text:
PCSExponent wrote:...At any rate, I have to agree with what you posted some years back (or was it flump? it's easy to distinguish between you 2 while reading your posts, but after data assimilation, all you 2 ever post runs into a single mental file under "muflmp") - we should skip all the "meddling" and award all golds in 100m & 200m from 1997 onwards to DF.
All gold medals? I sense their frustration [and their gift of hyperbole] but that's overkill. It has been mentioned on this thread already and it bears repeating, I SWEAR FOR NO (WO)MAN! However, I do think the biggest losers are American athletes - who because of American sprint depth - have to walk away from the sport because they don't have the $$ to properly develop; couldn't get the lane in Europe or the contract with the shoe company when they don't make a team.
Back to the immediate ramifications of the thread...if this is like last few years, then USADA will announce 2 - 3 more disqualifications before World Champs with the last being within a month of the Daegu Opening Ceremonies.

subset: commoncrawl


text:
Amura Japanese Restaurant, Lake Mary
Below are pictures and videos. Select what you want to view below.
Explore the Lake Mary, Florida Travel Guide
Popular Hotels
La Quinta Inn & Suites Orlando Lake Mary
Extended Stay America-Orlando-Lake Mary-1036 Greenwood Blvd
Hampton Inn & Suites Lake Mary At Colonial Townpark
Extended Stay America-Orlando-Lake Mary-1040 Greenwood Blvd
The Westin Lake Mary Orlando North
Popular Attractions


text:
- Activism's slippery slope: Anonymous targets children's hospital
- New iPad rumor rollup for week ending April 23
- Apple users put at risk by 3-week delay between OS X and iOS patches, researchers say
- Tip of the Hat: Heartbleed prompts chastened tech giants to fund OpenSSL
- 'Francophoned' cybertheft operation reportedly back in action
Consolidating Server and Network Equipment in Legacy Computer Rooms
Most IT racks have the same look, but rarely have the same feel. We have developed racks specifically for servers and networking which account for important details like cable management and power distribution. This solution pairs our optimised rack solutions with a high availability UPS for protecting all of your critical equipment as simply as possible. Read more.
Please supply your email address to access the content.
Most Read
Sign up now to get free exclusive access to reports, research and invitation only events.
Most Commented
Featured Whitepapers
Simple, Proven, Tranformative
A cheat Sheet for Google Apps for Business
Most Popular Whitepapers
Stop Paying the Earth for Global Roaming
Why do we continue to pay the earth for global roaming? With Telstra increasing global roaming charges by 100-500% in over 180 countries, bill shock can only get worse. This paper investigates why, what and how your company can address the need for global coverage.
Latest Jobs


text: My old pump did this also. It was for 2 houses and cattle. It just couldnt keep up with demand. Did ok as long as only one thing was on. The pump was worn out. I think mine was about 16-18 years old. Got a new one, solved the problem and this was 13 years ago now. Hope mine last's a few more years!


text:
E-Mail this page
Printable Format
SRA will lead a team of 15 to compete for task orders
SRA International has announced its teammates for the Homeland Security Department's $11 billion Technical, Acquisition, and Business Support Services contract, or TABSS.
SRA International was one of 12 winners when the contract was awarded in late 2012.
The SRA team consists of:
Under TABSS, SRA and its team will compete for task orders with the other winners for work across 39 program management, engineering and technical support service areas that comprise Domain 1 of the contract, the company said.
About the Author
Mark Hoover is a staff writer with Washington Technology. You can contact him at email@example.com, or connect with him on Twitter at @mhooverWT.
Advanced Search
In an exclusive for WT Insider members, we are collecting all of the contract awards we cover into a database that you can sort by contractor, agency, value and other parameters. You can also download it into a spreadsheet.
Read More
Editor Nick Wakeman explores the puzzle of why SBA has been so silent on the latest contractor fraud scandal when it has been so quick to act in other cases.
Read More
How do best-in-class project-based companies create and actively mature successful organizations? They find the right mix of people, processes and tools that enable them to effectively manage the project lifecycle. REGISTER for this webinar to hear how properly managing the cycle of capture, bid, accounting, execution, IPM and analysis will allow you to better manage your programs to stay on scope, schedule and budget.
Learn More!
Join Washington Technology's Editor-in-Chief Nick Wakeman as he analyzes the annual Top 100 list and reveals critical insights into how market trends have impacted its composition. You'll learn what movements of individual companies means and how the market overall is being impacted by the current budget environment, how the Top 100 rankings reflect the major trends in the market today and how the biggest companies in the market are adapting to today's competitive environment.
Learn More!


text:
Enclume Low Ceiling Oval Pot Racks
- Online Only
- Summary
Perfect for low ceilings (or tall cooks), this rack holds as many pots and pans as Enclume's bestselling oval rack, but has a lower profile. Designed to hold the heaviest cookware, the rack is hand forged in the Pacific Northwest by the master craftsmen at Enclume, America's leading manufacturer of cooking racks since 1973.
- Heavy-duty hammered-steel grid and frame, protected by a durable wax finish.
- 6 straight pot hooks hang cookware facing outward.
- 12 angled pot hooks allow cookware pieces to nest together.
- Rack: 37" x 20 1/2" x 7 1/2" high (from ceiling to bottom of pot hook).
- Hooks: 4 1/2" long.
- Mounting hardware included.
- Use & Care
- Assembly required.
- Professional installation recommended.
- Mounts on 16" centers, in-line or perpendicular.
- Must be anchored to solid wood joists or beams.
- Shipping
Shipping Information
This item will be shipped directly from the manufacturer and is not eligible for rush shipping. Please allow two to three weeks for delivery.
Shipping Rates
The shipping rate varies depending on your order total and shipping destination. View Shipping Options and Charges.
Return Policy
At Williams-Sonoma, we take great pride in the quality and craftsmanship of our products. If, within 30 days, you are not completely satisfied with your purchase for any reason, please return the item for an exchange or refund of the merchandise value. View Full Return Policy.


text:
Welcome to the Nevada Department of Health and Human
Services website. Our user-friendly format allows a
visitor to use drop-down menus to navigate more quickly
to a desired location. Your comments and suggestions
regarding the website can be sent to
The Nevada Department of Health and Human Services promotes the health and well-being of Nevadans and our visitors through the delivery and facilitation of essential services. Our goal is to strengthen families, protect public health, and assist individuals in achieving the highest level of self-sufficiency.
Our staff of some 5200 employees is here to serve and meet your needs. I invite you to contact us with any questions or specific needs that we may be able to address.
NOTE: Pursuant to changes made by the 2009 Legislature, the Office of Disabilities Services, Disability RX and Senior RX have been moved into and merged with the Division for Aging Services as the new Aging & Disability Services Division.


text:
Scotch-Weld™ DP-8010NS is a two-part acrylic-based adhesive (10:1 ratio by volume) that can bond many low surface energy plastics, including many grades of polypropylene, polyethylene, and TPO's without special surface preparation. It has a long (up to 10 minutes) open time and good work life (up to 2 hours).. Scotch-Weld™ DP-8010NS can replace mechanical fasteners i.e. screws and rivets, and plastic welding that typically require two-step processes which include chemical etchants, priming or surface treatments in many applications prior to bonding.. .
You are already a registered user on SDB.Please enter SHIP ME promo if you have not already used it previously.
Toll Free Phone1-877-255-3415
Hours: 8am - 5pm CST, Monday - Friday.


text:
Alamo Colleges Education Services is a secure portal connecting Faculty, Staff & Students to Academic Resources, Email, and other Online Resources.
Support Contacts Helpdesk (210) 485-0555 Weather Line (210) 485-0189
Online Catalog
Lib Guides
Library Instruction
Library Services
Distance Learning
Academic Calendar
Emergency Information
Student Resources
Visit Our Campus
The following links are Scholarships not included in the Alamo Colleges Online Application.
Delta Kappa Gamma Society Int'l (future teachers)
Jan. 20
The AHS Vertical Flight Foundation
Feb. 1
Boren Study Abroad Scholarship (Study Abroad)
Feb. 5
American Physical Society - Minorities in Physics Scholarship
Feb. 7
Assistance League of San Antonio (For students transferring to a university in Fall 2014)
Feb. 14
Dr. Martin Luther King, Jr. Scholarship
Feb. 21
CBCF General Mills Health Scholarship
Feb. 28
Buick Achievers Scholarship
Generations FCU Future Leaders
Society of Exploration Geophysicists
Mar. 1
American Chemical Society - ACS Scholars Award (For Minority Students)
Irene S. Wischer Foundation Scholarship
Mar. 3
Two Ten Footwear Foundation Scholarship
National Society of Accountants
Otto D. Grove Scholarship
Mar. 12
SACU Bridge for U Scholarship
Mar. 14
Texas Nursery & Landscape Association Scholarship
San Antonio Youth Education Scholarships
Mar. 15
Texas Energy Council Scholarship
Mar. 20
EWI - Adult Students in Scholastic Transition
Mar. 22
Shire ADHD Scholarships
Mar. 19
Worldstudio AIGA Scholarship
Mar. 28
LULAC Rey Feo Scholarship
Mar. 31
National Aviation Explorer Scholarship
Emma Freeman Memorial Scholarship (SA Lighthouse for the Blind)
Apr. 1
Printing Industries of America - Print and Graphics Scholarship
Jere W. Thompson Jr. Scholarship
Education Portal - Criminal Justice & Law Enforcement Scholarship
Education Portal - Liberal Arts & General Studies
Education Portal - Architecture, Drafting, & Related Fields
Education Portal - Computer Science & Computer Engineering
Education Portal - Undergraduate Distance Learning in Any Major or Subject
Rotary Club Youth Scholarship
Apr. 4
Verbal Ink Transcription Services Scholarship
Apr. 15
MyBookBuyer.com Textbooks for a Year Scholarship
Congressional Hispanic Caucus Institute
Apr 16
The Colburn-Pledge Music Scholarship Foundation
Apr. 23
Peace Officers Memorial Foundation (For dependents of Peace Officers)
Apr. 26
A Place for Mom Senior Care Innovation Scholarship
Apr. 30
Sell Used Books College Essay Contest
Dr. Alma S. Adams Scholarships
Jacobsen Turfgrass Scholarship
May 1
Jack Kent Cooke Foundation Undergraduate Transfer Scholarship
SHPE Foundation Scholarship
HACU Scholarships
May 25
Adelante Scholarships
H-E-B/Adelante Future Leaders Scholarship
Adelante Scoring for Education Scholarship
Adelante/Ford Motor Company Future Leaders Scholarship
Abercrombie & Fitch Future Leaders Scholarship
Adelante - Gilbert G. Pompa Memorial Endowed Scholarship (Pre-Law)
Big Fish Games Online Games Scholarship $2500
May 31
Tylenol Future Care Scholarship (Healthcare)
Adelante HOPE Scholarship
Jun. 12
LULAC Parent/Child Scholarship
Jun. 18
Texas Urban Scholarship Fund
Jul. 8
TEACH Early Childcare TEXAS Scholarship
Alamo Council for the Blind Scholarship
Jul. 15
IES Abroad Scholarships
Competition Accessories
Mar 15
Scholarship Coordinator:Leticia C. firstname.lastname@example.com
Location:College Student Center (CSC-101)
1400 W. Villaret Blvd, San Antonio, Texas 78224 (210) 486-3000


text:
|Systematic (IUPAC) name
|Clinical data
|Trade names
|Lanzek, Zypadhera, Zyprexa
|Licence data
|US FDA:link
|Pregnancy cat.
|Legal status
|Prescription Only (S4) (AU) POM (UK) ℞-only (US)
|oral, intramuscular
|Pharmacokinetic data
|Protein binding
|Hepatic (direct glucuronidation and CYP1A2 mediated oxidation)
|33 hours, 51.8 hours (elderly)[2]
|Urine (57%; 7% as unchanged drug), faeces (30%)[2][3]
|CAS number
|ATC code
|IUPHAR ligand
|Chemical data
|Mol. mass
|Physical data
|Melt. point
|Solubility in water
|Practically insoluble in water mg/mL (20 °C)
|(what is this?) (verify)
Olanzapine (sold under the brand names Zyprexa, Zypadhera and Lanzek or in combination with fluoxetine, Symbyax) is an atypical antipsychotic, approved by the U.S. Food and Drug Administration (FDA) for the treatment of schizophrenia and bipolar disorder.[4] Olanzapine is structurally similar to clozapine and quetiapine, but is classified as a thienobenzodiazepine. The olanzapine formulations are manufactured and marketed by the pharmaceutical company Eli Lilly and Company; the drug went generic in 2011. Sales of Zyprexa in 2008 were $2.2B in the US alone, and $4.7B in total.[5]
- 1 Medical uses
- 2 Adverse effects
- 2.1 By incidence
- 2.2 Paradoxical effects
- 2.3 Metabolic effects
- 2.4 Pregnancy/Lactation
- 2.5 Animal toxicology
- 2.6 Discontinuation
- 2.7 Overdose
- 3 Pharmacology
- 4 Dosage forms
- 5 Metabolism
- 6 Society and culture
- 7 Chemistry
- 8 Research
- 9 References
- 10 External links
Medical uses[edit]
The benefits of olanzapine in schizophrenia are difficult to determine as more than half of people in trials quit before the six week completion date.[6] In light of this, the positive effects of olanzapine appear equivalent to typical antipsychotics with fewer extrapyramidal side effects but greater weight gain.[6] When compared to other atypical antipsychotics, the available data suggests that olanzapine may be slightly more effective (although amisulpride and clozapine do appear to be slightly more effective[7]); however, it produced more weight gain and other metabolic problems.[7][8]
Evidence does not support the use of atypical antipsychotics including olanzapine in eating disorders.[9]
Case-reports, open-label, and small pilot studies suggest efficacy of olanzapine for the treatment of some anxiety spectrum disorders (e.g. generalized anxiety disorder,[10] panic disorder,[11] delusional parasitosis,[12] post-traumatic stress disorder);[13] however, olanzapine has not been rigorously evaluated in randomized, placebo-controlled trials for this use. Olanzapine is no less effective than lithium or valproate, and more effective than placebo in treating bipolar disorder.[14] It has also been used for Tourette syndrome and stuttering.[15]
Citing an increased risk of stroke, in 2004 the Committee on the Safety of Medicines (CSM) in the UK issued a warning that olanzapine and risperidone, both atypical antipsychotic medications, should not be given to elderly patients with dementia. In the U.S., olanzapine comes with a black box warning for increased risk of death in elderly patients. It is not approved for use in patients with dementia-related psychosis.[16] However, a BBC investigation in June 2008 found that this advice was being widely ignored by British doctors.[17]
Adverse effects[edit]
The principal side effect of olanzapine is weight gain, which may be profound in some cases and/or associated with derangements in the blood lipid and blood sugar profiles (see section Metabolic effects). A recent meta-analysis of the efficacy and tolerability of 15 antipsychotic drugs (APDs) found that it had the highest propensity for causing weight gain out of the 15 APD compared with a SMD of 0.74[7] Extrapyramidal side effects, although potentially serious, are infrequent to rare from olanzapine[18] but may include tremors and muscle rigidity.
By incidence[edit]
Several patient groups are at a heightened risk of side effects from olanzapine and antipsychotics in general. Olanzapine may produce non-trivial hyperglycemia in patients with diabetes mellitus. Likewise, the elderly are at a greater risk of falls and accidental injury. Young males appear to be at heightened risk of dystonic reactions, although these are relatively rare with olanzapine. Most antipsychotics, including olanzapine, may disrupt the body's natural thermoregulatory systems, thus permitting excursions to dangerous levels when situations (exposure to heat, strenuous exercise) occur.[2][19][20][21][3]
Very common (>10% incidence)[edit]
- Weight gain (dose-dependent). Weight gain of over 7% of a person's initial body weight prior to treatment is in this category of very common too with some estimates of its incidence putting it at around 40.6%. This AE is most likely the result of its potent 5-HT2C receptor and H1 receptor blockade (or more specifically inverse agonism).[22]
- Somnolence (dose-dependent). Tends to produce a moderate amount of sedation, less than clozapine and chlorpromazine but more than aripiprazole, amisulpride, paliperidone and sertindole and approximately that of quetiapine and risperidone.[7]
- Hyperprolactinemia elevated blood levels of the hormone, prolactin. Prolactin is one of the hormones that plays a key role in lactation. Long-term uncontrolled hyperprolactinaemia can lead to bone demineralisation (osteoporosis) and an increased risk of fractures (breaks). It tends to produce hyperolactinaemia less often than risperidone, paliperidone and the typical antipsychotics but more often than quetiapine and clozapine.
- Hypertriglyceridaemia (elevated blood triglycerides)
- Hypercholesterolaemia (elevated blood cholesterol levels)
- Hyperglycaemia (elevated blood glucose levels). This may be the result of olanzapine's inhibitory effects on the M3 receptor which regulates the release of insulin from the pancreas.[22]
Common (1-10% incidence)[edit]
- Extrapyramidal symptoms (EPS) (dose-dependent). Tends to produce less extrapyramidal side effects than typical antipsychotics but more extrapyramidal side effects than sertindole, clozapine and quetiapine.[23][24]
- Mild and transient constipation and xerostomia (dry mouth)
- Dizziness
- Weight gain of over 15% of one's initial body weight. Is reported to occur in approximately 7.1% of patients.
- Glucosuria (glucose in the urine. This is a consequence of hyperglycaemia)
- Accidental injury
- Insomnia
- Orthostatic hypotension (a drop in blood pressure that occurs upon standing up)
- Transient, asymptomatic elevations of hepatic aminotransferases (ALT, AST), especially in early treatment. ALT & AST are liver enzymes which are often tested for as a measure of liver function.
- Dyspepsia (indigestion)
- Erectile dysfunction. This is most likely the result of hyperprolactinaemia.
- Decreased libido. This is most likely the result of hyperprolactinaemia.
- Rash
- Asthenia (weakness)
- Fatigue
- Oedema the accumulation of fluid in the tissues of the body leading to swelling
- Akathisia An inner sense of restlessness that presents itself with the inability to stay still.
- Parkinsonism (tremor, muscle rigidity, reduced ability to move and being unstable on one's feet.
- Dyskinesia Abnormal, involuntary, repetitive and pointless movements.
Uncommon (0.1-1% incidence)[edit]
- Leukopaenia a comparatively low white blood cell (the cells that defend the body from foreign invaders) count.
- Neutropaenia a reduced neutrophil (the white blood cells that kill bacteria) count.
- Bradycardia (low heart rate)
- QTc interval prolongation (an abnormality in the electrical cycle of the heart)
- Photosensitivity reaction
- Alopecia (hair loss)
- Urinary incontinence
- Urinary retention, the inability to urinate.
- Amenorrhea the cessation of menses (a woman's menstrual cycles). This is a complication of hyperprolactinaemia.
- Breast enlargement (in either sex). This is a complication of hyperprolactinaemia.
- Galactorrhoea (expulsion of milk from the breasts that's unrelated to pregnancy or lactation. Most likely the result of hyperprolactinaemia)
- High creatine phosphokinase (an abnormal laboratory finding)
- Increased total bilirubin (a by product of the breakdown of haem - a part of blood cells that is used to carry oxygen. In most people this is an indication of impaired liver function)
Rare (0.01-0.1% incidence)[edit]
- Hepatitis (swelling of the liver)
- Rash
- Seizures
Very rare (<0.01% incidence)[edit]
- Agranulocytosis, a potentially fatal drop in white blood cell count, basically an exaggerated form of leukopaenia.
- Thrombocytopaenia. A drop in blood platelet counts which are involved in blood clotting.
- Thromboembolism (blood clots; including pulmonary embolism and deep vein thrombosis)
- Rhabdomyolysis (breakdown of muscle tissue leading to the release of myoglobin into the bloodstream which in turn damages the kidneys)
- Alkaline phosphatase increased (an abnormal laboratory parameter)
- Priapism (a long and painful erection)
- Urinary hesitation
- Pancreatitis, swelling of the pancreas which supplies the body with insulin.
- Neuroleptic malignant syndrome a potentially fatal complication of antipsychotic drug treatment. Presents with hyperthermia, tremor, tachycardia (high heart rate), mental status change (e.g. confusion), etc.
- Jaundice, which is basically when the body's ability to clear a by product (called bilirubin) of the breakdown of an essential component of the blood called haem, is impaired leading to yellow discolouration of the skin, eyes and mucous membranes.
- Diabetic coma
- Diabetic ketoacidosis. Type II diabetes mellitus is basically where the body cannot effectively utilise sugars to produce energy due to the fact that its cells have become unresponsive to the hormone, insulin, which allows cells to utilise sugars for energy. This in turn forces the body to burn fats for energy and fats require conversion to ketone bodies in order to be utilised by the cells of the body as an energy source. The ketone bodies are acidic hence when the body is entirely reliant on these ketone bodies for energy the levels in the blood reaches a point where it overwhelms the body's natural mechanisms to keep blood pH (a measure of acidity) within a safe range, leading to the blood becoming acidic which is potentially damaging to the tissues of the body due to the ability of acidic environments to denature the proteins of the body.
- Sudden cardiac death
- Anaphylactic reaction a potentially life-threatening allergic reaction.
Paradoxical effects[edit]
While olanzapine is used therapeutically to treat serious mental illness, occasionally it can have the opposite effect and provoke serious paradoxical reactions in a small subgroup of people, with the drug causing unusual changes in personality, thoughts or behavior; hallucinations and suicidal ideation have also been linked to olanzapine use.[25]
Metabolic effects[edit]
The U.S. Food and Drug Administration requires all atypical antipsychotics to include a warning about the risk of developing hyperglycemia and diabetes, both of which are factors in the metabolic syndrome. These effects may be related to the drugs' ability to induce weight gain, although there are some reports of metabolic changes in the absence of weight gain,[26][27] Studies have indicated that olanzapine carries a greater risk of causing and exacerbating diabetes than another commonly prescribed atypical antipsychotic, Risperidone. Of all the atypical antipsychotics, olanzapine is one of the most likely to induce weight gain based on various measures.[28][29][30][31][32] The effect is dose dependent in humans[33] and animal models of olanzapine-induced metabolic side effects.[34] Olanzapine may directly affect adipocyte function, promoting fat deposition.[35] There are some case reports of olanzapine-induced diabetic ketoacidosis.[36] Olanzapine may decrease insulin sensitivity,[37][38] though one 3-week study seems to refute this.[39] It may also increase triglyceride levels.[29]
Recent studies have established that:
- olanzapine and clozapine disturb normal metabolism by forcing the body to preferentially derive its energy from fat (instead of privileging carbohydrates). Thus forcing levels of carbohydrates to remain high which, in turn, would cause the body to develop insulin resistance (reduction of insulin sensitivity).[40]
- olanzapine promotes fat accumulation: due to disturbances in fat metabolism, rodents become fatter (but don't have their weight increasing at first). Being fatter, they do less exercise, burning less fat and gaining weight.[41]
- olanzapine may cause body weight gain and hyperphagia by altering appetite signaling in the brain and periphery[42]
- olanzapine may induce hyperglycaemia leading to diabetes side effects by altering insulin secretion from the pancreatic beta cell through blockade of the muscarinic M3 receptor[43]
Despite weight gain, a large multi-center randomized National Institute of Mental Health study found that olanzapine was better at controlling symptoms because patients were more likely to remain on olanzapine than the other drugs.[44] One small, open-label, non-randomized study suggests that taking olanzapine by orally dissolving tablets may induce less weight gain,[45] but this has not been substantiated in a blinded experimental setting.
Olanzapine is associated with the highest placental exposure of any atypical antipsychotic.[23] Despite this the available evidence suggests it is safe during pregnancy, although the evidence is insufficient strong to say anything with a high degree of confidence.[23] Olanzapine is associated with weight gain which according to recent studies may put olanzapine-treated patients' offspring at a heightened risk for neural tube defects (e.g. spina bifida).[46][47] Breastfeeding in women taking olanzapine is advised against due to the fact that olanzapine is secreted in breast milk with one study finding that the exposure to the infant (in mg per kg of body weight, that is) is about 1.8% that to the mother.[2]
Animal toxicology[edit]
In a placebo-compared study of six Macaque monkeys receiving doses of olanzapine resulting in drug levels comparable to those seen in subjects with schizophrenia treated with these medications for between 17 and 27 months, significant total brain volume and weight decreases (8-11%) were detected. Higher losses in specific regions of the brain did reach statistical significance, eg/ The mean gray matter volume of the frontal lobes was significantly reduced(15.2%) compared to controls[48] In latter studies of the stored samples, the changes were attributed to astrocyte and oligodendrocyte loss,[49] There was a 5% loss in the number of neurons. Even though this was not statistically significant it is highly clinically significant and in line with the loss found in the brains of patients diagnosed with schizophrenia (see the references in Konopaske et al. 2008 above). This study however was contradicted by an earlier primate study, conducted by Selemon et al. in 1999,[50] which found that at therapeutic dosages, olanzapine increased glial counts in monkeys. To date, the effect of olanzapine on glia remains an open question.
Olanzapine has demonstrated carcinogenic effects in multiple studies when exposed chronically to female mice and rats, but not male mice and rats. The tumors found were in either the liver or mammary glands of the animals.[51]
The British National Formulary recommends a gradual withdrawal when discontinuing anti-psychotic treatment to avoid acute withdrawal syndrome or rapid relapse.[52] Due to compensatory changes at dopamine, serotonin, adrenergic and histamine receptor sites in the central nervous system, withdrawal symptoms can occur during abrupt or over-rapid reduction in dosage. However, despite increasing demand for safe and effective antipsychotic withdrawal protocols or dose-reduction schedules, no specific guidelines with proven safety and efficacy are currently available. Support groups such as the Icarus Project, and other online forums provide resources and social support for those attempting to discontinue antipsychotics and other psychiatric medications.[53] Withdrawal symptoms reported to occur after discontinuation of antipsychotics include nausea, emesis, lightheadedness, diaphoresis, dyskinesia, orthostatic hypotension, tachycardia, nervousness, dizziness, headache, excessive non-stop crying, and anxiety.[54][55] Some have argued additional somatic and psychiatric symptoms associated with dopaminergic hypersensitivity, including dyskinesia and acute psychosis, are common features of withdrawal in individuals treated with neuroleptics.[56][57][58][59] Thus, some suggest the withdrawal process itself may be schizo-mimetic, producing schizophrenia-like symptoms even in previously healthy patients.[60]
Symptoms of an overdose include tachycardia, agitation, dysarthria, decreased consciousness and coma. Death has been reported after an acute overdose of 450 mg, but also survival after an acute overdose of 2000 mg.[61] There is no known specific antidote for olanzapine overdose, and even physicians are recommended to call a certified poison control center for information on the treatment of such a case.[61] Olanzapine is considered moderately toxic in overdose; more toxic than quetiapine, aripiprazole and the SSRIs and less toxic than the MAOIs and TCAs.[23]
Olanzapine has a higher affinity for 5-HT2A serotonin receptors than D2 dopamine receptors, which is a common property of all atypical antipsychotics, aside from the benzamide antipsychotics such as amisulpride. Olanzapine also had the highest affinity of any second-generation antipsychotic towards the P-glycoprotein in one in vitro study.[62] P-glycoprotein transports a number of drugs across a number of different biological membranes including the blood-brain barrier, which could mean that less brain exposure to olanzapine results from this interaction with the P-glycoprotein.[63]
|Ki (nM)[64]
|Biologic action and notes[22]
|Inverse agonist. May underlie the "atypicality" of the newer antipsychotics like olanzapine. May contribute to sedating effects.
|Inverse agonist/antagonist.
|Inverse agonist. May underlie the appetite-stimulating effects of olanzapine.
|Antagonist. Possibly responsible, at least in part, for its antiemetic action.
|Antagonist. Likely responsible for the orthostatic hypotension seen with its use.[22]
|Antagonist. Likely the chief receptor responsible for the anticholinergic effects seen with olanzapine's use.[22]
|Antagonist. Possible role in type 2 diabetes side-effects [65]
|Antagonist. Likely responsible for the therapeutic effects of olanzapine against the positive symptoms of schizophrenia.[22]
|Inverse agonist. Likely responsible for the sedative effects of olanzapine.[22]
Olanzapine is a potent antagonist of the muscarinic M3 receptor,[66] which may underlie its diabetogenic side effects.[65][67] Additionally olanzapine also exhibits a relatively low affinity for serotonin 5-HT1, GABAA, beta-adrenergic receptors, and benzodiazepine binding sites.[68] The mode of action of olanzapine's antipsychotic activity is unknown. It may involve antagonism of dopamine and serotonin receptors. Antagonism of dopamine receptors is associated with extrapyramidal effects such as tardive dyskinesia(TD), and with therapeutic effects. Antagonism of muscarinic acetylcholine receptors is associated with anticholinergic side effects such as dry mouth and constipation, in addition it may suppress or reduce the emergence of extrapyramidal effects for the duration of treatment, however it offers no protection against the development of tardive dyskinesia. In common with other second generation (atypical) antipsychotics, olanzapine poses a relatively low risk of extrapyramidal side effects including TD, due to its high affinity for the D1 receptor over the D2 receptor.[69]
Antagonizing H1 histamine receptors causes sedation and may cause weight gain, although antagonistic actions at serotonin 5-HT2C and dopamine D2 receptors have also been associated with weight gain and appetite stimulation.[70]
Olanzapine also binds weakly to the GABA-A, beta-adrenergic and benzodiazepine (BZD) receptors.[18]
Dosage forms[edit]
Olanzapine is marketed in a number of countries, with tablets ranging from 2.5 to 20 milligrams. Zyprexa (and generic Olanzapine) is available as an orally-disintegrating "wafer" which rapidly dissolves in saliva. It is also available in 10 milligram vials for intramuscular injection.[4]
Olanzapine is metabolized by the cytochrome P450 system; principally by isozyme 1A2 and to a lesser extent by 2D6. By these mechanisms more than 40% of the oral dose, on average, is removed by the hepatic first-pass effect.[18] Drugs or agents that increase the activity of CYP1A2, notably tobacco smoke, may significantly increase hepatic first-pass clearance of Olanzapine; conversely, drugs which inhibit 1A2 activity (examples: Ciprofloxacin, Fluvoxamine) may reduce Olanzapine clearance.[4]
Society and culture[edit]
Regulatory status[edit]
Olanzapine is approved by the FDA for:
- Treatment — in combination with fluoxetine — of depressive episodes associated with bipolar disorder (December 2003).[71]
- Long-term treatment of bipolar I disorder (January 2004).[72][73]
- Treatment — in combination with fluoxetine — of resistant depression (March 2009).[74]
- Oral formulation: acute and maintenance treatment of schizophrenia in adults, acute treatment of manic or mixed episodes associated with bipolar I disorder (monotherapy and in combination with lithium or sodium valproate)
- Intramuscular formulation: acute agitation associated with schizophrenia and bipolar I mania in adults
- Oral formulation combined with fluoxetine: treatment of acute depressive episodes associated with bipolar I disorder in adults, or treatment of acute, resistant depression in adults [75]
- Short-term treatment of acute manic episodes associated with bipolar I disorder (March 2000).[77]
- Short-term treatment of schizophrenia instead of the management of the manifestations of psychotic disorders (March 2000).[77]
- Maintaining treatment response in schizophrenic patients who had been stable for approximately eight weeks and were then followed for a period of up to eight months (November 2000).[77]
Controversy, lawsuits and settlements[edit]
Eli Lilly has faced many lawsuits by from people who claimed they developed diabetes or other diseases after taking Zyprexa. In 2006, Lilly paid $700 million to settle 8,000 of these lawsuits.[78] In 2007, Eli Lilly agreed to pay up to $500 million to settle 18,000 more lawsuits.[citation needed]
In 2009 Eli Lilly pled guilty to a criminal misdemeanor charge of illegally marketing Zyprexa for off-label use and agreed to pay $1.4 billion.[79] Although Lilly had evidence that it is not effective for dementia, Zyprexa was marketed for elderly Alzheimer's patients.[80] The drug carries an F.D.A. warning that it increases the risk of death in older patients with dementia-related psychosis.[81]
According to the New York Times, "Eli Lilly has engaged in a decade-long effort to play down the health risks of Zyprexa according to hundreds of internal Lilly documents and e-mail messages among top company managers",[82] most of which had been disclosed as the result of the lawsuits by individuals who had taken the drug, though other documents had been stolen.[83] Eli Lilly filed a protection order to stop the dissemination of some of the documents which the judge believed to be confidential and "not generally appropriate for public consumption".[83] Temporary injunctions required those who had received the documents to return them and to remove them from websites.[84] Judge Jack B. Weinstein issued a permanent judgement against further dissemination of the documents and requiring their return by a number of parties named by Lilly.[83] On January 8, 2007, Judge Jack B. Weinstein refused the Electronic Frontier Foundation's motion to stay his order.[85] The documents given to The New York Times by Jim Gottstein show that Lilly executives may have kept important information from doctors about Zyprexa's links to obesity and its tendency to raise blood sugar — both known risk factors for diabetes. The Times of London also reported that as early as October 1998, Lilly considered the risk of drug-induced obesity to be a "top threat" to Zyprexa sales.[86] On October 9, 2000, senior Lilly research physician Robert Baker noted that an academic advisory board he belonged to was "quite impressed by the magnitude of weight gain on olanzapine and implications for glucose."[86]
Olanzapine can be prepared starting from malononitrile and propionaldehyde:[87]
Olanzapine has been investigated for use as an antiemetic, particularly for the control of chemotherapy-induced nausea and vomiting (CINV). A 2007 study demonstrated its successful potential for this use, achieving a complete response in the acute prevention of nausea and vomiting in 100% of patients treated with moderately and highly-emetogenic chemotherapy, when used in combination with palonosetron and dexamethasone.[88]
Olanzapine has been considered as part of an early psychosis approach for schizophrenia. The Prevention through Risk Identification, Management, and Education (PRIME) study, funded by the National Institute of Mental Healthand Eli Lilly, tested the hypothesis that olanzapine might prevent the onset of psychosis in people at very high risk for schizophrenia. The study examined 60 patients with prodromalschizophrenia, who were at an estimated risk of 36–54% of developing schizophrenia within a year, and treated half with olanzapine and half with placebo.[89] In this study, patients receiving olanzapine did not have a significantly lower risk of progressing to psychosis. Olanzapine was effective for treating the prodromal symptoms, but was associated with significant weight gain.[90]
- ^ Burton, Michael E.; Shaw, Leslie M.; Schentag, Jerome J.; Evans, William E. (May 1, 2005). Applied Pharmacokinetics & Pharmacodynamics: Principles of Therapeutic Drug Monitoring (4th ed.). Lippincott Williams & Wilkins. p. 815. ISBN 978-0-7817-4431-7.
- ^ a b c d e "PRODUCT INFORMATION OLANZAPINE SANDOZ® 2.5mg/5mg/7.5mg/10mg/15mg/20mg FILM-COATED TABLETS" (PDF). TGA eBusiness Services. Sandoz Pty Ltd. 8 June 2012. Retrieved 26 November 2013.
- ^ a b "Zyprexa, Zyprexa Relprevv (olanzapine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 26 November 2013.
- ^ a b c "Olanzapine Prescribing Information" (PDF). Eli Lilly and Company. 2009-03-19. Retrieved 2009-09-06.
- ^ "Lilly 2008 Annual Report" (PDF). Lilly. 2009. Retrieved 2009-08-06.
- ^ a b Duggan, Lorna; Fenton, Mark; Dardennes, John; El-Dosoky, Roland; Indran, Ahmed; Indran, Saroja (2005). "Olanzapine for schizophrenia". In Duggan, Lorna. Cochrane Database of Systematic Reviews (2): CD001359. doi:10.1002/14651858.CD001359.pub2. PMID 10796640.
- ^ a b c d Leucht S, Cipriani A, Spineli L, Mavridis D, Örey D, Richter F, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. The Lancet [Internet]. 2013 Jun 27 [cited 2013 Sep 19];382(9896) 951–62. Available from:http://www.sciencedirect.com/science/article/pii/S0140673613607333
- ^ Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Duggan, Lorna; Kissling, Werner; Leucht, Stefan (2010). "Olanzapine versus other atypical antipsychotics for schizophrenia". In Komossa, Katja. Cochrane Database of Systematic Reviews (3): CD006654. doi:10.1002/14651858.CD006654.pub2. PMID 20238348.
- ^ Maglione, Margaret; Maher, Alicia Ruelaz; Hu, Jianhui; Wang, Zhen; Shanman, Roberta; Shekelle, Paul G; Roth, Beth; Hilton, Lara et al. (2011). Off-Label Use of Atypical Antipsychotics: An Update. PMID 22132426.
- ^ Pollack, Mark H.; Simon, Naomi M.; Zalta, Alyson K.; Worthington, John J.; Hoge, Elizabeth A.; Mick, Eric; Kinrys, Gustavo; Oppenheimer, Julia (2006). "Olanzapine Augmentation of Fluoxetine for Refractory Generalized Anxiety Disorder: A Placebo Controlled Study". Biological Psychiatry 59 (3): 211–5. doi:10.1016/j.biopsych.2005.07.005. PMID 16139813.
- ^ Sepede, Gianna; De Berardis, Domenico; Gambi, Francesco; Campanella, Daniela; La Rovere, Raffaella; d'Amico, Michele; Cicconetti, Alessandra; Penna, Laura; Peca, Silvana; Carano, Alessandro; Mancini, Enrico; Salerno, Rosa Maria; Ferro, Filippo Maria (2006). "Olanzapine Augmentation in Treatment-Resistant Panic Disorder". Journal of Clinical Psychopharmacology 26 (1): 45–9. doi:10.1097/01.jcp.0000195108.01898.17. PMID 16415705.
- ^ Meehan, William J.; Badreshia, Sonia; MacKley, Christine L. (2006). "Successful Treatment of Delusions of Parasitosis with Olanzapine". Archives of Dermatology 142 (3): 352–5. doi:10.1001/archderm.142.3.352. PMID 16549712.
- ^ Jakovljević, M.; Sagud, M.; Mihaljevic-Peles, A. (2003). "Olanzapine in the treatment-resistant, combat-related PTSD – a series of case reports". Acta Psychiatrica Scandinavica 107 (5): 394–6; discussion 396. doi:10.1034/j.1600-0447.2003.00065.x. PMID 12752037.
- ^ Review of olanzapine in the management of bipolar disorders Neuropsychiatr Dis Treat. 2007 October; 3(5): 579–587.
- ^ Scott, Lisa (Winter 2006). "Genetic and Neurological Factors in Stuttering". Stuttering Foundation of America.
- ^ "Important Safety Information for Olanzapine". Zyprexa package insert. Eli Lilly & Company. 2007. Archived from the original on 2007-11-23. Retrieved 2007-12-03. "Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. [...] ZYPREXA (olanzapine) is not approved for the treatment of elderly patients with dementia-related psychosis."
- ^ "Doctors 'ignoring drugs warning'". BBC News. 17 June 2008. Retrieved 2008-06-22.
- ^ a b c Lexi-Comp Inc. (2010) Lexi-Comp Drug Information Handbook 19th North American Ed. Hudson, OH: Lexi-Comp Inc. ISBN 978-1-59195-278-7.
- ^ Stöllberger, C., Lutz, W. and Finsterer, J. (2009), Heat-related side-effects of neurological and non-neurological medication may increase heatwave fatalities. European Journal of Neurology, 16: 879–882.
- ^ "OLANZAPINE (olanzapine) tablet OLANZAPINE (olanzapine) tablet, orally disintegrating [Prasco Laboratories]". DailyMed. Prasco Laboratories. September 2013. Retrieved 26 November 2013.
- ^ "Olanzapine 10 mg tablets - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Aurobindo Pharma - Milpharm Ltd. 17 May 2013. Retrieved 26 November 2013.
- ^ a b c d e f g Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (in English) (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.
- ^ a b c d Taylor, D; Paton, C; Shitij, K (2012). The Maudsley prescribing guidelines in psychiatry (in English). West Sussex: Wiley-Blackwell. ISBN 978-0-470-97948-8.
- ^ Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
- ^ Cerner Multum Incorporated (27 September 2011). "Olanzapine". Drugs.com.
- ^ Ramankutty, G. (2002). "Olanzapine-induced destabilization of diabetes in the absence of weight gain". Acta Psychiatrica Scandinavica 105 (3): 235–6; discussion 236–7. doi:10.1034/j.1600-0447.2002.2c257a.x. PMID 11939979.
- ^ Lambert, Michael T.; Copeland, Laurel A.; Sampson, Nancy; Duffy, Sonia A. (2006). "New-onset type-2 diabetes associated with atypical antipsychotic medications". Progress in Neuro-Psychopharmacology and Biological Psychiatry 30 (5): 919–23. doi:10.1016/j.pnpbp.2006.02.007. PMID 16581171.
- ^ Moyer, Paula (Oct 25, 2005). "CAFE Study Shows Varying Benefits Among Atypical Antipsychotics". Medscape Medical News (WebMD). Retrieved 2007-12-03.
- ^ a b AstraZeneca Pharmaceuticals (4 April 2006). "Efficacy and Tolerability of Olanzapine, Quetiapine and Risperidone in the Treatment of First Episode Psychosis: A Randomised Double Blind 52 Week Comparison". AstraZeneca Clinical Trials. AstraZeneca PLC. Archived from the original on 2007-11-13. Retrieved 2007-12-03. "At week 12, the olanzapine-treated group had more weight gain, a higher increase in [ body mass index ], and a higher proportion of patients with a BMI increase of at least 1 unit compared with the quetiapine and risperidone groups (p<=0.01)."
- ^ Wirshing, Donna A.; Wirshing, William C.; Kysar, Lisa; Berisford, M. Andrew; Goldstein, Danielle; Pashdag, Joanna; Mintz, Jim; Marder, Stephen R. (1999). "Novel Antipsychotics". The Journal of Clinical Psychiatry 60 (6): 358–63. doi:10.4088/JCP.v60n0602. PMID 10401912.
- ^ "NIMH study to guide treatment choices for schizophrenia" (Press release). National Institute of Mental Health. 19 September 2005. Retrieved 2006-12-18.
- ^ McEvoy, J. P.; Lieberman, J. A.; Perkins, D. O.; Hamer, R. M.; Gu, H.; Lazarus, A.; Sweitzer, D.; Olexy, C.; Weiden, P.; Strakowski, SD (2007). "Efficacy and Tolerability of Olanzapine, Quetiapine, and Risperidone in the Treatment of Early Psychosis: A Randomized, Double-Blind 52-Week Comparison". American Journal of Psychiatry 164 (7): 1050–60. doi:10.1176/appi.ajp.164.7.1050. PMID 17606657.
- ^ Nemeroff, CB (1997). "Dosing the antipsychotic medication olanzapine". The Journal of Clinical Psychiatry 58 (Suppl 10): 45–9. PMID 9265916.
- ^ Weston-Green, Katrina; Huang, Xu-Feng; Deng, Chao (2011). "Olanzapine treatment and metabolic dysfunction: A dose response study in female Sprague Dawley rats". Behavioural Brain Research 217 (2): 337–46. doi:10.1016/j.bbr.2010.10.039. PMID 21056063.
- ^ Vestri, Helliner S; Maianu, Lidia; Moellering, Douglas R; Garvey, W Timothy (2006). "Atypical Antipsychotic Drugs Directly Impair Insulin Action in Adipocytes: Effects on Glucose Transport, Lipogenesis, and Antilipolysis". Neuropsychopharmacology 32 (4): 765–72. doi:10.1038/sj.npp.1301142. PMID 16823387.
- ^ Fulbright, A. R.; Breedlove, K. T. (2006). "Complete Resolution of Olanzapine-Induced Diabetic Ketoacidosis". Journal of Pharmacy Practice 19 (4): 255–8. doi:10.1177/0897190006294180.
- ^ Chiu, Chih-Chiang; Chen, Chun-Hsin; Chen, Bo-Yu; Yu, Shu-Han; Lu, Mong-Liang (2010). "The time-dependent change of insulin secretion in schizophrenic patients treated with olanzapine". Progress in Neuro-Psychopharmacology and Biological Psychiatry 34 (6): 866–70. doi:10.1016/j.pnpbp.2010.04.003. PMID 20394794.
- ^ Sacher, Julia; Mossaheb, Nilufar; Spindelegger, Christoph; Klein, Nikolas; Geiss-Granadia, Thomas; Sauermann, Robert; Lackner, Edith; Joukhadar, Christian; Müller, Markus; Kasper, Siegfried (2007). "Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers". Neuropsychopharmacology 33 (7): 1633–41. doi:10.1038/sj.npp.1301541. PMID 17712347.
- ^ Sowell, M.; Mukhopadhyay, N; Cavazzoni, P; Carlson, C; Mudaliar, S; Chinnapongse, S; Ray, A; Davis, T et al. (2003). "Evaluation of Insulin Sensitivity in Healthy Volunteers Treated with Olanzapine, Risperidone, or Placebo: A Prospective, Randomized Study Using the Two-Step Hyperinsulinemic, Euglycemic Clamp". Journal of Clinical Endocrinology & Metabolism 88 (12): 5875–80. doi:10.1210/jc.2002-021884. PMID 14671184.
- ^ Albaugh, V. L.; Vary, T. C.; Ilkayeva, O.; Wenner, B. R.; Maresca, K. P.; Joyal, J. L.; Breazeale, S.; Elich, T. D.; Lang, C. H.; Lynch, C. J. (2010). "Atypical Antipsychotics Rapidly and Inappropriately Switch Peripheral Fuel Utilization to Lipids, Impairing Metabolic Flexibility in Rodents". Schizophrenia Bulletin 38 (1): 153–66. doi:10.1093/schbul/sbq053. PMC 3245588. PMID 20494946.
- ^ Albaugh, V L; Judson, J G; She, P; Lang, C H; Maresca, K P; Joyal, J L; Lynch, C J (2010). "Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis". Molecular Psychiatry 16 (5): 569–81. doi:10.1038/mp.2010.33. PMC 2892549. PMID 20308992.
- ^ Weston-Green, Katrina; Huang, Xu-Feng; Deng, Chao (2012). "Alterations to Melanocortinergic, GABAergic and Cannabinoid Neurotransmission Associated with Olanzapine-Induced Weight Gain". In Chang, Alice Y. W. PLoS ONE 7 (3): e33548. Bibcode:2012PLoSO...733548W. doi:10.1371/journal.pone.0033548. PMC 3306411. PMID 22438946.
- ^ Weston-Green, Katrina; Huang, Xu-Feng; Lian, Jiamei; Deng, Chao (2012). "Effects of olanzapine on muscarinic M3 receptor binding density in the brain relates to weight gain, plasma insulin and metabolic hormone levels". European Neuropsychopharmacology 22 (5): 364–73. doi:10.1016/j.euroneuro.2011.09.003. PMID 21982116.
- ^ Carey, Benedict (September 20, 2005). "Little Difference Found in Schizophrenia Drugs". The New York Times. Retrieved 2007-12-03.
- ^ de Haan, Lieuwe; Van Amelsvoort, Therese; Rosien, Kim; Linszen, Don (2004). "Weight loss after switching from conventional olanzapine tablets to orally disintegrating olanzapine tablets". Psychopharmacology 175 (3): 389–90. doi:10.1007/s00213-004-1951-2. PMID 15322727.
- ^ Rasmussen, SA; Chu, SY; Kim, SY; Schmid, CH; Lau, J (June 2008). "Maternal obesity and risk of neural tube defects: a metaanalysis". American Journal of Obstetrics & Gynecology 198 (6): 611–619. doi:10.1016/j.ajog.2008.04.021. PMID 18538144.
- ^ McMahon, DM; Liu, J; Zhang, H; Torres, ME; Best, RG (February 2013). "Maternal obesity, folate intake, and neural tube defects in offspring". Birth Defects Research Part A: Clinical and Molecular Teratology 97 (2): 115–122. doi:10.1002/bdra.23113. PMID 23404872.
- ^ Dorph-Petersen, Karl-Anton; Pierri, Joseph N; Perel, James M; Sun, Zhuoxin; Sampson, Allan R; Lewis, David A (2005). "The Influence of Chronic Exposure to Antipsychotic Medications on Brain Size before and after Tissue Fixation: A Comparison of Haloperidol and Olanzapine in Macaque Monkeys". Neuropsychopharmacology 30 (9): 1649–61. doi:10.1038/sj.npp.1300710. PMID 15756305.
- ^ Konopaske, Glenn T.; Dorph-Petersen, Karl-Anton; Sweet, Robert A.; Pierri, Joseph N.; Zhang, Wei; Sampson, Allan R.; Lewis, David A. (2008). "Effect of Chronic Antipsychotic Exposure on Astrocyte and Oligodendrocyte Numbers in Macaque Monkeys". Biological Psychiatry 63 (8): 759–65. doi:10.1016/j.biopsych.2007.08.018. PMC 2386415. PMID 17945195.
- ^ Selemon, Lynn D.; Lidow, Michael S.; Goldman-Rakic, Patricia S. (1999). "Increased volume and glial density in primate prefrontal cortex associated with chronic antipsychotic drug exposure". Biological Psychiatry 46 (2): 161–72. doi:10.1016/S0006-3223(99)00113-4. PMID 10418690.
- ^ Brambilla, Giovanni; Mattioli, Francesca; Martelli, Antonietta (2009). "Genotoxic and carcinogenic effects of antipsychotics and antidepressants". Toxicology 261 (3): 77–88. doi:10.1016/j.tox.2009.04.056. PMID 19410629.
- ^ "4.2.1 Antipsychotic drugs". British National Formulary (57th ed.). London and Chicago: Pharmaceutical Press. March 2009. pp. 221–31. ISBN 978-0-85711-065-7. "Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse."
- ^ "Harm Reduction Guide To Coming Off Psychiatric Drugs & Withdrawal". Icarus Project. April 23, 2008.
- ^ Kim, Deborah R. (2005). "Quetiapine Discontinuation Syndrome". American Journal of Psychiatry 162 (5): 1020. doi:10.1176/appi.ajp.162.5.1020. PMID 15863814.
- ^ Michaelides, Costas; Thakore-James, Manisha; Durso, Raymon (2005). "Reversible withdrawal dyskinesia associated with quetiapine". Movement Disorders 20 (6): 769–70. doi:10.1002/mds.20427. PMID 15747370.
- ^ Chouinard, G; Jones, BD (1980). "Neuroleptic-induced supersensitivity psychosis: Clinical and pharmacologic characteristics". The American Journal of Psychiatry 137 (1): 16–21. PMID 6101522.
- ^ Miller, R; Chouinard, G (1993). "Loss of striatal cholinergic neurons as a basis for tardive and L-dopa-induced dyskinesias, neuroleptic-induced supersensitivity psychosis and refractory schizophrenia". Biological Psychiatry 34 (10): 713–38. doi:10.1016/0006-3223(93)90044-E. PMID 7904833.
- ^ Chouinard, G; Jones, BD; Annable, L (1978). "Neuroleptic-induced supersensitivity psychosis". The American Journal of Psychiatry 135 (11): 1409–10. PMID 30291.
- ^ Seeman, Philip; Weinshenker, David; Quirion, Remi; Srivastava, Lalit K.; Bhardwaj, Sanjeev K.; Grandy, David K.; Premont, Richard T.; Sotnikova, Tatyana D.; Boksa, Patricia; El-Ghundi, M; O'Dowd, BF; George, SR; Perreault, ML; Männistö, PT; Robinson, S; Palmiter, RD; Tallerico, T (2005). "Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis". Proceedings of the National Academy of Sciences 102 (9): 3513–8. Bibcode:2005PNAS..102.3513S. doi:10.1073/pnas.0409766102. JSTOR 3374957. PMC 548961. PMID 15716360.
- ^ Moncrieff, J. (2006). "Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse". Acta Psychiatrica Scandinavica 114 (1): 3–13. doi:10.1111/j.1600-0447.2006.00787.x. PMID 16774655.
- ^ a b "Symbyax (Olanzapine and fluoxetine) drug overdose and contraindication information". RxList: The Internet Drug Index. WebMD. 2007. Retrieved 2007-12-03.
- ^ Wang, JS; Zhu, HJ; Markowitz, JS; Donovan, JL; DeVane, CL (September 2006). "Evaluation of antipsychotic drugs as inhibitors of multidrug resistance transporter P-glycoprotein". Psychopharmacology (Berl) 187 (4): 415–423. doi:10.1007/s00213-006-0437-9. PMID 16810505.
- ^ Moons, T; de Roo, M; Claes, S; Dom, G (August 2011). "Relationship between P-glycoprotein and second-generation antipsychotics". Pharmacogenomics 12 (8): 1193–1211. doi:10.2217/pgs.11.55. PMID 21843066.
- ^ Roth, BL; Driscol, J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 26 November 2013.
- ^ a b Weston-Green, Katrina; Huang, Deng (10 October 2013). "Second Generation Antipsychotic-Induced Type 2 Diabetes: A Role for the Muscarinic M3 Receptor". CNS Drugs 27: 1069–1080. doi:10.1007/s40263-013-0115-5. PMID 24114586. Retrieved 15 February 2014.
- ^ Johnson, D. E.; Yamazaki, H.; Ward, K. M.; Schmidt, A. W.; Lebel, W. S.; Treadway, J. L.; Gibbs, E. M.; Zawalich, W. S. et al. (2005). "Inhibitory Effects of Antipsychotics on Carbachol-Enhanced Insulin Secretion from Perifused Rat Islets: Role of Muscarinic Antagonism in Antipsychotic-Induced Diabetes and Hyperglycemia". Diabetes 54 (5): 1552–8. doi:10.2337/diabetes.54.5.1552. PMID 15855345.
- ^ Silvestre, J.S.; Prous, J. (2005). "Research on adverse drug events. I. Muscarinic M3 receptor binding affinity could predict the risk of antipsychotics to induce type 2 diabetes". Methods and Findings in Experimental and Clinical Pharmacology 27 (5): 289–304. doi:10.1358/mf.2005.27.5.908643. PMID 16082416.
- ^ "olanzapine". NCI Drug Dictionary. National Cancer Institute.
- ^ Lemke TL, Williams DA (2009) Foye's Medicinal Chemistry, 6th edition. Wolters Kluwer: New Delhi. ISBN 978-81-89960-30-8.
- ^ "Medication and Weight Control"
- ^ "NDA 21-520" (PDF). Food and Drug Administration. 2003-12-24. Retrieved 2009-09-06.
- ^ "NDA 20-592 / S-019" (PDF). Food and Drug Administration. 2004-01-14. Retrieved 2009-09-06.
- ^ Pillarella J, Higashi A, Alexander GC, Conti R (2012). "Trends in the use of atypical antipsychotics for the treatment of bipolar disorder in the United States, 1998-2009". Psychiatric Services 63 (1): 83–86. doi:10.1176/appi.ps.201100092. PMID 22227765.
- ^ Forbes.com[dead link]
- ^ treatment resistant depression defined as major depressive disorder in adult patients who do not respond to two separate trials of different antidepressants of adequate dose and duration in the current episode
- ^ "NDA 20-592" (PDF). Food and Drug Administration. 1996-09-06. Retrieved 2009-09-06.
- ^ a b c d "Eli Lilly and Company Agrees to Pay $1.415 Billion to Resolve Allegations of Off-label Promotion of Zyprexa". U.S. Justice Department. 2009-01-15. Retrieved 2012-07-09.
- ^ Berenson, Alex (January 4, 2007). "Mother Wonders if Psychosis Drug Helped Kill Son". The New York Times. Retrieved May 21, 2013.
- ^ MSN.com Lilly settles Zyprexa suit for $1.42 billion. The Associated Press, January 15, 2009
- ^ Fisk, Margaret Cronin; Lopatto, Elizabeth; Feeley, Jef (June 1, 2009). "Lilly Sold Drug for Dementia Knowing It Didn't Help, Files Show". Bloomberg. Retrieved May 21, 2013.
- ^ Berenson, Alex (December 18, 2006). "Drug Files Show Maker Promoted Unapproved Use". The New York Times. Retrieved May 21, 2013.
- ^ Berenson, Alex (December 17, 2006). "Eli Lilly Said to Play Down Risk of Top Pill". The New York Times. Retrieved May 21, 2013.
- ^ a b c L-Z\In re Zyprexa\Documents Leak\Injunction Memo & Order\FINAL INJUNCTION MEMO 2.13.07.wpd
- ^ EFF.org
- ^ Press Releases: January, 2007 | Electronic Frontier Foundation
- ^ a b Eli Lilly was Concerned by Zyprexa Side-Effects from 1998,[dead link] The Times (London), January 23, 2007
- ^ Navari, Rudolph M.; Einhorn, Lawrence H.; Loehrer Pj, Patrick J.; Passik, Steven D.; Vinson, Jake; McClean, John; Chowhan, Naveed; Hanna, Nasser H.; Johnson, Cynthia S. (2007). "A phase II trial of olanzapine, dexamethasone, and palonosetron for the prevention of chemotherapy-induced nausea and vomiting: A Hoosier oncology group study". Supportive Care in Cancer 15 (11): 1285–91. doi:10.1007/s00520-007-0248-5. PMID 17375339.
- ^ McGlashan, T.H; Zipursky, R.B; Perkins, D; Addington, J; Miller, T.J; Woods, S.W; Hawkins, K.A; Hoffman, R; Lindborg, S; Tohen, M; Breier, A (2003). "The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis". Schizophrenia Research 61 (1): 7–18. doi:10.1016/S0920-9964(02)00439-5. PMID 12648731.
- ^ McGlashan, Thomas H.; Zipursky, Robert B.; Perkins, Diana; Addington, Jean; Miller, Tandy; Woods, Scott W.; Hawkins, Keith A.; Hoffman, Ralph E.; Preda, Adrian; Epstein, I; Addington, D; Lindborg, S; Trzaskoma, Q; Tohen, M; Breier, A (2006). "Randomized, Double-Blind Trial of Olanzapine Versus Placebo in Patients Prodromally Symptomatic for Psychosis". American Journal of Psychiatry 163 (5): 790–9. doi:10.1176/appi.ajp.163.5.790. PMID 16648318.
External links[edit]
- Zyprexa.com - official Zyprexa brand website from Eli Lilly and Company
- Zyprexa package insert
- Berenson, Alex (December 17, 2006). "Lilly Settles With 18,000 Over Zyprexa". New York Times.


text:
Study of Bevacizumab Followed by Bevacizumab Consolidation for Ovarian Cancer
Recruitment status was Active, not recruiting
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
The purpose of this study is to evaluate the tolerability of intraperitoneal cisplatin with intravenous paclitaxel and Avastin as defined by the proportion of patients able to complete 6 cycles of treatment.
Advanced Ovarian Carcinoma
Primary Peritoneal Carcinoma
Ovarian Carcinosarcoma
Drug: Avastin
Phase 2
|Study Type:
|Study Design:
|Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:
|Phase II Study of Paclitaxel, Intraperitoneal Cisplatin and IV Bevacizumab Followed by Bevacizumab Consolidation for Advanced Ovarian and Peritoneal Carcinoma
- Evaluating the tolerability of intraperitoneal cisplatin with intravenous paclitaxel and Avastin as defined by the proportion of patients able to complete 6 cycles of treatment. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Describe toxicities associated with intraperitoneal cisplatin with intravenous paclitaxel and Avastin. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
|Estimated Enrollment:
|Study Start Date:
|July 2007
|Estimated Study Completion Date:
|July 2012
|Estimated Primary Completion Date:
|July 2012 (Final data collection date for primary outcome measure)
Drug: Avastin
- Avastin
- Bevacizumab
Initial Treatment:
Paclitaxel 135mg/m2 IV Day 1 every 21 days x 6 cycles, Cisplatin 75mg/m2 IP Day 2 every 21 days x 6 cycles, Bevacizumab 15mg/kg Day 1 IV every 21 days x 5 cycles (beginning with cycle 2)
Consolidation Treatment:
Avastin 15mg/kg IV every 21 days x 12 cycles
Ovarian cancer is the leading cause of death from gynecologic cancer in the United States. The high death rate stems from late presentation and tumor that has spread beyond the ovary at the time of diagnoses.
Ovarian cancer typically spreads throughout the peritoneal cavity. Three randomized clinical trial have recently demonstrated the superiority of intraperitoneal(IP) over intravenous platinum based chemotherapy in optimally debulked advance ovarian cancer. The success of Bevacizumab in metastatic colorectal cancer has led to trials evaluating its' efficacy in advanced ovarian cancer. Based on the mechanism of action of Bevacizumab, there may be benefit of extended therapy with this agent.
|Ages Eligible for Study:
|18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
Inclusion Criteria:
- Patients with stage II and III epithelial ovarian carcinoma, primary peritoneal carcinoma, or ovarian carcinosarcoma.
- Adequate bone marrow, renal, and hepatic function
- Patients must be entered no more than twelve weeks postoperatively
Exclusion Criteria:
- Patients with epithelial ovarian carcinoma of low malignant potential (borderline carcinomas).
- Stage IV or suboptimally debulked disease following primary cytoreductive surgery
- Patients who have received prior radiotherapy or chemotherapy.
|United States, Oklahoma
|University of Oklahoma Health Sciences Center
|Oklahoma City, Oklahoma, United States, 73104
|Principal Investigator:
|D. Scott McMeekin, MD
|University of Oklahoma
No publications provided
|Responsible Party:
|University of Oklahoma
|ClinicalTrials.gov Identifier:
|NCT00511992 History of Changes
|Other Study ID Numbers:
|AVF3953 McMeekin
|Study First Received:
|August 3, 2007
|Last Updated:
|October 27, 2011
|Health Authority:
|United States: Food and Drug Administration
United States: Institutional Review Board
Keywords provided by University of Oklahoma:
Ovarian Cancer
Gynecologic Cancer
Ovarian Carcinoma
Peritoneal Carcinoma
IP chemotherapy
Additional relevant MeSH terms:
Mixed Tumor, Mullerian
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Complex and Mixed
Neoplasms, Connective and Soft Tissue
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
ClinicalTrials.gov processed this record on April 22, 2014


text:
Some of "C"s little 3 and 4 year old friends
were over here for some of my summer art camp classes this week
and they LOVED her new tray -- it was very popular.
That would be perfect for my soon-to-be 3 year old son. He loves tools and wants to be a builder/farmer. He has plenty of time to make up his mind. He would love the real nuts and bolts. Thank you for sharing.
I can see children just LOVING this! I think when our little Matilda gets old enough, we'll have to do this one!
again...thank you for the continued wealth of ideas and inspiration!
xo maureen
A friend who does woodworking with a group of kids at our church showed me a cool trick one day. If you need to hold a nail for a child to hit, use pliers. I know it is simple but I wouldn't have thought of it myself. I thought your husband would like to know, just in case he didn't think of it either.
Yes, thank you for the pliers advice!
I've heard you can use a comb to hold a nail for a child who is learning to hammer as well!
: ) Fondly,
My son goes to a wonderful Montessori school and has been doing woodworking since he was 3! Without Montessori, I don't know if I ever would have been brave enough to let him handle a hammer at such a young age. But, I have realized (through his school) that if taught how to correctly use and care for tools, little ones love woodworking and can do it without getting hurt. He has brought home so many neat creations from school and also works on his own projects at home with me. He also likes nailing bottle caps to small pieces of wood.


text:
Families whose luck and blessings have experienced peaks and valleys. Families who survived their valleys because of programs that allowed them to have some form of daily nutrition and some way to maintain a roof over their head. Families who were able to rise out of those valleys to secure sound employment. Families whose children are able to attend college as first-generation students through scholarships combined with grants and loans offered at low rates.
We must redefine welfare in America. In some cases we should rectify abuses, but in other cases we need to recognize that helping poor students and hard-working families is a Godly thing to do, allowing them the opportunity to "pull themselves up by their bootstraps."
We must be thankful for what we have, compassionate for those who have not, and understanding that we could easily be in their shoes. "And the King shall answer and say unto them, Verily I say unto you, Inasmuch as ye have done it unto one of the least of these my brethren, ye have done it unto me." — Matthew 25:40.
Brett Johnson


text:
Suggest new AALD acronym or abbreviation definition
Please use this form if you are sure that such acronym or abbreviation exists and widely known.
Please make sure that the information you suggest for database inclusion is correct and doesn't contain any errors.
All suggestions are filtered for spam, invalid or non-common entries and only then checked by one of our editors.
Fields marked with red asterisk * are mandatory.


text:
Well, it is spring again. That warm, nice and bright season comes again. So let's prepare somthing special to welcome her – Pick up a perfect bag and enjoy a perfect spring. A perfect bag can not only knock off pounds visually (no kidding!), it'll also polish up your style in a flash.
Firstly, let's learn something about bag types.
- Tote – An open-top bag with straps or handles.
- Hobo bag – A crescent-shaped shoulder bag.
- Satchel – A satchel bag is often with a strap. The strap is often worn so that it diagonally crosses the body, with the bag hanging on the opposite hip, rather than hanging directly down from the shoulder.
- Clutch – A small, handheld bag or a larger, geometric shape that is tucked under the arm.
- Messenger Bag – A large, soft shoulder bag with long straps (often worn across the body).
Seondly: Scale
While the shape should oppose your body type for maximum flattery, the size of the bag should be in proportion to your figure. Generally speaking, a woman who is 6 feet tall and a size 14 would look lost with a teensy hand-held bag. A petite size 0 would look overwhelmed by an enormous slouchy bag. A shoulder bag's length (where the bottom of the bag hits your body) will accentuate whatever part of the body it comes near. For example, a shoulder bag that ends around the hips will play up your hip width (the eye is drawn to the bag). Most women look great with a bag that hits mid-torso because it flatters the waist.


text:
Let say i am zoomed in, 500%, and i want to go beyond the edge, right edge, and when i try to drag it using hand tool it doesn't work, scrollbar doesn't work.
Take the 2-minute tour ×
Graphic Design Stack Exchange is a question and answer site for professional graphic designers and non-designers trying to do their own graphic design. It's 100% free, no registration required.
There are additional plug ins from Adobe you can install. If you install the optional "Always Overscroll" plug in, you can always scroll past the canvas.
In addition, if you are in Full Screen Mode (View > Screen Mode or tap the F key) you can also always move paste the canvas.


text:
Has this ever been tossed about by the band?
Was wondering if the guyzz have ever thought about doing an album with covers of blues tunes from their favorite blues artists. I know they do a few anyway(i.e. Dust My Broom, Future Blues , One Foot In The Blues etc) but I would love to see a 12-15 track album with covers of Jimmy Reed, Lightnin' Hopkins, Hound Dog Taylor and others. Hound Dog Taylor's tone is as close to BFG as you will get from an old blues artist. I could just see BFG remaking Hound Dog's "My Baby's Coming Home" ZZ style. It would be a killer!!!!!! {:)>>>>
If you guys are reading this, please consider! Could be an album to cherish. Potential title for the album- "Scattered, Smothered, and Covered"
Potential ideas:
"My Baby's Coming Home" - Hound Dog Taylor
"Look On Yonder's Wall" - Hound Dog Taylor
" Movin' On Out Boogie" - Lightnin' Hopkins
" You Shook Me" - Willie Dixon
Anything by Jimmy Reed
Replies to This Posting
Re: Has this ever been tossed about by the band?
Thats a pretty cool idea. I've read that BFG has a solo blues album in the wings. Maybe that will use some of these great tracks!!


text:
Waterproof, breathable, and highly abrasion resistant MemBrain® fabric is seam taped and micro stitched to create this durable outdoor pant. Tailored to help you move over any terrain with ease thanks to an athletic cut and built-in anatomic articulation zones. Plenty of zippered and water-resistant pockets hold your essentials, and features like boot loops and ankle zippers cater to the extreme adventure set.
Look for this item to be back and available in the Fall.
Marmot Membrain™ lamination utilizes advance technology that balances the best in performance of breathability, waterproofness, and water repellency with excellent durability. With a minimum of 10, 000mm / 10,000mm performance it's guaranteed to keep you dry and comfortable in the worst of weather.
Marmot Membrain™ technology offers excellent weather protection with interior comfort. The hydrophilic nature of the PU lamination reduces internal condensation and increases comfort range by reducing the chilling effect caused by converting condensation build up back into vapor.
This 2 Layer Lamination combined with superior face fabrics, create a soft, quiet waterproof and breathability fabric with superior performance. With excellent breathability, and long term durable waterproofness this advance fabric technology brings a new level of performance to value conscious consumers.
Waterproofness: 10,000 mm minimum JIS-L 1092
Breathability: 10,000 gm / 24h minimum JIGS-1099 B1
Hohenstein RET: 6 to 8
Technology: 2 layer Hydrophilic PU Lamination
Why do we encourage proper care of our clothing and gear?
Because you have invested in (or are thinking about investing in) one of the most technically advanced pieces of apparel or equipment you'll ever own and we want to make sure you have the information you need to protect and care for your purchase. Proper care assures you will optimize the performance of your Marmot product and maximize its service-life.
Clothing Care


text:
Thursday, April 24, 2014
By Kevin Miller firstname.lastname@example.com
Staff Writer
WASHINGTON -- Maine Reps. Mike Michaud and Chellie Pingree voted in support of a fiscal cliff bill late Tuesday that avoids income tax hikes for the middle class and prevents a sharp increase in milk prices but sets the stage for difficult congressional battles over spending.
In this Oct. 22, 2009, file photo, Maine's Republican senators, Olympia Snowe, left, and Susan Collins, are seen on Capitol Hill in Washington.
2009 file photo/The Associated Press
Here are some of the ways the fiscal cliff compromise will affect Maine:
Income taxes: Income tax rates will remain the same for everyone except individuals earning $400,000 or more and couples earning in excess of $450,000. Exact figures for maine were not available on tuesday. However, it appears several thousand of maine's 500,000-plus taxpaying "households" -- meaning individuals or families -- will see an income tax increase. A maine revenue services official estimated that less than 10,000 individuals or families in maine earned either $200,000 or $250,000, respectively, so the number affected under the current bill will be even smaller.
Unemployment: The bill will allow those who have been unemployed for six months or longer to continue to qualify for unemployment benefits next year. Between 6,400 and 7,100 Mainers would have lost access to unemployment benefits without an extension.
Payroll taxes: The bill allows a temporary "payroll tax holiday" to expire, meaning that the vast majority of workers nationwide will see their paychecks shrink by 2 percent. Congress reduced the payroll tax -- which is used to help pay for social security -- two years ago due to the recession. Maine revenue services estimated that 2 percent increase translates into $355.1 million in Maine.
Wind power: Wind energy companies received a one-year extension on a 2.2 cent tax credit for every kilowatt hour generated from wind power facilities. Maine has more than a half-dozen commercial wind energy facilities operating in the state with numerous more under development.
Spending cuts: The compromise simply delays roughly $110 billion in across-the-board spending cuts for two months. There is concern about how the cuts will affect programs across Maine, from the low-income home energy assistance program to defense contractors such as the Bath Iron Works shipyard.
Pingree and Michaud -- both Democrats -- voted for the bill roughly 21 hours after Maine's two Republican senators, Olympia Snowe and Susan Collins, joined the overwhelming majority of their Senate colleagues in backing the legislation.
The numerous compromises in the bill caused angst on both sides of the aisle.
"I felt like that, for a lot of us, it was certainly not a perfect bill and not a perfect negotiation but it would have been much worse to let this drag on and to go over the cliff," Pingree said moments after the roughly 11 p.m. vote.
Michaud said the bill provides tax predictability to Maine families while extending important tax credits for families and businesses. Michaud also noted that the bill prevents a 27 percent cut in Medicare reimbursement rates for doctors, which many feared could cause some physicians to turn away patients or close their offices.
"I'm disappointed that House leadership and the White House waited until the last minute and could not accomplish a larger deal to address the debt, debt ceiling, as well as taxes," Michaud said in a statement. "But I look forward to working with my colleagues on both sides of the aisle to tackle those issues in the coming weeks."
Pingree said that, in addition to the tax provisions, she was pleased that the bill extends unemployment benefits for those struggling to find work and prevents a law change that would have nearly doubled the price of milk.
"This is about making sure the country doesn't go backward in this economic recovery," said Pingree, who is married to S. Donald Sussman, majority share owner of MaineToday Media, publisher of the Portland Press Herald.
The bill now headed to President Obama's desk maintains current income tax rates for most families. Individuals earning $400,000 or more and households earning in excess of $450,000 will see their income tax rates rise from 35 percent to 39.6 percent.
The bill also shields nearly 30 million middle-income families from the alternative minimum tax, or AMT; extends tax credits for families with children; continues unemployment benefits for more than 6,000 Mainers and 2 million nationwide who have been jobless for six months or longer; and renews for one more year tax credits on wind energy companies.
Most workers will still see their paychecks shrink, however, because Congress opted not to extend a temporary 2 percent payroll tax cut that helps fund Social Security. And Congress will have to deal with how to administer across-the-board spending cuts that have been suspended for two months.
The Senate had passed the bill by a vote of 89-8 at 2 am. Tuesday, following last-minute negotiations between Republicans and Vice President Joe Biden.
"It's not the bill that I would have written but, on balance, I think that it will help protect our middle-income families and our small businesses, in many cases, and prevent us from inflicting a severe shock on our economy," Collins said while leaving the Capitol complex early Tuesday morning.
Collins said she was disappointed that the compromise delayed decisions on the spending cuts -- also known as sequestration -- that have created uncertainty in Maine businesses, particularly those in the defense industry.
But Collins said she believed it was important to prevent an average tax increase of more than $2,000 on Maine families and was pleased with language in the bill to avoid a spike in milk prices.
(Continued on page 2)


text:
U.S. Rep. Elizabeth Esty, D-5th District, has accepted tens of thousands of dollars in campaign contributions from people in the energy and environmental industries, which are regulated by her husband, Dan Esty, commissioner of the state Department of Energy and Environmental Protection.
And although she returned $3,500 of those contributions late last month amid political controversy, it appeared Friday that she plans to keep the rest.
It's an unusual situation — a husband whose state agency can affect people who give money to his wife's campaign — and recent events have shown that it could mean political trouble for the first-term congresswoman who is only a year away from her re-election campaign.
On April 25, Elizabeth Esty responded to political criticism by returning $3,500 in campaign contributions received since 2011 from executives and lobbyists from Northeast Utilities, which is regulated by DEEP.
The National Republican Campaign Committee had demanded that she return the money and claimed that Dan Esty gave "favorable treatment" to NU as DEEP commissioner. Dan Esty has denied that, and a spokesman for Elizabeth Esty said she was only returning the $3,500 to end an "unnecessary distraction."
But what about all that other money from people in the energy and environment fields?
Federal campaign records show that Elizabeth Esty has taken in at least $30,000 from employees and lobbyists for energy and environmental businesses toward her successful 2012 campaign and upcoming 2014 effort.
No one has raised an allegation of illegality, but, in politics, the appearance of favoritism or potential impropriety can be enough to cause problems.
In the wake of Esty's recent return of the NU-related contributions, The Courant asked Friday where she draws the line between contributions she'll accept, and those she'll decline, from the energy and environment sectors.
"Elizabeth is proud to have received support from thousands of people across Connecticut and across the country including many leaders in the environmental and energy fields who respect her record, knowledge, and work on these complex issues," her spokesman, Jeb Fain, said in an email, concluding: "She returned $3,500 in contributions from NU employees in the interest of ending an unnecessary distraction."
Fain was asked if that means Esty will keep the rest of the campaign contributions from the energy and environmental sectors her husband regulates, and will continue to accept such donations in the future. He didn't respond to that, or to a request to speak to the congresswoman.
Back in Oct. 2011, when Esty got the first of the contributions from NU executives that she finally returned late last month, the director of the Center for Responsive Politics said that it was an issue worth watching. The reason: Corporate executives could be "seeking favor" from an official whose agency regulates them by giving campaign contributions to his wife, said Sheila Krumholz, head of the Washington, D.C., organization.
Not all of Elizabeth Esty's contributors from the energy and environment fields have had actual dealings with DEEP or now fall under its direct jurisdiction – many are from out of state – but some have Connecticut connections. For example:
•Three Connecticut lobbyists, registered to contact DEEP for companies including EquiPower Resources Corp., GDF SUEZ-FirstLight Power, and Norwich Public Utilities, made individual contributions totaling $4,000 in 2012 and 2013 to Elizabeth Esty's 2014 campaign committee.
•Contributing $750 since 2011 were the two principal executives of BNE Energy Inc., developers of a controversial, proposed wind farm in Colebrook approved by state regulators.
•Two out-of-state executives with NRG Energy Inc., a company with government-regulated facilities throughout the U.S., including Connecticut, gave a combined $2,500.
Other contributions came from people employed in environmental consulting and in natural gas, wind or solar power businesses.
The political circumstances surrounding the return of the $3,500 in NU-linked contributions were more volatile than other cases because of the financial history between NU and Dan Esty: He received $205,000 from NU as its consultant from 1997 to 2005, years before he became Gov. Dannel P. Malloy's DEEP commissioner in 2011.
That past relationship, combined with Dan Esty's participation in an April 23 conference call hosted by an investment firm that had recently upgraded its rating of NU's stock, sparked the National Republican Campaign Committee's public demand for Elizabeth Esty to return the $3,500.
But the campaign committee also raised the broader issue that Krumholz did in 2011: When people regulated by the commissioner contribute to his wife's campaign, it can raise questions.
NOTE: This column was posted online at courant.com Friday night. On Saturday morning, statements were issued by state Republican Party Chairman Jerry Labriola and Mark Greenberg, who is seeking the GOP nomination to run against Elizabeth Esty in the 2014 congressional election:
Labriola said: "These donations raise a number of questions: Will Elizabeth Esty return these donations as she did the previous improper donations late last month? If not, on what grounds will she keep the money? Will Governor Malloy instruct his Commissioner to advise companies he regulates to refrain from making donations to his wife because of the strong appearance of impropriety they create? Common sense would tell anyone that this 'regulated by one half of the household, while donating to the other half' is a very bad arrangement."
Greenberg said: "Nearly two years ago, I called on then-candidate Elizabeth Esty to return any campaign donations she received from companies regulated by her husband. ... Elizabeth refused to acknowledge this blatant conflict of interest until recently when she returned the NU donations under heavy public pressure and media exposure.
"Clearly, these newly reported donations only make her conflict of interest much worse and more expansive. Rep. Esty should immediately return all of the donations and she should ... refrain from taking donations from companies regulated by her husband in the future. This conflict of interest is stunning for how blatant it is. It is an 'in your face' conflict of interest."
The executive director for the state Democratic Party, Jonathan Harris, responded: "Republicans in Connecticut have become like the Republicans in Washington; they have no ideas, so they spend all their time attacking and blocking. It's all rather sad and depressing.
"The Republican Party has been attacking and trying to make an issue of this for the past couple of years. With each attack, Elizabeth has addressed the issue in a forthright manner. The voters had a chance to assess those attacks and her responses and decided to elect Elizabeth to Congress. Case closed."
Jon Lender is a reporter on The Courant's investigative desk, with a focus on government and politics. Contact him at email@example.com, 860-241-6524, or c/o The Hartford Courant, 285 Broad St., Hartford, CT 06115 and find him on Twitter@jonlender.


text:
Ladies' (1)
Men's (4)
White (5)
Gold (3)
Tungsten (2)
Black (1)
White (3)
Yellow (1)
Compare up to 5 Items
Receive a $50 Offer When You Sign Up for Email*
No Thank You
*Valid for new registrations only.
A welcome email will be sent with your offer information.
Privacy Policy


text:
Caldwell Orange Peel 8" Self-Adhesive Sight-In Target
Product Family #: 2135324032
Suggested Products
Substitute Products
- Birchwood Casey Shoot-N-C 8" Sight-In Target ... $5.09 - $10.29 Select Options
- Caldwell Orange Peel Target 8" Self-Adhesive Bullseye Package... $10.29 Available
- EZ Target Sight-In Replacement Pad Target 11" x 17" Paper... $5.09 Available
- Champion VisiShot 8" Bullseye Target 8.5" x 11" Paper Package... $5.09 Available
- Caldwell Orange Peel Target Self-Adhesive Silhouette... $3.09 - $10.29 Select Options
- Caldwell Plain Paper Target 8" Sight-In Package of 25... $3.29 Available
- Caldwell Orange Peel 16" Self-Adhesive Sight-In Target... $8.09 - $13.79 Select Options
- Birchwood Casey Shoot-N-C Target 6" Bullseye Package of 12... $8.19 Available
- Caldwell Plain Paper Target 8" Bullseye Package of 25... $3.29 Available
- Birchwood Casey Shoot-N-C 12" Sight-In Target Kit Package of 4... $7.09 Available
Others Bought
- MTM Flip-Top Ammo Box 10mm Auto, 40 S&W, 45 ACP 50-Round... $1.99 Select Options
- Remington Slugger Ammunition 20 Gauge 2-3/4" 1/2 oz High... $5.09 Available
- Winchester Super-X High Brass Ammunition 12 Gauge 2-3/4" 1-1/4... $14.49 - $134.99 Select Options
- Federal Premium Personal Defense Ammunition 9mm Luger 115... $20.49 Available
- Remington Express Ammunition 16 Gauge 2-3/4" 1-1/8 oz #6 Shot... $16.99 Out of Stock, Backorder OK
- Redding T-7 Turret Press Turret with Bushings... $62.99 Available
- Hornady Rim Thickness Gage 17-22 Caliber... $29.99 Available
- Redding Taper Crimp Die 44 Special, 44 Remington Magnum... $26.49 Available
- Hoppe's BoreSnake Bore Cleaner Rifle 338, 340 Caliber... $12.99 Available
- Wilson Combat 1-Piece Full Length Recoil Spring Guide Rod with... $29.99 Available
- Woodman's Pal Round Stone Two-Grit Electro-Silicone Sharpener... $20.49 Available
- Collector's Armoury Replica Old West Indian Police Badge Brass... $6.99 Available
Product Information
Orange Peel Targets consist of a black bullseye on a bright orange background. A hit on the bullseye is rewarded with a bright green ring that is easily seen at a distance. A miss on the orange border leaves a bright white ring. Either way, the target is easily scored without leaving the firing line. Each target also features a convenient self-adhesive backing.
Technical Information
Targets have a black bullseye that will turn green where hit
Target background is orange and will turn white where hit
Sheets are adhesive-backed
Technical Information
Know someone who may like this? Email this Page to a Friend
Customer Reviews
The statements and opinions expressed within Customer Reviews reflect each author's personal perspective and do not imply endorsement by MidwayUSA, its Employees or any other organization. Customers should in no way infer that MidwayUSA has validated review information as safe, accurate or appropriate.
NOTE: Prices, specifications and availability are subject to change without notice.
We reserve the right to correct typographic, photographic and/or descriptive errors.
We reserve the right to correct typographic, photographic and/or descriptive errors.


text:
About AQ
About Aquinas
About Grand Rapids
Adult Undergraduate
Financial Aid
A-Z Dept. Listing
Course Catalog
Service Learning
International Programs
Campus Life
Residence Life
The Moose
"He who does not know foreign languages does not know anything about his own." - Johann Wolfgang von Goethe
German – the most widely-spoken language in Europe – is the leading language of science, literature, art, music, philosophy and history, and Germany's economy is the largest one in the European Union.
Whether you have German ancestry, want to learn more about the German language and culture, and other German-speaking countries in Europe (Germany, Austria, Switzerland, Liechtenstein, Luxembourg), learn about the German literature, traditions, contemporary German film, and business; or immerse yourself in one of our four German Study Abroad Programs in Tübingen, Lüneburg, Freiburg, and Mayen – the Aquinas German Program is here to answer your questions and meet your needs.
For more information please contact Dr. Katharina Häusler-Gross at firstname.lastname@example.com, call (616) 632-2122, or stop by my office in AB 9C in the Department of World Languages.
German Events in the U.S. - do Deutsch
German Word of the Week
New AQ International Programs Germany Video
>Watch it online
German Alumni Profiles
Andrew Demshuk '02 has been appointed as assistant professor of German history at the University of Alabama at Birmingham. >Read More
The European Union (Helpful info for FL230)
What you can DO with German?
Here are just some examples (from the University of St. Thomas):
10 Reasons for German
German Fun Facts
German Quizzes and Games
German Radio
Deutsche Welle (News & more)
Welcome to Germany.info
Der Spiegel (online)
Jugendmagazin Spiesser
Facts about Germany


text:
Boom was traced to a battery in a hydraulic ladder in lobby that was used for insulation project
|Important: Please note that this message cannot be edited after it is posted. If the article you are commenting on is not a secure law enforcement-only article, anyone visiting the PoliceOne site will be able to view your comment. If you are commenting on a secure law enforcement only article, only confirmed law enforcement officers will see your comment.
The comments below are member-generated and do not necessarily reflect the opinions of PoliceOne or its staff.
|Be the first to comment on this article.
|from |
|<< < |
|| > >>
Officials expressed confidence in heightened security measures while acknowledging the challenge of protecting an estimated 1M spectators and 36K runners
Police say they've taken a man into custody in connection with two unattended backpacks
Survivors, first responders and family members of those killed came together Tuesday to mark the anniversary of the Boston Marathon bombing
San Francisco 49ers linebacker Aldon Smith was arrested Sunday after authorities said he became belligerent and threatened that he had a bomb
A Boston police officer died on duty following a medical emergency


text:
You must earn 10,000 points to post other members' whiteboard
Good morning! May you begin this day with a smile on your face, and with happiness for your soul to embrace. Barb :)
Glad to your newest buddy. Where in Jersey are you located? I'm in Phila. Area in the far western counties around Philly.
Hey GB gd83goldwinger is dealing with his wife's cousin passing suddenly from influenza H1N1. Cousin came home not feeling good on the 3rd an by the 10th he passed away from it. He wanted me 2 pass the word to all my gas buddies to give a little condolences to his wife for her loss. He would greatly appreciate it for giving him a helping hand. Her profile name is rouxnthehouse. He said its been a rough three months for both of them. FHB
Feliz e Prospero Ano para voce!
Gas Buddy friends bring happiness throughout the year! Especially a gas buddy friend like you! Happy New Year! Barb
A New Year is the time to unfold new horizons
and realize new dreams.
Remembering to rejoice in the simple pleasures while gearing up for the new challenges.....May God Bless You in 2014
Wishing you and your family the blessings of the season and joyful, safe and warm holiday celebrations.............Michael
Thank you, Merry Christmas to you and your family..and a better NEW YEAR 2014 for everyone
Thank you, and may I wish you a very MERRY CHRISTMAS and a
HAPPY NEW YEAR, Your Buddy, David..........QQ
Happy Holidays my friend and a happy new year


text:
Walter Benton's "This Is My Beloved" provided the text for Arthur Prysock's recording of the same title.
The process of writing evolves one's consciousness and transforms the aspiring writer into an individual that he or she never fully imagined becoming. "
—Gale Contemporary Authors
About Aberjhani
A native of Savannah, Georgia (USA) Aberjhani is a winner of the Thomas Jefferson Award for his journalism, the Choice Academic Title and Best History Book Awards for his historical writings, the Creative Loafing Critic's Pick Best Savannah Author Award for...
Causes Aberjhani * Supports
I make contributions to a number of charities through my lenses on Squidoo but the following are a few that interest me the most:
Aberjhani's Favorite Books
My favorite books are pretty easy to tell because I generally write reviews about them and post and publish the reviews on in various magazines and websites,...