, following assigned treatment, significant increases in QRS duration were detected in the experimental and mannitol groups compared with the control group. A significant lowering of MAP was found in the experimental group compared with the control group. No significant difference between groups was noted in HR or CI. The swine treated with hypertonic sodium bicarbonate had a statistically significant increase in pH, plasma sodium concentration, and base excess compared with the other groups. CONCLUSIONS: Hypertonic sodium bicarbonate was ineffective in reversing the widening of QRS interval associated with Taxus poisoning in this swine model.

Animals↗

[Root microstructure and distribution of the endophytic fungi in Taxus chinensis var. mairei].

OBJECTIVE: To study the root microstructure and the distribution of the endophytic fungi in Taxus chinensis var. mairei. METHODS: The roots of Taxus chinensis var. mairei at nature were cut with paraffin, dyed and observed by microscope. RESULTS: The secondary structure of the roots of Taxus chinensis var. mairei consisted of the periderm and vascular cylinder (stele). Axial and radial systems formed the secondary xylem of the roots. Tracheids and xylary parenchyma cells constituted the axial system, and xylary radial formed the radial systems. The secondary phloem consisted of sieve cells and phloem parenchymas. Only a small quantity of phloem fibers were distributed in the secondary phloem, and the phloem ray was unconspicuous. Many endophytic mycelia penetrated in the velamina. CONCLUSIONS: The secondary structure of the root of Taxus chinensis var. mairei accords with that of other gymnosperms and dicotyledons, although its secondary xylem is constituted with tracheids and sieve cells. The endophytic mycelia exists in the local cells of velamina in the roots of Taxus chinensis var. mairei.

Fungi↗

Impact of moderate renal insufficiency on restenosis and adverse clinical events after paclitaxel-eluting and bare metal stent implantation: results from the TAXUS-IV Trial.

BACKGROUND: Mortality and restenosis may be increased in patients with mild to moderate renal insufficiency (RI) after coronary stent implantation. Whether drug-eluting stents safely reduce restenosis and enhance event-free survival in these patients is unknown. We sought to evaluate the impact of baseline RI on clinical and angiographic outcomes in patients undergoing elective percutaneous coronary intervention using either bare metal or paclitaxel-eluting stents. METHODS: In the TAXUS-IV trial, 1314 patients were randomized to either the polymer-based paclitaxel-eluting TAXUS stent or an identical-appearing bare metal stent. Outcomes were stratified on the basis of the presence of RI, defined as a baseline creatinine clearance < 60 cm3/min calculated by the Cockcroft-Gault formula. RESULTS: Baseline RI was present in 223 (17.2%) patients, in whom the mean creatinine clearance was 49.6 +/- 8.5 cm3/min. Compared with bare metal stents, treatment with the TAXUS stent resulted in lower rates of 9-month angiographic restenosis rates in both patients with (2.1% vs 20.5%, P = .009) and without (9.2% vs 27.8%, P < .0001) baseline RI. Similarly, 1-year target lesion revascularization rates were reduced with the TAXUS stent in patients with (3.3% vs 12.2%, P = .01) and without (4.7% vs 15.8%, P < .0001) baseline RI. The occurrence of death, myocardial infarction, and stent thrombosis at 1 year were similar in both randomization groups, independent of renal function. CONCLUSIONS: The polymer-based paclitaxel-eluting TAXUS stent safely reduces clinical and angiographic restenosis in patients with preserved as well as moderate impairment of baseline renal function.

Aged↗

Two-year-plus follow-up of a paclitaxel-eluting stent in de novo coronary narrowings (TAXUS I).

Early results with polymer-based paclitaxel-eluting stents have shown significant improvements in the clinical and angiographic parameters of restenosis, as well as excellent safety outcomes. However, the duration of these beneficial effects is unknown. Therefore, the clinical outcomes of the TAXUS I study population were evaluated at 2- and 3-year follow-up. In TAXUS I, 61 patients with single, focal coronary lesions were randomly assigned to receive either a paclitaxel-eluting TAXUS stent (n = 31) or a bare metal control stent (n = 30). Low rates of composite major adverse cardiac events (MACEs) reported at 1-year follow-up (3.2% TAXUS vs 10.0% control) were maintained at 2 and 3 years, with no additional MACEs in either treatment group 1 year after implantation. The single target vessel revascularization in the TAXUS group was remote from the target lesion in contrast to 3 target lesion revascularizations in the control group.

Aged↗

Preparation of single cells from aggregated Taxus suspension cultures for population analysis.

A method for the isolation of single plant cells from Taxus suspension cultures has been developed for the analysis of single cells via rapid throughput techniques such as flow cytometry. Several cell wall specific enzymes, such as pectinase, pectolyase Y-23, macerozyme, Driselase(R), and cellulase were tested for efficacy in producing single cell suspensions. The method was optimized for single cell yield, viability, time, and representivity of aggregated cell cultures. The best combination for single cell isolation was found to be 0.5% (w/v) pectolyase Y-23 and 0.04% (w/v) cellulase. High viability (>95%) and high yields of single cell aggregates (>90%) were obtained following 4 hours of digestion for four separate Taxus cell lines. In addition, methyl jasmonate elicitation (200 microM) was found to have no effect on three of the four tested Taxus lines. Isolated single cells were statistically similar to untreated cell cultures for peroxidase activity (model cell wall protein) and paclitaxel content (secondary metabolite produced in Taxus cell cultures). In comparison, protoplasts showed marked changes in both peroxidase activity and paclitaxel content as compared to untreated cultures. The use of flow cytometry was demonstrated with isolated cells that were found to have > 99% viability upon staining with fluorescein diacetate. The development of a method for the isolation of single plant cells will allow the study of population dynamics and culture variability on a single cell level for the development of population models of plant cell cultures and secondary metabolism.

Cell Aggregation↗

Fatal yew (Taxus sp) poisoning in Willamette Valley, Oregon, horses.

Despite the well-founded reputation of plants of the genus Taxus as being amongst the most toxic plants for domestic livestock in the US, there are surprisingly few published case reports of yew poisoning in horses. This report documents 2 acute fatalities in horses in the central Willamette Valley, OR associated with the consumption of Taxus sp. The predominant features of the intoxication were peracute death, with no signs of struggling or convulsions, in otherwise fit and well managed adult horses. The most significant gross necropsy findings were limited to pulmonary congestion and hemorrhage, suggestive of acute circulatory disturbance. A diagnosis of Taxus sp poisoning was confirmed on the basis of a history of potential exposure, by the identification of yew leaves in the gastric contents of the horses, and by the subsequent identification of yew clippings in the pasture. The literature relevant to Taxus sp poisoning in horses is reviewed.

Animals↗

Taxol content of various Taxus species in Hungary.

The anticancer drug taxol was separated and quantitatively determined in bark and foliage of different Taxus species by high-performance liquid chromatography to prove the presence of taxol in Hungarian Taxus species. The measurements were carried out with photodiode array detection using a porous graphitized carbon column, and a water:dioxan 54:46 v/v eluent. Taxol was established as being present in measurable amounts in each Hungarian Taxus species. According to the results bark was richer in taxol than foliage. It could also be observed that the older the bark or foliage, the more taxol it contained. The validation process proved that the method is reliable and can be used for the separation and quantitative determination of taxol in both the bark and foliage of Taxus species grown in Hungary.

Antineoplastic Agents, Phytogenic↗

Impact of platelet glycoprotein IIb/IIIa Inhibition on the paclitaxel-eluting stent in patients with stable or unstable angina pectoris or provocable myocardial ischemia (a TAXUS IV substudy).

Whether the benefits that glycoprotein IIb/IIIa inhibitors confer in patients who undergo bare metal stent implantation extend to drug-eluting stents is unknown. We performed a prespecified subgroup analysis of the TAXUS IV study population to examine the effect of procedural glycoprotein IIb/IIIa inhibition during paclitaxel-eluting stent implantation on periprocedural creatine kinase-MB (CK-MB) levels. Glycoprotein (GP) IIb/IIIa inhibitors were administered to 57.7% of patients who had been randomized to receive the TAXUS stent and to 56.7% of those who had been randomized to receive the control stent. Among patients who received the TAXUS stent, the rate of CK-MB increases of >3 times the normal level was 2.6-fold higher in those who received a GP IIb/IIIa inhibitor than in those who did not (11.4% vs 4.4%, p = 0.0015). Composite rates of major adverse cardiac events and target vessel failure were also higher at 1 month in the GP IIb/IIIa group. By multivariate analysis, use of GP IIb/IIIa inhibitors during stenting with the TAXUS stent was an independent predictor of CK-MB increases >3 times the normal level. Further studies are warranted.

Abciximab↗