INTELLIGENCE, Table of Contents
posted by stinkrock at 10:21 PM
5 comments
17 March 2008
INTELLIGENCE, Article III
Have I plateaued the mountainous peak that is the intellect of the average scoundrel aged a decade or more? Again, this purveyor of choice anecdotes stands proudly before his peers, trembling with the anticipation of a gazelle that senses the hunting prowess of the lioness. Oh, to be a giraffe!
Ha ha! Ha HA, I say! Now we are arriving at a metaphorical ship-christening. Might we assuage the ruffian who, in such a myopic approach to seeking enlightenment, hath instead mistaken a sesquipedalean for an intellectual?
To cement my intellectual standing among junior high school students, the purveyors of pubescent exhilaration (Farrahus Fawcettus Oglus Erectus), I offer the foolproof: insights, new perspectives, remembrances of civilizations past and present, the very philosophies of life that propel us like so many seagulls into so many aeroplane engines at the airport JFK: this knowledge is yours:
Corporate Rock STILL sucks.
Finally, a churlish non-sequitur: I am drawn quite fondly to the machinations of troubadours who engage in superficial deconstructions of the humour of and or pertaining to flatulence.
Ha ha! Ha HA, I say! Now we are arriving at a metaphorical ship-christening. Might we assuage the ruffian who, in such a myopic approach to seeking enlightenment, hath instead mistaken a sesquipedalean for an intellectual?
To cement my intellectual standing among junior high school students, the purveyors of pubescent exhilaration (Farrahus Fawcettus Oglus Erectus), I offer the foolproof: insights, new perspectives, remembrances of civilizations past and present, the very philosophies of life that propel us like so many seagulls into so many aeroplane engines at the airport JFK: this knowledge is yours:
Corporate Rock STILL sucks.
Finally, a churlish non-sequitur: I am drawn quite fondly to the machinations of troubadours who engage in superficial deconstructions of the humour of and or pertaining to flatulence.
posted by stinkrock at 9:32 PM
1 comments
Intelligence, Pt. 2.
Nope. I mean, nay! 'Tis extraordinarily misguided!
Let me try another attempt: Here's an article from the esteemed New England Journal of Medicine entitled "Treatment of Patients with the Hypereosinophilic Syndrome with Mepolizumab", if only because it's the working title of the next Stereolab record.
Marc E. Rothenberg, M.D., Ph.D., Amy D. Klion, M.D., Florence E. Roufosse, M.D., Ph.D., Jean Emmanuel Kahn, M.D., Peter F. Weller, M.D., Hans-Uwe Simon, M.D., Ph.D., Lawrence B. Schwartz, M.D., Ph.D., Lanny J. Rosenwasser, M.D., Johannes Ring, M.D., Ph.D., Elaine F. Griffin, D.Phil., Ann E. Haig, B.S.N., Paul I.H. Frewer, M.Sc., Jacqueline M. Parkin, M.B., B.S., Ph.D., Gerald J. Gleich, M.D., for the Mepolizumab HES Study Group
This Article
- Abstract
- Supplementary Material
Tools and Services
- Add to Personal Archive
- Add to Citation Manager
- Notify a Friend
- E-mail When Cited
More Information
- PubMed Citation
ABSTRACT
Background The hypereosinophilic syndrome is a group of diseases characterized by persistent blood eosinophilia, defined as more than 1500 cells per microliter with end-organ involvement and no recognized secondary cause. Although most patients have a response to corticosteroids, side effects are common and can lead to considerable morbidity.
Methods We conducted an international, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of an anti–interleukin-5 monoclonal antibody, mepolizumab, in patients with the hypereosinophilic syndrome. Patients were negative for the FIP1L1–PDGFRA fusion gene and required prednisone monotherapy, 20 to 60 mg per day, to maintain a stable clinical status and a blood eosinophil count of less than 1000 per microliter. Patients received either intravenous mepolizumab or placebo while the prednisone dose was tapered. The primary end point was the reduction of the prednisone dose to 10 mg or less per day for 8 or more consecutive weeks.
Results The primary end point was reached in 84% of patients in the mepolizumab group, as compared with 43% of patients in the placebo group (hazard ratio, 2.90; 95% confidence interval [CI], 1.59 to 5.26; P<0.001) with no increase in clinical activity of the hypereosinophilic syndrome. A blood eosinophil count of less than 600 per microliter for 8 or more consecutive weeks was achieved in 95% of patients receiving mepolizumab, as compared with 45% of patients receiving placebo (hazard ratio, 3.53; 95% CI, 1.94 to 6.45; P<0.001). Serious adverse events occurred in seven patients receiving mepolizumab (14 events, including one death; mean [±SD] duration of exposure, 6.7±1.9 months) and in five patients receiving placebo (7 events; mean duration of exposure, 4.3±2.6 months).
Conclusions Our study shows that treatment with mepolizumab, an agent designed to target eosinophils, can result in corticosteroid-sparing for patients negative for FIP1L1–PDGFRA who have the hypereosinophilic syndrome. (ClinicalTrials.gov number, NCT00086658 [ClinicalTrials.gov] .)
The hypereosinophilic syndrome consists of several heterogeneous disorders characterized by sustained blood eosinophilia and eosinophil-related end-organ damage, with no identifiable cause, such as parasitic infection.1 The objective of treatment is long-term reduction of blood and tissue eosinophil levels to prevent end-organ damage and thromboembolic events. Except for the myeloproliferative variant of the hypereosinophilic syndrome (associated with the Fip1-like 1–platelet-derived growth factor receptor {alpha} fusion gene [FIP1L1–PDGFRA]), for which imatinib mesylate is considered first-line therapy, current management is based on long-term systemic corticosteroids.1,2,3,4
Eosinophil development from hematopoietic progenitors is regulated mainly by interleukin-5,5 which has a selective role in eosinophil maturation, differentiation, mobilization, activation, and survival.5,6,7,8,9,10,11 Since interleukin-5 appears to contribute to the pathogenesis of some phenotypes of the hypereosinophilic syndrome,12 interleukin-5 inhibition is a logical therapeutic target for this disease.
Mepolizumab is a fully humanized, anti–interleukin-5 monoclonal immunoglobulin G1 antibody with a half-life of approximately 19 days; it does not fix complement.13,14 By binding to free interleukin-5 with high affinity and specificity, it prevents interleukin-5 from associating with the interleukin-5 receptor {alpha} chain on the surface of eosinophils and their progenitors. In preliminary studies of healthy volunteers and patients with atopy, mepolizumab had few side effects and lowered blood eosinophil levels.15,16,17,18,19 Subsequent studies suggested that mepolizumab may have clinical value in patients with the hypereosinophilic syndrome.20,21,22
After these initial reports, we conducted a randomized, double-blind, placebo-controlled trial of targeted therapy for patients with the hypereosinophilic syndrome. Our aim was to evaluate the effects of mepolizumab on corticosteroid sparing and the maintenance of clinical stability in patients with disease that requires control with the use of corticosteroids.
Methods
Study Population
The study patients were 18 to 85 years of age and had the hypereosinophilic syndrome (defined as a blood eosinophil count >1500 per microliter for ≥6 months and eosinophilia-related organ involvement or dysfunction, with no identifiable secondary cause of eosinophilia23). All patients were negative for the FIP1L1–PDGFRA fusion gene, on the basis of in situ hybridization to detect deletion of the cysteine-rich hydrophobic domain 2 (CHIC2) locus, a FIP1L1–PDGFRA surrogate, in peripheral-blood mononuclear cells.24
Study Design
Our randomized, double-blind, placebo-controlled, parallel-group, multicenter study, involved 26 sites in the United States, Canada, Belgium, France, Germany, Italy, Switzerland, and Australia. It was conducted from March 2004 through March 2006. After screening, patients entered a run-in period of up to 6 weeks, during which noncorticosteroid medications for the hypereosinophilic syndrome were discontinued and prednisone monotherapy (20 to 60 mg per day for at least 1 week) was administered to achieve a stable clinical status (defined as no new or worsening clinical signs or symptoms of the hypereosinophilic syndrome and a blood eosinophil count of <1000 per microliter). Methylprednisolone, prednisolone, or triamcinolone could be used at a dose equivalent to that of prednisone, at the investigator's discretion. (See Supplementary Appendix 1, available with the full text of this article at www.nejm.org, for details on blinding, exclusion criteria, eosinophil-derived neurotoxin enzyme-linked immunosorbent assay methods, and corticosteroid conversion.)
Patients whose clinical symptoms were stabilized with the use of prednisone monotherapy (20 to 60 mg per day) or the equivalent were randomly assigned in a one-to-one ratio to receive intravenous infusions of either mepolizumab (750 mg) or placebo (saline) and were stratified according to the daily prednisone dose (≤30 mg or >30 mg) at baseline. Mepolizumab or placebo was administered every 4 weeks during a 36-week period (final infusion at week 32). The prednisone dose was tapered, starting at week 1, using a predefined algorithm based on eosinophil counts and clinical manifestations of the hypereosinophilic syndrome (Figure 1A). Week 32 was the last visit at which a taper dose could be prescribed; the patient then took that dose until week 36, the end of the treatment period. This approach to corticosteroid dosing was used to maintain control by allowing for corticosteroid rescue therapy for disease flares.
Figure 1
View larger version (33K):
[in this window]
[in a new window]
Get Slide
Figure 1. Study Design and Enrollment and Follow-up of Patients.
Panel A illustrates the study design and the prednisone tapering algorithm. The dose of prednisone (or equivalent) was adjusted at weekly clinic visits according to the blood eosinophil count and the clinical activity of the hypereosinophilic syndrome (HES). At the discretion of the investigator, tapering below 20 mg per day could have been achieved through alternate-day dosing, and tapering below 10 mg per day could have been more gradual, with a decrease in dose of less than 2.5 mg per day per week. Panel B shows the screening, enrollment, random assignment, and follow-up of patients. Patients could have had more than one type of protocol violation.
Patients who completed the trial or withdrew early but received at least two doses of the study drug entered an open-label extension study evaluating the long-term safety, efficacy, and optimal dosing frequency of intravenous mepolizumab. Patients choosing not to continue in the extension study completed a safety follow-up visit 3 months after their last dose of study medication.
Clinical Efficacy
The primary end point was the reduction of the prednisone dose to 10 mg or less per day (or the equivalent) for 8 or more consecutive weeks. A prednisone dose of 10 mg or less per day was considered clinically meaningful and a response lasting 8 weeks was considered durable. All end points were analyzed with the use of data from the intention-to-treat population (85 patients who provided written informed consent, were randomly assigned to a study drug, and received at least one dose). The primary end point data were confirmed in a modified per-protocol population (78 patients). Protocol violations (by two patients in the placebo group and five in the mepolizumab group) included a lack of documented history of the hypereosinophilic syndrome, use of unapproved concomitant medications, inability to stabilize the prednisone dose within the specified range during screening, and a prednisone dose of less than 20 mg per day at study entry. Data from the patients who violated the protocol were included in the intention-to-treat analysis.
Secondary end points were a blood eosinophil count of less than 600 per microliter for 8 or more consecutive weeks, the time to treatment failure (defined as clinical worsening requiring other therapy for the hypereosinophilic syndrome, a prednisone dose of >60 mg per day, or withdrawal from the study for any reason), a prednisone dose of 7.5 mg or less per day, receipt of no prednisone for 1 day or more, the mean daily prednisone dose at week 36, and a prednisone dose of 10 mg or less per day by week 20 and for 8 or more consecutive weeks. Post hoc exploratory end points included a prednisone dose of 10 mg or less per day for 24 or more weeks and the receipt of no prednisone during the treatment period, maintained until study completion.
We assessed the effects of the study drug on physical or psychological symptoms of the hypereosinophilic syndrome, health status, and limitations of daily living, using the Medical Outcomes Study 12-item Short Form General Health Survey (SF-12) (version 2) physical and mental component summary scores and the Rotterdam Symptom Checklist.
Safety
Safety was assessed with the use of adverse event reports, laboratory tests (clinical chemical and hematologic tests and urinalysis), electrocardiograms, physical examinations, and vital signs recorded both before and after infusion.
Statistical Analysis
We calculated that 84 patients who could be evaluated (42 per study group) would be required to provide a statistical power of 90%, at a two-sided significance level of 5%, to detect a difference of 33% between the two study groups in the percentage of patients in whom in the primary end point was reached (assuming the percentage of patients with a prednisone dose of ≤10 mg per day for ≥8 weeks was 80% in the mepolizumab group and 47% in the placebo group). Differences in the incidences of the primary end point were tested using a Cochran–Mantel–Haenszel test, with stratification according to the prednisone (or the equivalent) dose (≤30 mg or >30 mg) at baseline, at a 5% two-sided significance level in the intention-to-treat population. In the primary prespecified analysis, odds ratios were also calculated. Relative risks (without stratification on the basis of prednisone dose at baseline) and hazard ratios (with stratification) were also calculated in post-hoc analyses. The proportional-hazards assumption was assessed by inspection of the log–log survival curves.
Adverse events were also summarized. A log-rank test was used to compare the time to an adverse event between the two study groups, including data from patients who withdrew from the study.
An investigator advisory board, including the authors and the sponsor, designed the study, with scientific guidance from the Food and Drug Administration and the European Committee for Proprietary Medicinal Products. The sponsor was responsible for data collection and quality control and held the data but made them available, after ensuring confidentiality, to all the authors. All the authors analyzed and interpreted the data, wrote the manuscript, made the decision to publish, and vouch for the completeness and accuracy of the data.
Results
Baseline Characteristics
Of the 107 patients screened, 85 were randomly assigned to treatment with mepolizumab (43 patients) or placebo (42 patients). The majority of patients in the mepolizumab group (36 of 43 [84%]) completed the trial, as compared with only 15 of 42 (36%) in the placebo group (Figure 1B). The most common reason for withdrawal was lack of efficacy (5 of 43 patients [12%] receiving mepolizumab and 21 of 42 [50%] receiving placebo).
There were no significant differences in demographic or disease characteristics between the study groups at the time of randomization (Table 1). Of note, the mean duration of disease was more than 5 years, and the majority of patients (82%) reported at least one clinical manifestation of the hypereosinophilic syndrome.
View this table:
[in this window]
[in a new window]
Get Slide
Table 1. Baseline Demographic and Disease Characteristics in the Intention-to-Treat Population.
Efficacy
Prednisone-Sparing Effects
Overall, for 36 patients (84%) receiving mepolizumab and 18 (43%) receiving placebo, the prednisone dose was reduced to ≤10 mg per day for ≥8 consecutive weeks during the 36-week treatment period (primary end point) (hazard ratio, 2.90; 95% confidence interval [CI], 1.59 to 5.26; P<0.001) (Table 2 and Figure 2A). Similar results were obtained when the primary end point was analyzed for the modified per-protocol population of 78 patients (hazard ratio, 3.27; 95% CI, 1.73 to 6.18; P<0.001). A significant difference between the two study groups was also found for the subgroups of prednisone dose at baseline, being more pronounced among patients requiring more than 30 mg per day than among those requiring 30 mg or less per day (Table 2). In the placebo group, the primary end point was more likely to be reached among patients who had been receiving 30 mg or less of prednisone at baseline (17 of 30 patients [57%]) than among those who had been receiving more than 30 mg (1 of 12 [8%]). In contrast, in the mepolizumab group, 26 of the 30 patients (87%) who had been receiving 30 mg or less of prednisone at baseline were responders, as were 10 of 13 (77%) who had been receiving more than 30 mg.
View this table:
[in this window]
[in a new window]
Get Slide
Table 2. Effects of Treatment on Corticosteroid Use and Eosinophil Counts in the Intention-to-Treat Population.
Figure 2
View larger version (27K):
[in this window]
[in a new window]
Get Slide
Figure 2. Efficacy of Mepolizumab Treatment.
Panel A shows the percentage of patients in whom the prednisone dose was reduced to 10 mg or less per day (or the equivalent) for 8 or more consecutive weeks (the primary end point). Panel B shows the percentage of patients in whom the prednisone dose was reduced to 10 mg or less per day for 24 or more consecutive weeks. Panel C shows the percentage of patients in whom the blood eosinophil count was maintained at or below 600 per microliter for 8 or more consecutive weeks. Panel D shows the mean prednisone (or the equivalent) daily dose during the study. The last-observation-carried-forward (LOCF) data are those from the second infusion onward. Panel E is a Kaplan–Meier plot of the time to treatment failure (defined as clinical worsening requiring other therapy for the hypereosinophilic syndrome, a prednisone dose of >60 mg per day, or study withdrawal for any reason) in the intention-to-treat population. Panel F shows the mean serum eosinophil-derived neurotoxin (EDN) values. The I bars in Panels D and F indicate standard errors.
All secondary and exploratory efficacy end points significantly favored the use of mepolizumab (P<0.001) (Table 2 and Figure 2B). Figure 2D shows the mean prednisone dose used during the study. (Additional efficacy analyses, with stratification on the basis of achievement of the primary end point and status of study completion, are presented in Supplementary Appendix 3.)
Blood Eosinophil Counts and Eosinophil-Derived Neurotoxin Levels
A blood eosinophil count of less than 600 per microliter for 8 or more consecutive weeks was reached in 41 of the 43 patients (95%) receiving mepolizumab, as compared with 19 of the 42 (45%) receiving placebo (P<0.001; hazard ratio, 3.53; 95% CI, 1.94 to 6.45) (Table 2 and Figure 2C). The difference between the study groups for this end point was significant in both subgroups of baseline prednisone dose (≤30 mg and >30 mg). Mean serum eosinophil-derived neurotoxin levels were significantly different between the two study groups at all time points evaluated (P<0.001, P<0.001, and P=0.005 for reductions between the mepolizumab group and the placebo group at weeks 12, 24, and 36, respectively) (Figure 2F).
Time to Treatment Failure
The time to treatment failure (defined as the number of days to clinical worsening requiring other therapy for the hypereosinophilic syndrome or an increase in the prednisone dose to >60 mg per day) was significantly shorter in the placebo group than in the mepolizumab group (P<0.001 by the log-rank test). Nine of 43 patients (21%) receiving mepolizumab and 29 of 42 (69%) receiving placebo had treatment failure. The median time to treatment failure in the placebo group was 136.5 days (95% CI, 106 to 199; Figure 2E); corresponding data could not be calculated for mepolizumab, since less than half the patients receiving that drug had treatment failure.
Health Outcomes
No significant differences between treatments were observed in the changes from baseline in SF-12 physical and mental component summary scores (Table 2) or the Rotterdam Symptom Checklist (Supplementary Appendix 3).
Safety
The mean (±SD) duration of exposure to study drug (defined as the time between the first and last infusions) was greater in the mepolizumab group (6.7±1.9 months) than in the placebo group (4.3±2.6 months) because of a lower withdrawal rate. Despite the longer exposure to mepolizumab, adverse events were reported at similar rates in the two study groups: 40 of 43 patients (93%) receiving mepolizumab and 41 of 42 (98%) receiving placebo (Table 3). An adverse event considered by the investigator to be related to the study drug occurred in 16 of 43 patients (37%) in the mepolizumab group and in 12 of 42 (29%) in the placebo group (Table 3). One patient receiving mepolizumab and four receiving placebo had adverse events leading to withdrawal; none of these events were considered by the investigator to be related to study drug. No clinically relevant trends or major safety concerns emerged from evaluation of the laboratory tests, vital signs, or electrocardiographic results.
View this table:
[in this window]
[in a new window]
Get Slide
Table 3. Adverse Events Reported during the 36-Week Study.
Serious adverse events occurred in seven patients receiving mepolizumab (14 events, including one death) and five patients receiving placebo (7 events) (Table 3), but none were deemed by the investigator to be related to the study drug. Serious adverse events in the mepolizumab group were asthma, clinical flares of the hypereosinophilic syndrome, pneumonia, renal failure, bronchitis, cardiac arrest, dehydration, hepatitis, pancreatitis, pyrexia, rhinitis, and spinal compression fracture. Serious adverse events in the placebo group were clinical flares of the hypereosinophilic syndrome, pneumonia, dysesthesia, eosinophilia, nephrotic syndrome, osteonecrosis, and polyneuropathy. An 18-year-old man with severe hypereosinophilic syndrome and a history of multiple cardiovascular coexisting conditions died 110 days after his first mepolizumab infusion, and 26 days after his fourth and last infusion, from a cardiac arrest attributed to dysrhythmia and internal pacemaker–defibrillator failure. (Supplementary Appendixes 2 and 4 contain additional information about adverse events.)
Discussion
The hypereosinophilic syndrome is a potentially severe and debilitating multisystem disorder associated with considerable morbidity, in part due to the side effects of treatments currently used for it. We report evidence that corticosteroid-sparing is enabled by mepolizumab in patients negative for FIP1L1–PDGFRA with the hypereosinophilic syndrome. Treatment with prednisone, which could be discontinued until study completion, was able to be stopped during the study in almost 50% of patients receiving mepolizumab.
Mepolizumab also was significantly more effective than placebo at stabilizing blood eosinophil counts. These effects are clinically relevant, given that reducing eosinophil levels is currently the primary treatment goal for patients with the hypereosinophilic syndrome and that long-term corticosteroid therapy is associated with a range of undesirable side effects.26,27,28 Since the corticosteroid threshold associated with clinically significant toxic effects has been established at approximately 7.5 mg per day of prednisone equivalent,27 it is notable that a prednisone dose of 7.5 mg or less per day in this study was achieved in significantly more patients receiving mepolizumab than in those receiving placebo.
No significant differences were found between the two study groups in SF-12 (version 2) assessments, which may reflect the protocol requirements for disease to be clinically stable at baseline and for stability to be maintained in order for the patient to remain in the trial. As such, the quality of life, as measured by the SF-12 survey, did not deteriorate during the study period. In addition, the baseline mental-component summary score in the mepolizumab group was similar to that for the general U.S. population,25 indicating that with treatment, patients did not feel impaired by their disease, making it difficult to show an improvement. The study population was composed of relatively young patients who were negative for FIP1L1–PDGFRA and had long-standing corticosteroid-responsive hypereosinophilic syndrome. The corticosteroid-sparing effects observed in our study suggest that mepolizumab has substantial potential to reduce treatment-related morbidity. Because this study was limited to patients who were receiving corticosteroid therapy and whose hypereosinophilic syndrome was clinically well controlled, no recommendations can be inferred regarding the use of mepolizumab for patients with acute presentations or who have not yet received corticosteroid therapy. The same holds true for patients with the hypereosinophilic syndrome that is unresponsive to systemic corticosteroids, as well as those positive for FIP1L1–PDGFRA.29
Mean serum interleukin-5 values at baseline were below the limit of detection (7.8 pg per milliliter) in most patients (Table 1). Such normal serum interleukin-5 levels are probably due to corticosteroid-induced suppression, since patients' symptoms were stabilized by means of corticosteroid therapy before randomization. The efficacy of mepolizumab in patients with physiologic levels of interleukin-5 suggests that this agent should not be reserved for patients with elevated serum interleukin-5 levels. Our results provide evidence that endogenous interleukin-5 in these patients with the hypereosinophilic syndrome has a critical role in regulating peripheral eosinophilia.
Our study assessed the effects of mepolizumab administered monthly during a 36-week treatment period, whereas previous studies of mepolizumab evaluated 12 weeks of treatment.15,17,18,22,30 Several of these studies focused on the treatment of asthma, showing significant reductions in blood, sputum, and bronchial eosinophil counts and safety but limited efficacy as measured by pulmonary-function testing.15,16,17,18 Much remains to be learned about the relation between blood and tissue eosinophilia and clinical response to treatment in patients with asthma and the hypereosinophilic syndrome. Although the number of patients in our trial was small, the preliminary findings suggest that the likelihood of achieving the primary end point with the use of mepolizumab was high in the patients with current conditions related to the hypereosinophilic syndrome. The primary end point was reached in 17 of the 19 patients with respiratory disorders, 5 of the 5 with cardiac disorders, 8 of the 8 with gastrointestinal disorders, 5 of the 6 with musculoskeletal disorders, and 8 of the 9 with nervous-system disorders, although in only 11 of the 16 patients with skin or subcutaneous manifestations (Table 1, and Supplementary Appendix 5).
In theory, since interleukin-5 potently primes eosinophils for enhanced responsiveness to activating signals,6 anti–interleukin-5 may be particularly helpful for reducing the eosinophil-mediated end-organ pathologic characteristics typically associated with the hypereosinophilic syndrome. Tissue and vascular damage results in part from the release of granule proteins, and mepolizumab treatment was associated with significant reductions in eosinophil-derived neurotoxin levels in our study (Figure 2F). In addition, the chronic tissue damage associated with the hypereosinophilic syndrome is thought to be mediated by eosinophil infiltration, and mepolizumab probably decreases tissue eosinophil levels in patients with the syndrome.21,22
Adverse effects were found in the mepolizumab group. One patient receiving mepolizumab had a fatal cardiac arrest, which was not considered to be drug-related by the investigator, who was unaware of the group assignment. Adverse events considered drug-related by the investigator were similar between the mepolizumab group and the placebo group. This finding is noteworthy, since the duration of exposure to study drug was approximately 56% longer for mepolizumab than for placebo, owing to the greater dropout rate (because of lack of efficacy) in the placebo group. In addition, some adverse events in both groups may have resulted from prednisone withdrawal rather than use of the study drug.
An ongoing, open-label extension trial, involving 78 patients from the current trial, will provide long-term information on potential safety issues, efficacy assessments, and optimal dosing frequency (see Supplementary Appendix 4 for details). This trial will help address whether long-term treatment with mepolizumab will durably reduce eosinophil counts while controlling disease.
In conclusion, our study demonstrated that mepolizumab treatment enabled clinically significant reductions in corticosteroid dose, and often corticosteroid discontinuation, in patients negative for FIP1L1–PDGFRA who had the hypereosinophilic syndrome. This proof-of-concept study shows that administration of anti–interleukin-5 antibodies, an eosinophil-specific and targeted therapy, has a potential clinical benefit.
Supported by grants from GlaxoSmithKline, the National Institutes of Health (M01 RR00064 and AI61097, to Dr. Gleich, and MO1 RR001032, to the Beth Israel Deaconess Medical Center), U.S. Public Health Service General Clinical Research Center (M01 RR 08084, to the Cincinnati Children's Medical Center), and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases.
Dr. Rothenberg reports receiving lecture fees from Merck and consulting fees from GlaxoSmithKline, Ception Therapeutics, Merck, and Cambridge Antibody Technology and having equity interests in Ception Therapeutics. Drs. Roufosse and Kahn report receiving consulting fees from GlaxoSmithKline. Dr. Weller reports receiving consulting fees from GlaxoSmithKline, Medimmune, Genzyme, and Microbia. Dr. Simon reports receiving consulting fees from GlaxoSmithKline, Pfizer, and Novartis and grant support from GlaxoSmithKline. Dr. Schwartz reports receiving consulting fees from GlaxoSmithKline, Genentech, and Novartis; royalties from Phadia through Virginia Commonwealth University for tryptase immunoassay licensing rights; and grant support from GlaxoSmithKline, the Philip Morris Foundation, and Pharming. Dr. Rosenwasser reports receiving consulting fees from Abbott Laboratories, Alcon Laboratories, Regeneron, GlaxoSmithKline, Novartis, AstraZeneca, and Genentech and lecture fees from Alcon Laboratories, Genentech, and Novartis. Dr. Ring reports receiving consulting fees from Astellas, Novartis, GlaxoSmithKline, and Schering-Plough. Dr. Griffin reports having been an employee of GlaxoSmithKline. Ms. Haig, Mr. Frewer, and Dr. Parkin report having equity interests in and being employees of GlaxoSmithKline. Dr. Gleich reports receiving consulting fees from GlaxoSmithKline, Genentech, and Novartis; lecture fees from Novartis, Genentech, and Sepracor; royalties from the Mayo Clinic for discoveries and patents; grant support from Jerini, Novartis, and GlaxoSmithKline; and having equity interests in Ception. No other potential conflict of interest relevant to this article was reported.
We thank the members of the medical, nursing, and research staff at the trial centers for their invaluable contributions to this study, as well as Ellen Lewis, Ph.D., for assistance with preparation of a previous version of the manuscript.
* Members of the Mepolizumab Hypereosinophilic Syndrome (HES) Study Group are listed in the Appendix.
Source Information
From the Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati (M.E.R.); the National Institute of Allergy and Infectious Diseases, Bethesda, MD (A.D.K.); Service de Médecine Interne, Hôpital Erasme, Université Libre de Bruxelles, and the Institute for Medical Immunology, Gosselies, Belgium (F.E.R.); Service de Médecine Interne, Hôpital Foch, Suresnes, France (J.E.K.); Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (P.F.W.); the University of Bern, Bern, Switzerland (H.-U.S.); Virginia Commonwealth University, Richmond (L.B.S.); Children's Mercy Hospital, Kansas City, MO (L.J.R.); Technische Universität München, Munich, Germany (J.R.); Envision Pharma, Horsham, United Kingdom (E.F.G.); GlaxoSmithKline, King of Prussia, PA (A.E.H.); GlaxoSmithKline, Middlesex, United Kingdom (P.I.H.F., J.M.P.); and University of Utah School of Medicine, Salt Lake City (G.J.G.).
This article (10.1056/NEJMoa070812) was published at www.nejm.org on March 16, 2008. It will appear in the March 20 issue of the Journal.
Address reprint requests to Dr. Rothenberg at the Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital and Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, or at rothenberg@cchmc.org.
References
1. Klion AD, Bochner BS, Gleich GJ, et al. Approaches to the treatment of hypereosinophilic syndromes: a workshop summary report. J Allergy Clin Immunol 2006;117:1292-a-1302. [CrossRef][ISI][Medline]
2. Gleich GJ, Leiferman KM. The hypereosinophilic syndromes: still more heterogeneity. Curr Opin Immunol 2005;17:679-684. [CrossRef][ISI][Medline]
3. Roufosse F, Goldman M, Cogan E. Hypereosinophilic syndrome: lymphoproliferative and myeloproliferative variants. Semin Respir Crit Care Med 2006;27:158-170. [CrossRef][ISI][Medline]
4. Wilkins HJ, Crane MM, Copeland K, Williams WV. Hypereosinophilic syndrome: an update. Am J Hematol 2005;80:148-157. [CrossRef][ISI][Medline]
5. Kariyawasam HH, Robinson DS. The eosinophil: the cell and its weapons, the cytokines, its locations. Semin Respir Crit Care Med 2006;27:117-127. [CrossRef][ISI][Medline]
6. Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol 2006;24:147-174. [CrossRef][ISI][Medline]
7. Lopez AF, Sanderson CJ, Gamble JR, Campbell HD, Young IG, Vadas MA. Recombinant human interleukin 5 is a selective activator of human eosinophil function. J Exp Med 1988;167:219-224. [Free Full Text]
8. Clutterbuck EJ, Hirst EM, Sanderson CJ. Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF. Blood 1989;73:1504-1512. [Free Full Text]
9. Sanderson CJ. Interleukin-5, eosinophils, and disease. Blood 1992;79:3101-3109. [Free Full Text]
10. Simon D, Braathen LR, Simon H-U. Eosinophils and atopic dermatitis. Allergy 2004;59:561-570. [CrossRef][ISI][Medline]
11. Sutton SA, Assa'ad AH, Rothenberg ME. Anti-IL-5 and hypereosinophilic syndromes. Clin Immunol 2005;115:51-60. [CrossRef][ISI][Medline]
12. Schrezenmeier H, Thomé SD, Tewald F, Fleischer B, Raghavachar A. Interleukin-5 is the predominant eosinophilopoietin produced by cloned T lymphocytes in hypereosinophilic syndrome. Exp Hematol 1993;21:358-365. [ISI][Medline]
13. Cook R, Applebaum R, Cusimano D, et al. Biological and biophysical characteristics of SB 240563, a high affinity humanized monoclonal antibody to IL-5. Am J Crit Care Med 1998;157:A604.
14. Hart TK, Cook RM, Zia-Amirhosseini P, et al. Preclinical efficacy and safety of mepolizumab (SB-240563), a humanized monoclonal antibody to IL-5, in cynomolgus monkeys. J Allergy Clin Immunol 2001;108:250-257. [CrossRef][ISI][Medline]
15. Büttner C, Lun A, Splettstoesser T, Kunkel G, Renz H. Monoclonal anti-interleukin-5 treatment suppresses eosinophil but not T-cell functions. Eur Respir J 2003;21:799-803. [Free Full Text]
16. Leckie MJ, ten Brinke A, Khan J, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000;356:2144-2148. [CrossRef][ISI][Medline]
17. Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS. Eosinophil's role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med 2003;167:199-204. [Free Full Text]
18. Menzies-Gow A, Flood-Page P, Sehmi R, et al. Anti-IL-5 (mepolizumab) therapy induces bone marrow eosinophil maturational arrest and decreases eosinophil progenitors in the bronchial mucosa of atopic asthmatics. J Allergy Clin Immunol 2003;111:714-719. [CrossRef][ISI][Medline]
19. Oldhoff JM, Darsow U, Werfel T, et al. Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis. Allergy 2005;60:693-696. [CrossRef][ISI][Medline]
20. Koury MJ, Newman JH, Murray JJ. Reversal of hypereosinophilic syndrome and lymphomatoid papulosis with mepolizumab and imatinib. Am J Med 2003;115:587-589. [ISI][Medline]
21. Plötz SG, Simon H-U, Darsow U, et al. Use of an anti-interleukin-5 antibody in the hypereosinophilic syndrome with eosinophilic dermatitis. N Engl J Med 2003;349:2334-2339. [Free Full Text]
22. Garrett JK, Jameson SC, Thomson B, et al. Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol 2004;113:115-119. [CrossRef][ISI][Medline]
23. Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine (Baltimore) 1975;54:1-27. [Medline]
24. Pardanani A, Ketterling RP, Brockman SR, et al. CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy. Blood 2003;102:3093-3096. [Free Full Text]
25. Ware JE, Kosinski M, Keller SD. SF-12: how to score the SF-12 Physical and Mental Health Summary Scales. Boston: The Health Institute, New England Medical Center, 1995.
26. Stanbury RM, Graham EM. Systemic corticosteroid therapy -- side effects and their management. Br J Ophthalmol 1998;82:704-708. [Free Full Text]
27. Wei L, MacDonald TM, Walker BR. Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Ann Intern Med 2004;141:764-770. [Free Full Text]
28. Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids -- new mechanisms for old drugs. N Engl J Med 2005;353:1711-1723. [Free Full Text]
29. Klion AD, Law MA, Noel P, Kim YJ, Haverty TP, Nutman TB. Safety and efficacy of the monoclonal anti-interleukin-5 antibody SCH55700 in the treatment of patients with hypereosinophilic syndrome. Blood 2004;103:2939-2941. [Free Full Text]
30. Phipps S, Flood-Page P, Menzies-Gow A, Ong YE, Kay AB. Intravenous anti-IL-5 monoclonal antibody reduces eosinophils and tenascin deposition in allergen-challenged human atopic skin. J Invest Dermatol 2004;122:1406-1412. [CrossRef][ISI][Medline]
Appendix
In addition to the authors, the members of the Mepolizumab HES Study Group are as follows: Australia: Sir Charles Gairdner Hospital, Perth — A. Singh, D. Joske; Royal North Shore Hospital, Sydney — L. Coyle; Mater Adult Hospital, Brisbane — K. Taylor; Royal Melbourne Hospital, Melbourne — J. Szer; Belgium: University Hospital Gasthuisberg, Leuven — D. Blockmans, G. Verhoef; Canada: Royal Victoria Hospital, Montreal — W. Carey; McMaster University, Hamilton, ON — J. Denburg; Cancer Care Nova Scotia, Halifax, NS — A. Padmos; University of Toronto, Toronto — N. Shear; Winnipeg Clinic, Winnipeg, MB — V. Taraska; France: Hôpital Foch, Suresnes — O. Blétry; Claude-Huriez Hospital, Lille — P.-Y. Hatron; Germany: Hannover Medical School, Hannover — A. Ganser; Rheumaklinik Bad Bramstedt and Universitätsklinikum Schleswig-Holstein, Bad Bramstedt — W. Gross; Italy: L. and A. Seràgnoli, University of Bologna, Bologna — M. Baccarani; Switzerland: Dermatologische Universitätsklinik und Poliklinik, Inselspital Bern, Bern — L.R. Braathen; United States: Cincinnati Children's Hospital Medical Center, Cincinnati — A. Assa'ad; University of Wisconsin School of Medicine, Madison — W. Busse; Mayo Clinic, Rochester, MN — J. Butterfield; University of Utah Health Sciences Center, Salt Lake City — K. Leiferman; Vanderbilt University Medical Center, Nashville — J. Murray, D. Hagaman; University of California San Diego School of Medicine, San Diego — J. Ramsdell; Beth Israel Deaconess Medical Center, Boston — J. Sheikh; National Institutes of Health, Bethesda, MD — C.A. Talar-Williams; University of Texas M.D. Anderson Cancer Center, Houston — S. Verstovsek; National Jewish Medical and Research Center, Denver — R. Weber.
posted by stinkrock at 9:24 PM
0 comments
Intelligence
Saw this meme over at misanthrope's and I'd thought I'd give it a shot:
Oops. As an experiment, let me try posting the entire length of The Gettysburg Address and T.S. Eliot's "The Waste Land". I want to see if it affects my score.
Four score and seven years ago, our fathers brought forth upon this continent a new nation: conceived in liberty, and dedicated to the proposition that all men are created equal.
Now we are engaged in a great civil war. . .testing whether that nation, or any nation so conceived and so dedicated. . . can long endure. We are met on a great battlefield of that war.
We have come to dedicate a portion of that field as a final resting place for those who here gave their lives that that nation might live. It is altogether fitting and proper that we should do this.
But, in a larger sense, we cannot dedicate. . .we cannot consecrate. . . we cannot hallow this ground. The brave men, living and dead, who struggled here have consecrated it, far above our poor power to add or detract. The world will little note, nor long remember, what we say here, but it can never forget what they did here.
It is for us the living, rather, to be dedicated here to the unfinished work which they who fought here have thus far so nobly advanced. It is rather for us to be here dedicated to the great task remaining before us. . .that from these honored dead we take increased devotion to that cause for which they gave the last full measure of devotion. . . that we here highly resolve that these dead shall not have died in vain. . . that this nation, under God, shall have a new birth of freedom. . . and that government of the people. . .by the people. . .for the people. . . shall not perish from the earth.
------------------
To err is human, to deflower, divine.
------------------
The Waste Land
I. THE BURIAL OF THE DEAD
APRIL is the cruellest month, breeding
Lilacs out of the dead land, mixing
Memory and desire, stirring
Dull roots with spring rain.
Winter kept us warm, covering
Earth in forgetful snow, feeding
A little life with dried tubers.
Summer surprised us, coming over the Starnbergersee
With a shower of rain; we stopped in the colonnade,
And went on in sunlight, into the Hofgarten,
And drank coffee, and talked for an hour.
Bin gar keine Russin, stamm' aus Litauen, echt deutsch.
And when we were children, staying at the archduke's,
My cousin's, he took me out on a sled,
And I was frightened. He said, Marie,
Marie, hold on tight. And down we went.
In the mountains, there you feel free.
I read, much of the night, and go south in the winter.
What are the roots that clutch, what branches grow
Out of this stony rubbish? Son of man,
You cannot say, or guess, for you know only
A heap of broken images, where the sun beats,
And the dead tree gives no shelter, the cricket no relief,
And the dry stone no sound of water. Only
There is shadow under this red rock,
(Come in under the shadow of this red rock),
And I will show you something different from either
Your shadow at morning striding behind you
Or your shadow at evening rising to meet you;
I will show you fear in a handful of dust.
Frisch weht der Wind
Der Heimat zu.
Mein Irisch Kind,
Wo weilest du?
'You gave me hyacinths first a year ago;
'They called me the hyacinth girl.'
—Yet when we came back, late, from the Hyacinth garden,
Your arms full, and your hair wet, I could not
Speak, and my eyes failed, I was neither
Living nor dead, and I knew nothing,
Looking into the heart of light, the silence.
Od' und leer das Meer.
Madame Sosostris, famous clairvoyante,
Had a bad cold, nevertheless
Is known to be the wisest woman in Europe,
With a wicked pack of cards. Here, said she,
Is your card, the drowned Phoenician Sailor,
(Those are pearls that were his eyes. Look!)
Here is Belladonna, the Lady of the Rocks,
The lady of situations.
Here is the man with three staves, and here the Wheel,
And here is the one-eyed merchant, and this card,
Which is blank, is something he carries on his back,
Which I am forbidden to see. I do not find
The Hanged Man. Fear death by water.
I see crowds of people, walking round in a ring.
Thank you. If you see dear Mrs. Equitone,
Tell her I bring the horoscope myself:
One must be so careful these days.
Unreal City,
Under the brown fog of a winter dawn,
A crowd flowed over London Bridge, so many,
I had not thought death had undone so many.
Sighs, short and infrequent, were exhaled,
And each man fixed his eyes before his feet.
Flowed up the hill and down King William Street,
To where Saint Mary Woolnoth kept the hours
With a dead sound on the final stroke of nine.
There I saw one I knew, and stopped him, crying 'Stetson!
'You who were with me in the ships at Mylae!
'That corpse you planted last year in your garden,
'Has it begun to sprout? Will it bloom this year?
'Or has the sudden frost disturbed its bed?
'Oh keep the Dog far hence, that's friend to men,
'Or with his nails he'll dig it up again!
'You! hypocrite lecteur!—mon semblable,—mon frère!'
II. A GAME OF CHESS
THE Chair she sat in, like a burnished throne,
Glowed on the marble, where the glass
Held up by standards wrought with fruited vines
From which a golden Cupidon peeped out
(Another hid his eyes behind his wing)
Doubled the flames of sevenbranched candelabra
Reflecting light upon the table as
The glitter of her jewels rose to meet it,
From satin cases poured in rich profusion;
In vials of ivory and coloured glass
Unstoppered, lurked her strange synthetic perfumes,
Unguent, powdered, or liquid—troubled, confused
And drowned the sense in odours; stirred by the air
That freshened from the window, these ascended
In fattening the prolonged candle-flames,
Flung their smoke into the laquearia,
Stirring the pattern on the coffered ceiling.
Huge sea-wood fed with copper
Burned green and orange, framed by the coloured stone,
In which sad light a carvèd dolphin swam.
Above the antique mantel was displayed
As though a window gave upon the sylvan scene
The change of Philomel, by the barbarous king
So rudely forced; yet there the nightingale
Filled all the desert with inviolable voice
And still she cried, and still the world pursues,
'Jug Jug' to dirty ears.
And other withered stumps of time
Were told upon the walls; staring forms
Leaned out, leaning, hushing the room enclosed.
Footsteps shuffled on the stair.
Under the firelight, under the brush, her hair
Spread out in fiery points
Glowed into words, then would be savagely still.
'My nerves are bad to-night. Yes, bad. Stay with me.
'Speak to me. Why do you never speak? Speak.
'What are you thinking of? What thinking? What?
'I never know what you are thinking. Think.'
I think we are in rats' alley
Where the dead men lost their bones.
'What is that noise?'
The wind under the door.
'What is that noise now? What is the wind doing?'
Nothing again nothing.
'Do
'You know nothing? Do you see nothing? Do you remember
'Nothing?'
I remember
Those are pearls that were his eyes.
'Are you alive, or not? Is there nothing in your head?'
But
O O O O that Shakespeherian Rag—
It's so elegant
So intelligent
'What shall I do now? What shall I do?'
'I shall rush out as I am, and walk the street
'With my hair down, so. What shall we do to-morrow?
'What shall we ever do?'
The hot water at ten.
And if it rains, a closed car at four.
And we shall play a game of chess,
Pressing lidless eyes and waiting for a knock upon the door.
When Lil's husband got demobbed, I said—
I didn't mince my words, I said to her myself,
HURRY UP PLEASE IT'S TIME
Now Albert's coming back, make yourself a bit smart.
He'll want to know what you done with that money he gave you
To get yourself some teeth. He did, I was there.
You have them all out, Lil, and get a nice set,
He said, I swear, I can't bear to look at you.
And no more can't I, I said, and think of poor Albert,
He's been in the army four years, he wants a good time,
And if you don't give it him, there's others will, I said.
Oh is there, she said. Something o' that, I said.
Then I'll know who to thank, she said, and give me a straight look.
HURRY UP PLEASE IT'S TIME
If you don't like it you can get on with it, I said.
Others can pick and choose if you can't.
But if Albert makes off, it won't be for lack of telling.
You ought to be ashamed, I said, to look so antique.
(And her only thirty-one.)
I can't help it, she said, pulling a long face,
It's them pills I took, to bring it off, she said.
(She's had five already, and nearly died of young George.)
The chemist said it would be alright, but I've never been the same.
You are a proper fool, I said.
Well, if Albert won't leave you alone, there it is, I said,
What you get married for if you don't want children?
HURRY UP PLEASE IT'S TIME
Well, that Sunday Albert was home, they had a hot gammon,
And they asked me in to dinner, to get the beauty of it hot—
HURRY UP PLEASE IT'S TIME
HURRY UP PLEASE IT'S TIME
Goonight Bill. Goonight Lou. Goonight May. Goonight.
Ta ta. Goonight. Goonight.
Good night, ladies, good night, sweet ladies, good night, good night.
III. THE FIRE SERMON
THE river's tent is broken: the last fingers of leaf
Clutch and sink into the wet bank. The wind
Crosses the brown land, unheard. The nymphs are departed.
Sweet Thames, run softly, till I end my song.
The river bears no empty bottles, sandwich papers,
Silk handkerchiefs, cardboard boxes, cigarette ends
Or other testimony of summer nights. The nymphs are departed.
And their friends, the loitering heirs of city directors;
Departed, have left no addresses.
By the waters of Leman I sat down and wept...
Sweet Thames, run softly till I end my song,
Sweet Thames, run softly, for I speak not loud or long.
But at my back in a cold blast I hear
The rattle of the bones, and chuckle spread from ear to ear.
A rat crept softly through the vegetation
Dragging its slimy belly on the bank
While I was fishing in the dull canal
On a winter evening round behind the gashouse
Musing upon the king my brother's wreck
And on the king my father's death before him.
White bodies naked on the low damp ground
And bones cast in a little low dry garret,
Rattled by the rat's foot only, year to year.
But at my back from time to time I hear
The sound of horns and motors, which shall bring
Sweeney to Mrs. Porter in the spring.
O the moon shone bright on Mrs. Porter
And on her daughter
They wash their feet in soda water
Et, O ces voix d'enfants, chantant dans la coupole!
Twit twit twit
Jug jug jug jug jug jug
So rudely forc'd.
Tereu
Unreal City
Under the brown fog of a winter noon
Mr. Eugenides, the Smyrna merchant
Unshaven, with a pocket full of currants
C.i.f. London: documents at sight,
Asked me in demotic French
To luncheon at the Cannon Street Hotel
Followed by a weekend at the Metropole.
At the violet hour, when the eyes and back
Turn upward from the desk, when the human engine waits
Like a taxi throbbing waiting,
I Tiresias, though blind, throbbing between two lives,
Old man with wrinkled female breasts, can see
At the violet hour, the evening hour that strives
Homeward, and brings the sailor home from sea,
The typist home at teatime, clears her breakfast, lights
Her stove, and lays out food in tins.
Out of the window perilously spread
Her drying combinations touched by the sun's last rays,
On the divan are piled (at night her bed)
Stockings, slippers, camisoles, and stays.
I Tiresias, old man with wrinkled dugs
Perceived the scene, and foretold the rest—
I too awaited the expected guest.
He, the young man carbuncular, arrives,
A small house agent's clerk, with one bold stare,
One of the low on whom assurance sits
As a silk hat on a Bradford millionaire.
The time is now propitious, as he guesses,
The meal is ended, she is bored and tired,
Endeavours to engage her in caresses
Which still are unreproved, if undesired.
Flushed and decided, he assaults at once;
Exploring hands encounter no defence;
His vanity requires no response,
And makes a welcome of indifference.
(And I Tiresias have foresuffered all
Enacted on this same divan or bed;
I who have sat by Thebes below the wall
And walked among the lowest of the dead.)
Bestows on final patronising kiss,
And gropes his way, finding the stairs unlit...
She turns and looks a moment in the glass,
Hardly aware of her departed lover;
Her brain allows one half-formed thought to pass:
'Well now that's done: and I'm glad it's over.'
When lovely woman stoops to folly and
Paces about her room again, alone,
She smoothes her hair with automatic hand,
And puts a record on the gramophone.
'This music crept by me upon the waters'
And along the Strand, up Queen Victoria Street.
O City city, I can sometimes hear
Beside a public bar in Lower Thames Street,
The pleasant whining of a mandoline
And a clatter and a chatter from within
Where fishmen lounge at noon: where the walls
Of Magnus Martyr hold
Inexplicable splendour of Ionian white and gold.
The river sweats
Oil and tar
The barges drift
With the turning tide
Red sails
Wide
To leeward, swing on the heavy spar.
The barges wash
Drifting logs
Down Greenwich reach
Past the Isle of Dogs.
Weialala leia
Wallala leialala
Elizabeth and Leicester
Beating oars
The stern was formed
A gilded shell
Red and gold
The brisk swell
Rippled both shores
Southwest wind
Carried down stream
The peal of bells
White towers
Weialala leia
Wallala leialala
'Trams and dusty trees.
Highbury bore me. Richmond and Kew
Undid me. By Richmond I raised my knees
Supine on the floor of a narrow canoe.'
'My feet are at Moorgate, and my heart
Under my feet. After the event
He wept. He promised "a new start".
I made no comment. What should I resent?'
'On Margate Sands.
I can connect
Nothing with nothing.
The broken fingernails of dirty hands.
My people humble people who expect
Nothing.'
la la
To Carthage then I came
Burning burning burning burning
O Lord Thou pluckest me out
O Lord Thou pluckest
burning
IV. DEATH BY WATER
PHLEBAS the Phoenician, a fortnight dead,
Forgot the cry of gulls, and the deep seas swell
And the profit and loss.
A current under sea
Picked his bones in whispers. As he rose and fell
He passed the stages of his age and youth
Entering the whirlpool.
Gentile or Jew
O you who turn the wheel and look to windward,
Consider Phlebas, who was once handsome and tall as you.
V. WHAT THE THUNDER SAID
AFTER the torchlight red on sweaty faces
After the frosty silence in the gardens
After the agony in stony places
The shouting and the crying
Prison and place and reverberation
Of thunder of spring over distant mountains
He who was living is now dead
We who were living are now dying
With a little patience
Here is no water but only rock
Rock and no water and the sandy road
The road winding above among the mountains
Which are mountains of rock without water
If there were water we should stop and drink
Amongst the rock one cannot stop or think
Sweat is dry and feet are in the sand
If there were only water amongst the rock
Dead mountain mouth of carious teeth that cannot spit
Here one can neither stand nor lie nor sit
There is not even silence in the mountains
But dry sterile thunder without rain
There is not even solitude in the mountains
But red sullen faces sneer and snarl
From doors of mudcracked houses
If there were water
And no rock
If there were rock
And also water
And water
A spring
A pool among the rock
If there were the sound of water only
Not the cicada
And dry grass singing
But sound of water over a rock
Where the hermit-thrush sings in the pine trees
Drip drop drip drop drop drop drop
But there is no water
Who is the third who walks always beside you?
When I count, there are only you and I together
But when I look ahead up the white road
There is always another one walking beside you
Gliding wrapt in a brown mantle, hooded
I do not know whether a man or a woman
—But who is that on the other side of you?
What is that sound high in the air
Murmur of maternal lamentation
Who are those hooded hordes swarming
Over endless plains, stumbling in cracked earth
Ringed by the flat horizon only
What is the city over the mountains
Cracks and reforms and bursts in the violet air
Falling towers
Jerusalem Athens Alexandria
Vienna London
Unreal
A woman drew her long black hair out tight
And fiddled whisper music on those strings
And bats with baby faces in the violet light
Whistled, and beat their wings
And crawled head downward down a blackened wall
And upside down in air were towers
Tolling reminiscent bells, that kept the hours
And voices singing out of empty cisterns and exhausted wells.
In this decayed hole among the mountains
In the faint moonlight, the grass is singing
Over the tumbled graves, about the chapel
There is the empty chapel, only the wind's home.
It has no windows, and the door swings,
Dry bones can harm no one.
Only a cock stood on the rooftree
Co co rico co co rico
In a flash of lightning. Then a damp gust
Bringing rain
Ganga was sunken, and the limp leaves
Waited for rain, while the black clouds
Gathered far distant, over Himavant.
The jungle crouched, humped in silence.
Then spoke the thunder
D A
Datta: what have we given?
My friend, blood shaking my heart
The awful daring of a moment's surrender
Which an age of prudence can never retract
By this, and this only, we have existed
Which is not to be found in our obituaries
Or in memories draped by the beneficent spider
Or under seals broken by the lean solicitor
In our empty rooms
D A
Dayadhvam: I have heard the key
Turn in the door once and turn once only
We think of the key, each in his prison
Thinking of the key, each confirms a prison
Only at nightfall, aetherial rumours
Revive for a moment a broken Coriolanus
D A
Damyata: The boat responded
Gaily, to the hand expert with sail and oar
The sea was calm, your heart would have responded
Gaily, when invited, beating obedient
To controlling hands
I sat upon the shore
Fishing, with the arid plain behind me
Shall I at least set my lands in order?
London Bridge is falling down falling down falling down
Poi s'ascose nel foco che gli affina
Quando fiam ceu chelidon—O swallow swallow
Le Prince d'Aquitaine à la tour abolie
These fragments I have shored against my ruins
Why then Ile fit you. Hieronymo's mad againe.
Datta. Dayadhvam. Damyata.
Shantih shantih shantih
--------------
Ok, let's see if that helps.
Oops. As an experiment, let me try posting the entire length of The Gettysburg Address and T.S. Eliot's "The Waste Land". I want to see if it affects my score.
Four score and seven years ago, our fathers brought forth upon this continent a new nation: conceived in liberty, and dedicated to the proposition that all men are created equal.
Now we are engaged in a great civil war. . .testing whether that nation, or any nation so conceived and so dedicated. . . can long endure. We are met on a great battlefield of that war.
We have come to dedicate a portion of that field as a final resting place for those who here gave their lives that that nation might live. It is altogether fitting and proper that we should do this.
But, in a larger sense, we cannot dedicate. . .we cannot consecrate. . . we cannot hallow this ground. The brave men, living and dead, who struggled here have consecrated it, far above our poor power to add or detract. The world will little note, nor long remember, what we say here, but it can never forget what they did here.
It is for us the living, rather, to be dedicated here to the unfinished work which they who fought here have thus far so nobly advanced. It is rather for us to be here dedicated to the great task remaining before us. . .that from these honored dead we take increased devotion to that cause for which they gave the last full measure of devotion. . . that we here highly resolve that these dead shall not have died in vain. . . that this nation, under God, shall have a new birth of freedom. . . and that government of the people. . .by the people. . .for the people. . . shall not perish from the earth.
------------------
To err is human, to deflower, divine.
------------------
The Waste Land
I. THE BURIAL OF THE DEAD
APRIL is the cruellest month, breeding
Lilacs out of the dead land, mixing
Memory and desire, stirring
Dull roots with spring rain.
Winter kept us warm, covering
Earth in forgetful snow, feeding
A little life with dried tubers.
Summer surprised us, coming over the Starnbergersee
With a shower of rain; we stopped in the colonnade,
And went on in sunlight, into the Hofgarten,
And drank coffee, and talked for an hour.
Bin gar keine Russin, stamm' aus Litauen, echt deutsch.
And when we were children, staying at the archduke's,
My cousin's, he took me out on a sled,
And I was frightened. He said, Marie,
Marie, hold on tight. And down we went.
In the mountains, there you feel free.
I read, much of the night, and go south in the winter.
What are the roots that clutch, what branches grow
Out of this stony rubbish? Son of man,
You cannot say, or guess, for you know only
A heap of broken images, where the sun beats,
And the dead tree gives no shelter, the cricket no relief,
And the dry stone no sound of water. Only
There is shadow under this red rock,
(Come in under the shadow of this red rock),
And I will show you something different from either
Your shadow at morning striding behind you
Or your shadow at evening rising to meet you;
I will show you fear in a handful of dust.
Frisch weht der Wind
Der Heimat zu.
Mein Irisch Kind,
Wo weilest du?
'You gave me hyacinths first a year ago;
'They called me the hyacinth girl.'
—Yet when we came back, late, from the Hyacinth garden,
Your arms full, and your hair wet, I could not
Speak, and my eyes failed, I was neither
Living nor dead, and I knew nothing,
Looking into the heart of light, the silence.
Od' und leer das Meer.
Madame Sosostris, famous clairvoyante,
Had a bad cold, nevertheless
Is known to be the wisest woman in Europe,
With a wicked pack of cards. Here, said she,
Is your card, the drowned Phoenician Sailor,
(Those are pearls that were his eyes. Look!)
Here is Belladonna, the Lady of the Rocks,
The lady of situations.
Here is the man with three staves, and here the Wheel,
And here is the one-eyed merchant, and this card,
Which is blank, is something he carries on his back,
Which I am forbidden to see. I do not find
The Hanged Man. Fear death by water.
I see crowds of people, walking round in a ring.
Thank you. If you see dear Mrs. Equitone,
Tell her I bring the horoscope myself:
One must be so careful these days.
Unreal City,
Under the brown fog of a winter dawn,
A crowd flowed over London Bridge, so many,
I had not thought death had undone so many.
Sighs, short and infrequent, were exhaled,
And each man fixed his eyes before his feet.
Flowed up the hill and down King William Street,
To where Saint Mary Woolnoth kept the hours
With a dead sound on the final stroke of nine.
There I saw one I knew, and stopped him, crying 'Stetson!
'You who were with me in the ships at Mylae!
'That corpse you planted last year in your garden,
'Has it begun to sprout? Will it bloom this year?
'Or has the sudden frost disturbed its bed?
'Oh keep the Dog far hence, that's friend to men,
'Or with his nails he'll dig it up again!
'You! hypocrite lecteur!—mon semblable,—mon frère!'
II. A GAME OF CHESS
THE Chair she sat in, like a burnished throne,
Glowed on the marble, where the glass
Held up by standards wrought with fruited vines
From which a golden Cupidon peeped out
(Another hid his eyes behind his wing)
Doubled the flames of sevenbranched candelabra
Reflecting light upon the table as
The glitter of her jewels rose to meet it,
From satin cases poured in rich profusion;
In vials of ivory and coloured glass
Unstoppered, lurked her strange synthetic perfumes,
Unguent, powdered, or liquid—troubled, confused
And drowned the sense in odours; stirred by the air
That freshened from the window, these ascended
In fattening the prolonged candle-flames,
Flung their smoke into the laquearia,
Stirring the pattern on the coffered ceiling.
Huge sea-wood fed with copper
Burned green and orange, framed by the coloured stone,
In which sad light a carvèd dolphin swam.
Above the antique mantel was displayed
As though a window gave upon the sylvan scene
The change of Philomel, by the barbarous king
So rudely forced; yet there the nightingale
Filled all the desert with inviolable voice
And still she cried, and still the world pursues,
'Jug Jug' to dirty ears.
And other withered stumps of time
Were told upon the walls; staring forms
Leaned out, leaning, hushing the room enclosed.
Footsteps shuffled on the stair.
Under the firelight, under the brush, her hair
Spread out in fiery points
Glowed into words, then would be savagely still.
'My nerves are bad to-night. Yes, bad. Stay with me.
'Speak to me. Why do you never speak? Speak.
'What are you thinking of? What thinking? What?
'I never know what you are thinking. Think.'
I think we are in rats' alley
Where the dead men lost their bones.
'What is that noise?'
The wind under the door.
'What is that noise now? What is the wind doing?'
Nothing again nothing.
'Do
'You know nothing? Do you see nothing? Do you remember
'Nothing?'
I remember
Those are pearls that were his eyes.
'Are you alive, or not? Is there nothing in your head?'
But
O O O O that Shakespeherian Rag—
It's so elegant
So intelligent
'What shall I do now? What shall I do?'
'I shall rush out as I am, and walk the street
'With my hair down, so. What shall we do to-morrow?
'What shall we ever do?'
The hot water at ten.
And if it rains, a closed car at four.
And we shall play a game of chess,
Pressing lidless eyes and waiting for a knock upon the door.
When Lil's husband got demobbed, I said—
I didn't mince my words, I said to her myself,
HURRY UP PLEASE IT'S TIME
Now Albert's coming back, make yourself a bit smart.
He'll want to know what you done with that money he gave you
To get yourself some teeth. He did, I was there.
You have them all out, Lil, and get a nice set,
He said, I swear, I can't bear to look at you.
And no more can't I, I said, and think of poor Albert,
He's been in the army four years, he wants a good time,
And if you don't give it him, there's others will, I said.
Oh is there, she said. Something o' that, I said.
Then I'll know who to thank, she said, and give me a straight look.
HURRY UP PLEASE IT'S TIME
If you don't like it you can get on with it, I said.
Others can pick and choose if you can't.
But if Albert makes off, it won't be for lack of telling.
You ought to be ashamed, I said, to look so antique.
(And her only thirty-one.)
I can't help it, she said, pulling a long face,
It's them pills I took, to bring it off, she said.
(She's had five already, and nearly died of young George.)
The chemist said it would be alright, but I've never been the same.
You are a proper fool, I said.
Well, if Albert won't leave you alone, there it is, I said,
What you get married for if you don't want children?
HURRY UP PLEASE IT'S TIME
Well, that Sunday Albert was home, they had a hot gammon,
And they asked me in to dinner, to get the beauty of it hot—
HURRY UP PLEASE IT'S TIME
HURRY UP PLEASE IT'S TIME
Goonight Bill. Goonight Lou. Goonight May. Goonight.
Ta ta. Goonight. Goonight.
Good night, ladies, good night, sweet ladies, good night, good night.
III. THE FIRE SERMON
THE river's tent is broken: the last fingers of leaf
Clutch and sink into the wet bank. The wind
Crosses the brown land, unheard. The nymphs are departed.
Sweet Thames, run softly, till I end my song.
The river bears no empty bottles, sandwich papers,
Silk handkerchiefs, cardboard boxes, cigarette ends
Or other testimony of summer nights. The nymphs are departed.
And their friends, the loitering heirs of city directors;
Departed, have left no addresses.
By the waters of Leman I sat down and wept...
Sweet Thames, run softly till I end my song,
Sweet Thames, run softly, for I speak not loud or long.
But at my back in a cold blast I hear
The rattle of the bones, and chuckle spread from ear to ear.
A rat crept softly through the vegetation
Dragging its slimy belly on the bank
While I was fishing in the dull canal
On a winter evening round behind the gashouse
Musing upon the king my brother's wreck
And on the king my father's death before him.
White bodies naked on the low damp ground
And bones cast in a little low dry garret,
Rattled by the rat's foot only, year to year.
But at my back from time to time I hear
The sound of horns and motors, which shall bring
Sweeney to Mrs. Porter in the spring.
O the moon shone bright on Mrs. Porter
And on her daughter
They wash their feet in soda water
Et, O ces voix d'enfants, chantant dans la coupole!
Twit twit twit
Jug jug jug jug jug jug
So rudely forc'd.
Tereu
Unreal City
Under the brown fog of a winter noon
Mr. Eugenides, the Smyrna merchant
Unshaven, with a pocket full of currants
C.i.f. London: documents at sight,
Asked me in demotic French
To luncheon at the Cannon Street Hotel
Followed by a weekend at the Metropole.
At the violet hour, when the eyes and back
Turn upward from the desk, when the human engine waits
Like a taxi throbbing waiting,
I Tiresias, though blind, throbbing between two lives,
Old man with wrinkled female breasts, can see
At the violet hour, the evening hour that strives
Homeward, and brings the sailor home from sea,
The typist home at teatime, clears her breakfast, lights
Her stove, and lays out food in tins.
Out of the window perilously spread
Her drying combinations touched by the sun's last rays,
On the divan are piled (at night her bed)
Stockings, slippers, camisoles, and stays.
I Tiresias, old man with wrinkled dugs
Perceived the scene, and foretold the rest—
I too awaited the expected guest.
He, the young man carbuncular, arrives,
A small house agent's clerk, with one bold stare,
One of the low on whom assurance sits
As a silk hat on a Bradford millionaire.
The time is now propitious, as he guesses,
The meal is ended, she is bored and tired,
Endeavours to engage her in caresses
Which still are unreproved, if undesired.
Flushed and decided, he assaults at once;
Exploring hands encounter no defence;
His vanity requires no response,
And makes a welcome of indifference.
(And I Tiresias have foresuffered all
Enacted on this same divan or bed;
I who have sat by Thebes below the wall
And walked among the lowest of the dead.)
Bestows on final patronising kiss,
And gropes his way, finding the stairs unlit...
She turns and looks a moment in the glass,
Hardly aware of her departed lover;
Her brain allows one half-formed thought to pass:
'Well now that's done: and I'm glad it's over.'
When lovely woman stoops to folly and
Paces about her room again, alone,
She smoothes her hair with automatic hand,
And puts a record on the gramophone.
'This music crept by me upon the waters'
And along the Strand, up Queen Victoria Street.
O City city, I can sometimes hear
Beside a public bar in Lower Thames Street,
The pleasant whining of a mandoline
And a clatter and a chatter from within
Where fishmen lounge at noon: where the walls
Of Magnus Martyr hold
Inexplicable splendour of Ionian white and gold.
The river sweats
Oil and tar
The barges drift
With the turning tide
Red sails
Wide
To leeward, swing on the heavy spar.
The barges wash
Drifting logs
Down Greenwich reach
Past the Isle of Dogs.
Weialala leia
Wallala leialala
Elizabeth and Leicester
Beating oars
The stern was formed
A gilded shell
Red and gold
The brisk swell
Rippled both shores
Southwest wind
Carried down stream
The peal of bells
White towers
Weialala leia
Wallala leialala
'Trams and dusty trees.
Highbury bore me. Richmond and Kew
Undid me. By Richmond I raised my knees
Supine on the floor of a narrow canoe.'
'My feet are at Moorgate, and my heart
Under my feet. After the event
He wept. He promised "a new start".
I made no comment. What should I resent?'
'On Margate Sands.
I can connect
Nothing with nothing.
The broken fingernails of dirty hands.
My people humble people who expect
Nothing.'
la la
To Carthage then I came
Burning burning burning burning
O Lord Thou pluckest me out
O Lord Thou pluckest
burning
IV. DEATH BY WATER
PHLEBAS the Phoenician, a fortnight dead,
Forgot the cry of gulls, and the deep seas swell
And the profit and loss.
A current under sea
Picked his bones in whispers. As he rose and fell
He passed the stages of his age and youth
Entering the whirlpool.
Gentile or Jew
O you who turn the wheel and look to windward,
Consider Phlebas, who was once handsome and tall as you.
V. WHAT THE THUNDER SAID
AFTER the torchlight red on sweaty faces
After the frosty silence in the gardens
After the agony in stony places
The shouting and the crying
Prison and place and reverberation
Of thunder of spring over distant mountains
He who was living is now dead
We who were living are now dying
With a little patience
Here is no water but only rock
Rock and no water and the sandy road
The road winding above among the mountains
Which are mountains of rock without water
If there were water we should stop and drink
Amongst the rock one cannot stop or think
Sweat is dry and feet are in the sand
If there were only water amongst the rock
Dead mountain mouth of carious teeth that cannot spit
Here one can neither stand nor lie nor sit
There is not even silence in the mountains
But dry sterile thunder without rain
There is not even solitude in the mountains
But red sullen faces sneer and snarl
From doors of mudcracked houses
If there were water
And no rock
If there were rock
And also water
And water
A spring
A pool among the rock
If there were the sound of water only
Not the cicada
And dry grass singing
But sound of water over a rock
Where the hermit-thrush sings in the pine trees
Drip drop drip drop drop drop drop
But there is no water
Who is the third who walks always beside you?
When I count, there are only you and I together
But when I look ahead up the white road
There is always another one walking beside you
Gliding wrapt in a brown mantle, hooded
I do not know whether a man or a woman
—But who is that on the other side of you?
What is that sound high in the air
Murmur of maternal lamentation
Who are those hooded hordes swarming
Over endless plains, stumbling in cracked earth
Ringed by the flat horizon only
What is the city over the mountains
Cracks and reforms and bursts in the violet air
Falling towers
Jerusalem Athens Alexandria
Vienna London
Unreal
A woman drew her long black hair out tight
And fiddled whisper music on those strings
And bats with baby faces in the violet light
Whistled, and beat their wings
And crawled head downward down a blackened wall
And upside down in air were towers
Tolling reminiscent bells, that kept the hours
And voices singing out of empty cisterns and exhausted wells.
In this decayed hole among the mountains
In the faint moonlight, the grass is singing
Over the tumbled graves, about the chapel
There is the empty chapel, only the wind's home.
It has no windows, and the door swings,
Dry bones can harm no one.
Only a cock stood on the rooftree
Co co rico co co rico
In a flash of lightning. Then a damp gust
Bringing rain
Ganga was sunken, and the limp leaves
Waited for rain, while the black clouds
Gathered far distant, over Himavant.
The jungle crouched, humped in silence.
Then spoke the thunder
D A
Datta: what have we given?
My friend, blood shaking my heart
The awful daring of a moment's surrender
Which an age of prudence can never retract
By this, and this only, we have existed
Which is not to be found in our obituaries
Or in memories draped by the beneficent spider
Or under seals broken by the lean solicitor
In our empty rooms
D A
Dayadhvam: I have heard the key
Turn in the door once and turn once only
We think of the key, each in his prison
Thinking of the key, each confirms a prison
Only at nightfall, aetherial rumours
Revive for a moment a broken Coriolanus
D A
Damyata: The boat responded
Gaily, to the hand expert with sail and oar
The sea was calm, your heart would have responded
Gaily, when invited, beating obedient
To controlling hands
I sat upon the shore
Fishing, with the arid plain behind me
Shall I at least set my lands in order?
London Bridge is falling down falling down falling down
Poi s'ascose nel foco che gli affina
Quando fiam ceu chelidon—O swallow swallow
Le Prince d'Aquitaine à la tour abolie
These fragments I have shored against my ruins
Why then Ile fit you. Hieronymo's mad againe.
Datta. Dayadhvam. Damyata.
Shantih shantih shantih
--------------
Ok, let's see if that helps.
posted by stinkrock at 9:14 PM
2 comments
13 March 2008
POLITICS
Since I went political a few minutes ago, let me go topical-political.
Eliot Spitzer has resigned as the governor of New York State. His replacement is a blind African-American man. I don't follow the news closely, but is it Stevie Wonder? Because that would rock.
Let me, Stinkrock, just say this--Eliot Spitzer is a fraud and a prick. And he's going to lose his marriage, and a lot of money in that settlement.
But here's the good news. Eliot Spitzer is loaded. *Lo-oaded*. He can pay his rightfully pissed-off wife whatever she asks for in reparations & alimony & whatnot.
But after that? Oh, you guessed it--then he can get right back to that hot DC paid-lady '70s salad. Orange jello and mandarin oranges, people. The catbird seat.
You go, Eliot! Politicians are people on the prowl, people to watch!
Eliot Spitzer has resigned as the governor of New York State. His replacement is a blind African-American man. I don't follow the news closely, but is it Stevie Wonder? Because that would rock.
Let me, Stinkrock, just say this--Eliot Spitzer is a fraud and a prick. And he's going to lose his marriage, and a lot of money in that settlement.
But here's the good news. Eliot Spitzer is loaded. *Lo-oaded*. He can pay his rightfully pissed-off wife whatever she asks for in reparations & alimony & whatnot.
But after that? Oh, you guessed it--then he can get right back to that hot DC paid-lady '70s salad. Orange jello and mandarin oranges, people. The catbird seat.
You go, Eliot! Politicians are people on the prowl, people to watch!
posted by stinkrock at 1:26 AM
2 comments
#2 In the Movie Characters I Want to Be
Elvis Presley. The only baby in history to kill his twin to get more play. Have you seen the babies in those movies? They race cars and go to pool parties. Am I right?
Here's a new Kennedy assassination theory: 'Suspicious Minds' travelled 6 years back in time and killed JFK.
Think about it: Elvis became a Nixon shill in his Liberacepepperoni period. When did Nixon become President? 1969. When did Suspicious Minds come out? 1969. Do the math, punks.
In 1960, when Nixon got his election stolen in Chicago because a nation of Americans wanted a president who could bed Marilyn Monroe, where was Suspicious Minds? If you know a lick about Nixon, you know that song could've won him that election. Checkers was still alive, man. Checkers was still alive!
So Nixon plotted his revenge. He invented time travel. And when he finally got the swivel chair in the Oval Office (dizzy!) he put his plan in motion.
Suspicious Minds belongs in a time vault. Nowhere in the annals of pop music exists a song so glorious, and so horribly wrong for so many reasons. Again, if you know a lick about Nixon, I don't have to explain this to you.
Where were you when Tricky Dick tricked time?
.
.
.
John F. Kennedy was in a car in Dallas, Texas. He was hit by a bullet - "Suspicious Minds", 7 years from the future, lodged carefully in his skull. Elvis, we never knew you. If I had a dime for every ass you grabbed...
Here's a new Kennedy assassination theory: 'Suspicious Minds' travelled 6 years back in time and killed JFK.
Think about it: Elvis became a Nixon shill in his Liberacepepperoni period. When did Nixon become President? 1969. When did Suspicious Minds come out? 1969. Do the math, punks.
In 1960, when Nixon got his election stolen in Chicago because a nation of Americans wanted a president who could bed Marilyn Monroe, where was Suspicious Minds? If you know a lick about Nixon, you know that song could've won him that election. Checkers was still alive, man. Checkers was still alive!
So Nixon plotted his revenge. He invented time travel. And when he finally got the swivel chair in the Oval Office (dizzy!) he put his plan in motion.
Suspicious Minds belongs in a time vault. Nowhere in the annals of pop music exists a song so glorious, and so horribly wrong for so many reasons. Again, if you know a lick about Nixon, I don't have to explain this to you.
Where were you when Tricky Dick tricked time?
.
.
.
John F. Kennedy was in a car in Dallas, Texas. He was hit by a bullet - "Suspicious Minds", 7 years from the future, lodged carefully in his skull. Elvis, we never knew you. If I had a dime for every ass you grabbed...
posted by stinkrock at 12:57 AM
0 comments
11 March 2008
DFACTOR
My very good friend over at Waved Rumor is leaving New York because we finally got a restraining order against him. As one of favorite working rock bands The Constantines put it, soon enough work and love will make a man out of you. This is a tribute.
Last Friday, Dave played a farewell show at Pianos to an adoring crowd of friends and lovers, playing a bunch of the great songs he's written over the last 10 years, and mixing them in with cover songs from bands who have propelled him forth.
Listening to them on Friday night, I realized how uncanny Dave is at writing songs in the present tense. His songs are calendar dates on my timeline here. They capture moments. For every song I heard a song and my memory countered with a story.
It was a special show because a number of guys who had played with Dave at some point in their lives joined him onstage to toss off a song. And as I looked around the room I realized how many people are addicted to his energy, his momentum, and his melodies. It was a party.
--------------------
I've always bugged Dfactor to put out a compilation of his catchiest songs, (because everyone who witnessed the glory that is 'Sizzlin' Sun' on Friday is not necessarily going to want to listen to 'Light Up the Whippets', which is a science experiment gone wrong if applied to whipped cream canisters, and a downright crime if applied to doggies.) But if he writes from his gut and heart the way he has since I've met him, then all is good.
Everyone who's been touched by Dave in his New York stay will miss him, and I stand proud in that formation. The Trouble Dolls are playing out tonight. Good luck, Dfactor. With much love.
Last Friday, Dave played a farewell show at Pianos to an adoring crowd of friends and lovers, playing a bunch of the great songs he's written over the last 10 years, and mixing them in with cover songs from bands who have propelled him forth.
Listening to them on Friday night, I realized how uncanny Dave is at writing songs in the present tense. His songs are calendar dates on my timeline here. They capture moments. For every song I heard a song and my memory countered with a story.
It was a special show because a number of guys who had played with Dave at some point in their lives joined him onstage to toss off a song. And as I looked around the room I realized how many people are addicted to his energy, his momentum, and his melodies. It was a party.
--------------------
I've always bugged Dfactor to put out a compilation of his catchiest songs, (because everyone who witnessed the glory that is 'Sizzlin' Sun' on Friday is not necessarily going to want to listen to 'Light Up the Whippets', which is a science experiment gone wrong if applied to whipped cream canisters, and a downright crime if applied to doggies.) But if he writes from his gut and heart the way he has since I've met him, then all is good.
Everyone who's been touched by Dave in his New York stay will miss him, and I stand proud in that formation. The Trouble Dolls are playing out tonight. Good luck, Dfactor. With much love.
posted by stinkrock at 9:31 PM
3 comments
03 March 2008
HOME
I realize the East Village of Manhattan has not realized its potential. How could skater kids afford such alluring haircuts if it had?
And as I pump carbon dioxide out of my lungs here in the 4th floor of the wreckage, I've gotta say: I don't miss the Ramones. I don't miss CBGB. I miss you.
New York is famous for chewing people up and spitting them out. Who's fighting? Who's kicking New York in the teeth?
And as I pump carbon dioxide out of my lungs here in the 4th floor of the wreckage, I've gotta say: I don't miss the Ramones. I don't miss CBGB. I miss you.
New York is famous for chewing people up and spitting them out. Who's fighting? Who's kicking New York in the teeth?
posted by stinkrock at 10:46 PM
1 comments
Links
- BANDS/MUSIC
- Strikes Again!
- Strikes Again! Myspace page
- Microdot
- Record Robot
- FRIENDS
- Thoughts from a room with no windows
- Savage Distortion
- Travelers Diagram
- Waved Rumor
- OTHER SITES
- Smoke and Mirrors studio
- Via Skyway studio
- NY1
Previous Posts
- RIP Richard Wright
- McCarren Pool
- Dangerousness
- Microdot
- Skybox
- A Meme
- Corporate Rock *still* sucks
- New Pornographers
- Also (plug)
- Walt Mink
Archives
- October 2005
- November 2005
- December 2005
- January 2006
- February 2006
- March 2006
- April 2006
- May 2006
- June 2006
- July 2006
- August 2006
- November 2006
- December 2006
- January 2007
- February 2007
- August 2007
- October 2007
- December 2007
- January 2008
- February 2008
- March 2008
- May 2008
- June 2008
- July 2008
- August 2008
- September 2008
