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Cannabis growers' cover melts away
Clever PSNI officers have been using the recent snowy, frosty weather as a means of spotting cannabis factories in local houses.
A tell-tale sign, they point out, could be a roof where snow melts while all around stays frosty and white. The plants need heat so the cannabis producers have to keep their place toasty.
Then again, a defrosting roof could also just be caused by poor insulation. And criminals, I suppose, could also fake a snowy roof with those spray cans you get in the craft aisles. That said, good try, PSNI. I doubt the cannabis cultivators are now dreaming of a white Christmas...
Belfast Telegraph


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The Peterborough DALROD Phantoms, Sponsored by Smart Solutions Group are pleased to announce the return of defenseman Robert Ferrara.
The local stay at home d man has made a fantastic 356 appearances for the Phantoms since 2006, with a brief spell also at Nottingham Lions and Peterborough Islanders.
Slava Koulikov commented on Robbie's return "I am very pleased Robbie will be returning with us next season, Robbie is a local guy from Peterborough and I know he is very proud to pull on the Phantoms jersey every match.
Robbie, is a great team guy to have around the locker room, he works very hard for the team and can play in any situation."
Slava Continues "While he isn't a big player in terms of size, he has great composure, does all the little things really well and the sort of player you can rely on.
His game is improving every season and I am looking forward to working with him again."
The 27 yr old, D man also spoke to us about his commitment to Phantoms, commenting "I am glad to be back with the Phantoms and looking forward to what will be hopefully another successful year.
Its exciting looking ahead to the new season in a new league where there are lots of new unknown elements.
I am sure Slava will get us drilled to not get distracted and go and compete for more silverware"
To Own and Loan Robbie Ferrara's home or away jersey for £150 each, please email firstname.lastname@example.com

subset: commoncrawl


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What is www.emt7.com? Know More About www.emt7.com
www.emt7.com is identified as a browser hijacker virus that has been designed by the cyber offenders in order to make money for their sponsors third party as well as developers. Usually, it generate revenue by rerouting PC users to its predefined sites or associated websites. Actually, the computer user have no interest to visit that website but even though they get rerouted to the certain websites unwillingly and frequently as well. In this way, website traffic as well as web page rank of that suspicious domain will increase and the revenue will also generated at the same time. In order to do so, first of all www.emt7.com hijacker virus will modify web browser's new tab, search and other vital settings. Consequently, whenever PC users try to access their web browser to surf the Internet they misguided to use those dubious websites that users had no intension to see.
Mostly, www.emt7.com virus infiltrates Windows based system and affect almost every popular web browsers like Google Chrome, Microsoft Edge, Mozilla Firefox, Safari, Internet Explorer, Opera and others without user's consent. Furthermore, this threat made its presence in the hidden form in shareware or freeware and when the users download free applications from an untrusted or hacked websites then along with the selected program this www.emt7.com hijacker virus also get entered on the associated computer. Thereafter, you may face several unwanted problems and your web browsing experience will be affected seriously.
Despite of these changes, some unknown extensions, toolbar and plug-ins also get attached with your active web browsers due to presence of www.emt7.com virus. As a result, whenever you will launch your web browser then it takes long time to get started completely. Also, it start displaying numerous fake pop-up warnings and notifications on the system screen. Although, you are highly advised that not to click on those otherwise lots of other nasty viruses will also get entered to your machine without your knowledge. In kind of situation, it would be better to delete www.emt7.com immediately from the computer to protect your PC from any damages.
Click Here to Free Download www.emt7.com Scanner Now
Removal Guide For www.emt7.com From PC
Know How To Remove www.emt7.com Manually
Easy www.emt7.com Removal From Windows Registry
First of all You need to restart your PC in Safe Mode and for that you can follow the below given steps.
Step 1. Start your PC and Hold F8 Keyword for few Second.
Step 2. Here you will find a Black screen with different option and you need to Click on Safe Mode option. Now your PC will start in safe mode and you can easily perform required activity to remove www.emt7.com in convenient manner.
Step 3. Now you advised to hot "Windows + R" Keys at the same time.
Step 4. In this step you can find Run option where in the text box you have to type "regedit" and then click OK button.
Step 5. Here you need to either click on Edit option in Menu or press CTRL+F button on the keyboard.
Step 6. After that you only have to type the name of infection in the box and then press Find Next option.
Here you can find all entries created by www.emt7.com on your PC and some are listed below that you need to delete as soon as possible.
Now Clean Corrupted Web Browsers
Sometimes it happens that due to invasion of browser redirect virus like www.emt7.com some unwanted plug-ins or toolbars get attached with the browser that you have to remove first and then you can rest your web browsers to make its functionality as it was earlier. In this regard steps are give below, take a look:-
Step 1. Launch your browser and click on Menu option at the Top right corner of the window. From the drop down list you have to select More Tools option and then Extensions.
Step 2. In this page you can find all unknown extensions created by www.emt7.com on your browser that you only have to select and remove by pressing delete button at the side of the window.
Know How To Reset Your Homepage
Before doing it, you can check for any unwanted pages created by this hijacker on the browser and if so then delete it immediately, for that you can follow the steps
Step 1. Open your browser and choose setting option from the Top right Menu.
Step 2. Under the On Startup option, you need to pick Open a Specific Page to set of pages. After that choose Set Pages option. You can also remove any unknown pages created by this threat from here by simply selecting and clicking on "X" button. Finally press OK to save changes.
Step 3. In the Appearance option, click Open Homepage button and tap on Change link option.
Resetting of Web browser for complete www.emt7.com Removal
Step 1. Start the Web browser and go to Menu icon and choose Settings option.
Step 2. In this page users are advised to select Show Advance Settings option and then press Reset Browser Settings.
Step 3. At last you need to click Reset button again to confirm the action.
Quickly Remove www.emt7.com and other Malware program From Control Panel
Step 1. Firstly, open your PC and then pick Start menu and from there you can choose Control Panel from the available list.
Step 2. Here you need to select Programs and then pick Uninstall a Program.
Step 3. Here you will find complete list of installed program and applications. You only have to choose www.emt7.com those programs that you want to uninstall by pressing button at the top Menu.
Still having any problem in getting rid of www.emt7.com, or have any doubt regarding this, feel free to ask our experts.


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Pic-of-The-day - "Lost in Abundance".
Spring Flowers in Niagara. Not sure what type of tree this is, but these big pink flowers are abundant in Niagara at this time of year.
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I'm also on Twitter, Redbubble, Flickr, Vimeo, YouTube, & Google+.


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I've been having some knee pain for the past week-and-a-half. Not terrible pain, just naggy, achy, something's-not-right pain. I had a great swim yesterday, my longest to date. And today my knee hurt worse. Bleh. So I called my physical therapist (my sister), who promptly told me that my pain was most likely my pes anserine, a tendon on the inner side of my knee. She told me to ice ( I knew that much), stretch, and not swim or run for a week. A week! I'm just getting going again after the holidays, this sucks! Anyway, she said I could bike so look for my training log for the next week to be filled with trainer workouts. The cadence sensor I ordered came in the mail today so that will hopefully add some interest to my workouts by knowing what I'm doing and being able to focus on specific feedback goals. I am planning to go to the pool and work on my pull with the pull buoy and just not do any kicking.
I also dropped my swim instructor. She was telling me to do things exactly the opposite of several reputable triathlon sites and books. I need to just concentrate on one methodology or the other and the form recommended in the books comes more naturally to me so I'm going with that for now.
I'm hoping to have a good week on the bike and be back to multisport training soon!


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The product listed here are for general craft use and there is no implied link to any licensed mark or use. These hard to find items are sold for convenience and not to lead a consumer to think they are associated with a particular organization.
There are no products matching the selection.


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Network Home
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Posts by Jeff Ousley
Military Age Restrictions: How Old is Too Old to Serve?
Why a Lender Sees Different Credit Scores Than What You See
New Report Shows Military Personnel Costs Spiraling Out of Control
Don't Spend That Bonus!
What Happens to Debt After a Loved One Passes?
You'll Never Guess Which Tool Lenders Are Using to Judge Your Finances
The Formula to a Balanced Budget
Should It Stay or Should It Go? What Financial Records You Need to Keep
Maximize Your Money Through Minimalism
UPDATE: It's Final! COLA Increase Approved for Disabled Veterans
DigiCam No More: Army Decides to Break the Pattern
A Call for Change to Deployment Pay
Female Service Members Fighting for a Place on the Battlefield
Vets Can Tap into New Military-to-Civilian Job Certification Program
New Military Recruiting Standards Signal the End of an Era
The Spectacular Rise and Fall of Tim Poe
A Word of Warning About Campus Debit Cards
New Law for Military Homeowners Allows More Options to Refinance
Sequestration Could Have Serious Consequences for Military Members
New Rules to Protect Veterans from For-Profit College Scams
Congress Considers Automatic COLA Increases
A Quick Rundown on Tax Extensions
Change in Deployment Leave Policy is a Breach of Trust for Soldiers
Stop Loss Compensation Program Extended for Eligible Service Members
Military Looking to Slim Down With Healthier Food Choices
Military Pay Raises Set to Shrink Under Proposed Budget
Considerations for the Post-Military Route to Retirement


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Here in Michigan a company spent several years and millions of dollars on permit applications and studies etc in hopes of building a clean coal fired plant.
Then last year the state denied the permit citing a lack of demand. Less than one month later they gave a permit for a wind farm despite the so called lack of demand.
The EPA and greentards intend to harass and break the energy producers.
Link to the EPA Fact Sheet on the changes that go into effect 1/2/11


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Zak onstage at SD in SL, with new hair and everything. Photo courtesy of Triana Caldera.
Sometime before my show today at the California Building at San Diego in SL I said to Kat, "Ya know, I think it'll be a pretty good show, but I'm not feeling like my voice is gonna be too spectacular today."
And of course, just to spite me, my voice was really in great shape, and I think it was one of my best shows of 2008 in terms of the performance. As you know, I'm far too humble to tout my own abilities (insert rolling eyes and huge smirk here), but for whatever reason, I was rocking San Diego today like it was the last gig on Earth. Really, really fun, with a nice sized crowd that stayed about 25 strong throughout most of the show, by my estimate.
I did play a new cover, as I've done lately at San Diego, and though I performed the entire group of original Zak Claxton tunes, I did not play a single cover this week that I'd done last week... I'm trying to keep it fresh for my repeat fans at this fun show.
So, sounded good, with a good crowd, and I never ask for more than that... except I got more! I had a bunch of friends show up, including Grace McDunnough (whose birthday is today), Doubledown Tandino, Djai Skjellerup, Tommy Cult, and others (in additional to my hostess Cher and my Greatest Fan, Triana). So it was just really fun and great to see folks, and I wish every one of my shows could be like today's!
Song Sample: "Falling Down" (Zak Claxton)
Here's what I played...
This Afternoon (Zak Claxton)
Summer Breeze (Seals & Crofts)
Thanks Anyway (Zak Claxton)
Court & Spark (Joni Mitchell)
Falling Down (Zak Claxton)
*Breaking Us in Two (Joe Jackson)
Always Tomorrow (Zak Claxton)
Any Major Dude (Steely Dan)
You're Like a Cloud (Zak Claxton)
What I Got (Sublime)
Ziggy Stardust (David Bowie)
Save It For Later (English Beat)
*Indicates first time I've performed this song in SL
Thanks to all who supported my show today at San Diego in SL!
Grace McDunnough, Smitty Boyau, Haruka Harris, Anutte Frankfurter, Triana Caldera, Tommy Cult, Djai Skjellerup, Doubledown Tandino, Esser Source, Roni Navarathna, HomeLess Martian, Senjata Witt, and of course the ever-gracious and fun Cher Harrington!


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Public Health
Maryland Department
CDC to launch anti-smoking campaign
By Meredith Cohn
March 19, 2012
The U.S. Centers for Disease Control and Prevention launched an ad campaign to show the damage done from smoking to smokers and their families. The ads began March 19 on television, radio, online and billboards, as well as in theaters, magazines and newspapers nationwide. Called "Tips from Smokers," the campaign will show former smokers living with diseases and disabilities. Specifically, the smokers suffer from lung and throat cancer, heart attacks, strokes and other diseases.
Ebola ruled out in one of two suspected cases at Washington, D.C.-area hospitals
By Scott Dance and The Baltimore Sun
October 4, 2014
Officials at two Washington, D.C.-area hospitals said Friday they had isolated patients over fears of Ebola after the nation's first case of the deadly virus was confirmed in Dallas this week. But officials at one of the hospitals, Shady Grove Adventist Hospital in Rockville, determined late Friday that their patient had malaria, not Ebola, hospital officials said in a statement late Friday. Howard University Hospital quarantined a patient who had recently traveled to Nigeria out of "an abundance of caution," officials said.
Women still drinking while pregnant, CDC says
By Andrea K. Walker
July 19, 2012
Women continue to mix cocktails and pregnancy despite the dangers it can pose to unborn babies. New government data found that 7.6 percent of women drank while pregnant and 1.4 percent of those moms binged on alcochol and beer. Binge drinking involves four or more drinks on one occasion. The Centers for Disease Control and Preventiion used data from a telephone survey of more than 345,000 women aged 18 to 44 to come up with its analysis. Of those, 13,880, or 4 percent, were pregnant.
Maryland prepares for cases of enterovirus
By Meredith Cohn and The Baltimore Sun
September 18, 2014
As an unusual strain of virus continues its march across the country — showing up most recently in Pennsylvania and Virginia — health officials in Maryland are warning doctors to be on the lookout and advising parents to prepare. Enterovirus is common, with millions in the United States sickened every year, most with mild cases. But the relatively rare strain called EV-D68 can cause severe respiratory illness in children with asthma or other health conditions, the U.S. Centers for Disease Control and Prevention warns.
CDC lowers lead poisoning threshold
By Timothy B. Wheeler, The Baltimore Sun
May 16, 2012
The number of young children deemed at risk of lead poisoning in Maryland and nationwide expanded drastically Wednesday as a federal health agency declared it would effectively cut in half its threshold for diagnosing the environmental illness. Acknowledging mounting evidence that children can suffer lasting harm from ingesting even minute amounts of lead, the Centers for Disease Control and Prevention said it would reduce the level at which it recommends that doctors, families and health authorities act to lower a child's exposure to the toxic metal.
CDC grants $12.5 million for HIV prevention in Maryland
By Meredith Cohn, The Baltimore Sun
January 4, 2012
Maryland will get $12.5 million from the U.S. Centers for Disease Control and Prevention to fund HIV prevention activities in the counties this year, down about $604,000 from last year, according to state health officials. The money comes from a $339 million pot of money doled out to states and a small number of cities according to their disease burden. And while Maryland's HIV caseload remains high, the grant dropped some because a share of the money was peeled off so the CDC could offer additional grants for innovative projects, which will be awarded in March.
Looking Out: CDC launches campaign encouraging HIV treatment
By Kevin Rector, The Baltimore Sun
September 18, 2014
The Centers for Disease Control and Prevention wants the American public to understand that HIV-positive people who receive treatment live longer and healthier lives compared to those who don't receive treatment, and has launched a new nationwide campaign to get the word out. The "HIV Treatment Works" campaign, announced Wednesday, is the CDC's "first communication campaign focused exclusively on encouraging treatment and care for people living with...
CDC: Outbreak of H1N1 flu appears to be peaking
December 1, 2009
The current wave of pandemic H1N1 flu appears to have peaked, with four weeks of declines in several key indicators, the Centers for Disease Control and Prevention said Monday. Despite those declines, the outbreak is continuing to take a heavy toll of hospitalizations and deaths, especially among children. Widespread activity of swine flu was reported in 32 states in the week ending Nov. 21, down from 43 states in the week before and 48 a month ago. Between Aug. 30 and Nov. 21, there were 29,348 laboratory-confirmed swine flu hospitalizations and 1,224 deaths in the United States, although those numbers are generally assumed to be very low. New figures are expected in a couple of weeks, but two weeks ago the CDC estimated that at least 4,000 people had died from swine flu, 98,000 had been hospitalized and 22 million had contracted the virus.
Syphilis increasing in men, CDC says
By LOS ANGELES TIMES
November 9, 2005
LOS ANGELES -- Men undertaking risky homosexual activity are fueling a sharp increase in the incidence of syphilis and a smaller but concerning rise in gonorrhea resistant to commonly used antibiotics, federal researchers said yesterday. Those increases come at a time when venereal disease rates among historically important risk groups, especially women and minorities, have been declining, according to a new report from the Centers for Disease Control and Prevention. San Francisco, as in previous years, had the highest incidence of syphilis, with a rate of 45.9 cases per 100,000 people.
CDC report faults practices of dentist who may have given AIDS to 3 patients
By Donna Leinwand and Donna Leinwand,Knight-Ridder News Service
January 17, 1991
WEST PALM BEACH, Fla. -- Infection-control techniques used by a Florida dentist did not measure up to national Centers for Disease Control standards and may have led to AIDS infections in three of his patients, according to the final draft of a CDC report to be published tomorrow.Genetic tests "strongly suggest" that Dr. David Acer somehow infected three of his patients, including Kimberly Bergalis, 22, who is suing her insurance provider for sending her to Dr. Acer, Ms. Bergalis' lawyers said.
Looking Out: CDC launches campaign encouraging HIV treatment
By Kevin Rector, The Baltimore Sun
September 18, 2014
The Centers for Disease Control and Prevention wants the American public to understand that HIV-positive people who receive treatment live longer and healthier lives compared to those who don't receive treatment, and has launched a new nationwide campaign to get the word out. The "HIV Treatment Works" campaign, announced Wednesday, is the CDC's "first communication campaign focused exclusively on encouraging treatment and care for people living with...
1 in 10 deaths among working-age adults alcohol related
By Meredith Cohn
July 10, 2014
Excessive drinking accounts for 10 percent of deaths among working-age adults, making it the leading cause of preventable death of Americans, according to new research from the U.S. Centers for Disease Control and Prevention . The alcohol use killed about 88,000 people aged 20 to 64 a year from 2006 to 2010, shortening their lives by about 30 years. They died from health effects including breast cancer, liver disease and heart disease, as well as from violence, alcohol poisoning and car crashes.
Funding superbug research is critical [Commentary]
Christian John Lillis
June 2, 2014
Anyone who has lost a loved one has experienced the five stages of grief: denial, anger, bargaining, depression and acceptance. Following my mother's death from one such infection, Clostridium difficile, or C. diff., in April 2010, I went through the stages also. In making the shift from depression to acceptance, my brother and I founded the Peggy Lillis Memorial Foundation to raise awareness of C. diff. In our anger at learning that a disease we'd never heard of, not only claimed our mother, but also kills more than 28,000 Americans every year, we committed to ensuring that her death would not be in vain.
Agencies investigating gastroenteritis outbreak in Harford Co.
By Sean Welsh, The Baltimore Sun
March 16, 2014
Complaints about stomach aches in Harford County might turn out to be more than a series of bellyaching. The Harford County Health Department and the Maryland Department of Health & Mental Hygiene are investigating an outbreak of stomach issues, a spokesman said Sunday night. "I can confirm a collaborative investigation between ourselves and the Maryland Department of Health & Mental Hygiene of what we believe at this time to be a restaurant-associated outbreak of gastroenteritis," said Harford County Health Department spokesman William Wiseman.
Lead is still poisoning our children
By Ruth Ann Norton
October 30, 2013
What if there was a completely preventable disease that affected one in 38 American children under the age of six and Congress effectively eliminated the funding that supports efforts to eradicate the cause of the disease? There is such a disease - lead poisoning - and Congress did slash funding for lead poisoning prevention at the Centers for Disease Control and Prevention (CDC) in the most recent federal budget. Every year more than half a million children are poisoned by lead in their homes, leaving them with irreversible brain damage that will affect them for the rest of their lives.
Fighting obesity with good nutrition
August 14, 2013
As The Sun recently noted, the Centers for Disease Control and Prevention issued a report explaining that obesity rates in the nation have declined ("Tide may be turning on U.S. childhood obesity - CDC," Aug. 6). Hooray! But if you look beneath that shiny veneer here in Maryland, you'll find that the glass is really half full. It's true that our state's obesity rate in low-income preschoolers, after decades of rising, began to level off from 2003 through 2008 and is now showing small declines.
State eyes guidelines on doctors with AIDS Md. medical society has task of implementing CDC policy.
By Sue Miller and By Sue Miller,Evening Sun Staff
July 16, 1991
The state medical society says it will move forward slowly to take on a leadership role to implement federal guidelines that yesterday urged doctors who perform "invasive" procedures and dentists who pull teeth and do root canals to quit if they become infected by the AIDS virus."
You're not just goldbricking if you have yuppie flu, CDC says
By Cox News Service
October 8, 1991
Atlanta - Evidence is mounting that Chronic Fatigue Syndrome, the so-called yuppie flu, is a physical illness, not a psychological one, despite the skepticism of some physicians.The earmarks of a real disease include a drug to treat it, the identification of an agent that may cause it and a Centers for Disease Control study to determine how many people have the disease and what its impact is.CDC officials in Atlanta asked doctors in four cities -- Atlanta; Reno, Nev.; Wichita, Kan.; and Grand Rapids, Mich.
It's Lyme season [Editorial]
Editorial from The Aegis
May 14, 2013
With some exceptions, any illness can strike anyone at any time. One of the more dangerous to emerge in recent decades is Lyme disease. Harford County, as many of us know either first-hand or because of someone we know, is not immune from the tick-borne disease. The revelation last week that Harford County Council President Billy Boniface has contracted the sickness is yet another reminder. Lyme disease is treatable, according to the Centers for Disease Control and Prevention, but it can also be debilitating.
One-fifth of teen births to moms already with kids
By Andrea K. Walker
April 2, 2013
One in 5 of teen births are from young moms who already have children, new CDC data shows. The Centers for Disease Control said Tuesday that although teen births have declined in the last two decades, one problem that remains is girls who get pregnant multiple times. There are about 183 "repeat teen births" each day, the CDC found. It is the second birth for 86 percent of the girls and the third birth for 13 percent of the moms. Teens with more than one child may find it difficult to finish school and get a good job. The babies are also often born premature.
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text: Vlad & Megs...(as is your job isn't hard enough as is...ush: ) I was wondering since we have all put SO much effort into creating a list of negative or "untrustworthy" eBay Sellers or sites...why don't we have a sticky post that actually names some of the decent sellers? I am NOT saying this b/c I want to sell my bags here...sure that would be nice, but I am not in a rush to make it to the Market Place & you both have your own reasons for everything. The though had just come up as I was reading all of the people that are selling fakes and the list is endless...so, maybe we should have a thread...where people can post successful transactions with certain eBay sellers...this might weed out most of the bad ones without having to bash them... Anyway, just a thought...you can even leave me out of the list ...I know I have already been brought up numerous times throughout the forum. Anyway, Just an idea....Kristy


text:
Listing is for simple sheer chemise
Available in black, white, ivory, or cream (darker than ivory).
Corset, bustle over skirt, skirt, ribbon and black underskirt are sold separately.
Wear under your corset, bodice, or cincher.
Please allow 2-3 weeks to ship.
Elastic gathering around shoulders, back and neckline.
Measure the fullest part of your bust:
X small 30-32 inches
Small 33-35
med 36-38
large 39-41
x-large 42-44
xxL 45-47
vol 48-52
Hand wash cool water, line dry.
Polyester Chiffon.
Exchange only on this item.
This product hasn't received any reviews yet. Be the first to review this product!


text:
Sorry, but copying text is forbidden on this website!
Thus when Leonato impulsively believes Claudio's words shaming of Hero he tries to destroy her completely, "Hence from her, let her die". Additionally he angrily speaks of her loss of honour as a blemish from which he cannot distance himself through short monosyllabic language, "O she is fallen into a pit of ink, that the wide sea hath drops too few to wash her clean again". Conflict is used to draw out the hidden truths that otherwise may not have been revealed.
Leonato and his household publicly 'publish' that Hero is dead is a bid to punish Claudio and to redeem himself he must accept the hand of Leonato's 'niece' which is really Hero, another example of deception within the play. She is masked implying that Claudio must wed blindly and a dramatic device used to hide feelings or create different character personas. The masking of Hero reveals that Claudio is truly repentant as he is willing to dedicate his life to an unknown woman for Hero and also that the society of marriage has little to do with love. The final irony within the play is the uncovering of Don John's deceit.
It is accidentally stumbled upon by the watch; Dogberry and Verges, two fools who Shakespeare uses as a witty device to create a malapropism. The characters use incorrect words without knowing their blunders to appear stupid and this is an example of comedy within the play that Shakespeare does not disguise subtly as he has previously, but puts bluntly to create the idea of a more modern slapstick humour. Dogberry, a dull witted fool, tries to give witty orders yet misplaces words unlike the intelligence of Beatrice and Benedick, 'we have now recovered the most dangerous piece of lechery,' which was intended to read treachery.
Borachio admits the deceit to the court finally, 'I have deceived even your very eyes; what your wisdoms could not discover, these shallow fools have brought to light,' which is an example of how Shakespeare uses irony as a humorous yet thought provoking device. The theme of conflict is carried through to the plays close as when Borachio confesses to staging the loss of Hero's innocence, Don Pedro describes this evidence as a sword that tears Claudio, 'Runs not this speech like iron through your blood?
' and Claudio replies that he has already symbolically condemned himself, 'I have drunk poison whiles he uttered it. ' In conclusion we as the audience can see how throughout the 'Much Ado About Nothing' there are many conflicts between different characters and around different themes in the play. Beatrice causes conflict, as she rebels against the Elizabethan stereotype of a woman and the role that she is expected to play by society. The audience at the time would have understood her difficulties and battles with societies prejudice against women.
In this way Beatrice is seen to be a reflection of Queen Elizabeth I, the monarch of that time. Elizabeth was well known for not ever marrying, and it is clear that Shakespeare took some influence when writing Beatrice's soliloquies from Queen Elizabeth's speeches of the time. For example in a letter Queen Elizabeth's wrote to the king of Sweden declining his proposal of marriage she says ""We do not conceive in our hearts to take a husband, but highly commend this single life. " The audience will soon hear Beatrice similarly say "Adams sons are my brethren, and truly I hold it a sin to match in my kindred.
" Beatrice and Benedick have a strong conflicting relationship throughout the play as they are fighting against each other in a "merry war" and also against themselves and their true feelings, which are later revealed to the audience and each other, we hear Benedick say, "I do not love anything in the world as well as you. " The audience are happy to see this conflict end well and though we are sure that their "merry war" will continue and keep their love alive, it shall be with humour and affection.
Another main theme in the play is that of betrayal and false accusations. When Hero is falsely accused by Don John and Claudio, this conflict brings about great dramatic effectiveness and dramatic irony as the audience knows the truth and are left wondering whether Hero will ever be acquitted. The matter is however solved, surprisingly by Dogberry, who nobody really takes seriously as he is ill educated. Leonato at first tells him to "be brief" and states "neighbours you are tedious".
However soon Dogberry and Verges reveal the truth and ironically become the saviours of Hero and Claudio's relationship. As the plays title suggests, many of the characters take part in observing, listening, or 'noting'. In order for a plot based on deceit to evolve the characters note each other often, for example when Beatrice is duped into believing that Benedick loves her the plotters conceal themselves in the garden so that Beatrice can note their conversation. "Look where Beatrice like a lapwing runs close by the ground to hear our conference," notes Hero.
Each line is a placed note for Beatrice to absorb and this is also relevant in the ploy to convince Benedick of Beatrice's adoration. Shakespeare explores the theme of deception on a variety of levels by showing how deception can have both positive and negative affects. For example the success of deception is shown in the duping of Beatrice and Benedick into falling in love with each other, and alternatively the use of deception in Don John leading Claudio into doubting Hero's fidelity and ultimately bring about her downfall.
Throughout "Much ado about nothing" there are conflicts presented to the audience which address more serious events, including some that border on tragedy, yet bring about excitement and dramatic tensions in the play to hold the viewers attention, all of which are resolved happily as we see at the end the weddings of the two couples. Pia Charters 11G Show preview only The above preview is unformatted text This student written piece of work is one of many that can be found in our GCSE Miscellaneous section.


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Fahey Realtors
471 Claremont Road, Bernardsville NJ
|After more than 30 years of experience, we've learned that your Real Estate decisions are personal and emotional. With this in mind, we created our full-service agency and continue to bring expertise coupled with unparalleled personal attention to help you make smart, informed decisions. Whether it's your first town home, a newly constructed estate or undeveloped property, we continually strive to give you the ultimate client experience at our "boutique" Real Estate Agency located in Bernardsville, NJ. Regardless of your price range, we are devoted to understanding your needs and delivering the customized service you deserve.


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This will make your night!!!!!
OH MY GOD!!! IM Crying laughing. Thanks!
OMG! there's NOTHING like a baby laughing!
That baby is just laughing so hard that I can't control myself watching him!!! Sooo cute!!!!
hahha theres sorta like a wheezing fit going on there hahaha. I bet that baby will be diesel when he grows up (abs from laughing a lot) hehe thanks for sharing Megs!!
too cute
That is priceless. Have to save that link for the bad days.
Adorable baby. Love his laugh.
awwwww....I want a baby now......he is sooooo cute.
Lol, how cute!!
I LOVE babies laughing! Too cute!
OMG, he's soooo cute! Made me bust out laughing! I remember when my kids were babies like that. There's absolutely nothing like a baby's belly laugh.
omgosh hahah too cute
LOL too cute.
OMG!!!!!!! Quads giggling!!!!
Another LAUGHING baby!!


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Vectomega® (Capsules), 60 Capsules
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According to 9to5Mac, Apple is again testing out the ability to wirelessly share files between iOS devices (and possibly Macs) via AirDrop on iOS.
AirDrop is already available for Macs, running OS X 10.7 (Lion) or higher, and allows users to easily share files between Macs without relying on Wi-Fi. Bringing AirDrop to iOS would likely provide this same functionality to iPhones, iPads, and iPod Touch.
Enabling AirDrop on iOS would likely spell the doom for NFC-outfitted iDevices, instead opening the door for Apple to provide a more integrated solution for nearby wireless communication. It would not be surprising to see Apple leverage its existing iTunes accounts, with over half a billion active accounts, to offer retailers an Apple solution for wireless payments. Overnight, over 100 million AirDrop-enabled iPhones could replace the need to carry several credit cards in your wallet.
If Apple plans to release AirDrop for iOS, we'll likely see it announced and demonstrated alongside iOS 7 at WWDC 2013 in just a few short days. Stay tuned! We'll be live-blogging the WWDC keynote!


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Internal DVD Drive
- Home
- Computer Parts
- Blu-Ray/CD/DVD Drives
- Internal DVD Drives
The internal DVD drive is perhaps the last disc-based technology that a company will ever use. As data consumption and dissemination evolves into technologies such as USB Flash Drives and cloud-based systems, DVDs are becoming used more as specialty devices for highly proprietary materials. However, this is exactly why... the technology should not be eschewed. The internal computer DVD drive provides one of the best modes for data centralization, storage, and protection that is currently available on the market. DVDs are reliable and are more than able to handle the sometimes-immense audio/visual files that must be used today without complaint.
Some of the top brand names producing internal DVD drives include Asus, HP, Lenovo, Dell and Fujitsu. These companies have a long history of being able create internal computer DVD drive components for any size or make of computer. An internal DVD drive from a less reputable company can cause more damage to a system than simply being unable to transfer data to and from a disc. An improperly managed internal DVD drive can compromise the safety of the entire workstation by presenting a wide-open exploit for malicious users.
Aside from consistency of performance, internal DVD drives should also be checked for their maximum data transfer speed and for the type of media that they require. DVDs come in two basic forms: +R and -R. A business should have an internal DVD drive system that accommodates both types of DVDs. Here at Connection, our representatives will help you find the models that would best serve your company and we are prepared to respond to any questions you may have.
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Manage Your Financial Problems
If you are young and buying your first home, it can be a critical time in your life. Nonetheless, it's also extremely exciting to imagine that you are setting off to own your property interestingly. This is really the American Dream at work! Chances are, your mortgage payment will be more expensive than whatever rent you were paying before you were a homeowner. You might be stressed over how to budget after you close on the house, yet you will catch on speedier than you might suspect. If you couldn't manage the cost of the house, the bank wouldn't have given you the loan, so motivate prepared to crunch some numbers and appreciate the first year living in your new abode.
Pay Attention to Your Lending Officer
Prior to your loan is even endorsed, you're lending officer should sit down with you at the bank and give you a snappy once-over of the numbers. If they don't, you should ask them to do as such, or discover a lending officer that will; it's absolutely OK to shop around for lenders, especially in this economy. When you meet with your lending officer, don't be reluctant to ask questions and/or take notes. When you lock to your interest rate, they will let you know precisely what your mortgage payment will be, and if you choose to keep your taxes and homeowner's insurance in escrow, they will calculate that in, as well.
Set a New Budget
Ideally, if you've purchased a house, you have officially set some sort of budget for your living expenses pre-homeownership. If you have, it should be generally easy to set a new budget that accounts for your increased living expenses. Just module the number from the bank for your regularly scheduled payments and make adjustments as necessary. You will need to remove some things; that is almost inevitable. In any case, ensure it is something you can live with.
Communicate with Your Partner or Roommate
If you are buying this house with your spouse or partner, or if you are having someone move in and pay rent, make sure to communicate expectations and concerns transparently. This can represent the deciding moment a partnership when it comes time to pay all that money at closing. When you figure out what everybody owes, ensure you tell everybody upfront. If you are having a renter live with you, it's not a bad idea to draw up a lease arrangement and have a lawyer look at it. That can save you a great deal of inconvenience down the road.
Learn to Cook
Cooking your own foods can be significantly inexpensive than eating out each night. When you cook, you often have lots of leftovers which you can eat the following night or for lunch the following day. It would be such a shame to waste your new, awesome kitchen in your new house, so if you don't definitely know how to cook some simple meals, now is a great time to learn how.


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1 Min Read
March 14 (Reuters) - EPISURF MEDICAL AB:
* EUROPEAN PATENT OFFICE HAS ANNOUNCED ITS INTENTION TO GRANT ANOTHER EUROPEAN PATENT FOR EPISURF Source text for Eikon: Further company coverage: (Gdynia Newsroom)
All quotes delayed a minimum of 15 minutes. See here for a complete list of exchanges and delays.
© 2018 Reuters. All Rights Reserved.


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Cecil CountyHome Menu
County Calendar
Christmas with the Ponies
- Date: 12/03/2017 11:00 AM - 6:00 PM
- Location: Freedom Hills Farm
33 Rolling Hills Ranch Lane
Port Deposit, Maryland 21904
- Room NumberNo
Return to full list >>
Fun for all ages. Pony rides, hay rides, live nativity and so much more! Food available for purchase.


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It may have been a short stay for Trevor Campbell and Grayson Frazier in the Southern California Regionals, but it likely didn't feel that way for the Glendale Community College No. 1 men's doubles team.
Not after a grueling two-and-a-half hour match ended the tandem's season in a 4-6, 6-4, 7-6 (8-6) loss to Saddleback College's Sena Sharifi and Pedro Campos in the round of 16 at Irvine Valley College.
"[We're] definitely [disappointed]," Campbell said. "But we competed.
"It was a good match, we played well. It got hot at some points, but it was good competition."
Campbell and Frazier suffered a key service break late in the second set and then Sharifi and Campos held their serve to even the match.


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Company profile
All sorts of tiling businesses could benefit from one of our insurance packages. Whatever trade you're in and whatever work you do, you'll want to know you're covered - just in case the worst happens. And with us you will. And there's £50 cash back* from your Tile Association subscription for sole trader and single members limited companies purchasing public liability insurance. We can also quote for your van or other commercial vehicles. http://www.jelfsmallbusiness.co.uk/tta-van-insurance/
- Terms and conditions may apply.
Address: Jelf, Apex Park, Wainwright Road, Worcester, WR4 9FN


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Good Quality Futon Bedstead - £47.10 delivered! (£51.20 w/o Quidco)
Was £68
-20% Voucher - £51.20
- 8% Quidco - £47.10
Looks like limited stock, only the double bedstead in Pine left.
IMHO it looks an extremely good quality bedframe.
Probably only worth it if you're shopping for a new bedframe, as the matress is an extra £72
Edit: If link doesn't work, see first post.
New code to use for 10% off: XX334
- Prufrock
Oops...meant XX334 will get you 20% off this bed, not 10%.
- Prufrock


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Vintage Motor Club, Sydney, NSW, Australia
About Us
Featured Vintage Cars
Featured Car - 1921 Rolls Royce Silver Ghost
Featured Car - 1925 Morris Bullnose Roadster
Featured Car - 1927 Sunbeam
Featured Car - 1928 Oldsmobile Tourer
Featured Car - 1928 Chevrolet Tourer
Featured Car - 1929 De Soto Coupe
Featured Car - 1929 Pontiac Roadster
Featured car - 1929 Plymouth Roadster
Featured Car - 1929 Studebaker Brooklands 8
Featured Car - 1930 Austin 7 Ulster
Featured Cars - 1930 Nash - Twin Ignition 8 & Single 6
Featured Car - 1930 Whippet 96A Tourer
VMC Photo Gallery
VMC Photos 2016
VMC Photos 2015
VMC Photos 2014
VMC Photos 2013
VMC Photos 2012
VMC Photos 2010-2011
VMC Photos Tasmania Tour 2009
VMC Photos 2003-2010
VMC Photos 1954-1964
VMC Historic & collectable vehicles
VMC Bulletin - articles from our Club magazine
What car is that?
Our Gatsby Cars
Councils and Federations of Car Clubs
Vintage car sites - history and restoration
Vintage car matters
60th Anniversary of the VMC
are welcome from anyone with an interest in the preservation, appreciation and driving of vintage cars.
Full Membershi
applicants must have a vintage car (made between 1919-1930) either under restoration or on the road. Cars must be original or authentically restored, not modified or customised. HVS vehicle registration through the VMC is only available to Full Members.
Associate Memberships
are available for those not currently owning a vintage car. We have a number of Associate Members who either formerly owned vintage cars or who enjoy being involved in the Club's tours and activities.
Membership fees are tailored to suit those living in the greater Sydney region or members in country NSW and interstate.
New to the hobby?
If you have never owned or restored a vintage car
then joining a club, even before you buy a restored car or start a restoration is recommended.
All good collector car clubs want new enthusiasts to
enjoy the hobby and not get turned off or caught out financially
by the difficult bits of old car restoration, repair and operation. The VMC offers experienced and practical help for those new to the hobby helping you avoid some of the traps and tribulations in getting started in the vintage cars. Even before your car is up and running the VMC offers members opportunities to be involved n vintage car rallies.
Do you have a vintage car sitting idle in the garage?
Looking for a club that really gets out and about and enjoys driving their vintage cars?
VMC rallies offer great
vintage motoring events, we welcome visitors so come along and experience real vintage driving.
Club Events
are held monthly, these vary from full or half-day runs, 1 day navigation drives, full weekend rallies, Easter Rallies and 10-14 day interstate tours (usually held biennially). Club members also support charity displays and participate in film and TV events. Whether driving or socialising together VMC members enjoy both friendship and fun centred on their vintage cars and the places and events these cars take them to.
Monthly Club Meetings
Meetings are fairly informal, sociable and are an opportunity to discuss rallies and tours, our own vehicles and vintage cars in general.
The VMC Bulletin
a full colour newsletter, is sent to all Full and Associate members 11 times per year in either email or print version and is exchanged with many other collector car clubs across Australia.
Vehicle Registration
storic Conditional Registration Scheme
VMC Full Members are entitled to access reduced cost Conditional Registration approved by the RTA NSW for
their eligible veteran, vintage and historic vehicles, subject to a road worthiness inspection by our Club Registrar and subsequently to the annual road worthiness inspection conducted by the Club or the provision of a current 'pink slip'. The Conditional Registration Scheme allows those vehicles on Historic plates to be driven to designated Club and other notified events.
The knowledge and skills
of enthusiastic fellow vintage car owners is a major feature of the VMC. Many members are very experienced amateur car restorers, several with multi-award winning vehicles, and many with cars that have enviable touring histories. The expertise of these members is readily shared with those who have cars in repair or under restoration.
To enquire about MEMBERSHIP please click on to our
Contact Form
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Labels: Cushings Help, forums, message boards, upgrade
David Unuane, MD (Doctor), Department of Endocrinology, Universitair Ziekenhuis Brussel, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium, Herman Tournaye, MD, PhD (Professor, Doctor), Brigitte Velkeniers, MD, PhD (Professor, Doctor), Kris Poppe, MD, PhD (Professor, Doctor)
Female infertility occurs in about 37% of all infertile couples and ovulatory disorders account for more than half of these. The ovaries are in continuous interaction with the other endocrine organs. The interplay may account for infertility occurring at different levels and may render the diagnosis of infertility a difficult exercise for the involved physician. A hypothalamic cause of female infertility should be considered in an appropriate clinical context, with tests pointing to a hypogonadotropic hypogonadism. It can be functional, physiological or related to organic causes. Hyperprolactinemia has well characterized effects on the normal gonadal function and treatment is well established.
Acromegaly and Cushing's disease may impair fertility at different levels, mechanisms involved however remain ill defined. Thyroid disorders, both hyperthyroidism and hypothyroidism, can interact with the ovaries, through a direct effect on ovarian function, but autoimmunity may be involved, as well as alterations of the sex hormone binding protein levels. Primary ovarian disorders, such as the polycystic ovary syndrome and primary ovarian insufficiency are frequent diseases, for which novel treatments are currently being developed and discussed.
We will propose an algorithm for the diagnosis and approach of the female patient presenting with infertility on the basis of the available evidence in literature.
Keywords: female infertility, pituitary, adrenal, ovarian, thyroid
From http://www.bprcem.com/article/PIIS1521690X1100087X/abstract?rss=yes
Labels: acromegaly, adrenal, Cushing's, hyperprolactinemia, infertility, PCOS, pituitary, thyroid
Source: Johns Hopkins Medicine
Newswise — Infertility is common among obese women, but the reasons remain poorly understood and few treatments exist. Now a team of Johns Hopkins Children's Center scientists, conducting experiments in mice, has uncovered what they consider surprising evidence that insulin resistance, long considered a prime suspect, has little to do with infertility in women with type-2 diabetes, polycystic ovary syndrome (PCOS) and metabolic syndrome, all obesity-related conditions in which the body becomes desensitized to insulin and loses the ability to regulate blood sugar.
In a report, published online Nov.10 in the journal Diabetes, the Johns Hopkins scientists say the real culprit appears to be insulin sensitivity in the ovaries and the pituitary.
The Johns Hopkins team said its findings show that these organs escape insulin resistance and, awash with high levels of circulating insulin common in obesity, develop abnormal cell signaling that disrupts ovulation and eventually leads to infertility.
"Our findings suggest that the focus should shift from treating insulin resistance in peripheral tissue to taming insulin sensitivity in the pituitary and ovaries," says lead investigator Sheng Wu, Ph.D., of the Johns Hopkins Children's Center. Scientists traditionally have treated obesity-induced infertility by lowering blood insulin to counter the effects of insulin resistance.
A 2010 study by the same team discovered that the pituitary gland, insensitive to insulin in lean mice, became sensitive to elevated levels of insulin seen in human and rodent obesity. By knocking out the insulin receptors in the pituitary glands of obese mice, the researchers were able to partially restore fertility, thus proving that abnormal insulin signaling in the pituitary was only part of the story.
"In the original study, disrupting insulin signaling in the pituitary restored 50 percent of fertility in obese mice, but the search was on for the accomplice," says senior investigator Andrew Wolfe, Ph.D., an endocrinologist at the Johns Hopkins Children's Center. "Our new findings point to the ovaries."
In the pituitary, faulty insulin signaling stimulates increased secretion of luteinizing hormone, the researchers say. In the ovary, it puts testosterone production into overdrive. Both disrupt ovulation, the researchers explain.
In the latest study, lean mice and mice made obese on a three-month high-fat diet received injections of progressively higher doses of insulin to mimic the effects of high circulating insulin seen in obesity, diabetes and PCOS. In lean mice, the ovaries and pituitaries were insensitive to the hormone at low-dose injections, and responded only when injected with higher doses of insulin. The "trigger" doses corresponded to insulin levels typically seen in obesity. Obese mice with naturally elevated insulin levels exhibited high levels of insulin signaling in their pituitary and ovarian cells. When injected with insulin, the livers and muscles of obese mice showed greatly reduced response to insulin -- or insulin resistance. Their ovaries and pituitary glands, however, responded to insulin injections, confirming that in obese mice, these reproductive organs escape the insulin resistance seen in other organs.
To determine insulin sensitivity, the researchers focused on two signaling proteins, IRS-1 and IRS-2, regulators of cell-insulin communication involved in the development of insulin resistance in liver and muscle tissue. The scientists hypothesized that in the pituitary and ovaries, these messenger proteins would remain dormant under normal insulin levels, but would get activated once exposed to high levels of insulin. Indeed, the researchers found, the pituitary glands of obese mice showed higher IRS-2 signaling activity compared with lean mice, while the ovaries of obese mice had higher signaling activity in both IRS-1 and IRS-2 proteins, compared with lean mice.
In a follow-up study now under way, the Hopkins team is trying to determine whether knocking out the insulin receptors in both the ovaries and the pituitary would fully restore fertility in obese mice with high insulin levels.
Other co-investigators on the study included Sara Divall, M.D., and Fred Wondisford, M.D., both of the Johns Hopkins Children's Center.
The research was funded by the Endocrine Fellow Foundation, by The Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health, and by the Baltimore Diabetes Research and Training Center, which is supported by the National Institute for Diabetes and Digestive and Kidney Diseases.
Founded in 1912 as the children's hospital of the Johns Hopkins Medical Institutions, the Johns Hopkins Children's Center offers one of the most comprehensive pediatric medical programs in the country, treating more than 90,000 children each year. Hopkins Children's is consistently ranked among the top children's hospitals in the nation.
Hopkins Children's is Maryland's largest children's hospital and the only state-designated Trauma Service and Burn Unit for pediatric patients. It has recognized Centers of Excellence in dozens of pediatric subspecialties, including allergy, cardiology, cystic fibrosis, gastroenterology, nephrology, neurology, neurosurgery, oncology, pulmonary, and transplant. For more information, please visitwww.hopkinschildrens.org
From http://www.newswise.com/articles/not-the-usual-suspects-animal-study-finds-su.../articles/list&category=medicine&page=1&search%5Bstatus%5D=3&search%5Bsort%5D=date+desc&search%5Bsection%5D=10&search%5Bhas_multimedia%5D=
By Lisa Smyth
A Northern Ireland man has defied medical predictions and overcome the effects of a rare condition that left him in a coma for three months.
Jonathan Fisher is a survivor of an Addisonian crisis which affected him so badly doctors feared he would never recover.
His mother ignored medical advice to switch off his life-support system as doctors believed he was brain dead.
However, convinced he could recover after noticing that he was reacting to her with the occasional slight movement of his little finger she refused to give up on her son.
Now — against all the odds — he has made a remarkable recovery and has regained many of the skills lost as a result of his condition.
Addison's disease is a rare disorder of the adrenal glands. It affects the production of two hormones — cortisol and aldosterone — which help to regulate blood pressure.
If left untreated, the amount of steroid hormones in the body will gradually fall and the symptoms of Addison's disease will get progressively worse.
Eventually, this will cause an adrenal crisis — when the symptoms become very severe and blood pressure drops to a dangerously low level. An adrenal crisis can be fatal if it is not treated immediately.
Jonathan can now get around Lisburn in his electric wheelchair and has even managed to complete his first book, August Always — a triumph as he has considerable speech impairment and great difficulty using his hands to operate a keyboard.
The process has been long and laborious but Jonathan said he was determined to share his experience with others.
"There are moments in life that define us, like birth and death," he said.
"Along the journey there will be crises of passion, of love, of faith and desire, but none so devastating as an Addisonian crisis. I am Jonathan Fisher, a survivor.
"August Always is my memoir. I believe in the incredible. I dream of a better future."
Addison's disease is a rare disorder of the adrenal glands which are located on top of the kidneys. The condition affects the production of two hormones. Cortisol, which helps to regulate blood pressure, maintaining blood glucose and heart function. And aldosterone which also helps regulate blood pressure. Addison's sufferers must get treatment if their blood pressure falls as it can be fatal.
From http://www.belfasttelegraph.co.uk/news/health/coma-man-defies-odds-to-write-book-16076458.html
Labels: Addison's, adrenal, Adrenal Crisis, steroids
Diabetes mellitus is a frequent complication of Cushing syndrome (CS) which is caused by chronic exposure to glucocorticoid excess, either endogenous or exogenous, and that is characterized by several clinical symptoms such as central obesity, purple striae, proximal muscle weakness, acne, hirsutism and neuropsychological disturbances.
Diabetes occurs as a consequence of an insulin-resistant state together with impaired insulin secretion which are induced by glucocorticoid excess. The management of patients with CS and diabetes mellitus includes the treatment of hyperglycemia and, when possible, the correction of glucocorticoid excess.
This review focuses on the disorders of glucose metabolism in patients exposed to glucocorticoid excess, addressing both the pathophysiological aspects and the clinical and therapeutic implications.
Read the entire article at http://www.cell.com/trends/endocrinology-metabolism/abstract/S1043-2760(11)00138-X
Labels: acne, Cushing's, diabetes, diabetes mellitus, glucocorticoids, hirsuitism, insulin, obesity, straie
Something new of interest to Cushies most every day. Please note that there is a current backlog of about three weeks for submitted bios to be added to the website.
November 10, 2011:
November 5, 2011:
November 2, 2011:
Labels: adrenal, bios, CushieWiki, Cushing's, FAQ, news items, pituitary
HELSINGBORG, Sweden and EXTON, Pa., Nov. 7, 2011 /PRNewswire/ -- The Swedish specialty pharma company, DuoCort Pharma, announced today that the European Commission has granted a European Marketing Authorisation for Plenadren®(hydrocortisone, modified release tablet), an orphan drug for treatment of adrenal insufficiency in adults, bringing these patients their first pharmaceutical innovation in over 50 years.
Developed by DuoCort Pharma, Plenadren® is a dual release hydrocortisone replacement therapy designed to better mimic the normal physiological cortisol profile in order to improve outcomes for patients suffering from adrenal insufficiency. Plenadren® is given as an oral tablet once daily. It has an outer layer releasing hydrocortisone immediately and an inner core releasing the rest of the drug more slowly during the day.
Although glucocorticoid hormone replacement therapy for adrenal insufficiency has been available for decades, studies have recorded complications and comorbidities including premature death, impaired quality of life, increased risk of cardiovascular diseases, and decreased bone mineral density in treated patients, most likely because it is difficult to match the natural secretion pattern of cortisol.
Maria Forss, CEO of DuoCort Pharma, said: "The marketing authorization for Plenadren® in Europe is an important step towards addressing the unmet needs of these patients."
The approval of Plenadren® follows the positive opinion adopted by the Committee for Medicinal Products for Human Use (CHMP) in July 2011. Plenadren® is now approved for marketing in all countries of the European Union (EU) as well as in the European Economic Area (EEA), namely Iceland, Norway and Lichtenstein.
Professor Gudmundur Johannsson of the Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden, and Chief Medical Officer of DuoCort Pharma, said: "Plenadren® offers a welcome new treatment option to help patients suffering from adrenal insufficiency. Plenadren® can improve therapy for many of the almost 200,000 patients in Europe who suffer from this disease and who need life-long cortisol replacement therapy for their survival."
On October 26, 2011, ViroPharma Incorporated (NASDAQ: VPHM) signed a definitive agreement to acquire DuoCort Pharma AB. The companies expect to complete the acquisition in November 2011. On closing, ViroPharma will pay an upfront closing cost of 220 million Swedish kroner (SEK) or $33 million in US dollars (USD). Additionally, there are contingent milestone payments of up to 860 million SEK or $130 million USD associated with manufacturing, sales thresholds and territory expansion.
About Adrenal insufficiency
Adrenal insufficiency (cortisol deficiency) is a rare, life-threatening disease that affects patients in their active years. To survive, patients suffering from this disease need lifelong replacement therapy with hydrocortisone. Treatment of adrenal insufficiency involves replacing, or substituting, the hormones that the patient's own adrenal glands are not producing. Cortisol is replaced using hydrocortisone, the synthetic form of cortisol.
About Plenadren® (hydrocortisone, modified release tablet)
Plenadren is the first true innovation in over 50 years in the treatment of adrenal insufficiency.
Hypersensitivity to the active substance of Plenadren or to any of the excipients may occur. During acute adrenal insufficiency, parenteral administration of hydrocortisone in high doses, together with physiological sodium chloride solution for injection, must be given. Use of Plenadren with potent CYP 3A4 inducers and inhibitors may merit an adjustment of hydrocortisone dosage. High (supra-physiological) dosages of cortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. Long-term treatment with higher than physiological hydrocortisone doses can lead to clinical features resembling Cushing's syndrome with increased adiposity, abdominal obesity, hypertension and diabetes, and thus result in an increased risk of cardiovascular morbidity and mortality. All glucocorticoids increase calcium excretion and reduce the bone remodeling rate. Patients with adrenal insufficiency on long term glucocorticoid replacement therapy have been found to have reduced bone mineral density. Psychiatric adverse events may occur with systemic glucocorticoids.
The most common adverse reactions observed in clinical studies have been fatigue, gastroenteritis, upper respiratory tract infection, sedation, vertigo and dry eyes.
About ViroPharma Incorporated
ViroPharma Incorporated is an international biopharmaceutical company committed to developing and commercializing novel solutions for physician specialists to address unmet medical needs of patients living with diseases that have few if any clinical therapeutic options, including C1 esterase inhibitor deficiency, treatment of seizures in children and adolescents, and C. difficile infection (CDI). Our goal is to provide rewarding careers to employees, to create new standards of care in the way serious diseases are treated, and to build international partnerships with the patients, advocates, and health care professionals we serve. ViroPharma's commercial products address diseases including hereditary angioedema (HAE), seizures in children and adolescents, and CDI; for full U.S. prescribing information on our products, please download the package inserts athttp://www.viropharma.com/Products.aspx; the prescribing information for other countries can be found atwww.viropharma.com.
ViroPharma routinely posts information, including press releases, which may be important to investors in the investor relations and media sections of our company's web site, www.viropharma.com. The company encourages investors to consult these sections for more information on ViroPharma and our business.
About DuoCort Pharma
DuoCort Pharma is a drug development company focused on improving glucocorticoid therapy. The company has its origins among researchers at the Sahlgrenska Academy at Gothenburg University and at Uppsala University in Sweden. DuoCort Pharma has developed Plenadren®, an improved glucocorticoid replacement therapy for patients with adrenal insufficiency, which is a rare disease. DuoCort Pharma has orphan drug designations in EU, Switzerland and the USA for Plenadren®. Plenadren® is a once daily, dual-release hydrocortisone oral tablet. It has an outer layer that releases the drug immediately and an inner core that releases the drug over the day. The tablets come in both 5 mg and 20 mg strengths. For more information please visit www.duocort.com.
DuoCort Pharma is a project company of the life science incubator PULS. For more information visit www.pulsinvest.se.
Disclosure Notice
Certain statements in this press release contain forward-looking statements that involve a number of risks and uncertainties. Forward-looking statements provide our current expectations or forecasts of future events, including statements about the benefits of the business combination transaction involving ViroPharma and DuoCort Pharma, including, among others, future financial and operating results, enhanced revenues, ViroPharma's plans, objectives, expectations and intentions and other statements that are not historical facts. The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the ability to achieve the other conditions to closing on the proposed schedule; the risk that the business will not be integrated successfully; the risk that revenues following the acquisition will be lower than expected, including the successful commercialization of Plenadren; potential for disruption from the transaction making it more difficult to maintain relationships with manufacturers, employees or other suppliers; competition and its effect on pricing, spending, third-party relationships and revenues; our ability to achieve favorable pricing for Plenadren from European regulatory authorities; the risk that the safety and/or efficacy results of existing clinical trials for Plenadren will not be consistent with the results of additional clinical studies, including the required registry study, or with commercial usage; market acceptance of Plenadren; and our inability to maintain the orphan drug status associated with Plenadren. These factors, and other factors, including, but not limited to those described in our annual report on Form 10-K for the year ended December 31, 2010 and quarterly reports on Form 10-Q filed with the Securities and Exchange Commission, could cause future results to differ materially from the expectations expressed in this press release. The forward-looking statements contained in this press release are made as of the date hereof and may become outdated over time. ViroPharma does not assume any responsibility for updating any forward-looking statements. These forward looking statements should not be relied upon as representing our assessments as of any date subsequent to the date of this press release.
SOURCE DuoCort Pharma
From http://www.prnewswire.com/news-releases/duocort-pharmas-orphan-drug-plenadren-granted-european-marketing-authorization-for-adrenal-insufficiency-133348658.html
BACKGROUND: Bilateral adrenalectomy (BLA) is a treatment option to alleviate symptoms in patients with ectopic Cushing's syndrome (ECS) for whom surgical treatment of the responsible nonpituitary tumor is not possible. ECS patients have an increased risk for complications, because of high cortisol levels, poor clinical condition, and metabolic disturbances. This study aims to evaluate the safety and long-term efficacy of endoscopic BLA for ECS.
METHODS: From 1990 to present, 38 patients were diagnosed and treated for ECS in the Erasmus University Medical Center, a tertiary referral center. Twenty-four patients were treated with BLA (21 endoscopic, 3 open), 9 patients were treated medically, and 5 patients could be cured by complete resection of the adrenocorticotropic hormone (ACTH)-producing tumor. The medical records were retrospectively reviewed and entered into a database. For evaluation of the efficacy of BLA, preoperative biochemical and physical symptoms were assessed and compared with postoperative data.
RESULTS: Endoscopic BLA was successfully completed in 20 of the 21 patients; one required conversion to open BLA. Intraoperative complications occurred in two (10%) patients, and postoperative complications occurred in three (14%) patients. Median hospitalization was 9 (2-95) days, and median operating time was 246 (205-347) min. Hypercortisolism was resolved in all patients. Improvements of hypertension, body weight, Cushingoid appearance, impaired muscle strength, and ankle edema were achieved in 87, 90, 65, 61, and 78% of the patients, respectively. Resolution of diabetes, hypokalemia, and metabolic alkalosis was achieved in 33, 89, and 80%, respectively.
CONCLUSION: Endoscopic BLA is a safe and effective treatment for patients with ectopic Cushing's syndrome.
From http://www.docguide.com/endoscopic-bilateral-adrenalectomy-patients-ectopic-cushings-syndrome?tsid=5
Labels: ACTH, adrenalectomy, BLA, Cushing's, ectopic, endoscopic, hypercortisolism, surgery
MENLO PARK, CA, Nov 07, 2011 (MARKETWIRE via COMTEX) -- Corcept Therapeutics IncorporatedCORT -1.58% , a pharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of severe metabolic and psychiatric disorders, today reported financial results for the quarter ended September 30, 2011, and updated its corporate progress.
"Following the acceptance by the U.S. Food and Drug Administration (FDA) of our New Drug Application (NDA) for the use of our lead product candidate, Korlym(TM), in Cushing's Syndrome," said Joseph Belanoff, M.D., Chief Executive Officer of Corcept, "we continue to focus our efforts on building our commercial capabilities to support the launch of Korlym, if Korlym is approved by the FDA, in order to allow us to provide an important treatment option to patients suffering from Cushing's Syndrome."
Corporate and Development Highlights
-- Received notification in October 2011 that the FDA had accepted our proposed brand name, Korlym (formerly referred to as CORLUX(R)), for our lead product candidate in the treatment of endogenous Cushing's Syndrome. -- Advanced our commercial launch preparations related to Korlym for the treatment of Cushing's Syndrome, including developing our internal infrastructure and engaging third-party vendors to provide market analytics and to support distribution and other logistical needs in the event Korlym is approved by the FDA. -- Received notification in October 2011 that the European Commission had granted Korlym Orphan Designation for the treatment of endogenous Cushing's Syndrome (hypercortisolism) in the European Union (EU). Benefits of Orphan Drug Designation in the EU are similar to those in the U.S., but include ten years of marketing exclusivity in all 27 member states, free scientific advice during drug development, access to a centralized review process and a reduction or complete waiver of fees levied by the European Medicines Agency. -- Enrolled additional patients in our double-blind placebo controlled Phase 3 trial of Korlym for the treatment of the psychotic features of psychotic depression. -- Continued the clinical portion of our Phase 1b/2a multi-dose safety and proof of concept studies of CORT 108297, one of our selective GR-II antagonists. -- Identified additional compounds from among our proprietary series of selective GR-II antagonists to advance toward an Investigational New Drug submission.
Third Quarter Financial Results
For the third quarter of 2011, Corcept reported a net loss of $6.4 million, or $0.08 per share, compared to a net loss of $7.1 million, or $0.10 per share, for the third quarter of 2010.
In the third quarter of 2011, research and development expenses decreased to $3.2 million from $5.2 million in the third quarter of 2010. This decrease in research and development expenses was due primarily to decreases in clinical trial costs related to drug-drug interaction and other NDA-supportive studies with Korlym, which were substantially completed in late 2010, and decreases in the clinical trial costs related to the Phase 1b/2a studies with CORT 108297. These decreases were partially offset by increased costs associated with the prosecution of our NDA for Korlym for the treatment of Cushing's Syndrome. General and administrative expenses increased to $3.2 million for the third quarter of 2011 from $1.9 million for the same period in 2010 due primarily to additional expenditures on commercialization activities for the potential launch of Korlym for Cushing's Syndrome.
Our cash balance as of September 30, 2011 was $45.9 million, up from $24.6 million at December 31, 2010. "We anticipate that our current cash balance is sufficient to fund the company through the end of 2012," said Charles Robb, the company's Chief Financial Officer.
Anticipated Activities for the Remainder of 2011
We continue to concentrate our efforts on advancing Korlym toward approval and commercialization for the treatment of Cushing's Syndrome. We also continue our efforts to be prepared to respond in a timely fashion to any questions posed by the FDA during the course of their review of our NDA.
"We are focused intently on developing the commercial and logistical capabilities we will need to make Korlym available to patients suffering from Cushing's Syndrome, should the FDA approve our drug for this indication," added Dr. Belanoff. "Korlym is the first step in unlocking the value of our scientific platform. The regulation of cortisol is a critical biological function; its dysregulation is equally critical in many important disease states. Our own research and research from increasing numbers of academic investigators point to the potential importance of cortisol antagonism in a wide variety of diseases. We believe our expanding library of selective cortisol antagonists may help address these unmet medical needs."
About Cushing's Syndrome
Endogenous Cushing's Syndrome is caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol and is generated by tumors that produce cortisol or ACTH. Cushing's Syndrome is an orphan indication which most commonly affects adults aged 20 to 50. An estimated 10 to 15 of every one million people are newly diagnosed with this syndrome each year, resulting in over 3,000 new patients in the United States. An estimated 20,000 patients in the United States have Cushing's Syndrome. Symptoms vary, but most people have one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Cushing's Syndrome can affect every organ system in the body and can be lethal if not treated effectively.
About Psychotic Depression
Psychotic depression is a serious psychiatric disorder that affects approximately three million people annually in the United States. It is more prevalent than either schizophrenia or bipolar I disorder. The disorder is characterized by severe depression accompanied by delusions, hallucinations or both. People with psychotic depression are approximately 70 times more likely to commit suicide than the general population and often require lengthy and expensive hospital stays. There is no FDA-approved treatment for psychotic depression.
About Weight Gain Caused by Antipsychotic Medications
The group of medications known as second-generation antipsychotics, including olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel) and clozapine (Clozaril), are widely used to treat schizophrenia and bipolar disorder. All medications in this group are associated with treatment emergent weight gain of varying degrees and also carry warning labels relating to treatment emergent hyperglycemia and diabetes mellitus. There is no FDA-approved treatment for the weight gain associated with the use of antipsychotic medications.
About Korlym
Corcept's first-generation compound, Korlym, also known as mifepristone, directly blocks the cortisol (GR-II) receptor and the progesterone (PR) receptor. Intellectual property protection is in place to protect important methods of use for Korlym. Corcept retains worldwide rights to its intellectual property related to Korlym.
About CORT 108297
CORT 108297 is a potent, selective antagonist of the cortisol (GR-II) receptor that we have discovered and for which Corcept owns worldwide intellectual property rights. In in vitro binding affinity and functional assays this compound has no affinity for the progesterone (PR), estrogen (ER), androgen (AR) or mineralocorticoid (GR-I) receptors.
About Corcept Therapeutics Incorporated
Corcept is a pharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of severe metabolic and psychiatric disorders. The company has completed its Phase 3 study of Korlym for the treatment of Cushing's Syndrome, and has an ongoing Phase 3 study of Korlym for the treatment of the psychotic features of psychotic depression. Corcept also has a Phase 2 program for CORT 108297, a selective GR-II antagonist that blocks the effects of cortisol but not progesterone. Corcept has developed an extensive intellectual property portfolio that covers the use of GR-II antagonists in the treatment of a wide variety of psychiatric and metabolic disorders, including the prevention of weight gain caused by the use of antipsychotic medication, as well as composition of matter patents for our selective GR-II antagonists.
Statements made in this news release, other than statements of historical fact, are forward-looking statements, including, for example, statements relating to the potential benefit of Korlym for patients diagnosed with Cushing's Syndrome, Corcept's clinical development and research programs, the outcome of the FDA's review of our NDA filing, our estimates for our capital requirements and needs for additional financing, the introduction of Korlym and future product candidates, including CORT 108297, the ability to create value from Korlym or other future product candidates or our scientific platform and our commercialization plans. Forward-looking statements are subject to a number of known and unknown risks and uncertainties that might cause actual results to differ materially from those expressed or implied by such statements. For example, there can be no assurances with respect to the cost, rate of spending, completion or success of clinical trials; financial projections may not be accurate; there can be no assurances that Corcept will pursue further activities with respect to the development of Korlym, CORT 108297, or any of its other selective GR-II antagonists. These and other risk factors are set forth in the Company's SEC filings, all of which are available from our website ( www.corcept.com ) or from the SEC's website ( www.sec.gov ). We disclaim any intention or duty to update any forward-looking statement made in this news release.
CORCEPT THERAPEUTICS INCORPORATED CONDENSED BALANCE SHEETS (in thousands) September 30, December 31, 2011 2010 -------------- -------------- (Unaudited) (Note) ASSETS: Current assets: Cash and cash equivalents $ 45,909 $ 24,578 Other current assets 427 418 -------------- -------------- Total current assets 46,336 24,996 Other assets 43 108 -------------- -------------- Total assets $ 46,379 $ 25,104 ============== ============== LIABILITIES AND STOCKHOLDERS' EQUITY: Current liabilities: Accounts payable $ 1,066 $ 817 Other current liabilities 1,647 3,043 -------------- -------------- Total current liabilities 2,713 3,860 Total stockholders' equity 43,666 21,244 -------------- -------------- Total liabilities and stockholders' equity $ 46,379 $ 25,104 ============== ============== Note: Derived from audited financial statements at that date. CORCEPT THERAPEUTICS INCORPORATED CONDENSED STATEMENTS OF OPERATIONS (in thousands, except per share amounts) (Unaudited) For the Three Months Ended For the Nine Months Ended September 30, September 30, -------------------------- -------------------------- 2011 2010 2011 2010 ------------ ------------ ------------ ------------ Operating expenses: Research and development* $ 3,228 $ 5,224 $ 14,355 $ 14,286 General and administrative* 3,209 1,881 8,049 5,327 ------------ ------------ ------------ ------------ Total operating expenses 6,437 7,105 22,404 19,613 ------------ ------------ ------------ ------------ Loss from operations (6,437) (7,105) (22,404) (19,613) Interest and other income, net 3 4 3 758 Other expense (1) (3) (17) (18) ------------ ------------ ------------ ------------ Net loss $ (6,435) $ (7,104) $ (22,418) $ (18,873) ============ ============ ============ ============ Basic and diluted net loss per share $ (0.08) $ (0.10) $ (0.27) $ (0.28) ============ ============ ============ ============ Shares used in computing basic and diluted net loss per share 84,188 72,045 83,000 66,982 ============ ============ ============ ============ *Includes non-cash stock-based compensation of the following: Research and development $ 110 $ 45 $ 432 $ 170 General and administrative 844 500 1,971 1,361 ------------ ------------ ------------ ------------ Total non-cash stock-based compensation $ 954 $ 545 $ 2,403 $ 1,531 ============ ============ ============ ============
CONTACT: Charles Robb Chief Financial Officer Corcept Therapeutics 650-688-8783 Email Contact www.corcept.com
SOURCE: Corcept Therapeutics
http://www2.marketwire.com/mw/emailprcntct?id=150008C85C40D638 http://www.corcept.com/
Labels: ACTH, Corlux, CORT 108297, cortisol, Cushing's, depression, FDA, Korlym, Mifepristone, progesterone, weight
Among the important early researchers in X-rays were Professor Ivan Pulyui, Sir William Crookes, Johann Wilhelm Hittorf, Eugen Goldstein, Heinrich Hertz, Philipp Lenard, Hermann von Helmholtz, Nikola Tesla, Thomas Edison, Charles Glover Barkla, Max von Laue, and Wilhelm Conrad Röntgen.
ROSAT image of X-ray fluorescence of, and occultation of the X-ray background by, the Moon. The use of X-rays for medical purposes (to develop into the field of radiation therapy) was pioneered by Major John Hall-Edwards in Birmingham, England. In 1908, he had to have his left arm amputated owing to the spread of X-ray dermatitis[1].The X-ray microscope was invented in the 1950s. The Chandra X-ray Observatory, launched on July 23, 1999, has been allowing the exploration of the very violent processes in the universe which produce X-rays. Unlike visible light, which is a relatively stable view of the universe, the X-ray universe is unstable, it features stars being torn apart by black holes, galactic collisions, and novas, neutron stars that build up layers of plasma that then explode into space. An X-ray laser device was proposed as part of the Reagan Administration's Strategic Defense Initiative in the 1980s, but the first and only test of the device (a sort of laser "blaster", or death ray, powered by a thermonuclear explosion) gave inconclusive results. For technical and political reasons, the overall project (including the X-ray laser) was de-funded (though was later revived by the second Bush Administration as National Missile Defense using different technologies).
Labels: Medical History, X-ray
Key points include: Advances and more frequent use of diagnostic radiology have led to the increased prevalence of endocrine incidentalomas; Pituitary, thyroid, and adrenal incidentalomas must be assessed for dysfunctional hormone secretion and malignant potential; Inpatient management of endocrine incidentalomas should include consultation of endocrine or surgical teams in cases of dysfunctional or malignant lesions; Post-discharge instructions shouldclearly delineate timelines for repeat imaging, laboratory testing, and subspecialist follow-up.
by Darlene Tad-y, MD, Section of Hospital Medicine, University of Colorado Denver
A 54-year-old man with a history of hypertension treated with hydrocholorothiazide and Type 2 diabetes mellitus is admitted with abdominal pain and found to have an incidental 2.1-cm left adrenal mass on CT scan of the abdomen. He denies symptoms of headache, palpitations, weight gain, or muscle weakness. His exam is significant for mildly elevated blood pressure. What is the best approach for evaluation and management of this incidental finding?
Incidentalomas are mass lesions that are inadvertently discovered during radiolographic diagnostic testing or treatment for other clinical conditions that are unrelated to the incidental mass. In recent decades, improvements in radiographic diagnostic techniques and sensitivity have led to increasing discovery of incidental lesions that are often in the absence of clinical signs or symptoms.1 Three commonly discovered lesions by hospitalists are pituitary, thyroid, and adrenal incidentalomas.2 The concerns associated with these findings relate to the potential for dysfunctional hormone secretion or malignancy.
Patients found with pituitary incidentalomas can be susceptible to several types of adverse outcomes: hormonal hypersecretion, hypopituitarism, neurologic morbidity due to tumor size, and malignancy in rare cases. Thyroid incidentalomas are impalpable nodules discovered in the setting of ultrasound or cross-sectional neck scans, such as positron emission tomography (PET) scans. Discovery of a thyroid incidentaloma raises concern for thyroid malignancy.3 The increased use of abdominal ultrasound, CT scans, and MRI has fueled the growing incidence of adrenal incidentalomas (AIs).
The discovery of an endocrine incidentaloma in the inpatient setting warrants a systematic approach that includes both diagnostic and potentially therapeutic management. A hospitalist should consider an approach that includes (see Table 1):
Pituitary incidentalomas. The prevalence of pituitary incidentalomas found by CT ranges from 3.7% to 20%, while the prevalence found by MRI approximates 10%. Autopsy studies have revealed a prevalence ranging from 1.5% to 26.7% for adenomas less than 10 mm, considered to be microadenomas. Broad categories of etiologies should be considered: pituitary adenoma, nonpituitary tumors, vascular lesions, infiltrative disorders, and others (see Table 2). The majority of pituitary adenomas secrete prolactin (30% to 40%) or are nonsecreting (30% to 40%). Adenomas secreting adrenocorticotropin hormone (ACTH, 2% to 10%), growth hormone (GH, 2% to 10%), thyroid-stimulating hormone (TSH, <1%), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) are much less common.2 Significant morbidity and premature mortality are associated with hyperprolactinemia, acromegaly (growth hormone excess), Cushing's syndrome, and hyperthyroidism. Additionally, up to 41% of patients with macroadenomas were found to have varying degrees of hypopituitarism due to compression of the hypothalamus, the hypothalamic-pituitary stalk, or the pituitary itself.4
Pituitary adenoma:
Non-pituitary tumors:
Vascular lesions:
ACTH=adrenocorticotropin hormone, GH=growth hormone, TSH=thyroid-stimulating hormone (thyrotropin), LH=luteinizing hormone, FSH=follicle-stimulating hormone
Recently, the Endocrine Society released consensus recommendations to guide the evaluation and treatment of pituitary incidentalomas, which are included in the approach outlined below.5 A detailed history and physical examination should be obtained with specific inquiry as to signs and symptoms of hormonal excess and mass effect from the tumor. Examples of symptoms of hormone excess can include:
Symptoms related to the mass effect of the tumor include visual field defects and hypopituitarism related to the deficient hormone, including:
The size and location of the pituitary lesion must be assessed. Lesions greater than 10 mm are considered macroademonas, and their size will affect their management. If the lesion was initially identified by CT scan, an MRI is recommended to better evaluate it.5 If the MRI locates the incidentaloma abutting the optic nerve or chiasm, then the patient should undergo a formal visual field examination.
Indications for an inpatient surgical referral for treatment include: a lesion larger than 2 cm, evidence of mass effect such as visual field defects, neurologic compromise, opthalmoplegia, hypopituitarism, a tumor abutting the optic nerve or chiasm, pituitary apoplexy, and hypersecretion of hormones other than prolactin. Patients with prolactinomas warrant an inpatient endo-crinology consult and may need medical management with a dopamine agonist. Hormone replacement therapy can also be provided for patients with hypopituitarism.2,5
For patients who do not meet the criteria for inpatient surgical therapy, follow-up management must be arranged at the time of discharge. Clinical, laboratory assessment, and an MRI should be scheduled six months after the initial finding of the incidentaloma with the patient's PCP or with an endocrinologist.5
Thyroid incidentalomas. The prevalence of thyroid nodules based on ultrasound studies ranges from 19% to 46%, with autopsy studies estimating an incidence of approximately 50%.2,6 Incidence of thyroid nodules also increases with age, as almost 60% of people over the age of 60 harbor a thyroid incidentaloma. The rate of malignancy in the general population has ranged between 8% and 24%; however, in the last decade, the rates have increased by 2.4 times as more sophisticated ultrasound techniques and liberal use of fine-needle aspiration (FNA) biopsies have detected subclinical disease.7,8
Etiologies for incidental thyroid nodules can be divided into benign and malignant causes. Benign etiologies include thyroid cyst (simple or complex), multinodular goiter, and Hashimoto's thryoiditis, while malignant causes include papillary, medullary, follicular, Hurthle cell, and anaplastic carcinomas, thyroid lymphomas, and rare instances of metastatic cancers.2,3
Targeted history and physical examination helps to characterize the thyroid incidentaloma. Historical features, such as palpitations, weight loss, anxiety, new onset atrial fibrillation, or menstrual irregularities, coupled with tachycardia, tremors, proximal muscle weakness, and a palpable nodule aid in the diagnosis of hyperthyroidism. Findings such as a family history of thyroid cancer, symptoms of hoarseness or dysphagia, rapid growth of the nodule, environmental or history of head or neck irradiation along with physical findings of a hard, fixed nodule, or cervical lymphadenopathy increase the suspicion for malignancy.2,7
The functionality of the nodule can be assessed by checking TSH, free T3, and free T4 levels. Suppression of TSH (< 0.1 mU/L) with elevated levels of free T3 and T4 indicates nodule production of excess thyroid hormone and warrants thyroid scintography. Thyroid scintography will identify the nodule as "hot" (hyperfunctioning) or "cold" (nonfunctioning).2
Regardless of the radiographic modality that initially identified the thyroid incidentaloma, a dedicated thyroid high-resolution ultrasound should be ordered to assess the size, multiplicity (single or multinodular), location, and character (solid, cystic, or mixed).7
Recommendations for proceeding to FNA to evaluate for malignancy differ among subspecialty societies. Generally, nodules larger than 1 cm or nodules smaller than 1 cm with risk factors for malignancy should be referred for FNA.2,7
If diagnostic workup identifies a patient with hyperthyroidism due to an autonomously functional nodule or a nodule that may be at high risk for malignancy, it is appropriate to involve an endocrinologist and possibly a surgical subspecialist prior to discharge. Management of hyperthyroidism can include starting antithyroid agents (methimazole or propylthiouracil), radioactive iodine ablation, or referral for surgery.
Preparation for discharge of the patient whose incidentaloma is nonfunctional or does not appear to be malignant should include appointments to recheck thyroid hormone levels, including TSH as well as a thyroid ultrasound within one year of the initial discovery.
Adrenal incidentaloma. The prevalence of AIs found by CT of the abdomen ranges from 0.4% to 4%, while autopsy studies have found a prevalence of 1.4% to 9% with increasing prevalence with age.2,9,10 The majority of AIs are benign and nonfunctioning adenomas, in the absence of known malignancy. Other differential diagnoses include Cushing's syndrome, pheochromocytoma, adrenocortical adenoma, aldosteronoma, and metastatic lesions.
Because functioning adrenal incidentalomas may be clinically silent, any patient found with an AI must undergo biochemical workup as part of their evaluation to assess for pheochromocytoma, Cushing's syndrome, and if he or she has a history of hypertension or hyperaldosteronism (Conn's syndrome). Table 3 outlines the approach for characterizing adrenal incidentalomas.2,11,12 An important point is that imaging studies are not useful in distinguishing a functioning versus nonfunctioning tumor but rather can help to discriminate malignant lesions.11
Inpatient surgical consult for resection is indicated if the patient is found to have pheochromocytoma, clinically apparent functioning adrenocortical adenoma, or a tumor size greater than 4 cm. Consultation with an endocrinologist is also recommended if biochemical tests are positive. If the diagnostic workup leads to suspicion for infection or metastatic disease, the patient should be referred for FNA.2,12
For patients whose lesions do not require surgical resection, repeat CT scan of the abdomen is recommended six months from the initial finding. Hospitalists should also arrange for the patient to repeat biochemical testing, including an overnight dexamethasone test.12,13
The patient underwent biochemical testing and was found to have normal levels of plasma-free metanephrines, a plasma aldosterone, plasma renin activity ratio less than 20, and a serum cortisol level of 7 mg/dL after his overnight dexamethasone suppression test. The 24-hour urine collection for free cortisol revealed elevated levels of cortisol in the urine, and the ACTH level was low.
Endocrinology and endocrine surgery teams were consulted, and recommended surgical resection. After surgical resection of his tumor, the patient was started on glucocorticoid replacement and was discharged with a follow-up appointment with endocrinology.
An inpatient approach to endocrine incidentalomas should include characterization of the clinical signs and symptoms, size, function, and malignant potential of the lesion. Based on this, inpatient surgical or medical management can be determined. Post-discharge management should include arrangements for surveillance testing and follow-up with appropriate subspecialists.
Dr. Tad-y is assistant professor of medicine and a hospitalist at the University of Colorado Denver.
From http://www.the-hospitalist.org/details/article/1380161/What_Is_the_Best_Approach_for_the_Evaluation_and_Management_of_Endocrine_Inciden.html