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This study was conducted to determine the maximum tolerated dose and dose-limiting toxicity of irinotecan (CPT-11) administered every 3 weeks to adults with progressive malignant glioma who were treated with enzyme-inducing antiepileptic drug (EIAED) therapy, and to compare the pharmacokinetics with those in patients not on EIAED therapy treated at the recommended phase 2 dose for other cancers. The CPT-11 dose was 350 mg/m2 i.v. every 3 weeks and remained fixed in patients not on EIAED therapy, but the dose was escalated by 50-mg/m2 increments in patients on EIAED therapy. CPT-11 and its metabo-lites SN-38, SN-38 glucuronide (SN-38G), and APC (7-ethyl-10[4-N-(5 aminopentanoic acid)-1-piperidine]-carbonyloxycamptothecin) were characterized in both groups. Patients on EIAEDs received 350 to 800 mg/m2 of CPT-11. Dose-limiting toxicity was due to grade 3 diarrhea despite maximal doses of loperamide. The systemic levels of CPT-11, APC, SN-38G, and SN-38 were all lower in the EIAED group. There was a moderate-to-fair relationship between CPT-11 dose and the area under the curve (AUC) for CPT-11 and APC over the dosage range of 350 to 800 mg/m2, but no relationship between CPT-11 dose and the AUC for SN-38 or SN-38G. At the 750-mg/m2 dose, the AUC for CPT-11 (21.6 μg × h/ml) matched the AUC (21.6 μg × h/ml) in the non-EIAED group treated with 350 mg/m2 of CPT-11. We conclude that the recommended phase 2 dose of CPT-11 for patients on EIAEDs is 750 mg/m2 when given every 3 weeks. A phase 2 study of patients with recurrent malignant glioma is ongoing to assess the efficacy of CPT-11 when the dose is stratified according to the use of EIAEDs.
The treatment of recurrent malignant gliomas using available chemotherapy drugs is ineffective for the prolongation of life in the majority of patients. The median time to tumor progression after treatment for patients with recurrent glioblastoma multiforme (GBM)3 is only 8 to 12 weeks, and fewer than 20% of patients are progression-free by 6 months (Hess et al., 1999). Patients with anaplastic gliomas other than GBM fare better, but fewer than half are progression-free at 6 months (Hess et al., 1999). The efficacy of chemotherapy for glioma has been limited because of the low activity of available antineoplastic agents, the compromised delivery of these agents to at least partially privileged intracranial sites, and the emergence or de novo presence of resistance to these agents. Irinotecan (CPT-11), a drug that is active against colon carcinoma, has been used to treat recurrent glioma. Preclinical activity of CPT-11 has been promising, with in vitro activity noted against a panel of xenografts derived from ependymoma, childhood and adult high-grade astrocytoma, and medulloblastoma (Hare et al., 1997). A phase 2 study of CPT-11 for malignant glioma was conducted at Duke University Medical Center using doses and schedules recommended for colon cancer (Friedman et al., 1999). The results suggested clinical efficacy with less toxicity, particularly diarrhea, than has been seen in other cancer patient populations. This low toxicity may be due to the treatment of many glioma patients with enzyme-inducing antiepileptic drug (EIAED) therapy, which could alter the exposure to CPT-11 in this population. However, reduced exposure to drug may also reduce efficacy.
CPT-11 (Mr anhydrous freebase, 587) is oxidized in the liver by the highly inducible CYP3A4, yielding 2 less active metabolites, APC (7-ethyl-10[4-N-(5 aminopentanoic acid)-1-piperidine]-carbonyloxycamptothecin [Mr 619]) and NPC (7-ethyl-10[4-(piperidine)-1-amino] carbonyloxycamptothecin [Mr 519]) (Haaz et al., 1998; Santos et al., 2000). Additionally, CPT-11 is bioactivated by hepatic and tissue carboxylesterases (predominately hCE2) to the potent topoisomerase-I inhibitor SN-38 [Mr anhydrous base, 393] (Humerickhouse et al., 2000; Khanna et al., 2000; Slatter et al., 1997). SN-38 is excreted unchanged or conjugated by the highly polymorphic and inducible uridine-diphosphoglucuronosyl transferase (UGT1A1)-generating SN-38 glucuronide [Mr 569] (Iyer et al., 1998). Subsequently, CPT-11 and its metabolites are exported from the hepatocytes by specific apical, membrane-bound transporters. The canalicular, multi-specific organic anion transporter multidrug resistance protein 2 (MRP2) reportedly is responsible for the biliary transport of the inactive carboxylate forms of CPT-11 and SN-38 as well as the lactone and carboxylate forms of SN-38 glucuronide (Chu et al., 1998). SN-38 has recently been identified as a substrate for the canalicular, ATP-binding cassette (ABC) transporter (ABCP, ABCG2), the breast cancer resistant protein (BCRP), and mitoxantrone-resistance half-transporter (MXR) (Brangi et al., 1999; Maliepaard et al., 2001).
Recent preclinical and clinical studies have demonstrated that EIAEDs can alter the metabolism and elimination of CPT-11 and its metabolites. Pretreatment of rats with the antiepileptic drug phenobarbital, an inducer of UGT1A1 and CYP3A4, has been shown to enhance the formation of SN-38G and decrease the area under the concentration-time curve (AUC) for both CPT-11 and SN-38. However, the non-EIAED valproic acid increased the AUC of SN-38, presumably by inhibiting the glucuronidation of SN-38 (Gupta et al., 1997). In contrast to the induction of UGT1A1 and CYP3A4, phenobarbital has recently been shown not to increase the expression of MRP2 in rat hepatocytes (Hagenbuch et al., 2001). A recent study of CPT-11 in patients with malignant gliomas receiving EIAEDs indicated significantly lower systemic exposure (decreased AUC) to CPT-11, SN-38, and SN-38G compared to historical controls (Friedman et al., 1999).
Based upon the background above, the North American Brain Tumor Consortium (NABTC) began a phase 1 study of CPT-11 in patients on EIAEDs to determine the optimal phase 2 dose when given every 3 weeks and to compare the pharmacokinetics with those in patients not on EIAEDs treated at the recommended phase 2 dose for other cancers. A phase 2 study has begun based upon the results of this trial.
Patients 18 years or older with histologically confirmed diagnosis of a progressive or recurrent malignant glioma were eligible to participate, provided they had measurable disease, a Karnofsky performance status of 60 or greater, and acceptable hematologic, liver, and renal function. The latter required an absolute neutrophil count 1500/mm3, a platelet count of 100,000/mm3, serum creatinine <1.5 mg/dl, serum bilirubin <1.5 mg/dl, and AST <3 times the institutional upper normal limits. Patients in the phase 1 portion (group B) of this study had undergone no more than 2 prior chemotherapy regimens, including 1 prior adjuvant therapy and 1 prior regimen for recurrent tumor, or 2 prior regimens for recurrent disease. Patients not on EIAED (group A) received a fixed dose of 350 mg/m2 and were considered part of an expanded phase 2 trial that will be reported separately. These patients had undergone no more than one prior chemotherapy regimen, either as adjuvant chemotherapy or for recurrent disease. In both groups, the interval from prior irradiation or chemotherapy had to be at least 4 weeks, and 6 weeks if prior nitrosourea therapy had been used.
The study was designed to include women and minorities but was not designed to measure differences of intervention effects. No exclusion was allowed based upon race. Patients were excluded if they were pregnant or breast feeding, if they had severe nonmalignant systemic disease or active infection, or if they had any uncontrolled medical conditions that, in the judgment of the investigator, would make the patient inappropriate for entry. Patients previously treated with CPT-11, topotecan, or other topoisomerase 1 inhibitors were also excluded. All patients were provided with and had to sign a written informed consent approved by the local institutional review board at each institution before treatment, informing them of the investigational nature of this study.
Patients who met eligibility requirements and signed an informed consent received an intravenous infusion of CPT-11 over a 90-min period every 3 weeks. The initial dose was 350 mg/m2 in both groups. Patients in group A (not on EIAEDs) continued to receive this dose throughout treatment until tumor progression, unacceptable toxicity, or completion of 12 treatment cycles. Patients in group B (on EIAEDs) were treated in groups of 3, beginning at the initial dose. If the first group of 3 patients did not experience dose-limiting toxicity (DLT), a subsequent group of 3 additional patients was enrolled, and the dose was increased by 50-mg/m2 increments. Cohorts of 3 patients were thus enrolled until the DLT was determined. Up to 3 patients were enrolled simultaneously. These patients were observed for DLT for at least 3 weeks from the first day of treatment before new patients were enrolled at the next higher dose. The following dose-escalation rules were used. Three patients were studied at the first dose level. If none of these 3 experienced DLT, then the dose was escalated to the next dose in 3 subsequent patients, but if 1 of 3 patients experienced DLT, then 3 more patients were enrolled at the same dose. If none of these 3 patients experienced DLT, then the dose was escalated to the next dose in 3 subsequent patients. If 1 or more of the additional 3 patients experienced DLT, the maximum tolerated dose (MTD) was considered to have been exceeded, and 3 more patients were treated at the next lower dose (if only 3 were treated at that dose). If 2 or more patients experienced a DLT, the MTD was considered to have been exceeded.
A treatment cycle was considered to be 1 infusion and a 3-week evaluation period. Doses assigned were not allowed to be escalated, and patients remained on that dose until tumor progression, unacceptable toxicity, or completion of 12 treatment cycles.
The definition of DLT for group B patients was based upon the National Cancer Institute (NCI) Common Toxicity Criteria scale (NCI, 1999) and included the following:
The definition of the MTD was the dose level at which 0/3 or 1/6 patients experienced DLT, with at least 2/3 or 2/6 patients experiencing DLT at the next higher dose.
Complete physical and neurological examinations, including Karnofsky performance status, were performed every other cycle. Weekly complete blood counts with differential and platelets were obtained throughout the course of treatment. Creatinine, BUN, total bilirubin, AST, and serum electrolyte counts were obtained before each cycle. Magnetic resonance imaging of the brain was done every other cycle to assess response. Patients with stable or responding disease received the same dose at the next cycle or a reduced dose if adverse events were observed in the current cycle. If a patient experienced a DLT, the dose of the subsequent cycle was reduced by one dose level (50 mg/m2). If a toxicity was thought to be directly related to CPT-11, subsequent doses were not re-escalated, even if there was minimal or no toxicity at the reduced dose. A new course of treatment could begin if the absolute neutrophil count was 1500/mm2 and the platelet count was 100,000/mm3 and any other treatment-related toxicity was grade 1. If, after a 1-week delay, toxicity was grade 1, treatment resumed. If the toxicity did not resolve in 1 week, a second week's delay was allowed, but retreatment required a reduction of 1 dose level. If retreatment had to be held off for more than 2 weeks, or if the administered dose would be 200 mg/m2, the patient was removed from the study. Routine prophylactic use of hematologic growth factors was not allowed in the first cycle of therapy. Therapeutic use in cycles complicated by neutropenic infection was allowed at the discretion of the treating physician. Because of the possibility of lacrimation, diaphoresis, flushing, abdominal cramping, diarrhea, or other symptoms of early cholinergic syndrome in patients receiving CPT-11, we allowed subcutaneous or intravenous administration of atropine, both therapeutically and prophylactically as needed.
Patients were removed from study if tumor progression was determined by MRI. In this phase 1 trial, the definition of progression was a 25% increase in the sum of the products of all measurable disease over the smallest sum observed, or clear worsening of any evaluable disease, or the appearance of any new lesion. Failure to return for evaluation due to death or deteriorating condition was considered to represent progression.
Heparinized blood samples (7 ml) were drawn via venipuncture or through an indwelling i.v. heparin lock. One milliliter of blood was withdrawn from the heparin lock and discarded before sample collection at the following times: before drug administration (baseline), 45 min into the infusion, and at the end of the infusions, then 15, 30, 60, and 90 min and 2, 3, 4, 6, 8, 10, and 24 h after the end of infusion on day 1 of a patient's first cycle, for a total of 14 samples per patient.
Blood samples were immediately centrifuged. Plasma was removed and frozen at 20°C for subsequent analysis by high-performance liquid chromatography (HPLC) for total concentrations of CPT-11 and SN-38 as well as for concentrations of SN-38 glucuronide (SN-38G) and APC. The total time of frozen storage was less than 1 year. The long-term stability of total CPT-11 and SN-38 in plasma has been documented to be at least 2 years when samples were stored at 20°C.
Plasma samples were analyzed for total concentrations of CPT-11, APC, and SN-38 by using a validated and sensitive HPLC method (Saltz et al., 1996). In brief, the plasma specimen was mixed with the internal standard (IS, camptothecin) in acidified ace-tonitrile to precipitate plasma proteins, and the mixture was incubated for 15 min at 40°C to convert the analytes to their respective lactones. After addition of triethylamine buffer (pH 4.2), the sample was centrifuged. The supernatant was transferred to an amber vial for injection (60 μl) onto the HPLC system. Chromatographic separation was achieved with a Zorbax-SB-C8 column (MacMod Analytical, Inc., Chadds Ford, Penn.) and a mobile phase consisting of 25:75 (v/v) acetonitrile/0.025 triethylamine buffer (pH 4.2). The fluorescence detector was operated at an excitation wavelength of 372 nm; the CPT-11 and APC were monitored at an emission wavelength of 425 nm; SN-38 and the IS were monitored at 535 nm. To determine the concentrations of SN-38 glucuronide, a separate portion of each plasma sample was hydrolyzed via the addition of a β-glucuronidase solution. The conversion reaction was terminated by precipitating the proteins using an acidified acetonitrile solution of the IS. The conversion of SN-38G to total SN-38 was 100%. The remainder of the procedure was repeated as described above.
The lower limits of quantitation of CPT-11 (expressed as the freebase, Mr 587), SN-38 (expressed as monohydrate, Mr 410), and APC (Mr 618) were 1.28 ng/ml, 0.480 ng/ml, and 0.960 ng/ml, respectively. The assay precision for CPT-11 [APC values in brackets], expressed as the coefficient of variation (% CV) of the estimated concentrations of quality control samples, was 4.9% [8.3%], 4.1% [9.3%], and 5.4% [7.0%], respectively, for the low (12.8 [1.20] ng/ml), medium (160 [12.0] ng/ml), and high (3200 [320] ng/ml) concentrations of CPT-11 [APC] and 10.8%, 3.5%, and 5.1%, respectively, for the low (1.2 ng/ml), medium (12.0 ng/ml), and high (320 ng/ml) concentrations of SN-38. Assay accuracy, expressed as the ratio (or percent) of the estimated to theoretical quality control standard concentrations, averaged 96% to 99% for CPT-11 [98%–101% for APC] and 96% to 101% for SN-38.
CPT-11, APC, SN-38, and SN-38G plasma concentrations were analyzed by non-compartmental methods. The time intervals relative to the start of the CPT-11 infusion and the actual sample times were used for the calculations of the time-to-peak curve and the plasma AUC. The maximal plasma concentration for CPT-11 was defined as the concentration achieved at the end of the 90-min infusion. The maximal plasma concentrations for APC, SN-38, and SN-38G were determined by visual inspection of each individual's plasma concentration-versus-time profile. Elimination rate constants were estimated by linear regression of the last 2 data points on the terminal log linear portion of the concentration-time curve. The terminal half-life (t1/2) was calculated by dividing 0.693 by the elimination rate constant. The AUC was calculated by using the linear trapezoidal rule up to the last measurable data point (for AUC0 – 24), then extrapolated to infinity (AUC). The systemic clearance for CPT-11 was determined by dividing the dose (in milligrams freebase of CPT-11 per meter squared) by the AUC. A metabolic ratio, estimated as the ratio of AUCSN-38 or AUCSN-38 + AUCSN-38G to AUCCPT-11, was used as a measure of the relative extent of the conversion of CPT-11 to SN-38. The relative extent of metabolism of CPT-11 to APC was estimated as AUCAPC/AUCCPT-11 and the relative extent of glucuronidation of SN-38 as the ratio of AUCSN-38 to AUCSN-38G.
The primary end points for this study were to describe toxicity and pharmacokinetics of CPT-11 in a dose-escalating phase 1 study and to define a recommended phase 2 dose. The dose for patients on EIAED therapy was escalated as described earlier, and the DLT, MTD, and safety were evaluated. When the dose escalation scheme described was used, the probability that the dose would be escalated to the next level, based on the true rate of DLT at the current dose, is given by the following:
Thus, if the true underlying proportion of DLT was 50% at any dose, there was a 17% chance of escalating to the next higher dose.
Pharmacokinetic variables for all compounds are reported as mean values ± SD. The relationships between the CPT-11 dose administered (mg/m2) and AUCs were analyzed by Spearman's correlation coefficient and linear regression analysis. Interpatient differences in the kinetics were assessed by the coefficient of variation, expressed as the ratio of the SD to the observed mean. Differences between the 2 groups with respect to the kinetic variables were evaluated by using an unpaired 2-tailed t test. Two-tailed probability values of less than 0.05 were regarded as statistically significant. Kinetic variables were also compared to those obtained from the Mayo Clinic trial that included 6 patients with non-CNS malignancies who received 340 mg/m2 of CPT-11 (Pitot et al., 2000). Relative metabolic ratios were then compared with those reported in 3 recent trials.
A total of 48 patients were enrolled in the phase 1 study (group B, Table 1). Three patients did not receive any drug, and 2 patients were ineligible, but treated. These 2 patients are included in the toxicity assessments. The median age was 47 years (range 19 – 77). The majority (37/48) of patients had recurrent GBM, and most had been treated with 1 or more prior chemotherapy regimens. Patients enrolled in the phase 2 study (group A) will be described in more detail in a separate report dealing with response to CPT-11. However, the median age was 53 years, and 75% were patients with recurrent GBM, treated with no more than 1 prior chemotherapy regimen.
The dose of CPT-11 ranged from 350 to 800 mg/m2. Dose-limiting toxicity was grade 3 diarrhea despite maximal loperamide support and was noted in 2/6 patients at a dose of 800 mg/m2. A third patient treated at this dose also had grade 3 diarrhea but did not receive maximal loperamide support. The recommended phase 2 dose is 750 mg/m2. No treatment-related deaths were reported. Table 2 describes the most common types of toxicity reported in the study.
There were 42 patients evaluable for response by MRI. All had progressed at the time of this report. Although it was not a response study, there were no reports of any patients who had an objective response (>50% decrease in size of tumor). The median progression-free survival time measured from the date of registration into the study was 6 weeks (6 weeks for GBM and 9 weeks for non-GBM). Ten patients were progression-free for 13 weeks or longer, and 3 patients were progression free for 6 months or longer.
Blood samples were obtained from patients during their first course of treatment. Sixteen patients were nonevaluable because of incomplete sample collections. Pharmacokinetic variables were characterized for 56 patients: 22 patients in group A (non-EIAEDs), who were treated with 350 mg/m2 of CPT-11, and 34 patients in group B (EIAEDs), who were treated with doses ranging from 350 to 800 mg/m2.
The pharmacokinetic characteristics for CPT-11, APC, SN-38, and SN-38G are summarized in Tables 3 and and4.4. Comparisons between the 2 groups at the 350-mg/m2 dose level are displayed in Table 5, which also includes the pharmacokinetic characteristics from the Mayo Clinic trial that included 6 patients with non-CNS malignancies who received 340 mg/m2 of CPT-11 (Pitot et al., 2000). Overall, the kinetic variables in patients receiving no anticonvulsants or steroids in our trial are similar to those of non-CNS malignancy patients. Unfortunately, kinetic characteristics were available for only 2 patients in the EIAED group at the 350-mg/m2 dose level. However, a comparison of the kinetics of the 2 groups revealed that the peak concentrations and AUCs of CPT-11 and SN-38 were substantially decreased in the EIAED-treated patients. Although not as substantial, a quantitative decrease in peak concentrations and AUCs for APC and SN-38G was also observed. CPT-11 clearance values (29.3 ± 7.11 l/h/m2, n = 34) for the EIAED group were increased 2-fold compared to those for the non-EIAED group (14.2 ± 4.12 l/h/m2, n = 7) or by 1.5-fold compared to those for patients receiving only dexamethasone and/or non-EIAEDs (20.1 ± 5.72 l/h/m2, n = 15).
The EIAED patients were empirically categorized into 4 groups (phenytoin, carbamazepine, phenobarbital, and combination EIAEDs) for the purposes of comparison (Table 6). The non-EIAED drugs, particularly gabapentin, had a small but statistically significant effect on the clearance of CPT-11 when compared to the clearance values for patients not receiving steroids or antiepileptic agents. Six patients were receiving valproic acid in combination with a non-EIAED. For those patients receiving valproic acid, CPT-11 clearance values (19 ± 2.98 l/h/m2) were unchanged compared to the clearance values for the other group A patients (18 ± 16.69 l/h/m2, P = 0.73). However, SN-38 AUCs (185 ± 49.94 ng × h/ml) were significantly lower for the patients receiving valproic acid compared to the SN-38 AUCs (552 ± 306 ng × h/ml, P = 0.01) for patients receiving other non-EIAEDs ± steroids. SN-38G AUCs of the 2 groups were not different (1113 ± 395 vs. 1713 ± 1182 ng × h/ml, P = 0.24). Likewise, there was no difference in the AUC values for CPT-11 and SN-38 for those patients receiving dexamethasone alone compared to the no-anticonvulsant group.
The relationship between CPT-11 dose and systemic exposure (AUC) was relatively linear (r2 = 0.64, P = 4.53E−06) over the dosage range of 350 to 800 mg/m2. Likewise, the clearance of CPT-11 was dose independent (r2 = 0.035). However, no proportionate increase was observed in the SN-38 or SN-38G AUC nor in the dose-normalized AUCs with increasing dosages of CPT-11 (r2 = 0.04). Additionally, there was a poor linear relationship between CPT-11 dose and APC systemic exposure (r2 = 0.35). The pharmacodynamic assessment of correlation between (a) CPT-11, APC, and SN-38 systemic exposure, (b) NCI grade of diarrhea, and (c) percent change in neutrophil count showed no correlations in either of the treatment groups.
At the MTD of 750 mg/m2, the AUC for CPT-11 (21.6 μg × h/ml) matched the AUC (18 μg × h/ml) in the group of patients receiving no anticonvulsants treated with 350 mg/m2 of CPT-11. The mean percent change in neutrophil count (nadir-baseline count/baseline count) was 62.4% (± 27%) for the non-EIAED group (350 mg/m2) and 58.2% (± 18%) for the EIAED group treated with 750 mg/m2 of CPT-11. There was considerable variability observed for the SN-38 AUCs at all of the dose levels. The mean AUC for SN-38 at the MTD was not statistically different from the SN-38 AUC at the 350-mg/m2 dose level for the non-EIAED patient group.
The goals of this study were to define the toxicity and pharmacokinetics of CPT-11 in patients receiving EIAED therapy and to establish a recommended phase 2 dose. For patients receiving non-EIAEDs, a fixed dose of 350 mg/m2 of CPT-11 was administered i.v. every 3 weeks. Dose escalations in the EIAED patient groups ranged from 350 to 800 mg/m2. The DLT at the 800-mg/m2 dose level was grade 3 diarrhea despite maximal doses of loperamide.
EIAEDs altered the pharmacokinetics of CPT-11 and its metabolites. At the comparative dose level of 350 mg/m2, peak concentrations and the AUC of CPT-11, APC, SN-38, and SN-38G were substantially lower in the EIAED patient group. A moderate-to-fair linear relationship existed between CPT-11 dose and AUC over the dosage range of 350 to 800 mg/m2. No relationship was observed between CPT-11 dose and the AUCs for SN-38 or SN-38G. The clearance of CPT-11 was dose independent. The clearance of CPT-11 in the EIAED group (29.3 ± 7.11 l/h/m2) was increased 1.6-fold compared to the clearance for the non-EIAED group (18.2 l/h/m2). The majority of the patients in the EIAED group were receiving phenytoin with or without dexamethasone. CPT-11 clearance values were highest among the patients receiving phenytoin or carbamazepine (30.1 and 28.1 l/h/m2, respectively) and were lowest among those receiving phenobarbital (23.6 l/h/m2). The relative influence of individual anticonvulsant agents and their dose effect on the pharmacokinetics of CPT-11 in glioma patients are also being evaluated in a larger database from 4 NCI-sponsored trials in glioma patients (Reid et al., 2001). As was observed in our study, the findings from the larger database suggest that the AUCs for CPT-11 and SN-38 were not altered by dexamethasone, a reported inducer of CYP3A4 and glucuronosyl transferase activity (McCune et al., 2000; Sutherland et al., 1993). Likewise, other covariates including age and gender did not influence CPT-11 or SN-38 AUCs. We also observed that the non-EIAEDs, especially gabapentin, appeared to have a small but statistically significant effect on CPT-11 clearance. Preclinical data (Gupta et al., 1997) indicated that we might observe an increase in SN-38 exposure in those patients receiving valproic acid due to the inhibition of UGT1A1 conjugation of SN-38. We actually observed the opposite effect. For the small number of patients receiving valproic acid in combination with another non-EIAED, SN-38 AUCs were comparatively lower. Additionally, the grade of diarrhea and the percent change in neutrophil counts in the valproic acid group were similar to those of the other group A patients. The same observation has been recently reported by other investigators (Raymond et al., 2003). Neither SN-38 exposure nor toxicity was increased in patients with glioblastoma who were treated with 350 mg/m2 of CPT-11 while receiving concomitant valproic acid.
The relative metabolism ratios observed in our trial are compared with those reported in 3 recent clinical trials in Table 7. The analytical procedures and sampling schedules were similar with a few noted exceptions. Investigators at the Mayo Clinic (Pitot et al., 2000) and the Rotterdam Cancer Institute (de Jonge et al., 2000) conducted their phase 1 dose-escalating trials in patients with non-CNS malignancies, in which CPT-11 was administered on an every-3-week schedule. Within comparative patient groups, the ratios are remarkably similar. Changes in the metabolic ratios are subject to metabolism as well as elimination and therefore are not a direct measure of conversions. However, the metabolic ratios viewed within the context of the metabolism and elimination of CPT-11 and SN-38 can provide speculative mechanisms by which EIAEDs influence the disposition of CPT-11 and its metabolites. EIAEDs increased the clearance of CPT-11. Increased conversion of CPT-11 to its predominant metabolite, APC, by induction of CYP3A4 is suggested by the APC-to-CPT-11 ratio of 48.8 in the EIAED groups versus 28.8 in the non-EIAED group. Enhanced elimination of CPT-11 via biliary transport mechanisms could have also occurred. The low SN-38-to-CPT-11 ratio of 1.5 for the EIAED group versus 3.1 for the non-EIAED group suggests a decreased conversion of CPT-11 to SN-38, consistent with the 1.9-fold decrease in CPT-11's AUC in the EIAED group. Saturation of the high-affinity, low-Km carboxylesterase with the higher doses of CPT-11 could have also accounted for the lower SN-38 AUCs. Additionally, enhanced elimination of SN-38 by one or more pathways, such as biliary elimination (MRP2, MXR) or glucuronidation, is also a plausible explanation. The comparatively low ratio of SN-38 to SN-38G of 18.0 in the EIAED group versus 35.1 in the non-EIAED group is suggestive of increased glucuronidation of SN-38 by the inducible UGT1A1. In conjunction, we observed approximately the same metabolic ratio for both the EIAED group and the non-EIAED group for the combined SN-38 + SN-38G-to-CPT-11 ratio, consistent with a decreased SN-38, increased SN-38G, and decreased CPT-11 in the EIAED group. EIAEDs appear to influence multiple pathways relevant to CPT-11 and SN-38 disposition.
Our pharmacokinetic results are somewhat in contrast with the recently reported phase 1 escalation trial in glioma patients treated with CPT-11 using the weekly schedule (Gilbert et al., 2003). Dose escalations ranged from 125 to 444 mg/m2 for patients receiving EIAEDs. CPT-11 clearance values were found to be dose dependent. At the reported MTD of 411 mg/m2, however, the mean clearance value for CPT-11 (29.7 l/h/m2) was virtually identical to our observed mean CPT-11 clearance value (29.3 l/h/m2) and to the clearance value that Friedman et al. (1999) reported (30.4 l/h/m2). Similarly to the find-ing in our study, no relationship was found between CPT-11 dose and SN-38G AUC values. We observed no relationship between CPT-11 dose and SN-38 AUCs. In contrast, a fair relationship (r2 = 0.46) between CPT-11 dose and SN-38 AUCs was reported by Gilbert et al. (2003). This latter observation again raises the issue of the saturability of the human carboxylesterase responsible for the conversion of CPT-11 to the active metabolite SN-38 (Slatter et al., 1997). Preliminary results from the pooled analysis of data from the 4 NCI-sponsored trials in glioma patients with CPT-11 doses ranging from 100 to 800 mg/m2 indicated that SN-38 AUCs did not increase at doses greater than 350 mg/m2 (Reid et al., 2001).
For patients receiving stable (2 weeks) doses of EIAEDs, the recommended phase 2 dose of CPT-11 is 750 mg/m2 repeated every 3 weeks. The efficacy of CPT-11 is currently being evaluated in an NABTC phase 2 trial for glioma patients receiving EIAEDs. As a translational message, our NABTC experiences strongly suggest that the newer second-generation non-EIAEDs with little or no enzyme-inducing potential should be used when clinically indicated for patients with gliomas.
The NABTC members express their gratitude to the Pharmacia Corporation, especially Drs. Larry Schaaf, J. Patrick McGovern, and Barbara Duncan, for the analytical support provided in this study.
The North American Brain Tumor Consortium investigators and grant numbers for this study are presented in the table below.
|NABTC Grant
|GCRC Grant
|University of California at San Francisco
|Michael Prados, M.D.*
Susan Chang, M.D.
M. Kelly Nicholas, M.D., Ph.D.
|The University of Texas M.D.
|W.K.A. Yung, M.D.*
|Anderson Cancer Center
|Kurt Jaeckle, M.D.
|University of Texas Southwestern Medical Center
|Karen Fink, M.D., Ph.D.*
|The Dana Farber Cancer Center
|Howard Fine, M.D.*
Patrick Wen, M.D.
|University of Pittsburgh
|David Schiff, M.D.*
|University of Texas Health Science Center at San Antonio
|John Kuhn, Pharm.D.*
|University of California, Los Angeles
|Timothy Cloughesy, M.D.*
|University of Michigan
|Harry Greenberg, M.D.*
Larry Junck, M.D.
|University of Wisconsin
|Minesh Mehta, M.D.*
I.H. Robbins, M.D., Ph.D.
Abbreviations used are as follows: GCRC 5 General Clinical Research Center, NABTC, North American Brain Tumor Consortium.
1The North American Brain Tumor Consortium Investigators and grant numbers are listed in the Appendix.
3Abbreviations used are as follows: APC, 7-ethyl-10[4-N-(5 aminopentanoic acid)-1-piperidine]-carbonyloxycamptothecin; AUC, area under the concentration-time curve; CPT-11, irinotecan; DLT, dose-limiting toxicity; EIAED, enzyme-inducing antiepileptic drug; GBM, glioblastoma multiforme; HPLC, high-performance liquid chromatography; IS, internal standard; MRP2, multidrug resistance protein 2; MTD, maximum tolerated dose; NABTC, North American Brain Tumor Consortium; NCI, National Cancer Institute; UGT1A1, uridine-diphosphoglucuronosyl transferase.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


text:
Accession Number : AD0660728
Title : PROFILING THE SUPERSONIC SECTION OF AN AXISYMMETRIC MAXIMUM THRUST NOZZLE,
Corporate Author : FOREIGN TECHNOLOGY DIV WRIGHT-PATTERSON AFB OHIO
Personal Author(s) : Sergienko,A. A. ; Sandomirskaya,I. D.
Report Date : 28 APR 1967
Pagination or Media Count : 30
Abstract : The problem of the optimum shaping of the supersonic portion of the nozzle is studied within the framework of the variational approach. Such degenerated variational problems are solved by means of the coupled variations at the different ends of the extremum curve which allow the positioning of the extremum curve through two assigned points. The basic relationships and the mathematical formulation of the problem are followed by a study of the extremum equation solution, the condition of transversality of the contour with fixed coordinate points, the presentation of the computational methods, a brief analysis of accuracy, and the presentation of the tabulated results. These show that the solution of the degenerated problem coincides with the solution obtained by means of the classical variational calculus of nondegenerate problems.
Descriptors : (*SUPERSONIC NOZZLES, GEOMETRIC FORMS), OPTIMIZATION, SUPERSONIC FLOW, CALCULUS OF VARIATIONS, USSR
Subject Categories : Aerodynamics
Fluid Mechanics
Distribution Statement : APPROVED FOR PUBLIC RELEASE

subset: commoncrawl


text:
Phillips Library opened in 1890 and was replaced by Franklin Library in 1914. Franklin Library is built on land donated by Sumner T. McKnight in the Phillips neighborhood of Minneapolis. It was the first of four Carnegie-funded libraries built in the city. Franklin was one of 13 libraries developed under nationally known library director Gratia Countryman, who was instrumental in expanding the city's library system in 1904-36. The library has received historic designation from the City of Minneapolis Heritage Preservation Commission and is listed on the National Register of Historic Places.
1314 E. Franklin Ave.
Minneapolis, MN 55404
Hennepin County Library offers a variety of classes and resources about small business management and creation, financial literacy and more.
Available with your library card, learning resource Lynda.com offers over 3,000 interactive video courses taught by experts.
Join us at Franklin Library to learn new things, be inspired and connect with others. Library events are free and open to all.
Join these volunteers who work closely with library staff to raise awareness of library services, raise funds, and plan programs and events.


text:
Tibby Trail, Westcliffe, Colorado
Tibby Trail, Westcliffe, Colorado 81252 - Enjoy all the Wet Mountain Valley has to offer from this 35 acre parcel blessed with wonderful views of the Sangre de Cristo and Wet mountains. There are secluded home sites on a property with beautiful Ponderosa Pine and Aspen and punctuated with rock outcroppings. Oak Creek flows through the bottom of the property in Dilley Ranch. Enjoy easy county rod access to the National Forest, Westcliffe and Front Range cities.
Listing Courtesy of Westcliffe Home & Ranch
"Bob Maiocco exceeded our expectations on every level. Not only does Bob have a very solid knowledge of the real estate market, his negotiating skills are second to none. Bob has a calm and even demeanor when dealing with sometimes stressful situations that can arise when buying or selling real estate. We could not have asked for a more strategic partner to help us navigate the process of making our largest financial purchase."


text:
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Does the guilt of being a working mother ever go away??(127 Posts)
I am a single parent (dad no access) and went back to work full time when my daughter was one.
She is now three and I have gone down to four days a week (in education so job very very demanding). I planned to do this to initially spend the day with her but most times I send her to day care on this day off so i can have the day to myself and actually spend the day sorting out house so free's up weekend for me and her etc.
A friend of a friend today said something which made me question my decision to work full time, along the lines of being surprised that I worked full time with a child sooo young.
I now feel guilty! I feel guilt for sending her in to day care for five days & guilty for spending the day off to myself.....
After Xmas I've booked us some toddler classes to make it out day etc but hen plan to send her to nursery half day as really need some time to myself as don't get on weekends. I don't plan to be a sahm and with only my income I can't afford it and don't really think id enjoy it.
We have very active weekends, managing household, going out, visiting family etc so we do spend as much time together as we can etc.
Just want some reassurance that I'm doing the right thing.
Shame on your 'friend'
You know what is right for your family.
I get working mum guilt, but I kind of figure that part of being a mum is random guilt over most things!!!
I think Mums are programmed to feel guilty no matter what they do.
Research suggests that girls whose Mums work go on to achieve more in life.
I think you sound like you're doing brilliantly. And it's very sensible of you to carve out that time for yourself, everyone needs a break to recharge themselves.
Yes. There comes a day when you realise none if it has anything to do with anyone else.
Most mothers work outside the home by the way.
You are doing the right thing. If I could, I'd give your friend a right telling off for being a judgemental, unhelpful fool. I work 4 days a week and don't feel guilty in the slightest. Neither should you - you sound like a great mum and role model for your daughter.
Ditch the guilt. You are doing a great job - why would guilt be a feature of your life? You have nothing to feel guilty about. You have a child to care for and provide for and you do both - job done.
Honestly this guilt thing is corrosive and a total waste of time.
And I speak as a single mother of two who works FT. I think I missed out on the guilt programming session
Always been a sahm so can't comment on the guilt thing but I've always admired working mums and a big hats off to single working mums.
You're doing your best. That matters. As for you friend saying what she did? Tactless at best and pretty shit at worst.
Aw don't feel guilty, it sounds like you're doing a totally amazing job for your daughter, and good-quality childcare combined with your love and time together will be giving her the very best start in life. Shame on your friend.
I work full time, I don't feel guilty. We'd probably get by on just my partner's earnings, but I enjoy working.
Tell your friend to button it
Did your friend offer to pay your bills? I thought not. Seems like you're doing just fine to me.
I don't have working mother guilt, I really don't. Of course there are days when I'd rather be at home with them (e.g. if they're poorly and have to go to Granny's), but I don't feel guilty about it.
I think I used to once upon a time, til I remembered that the SAHM was an invention of the 50s - before that poor women have always had to work, and rich women had nannies. As long as children have a loving bond with their carers, there is no need for it to be their mum 24/7. And as a pp says, girls with working mum's actually do better in adult life.
Your friend clearly has no clue. You need to work to pay the bills - were you supposed to live on fresh air until your daughter started school?
I also think you are really sensible taking that time to get ontop of home jobs. I juggle laundry and other bits around working from home but still spend several hours of my only weekday with DD cleaning.
To ease the guilt can you get family to help at the weekend?
When I feel guilty I have a think about changes I can make. If I can't then I try and put it one side. But if I can then I change.
The guilt never starts if you think it's OK for people who have children to also have jobs.
4 days of working, 1 day to catch up on admin and chores, whole weekend with your child sounds a great balance.
I am impressed that you have figured out how to have regular childfree time when you are parenting completely by yourself.
That is so important for your own wellbeing.
"Mum's" was my illiterate phone auto-correcting me!
It doesn't sound much of a friend.
I no longer feel guilt by working but that's because they are both in school
You are doing the right thing op.
You are doing what millions of women and men do world wide you work to provide for your child and ensure she is cared for and safe while you are away from her.
People would question you as a sahm on benefits. You won't win.
She will he fine and you are setting her a great example. And time to yourself is essential
I'd have her at home with you on a Friday and not have your weekends so hectic , there's no point rushing around and knackering yourself out for the rest of the week
My dd went to nursery when she was a year old and is still really good friends with children she met there. nursery was a really positive thing for her and my working kept me sane solvent and supported by work friends. Sounds like you're doing really well - well done
The guilt of being a parent never goes. The guilt was part of the contract you signed at birth 😂.
Parents never win 😂
(You're doing fine )
Friend can fuck off and mind their own business. I also get the 'oh poor you, working full time, isn't it sad you miss their childhood..'. Oddly those people have not offered to pay my mortgage.
Never felt guilty, always worked full time (with a part time job on top and I volunteer). I am not very maternal and while I love my DS dearly I would never be able to be a SAHM, it would drive me mad. I am in awe of those who can do it without wanting to commit murder.
Another one here who missed out on the guilt programming. I went back to work FT 6 months ago when DS was 1 - yes it's chaotic and there have been some fairly awful weeks when DH, DS and/or I have all been sick with something or other, but we are muddling through and have such lovely weekends together which make it all worthwhile. Plus I (mostly) enjoy my job, I really enjoy the salary that comes with it, and why on earth should I feel guilty when DH doesn't?
We are thinking of trying for DC2 soon and if/when that happens I might think about going down to 4 days a week, but the thought of stopping working altogether (as some of my friends are planning to do) has never crossed my mind. I would be a terrible SAHM - my mum SAHM and I am full of admiration for her as she did such a great job of it
whereas I was champing at the bit to get back to work after mat leave
So in short - it sounds like you are doing an amazing job, you have absolutely nothing to feel guilty about (you should feel nothing but pride in how well you are balancing your work, your daughter and your personal needs) and your friend should keep her unhelpful "opinions" to herself
I went back to work when dd was 6 months and was full time when she was a year. Now she is at school I have been able to afford to drop to 4 days and have the same set up as you. It makes so much difference to the quality of our weekends together having a day to get all the boring stuff sorted!
I have had plenty of comments about working full-time and just ignore them. It was what we needed to do for our family and dd loved going to nursery. I refuse to feel guilty for it and the fact is they would never dream of saying it to a man, so why should I be different because i don't have a penis.
Both my parents worked when I was a child and I don't remember it ever being an issue. I also think this played a factor in me never questioning that I would work as much as needed when dd was little.
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text:
This triple-threat cleanser from (MALIN + GOETZ) dissolves dirt and oil, clears acne, and balances skin's pH. The amino acid-based foaming gel taps naturally antibacterial grapefruit to prevent blemishes and exfoliate, while hydrating glycerin and sodium pca leave your complexion soft, not taut. It's gentle enough for sensitive skin, and rinses away completely—no need for toner. (So...quintuple-threat?)
This product smells great, but it burned my eyes and left them red and dry for about an hour after using. I had taken off my makeup with argon oil and just needed to wash the oil off- it was painful. Also, I'm not sure what benefit amino acids have on the skin. That seems an odd thing to advertise IMO.1


text:
So yeah, this is our big non-wedding splurge of 2010. It's the weekend I pretend I'm not a cranky nearly-30-year old and I rock out with the kiddies in the Coachella heat. It's the weekend I give up on style and admit that I need ugly-but-comfortable sandals to tackle the festival grounds. And hopefully, it's the weekend that all of the following bands rock us. Hard.
- Jay Z
- Portugal the Man
- Beach House
- Corrine Baily Rae
- Muse
- Dead Weather
- Sia
- Local Natives
- Julian Casablancas
- Spoon
- Phoenix
- Pavement
- Thom York


text:
Business & human rights and corporate social responsibility (CSR), these are concepts that modern companies can no longer avoid. For years now, businesses are increasingly held accountable for the manner in which they operate in society. This applies not only to the large multinationals: banks, pension funds and other investors receive critical questions about how and where their money is spent. Small and medium-sized companies that operate internationally are similarly faced with these issues. Recent examples are the flower and clothing industry.
The topic also increasingly transcends the 'classic' areas of CSR, such as child labor and exploitation. Matters such as environmental damage, corruption, international sanctions and the relation with indigenous peoples are increasingly under the scrutiny of lawmakers, supervisory authorities and the media.
Aside from this, the scope of corporate social responsibility has also expanded. Not only is the conduct of a company vis-à-vis its own environment examined, the actions of its suppliers and customers elsewhere in the supply chain are also a subject of interest. 'What is the origin of my raw minerals, and how are my products subsequently used by my customers?' These are questions that confront contemporary companies more and more.
All in all, these developments are resulting in the expansion of the responsibilities and liabilities of both investors and business enterprises. This can be within the context of civil law liabilities (see also our department of International law & human rights), but the responsibilities and risks for businesses according to criminal law have also increased significantly. In that respect, the Dutch government increasingly acts as catalyst for new laws, also on a European level. Following political pressure (consider e.g. the clothing industry in Bangladesh), alleged human rights violations are actively dealt with. As a result, the spectrum of administrative and criminal measures through which companies can be prosecuted and sanctioned has grown substantially over the past few years. As such, transnational business enterprises increasingly require specialized legal advice.
Prakken d'Oliveira and Business & Human Rights
The lawyers at Prakken d'Oliveira are focused on the legal aspects of corporate social responsibility. As the sole Dutch firm specialized in human rights, we have ample experience in the area of business & human rights. Notable cases by our firm include a case against Shell for environmental damage in Nigeria, criminal charges against the Rabobank for involvement in money-laundering and a civil law claim against FIFA for its role in the violation of international labor rights in Qatar. We represent both respondents (business enterprises) and victims of human rights violations.
Prakken d'Oliveira also specializes in business & human rights in conflict areas. The risks in conflict areas are always acute and real. The situation on the ground is unsafe and chaotic, and normal government institutions often no longer function. This requires a specialized approach, that will often deviate from the 'standard' legal services offered in peacetime situations. In those cases, our experience with international as well as local investigations has great added value. We take the matter further than other firms. We have a broad international network that helps us assess the situation on the ground and obtain advice on local laws. Our specialist solutions and significant expertise in the areas of international law and the laws of war allow us to offer a unique services.
Apart from this, we also draw on our extensive experience in the advisory practice with regard to (international) sanctions. This knowledge helps us e.g. to advise companies that wish to expand their operations to new (high risk) countries, or who are suddenly confronted with a changing political reality in the countries in which they operate. As an example, sanctions that are imposed on one or more conflicting parties can have a direct influence on business opportunities. Our firm can provide specialized advice in such cases, if needs be by litigating the matter all the way to Strasbourg (European Court of Human Rights) or Luxemburg (European Court of Justice).
Liesbeth Zegveld, Michiel Pestman, Göran Sluiter, Marieke van Eik, Channa Samkalden, Tamara Buruma, Barbara van Straaten


text:
Summary of Week 4 of Human Capital Strategy for Social Enterprises (Novoed – Acumen / Hitachi Foundation)
Performance management typically includes goal setting, metrics or reliable measures, feedback, and outcomes. Feedback on how employees are delivering results should occur regularly (instead of just during performance reviews). I liked the idea of Netflix's anonymous informal 360-degree system. Even though they moved on to signed feedback, I think it would be a good start for our NGO to get into the culture of providing feedback!


text:
Dippers. Made for dipping.
I like to use mine to eat peanut butter from the jar.
Great for use on the table for serving hummus and other dips
approx 13 x 2 cm
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- Home
- Craft & Hobby
- Craft Glue, Adhesives & Finishes
- Glue Dots & Other Adhesive Dots
- Glue Dots® Craft Adhesive Roll
Glue Dots® Craft Adhesive Roll
Product ID: GD8165
Craft Glue Dots are 1/2 inch double-sided adhesives perfect for arts and crafts, school projects, framing/matting, home décor, scrapbooking and woodworking. Glue Dots bond to most surfaces including paper, plastic, metal, wood, foam, textiles and more. 200 clear adhesive dots per roll. 1 roll/pkg.
Material: Other
Product Type: Glue Dots & Glue Sticks
Shape: Other
Our Price: $3.47
200 piece per package.


text:
Fish School
Fish School
By Nancy Poydar
Holiday House, Hardcover, 9780823421404, 1pp.
Publication Date: August 1, 2009
List Price: $16.95*
* Individual store prices may vary.
Buy at Local Store
Enter your zip code below to purchase from an indie close to you.
Not Currently Available for Direct Purchase
Can a goldfish really learn? Charlie is sure that his pet goldfish, Wishy, can. So when his class visits the aquarium, Charlie puts Wishy in a plastic bag and takes him along in his backpack, in this fun, fact-filled story. Full color.


text:
Singapore :
Palawan Beach
There is a suspension bridge that leads to a small islet off the coast which is said to be the southernmost point of continental Asia, or Asia's closest point to the Equator.[15] There are several bars along the beach offering food and beverage options to visitors.
hotels nearby
map and directions
food and drinks
more information


text:
Ask @shaylalittle:
ςΉάΨLά Lïττιε ♪Latest answers
sure lol
rate 9.5 xxxThe boy who twerks ;)
thank ya
who is steven yeun?
omg! @steveyeun he is the best actor in the world! He is my fav off of The Walking Dead!! and the love of my life!! I am a very big fan of him! i love him! he is sooo cool! and he is soooooo good looking! if he dies on The Walking Dead i will die! but i have faith that he will not die! i love you steven!! #Glenn
You look so cute and pretty. You must be the most cutest girl at your school, right?
umm who is this??
Picture of you getting a wedgie
umm i dont have one
like if people think your cute?
ok.. sure lol
Do you like dogs?
no i love dogs!
2 pointer
Yellow :)Conner G. Sloan
Iced teaTiff Ann ❥
Post a selfie?
no first i wanna know who you are
Are you single? ;) bc you fine girl
yeah and tanks but no im not!
Probably Daryl! But I really like everyone!
i like Glenn!!!!!!
OH MY GOD!!!!! That's awesome!!! AND you're a fan of the Walking Dead!?!? I think we should be best friends!!!!
who is your favorite character?? lol
Little bit, I miss youu!Aerial Humphreys
I miss you more!!!!!! ∞
who is you guy best friend
Jacob Hanna
What is the last thing you said to someone?
dad i want the new just dance! he said "why do you need another one, this will many 5!" lol
Are you an art lover?
What are you wearing right now?


text:
3 Bedrooms Detached Bungalow for sale
12 Ullswater Place, Cannock, WS11 1DX
Well equipped deceptively spacious three bedroomed detached bungalow located in popular cul-de-sac convenient for facilities at the town centre
£219,000 Offers Over
Details on application
2 Bedrooms Apartment Flat for sale
Riverside Court, Girton Road, Cannock
Marwood homes are pleased to offer for sale this refurbished modern first floor apartment with no chain involved.nnit is situated on a girton road just a minute away from cannock town…
A two bedroom first floor apartment ideally located close to cannock town centre. the property benefits from having a modern refitted kitchen and is double glazed throughout. ideal…
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A well presented two bedroom 1st floor apartment ideally located close to cannock town centre. the property benefits from having a refitted bathroom and is double glazed throughout.…
Marketed by:
Chariot Estates, Burntwood
9a, Cannock Road
Tel: See phone number 01543 686877


text:
Mike Hingley (github)
Frist!... yay
gleemonk (unregistered)
Ey Chris, I forgot my SVN password again. Could you be a doll and reset it for me? Just set it to "gleemonk1" THANKS!
JustSomeDudette (unregistered)
Are you sure you don't want it set to hunter2?
Chris (unregistered)
If you call me "doll" one more time, I will reset your password to something impossible every 10 minutes for the rest of your time here.
Confused (unregistered)
The only WTF I can find is that a develoer gets an accidental job offer that the company didn't indend, gets into a plush job of SCM guru and is left mostly alone.
Where do I sign up for that job offer on a golden tray?
Brian Boorman (google)
Where do I sign up for that job offer on a golden tray?
Apparently at MetLife.
Hannes (unregistered)
Sounds like a really nice job. If the pay is decent as well... sign me up!
Unhelpful (unregistered)
Remember, you have to fail the interview for a different position to get this job. It's like an annoying videogame, but even less fun, because you don't even know what you'll be doing for money in the end.
Reality (unregistered)
Some might say the company is wasteful to keep him on staff for doing essentially nothing. The reality though, is he's probably more valuable than most employees. He's the in-house therapist and a source of sympathy and reason in a corporate hell.
Reality (unregistered)
When life hands you lemons, make lemonade in your ass. Then you make life drink every drop of it.
Lance Spencer (unregistered)
Lance Spencer (unregistered)
Sorry Nate but I am now a slave to the BBC.
And Tyrone, if you don't answer me, I'll just text Jamal.
Randal L. Schwartz (google)
The real WTF is that this is Flag Day (in the US), and the WTF is that it's not a Flag Day WTF [https://en.wikipedia.org/wiki/Flag_day_(computing)]
grasshoppa (unregistered)
Apparently at MetLife.
As a vendor who "interfaces" ( technically ) with that...."company"...that makes so much sense.
I drink a lot.
PenguinF (unregistered)
Chris reminds me of Virgil in Dante's Inferno.
Gracie (unregistered)
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Stephen Brian (unregistered)
If companies have hired any employees then it is the responsibility of them to provide full accidental insurance as well. It is important for their employees because no body knows what might happens next. Government also should take any step regarding this before any serious injury took place.
Zenith (unregistered)
I read "Doghouse" as "Donegal."
crystal Davies (unregistered)
I Basically think we all don't have to face all these deceit and lies from our spouse...in a case of mine wen i got sick and tired of all the lies and deceit i had to contact a friend of mine to get me the contact of one of the best hackers in the states ..then i met firstname.lastname@example.com..He saved me from the lies of my cheating husband by hacking his phone..Incase you need help with hacking any phone or account or other jobs contact him via email/phone firstname.lastname@example.com or +1 916 378 4978 Tell him i reffered you.He will help you
crystal Davies (unregistered)
I Basically think we all don't have to face all these deceit and lies from our spouse...in a case of mine wen i got sick and tired of all the lies and deceit i had to contact a friend of mine to get me the contact of one of the best hackers in the states ..then i met firstname.lastname@example.com..He saved me from the lies of my cheating husband by hacking his phone..Incase you need help with hacking any phone or account or other jobs contact him via email/phone email@example.com or +1 916 378 4978 Tell him i reffered you.He will help you
alston01 (unregistered)
great post,
- mitchel (unregistered)
Bradshaw Layfield (unregistered)
What a tremendous way to land yourself in a job. A really inspiring story of how a nobody became a source control guy in a leading tech company. uk academic writers
Garret Jacobs (google)
Your article gives me UK Coursework Help lot of information about accidental hire the particular accidental.
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Have you guys checked out this guy email@example.com dude's a Great successful hacker,involved with cloning phones, hacked into my ex's gmail and facbook, what let me knowing she was infidel and also gave my nephew some really outstanding school scores which he upgraded himself, cool way to have financial freedom as well. Get your bank blank atm cards which could debit money from any a.t.m machine. Make $20,000 and more in a couple days. Bank transfers and wire transfers as well as Paypal jobs, hes that good,had to make him my personal hacker. You could mail him as well if you got issues, he's as discreet and professional too.He's kinda picky though so make mention of the reference. OLIVER referred you. Your welcome.......
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text:
Search Results | larry bodine
2017 Attorney Social Media & Digital Marketing Survey
Virtually every business, including law firms and attorneys, are using digital and social media marketing as a strategy to reach clients and prospects. Now you can see if and how you're outpacing your competitors by taking the 2017 Attorney Social Media & Digital Marketing Survey. Healy Consulting & Communications and Ajax Strategies, in conjunction with LawMarketing.com, are conducting the annual study on a nationwide basis to understand […]Continue reading...


text:
Tuesday, September 08, 2015
I feel like such a slacker when I miss Monday and post our meal plans on Tuesdays. But, once again, this is more for me and my memory than anything.
Here we go! Dinner this week at Casa de Estrella (that's Star in Spanish, in case you didn't know...)
Monday: Leftovers. We had a fun weekend, full of family, friends, and food, which carried over to yesterday.
Tuesday: BBQ Ranch Crockpot Meatball...made into sandwiches on my favorite Sams Club French Bread loaves ($2.77 for 2 HUGE loaves!). Big family hack: meatballs last longer if you serve them as sandwiches.
Wednesday: French Toast Bake. Not exactly figure-friendly, but it is sooooo easy and yummy that it stays in the rotation.
Thursday: Bacon Lovers Mac & Cheese. Again, I won't be losing any weight with this one, but it'll be easy to throw together and serve before ball games.
Friday: Cowboy Chicken Wraps.
Weekend (or carry-over to next week if I can get out of cooking on Saturday/Sunday): Breakfast Burritos
Labels: meal planning Monday, recipe
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text:
Alternative Titles
English: First Girl
Synonyms: Fuasuto Garu
Japanese: ファースト・ガール
Type: Manga
Volumes: 5
Chapters: 18
Status: Finished
Published: 2002 to 2003
Authors: Saitou, Chiho (Story & Art)
Serialization: Flowers (Monthly)
Score: 7.361 (scored by 1629 users)
1 indicates a weighted score. Please note that 'Not yet published' titles are excluded.
Ranked: #48542
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Popularity: #2487
Members: 3,049
Favorites: 31


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Don't let the issue of online security hamper your plans for success on the internet
Dan Little
Reading the news recently one can't help but notice that there are a variety of articles available about high profile internet security breaches. These include attacks on the British security service and engineering firms, as well as multiple attacks on American and Chinese sites. Perhaps even more worrisome is that the government is well-prepared to defend against such attacks, which surely leaves little hope for those of us who aren't.
A recent article on thisismoney.co.uk stated that cyber crime is reaching 'a disturbing level', with some credit card details on sale for just 70p (that's about $1.12). If this is the case, how can a business on the internet possibly hope to protect their financial interests online?
Well, regardless of what measures you take there will always be a risk, but there is no reason why you can't minimise this risk. Just in the same way that a land-based business will never be able to eliminate the threat of robbery, an internet business can never eliminate the threat of cyber-attack.
So, what can you do to help secure your business from cyber attacks?
- Use a router or a modem with a high-quality built in firewall. Make sure that you change the admin and password details for your router as well, just to ensure that no-one can secretly disable your firewall. Your router's instructions should provide you with details of how to do this.
- What is a firewall? A firewall is an automated security system that detects unauthorised access to your computer and shuts it down before it manages to infiltrate your system. However, like any wall, it can be broken. So you should also: Install a second firewall, anti-virus and spyware detection on your computer. Use reputable products to avoid sub-standard service and make sure you update them regularly. If you have a firewall on your computer too, you make your system doubly hard to penetrate.
- Use different passwords for everything, but write them down in a folder and padlock them in a safe. This means that if you forget one you can easily access your files, but that people trying to access them won't be able to crack one password and then use it to access everything you have.
- Be aware of scams: it sounds simple, but don't reply to suspicious junk mail, never give out your bank details to anyone who just asks for them and always try and verify that people are who they say they are. IF you're unsure, give their telephone number a ring and make sure that it is actually the company trying to reach you.
If you follow these simple guidelines you can minimise the risks posed to you and your online business. In all my years of owning an online company, I've followed these principles and have not been cyber-robbed. However, I don't plan on becoming complacent any time soon, and neither should you! Nevertheless, don't let the issue of online security hamper your plans for success on the internet.
Hope this helps.
Dan Little
Related posts:
Work From Home? Run a Small Business? Welcome to the Tax Nightmare
Work at Home Mum Makes £4,000+ Per Month Online
Surveys for Money :: Do They Work?
Tips For Success To Make Money Online: Work From Home
Top 5 myths about making money on the net


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Ty's Tater-Tot Cassie
Be the first to review
READY IN: 45mins
Recipe by Show-Me-Girl
Tator-Tot Casserole my style.
See Discussion:
Ingredients Nutrition
- 1 lb ground beef
- 1 lb ground pork
- 2 (8 ounce) cans French style green beans
- 2 (8 ounce) cans cream of mushroom soup
- 1 (3 ounce) can sliced mushrooms, drained
- 1 (8 ounce) can sliced water chestnuts, drained
- 1 cup Velveeta cheese, cubed
- 1 cup shredded cheese
season with
- Worcestershire sauce
- lawrys season salt
- ground black pepper
- garlic powder
- 2 tablespoons French onion soup mix
- 25 tater tots, to cover
Directions See How It's Made
- Preheat oven to 375. Brown ground beef and pork together add seasonings to taste; drain. In pot or mixing bowl add all ingredients but the shredded cheese and Tator tots, Mix Well. You may want to add a small amount of water to get the onion mix and creams to mix well. Spray 9x13 with cooking spray pour in casserole ingredients and top with tator tots. Bake for approximately 20-30 minutes until bubbly and heated through. Remove from oven and topy with shredded cheese! Enjoy.


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So my last book would not let me publish anymore chapters, so this book will work the same and have the same sort of ideas behind it! So if you find this book, try reading the first one before this one, just to get an understanding.
XBloodrayneX Jul 25
Sagittarius (f) x Virgo? (m) One of the only ones I didn't see. x3
marlynguiro Jun 06
Can you do a lyl lemon? Either Scorpio (F) x Pisces (M) or Saggitarius (F) x Leo (M) are welcome Thanks chu! :3
TheMostAss Jun 19
MY BODY IS ALREAY BURNT FROM THE BEACH YESTERDAY!WHY ARE YOU BOILING ME EVEN MORE!?IT HURTS..IT HURTS..But it's hot ;)
__Yukari__ Sep 04, 2016
Emmm...could you pleeeeaaaase do a (f)Capricorn × (m) Scorpio?
HeyYoBighed Sep 04, 2016
I commented about the Taurus and Virgo story on your other book, are we going to see it here?
BTS-infiresme Sep 03, 2016
I really liked te zodiac extent ion could you plz write more of that


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Corporate Travel
The world of business life is fast paced and demanding. Let Custom Limousine Inc. take some of the work off your shoulders... Read More
Date Night
Kansas City is the perfect town for a beautiful date night for you and your special someone. Show them how much you... Read More
Sporting Event Party Bus
"Take me out to the ball game, or get me to the Cauldron of Sporting KC!" If you're uttering these words to... Read More
Birthday Party Bus
Celebrate your birthday in a new exciting way with Custom Limousine Inc., aboard our luxurious convoy of party busses. Be the envy... Read More
Tom Petty is Coming to KC!
Are you attending one of the biggest rock and roll concerts in Kansas City? Are you seeing Tom Petty and The Heartbreaks... Read More
Tour De KC with Trolley Tour Service
Kick off your summer with a gorgeous, scenic view of Kansas City, Missouri. Nestled in the heart of the Midwest, Kansas City... Read More
The Ultimate KC Royals Baseball Experience
The Royals are turning around their slow start and that means another summer of meaningful baseball in Kansas City. Kansas City is... Read More


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There are total 14 letters in Supplicatingly, Starting with S and ending with Y.
Total 1174 words created by multiple letters combination of Supplicatingly in English Dictionary.
Words that starting with Supplicatingly
Words that containing Supplicatingly
Words that ending with Supplicatingly
Definition of the word Supplicatingly, Meaning of Supplicatingly word :
adv. - In a supplicating manner.


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What is JotForm?
JotForm is a free online form builder which helps you create online forms without writing a single line of code. No sign-up required.
At JotForm, we want to make sure that you're getting the online form builder help that you need. Our friendly customer support team is available 24/7.
We believe that if one user has a question, there could be more users who may have the same question. This is why many of our support forum threads are public and available to be searched and viewed. If you'd like help immediately, feel free to search for a similar question, or submit your question or concern.
hide decimal places using form calculationAsked by southind on March 24, 2017 at 10:26 PM
i need to hide decimal places using my form calculation. please help
You can set the number of decimal places to show in your jotform, to hide them you can set them to 0. To do so:
1- Open the form calculation menu.
2- Click on Advanced at the bottom part of the Menu.
3- Go to "Decimal Places in Numerical Results" and set that to 0.
If you need any more information about the Form Calculation Widget please refer to this guide.
How to Perform Form Calculation Using a Widget.


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Welcome To Eyeworld Vision Center
- Your choice of quality frame up to $99 value. (Included Frames)
- Single Vision or Lined Bifocals (FT28) lenses to 4.00D (CR-39)
- Eyeglass Case
- Free lifetime adjustments
This coupon must be printed and presented at the time of purchase. Not valid with insurance, other special offers or previous purchases. Does not include eye examination.
To all of our loyal supporters:
In 2010 we will celebrate our 25th year serving the eye care needs of South Alabama.
I think back to our early days, (1985 in Chickasaw) and I'm astonished at your level of support
throughout the years. Thank you!
We're fully aware that our accomplishments are not simply attributable to good management
or hard-working employees. We grew and prospered with God's Blessing and because we
found some great friends like you who gave us loyal support along the way. We want to let
you know how much we appreciate you continuing to rely on our office for your vision care
So this is a thank-you note—for allowing us to care for your vision needs, for putting up with
occasional errors due to "growing pains," and just for helping to put Eyeworld Vision Center
on the map. The future looks bright, and we want to acknowledge your contribution to this
rosy outlook. As we say in Alabama, "'Preciate it!"
Phil and Sherry Gillette
1088 Industrial Parkway I-65 Exit 13 Across From Wal-Mart.
Phone 251-675-3666 Fax 251-675-9366 Toll Free 1-800-453-0912
7930 Moffett Rd. 1 Block West of Schillinger Rd. Across From WalMart
Phone 251-645-2991 Fax 251-645-0723


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UK Commonwealth of the Bahamas
In the year 2000, Bircham International University is incorporated in the British Commonwealth of the Bahamas, according to the "IBC Act 1989" and is legalized and registered in the General registry of the Bahamas with the number 103.326B.
In the year 2003, Bircham International University ceased its activities in the Commonwealth of the Bahamas and focused its legal status both in Spain, European Union and the USA, as a non profit organization.
UK Commonwealth of the Bahamas
Reference - Legal. Year: 2000... 2003.
Check document below.
Replaced by (Click below for more info):
USA State of Delaware
Check more world references about Bircham University.
Check professional references for BIU graduates.
Check BIU graduate's opinion and testimony.
Check Bircham University degree validation services.
Check the complete Bircham International University network.
UK Commonwealth of the Bahamas
& Bircham International University.


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Ipanema has created world-class restaurants, shops, and cafes. At the forefront of the beach culture are the many surfers and sun worshippers who socialize daily at the beach. Every Sunday, the roadway closest to the beach is closed to motor vehicles and local residents and tourists use the opportunity to ride bikes, roller skate, skateboard and walk along the ocean. Ipanema holds its own street parade during Carnival festivities, and the Banda de Ipanema attracts up to 50,000 people to the streets of Ipanema for Carnival.
Ipanema Elizabeth
2 Bedrooms / 2 Bathrooms
Posto 10 Nice
2 Bedrooms / 2 Bathrooms
Ipanema Costa Oceanfront
3 Bedrooms / 2 Bathrooms
Availability / Pricing
We needed an apartment for 6 people for a three-night stay in Rio, and Rio Upscale's apartment in Ipanema was the perfect fit for us. It was in a great part of Ipanema and only a block away from the middle of Ipanema beach. Aside from the great location,
we couldn't have asked for a better apartment. The apartment had a 24-hour doorman, always leaving us feeling very secure and taken care of. The apartment itself was clean, sleek and modern. The rooms were perfect for 6 people, and we had a lot of closet space for our luggage. The kitchen was modern with new appliances and a washer and dryer which was key since we were halfway through our trip in Brazil. The apartment was outfitted with all the comforts of home, and we only wish that we had been able to stay longer to enjoy the apartment and the neighborhood.
Chad was also great to work with. He always made himself available to answer any questions we had and was completely flexible with meeting us upon check-in and check-out. I would definitely stay in this apartment again and recommend this service for anyone looking to stay in Rio.


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Artist's description:
They are gentle,graceful and beautiful. The ode to lilies-to their beauty and self-sufficiency.
Materials used:
Oil on canvas
Bouquet of lilies. (2016)
Oil painting by Natalia Lugovskaya
- Oil painting on Canvas
- One of a kind artwork
- Size: 21.65 x 29.53 x 0.79 in (unframed) / 21.65 x 29.53 in (actual image size)
- This artwork is sold unframed
- Signed on the front
- Ready to hang
- Style: Photorealistic
- Subject: Flowers and plants
More by Natalia Lugovskaya View all
View all
Ocean Blues original art, 140/70
Oil paintingby Natalia Lugovskaya
Colorful fantasy 2
Oil paintingby Natalia Lugovskaya
Floral stiill life
Oil paintingby Natalia Lugovskaya


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This property is no longer available.Search for Available Property.
4 acres in Benton County, Missouri
Built as an artist retreat!!! This home is incredible. You will be in awe of this amazing structure. With it's simple concept artistic design, you will never get bored with all the different angles you can view your amazing property from. Sitting on 3.5+ acres this home features 2, could be 3 bedrooms and 1 1/2 baths. There is a loft overlooking the kitchen and living room, and an exterior stair tower connected to the house with an upper deck. Get in touch with your inner artist with this one. You won't be disappointed.
Tax Data (Show Tax Data)
Tax data is not available for this listing.
Contact the Seller for more information.
Other Land for Sale in Benton County
- Properties for Sale in Nearby Counties
- Camden County Land for Sale
- Henry County Land for Sale
- Hickory County Land for Sale
- Morgan County Land for Sale
- Pettis County Land for Sale
- Saint Clair County Land for Sale
NOTE: The information contained herein is provided as general information only and has been obtained from sources deemed reliable. It is provided without any guaranty, warranty or representation, expressed or implied, made by Lands of America, or any related entity, as to the accuracy or completeness of the information. The information is presented subject to errors, omissions, change of price or conditions, prior sale or withdrawal without notice. Prospective purchasers should make their own investigations, projections and conclusions concerning the information.


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Product Description
Award winning Hogsback brewery ales and fiery chilli treats!
A delicious hamper just for him with a selection of award winning ales, delicious cider and fiery treats.
Gift Box Includes:
The Hogs Back first ever brew, Traditional English Ale (TEA) – 4.2% A 'Classic Best Bitter' – The brewery's flagship ale, amber in colour with a hoppy and slightly fruity aroma supported by malt in the taste. A well-crafted, bittersweet beer with a long dry finish.
Hogsback Advent Ale – 4.4% deep chestnut coloured, fruity nosed ale with liquorice flavours and a dark chocolate after taste. An ideal beer to celebrate the coming of Christmas.
Hogsback traditional cloudy English cider – A full flavoured 5% Cider made traditionally by adding back the bittersweet apple juice at the end of the oak barrel fermentation, which creates the Cidre Doux style of Brittany/Normandy. Cloudy, gently sparkling and wonderfully 'appley'.
Eat 17 artisan chilli bacon jam, 105g, perfect for spreading on the double baked biscotti.
New forest twice baked biscotti – indian spice, 100g
The real smoked nut company, hickory smoked cashews with cracked black pepper.
Fiery thai chilli crackers, 70g,
Mr.Trotters jalapeño chilli pork crackling, 60g
We can include a personalised hand written card with all of our gift boxes, just let us know what you would like it to say – Maximum 25 words.
Christmas corporate gifts
We all know how important it is to say thank you to the customers, clients and teams that provide the vital support throughout the year.
However, with mounting workloads it's easy to run out of time to find a gift that feels unique and personal to the recipient. That's where we can help you deliver that meaningful thank you gift.
On occasion we may need to amend products to improve our service to you


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Nissen flytter
André Jensen
Trace a face from a magazine onto acetate. Paint or collage colors underneath for a new/abstract face. Would be cool for self-portraits
the way i feel is always written on my face.. //what a beautiful drawing/ not sure of the artist i think the reason i like other peoples art is because i would think that i would draw theire art
we took photographs of students posing as if they were erasing their faces. The students cut out an area of the photograph, glued the remaining portion of the photo onto paper, and used pencil to draw the missing portion of their faces.
The Calvert Canvas: Adventures in Middle School Art!: self portrait
Fashion sketch`
Half-Face portrait, grade 8. Pencil
Alexej von Jawlensky - Self-portrait with top-hat [1904]
Egon Schiele. Self portrait. Schiele might be my favorite portrait painter.


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the back with the magnet, simple.
Friday, 9 October 2009
Eye'm stuck on you
the back with the magnet, simple.
6 comments:
The perfect dieter's fridge magnet- every time you go to sneak something yummy there's someone watching...... Eeeeekkkkk!!ReplyDelete
Fingers crossed for tomorrow for you!
So funny & creepy. It would be fun to add noses, mouths & ears so you could make mix & match faces.ReplyDelete
hahaha, love them! xxxxReplyDelete
Eww! It is creepy!ReplyDelete
I think these are way cool and lots of fun for Halloween! I'll be linking. I like Heather's idea for other face parts too. Maybe family members!ReplyDelete
Heather - other face parts did cross my mind but for now the eyes are creepy enough, and yes, hubby hates them :o)ReplyDelete
I loooove comments, so thank you for taking the time to leave one.
If you put your email address in the box provided I can answer your questions directly too, I hate spam so don't expect to get any from me, corned beef on the other hand....


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Boston World Music Meetup Group Message Board › Do you know somebody who would like to move for September? Rentals available.
|A former member
Two rooms are available this September for rent in a three bedroom apartment.
Room 1 is a small room perfect for somebody on a tight budget with a single bed. Deep closet is outside of the room in the hallway. Rent is $335.
Room 2 is a good sized room for somebody with more furniture. It has two windows and rent is $385.
Both rooms will be available for Sept. 1st move in date and you would be signing a one year lease.
The third room is mine. I'm helping the landlord to fill the other rooms. I am a clean, cooperative, mature professional.
The rent is a great price considering proximity to Boston and convenience. You can drive or take public transit. For those who drive parking is easy. As a Chelsea resident you can get a fast pass transponder for your car and get into the city over the Tobin Bridge for only 30 cents and you're in the city in about 10 minutes. For those who take public transportation the bus stop is right across the street and in about 20 minutes you arrive to Haymarket T station downtown. Either driving or hopping on public transit is a breeze.
The landlord likes to retain young professionals and students. I know one tenant who has lived here on the first floor for over 10 years and his rent hasn't been raised once. The building has a total of 6 units yet it is a quiet environment. This location is NOT ideal for young people who want a place to party.
The space is bright and sunny. Shared utilities are split 3 ways. The kitchen is not the fanciest but it is very spacious which compensates for no living room. The bathroom has been newly renovated in marble and tile. There is a locked storage space in the basement as well as more space in an extra room at the end of our unit. Another great plus is the coin operated washer and dryer in the basement.
We are very close to the Chelsea Market Basket supermarket plaza. The new Market Basket location is awesome, cheapest place to buy food in the Boston area. Plus there are brand new stores popping up including, Starbucks, Radio Shack, Five Guys, Home Goods, TJ max, Dockside Restaurant and Super Cuts. Not bad for our little community of Chelsea!
Money needed to move in equals 3 months' rent upfront. This consists of first months rent, security deposit, and last months rent. So if you take room 1 you will pay $1,005 and if you take room two you will pay $1,155.
No pets
Non smokers only
Credit & background check
Landlord prefers single residents only.
If interested please respond by telling me a little bit about yourself.
Thank you! Priscilla
Already a member? Log in.
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Meetup members, Log in
By clicking "Sign up" or "Sign up using Facebook", you confirm that you accept our Terms of Service & Privacy Policy


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Sq. Feet
Year Built
Days On Site
27 Photos
Home Description: 17072 E Lema Cir
Authentic Sante Fe style finishes and casual, Southwest livability are perfect for families, visiting guests or grandchildren! Enjoy iconic Fountain Hills view of Red Rock Mtn, Palomino Mtns and Four Peaks. The large backyard features pebble finish pool with water feature & resort style shallow wading area. An over-sized covered patio is perfect for entertaining while kids play area & sand box is close by. This amazing home on 1/2 acre overlooks the 12th green & 13th tee of Desert Canyon Golf Course and offers an RV gate & 3-car garage. Enjoy open concept living with custom Knotty Pine 8 ft. doors, Vega beams & authentic Saltillo tile, art & media niches throughout and 2 Gas kiva fireplaces.
Available now at $585,000
The average asking price of a 3 bedroom Fountain Hills home in this zip code is
$586,982 (0.3% more than this home).
This home is priced at $252/sqft,
which is 12.7% less than similar homes
in the 85268 zip code.
Map |
Street |
Birds Eye
Birds Eye
17072 E Lema Cir Fountain Hills AZ 85268
Driving Directions:
SHEA TO SAGUARO - Left To Monterey- Left To Rough Circle - Right To Lema - House On Right
Similar to: 17072 E Lema Cir
For Sale Near: 17072 E Lema Cir
School Information
Area Stats
These statistics are updated daily from the Metropolitan Phoenix Board of REALTORS® Multiple Listing Service. For further analysis or
to obtain statistics not shown below please call Highgarden Real Estate at
(480) 485-4784 and speak with one of our real estate consultants.
Listing Courtesy of Sonoran Lifestyle Real Estate.
For information or to schedule a viewing of this property (MLS# 5633277) located at 17072 E Lema Cir Fountain Hills AZ 85268, call: 480-485-4784
17072 E Lema Cir, Fountain Hills AZ is a single family home of 2319 sqft and
is currently priced at $585,000
This single family home has 3 bedrooms and was built in 1999.
A comparable home for sale at 16508 E Kingstree Blvd in Fountain Hills is listed at $550,000.
This home on 17072 E Lema Cir has not had a price change.
In addition to single family homes, Highgarden also makes it easy to find Condos, New Homes and Foreclosures
in Fountain Hills, AZ.
Mirage Pointe Estates, Bella Lago and Diamante Del Lago are nearby neighborhoods.
MLS 5633277 has been posted on this site since 7/15/2017 (34 days ago).
Same day showings available 7 days / week8am - 9pm


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Most orders ship within 1 business day. Shipping times for:
* Excludes Alaska and Hawaii
Even big or heavy items, nebulizers and oxygen supplies, ship free. If your order
total is $75+, the shipping's on us!
PARI Vios
Omron Micro-Air Electronic Nebulizer System NE-U22V1
PARI LC Sprint Reusable Nebulizer Set
Medquip Penguin Nebulizer System
Handi-Air Tote Wheeled Oxygen Carrier
Respironics EasyLife Nasal CPAP Mask - no longer selling
Health-Ox Fingertip Pulse Oximeter
Two humidifiers in one! Crane's Digital Ultrasonic Cool and Warm Mist Germ Defense Humidifier with Ionizer offers the unique benefits of Antimicrobial Product Protection embedded in the water tank meant to fight mold and mildew, producing a germ free mist. This is an ultrasonic humidifier making it whisper quiet as it empties the 1.2 gallon water tank.
Crane's Digital Cool/Warm Mist Humidifier runs silently up to 24 hours with an auto-off function when the water tank is empty. Includes ionizer for fresher air, digital display with timer for 1-12 hour operation, control touch panel, 360 degree rotating nozzle to direct mist where you want, emits 2.5 gallons of moisture per day, energy efficient, and does not require a filter to operate.
What's in the box: humidifier, water tank, instructions.
Question will be displayed after moderation.
Product works great, very quite to use. Features are very easy to use. I am looking at buying 2-3 more for the other rooms in or house. I have a child with lung problems and this really works will for him. I would HIGHLY recommend this product.


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WP/Mac on MacTel!!!
Expand Messages
- There is now a way to run WordPerfect/Mac on Intel-based Macintoshes!
- Download a copy of Parallels Workstation:
Which will allow you to run Windows XP on your Intel-based Mac, and to
run Windows concurrently with OS X.
- Purchase a copy of Windows XP Pro (or Home) SP2
- Download a copy of SoftMac Xpress
Which allows you to run an old version of the Mac OS under Windows
- Install Macintosh OS 8.1
WP/Mac will now run on your MacTel machine!
Randy B. Singer
Co-Author of: The Macintosh Bible (4th, 5th and 6th editions)
Routine OS X Maintenance and Generic Troubleshooting
- --- In firstname.lastname@example.com, Randy B. Singer <randy@...> wrote:
> WP/Mac will now run on your MacTel machine!I nominate Randy for WPMac hero of the month. This is really
good news (and I suspect other methods will follow, since
the chorus of OSX users of two or three dedicated Classic
programs, e.g. Framemaker, is growing).
--- In email@example.com, S Zaveloff <zaveloff@...> wrote:
> Why bother. If you're going to run Windows concurrently, why not
> just run WordPerfect for Windows?
WPWin, all versions, is a much different program from WPMac.
John R.
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