text:
Cumbrian loan shark must pay back £50k or face prison term
Last updated at 13:30, Friday, 27 April 2012
A loan shark must pay back more than £50,000 or face 18 months in prison.
Related: Cumbrian loan shark who made £36,000 from money lending avoids jail
Paul Gilpin appeared at Carlisle Crown Court today for a Proceeds of Crime hearing.
Gilpin, of Thorny Road, Thornhill, near Egremont, ran his business for nearly eight years, netting about £100 a week on top of his regular wages from his job in the construction industry.
He had more than 40 customers, to whom he lent relatively small amounts of money, usually for short periods of time.
The loans - some charged at 70 per cent - enabled him to buy two houses.
The court was told Gilpin's realisable assets amounted to £50,543.11.
Last year Gilpin was given a nine-month prison sentence, suspended for two years and ordered to do 250 hours' unpaid work in the community after he pleaded guilty to carrying on a consumer credit business without the necessary licence and laundering the money he made from it.
Gilpin must pay the money by October 1.
The prosecution was brought by Birmingham Trading Standards.
After the hearing, Angela Jones, Trading Standards service manager at Cumbria County Council, said: "This result is great news for Cumbria Trading Standards and the Illegal Money Lending team, we hope that this will send a stark warning to those engaged in illegal money lending that we will do all we can to tackle this despicable crime.
"We will continue to work in partnership to target loan sharks operating in our communities and prevent the most vulnerable from being trapped in debt and misery to unlicensed lenders."
And Tony Quigley, head of the England Illegal Money Lending Team, said: "Loan sharks are motivated purely by greed.
"They do not offer a community service and cause nothing but misery. Through proceeds of crime legislation we are able to hit illegal money lenders where it hurts, preventing them from profiting through crime.
"Today's result sends a clear message that we will tackle this crime and strip offenders of their ill-gotten gains."
First published at 13:21, Friday, 27 April 2012
Published by http://www.newsandstar.co.uk
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Stuffed Edam Cheese
30 Mar 2010
|Whole edam cheese
|Dry sherry
|1⁄2 Cup (8 tbs)
|Prepared mustard
|1 1⁄2 Teaspoon
|Worcestershire sauce
|1 Teaspoon
|Cayenne pepper
|1 Dash
|Heavy cream
|1⁄4 Cup (4 tbs)
Remove red wax coating of cheese.
Cut a 2-inch piece off the top.
Carefully scoop out the cheese, leaving a 1-inch thick shell.
Grate the cheese and blend with ingredients in order given.
Stuff the shell.
Rate It
0 Comments
Stuffed Edam Cheese Recipe

subset: commoncrawl


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Season 2 Episode #213
Mountain Lions; Fur Trapping; Urban Falcons
Segments in this Episode
Oregon Field Guide
Mountain LionsOPB | Feb. 1, 1991 7:30 p.m.
Head into the snow-covered mountains as researchers study cougar behavior.
Oregon Field Guide
Fur TrappingOPB | Feb. 1, 1991 7:30 p.m.
Many species of animal are trapped for fur in Oregon, despite protests.
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Almost disappearing entirely, Peregrine Falcons struggle to make a comeback in Oregon.
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Folks on the Emerald Coast are used to rain. READ MORE
If tropical weather approaches the U.S. next year, coastal residents will see new, separate warnings about storm surge in addition to those about winds, the National Hurricane Center said Thursday. READ MORE
Hurricane season has ended with a whimper. READ MORE
Folks along the Emerald Coast woke up Tuesday morning to ice and freezing temperatures. Another round of cold weather was expected Tuesday night.
Photos by Nick Tomecek, Daily News staff photog... READ MORE
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Folks in the Navarre area took these photos of a waterspout Tuesday morning and shared them with the Daily News. READ MORE


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Video-on-demand firm has access to 9,000 films
Supermarket behemoth Tesco has bought an 80 per cent stake in blinkbox, the British video-on-demand firm.
As a majority shareholder for blinkbox, the world's number three retailer has gained access to a catalogue of over 9,000 Hollywood films, as well as numerous television series.
.relatedLinksLeft { font-size:12px; width:300px; margin:12px 12px 12px 0; float:left; padding:0px 0px 10px 0px; background:#ececec; } h3.rlTitle {margin:0px; display:block; padding:5px 0 4px 15px !important; background:#ddd; }
The website, which has achieved a following of 2 million monthly viewers since its launch in April 2008, will allow Tesco to revamp its product line a day after missing profit hopes in its main UK market.
Richard Brasher, UK chief executive for Tesco, commented: "Whether customers want to own the DVD, download a digital movie, stream a rental or all three, Tesco is committed to giving customers choice.
"We want to allow them to decide how they access entertainment content and on which devices, whether it's on PC, TV or tablet."
The supermarket group is currently in the midst of increasing its online retail investment with plans in motion to launch a rival to Amazon's Marketplace in late 2011 or early 2012.
Would you stream a movie from Tesco? Were you a blinkbox user before the takeover? Let us know via our Facebook and Twitter pages.
Via: Reuters


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Unique, family-friendly museums in the U.S.
People have passions for all sorts of things. Fortunately, that fever often needs to be shared and has resulted in unusual museums.
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People Pets
The Cutest Pets on Twitter This Week!We put the call out on Twitter for your cutest photos and you delivered! See our first-place furballs and some runners-up from our daily #cutepic photo contest
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how do you clean this throw?
It's all good. ..it's good for cold weather....
Eddie Bauer Ultra Plush Sherpa Throw
Keep warm on chilly nights with this soft plaid sherpa throw. One side of the throw has popcorn fleece, and the other side is polar fleece. It is available in tan, blue, and red so you can choose a color that fits your personal style or bedding.
ITEM#: 14792622This attractive, comfortable sherpa throw blanket from Eddie Bauer features a versatile plaid design over color options that fit any home decor. Add a stylish accent to any room with this soft, polyester blanket. The gorgeous Eddie Bauer throw is long enough to keep even your taller guests warm. One side of the throw is popcorn fleece, the other is polar fleece, and both sides are well-made and elegant. This machine-washable soft blanket can be used both indoors and outdoors to keep warm on chilly nights.
- Construction: 160 gsm Polar Fleece reverses to 250 gsm Popcorn Fleece
- Weave: Plain
- Design: Plaid
- Color options: Red, Blue, Tan
- Materials: 100-percent polyester
- Care instructions: Machine wash
- Dimensions: 50 inches wide x 70 inches long
The digital images we display have the most accurate color possible. However, due to differences in computer monitors, we cannot be responsible for variations in color between the actual product and your screen.
|Outdoor Plush
|Set Include
|1 Piece
|Brown Multi Red
|See description
|See description
|Model Number
|EB Sherpa Throw
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GREAT THROW FOR THE GUY IN YOUR LIFERead More
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I bought these blankets as gifts for my parents, but when they arrived I wanted to keep them for my own. They're made from high-quality materials, they're warmer and more substantial than a decorative throw, and the size dimensions of them are fantastic. As a relatively tall person, I have had a tough time finding throws that cover more than just my legs. I knew the same would be true for my folks, so I was very happy to see the actual size when they arrived in the mail. In addition, my mom has told me how much she loves them and how warm they are every single time I visit. Maybe that's a sign of a bad memory, or maybe she just likes them that much. Either way, I'm calling it a success.Read More
This is a very cozy throw ! Easy care, wash and dry. I liked it so much that I purchased a second one to give as a gift.Read More
Eddie Bauer Sherpa Throw
This ia an excellent throw blanket. Well made and very attractive. I use it all the time - while watching TV on my sofa and when the nights get cool, I cover it on my down comforter,. Good quality, reasonable, just the right size for a throw blanket.Read More
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Tags: Hitachi Construction Machinery Co.
Hitachi's new Zaxis-5 Series excavators
Hitachi Construction Machinery Co. says its new Zaxis-5 Series excavators — ZX160LC-5, ZX180LC-5, ZX210-5, and ZX201LC-5 — feature Isuzu Interim Tier 4 engines that deliver high productivity with fuel efficiency. A muffler filter helps reduce emissions by capturing air pollutants. ... Read More...
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Komatipoort is conveniently situated 8km from the Crocodile Bridge Gate to Kruger National Park. Bordering Mozambique and 65km from the border of Swaziland, it's a perfect base to explore these diverse worlds.
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An oasis of peace and trees, the town is small, quiet and safe, with a few local restaurants and excellent accommodation ranging from backpackers to luxury lodges and self-catering facilities.
Within an hour's drive you can...


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Peterson Going to Alaska-Fairbanks Next Season
Posted: 04/10/2012 - After playing in his second and final season in the USHL, Tri-City Storm defenseman J.D. Peterson made his commitment official to the University of Alaska-Fairbanks Nanooks.
Posted: 04/10/2012 - After playing in his second and final season in the USHL, Tri-City Storm defenseman J.D. Peterson made his commitment official to the University of Alaska-Fairbanks Nanooks.
Posted: 04/10/2012 - The Nebraska Game and Parks Commission says the spring turkey season for shotgun hunters opens Saturday.
Posted: 04/07/2012 - Participants in the 2012 Tour de Nebraska will spend five days pedaling through the northeast part of the state.
Updated: 04/05/2012 - Kevin Roy is enjoying one of the greatest individual seasons in Lincoln Stars history, breaking the organization's single-season scoring record and leading the Stars back to the USHL playoffs.
Updated: 04/03/2012 - 10/11 Sports Director Kevin Sjuts caught up with the Harlem Globetrotters to improve his skills.
Updated: 03/30/2012 - Jim Weeks, who coached 24 years at Beatrice High School, is the new head men's basketball coach at Doane College.
Updated: 03/30/2012 - The route is set and registration is open for the 2012 Cornhusker State Games Torch Run.
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Posted: 03/17/2012 - North Carolina's Harrison Barnes and Creighton's Doug McDermott are former teammates from Ames High School. Creighton and North Carolina meet Sunday in a Midwest Regional game.
Posted: 03/16/2012 - Creighton erased an 11-point deficit to beat Alabama and earn its first NCAA Tournament win since 2002.
Posted: 03/11/2012 - The No. 2 Concorida Bulldogs women's basketball squad earned a hard fought 80-68 win over No. 7 Grand View (Iowa) in the quarterfinals of the NAIA Division II National Championships on Saturday, March 10 in Sioux City, Iowa.
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Spring Barley Risotto with Asparagus and Lemon
6 comments | Leave Comment
Spring Barley Risotto with Asparagus and Lemon
I love the consistency of risotto but am always looking for a way to incorporate more nutrition into a recipe. The natural starch of the barley grain adds creaminess to this dish. The use of saffron mimics the classic risotto Milanese which some connect to the Venetian Jewish community.
- Prep Time : 15 min
- Cook Time : 40 min
- Ready Time : 55 min
- 2 ¾ cups vegetable broth or water and 1 Telma vegetable bouillon cube
- 1/8 teaspoon saffron threads, slightly crumbled
- 10 asparagus, tough ends removed
- 2 tablespoons extra virgin olive oil
- 1 medium onion, diced into ¼ inch dice
- 2 cloves of garlic, finely minced
- 1 cup pearled barley
- ½ cup white wine, Sauvignon Blanc or Viognier
- ½ teaspoon kosher salt, or to taste
- 15 grindings of black pepper, or to taste
- Finely grated zest from ½ lemon (about 1 teaspoon)
- ½- ¾ cup grated fresh Parrano or Parmesan cheese
- 1-2 tablespoons unsalted butter, optional
- ¼ cup toasted, slivered almonds (1 Tablespoon removed for garnish)
- Combine the broth and the crushed saffron threads in a 1 quart pot and bring to a simmer.
- Meanwhile, remove the tough ends of the asparagus, wash, and cut the stalks on the diagonal into ½ inch pieces reserving 1 ½ inches of the tip.
- When liquid is simmering drop in the asparagus stalk pieces and blanch for 2 minutes until bright green and slightly tender. Remove with a slotted spoon to a small glass bowl. Add the tips to the simmering broth and cook for 1 minute. Remove from broth and set aside. Keep broth warm while you prepare the barley.
- Heat a three quart saucepan over high heat for 10 seconds. Add the extra virgin olive oil and heat for 10 seconds. Add the onion and garlic and reduce heat to medium. Sauté mixture until onions are slightly golden but do not let garlic burn.
- Add the barley and stir to coat with the onion mixture and oil.
- Add the wine and stir constantly until the wine is absorbed. Add all of the simmering broth, stir, and then cover and reduce heat to low. Stir the barley mixture every 5 minutes or so to prevent sticking and burning. If all the liquid has been absorbed and the barley appears too hard and/or dry, then add another ¼ cup of water and cook for another 5 minutes. The barley will be firm, but tender after 30-35 minutes.
- Remove the pot from the heat and stir in the salt, pepper and lemon zest until well combined.
- Gently combine the grated cheese into the mixture and when evenly distributed and melted add the almonds and the reserved asparagus pieces (MINUS 5 asparagus tips for garnish).
- Immediately serve the barley risotto in a nice dish garnished with the reserved tablespoon of almonds and the 5 remaining asparagus tips.Tina's Tidbits:
- The "pearling" of the barley grain exposes its starchy interior to the liquid and creates the creamy consistency of this dish
- Parrano cheese is similar to a gouda cheese in consistency but has the sharp tang of a Parmesan Reggiano; either can be used
- If you want an even richer consistency, add 1-2 tablespoons of unsalted butter to this or any hot barley dish
About Tina Wasserman
6 Responses to Spring Barley Risotto with Asparagus and Lemon
Easy to make a great change of pace. We don't have any gluten problems in our family, but there are times I want to cook gluten free and this recipe did the trick! Next time I think I may try pine nuts.
I am so glad you like it. But remember, for Celiac patients, there is gluten in barley so continue to enjoy the alternative that is filled with nutrients but be aware.-Tina
Made this for supper and was afraid it wouldn't be enough for my husband so I made egg omelets and served on top. Was really good. Never eat risotto before but will again this way.
Omelet on top is a great way to include protein into the meal! Good for you! I always want people to "tweak" my recipes if they want to. Thanks for sharing.
Leave a Reply
Posted in
Dairy , Dinner, Lunch, Main, Side Dish, Starches , Shavuot , Italian , Cooking for a Crowd, Dinner Tonight , Budget, Comfort Food, Kid Friendly , Rice, Grains, & Pasta ,


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Table setting at a luxury wedding reception in a large ballroom
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text: Presidents--United States United States. S.l. Presidents' spouses--United States Presidents' spouses. Hoover Herbert Hoover, Herbert, 1874-1964. 1874 1964 s.n. 2006 Wills William Wills, William. Wills Sue Wills, Sue. Hoover Lou Henry Hoover, Lou Henry, 1874-1944. 1874 1944 Presidents and their first ladies, dramatically speaking Presidents. Herbert & Lou Hoover Biography en Not rated. 2006 80939806 Herbert and Lou Hoover president and first lady, 1929-33


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JACKSONVILLE, Fla. -- Now that defensive coordinator Romeo Crennel owns a share of a third Super Bowl title in four seasons with the Patriots, he's ready to embark on a new challenge.
Crennel, courted by Cleveland before the playoffs began, has accepted the Browns' offer to be their new head coach. His agent will travel to Cleveland on Monday to begin contract negotiations.
As the Patriots celebrated their latest Super Bowl win, Crennel said he was thrilled the Browns called with their offer.
"It felt real good," The Associated Press quoted him as saying. "I've been in this business for a little while. I've always been told if you work hard and you're good at what you do, you'll get an opportunity to move up."
Joe Linta, Crennel's agent, told The Associated Press that Browns president John Collins called him "about
two minutes" after the Patriots beat the Philadelphia Eagles to
offer Crennel his first head coaching job.
"He has accepted, pending us working out a contract," Linta
told the AP. "Hopefully, we can get it done
quickly and he can begin putting together a staff."
Linta said he'll be on a 6:30 a.m. Monday flight to Cleveland
and will go straight to the team's headquarters in suburban Berea
to begin contract talks.
Browns owner Randy Lerner will be in Cleveland on Wednesday, the expected day of Crennel's introductory news conference. It is believed that Crennel, who at 57 will become one of the oldest coordinators of this era to earn his first head-coaching job, will seek a five-year contract.
Crennel will be one of a record six black head coaches in the league in 2005. He has been an assistant in the NFL since 1981 and a coordinator for six seasons.
Linta told the he will seek a five- or six-year deal for Crennel.
"He's not like most first-time coaches," Linta said. "He's a
guy with more credentials. Although he hasn't been a head coach, he
has five Super Bowl rings. The Browns aren't just getting a coach.
They're buying into a program. They are getting 25 years of
experience and knowledge."
Given the fait accompli assumptions on Crennel's hiring over the past week or more, attention in some quarters has turned to who he will hire as coordinators. League sources have confirmed the various reports that current Cowboys offensive coordinator Maurice Carthon will move to Cleveland in the same capacity. Crennel is expected to pursue current Patriots secondary coach Eric Mangini for the defensive coordinator spot, but will have competition from several teams for Mangini.
Len Pasquarelli is a senior NFL writer for ESPN.com. To check out Len's chat archive, click here.


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Article: Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA): long-term follow-up of the Northwestern University experience.[Show abstract] [Hide abstract]
ABSTRACT: 2-Chlorodeoxyadenosine (2-CdA), a purine analog, has become universally accepted as the agent of choice in treating hairy cell leukemia (HCL). However, few studies have reported long-term outcomes after 2-CdA treatment. Between January 1990 and June 2003, 86 consecutive patients with HCL were treated with a single 7-day course of 2-CdA by continuous infusion at a dose of 0.1 mg/kg per day. Of the 86 patients (mean age: 49 years), 67 patients (79%) achieved a complete remission (CR); 18 patients (21%) achieved a partial remission (PR); and 1 patient's response was unable to be assessed. The progression-free survival (PFS) for initial relapse after 12 years was 54%. At a median follow-up of 9.7 years (range, 0.3-13.8 years), 31 (36%) of 85 patients relapsed. There were 23 relapsed patients treated with a second cycle of 2-CdA; 2 patients were treated with alternative agents; and 6 patients were observed. Of the 23 relapsed patients retreated with 2-CdA, 12 (52%) achieved a CR and 7 (30%) patients achieved a PR (overall response rate: 83%). The overall survival (OS) rate after 12 years was 87%. There were 15 patients (17%) who developed other malignancies. Long-term follow-up of up to 14 years (median: 9.7 years) showed an excellent PFS and OS for HCL patients after 2-CdA treatment.Blood 08/2005; 106(1):241-6. DOI:10.1182/blood-2005-01-0173 · 9.78 Impact Factor
Article: Technetium-99m sulfur colloid scanning and correlative magnetic resonance imaging in patients with hairy cell leukemia and hypocellular bone marrow biopsies after 2-chlorodeoxyadenosine.[Show abstract] [Hide abstract]
ABSTRACT: It has been observed that some patients in complete remission (CR) after 2-chlorodeoxyadenosine (2-CdA) for hairy cell leukemia (HCL) have hypocellular bone marrow biopsies despite normal peripheral blood cell counts. This discrepancy between bone marrow cellularity and peripheral blood cell counts suggests the possibility of abnormal sites of hematopoiesis. To determine sites of hematopoiesis, 11 radionuclide scans using technetium-99m (99mTc) sulfur colloid were performed in eight patients. Although no single, pattern was observed on the 99mTc sulfur colloid scans, two of the eight patients, both with virtually aplastic marrows, had multiple areas of increased uptake in the distal appendicular skeleton, suggesting abnormal sites of hematopoiesis. The same two patients had magnetic resonance imaging (MRI), which confirmed the abnormal sites of hematopoiesis.Leukemia and Lymphoma 10/1999; 35(1-2):171-7. DOI:10.3109/10428199909145716 · 2.61 Impact Factor
Article: Minimal residual disease in patients with hairy cell leukemia in complete remission treated with 2-chlorodeoxyadenosine or 2-deoxycoformycin and prediction of early relapse.[Show abstract] [Hide abstract]
ABSTRACT: The purine nucleoside analogues 2-chlorodeoxyadenosine (2-CdA) and 2'-deoxycoformycin (2'-DCF) induce complete remission (CR) in the majority of patients with hairy cell leukemia. However, minimal residual disease (MRD) has been detected in bone marrow core biopsies using immunohistochemical techniques in patients achieving CR by conventional criteria. This study was designed to compare the prevalence of MRD with each agent in patients in CR by using conventional criteria and the relapse-free survival for patients with and without MRD. Bone marrow biopsies from 39 patients treated with a single cycle of 2-CdA and 27 patients treated with multiple cycles of 2'-DCF were studied. The monoclonal antibodies anti-CD20, DBA.44, and anti-CD45RO were used to evaluate the paraffin-embedded bone marrow core biopsies for MRD. Five of 39 patients (13%) treated with 2-CdA had MRD, as compared to 7 of 27 patients (26%) treated with 2'-DCF (two-tailed P = 0.21). Relapse has occurred in two of the five patients with MRD after 2-CdA treatment and in four of the seven patients with MRD after 2'-DCF treatment. In total, 6 of the 12 patients (50%) with MRD have relapsed, whereas 3 of 54 patients (6%) without MRD have relapsed, and 2 patients have died without evidence of relapse. The estimated 4-year relapse-free survival among patients with MRD is 55% (+/- 15%, SE), compared to 88% (+/- 5%, SE) among patients without MRD (two-tailed P = 0.0023). The prevalence of MRD detected in a subset of patients in CR after either 2-CdA or 2'-DCF treatment did not differ significantly. However, the presence of MRD is associated with an increased risk of relapse.Clinical Cancer Research 08/1999; 5(7):1665-70. · 8.19 Impact Factor
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ABSTRACT: Although hairy-cell leukemia (HCL) is uncommon, remarkable progress has been made in the treatment of patients with this disease. Because of their unique mechanisms of action, the purine analogs, 2'-deoxycoformycin (2'-DCF) and 2-chlorodeoxyadenosine (2-CdA), are naturally targeted to lymphocytes and are cytotoxic to both resting and dividing cells. Both of these agents induce durable complete remissions (CRs) in the overwhelming majority of patients. Remarkably, equally high rates of durable CR are achieved in both untreated and previously treated patients. Furthermore, patients with large tumor burdens fare as well as those with minimal disease. Therefore, these agents have emerged as the treatments of choice for all patients with hairy-cell leukemia and have supplanted earlier treatments such as splenectomy and interferon-alpha (IFN-alpha). Since a single 7-day cycle of 2-CdA leads to excellent outcomes and is associated with few toxicities other than culture-negative fever, this agent is particularly attractive and may offer some advantages. However, given the indolent natural history of HCL, long-term follow-up study will be required to determine if one purine analog offers a survival advantage over the other.Seminars in Hematology 05/1999; 36(2):155-63. · 2.46 Impact Factor
- Journal of Clinical Oncology 03/1998; 16(3):1232-3. · 17.88 Impact Factor
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ABSTRACT: Hypocholesterolemia is a well-documented phenomenon associated with a variety of hematological malignancies and nonmalignant disorders associated with splenomegaly. To determine the incidence of hypocholesterolemia in patients with hairy cell leukemia (HCL), we measured the serum cholesterol levels before and after a single cycle of 2-chlorodeoxyadenosine (2-CdA) in 46 patients. The mean pre-treatment serum cholesterol level was 152.8 mg/dl (range, 60 to 293 mg/dl). The mean post-treatment serum cholesterol level was 190.0 mg/dl. This was significantly higher than the pre-treatment values (P <0.0001). Twelve patients who had previously undergone splenectomy showed a similar response to treatment, with a pre-treatment value of 180.0 mg/dl and a post-treatment value of 219.8 mg/dl (P < 0.0001). However, there was a significant difference in the pre-treatment serum cholesterol levels in the nonsplenectomized patients (143.0 mg/dl) compared to the splenectomized patients (180.0 mg/dl) (P < 0.03). The pre-treatment serum cholesterol did not correlate with the pre-treatment splenic index (correlation coefficient = -0.39, P < 0.065). Similarly, there was no correlation between the change in splenic index and the change in serum cholesterol level post-treatment. These findings suggest that hypocholesterolemia in HCL is related to tumor burden and not to splenomegaly alone. Since cholesterol is critical to hairy cell metabolism and structure, treatment strategies interfering with cholesterol synthesis may be productive.American Journal of Hematology 07/1997; 55(3):129-33. DOI:10.1002/(SICI)1096-8652(199707)55:33.3.CO;2-Z · 3.48 Impact Factor
Article: Relapse of hairy cell leukemia after 2-chlorodeoxyadenosine: long-term follow-up of the Northwestern University experience.[Show abstract] [Hide abstract]
ABSTRACT: Although 2-chlorodeoxyadenosine (2-CdA) is effective in inducing complete remissions (CRs) in the majority of patients with hairy cell leukemia (HCL), neither the actual relapse rate, the clinical factors that may predict relapse, the long-term outcome, nor the response rate to re-treatment at relapse has been clearly determined. Fifty-two consecutive patients with previously untreated or treated HCL were treated with 2-CdA at a dose of 0.1 mg/kg/d by continuous intravenous infusion for 7 days. Of 50 assessable patients, 40 (80%) achieved CR, and 9 (18%) achieved partial remission (PR). A total of 7 patients (14%) have relapsed, at a median duration of 24 months (range, 12 to 44). Of the 7 relapsed patients, 5 were re-treated with a second cycle of 2-CdA; 2 achieved a second CR and 3 attained a PR. The progression-free survival (PFS) rate is 72% at 4 years for all 52 patients and 83% for patients achieving CR. The overall survival (OS) rate is 86% at 4 years. Only prior therapy was predictive of relapse. The majority of patients achieve durable CRs with a single cycle of 2-CdA. The relapse rate is low and the long-term prognosis is excellent. The few patients who relapse can attain second remissions after re-treatment with 2-CdA.Blood 10/1996; 88(6):1954-9. · 9.78 Impact Factor
Article: Minimal residual disease may predict bone marrow relapse in patients with hairy cell leukemia treated with 2-chlorodeoxyadenosine.[Show abstract] [Hide abstract]
ABSTRACT: Minimal residual disease (MRD) can be detected in bone marrow core biopsies of patients with hairy cell leukemia (HCL) after treatment with 2-chlorodeoxyadenosine (2-CdA) using immunohistochemical (IHC) techniques. The purpose of this study was to determine whether the presence of MRD predicts bone marrow relapse. We studied paraffin-embedded bone marrow core biopsies from 39 patients with HCL in complete remission (CR) 3 months after a single cycle of 2-CdA. Biopsies performed 3 months posttherapy and annually thereafter were examined by routine hematoxylin and eosin (H&E) staining and IHC using the monoclonal antibodies (MoAbs) anti-CD45RO, anti-CD20, and DBA.44. At 3 months after therapy, 5 of 39 (13%) patients had MRD detectable by IHC that was not evident by routine H&E staining. Two of the five patients (40%) with MRD at 3 months have relapsed, whereas only 2 of 27 (7%) patients with no MRD and at least 1 year of follow up relapsed (P = .11). Over the 3-year follow-up period, two additional patients developed MRD. Overall, three of six (50%) patients with MRD detected at any time after therapy have relapsed, whereas only 1 of 25 (4%) patients without MRD has relapsed (P = .016). These data suggest that the presence of MRD after treatment with 2-CdA may predict relapse.Blood 02/1996; 87(4):1556-60. · 9.78 Impact Factor
- Seminars in Hematology 02/1996; 33(1 Suppl 1):23-7. · 2.46 Impact Factor
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ABSTRACT: This case report reviews the unique development of a vasculitic syndrome involving medium-sized arteries in a man with chronic myelomonocytic leukemia (CMMoL). This case has many features in common with cutaneous polyarteritis nodosa (CPAN), and this may represent the first instance in which CPAN developed in the setting of CMMoL.American Journal of Hematology 12/1995; 50(4):310-2. DOI:10.1002/ajh.2830500418 · 3.48 Impact Factor
- Blood 11/1995; 86(7):2463-74. · 9.78 Impact Factor
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ABSTRACT: Cladribine (2-CdA), a purine analog resistant to adenosine deaminase, has significant activity in a variety of lymphoproliferative diseases. This study was designed to determine the efficacy of 2-CdA in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). Twenty-six patients aged 40 to 88 years (median, 64) who either had relapsed after an initial response or were refractory to conventional chemotherapy with at least an alkylating agent were treated with 2-CdA 0.1 mg/kg/d by continuous intravenous infusion for either 5 or 7 days every 28 days for a maximum of six cycles. No complete remissions (CRs) occurred. Eight of 26 patients (31%) achieved a partial remission (PR). The actuarial median time to progression (TTF) in responding patients is 16 months (range, 6 to 22). The actuarial median survival duration of the responding patients is 12 months (range, 8 to 28). Eight of 26 patients (31%) sustained early toxicity. Seven of these eight patients died before the first reevaluation of infection (n = 3), pericardial tamponade (n = 1), Stevens-Johnson syndrome (n = 1), and stroke (n = 2). No nausea, emesis, alopecia, or renal, hepatic, or cardiac toxicity was observed. 2-CdA has activity in patients with relapsed or refractory CLL. However, patients who have received multiple prior regimens that included fludarabine are less likely to respond, and there can be significant morbidity. Treatment of patients with less prior therapy earlier in the natural history of the disease may lead to improved and more durable responses.Journal of Clinical Oncology 05/1995; 13(4):983-8. · 17.88 Impact Factor
Article: 2-Chlorodeoxyadenosine is an active salvage therapy in advanced indolent non-Hodgkin's lymphoma.[Show abstract] [Hide abstract]
ABSTRACT: To determine the response rate to 2-chlorodeoxyadenosine (2-CdA; cladribine) in patients with advanced indolent non-Hodgkin's lymphoma (NHL) who fail to respond to or progress after a response to standard chemotherapy drugs. Twenty-one patients were treated with at least one cycle of 2-CdA 0.1 mg/kg/d by continuous infusion for 5 or 7 days. The overall response rate (complete response [CR] and partial response [PR]) was nine of 21 patients (43%; 95% confidence interval, 22% to 64%). Unmaintained durable responses (longest follow-up, 29+ months) have been observed. The treatment was well tolerated by all patients. The major toxicity was related to myelosuppression (predominantly neutropenia) and immunosuppression with infection. The purine analog 2-CdA is an active salvage therapy in pretreated patients with indolent NHL, and deserves further assessment in untreated patients and in combination with other chemotherapy agents.Journal of Clinical Oncology 05/1994; 12(4):788-92. · 17.88 Impact Factor
Article: Prospective evaluation of internal adenopathy in a cohort of 43 patients with hairy cell leukemia.[Show abstract] [Hide abstract]
ABSTRACT: To determine the role of computed tomography (CT) in patients with hairy cell leukemia (HCL), we report a series of 43 patients prospectively evaluated for internal adenopathy by CT before and after treatment with 2-chlorodeoxyadenosine (2-CdA). CT was performed on 43 consecutive patients with HCL before and 3 months after a single cycle of 2-CdA. Twenty-four patients were previously diagnosed and 19 were newly diagnosed. Adenopathy was considered bulky if the greatest dimension of any confluent mass was between 5 and 10 cm and massive if greater than 10 cm. Internal adenopathy was present in six of 43 patients (14%). Three of the six patients had massive abdominal adenopathy and one had bulky abdominal adenopathy. All six patients with adenopathy were previously diagnosed, while none of the 19 newly diagnosed patients had internal adenopathy. In those patients previously diagnosed, the six with adenopathy had a median disease duration of 68 months, while the 18 patients without adenopathy had a median disease duration of 24 months (P = .01). Adenopathy was more common in splenectomized patients. In previously diagnosed patients, adenopathy occurred in five of 10 (50%) splenectomized patients and one of 14 (7%) nonsplenectomized patients (P = .05). However, the 10 splenectomized patients had a median disease duration of 56 months, while the 14 nonsplenectomized patients had a median disease duration of 16 months (P = .004). All six patients had significant reduction in adenopathy 3 months after 2-CdA and were without residual HCL in the bone marrow. Significant internal adenopathy in patients with HCL is more frequent than previously recognized. Adenopathy is rare at diagnosis and appears to be related to disease duration. As patients treated with 2-CdA have long disease-free survival durations, detection of significant adenopathy by CT scan may be important; however, routine CT scans are not recommended at the time of diagnosis.Journal of Clinical Oncology 03/1994; 12(2):268-72. · 17.88 Impact Factor
Article: Assessment of complete remission after 2-chlorodeoxyadenosine for hairy cell leukemia: utility of marrow immunostaining and measurement of splenic index.[Show abstract] [Hide abstract]
ABSTRACT: 2-Chlorodeoxyadenosine (2-CdA) yields high complete remission (CR) rates in patients with hairy cell leukemia (HCL) Two approaches were used to detect minimal residual disease. We studied two B-lineage antibodies, L26 and MB2, and a T-lineage antibody, UCHL-1, in fixed marrow core biopsies from 34 patients with HCL before and after 2-CdA to detect minimal residual in the marrow. In addition, the splenic index was calculated before and after treatment to detect residual splenomegaly. Prior to therapy, hairy cells exhibited intense cytoplasmic membrane reactivity with L26 and strong intracytoplasmic reactivity with MB2. UCHL-1 did not react with hairy cells. Thirty-one patients were assessable 3 months after therapy. Five of 24 (21%) patients in CR by routine evaluation had residual HCL detected by immunostaining. Four of these 5 patients have been reevaluated at 1 year. One patient relapsed by routine evaluation, 2 remained positive by immunostaining alone, and 1 patient became negative by immunostaining. A total of 19 patients have been evaluated at 1 year and 17 remain in CR. Three of these 17 were positive by immunostaining, 2 of whom had been positive at 3 months and 1 additional patient who became positive by immunostaining at 1 year. Of 9 patients evaluated at 2 years, an additional 2 of 3 patients with minimal residual disease detected previously by immunostaining at 3 months relapsed by routine morphology and 1 had persistent positive immunostaining. Only 1 patient in remission by morphology and immunostaining has relapsed.(ABSTRACT TRUNCATED AT 250 WORDS)Leukemia and Lymphoma 02/1994; 14 Suppl 1:133-8. · 2.61 Impact Factor
Article: New insights into the pathogenesis of coagulation dysfunction in acute promyelocytic leukemia.[Show abstract] [Hide abstract]
ABSTRACT: Patients with acute promyelocytic leukemia (APL) are at high risk for the development of life-threatening thrombotic and hemorrhagic complications, particularly during induction chemotherapy. This propensity has been attributed to the release of tissue factor (TF)-like procoagulants from the leukemic cells leading to disseminated intravascular coagulation (DIC). However, recent data suggest that the pathogenesis of the coagulopathy is more complicated and may involve activation of the generalized proteolytic cascade resulting in either clotting and/or excessive fibrinolysis. Furthermore, controversy exists regarding the mechanism(s) responsible for the activation of either clotting or fibrinolysis. The malignant promyelocyte may act directly to activate coagulation and/or fibrinolysis. Alternatively, reactive inflammatory cells, which express procoagulant and/or profibrinolytic activities may play an essential role. A third possibility may involve endothelial cell expression of mediators with procoagulant/profibrinolytic properties. Putative profibrinolytic mechanisms include the release of urokinase-type and tissue-type plasminogen activators, decreases in plasminogen activator inhibitor-1 and 2, and decreases in alpha-2 plasmin inhibitor. Putative procoagulant mechanisms include the release of tissue factor, Cancer Procoagulant, or cytokines such as interleukin-1, tumor necrosis factor and vascular permeability factor. Putative anticoagulant mediators include annexins, a group of proteins in human tissue which bind phospholipids and have anticoagulant activity, which have been reported in patients with APL. The current treatment of APL is rapidly evolving because of the efficacy of all-trans retinoic acid (ATRA). All-trans retinoic acid promotes terminal differentiation of leukemic promyelocytes leading to complete remission in the majority of patients with APL with rapid resolution of the coagulopathy. Although the mechanism by which this occurs has not been established, preliminary data suggest that ATRA blocks the downregulation of the thrombomodulin gene and the up-regulation of the tissue factor gene induced by tumor necrosis factor. Since APL is a relatively uncommon disorder, the collaboration of cooperative oncology groups will be important to study patients receiving ATRA or conventional chemotherapy to further elucidate the mechanism(s) of the coagulopathy.Leukemia and Lymphoma 10/1993; 11(1-2):27-36. DOI:10.3109/10428199309054728 · 2.61 Impact Factor
Article: Detection of minimal residual disease by immunostaining of bone marrow biopsies after 2-chlorodeoxyadenosine for hairy cell leukemia.[Show abstract] [Hide abstract]
ABSTRACT: 2-Chlorodeoxyadenosine (2-CdA) yields high complete remission (CR) rates in patients with hairy cell leukemia (HCL). In an effort to detect minimal residual disease, we studied two B-lineage antibodies, L26 and MB2, and a T-lineage antibody, UCHL-1, in fixed marrow core biopsies from 34 patients with HCL before and after 2-CdA. Before therapy, hairy cells exhibited intense cytoplasmic membrane reactivity with L26 and strong intracytoplasmic reactivity with MB2. UCHL-1 did not react with hairy cells. Thirty-one patients were assessable 3 months after therapy. Five of 24 (21%) patients in CR by routine evaluation had residual HCL detected by immunostaining. Four of these 5 patients have been reevaluated at 1 year. One patient relapsed by routine evaluation, 2 remained positive by immunostaining alone, and 1 patient became negative by immunostaining. A total of 19 patients have been evaluated at 1 year. Only 1 additional patient has become positive by immunostaining alone. Immunostaining using the B-lineage antibodies highlighted the presence of hairy cells with preservation of morphology. This assisted in quantifying the extent of disease, particularly when hairy cells were interstitial and blended with surrounding hematopoietic tissue, when hairy cells were present in hypocellular marrows, when hairy cells were spindle-shaped, and when marrows were markedly fibrotic. Because immunostaining can be easily performed on routinely processed marrows, it is an attractive method to detect minimal residual disease. Our data suggest that some patients in apparent CR after 2-CdA may have minimal residual disease. Patients will need to be observed prospectively to determine if residual disease will be predictive of relapse.Blood 10/1993; 82(6):1798-802. · 9.78 Impact Factor
Article: Erythema nodosum associated with all-trans-retinoic acid in the treatment of acute promyelocytic leukemia.[Show abstract] [Hide abstract]
ABSTRACT: A patient with acute promyelocytic leukemia is presented. During treatment with all-trans-retinoic acid, erythema nodosum developed. Treatment with all-trans-retinoic acid was continued, the erythema nodosum resolved with steroid treatment, and a complete remission was attained. This case is the first report of erythema nodosum associated with all-trans-retinoic acid.Leukemia 06/1993; 7(5):758-9. · 9.38 Impact Factor
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ABSTRACT: A rare variant of acute promyelocytic leukemia (APL) is associated with basophilic differentiation. Such a patient presented with basophilia, headaches, and diffuse engorgement of superficial blood vessels, attributable to hyperhistaminemia. Karyotype analysis showed a clonal rearrangement of chromosome 12p13 in addition to the t(15;17). During treatment with all-trans-retinoic acid (TRA), the absolute basophil count rose steadily during the first week, then declined. By one month, the basophilia resolved, an abrupt rise occurred in both the platelet and absolute neutrophil count, and the bone core biopsy showed complete maturation of all cell lines. Abnormalities of chromosome 12p13 in acute myelogenous leukemia have been associated with basophilia. Since every cell in our patient with t(12p13;?) also had the t(15;17), we speculate that the basophilia was due to clonal evolution with acquisition of the t(12p13;?). In two out of five other reported cases, abnormalities of chromosomes known to be associated with basophilia were present in addition to t(15;17). It is possible that the basophilia in this variant is reactive; however, since TRA induces differentiation of leukemic promyelocytes into mature neutrophils, we speculate that the leukemic promyelocytes in our patient differentiated into basophils. Future studies employing either fluorescent in situ hybridization or polymerase chain reaction using a probe to the breakpoint on t(15;17) may establish whether or not the basophils derive from the leukemic clone.Leukemia 05/1993; 7(4):521-6. · 9.38 Impact Factor
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ABSTRACT: Since the only three cases of granulocytic sarcoma among patients with acute myeloid leukemia (AML) seen at our institution during the last 12 years were each associated with the 8;21 translocation [t(8;21)], we sought to determine if this association is specific and more frequent than previously recognized. We report three patients with AML and t(8;21) who developed granulocytic sarcomas, and review the world literature. Between 1980 and 1992, 53 cases of AML French-American-British (FAB) M2 were identified at our institution. Eight (15%) patients had t(8;21). Three of these eight patients (38%) developed granulocytic sarcoma. All three of our patients received conventional intensive antileukemic chemotherapy yet had short relapse-free survival durations. Several series of patients with t(8;21) report that granulocytic sarcomas occur in approximately 18% of this population, which is four times the expected incidence in AML. Thirty-seven cases have been previously reported. Although karyotype analyses were not reported in many cases of granulocytic sarcoma in the literature, the vast majority of abnormal karyotypes in patients with AML involved t(8;21). Recent work with a cell line derived from a patient with t(8;21) indicates that such cells are unusually adherent to culture bottles and are aggregable Our data suggest that this association is more common than generally recognized and may be specific. Patients with t(8;21) should be observed closely for signs and symptoms of granulocytic sarcoma. These patients may have a less favorable prognosis than other patients with t(8;21). Cooperative oncology groups should retrospectively identify patients with AML and t(8;21) who had a poor outcome to determine if they had a disproportionate incidence of granulocytic sarcoma. If so, aggressive therapy such as bone marrow transplantation may be warranted early in the therapeutic strategy.Journal of Clinical Oncology 05/1993; 11(4):690-7. · 17.88 Impact Factor
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Barbershop Music Festival at Carnegie Hall, Presented by Manhattan Concert Productions
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The last date listed for Barbershop Festival 2013 Presented by Manhattan Concert Productions was Sunday December 1, 2013 / 8:30pm.
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The quartets were wonderful.
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It was excellent. Great voices. Funny guys. Would go again in a minute.
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Very entertaining. It was a unique experience for this New York City man. The way they harmonize makes many of the songs they sing sound like they have musical accompaniment.
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The Barbershop Festival show was fantastic and very entertaining. The music was incredible and some parts of the show was hilarious also. What a great evening of entertainment. I would recommend it to everyone.
About the Ticket Supplier: Manhattan Concert Productions
Manhattan Concert Productions is an esteemed production company dedicated to excellence in music making, hospitality and travel details. Through their Masterwork, Octavo, Children's Choir, Cathedral, Broadway, Debut, and Symphonic Series' alongside New York City Jazz Festival, MCP has provided opportunity to thousands of musicians in choirs, bands and orchestras that have performed at famous venues throughout the United States and many countries abroad.


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2201 East 49th Street
Commute to Downtown Cleveland
Most errands require a car.
A few nearby public transportation options.
Flat as a pancake, minimal bike lanes.
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2201 East 49th Street has a Walk Score of 49 out of 100. This location is a Car-Dependent neighborhood so most errands require a car.
This location is in the Central neighborhood in Cleveland. Nearby parks include Grant Park, Portland-Outhwaite Recreation Center and Central Avenue Recreation Center.
Explore how far you can travel by car, bus, bike and foot from 2201 East 49th Street.
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2 East 55th / East 79th
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2201 East 49th Street is in the Central neighborhood. Central is the 10th most walkable neighborhood in Cleveland with a neighborhood Walk Score of 64.
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UCP2 (uncoupling protein 2) plays an important role in cardiovascular diseases and recent studies have suggested that the A55V polymorphism can cause UCP2 dysfunction. The main aim was to investigate the association of A55V polymorphism with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease and preserved left ventricular function.
The participants of the MASS II were genotyped for the A55V polymorphism using allele-specific PCR assay. Survival curves were calculated with the Kaplan–Meier method and evaluated with the log-rank statistic. The relationship between baseline variables and the composite end-point of cardiac death, acute myocardial infarction (AMI), refractory angina requiring revascularization and cerebrovascular accident were assessed using a Cox proportional hazards survival model.
There were no significant differences for baseline variables according genotypes. After 2 years of follow-up, dysglycemic patients harboring the VV genotype had higher occurrence of AMI (p=0.026), Death+AMI (p=0.033), new revascularization intervention (p=0.009) and combined events (p=0.037) as compared with patients carrying other genotypes. This association was not evident in normoglycemic patients.
These findings support the hypothesis that A55V polymorphism is associated with UCP2 functional alterations that increase the risk of cardiovascular events in patients with previous coronary artery disease and dysglycemia.
Keywords:UCP2; A55V polymorphism; Coronary artery disease; Diabetes
Cardiovascular diseases are the leading causes of death among adults [1]. Many risk factors such as age, gender, lipid abnormalities, hypertension, smoking, and genetic factors influence the occurrence and progress of the different atherosclerotic processes and diabetes. Indeed, 70% of patients with acute myocardial infarction (AMI) have either diabetes or impaired glucose tolerance [2].
Reactive oxygen species (ROS) and inflammatory cells, particularly monocytes and macrophages, have a major role in the pathogenesis of atherosclerosis [1]. ROS are also associated with the pathogenesis of atherosclerotic macrovascular disease in diabetic patients. At least four molecular mechanisms have been implicated in glucose-mediated vascular damage (advanced glycation end-products, AGE, Protein kinase C, polyol and hexosamine pathway). All of them seem to be related to overproduction of superoxide by the mitochondrial electron-transport chain, as a response to hyperglycemia [3].
In this context, UCP2 (uncoupling protein 2), a physiological down-regulator of ROS, might play an important role in cardiovascular diseases. Several studies have already described that UCP2 has an anti-atherogenic effect in the vascular wall [4], improves tolerance to cardiac ischemia [5,6] and protects cardiomyocytes from oxidative stress-induced cell death [7]. This role of UCP2 was demonstrated in transplanted mice (UCP2 -/-), which have presented larger atherosclerotic lesions, increased nitrotyrosine staining, suggesting enhanced oxidative stress, and a significant increase in macrophage accumulation in vascular lesions [8].
Nowadays, the exact functions of UCP proteins are not fully established and may be different according to assayed specific tissue. In β cells, UCP2 over expression leads to decreased insulin secretion. Thus, UCP2 disturbances can be related to the causes and complications of type 2 diabetes mellitus, both related to increased ROS production.
The A55V polymorphism has been associated with energy metabolism misbalance [9], higher risk of type 2 diabetes, lower HDL, high atherogenic index [10] and lower levels of leptin [11]. Besides, other studies have already associated VV genotype to lower degree of uncoupling, more efficient energy utilization, lower fat oxidation and increased ROS production suggesting that A55V cause UCP2 dysfunction [12,13].
In this scenario, the main aim of this study was to investigate whether the A55V polymorphism is associated to cardiovascular events in a group of 611 patients enrolled in the MASS II [14,15], a study that compared therapeutic strategies for individuals with multi-vessel coronary artery disease (CAD).
Patient selection
Studied patients were selected from the prospective, randomized and controlled Medicine, Angioplasty, or are medical treatment, angioplasty or stent (percutaneous coronary intervention, PCI), and myocardial revascularization (coronary artery bypass grafting, CABG) in patients with multi-vessel stable CAD with preserved left ventricular function [14,15].
Methodological details were described by Hueb et al. Briefly, patients with angiographically documented proximal multivessel coronary stenosis of more than 70% by visual assessment and documented ischemia were considered for inclusion. Ischemia was documented by either stress testing or the typical stable angina assessment of the Canadian Cardiovascular Society (CCS) (class II or III). Patients were enrolled and randomized if there was agreement on the part of the surgeon and interventionist that revascularization could be attained by either strategy. Exclusion criteria included unstable angina or acute MI requiring emergency revascularization, ventricular aneurysm requiring surgical repair, left ventricular ejection fraction of <40%, a history of PCI or CABG, and single-vessel disease. Patients were also excluded: if they had a history of congenital heart disease, valvular heart disease, or cardiomyopathy; if they were unable to understand or cooperate with the protocol requirements or to return for follow-up; or if they had left main coronary artery stenosis of 50% or more, or suspected or known pregnancy or another coexisting condition that was a contraindication to CABG or PCI. Patients were then randomized to continue with aggressive medical therapy (MT) alone or to undergo PCI or CABG concurrently with MT [14,15].
Two thousand seventy-six candidates who had indications for myocardial revascularization were evaluated from May 1995 to May 2000. Of these, 611 patients were eligible and met all inclusion criteria to be randomly assigned to 1 of the 3 therapeutic groups: medical treatment (n = 203), PCI (n = 205), and CABG (n = 203). The primary end-point of this study was to compare the frequencies of major cardiac events, such as acute MI, overall mortality or refractory angina requiring revascularization procedures and stroke. The main conclusion of the MASSII was relatively low rates of death with all 3 treatment regimens during the first and second follow-up years.
All subjects gave informed consent, and the Ethics Committee of the Heart Institute of the University of Sao Paulo - Brazil approved the study.
Data collection
The beginning of treatment was considered to be the randomized date and patients were studied by the intention to treat principle. The follow-up time for all patients in this study was 5 years with clinical visits conducted in a 6-month interval. The collected demographic and laboratory data included age, gender, angiographic findings and traditional risk factors, such as history of previous coronary events, hypertension, diabetes, BMI (body mass index), severity of angina, smoking status, and cholesterol and triglycerides profile. Blood samples were obtained from each participant at randomization.
Symptoms of angina were graded according to their severity and were considered refractory only when patients had been treated with full anti-ischemic therapies. Myocardial infarction was defined as the presence of significant new Q waves in at least 2 ECG leads or symptoms compatible to MI associated with creatinine kinase-MB elevations. Cardiac mortality was defined when patient died of MI.
Glycemic status was defined using effective WHO classifications at that time of the randomization. Briefly, diabetic patients should present classic symptoms of hyperglycemia and an abnormal blood test [plasma glucose concentration ≥7 mmol/L (or 126 mg/dL) or ≥11.1 mmol/L (or 200 mg/dL) 2 hours after a 75 g glucose drink]. Impaired glucose tolerance were diagnosed in patients with fasting plasma glucose <7.0 mmol/L (or 126 mg/dL) and 2 hour post 75 g glucose drink of ≥ 7.8 mmol/L or 140 mg/dL and <11.1 mmol/L (or 200 mg/dL). Patients with diabetes and impaired glucose tolerance composed the dysglycemic group.
A55V genotyping
Genomic DNA was extracted from leukocytes in samples of whole blood following standard techniques [16]. Genotyping was performed with an Array Tape technology (Douglas Scientific, Alexandria MN). A modified allele-specific PCR assay as described by Myakishev et al. was used [17]. Briefly, PCR were performed with 50 ng of genomic DNA in a total volume of 10 μlL containing 5 pmol of each primer, 100 μmol dNTPs, 0.3 U Taq DNA polymerase (Lab Trade, Brazil). An average genotyping success rate of more than 95% was obtained and, as quality control, an average genotyping accuracy of more than 98% was observed by re-genotyping of 32 samples.
Statistical analysis
Categorical variables were presented as percentage while continuous variables were presented as mean ± standard deviation. General characteristics, biochemical and cardiovascular event frequencies were analyzed using Student's t test for continuous variables and the Chi-square test or Fisher's test for categorical variables. Survival curves were constructed with the Kaplan–Meier method and differences between the curves were evaluated with the log-rank statistic. We assessed the relationship between baseline variables and composite end-point events using a Cox proportional hazards survival model. Hazard ratios (relative risks) with 95% confidence intervals (CI) demonstrate the risk for combined events. Multiple testing correction was not performed. A value of p≤0.05 was considered significant for comparisons. Statistical analyses were performed with SPSS 13.0 for Windows. The Hardy-Weinberg equilibrium was conducted with Haploview 4.0.
The genotypic distribution for the A55V polymorphism was 20.7% of AA (n=116), 47.8% of AV (n=267) and 31.5% of VV (n= 176). Genotypic distributions were in accordance with the predicted by the Hardy-Weinberg equilibrium.
The Ala/Ala (AA) and the Ala/Val (AV) genotypes were combined and compared with the Val/Val (VV) genotype group. There was no significant difference in baseline values between these groups (Table 1).
Table 1. Baseline clinical characteristics
From 611 eligible patients, 559 individuals were genotyped and followed-up. There were 260 dysglycemic patients (148 diabetic and 112 glucose intolerants) and 299 patients with normal glucose tolerance as shown in Table 1. There were no differences between normoglycemic and dysglycemic patients regarding to cardiovascular events incidence during the first two follow-up years (Table 2).
Table 2. Cardiovascular event incidences in the entire cohort of patients, in the dysglycemic patients and in the normoglycemic patients
Stratifying our analysis by glucose homeostasis, significant differences were found in the subgroup of patients with dysglycemia after two years of follow-up. Patients carrying the VV genotype had a higher incidence of AMI (p=0.026), death+AMI (p=0.033), necessity of a new revascularization intervention (p=0.009) and combined events (p=0.037) (Table 2). Curiously, differences according to genotypic groups after 5 years of follow-up were not observed in dysglycemic, except for the variable AMI (p=0.025). For the normoglycemic patient group, no significant difference was found according to genotypes (Table 2).
Similar results were found when Kaplan-Meier survival curves were constructed. There were significant differences for the incidence of AMI, new revascularization procedures and combined events as shown in Figure 1. Finally, modeling end-point events using a Cox proportional hazards model adjusted for age, sex, randomized treatment, and BMI, a significant interaction between dysglycemia and UCP2 genotype was observed for combined end-points (p = 0.03), incident myocardial infarction (p = 0.009), and new revascularization procedure (p = 023).
Figure 1. Survival curves of dysglycemic patients genotyped for the polymorphism A55V.
We investigated the relationship between the A55V polymorphism and the incidence of cardiovascular events in patients with CAD. Our main findings showed that A55V is associated to increased risk of cardiovascular events in patients with previous CAD and dysglycemia after two years of follow-up.
Other studies have already suggested that A55V polymorphism cause UCP2 dysfunction [12,13] supporting our findings. However, functional studies are necessary to confirm these affirmations and explain the association of VV genotype and cardiovascular events observed only in disglycemic patients. In this way, the CARDIA study reported the presence of diabetes in 5.8% of participants homozygous for the V allele which was statistically greater than the 3.3% and 3.7% in the AA and AV genotypes, respectively [13]. These results extend the findings from studies of Ala55Val or other UCP2 polymorphisms involved in the development of type 2 diabetes mellitus [18,19].
In our study, dysglycemic patients presented higher incidence of AMI, necessity of a new revascularization intervention and combined events, despite mortality being the same. Actually, it was described that functional alterations in UCP2 leads to a higher production of ROS that is already increased in dysglycemic patients and can worsen the macrovascular disease and the atherosclerotic process [3].
A study described that, in humans, the extent of uncoupling is partially regulated by the genetic polymorphism Ala55Val, in which the VV genotype uncouples at a lower rate than the AA genotype [20]. Other studies reported that the A allele was associated with the presence of higher oxidative stress markers and showed synergistic effect with other risk factors (obesity, hypertension and diabetes) [21,22].
There are some limitations in our study. First, we were not able to perform replication studies in a similar sample because there are very few studies similar to MASSII in the literature. Second, our sample size only provide 80% power to detect an association with death, AMI, revascularization intervention, events variables with an effect size of 1.7–2.4 or 1.8–3.6 for the A55V polymorphism in the total group and in the dysglycemic patients, respectively. We recognize that such effects are highly unlikely for common genetic variants and reaffirm the need for the development of increased samples of multivessel CAD patients with long-term follow-up period for the identification of more modest effects. Third, it is not possible to completely exclude the interaction between the use of concomitant drugs, other genetic markers, ethnicity and other covariates on our findings. We only analyzed the A55V polymorphism despite of others polymorphisms in the UCP2 gene have already been identified and some of them are in linkage disequilibrium with A55V. For example, A866>G has already been associated to increased cardiovascular events risk, cardiometabolic disease and it represents a novel candidate gene for beta-blocker response, particularly among patients with diabetes [23].
A recent meta-analysis has showed that the UCP2 -866G/A polymorphism is unlikely associated with increased type 2 diabetes risk in the Asian and European descent. In contrast, further results indicate that the UCP2 Ala55Val and UCP3 -55C/T polymorphisms may indeed be risk factors for susceptibility to type 2 diabetes in individuals of Asian descent, but not in individuals of European descent [24].
After 2 years of follow-up, dysglycemic patients carrying the VV genotype had higher incidence of AMI, death+AMI, new revascularization intervention and combined events compared to patients carrying other genotypes. After 5 years of follow-up, we were not able in detect these differences according to genotypic groups, except for AMI incidence. We speculate that the predictive effect of UCP2 genotype in dysglycemic patients could be related to the time of illness. On the other hand, there is no experimental evidence suggesting that the duration of diabetes could play a role in this result. Further studies are necessary to establish the role of VV genotype as an independent genetic marker of cardiovascular events in this specific subgroup.
Taken together, our findings corroborate the hypothesis that A55V polymorphism is associated with UCP2 functional alterations that may increase the risk of cardiovascular events in patients with previous CAD and dysglycemia.
UCP: Uncoupling protein 2; CAD: Coronary artery disease; MASSII: Medical angioplasty or surgery study II; AMI: Acute myocardial infarction; ROS: Reactive oxygen species; PCI: Percutaneous coronary intervention; CABG: Coronary artery bypass grafting; CCS: Canadian cardiovascular society; MT: Medical therapy; MI: Myocardial infarction; BMI: Body mass index; WHO: World health organization
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
LGP and LSS carried out part of the molecular genetic studies, performed the statistical analysis and drafted the manuscript. LGP and PCJLS performed the revision and statistical analysis of the manuscript. NEF carried out part of the molecular genetic studies. WAH and JEK conceived the study, and participated in its design. ACP conceived the study, participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.
Financial support provided in part by a research grant from the Zerbini Foundation, Sao Paulo, Brazil. PCJLS is recipient from fellowship from FAPESP, Proc. 2010-17465-8, Sao Paulo, Brazil.
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Pre-publication history
The pre-publication history for this paper can be accessed here:


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Vehicles with Incentives & Rebates
The 2016 Acura ILX comes with a slew of upgrades compared to last year. All models get a 2.4-liter 4-cylinder and 8-speed automatic transmission. The chassis is 12-percent stiffer, the steering is sharper, there are more high-tech driver aids, and the nose and tail get refreshed, including Acura's Jewel-Eye headlights.
Aside from a new paint color, the only major difference in the 2015 Acura ILX lineup is the absence of the ILX Hybrid. That's fine, since the ILX got a few much-needed upgrades last year, like the addition of active noise cancellation and an upgraded audio system.
The 2014 Acura ILX entry-level luxury sedan is aimed at a spot that's just below the BMW 3 Series and Audi A4 in size, price, performance and, admittedly, prestige, and represents an affordable path into the more luxurious end of the car market. There are two 4-cylinder engine choices, an automatic or manual transmission, and a hybrid version. The 2014 ILX offers a sleek, upbeat look, snappy performance, crisp handling, a stylish interior and levels of technology, convenience and safety commensurate with buyers' expectations.


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More than five years after a controversial letter was published attacking gay activists as being "just as immoral as pedophiles," a human rights panel will begin a hearing today that one lawyer calls Alberta's most important human rights and free speech case to date.
The complaint launched against Rev. Stephen Boissoin by University of Calgary professor Darren Lund has led gay rights organizations, Christian lobby groups and even the Alberta government to weigh in -- and not all of them in the corners most would expect.
Today will be the start of what's likely to be three days of hearings that will pit Boissoin's arguments of free speech against Lund's argument that Boissoin's letter promoted hatred against gays.
"It's going to be a very significant case, probably the most significant constitutional case involving human rights legislation that has ever been considered in Alberta," said Gerald Chipeur, Boissoin's lawyer.
The controversy stems from a letter written by Boissoin, then a Red Deer youth pastor, that was published in the Red Deer Advocate in June 2002.
In it, Boissoin wrote "my banner has now been raised and war has been declared" against those who are part of the "homosexual machine."
"From kindergarten class on, our children, your grandchildren are being strategically targeted, psychologically abused and brainwashed by homosexual and pro-homosexual educators," he wrote.
"Your children are being warped into believing that same-sex families are acceptable; that kissing men is appropriate."
Boissoin went on to attack gay activists as "spreading their psychological disease," saying they were "just as immoral as the pedophiles, drug dealers and pimps that plague our communities."
"Where homosexuality flourishes, all manner of wickedness abounds," he wrote.
The letter led to a complaint from Lund, then a high school teacher in Red Deer.
Lund, a married father who is not homosexual, is a longtime human rights activist who has won the Alberta Centennial Medal and a national education award.
Now an education professor at the University of Calgary, he said he was glad the case will finally be heard, five years after the letter that sparked it was published.
"It's been a long time coming," he said. "I'm eager for the panel to make a ruling on this case."
In between the letter's publication and today's hearing, Boissoin launched an unsuccessful $400,000 defamation suit against Lund.
Chipeur said the debate for today's hearing comes down to free speech: if Boissoin is rapped for his letter, it could silence any political debate on the issue, he argued.
The letter doesn't fall under the legal definition of discrimination, he added, largely because those laws weren't meant to censor or restrict public debate.
The Alberta government has intervener status in the hearing and will be backing Lund.
A national gay rights group, meanwhile, has said it won't be supporting him. EGALE (Equality for Gays and Lesbians Everywhere) has said that Boissoin has a right to express his opinions in the public arena, though it notes it vehemently disagrees with them.
"It is far better that Boissoin expose his views than have them pushed underground," the group said in a 2005 statement. "Under the glaring light of public scrutiny, his ideas will most likely wither and die."
Boissoin has been getting support from Concerned Christians Canada Ltd., a Christian lobby group he used to head at a local level that is also named in the human rights complaint.
The group has tried to lead campaigns against Lund.
It also helped to organize a 2005 legal defence fundraiser for Boissoin and others that featured Calgary Catholic Bishop Fred Henry.
Henry, along with members of the Christian Heritage Party, defended freedom of expression and of religion.
There have been other rallying cries to back Boissoin in the past five years, including from American religious rights groups and former Ku Klux Klan leader David Duke.
The one-person panel will be chaired by Lori Andreachuk, a lawyer from Lethbridge.


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