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I haven't had a shower today. Or brushed my hair. I was convinced I would make it to CrossFit at some point. And I never did. So I've been in full gym paraphernalia all day... With unbrushed hair and unbathed body.
Yes- I went to Publix like…Continue
Added by Kate on September 21, 2015 at 9:28pm — No Comments
I was talking with a friend the other day and realized she apologized endlessly during our conversation. She was sorry for being mad at someone, for laughing too loudly, for talking too much, and a few other things. I never mentioned any of these things as she spoke, and realized many people apologize for almost everything.
I noticed this in her because I noticed it in myself several years ago. …
Added by Dea Lenihan on September 16, 2015 at 6:34pm — 2 Comments
Added by imperfectmom247 on September 16, 2015 at 1:20pm — No Comments
A wise person one told me just do it, you never know what will come of it.
I heard those words as a young person, and they stuck.
Yes, we should make the most out of every situation and try and look to the bright side, but I'm talking about looking at more than just one side of the thing you are doing.…
Added by Dea Lenihan on September 13, 2015 at 2:12pm — No Comments
They warn you about the pain of childbirth. They even express all the different means for managing said pain and in such depth that there are literally tons of books written on the topic! Ways to manage the pain often include Lamaze, water therapy, epidural, hypnosis, etc. I opted for hypnosis when this little lady graced us with her presence.…
Added by Kat Tom on September 9, 2015 at 11:25pm — 2 Comments
Added by Wendy Mallins on August 27, 2015 at 6:21am — No Comments
When Bonnie Toews and John Christiansen decided to take their first holiday to Africa together in their 70's, the experience was not only amazing, but life changing.
I read this book with my Grandsons and before they opened it, the first thing they wanted to know is "Who are Bibi and Babu? Of course I…Continue
Added by Susan Keefe on August 24, 2015 at 9:28am — No Comments
Life in itself can get so busy. There's always something to do, always an appointment, always someone depending on us, always preparation for another day...before you know it days turn into weeks, weeks turn into months and so on. …
Added by Natalie P. on August 18, 2015 at 1:25pm — No Comments
Someone was really sane to say it takes days, weeks, months n sometimes years before our thoughts start taking its shape n become a reality. Here I am a live example of slow n steady wins the race ....
It was an out of the world feeling to become a mother but not to forget equally stressful..as had to deal with everything for the first time and couldn't afford to take a chance cause a life…
Added by Manjusha Pandey on August 6, 2015 at 2:00am — No Comments
My husband and I took a trip to Aruba a few years ago and when we came home I was pregnant.
Oh I was so happy and HUNGRY!! I would wake up at 5:30 am starving and ate all day. Of course I googled EVERYTHING and it said your appetite increases with a boy and folks if…Continue
Added by imperfectmom247 on August 5, 2015 at 6:04pm — No Comments
Ever forget to put your fairy wings on and be your kids tooth fairy? Well I did.
Okay so here's my side of…Continue
Added by imperfectmom247 on August 1, 2015 at 1:02pm — No Comments
Hey girl what up!!! Do you remember yesterday when you stepped out of your car and walked onto a broom brush and the pole came and popped you in the ear? see I feel you practiced very good self control when you had the urge to kill your 8 year old from her belly laughing so hard.
Although you restrained yourself from that you didn't do so hot last night with your night…Continue
Added by imperfectmom247 on July 23, 2015 at 1:43pm — No Comments
Ever have the feeling of "Holy moly everything is too much" the sad thing is my plate isn't even full, I just don't handle things all that well. I can have one thing to do andI feel as if it's the end of the world. #sissy.
Having two kids isn't even the issue its me and it's just so happens my stress retainer is teeny tiny. So anything small large medium, I'm…Continue
Added by imperfectmom247 on July 22, 2015 at 8:15pm — No Comments
"Life is short. Have an affair." - Ashley Madison
One more "lesson" or disorder - rather, for me to metabolize while watching the news with Alex, my thirteen-year old. The news of ashleymadison.com, the site which helps married couples cheat, unfolded over our breakfast together. I could have changed the channel, however Alex is beyond my clumsy protectiveness. He is curious. He wants the truth. …Continue
Added by sarah katopodis on July 22, 2015 at 7:30am — No Comments
How do I juggle being a good mother and running Filihood?
I can tell you this... I definitely do not always succeed! It is obvious that when you regularly have to "downgrade"…
Added by Dorte Damgaard Sejthen on June 23, 2015 at 7:00am — No Comments
My thoughts on the subject of having a child in the midst of a hectic time for my business
Honestly, I couldn't cope with the idea, when I found out I was pregnant. The timing was lousy, and originally I didn't intend having more children (I already have e beautiful 11…
Added by Dorte Damgaard Sejthen on June 23, 2015 at 6:30am — No Comments
Added by Lauren Markman on April 8, 2015 at 6:46am — No Comments
At the beginning of the school year I shared a post titled "6 Tips That…Continue
Added by Gabriella L. on March 13, 2015 at 10:30pm — No Comments
I must admit, if you would have asked me my thoughts on ageing 10 years ago my reply would have been a negative one. And why not!?! Everything I had seen on television, in magazines, conversations with friends, etc. told me that once you get grays & wrinkles your life was pretty much over; you mine as well curl up into a ball and wait to die. Nothing about getting old seemed glamorous. Old people always complain about this breaking, that not working like it used to, etc. Ugh! Who…Continue
Added by Kat Tom on March 2, 2015 at 9:36pm — No Comments
Added by Jennifer Weedon Palazzo on January 27, 2015 at 2:00pm — No Comments


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In 1993, Krall released her first album, Stepping Out, which she recorded with John Clayton and Jeff Hamilton. It caught the attention of producer Tommy LiPuma, who produced her second album, Only Trust Your Heart (1995).
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For all these despicable revelations tumbling out of the hateful heart of Donald Sterling, there promises construction of a roadmap to redemption for the Los Angeles Clippers and the NBA. There's a way out for the most hated man in Los Angeles now, a way out for the commissioner's office and the owners responsible for long legitimizing and harboring a bigot and slumlord, according to Yahoo Sports.
Source: Magic Johnson open to buying Clippers
Magic Johnson and his billionaire backers, the Guggenheim Partners, want a chance to purchase the Los Angeles Clippers, league sources told Yahoo Sports. "Magic's absolutely interested," one source closely connected to Johnson's business interests told Yahoo Sports on Sunday night.
To bail themselves out of the NBA's worst crisis of credibility since the Tim Donaghy officiating scandal, the easy part for the NBA will be enlisting the eagerness and financial muscle of Magic Johnson and Mark Walter of the Guggenheim Partners – owners of the Los Angeles Dodgers, Yahoo Sports reports.
H/T: Yahoo
See this story on sports.yahoo.com


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Ex-Free Press critic John Guinn
Former Free Press classical music critic John Guinn, who also taught music at local universities and was well-known as a church organist and public lecturer on music, died Friday. He was 77 and lived in Grosse Pointe.
Mr. Guinn, who began writing free-lance reviews for the Free Press in the 1970s, was a staff critic from 1979-95. He was a traditionalist and a passionate defender of romantic expression, favoring warm-hearted interpretations delivered with a strong personality. He abhorred technically secure but bland playing, but was equally disdainful of showboating.
Mr. Guinn preferred standard repertoire to new music, and he had a particularly acute ear for opera. He had strong opinions, and longtime observers noted that that once he made up his mind about an artist, he rarely, if ever, changed his tune. He wrote in straightforward, clear prose whose bluntness could ruffle feathers, but he was respected by Detroits musical elite.
He was very musical, said David DiChiera, founding director of Michigan Opera Theatre. He understood voices, and he was a very astute person. He was the real thing: a legitimate critic who cared deeply about music.
When Mr. Guinn loved a work or performance, he embraced it fully. In 1989, he wrote about soprano Joan Sutherland, then 62 and at the tail end of her career, in a MOT production of Bellinis Norma.
Compared to the squeals, squeaks and squawks that are allowed to come forth from some operatic throats much younger than Dame Joans, times inroads are minimal, he wrote. Her top notes, for example, are most often free and clear. Her coloratura ability is as flawless as ever. And her trill, that ravishing attribute, begins slowly, increases in speed until it is a glorious blur of sound and then, with the flick an appoggiatura, concludes succinctly, remains intact.
When a concert disappointed him, however, Mr. Guinn held nothing back. He once suggested that a Detroit Symphony Orchestra reading of Bela Bartoks Music for Strings, Percussion and Celesta conducted by Yehudi Menuin, was the worst live performance it has ever given.
Attacks and releases were constantly ragged, tonal and pitch unity regularly fell apart, personality and character were not to be found anywhere. Every tempo change precipitated rhythmic chaos of several measures duration, every attempt at dynamic and rhythmic expansion ended in disaster.
Mr. Guinn was born in Charleston, W. Va. He received bachelors and masters degrees in music from the University of Notre Dame. He taught at the University of Detroit for 14 years, beginning in the 1960s, and chaired the music department for two years.
After leaving the Free Press, he became adjunct assistant professor of music at Wayne State University in 1995, teaching theory, history, criticism and group piano. He also was a church organist, and since 2003 was music minister at St. Ambrose Church in Grosse Pointe Park.
Mr. Guinn was coeditor of the St. James Opera Encyclopedia, and he continued to write reviews for various publications until his death, including Opera News. In 2000, he staged a production of Gian-Carlo Menottis opera Amahl and the Night Visitors, at Music Hall Center for the Performing Arts in Detroit.
He is survived by his wife, Catherine, and a sister. A funeral mass is at 11 a.m. Wednesday at St. Ambrose, 15020 Hampton Road. The family will gather at 10 a.m.


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Check out the changes in the Ford Explorer 4X4 XLT 4.6L from 2005 to 2006. Just one of the many things possible with the 4-Car Compar-A-Graph!
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Saturday, September 26, 2015 —
This week on The Auto Lab, Robert Erskine's guest will be
Sarah Sillars, Recently Appointed First Woman CEO of the Institute Of Advanced Motorists in the UK
Want more information? Search the web!
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Posted January 25, 2013 on AP on Fox
Sidney Crosby fed his inner Canadian by walking to his team's pre-game skate. ''I just wanted to get outside and experience a Canadian winter again,'' said Crosby, whose Pittsburgh Penguins play the Winnipeg Jets on Friday night. ''Believe it or not you miss it a little bit. You miss seeing the snow.'' Winnipeg delivered on the snow with a side helping of temperatures of minus 9. ''It's hockey weather, so it's nice to get out. ... I definitely forgot how cold it was but it's nice to be here,'' Crosby said. He said he was well dressed and it wasn't that long a walk, ''but if it was any longer, it might have been a little tougher, that's for sure.'' Crosby didn't play with the team when the Penguins visited Winnipeg last season. But he has played at the MTS Centre before as a member of Canada's world junior team. ''It's exciting,'' he said, referring to his NHL debut at MTS. ''Any time you play at a newer venue or somewhere you haven't played in a while, I think you always get e...
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text: More from SI Report: Dodgers release pitcher Freddy Garcia Report: Dodgers release pitcher Freddy Garcia Marshawn Lynch sports gold cleats for Super Bowl Marshawn Lynch sports gold cleats for Super Bowl Louisville vs. FIU: Game time, live stream, TV coverage Louisville vs. FIU: Game time, live stream, TV coverage Pittsburgh-area high school football player dies after... Pittsburgh-area high school football player dies after... Close Tweet0 Share0 Comment0 Share0 Share0 Stumble It0 Print0 More SI Wire Rockets point guard Patrick Beverley to have MRI on right knee by Chris Mascaro Email Posted: Mon Apr. 21, 2014 Updated: Thu Jun. 12, 2014 Patrick Beverley averaged 10.2 points per game in the regular season. (Bob Levey/Getty Images)Rockets point guard Patrick Beverley will have an MRI on his right knee on Monday after spraining it in a 122-120 overtime loss to the Trail Blazers in Game 1 of Houston's playoff series on Sunday night, according to an ESPN.com report. Beverley missed eight games late in the regular season with a torn meniscus in that same knee.Sunday's game was only the fourth Beverley has played since the meniscus tear, which occurred on March 27. Dr. James Andrews said the tear did not require surgery, according to Marc Stein of ESPN.com.DEITSCH: Jeff Van Gundy predicts Rockets will win NBA titleBeverley appeared to be injured when LaMarcus Aldridge knocked him to the floor on a hard screen with 1:04 left in overtime. Aldridge scored a franchise playoff-record 46 points for Portland.Beverley, known to be a pesky defender, remained in the game until he fouled out with 44 seconds left. He even recorded a block after the injury.He initially shrugged off trainers to stay in the game, but he needed help to get off the court following the game, according to TNT.The second-year man out of Arkansas played 38 minutes, scoring nine points on 3-of-8 shooting with six rebounds and two assists."All of us are saddened by the fact that Pat hurt his knee again," Dwight Howard said, according to the Houston Chronicle. "I didn't want to see anything happen to him. ... It hurts all of us. We just have to step up here as a team and win it for him."Game 2 is Wednesday night in Houston. SI WIRE: Sixers owner Josh Harris calls season 'huge success' Promoted Stories Comments


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Prasad had recently asked telecom operators to optimize their network and make desirable investments to overcome rampant call drops and ensure service quality in the country.
The Department of Telecom has not accepted a proposal of telecom operators for not charging licence fee and spectrum usage charge on the amount received from trading of airwaves.
The panel may also consider TRAI recommendation on allowing virtual network operators (VNO) to operate in the country.
Telecom giant British Telecom has announced plans to shut down its call centres in India to bring them back to Britain following complaints of poor customer service.
Videocon Telecommunications today said it is in talks with three telecom operators for spectrum sharing and trading agreement and expects the close the deal soon.
The Department of Telecommunications (DoT) is planning another bumper auction of telecom spectrum that may even surpass record sales in March
With the grant of license, the government would provide broadband and internet services through Arasu Cable TV.
"The ownership right will be of government of India. That right of trade he can trade with someone else fully between two service providers," Prasad said.


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I currently have a Jamis Komodo 3.0 I ride SS, and am looking to upgrade to an all mountain bike. I found this listing the other day, but am worried about the fork.
2009 Norco Six II Large Freeride/All Mountain 160mm
My ride right now has a Marzocchi Bomber fork that is older, but works well for me and is fairly plush (never bottomed out), works well, but is heavy. Would I be able to swap out the forks then sell my current ride for a decent value, or will the Marzocchi 55 ATA drop the value of the bike? There have been some bad reviews about possible defects on the fork, so I am worried I may not be able to sell it if I decide to go that route.
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EAA Chapter 284 will hold its July 2015 meeting on Sunday, July 12th at 2:30 PM at Red Stewart Airfield. The meeting topic will include AirVenture planning. We will have a chapter camping area between 29th and 30th, just off of Schaick. This is a very convenient and central location. If you are planning on flying in to AirVenture and want to camp with we will have someone bring you camping gear with them. Please bring your gear to Sunday's meeting.
EAA284 Chapter Meeting June 14 2015
EAA Chapter 284 will hold its June Chapter meeting on Sunday, June 14, 2015 at Red Stewart Airfield. Time is 2:30 PM.
Last Month Mike McKosky visited the Manufactory, a makerspace in Cincinnati. I have asked him to do a presentation on what he has learned and share it with the membership. Mike also crews at the glider port on the second Sundays and is not sure that he will be able to do both, Let's hope that he is able to spend some time at our meeting.
Online resource links for having parts made
At Sunday's meeting we had some discussion about having some parts made by online. Bob Luken has started to put together some resources for members to consider. ( no recommendation — do your own research)
If you have any specific experience please share it so that members may benefit.
EAA284 Chapter Meeting May 17 2015
EAA Chapter 284 will hold its May chapter meeting on Sunday, May 17th. Note that this is the 3rd Sunday, rather than the second Sunday. Meeting time will be 2:30 PM.
May 3rd:
EAA Chapter 48 will hold its annual Funday Sunday Fly In and Pancake Breakfast on Sunday May 3, 2015 at Moraine Airpark (I73). Breakfast from 8 AM until about 11 AM. This is the first local fly in of the year. For Chapter 48 it is about their 54th fly in.
Bob Luken's Fisher Celebrity project is at Moraine and chapter members will be able to see it after about 12 noon.
EAA284 Chapter Meeting April 12 2015
EAA284 Chapter Meeting March 8 2015
The March meeting of EAA Chapter 284 will be Sunday, March 8th at 2:30 PM. Note that this is a change from our normal meeting time of 2 PM. The meeting will be held at Red Stewart Airfield.
Daylight Savings Time begins on Sunday, March 8, 2015. So, remember to set your clocks ahead by 1 hour.


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Beach House, Marine Crescent (£625pcm) - LET AGREED
A lovely 2 bed lower ground floor flat situated right opposite the seafront in Folkestone. This spacious property benefits from double glazing, gas central heating and has courtyards to the front and rear.
For your added comfort there is a modern kitchen with integrated fridge, freezer, washer-dryer and dishwasher.
The 2 bedrooms have built in wardrobes as well as en-suite bathroom and shower room and there is a separate wc in the hallway.
The current EPC rating is D(62)
For more information and to arrange a viewing please call 01303 223999.
Current properties to rent
For a full list of our current rental properties please click on the following link;


text: Idea Exchange: Heating pads keep fluids toasty Mar 01, 2011 By dvm360.com staff VETERINARY MEDICINE To have warm fluids available when we need them, we lay a couple of unopened fluid bags on a heating pad set on low and then place another heating pad on top. This way warm fluids are always on hand but with less muss and fuss than with other methods. If we don't use them, it's no big deal. Dr. Lee Roberts Greencastle, Ind. Related linksRead more Idea Exchange tipsIdea Exchange: Pipe insulation keeps fluids flowing Hot topics on dvm360Texas board seeks to revoke Dr. Kristen Lindsey's license Getting the fat off Skinny 5 reasons your boss isn't paying you more 5 ways to get started with Fear-Free veterinary practice Vetcetera: The Fairness to Pet Owners Act is back


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- Northern New York Newspapers
- Watertown
- Ogdensburg
- Massena-Potsdam
- Lowville
- Carthage
- Malone
- NNY Business
- NNY Living
- NNY Ads
Those of us who are Republican voters have a primary coming later this month. It appears we can opt for a local man, family man, businessman and father.
He grew up here, attending local schools and still resides here in the 21st Congressional District. Matt Doheny has been here working and trying to earn our votes.
Elise Stefanik is not a longtime local resident and is sensing a possible Republican sweep in November. Her reported history is she worked as a White House domestic policy council staffer from 2006 to 2009.
It has been reported that she spent some summers in the district but didn't reside here until recently. I wonder if the term "carpetbagger" could apply.
But the most damning accusations is that she is a D.C. insider. And when you see Karl Rove's American Crossroads supporting Ms. Stefanik, that speaks volumes.
If you like higher taxes, vote for Ms. Stefanik; she refused to sign a no tax increase pledge that Mr. Doheny has signed. If you are a big fan of Rep. and House Majority Leader Eric Cantor, Rep. Paul Ryan, et al., vote for Ms. Stefanik.
The American Crossroads ad says that Mr. Doheny is a flawed candidate. I recall former President William J. Clinton saying that he tried marijuana, but "I didn't inhale."
We are not electing a pope. Whoever is elected, if they don't perform, they can be rejected in the next election.
However, if you dislike American Crossroads and the Washington insiders as a whole, I believe we have a local option. Just look to Virginia's District 7; Rep. Eric Cantor has lost his primary bid. So maybe local voters can make a difference and the Washington insiders can lose.
I an not a contributor, volunteer or campaign worker for Mr. Doheny. And as to the Watertown Daily Times, they have staked their flag with the Democrat cause per their editorials.
Alan Woodall
Thousands of readers like you have made Northern New York Newspapers the number one ranked website* for local news and sports coverage in the north country.
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Wayfair Business JOIN FREE!
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Product Information:
A perfect fit for your child's twin bed, this headboard is made of durable PVC laminate that is waterproof and is easy to clean. The four colorful drawers are removable, foldable and great for holding art supplies, paper, books, toys and much more.
Product Details
Additional Documents
Weights & Dimensions
|Headboard Design: Bookcase
|Frame Material: PVC laminate
|Gender: Boy
|Freestanding: Yes
|Frame Required: No
|Type: Headboard
|Finish: Beach
|Size: Twin
|Distressed: No
|Number of Items Included: 1
|Non Toxic: Yes
|Upholstered: No
|Exterior Shelves Included: No
Drawers Included: Yes
|Wall Mounted: No
|Lighting Included: No
|Hidden Storage: No
|Country of Manufacture: China
|Assembly Required: Yes
|Additional Parts Required: Yes
About the ManufacturerAfter being in business for 10 years the 4D Concepts customer has learned to expect quality, design and value. The company creed "The customer is #1" has helped launch a dialogue with their customers concerning lifestyle. This dialogue has aided in generating conversation that reinforces the importance of quality, design and value in every piece of furniture they create.
4D Concepts offers a diverse line of furniture with everything from TV stands to headboards and baker's racks to ottomans. Every piece of furniture is designed with quality and value in mind. As a result 4D Concepts offers practical products, such as the 15 Drawer Multi-Colored Rolling Storage Tower, and attractive, trasitional furniture, such as the Chair and Ottoman in Beige.
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Make any meal extra special by presenting it on a truly extraordinary dinner plate. Waterford Fine China introduces Ballet, a new collection of fine bone china. The Ballet Ribbon pattern owes its contemporary look to a fanciful interpretation of silk and satin ribbons which caress a dancer's costume and precious pointe shoes.
Product Details
Special Offer:
12 Issues of Golf Magazine
Included with purchase ($20 value).
Weights & Dimensions
|Material: China
|Pattern: Solid color
|Oven Safe: No
|Refrigerator Safe: Yes
|Stackable: Yes
|Function: Fine China
|Product Type: Dinner plate
|Style: Traditional
|Color: White
|Number of Items Included: 1
|Non-Toxic: Yes
|Lead-Free: Yes
|Shape: Round
|Stove Safe: No
|Freezer Safe: Yes
|Food Safe: Yes
|FDA Compliant: Yes
|PTFE Free: Yes
|PFOA Free: Yes
|SFI Certified: Yes
|California Proposition 65 Compliant: Yes
About the ManufacturerWaterford Crystal designs, manufactures and markets an extensive range of crystal objects d'art, stemware, dinnerware and gifts for distribution throughout the world. In recent years, Waterford has built upon its reputation as a leading source of prestigious tabletop and gift products by expanding into several new businesses. Waterford Crystal has become almost a synonym for the finest quality crystal sought after by collectors and connoisseurs around the world.
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Free Shipping on orders over $49.00
Ships to:
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Enter your shipping zip or postal code to calculate shipping estimatesGet Delivery Estimate
We want you to love it. If you don't, you may return your purchase within 30 days of delivery. All you need to do is visit our Self-Service Return Center for instructions. Return credits are issued within 24 hours once the item is received and inspected. Please note that shipping charges are non-refundable. The cost of return shipping will be deducted from your refund. 30-Day Return Policy
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I'm an amateur photographer in my free time. I try to take pictures of things other than my kid and my dog. It's difficult though- I find them bo...


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Talk:Chelsham, SurreyEdit This Page
From FamilySearch Wiki
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| This question or concern is currently unresolved.
This is a Historical Records issue.
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Amazingly nice and knowledgable crew who care.
Nice and clean establishment. Fish are health and great customer service the owner is the best.
Excellent aquarium
Foursquare © 2015 Lovingly made in NYC & SF
6th Ave Aquarium and Flowers
Pet Store
425 Clement St (6th Ave)
"Best Fish store in the BayArea. Lots of variety and cheapest prices around the bay"
Pet Central
660 Broadway (btwn Stockton St. & Grant Ave.)
"Head downstairs and to the back of the store to see undersea creatures that you'd only expect in the Academy of Sciences aquarium."
Cole Valley Pets
910 Cole St (at Carl)
"Ask about their discounts on canned dog food. They have frequent shopper discounts too! Super friendly staff!"
Make sure your information is up to date. Plus use our free tools to find new customers.
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Hollywood TansRead MoreAt Hollywood Tans, tanning experts provide dozens of routes to bronzed skin. Sleek, spacious vertical tanning booths deepen tans in eight minutes, and Mystic Tan booths spritz bodies with a custom bronzing serum that clings to skin for up to a week. Hollywood Tans' line of shower gels, lotions, and tan amplifiers helps to preserve tans far more easily than never showering again. Staff members happily advise first-time tanners on the best skincare regimen or tanning tactics, and makeup artists accent golden skin with mineral makeup from the makeup bar.141 E Main StNewark, DE US
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California SunRead MoreA perfect tan can change your look at the drop of a hat. Visit California Sun in Newark for an exciting transformation! This salon helps find the Brazilian, bronzed beauty in you after experiencing such tanning services like tanning beds, spray tan, and airbrush tan. At this salon, you can opt for an alternative medical service, such as acne treatment. California Sun makes sure you always look your best no matter what time of year, so get that beach glow going whenever you feel like it's time for a tan.670 Peoples PlzNewark, DE US


text:
- 36Promote
Phone Cases
Just before the i-phoneby Wood-n-Images
Protect your iPhone with a one-piece, impact resistant, flexible plastic hard case featuring an extremely slim profile. Simply snap the case onto your iPhone for solid protection and direct access to all device features.
One of the last remaining public phones. one has to love the messages, and the business posting on the phone booth.
Awesome & nostalgic!! :)
YES! Totally love this!
Thanks MoArt
ohhhh this is sooo cool!!! :D
Thanks Carina.
great work
Thanks Justart
Awesome. I love that it is also an iPhone skin/case.
Thanks Halahblue, and I sold several as I=phone cases so far. I thought it was just right for such a use.
It made me wish I had one, so instead I sent the link to my brother.
(Who does have an iphone)
✯ ✯ ✯ ✯ ✯ 👍 !!!
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CMS Network (London) Ltd.
The Delivery Group combines Secured Mail and CMS Network (UK) to create a new force in the post and parcel sector. LONDON 9th APRIL 2015: Next Wave Partners LLP is delighted to announce the creation of The Delivery Group Limited which has been formed to combine CMS Network (UK) Limited ("CMS") with its existing portfolio company, Secured Mail. [Full press release here]More
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"CMS have provided us with an outstanding service since 2008. A reliable, professional and trusted partner"
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text:
News All news
The European premiere of "Souvenance" in Munich was met with standing ovations
The European premiere of Anouar Brahem's "Souvenance", at the Prinzregententheater in Munich, was met with standing ovations. At the sold-out concert Brahem was accompanied by Francois Couturier, Klaus Gesing, Björn Meyer and the Tallinna Kammerorkester / Tallinn Chamber Orchestra, conducted by Risto Joost.
The German public television ARD included the event extensively in their late news.
New album "Souvenance"
New Release : Double Album Anouar Brahem "Souvenance"
Music for oud, quartet and string orchestra
Dates All dates
Basilica di Santa Maria Maggiore
, Italy
Anouar Brahem Quartet Anouar Brahem: oud, François Couturier: piano, Klaus Gesing: bass clarinet, Bjorn Meyer: bass
, Belgium
Anouar Brahem Anouar Brahem: oud, François Couturier: piano, Klaus Gesing: bass clarinet, Bjorn Meyer: bass & Orchestre Royal de Chambre de Wallonie, Frank Braley: Conductor


text:
|Publication number
|Publication type
|Application number
|Publication date
|17 Nov 2005
|Filing date
|21 Jul 2005
|Priority date
|4 Nov 1997
|Also published as
|Publication number
|Maria Palasis, James Barry, Louis Ellis, Gary Hendrickson, Kent Harrison, Lixiao Wang
|Original Assignee
|Boston Scientific Scimed, Inc.
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (15), Referenced by (23), Classifications (33), Legal Events (2)
|External Links: USPTO, USPTO Assignment, Espacenet
This application is a continuation of and claims priority to, U.S. patent application Ser. No. 10,837,612, filed May 4, 2004, and entitled "METHODS FOR DELIVERING A THERAPEUTIC IMPLANT TO TISSUE," which is a continuation of U.S. Pat. No. 6,749,617, filed Nov. 8, 2000, entitled "CATHETER AND IMPLANTS FOR THE DELIVERY OF THERAPEUTIC AGENTS TO TISSUES," which is a continuation-in-part of, and claims priority to, U.S. Pat. No. 6,238,406, filed Mar. 1, 2000, entitled "PERCUTANEOUS MYOCARDIAL REVASCULARIZATION GROWTH FACTOR MEDIUMS AND METHODS" which is a divisional of U.S. Pat. No. 6,045,565, which issued Apr. 4, 2000 and is entitled "PERCUTANEOUS MYOCARDIAL REVASCULARIZATION GROWTH FACTOR MEDIUMS AND METHODS" which claims the priority benefit of U.S. Provisional Patent Application Ser. No. 60/064,210, filed Nov. 4, 1997, entitled "TRANSMYOCARDIAL REVASCULARIZATION GROWTH FACTOR MEDIUMS AND METHOD" and U.S. Pat. No. 5,968,059, which issued Oct. 19, 1999, entitled "TRANS MYOCARDIAL REVASCULARIZATION CATHETER AND METHOD".
The present invention relates generally to the application of non-invasive techniques to the delivery of therapeutic agents. Specifically, the present invention relates to an injection catheter for the treatment of heart diseases or other organs by the injection of therapeutic agents and/or placement of implants.
A number of techniques are available for treating heart disease and diseases of other organs percutaneously. An example of one such technique is percutaneous myocardial revascularization (PMR). This procedure is performed to increase blood perfusion through the myocardium of a patient. For example, in some patients, the number of lesions in coronary vessels is so great, or the location so remote in the patient vasculature, that restoring blood flow to the heart muscle is difficult. Percutaneous myocardial revascularization (PMR) has been developed as an alternative to techniques which are directed at by-passing or removing lesions. PMR is performed by boring holes directly into the myocardium of the heart. Positive results have been demonstrated in some human patients receiving PMR treatments. These results are believed to be caused in part by blood flowing from within a heart chamber through patent holes formed by PMR to the myocardial tissue. Suitable PMR holes have been proposed to be burned by laser, cut by mechanical means, and burned by radio frequency devices. Increased blood flow to the myocardium is also believed to be caused in part by the healing response to wound formation, specifically, the formation of new blood vessels in response to the newly created wound.
What remains to be provided are improvements and devices for enhancing the effectiveness of percutaneous myocardial revascularization. What also remains is the extension of these and other refinements to the treatment of various types of heart disease and diseases of other organs.
The present invention includes devices and methods for treatment of heart disease and diseases of other organs. The primary focus of the devices and methods of the present invention is the treatment of heart disease, but it should be appreciated that, as explained in more detail below, the devices and methods can be used to treat the diseases of other organs. In some instances, the techniques will vary depending upon the disease being treated.
An exemplary embodiment of the present invention includes, devices and methods for increasing blood circulation to the myocardium. Circulation can be increased through patent holes into the myocardium from a heart chamber and from new blood vessel growth. New blood vessels can provide blood supplied from within a heart chamber, such as the left ventricle, and from pre-existing vessels in nearby healthy heart tissue. New vessel growth can be promoted by the healing response to wounds created in accordance with the present invention. New vessel growth can also be promoted by angiogenic substances supplied to the myocardium in accordance with the present invention.
One set of methods according to the present invention utilizes implants such as tubes implanted into the myocardium, preferably from within the heart, delivered by a catheter. The tubes preferably contain, or are coated with, an angiogenic substance capable of being released over time. These tubes can be biodegradable, being absorbed by the body, some embodiment tubes leaving a patent hole in the myocardium surrounded by the absorbed angiogenic material. Other PMR tubes are not biodegradable, but have lumens therethrough with side holes along the tube length, providing access to the myocardiurn from with the lumen. The non-biodegradable tube can be formed from a metal, polymer or other bio-stable material. The nonbiodegradable tubes are preferably coated with and contain releasable angiogenic material, promoting new vessel growth along the length of the tube, where the new vessels may be supplied with blood through the tube side holes. One method utilizes PMR tubes implanted into the myocardium from outside the heart and can be performed during open heart surgery or during a minimally invasive procedure. In one embodiment, a growth factor may be infused in a slow release polymer. The growth factor or drug and polymer can be placed in a tube having side poles for drug release. By placing the growth factor or drug in the polymer the growth factor or drug can be slowly released into the myocardium. after implantation of the tube therein. In one embodiment of the tube containing the growth factor or drug and slow release polymer, the tube includes side holes and sealed ends.
Another set of methods according to the present invention involves injecting angiogenic material into the myocardium. A preferred method includes creating small bore holes or direct needle injection, for example using micro needles, into the myocardium utilizing a catheter within the heart. In the case of hole creation, a fluid, gel, polymer (biodegradable or biostable) or adhesive carrying an angiogenic material is injected into the hole. As the angiogenic substance is absorbed into the myocardium, in one method, a patent hole remains surrounded by myocardial tissue treated with angiogenic material. In another method, the injection hole closes, leaving no patent hole. New vessel growth is promoted by both the healing response to the wound and by the angiogenic substance. Blood circulation to myocardial tissue is increased by both the presence of the patent hole and the presence of new blood vessels supplied by existing coronary vessels and the heart interior. An alternative method utilizes angiogenic material injected into the myocardium from the exterior of the heart, in conjunction with open heart surgery or during a minimally invasive procedure.
In yet another alternate method, angiogenic materials delivered to the heart to promote new vessel growth. The new vessel growth is the consequence of the angiogenic material, for example, growth factor and any tissue reaction such as inflammation, rather than wounding the tissue.
Yet another set of methods includes externally wounding the heart and applying an external patch containing an angiogenic substance to the wound. The wound preferably penetrates into the myocardium. The healing response, enhanced by the angiogenic material, promotes new vessel growth near the wound. While the wound does not normally penetrate through to the heart chamber interior, new vessel formation can reach the chamber interior and also connect with pre-existing vessels in healthy heart muscle. A wound or series of wounds extending from healthy into hibernating tissue can create a network of vessels from healthy into hibernating tissue, supplying the hibernating tissue with blood. In another method, an external patch containing angiogenic material is applied to the heart without significant injury to the heart.
Any therapeutic agent, including small molecular drugs, proteins, genes and cells which could promote angiogenesis, protect tissues (i.e., cardiac protection), or promote tissue regeneration including Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factors (FGFs) is believed to be suitable for use with present invention. Carriers for the therapeutic agents of the present invention include polymers and angiopoietins including biodegradable and biostable hydrogels, and dissoluble polymers. Adhesives suitable for binding the present invention include fibrin glues and cyanoacrylates.
The injection of therapeutic agents and implantation of implants such as tubes for the placement of patches, is believed to have application to the treatment of other forms of heart disease in addition to the context of percutaneous myocardial revascularization. Some of these diseases include, for example, heart failure, myocardial infarction, and cancers, for example of the bladder, liver and kidneys.
Referring now to the drawings wherein like reference numerals indicate like elements throughout the several views, a human heart 20 having an aorta 22, a left ventricle 30, and a myocardium 28 is illustrated in
After degradation of the biodegradable material, holes 32 can remain patent while the angiogenic material has promoted blood vessel growth near the hole walls and into the myocardium. Holes 32 can also close, leaving no patent hole but leaving newly formed blood vessels. The inventors believe the new vessel growth will be significantly enhanced by the angiogenic substance, thereby increasing blood flow from inside the left ventricle to the myocardium of the left ventricle. New vessel growth is expected to join with other vessels at anastomoses, forming a larger network of blood vessels in the myocardium supplied by blood from the left ventricle and blood from other vessels supplied by coronary arteries. Preferred substances for encouraging tissue growth of ischemic tissue include Vascular Endothelial Growth Factor (VEGF), Fibroblast Growth Factor (FGF), PDGF, angiopoietins (Ang1, Ang2), estrogen or genes effecting the production of growth factors such as MCP-1 and HIFI-α, DEL-1, Tat, and Akt.
Catheter 24 can be used to treat heart failure and the heart after myocardial infarction by directly injecting agents or implants into the diseased myocardium. Agents for treating heart failure include positive inotropic agents, diuretics, vasodilators, neurohormonal antagonists, calcium channel blockers, anti-ischemic agents, antiarrhythmics, anticoagulants; and natruiretic peptides, such as BNP, endothelian, growth hormone, and adenosine receptor antagonists. Survival genes or proteins may be used to treat heart tissue following myocardial infarction. These include, for example, AKT kinases, cyclases, i.e., adenylyl cyclase VI, IkB, or any anti-apoptotic molecule or protein, or other molecules which aid in heart muscle regeneration, such as the angiogenesis inducing agents listed above.
Catheter 24 can be used to treat cancers by injecting agents or implants into solid tumors or cancerous tissues, which are accessible endoluminally. Such agents for treatment of cancers include, for example, cytoxic proteins, such as FASL and TK/gancyclovir; or cytostatic agents, such as Rb or p53, or the genes encoding these proteins. Anti-angiogenic molecules can also be injected to treat cancer; these include, for example, endostatin, angiostatin, thrombospondin, dox-RGD, antibodies to or small molecule inhibitors of VEGF and other endogenous angiogenic molecules or other small molecules such as paclitaxel, 5-FU, etc.
Similarly to the substance for encouraging tissue growth used for the PMR treatment, the agents used to treat heart failure and the heart after myocardial infarction, as well as the agents used to treat cancer, can be incorporated into a carrier material. This material is preferably biodegradable or dissoluble but can be substantially bio-stable or non-biodegradable. The carrier material preferably holds the therapeutic agents in proximity to the tissue to be treated.
Such carriers can include, among others, biodegradable polymers suitable for use in the present invention include: poly(L-lactide) (PLLA), poly(D,L-lactide) (PLA), poly(glycolide) (PGA), poly(L-lactide-co-D.L. Lactide) (PLLA/PLA), poly(L-lactide-coglycolide) (PLA/PGA), poly(glocolide-co-trimethylene carbonate) (PGA/PTMC), polydioxanone (PDS), polycaprolactone (PCL), polyhydroxybutyrate (PHBT), poly(phosphazenes), poly(D,L-lactide-co-caprolactone) (PLA/PCL), poly(glycolide-cocaprolactone) (PGA/PCL), poly(phosphase ester) and polyanhydrides. Other materials suitable for mixing with growth factors include, for example: hydrogels, polyethylene oxide and its copolymers, polyvinylpyrolidone, polyacrylates, polyesters, gelatins, collagens, proteins, alginates, karaya gum, guar gum, agar, algin, carrageenans, pectins, xanthan, starch based gums, hydroxyalkyl and ethyl ethers of cellulose, sodium carboxymethyl cellulose, polyvinyl alcohol, and polyurethanes.
Proximal shaft 44 is preferably formed from a stainless steel hypotube which is more rigid than distal. shaft 46. Shaft 44 defines a lumen 56 extending longitudinally therethrough. Proximal shaft 44 preferably extends the substantial majority of the length of inner shaft 38, to enhance the pushability and torqueability of inner shaft 38. It should be understood that although hypotube construction is preferred for proximal shaft 44, shaft 44 could be formed in the same manner as distal shaft 46 as described in more detail below or from another sufficiently torqueable and pushable construction as known in the art.
Distal shaft portion 46 is preferably more flexible than proximal shaft 44 to enhance trackability of inner shaft 38 proximate cutting tip 40. Distal shaft 46 can be formed from a helical coil 58 defining an elongate lumen 60 therethrough in fluid communication with lumen 56 of proximal shaft 44 and lumen 52 of cutting tip 40. Coil 58 can be surrounded by a polymer sheath 62. Sheath 62 may be PTFE, a shrink wrap or other similar biocompatible material known to those skilled in the art. The inside coil 58 forming the lumen wall of lumen 60 can be similarly coated. Shaft 46 can also be formed from an elastic alloy such as Nitinol.
Tip 40 and proximal shaft 44 can be connected to distal shaft 46 by two short tubular segments 64 and inserted within lumens 56 and 60, and 56 and 52, respectively. Tubular segments 64 can be small diameter hypotube segments or other sufficiently durable and biocompatible tubular members defining lumens in fluid communication with lumens 52, 56 and 60. An adhesive, braze or swage can be used to attach segments 64 to shafts 44 and 46 and tip 40.
In use, cutting tip 40 of inner shaft 38 can be delivered intravascularly to the heart wall and myocardium. by a catheter tube or tubes. In one embodiment, once cutting tip 40 has been. brought into contact with the heart wall, motor 48 can be activated to rotate cutting tip 40 and consequently blade 42. By further advancing cutting tip 40 into the myocardium of the heart, tissue in the path of the rotating blade will disintegrate. The disintegrated tissue can be aspirated through the lumen 52 extending through inner shaft 38. It can be appreciated that cutting tip 40 can penetrate the myocardium without being rotated. However, disintegration of tissue will generally not occur without rotating of tip 40.
Generally, the hole depth is preferably between ⅓ and � the thickness of the heart wall. The hole, however, could completely penetrate the myocardium for delivery of therapeutic agents to the pericardial space. The specific hole depth is determined on a case by case basis for each patient. Ultrasonic techniques may be used to view the patient's heart to determine the appropriate depth of the holes. In one method, radiopaque or contrast material is injected into the hole, in part to determine hole depth. A hole can be cut or formed, followed by radiopaque material injection and hole depth visualization using a method such as fluoroscopy. The cutting, radiopaque injection, and depth visualization cycle can be repeated until the desired hole depth is achieved. The depth of the holes will be generally proportional to the depth of penetration of cutting tip 40 into the myocardium. The rotation rate of cutting tip 40 may vary upon the character of the heart tissue encountered but should be rapid enough to disintegrate the tissue in the path of the cutting tip. The imaging agent can be incorporated into or mixed with a growth factor drug.
Inner shaft 38 and lumen 52 can be used to deliver angiogenic substances and adhesives and other carriers within the myocardium while tip 40 is still in place. In a preferred method, adhesives cure after leaving the tip. One method uses moisture cured adhesives. Once the angiogenic material has adhered to the walls of the hole bored into the myocardium., the angiogenic substance is more likely to remain in place within the myocardium. Adhesives preferably bind angiogenic material to the hole walls with a strength sufficient to resist immediate expulsion from the hole while being degradable or absorbable so as to allow diffusion of angiogenic material from the adhesive and absorption of angiogenic material into the myocardium. Inclusion of a fluoroscopic agent or radiopaque material with the angiogenic material can aid in visualizing expelled material.
Referring now to
A preferred embodiment tube has a circular cross section, a lumen 70, side holes 74, proximal port 80 and distal port 68, allowing blood flow through proximal port 80, lumen 70, side holes 74, distal port 68 and into myocardial tissue. Tube 66 is preferably formed of a biodegradable polymeric material, discussed further below. One embodiment has tubular walls porous to blood passage rather than larger, discrete holes. Another embodiment has no lumen and is formed of time-released therapeutics embedded in biodegradable material, such that the angiogenic substance is delivered within the myocardial tissue and the tube dissolves, possibly leaving a patent hole surrounded by tissue treated with angiogenic substance. While the preferred tube embodiment has a round cross-section, other embodiments have triangular, square, and elongate rectangular cross sections. Tube 66 preferably has a cutting tip 72 for easing insertion into the myocardium. Tubes can also have barbed outer surfaces to aid in retaining the spike within the myocardium. The tube can include radiopaque material or contrast as an aid in visualizing fluoroscopically where tubes have already been implanted. The tubes can be implanted in a pattern, leading from healthy tissue to hibernating tissue, creating a network of new blood vessels carrying both blood supplied from coronary arteries and the heart chamber itself.
The tube can be delivered through the lumen of a catheter from within a heart chamber. Tubes can also be delivered externally into the myocardium, either during open heart surgery or during a minimally invasive procedure. Tubes delivered externally preferably have lumens, side holes, closed proximal ends to minimize blood loss, and outside surface barbs to lessen the risk of the tube being expelled from the heart muscle. In a minimally invasive procedure, the PMR tubes can be injected through an elongate catheter into the pericardium. The PMR tubes can be injected entirely through the myocardium or can stop short of such penetration. The inventors believe the externally inserted PMR tubes can significantly promote vascularization within the myocardium, even where the PMR tubes do not penetrate through to the endocardium.
Although tubes 66 have been described herein with respect to PMR, it is anticipated that the tubes can be used for the treatment of heart failure and the heart after myocardial infarction by incorporating the therapeutic agents described above with respect to these conditions. It is also believed that the tubes could be used for treating cancer by incorporating the therapeutic agents described above.
Tubes 92 and 93 should be long enough and flexible enough to be advanced intraluminally to a desired body organ such as the heart, liver, bladder, or kidneys. The diameter of tube 92 should be sufficiently small to be advanced through the desired body lumen. Tubes 92 and 93 can be formed from biocompatible polymers or other materials known to those skilled in the art. Tubes 97 and 98 can be adhered to tubes 92 and 93 respectively by materials known to those skilled in the art. Tubes 97 and 98 can be hypotubes made from a metallic material or from a sufficiently rigid polymer or other material that they can be advanced into tissue for fluid injection therein.
As an alternative to the tubular implants described above, catheter 91 can be used to form an in situ implant. For example, a polymer could be pre-mixed with any of the therapeutic agents described above for treatment of the heart, liver, kidneys, bladder or other organs and solid tumors. The polymer pre-mix could be infused through, for example, lumen 94 into a tissue to be treated. At the same location a cross-linking agent could be infused through lumen 95 into the tissue. This would result in the polymer becoming cross-linked and solidifying in tissue. The cross-linking agent can also be mixed into a contrast solution such that the implants would become radiopaque. An example polymer to be pre-mixed with the therapeutic agent is alginate polymer, which can be cross-linked by multivalent ions. In another example, the polymer, if a polycation, gelatin, chitosan or the like which can be delivered through one lumen and the therapeutic agent if a polyanion such as DNA can be delivered through the second lumen. A polyelectrolyte complex will be formed when the polycation mixes with the polyanion, forming a solid material.
The polymer can be bio-stable or biodegradable, including dissoluble polymers. After the implants are placed in the tissue, the therapeutic agent is slowly released. The rate of release of the therapeutic agent to the surrounding tissue may be controlled by, for example, 1) diffusion of the agent through the polymer implant if the polymer implant is bio-stable; 2) by the rate of polymer degradation or dissolution if the implant is made of a biodegradable or dissolvable implant; or 3) by the rate of ion exchange if the implant is formed using two oppositely changed polyelectrolytes. In this manner, therapeutic agents may be delivered to tissue over periods of days, weeks, or a longer period of time.
An alternate embodiment of an implant which can be injected through a single lumen catheter such as that shown in
Referring now to
Patch 90 is preferably biodegradable, capable of being absorbed by the body after it is no longer needed. One patch includes a reservoir of angiogenic substance that leaches out the inside of the patch, supplying more wound healing and angiogenic compound over time.
Externally wounding the heart and applying a patch can be performed in conjunction with open heart surgery, where the heart is available for such a procedure. Minimally invasive procedures can also be used to access the heart for externally wounding the heart, creating wound and applying patch through a relatively small opening. Applicants believe externally wounding the heart triggers a healing response within the myocardium, including the formation of new blood vessels to the wounded area. While the incisions preferably do not penetrate through the entire thickness of the chamber wall, applicants believe the incisions within the myocardium trigger new blood vessel growth within the myocardium which can be supplied by vessels within the heart chamber or by other coronary vessels. While it is believed to be preferable to wound the tissue prior to placement of the patch, the patch is believed to have therapeutic value as well when placed on tissue that has not been wounded.
A variety of angiogenic substances and growth factors can be used in accordance with the present invention. Growth factors such as Fibroblast Growth Factor (FGF, FGF-1, FGF-2), Vascular Endothelial Growth Factors (VEGF) (all constructs including VEGF-2) and Endothelial Mitogenic Growth Factors are among the growth factors preferred for use with the present invention. Angiogenic substances such as estrogen, including estradiol (E2), estriol (E3) and 17-Beta Estradiol are also believed suitable for use with the present invention. Estrogen is believed to induce angiogenesis and increase permeability. This provides increased local blood circulation through neovascularization. Gene transfer into the heart tissue can be done as well.
The therapeutic agents used in the present invention also include, for example, pharmaceutically active compounds, proteins, oligonucleotides, ribozymes, anti-sense genes, DNA compacting agents, gene/vector systems (i.e., anything that allows for the uptake and expression of nucleic acids), nucleic acids (including, for example, recombinant nucleic acids; naked DNA, cDNA, RNA; DNA, cDNA or RNA in a noninfectious vector or in a viral vector which may have attached peptide targeting sequences; antisense nucleic acid (RNA or DNA); and DNA chimeras which include gene sequences and encoding for ferry proteins such as membrane translocating sequences ("MTS") and herpes simplex virus-1 ("VP22"), and viral liposomes and cationic polymers that are selected from a number of types depending on the desired application. For example, biologically active solutes include anti-thrombogenic agents such as heparin, heparin derivatives, urokinase, PPACK (dextrophenylalanine proline arginine chloromethylketone), rapamycin, probucol, and verapamil; angiogenic and anti-angiogenic agents; anti-proliferative agents such as enoxaprin, angiopeptin, or monoclonal antibodies capable of blocking smooth muscle cell proliferation, hirudin, and acetylsalicylic acid; anti-inflammatory agents such as dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, and mesalamine; antineoplastic/antiproliferative/anti-mitotic agents such as paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin and thymidine kinase inhibitors; anesthetic agents such as lidocaine, bupivacaine, and ropivacaine; anticoagulants such as D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compounds, heparin, antithrombin compounds, platelet receptor antagonists, anti-thrombin antibodies, anti-platelet receptor antibodies, aspirin, prostaglandin inhibitors, platelet inhibitors and tick antiplatelet factors; vascular cell growth promoters such as growth factors, growth factor receptor antagonists, transcriptional activators, and translational promoters; vascular cell growth inhibitors such as growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules consisting of a growth factor and a cytotoxin, bifunctional molecules consisting of an antibody and a cytotoxin; cholesterol-lowering agents; vasodilating agents; agents which interfere with endogenous vascoactive mechanisms, and combinations thereof. Cells of human origin can be used (autologous or allogeneic) or from an animal source (xenogeneic), genetically engineered if desired to deliver proteins of interest at the transplant site. The delivery media can be formulated as needed to maintain cell function and viability.
Polynucleotide sequences useful in the practice of the present invention include DNA or RNA sequences having a therapeutic effect after being taken up by a cell. Examples of therapeutic polynucleotides include anti-sense DNA and RNA; DNA coding for an antisense RNA; or DNA coding for tRNA or rRNA to replace defective or deficient endogenous molecules. The polynucleotides of the invention can also code for therapeutic peptides. A polypeptide is understood to be any translation product of a polynucleotide regardless of size, and whether glycosylated or not. Therapeutic polypeptides include as a primary example, those polypeptides that can compensate for defective or deficient species in an animal, or those that act through toxic effects to limit or remove harmful cells from the body. In addition, the polypeptides or proteins that can used include without limitation, angiogenic factors including acidic and basic fibroblast growth factors, vascular endothelial growth factor, epidermal growth factor, transforming growth factor α and β, platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor α, hepatocyte growth factor and insulin-like growth factor; growth factors; cell cycle inhibitors including CDK inhibitors; thymidine kinase ("TK") and other agents useful for interfering with cell proliferation, including agents for treating malignancies; and combinations thereof. Still other useful factors, which can be provided as polypeptides or as DNA encoding these polypeptides, include monocyte chemoattractant protein ("MCP-1"), and the family of bone morphogenic proteins ("BWPs"). The known proteins include BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr1), BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16. Currently preferred BMPs are any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 and BMP-7. These dimeric proteins can be provided as homodimers, heterodimers, or combinations thereof, alone or together with other molecules. Alternatively or, in addition, molecules capable of inducing an upstream or downstream effect of a DMP can be provided. Such molecules include any of the "hedgehog" proteins, or the DNAs encoding them.
In one exemplary embodiment of the present invention, the medical device has recombinant nucleic acid incorporated therein, wherein the recombinant nucleic acid comprises a viral vector having linked thereto an exogenous nucleic acid sequence. "Exogenous nucleic acid sequence" is used herein to mean a sequence of nucleic acids that is exogenous to the virus from which the vector is derived. The concentration of the viral vector, preferably an adenoviral vector, is at least about 1010 plaque forming units ("p.f.u."), preferably at least about 1011, p.f.u. Alternatively, the concentration of the viral vector is limited by the concentration that results in an undesirable immune response from a patient.
A variety of adhesives are suitable for the present invention, both for adhering a patch over a heart wound, and for retaining angiogenic material within a wound. Biodegradable polymer and materials are suitable for mixing with the therapeutic agents as described with respect to the other embodiments above. One adhesive is a hydrogel composed of gelatin and poly(L-glutamic acid)(PLGA). The hydrogel is formed by chemically cross linking gelatin and poly(L-glutamic acid). Another adhesive is fibrin glue. One suitable fibrin glue includes fibrinogen, thrombin, calcium chloride and factor VIII. Another family of adhesives is cyanoacrylates. Preferred cyanoacrylates include butyl-2-cyanoacrylate (Histoacryl), ethyl-2-cyanoacrylate, and octyl-2-cyanoacrylate. Gelatin-resorcinol formaldehyde-glutaraldehyde is another suitable adhesive.
Applicants believe many polymers having suitable adhesive properties can also be utilized, including without limitation: polyurethanes having amino groups, di- and trifunctional diols; polyvinyl acetates; polyamides; polyvinyl alcohols; polystyrenes; polylactides; polylactones; block co-polymers including polyesters, polyamides, and polyurethanes; and combinations and mixtures thereof.
Growth factors, angiogenic substances and biodegradable carriers and adhesives can be applied internally to punctures within heart chamber walls, externally to external heart wounds, and incorporated into tubes or spikes for implantation into the myocardium or other organs or solid tumors.
It is anticipated that the patch of the present invention can be used to treat heart failure, heart tissue following myocardial infarction and cancers, in addition to ischemic tissue. In each instance, the therapeutic agents described above with respect to those conditions could be incorporated into the patch for delivery to the tissue. In the case of heart failure, the treatment of heart tissue following myocardial infarction and the treatment of cancer, it is believed that the patch would be placed directly on, or in close proximity to the tissue to be treated.
Gun 112 includes a body 116. Slidably disposed within body 116 and schematically shown in
Catheter 114 includes an inner tubular shaft 126. Inner tubular shaft 126 includes a sharpened distal end 127. Like syringe 118, slider 120 and plunger 124, inner shaft 126 can be moved proximally or distally as shown by the arrows. More particularly, inner shaft 126 can be moved from a proximal position A wherein tip 127 is disposed within an outer shaft 129 of catheter 114 to a second position B, wherein tip 127 is disposed distally of outer shaft 129.
Syringe 118 includes an inner chamber 130 for containing a dosage of a drug or other fluid. Disposed at the distal end of plunger 124 is a plunger seal 132. Syringe 118 including plunger seal 132 preferably are prepacked to contain a quantity of drug, agent or other fluid prior to placement in gun 112. Syringe 118 includes a Luer fitting 128 or similar attachment device to fluidly connect inner shaft 126 to syringe 118. The proximal ends of plunger 124 includes a handle 134. Handle 134 can be used to rotate plunger 124 about its longitudinal axis within housing 116. Plunger 124 includes a plurality of teeth 136 extending therefrom. Syringe 118 also includes a cradle 138 in which is disposed a one-way plunger lock 140 which is biased toward plunger 124 by spring 142. Lock 140 includes one or more teeth having a slope which allows teeth 136 of plunger 124 to be advanced distally thereover, but engages with teeth 136 to prevent plunger 124 from being withdrawn proximally. Plunger 124 can, however, be withdrawn proximally if it is rotated about its longitudinal axis by using handle 134 such that teeth 136 are disposed away from lock 140, for example, pointed upward rather than downward as shown in
Slider 120 includes a syringe restraint member 144 which includes a surface engageable with cradle 138 of syringe 118. A plunger advancing member 146 is pivotally attached to slider 120 by pin 148. A spring 150 biases advancing member 146 toward a vertical position as shown in
Catheter 114 includes a preferably radiopaque, atraumatic hood 163 at its distal end and a manifold 164 at its proximal end. Manifold 164 includes a port 166 for infusion or withdrawal of fluids from catheter 114 through a lumen defined between inner shaft 126 and outer shaft 129. Manifold 164 also includes a flange 168 engageable with a portion of body 116 to connect body 116 to catheter 114.
It can be appreciated by those skilled in the art that there are numerous materials which can be advantageously used to construct the apparatus disclosed herein. These materials should be selected in view of the use to which the apparatus is put.
In use, catheter 114 can be advanced into a chamber of the heart, for example, the left ventricle through a femoral, brachial or carotid artery approach similar to catheter 24 of
Substantially simultaneously with the advancement of tip 127 from position A to position B, plunger advancing member 146 will engage the proximal side of one of the teeth 136 and advance plunger 136 distally into reservoir 130 to advance a dosage of drug or growth factor through inner shaft 126 and out tip 127 which, in position B would be disposed within the myocardium. The amount of the dosage can be regulated by limiting the travel of trigger 122 by adjusting screw 160. It can be appreciated that ring 182 should limit the travel in the distal direction of inner shaft 126 and syringe 118 to a distance less than the distal travel of plunger 124 such that there can be relative advancement of plunger 124 into chamber 130 to advance drug or growth factor through inner shaft 126.
When trigger 122 is released, it will pivot in a counterclockwise direction back to the position shown in
Marker 200 can be used for mapping purposes, for example, to define a target zone or perimeter for subsequent PMR treatment. Marker 200 can also be used chronically for future PMR treatments, diagnosis and monitoring. Marker 200 can also be coated or impregnated with a growth factor, drug or other therapeutic agent.
Manifold 264 includes a flange 302 which could be used to engage a portion of gun body 116 in a manner similar to that of flange 168 of manifold 164 described above. Within manifold 262 includes a plurality of steps 304, 305 and 306 disposed therein. Disposed proximate the proximal end of proximal portion 190 of inner shaft 126 is an alternate embodiment of a Luer fitting 274, which can engage Luer fitting 128 of syringe 118 of gun 116. Luer fitting 274 includes threads 272. At the distal end of Luer fitting 274 is a step engaging member 300. A spring 278 is fixed at its proximal end within manifold 274 and at its distal end to Luer fitting 274. Spring 278 is biased to draw Luer fitting 274 distally.
It can be appreciated that the further engaging member 300 advances distally, the farther inner shaft 126 and thus distal tip 227 will advance distally. Thus, using manifold 264 and Luer fitting 274, the depth of penetration into the heart wall of tip 227 can be controlled. It is, in fact, contemplated that the depth of penetration could be adjusted such that tip 222 would completely penetrate the heart wall to dispose tip 227 between the epicardium and the pericardial. sac. If tip 227 is disposed in such a location, catheter 114 could be used to deliver drugs, growth factors or other therapeutic agents or fluids within the pericardial. sac.
It can be appreciated that the distal. movement of inner shaft 126 can be limited by steps 304, 305 or 306 or manifold 264, by configuration as shown with respect to manifold 164 above, or by swage 196 engaging hood 163 as shown in
Slidably disposed within housing 352 is a fitting 366 which can be a Luer fitting having threads 368. Fitting 366 is slidable proximally and distally in the direction shown by the arrows. Fitting 366 is preferably connected at its distal end to inner shaft 126 and preferably defines a lumen 174 extending therethrough in fluid communication with the lumen through inner shaft 126. The catch arm 370 extends in a distal direction to its distal end 372. Fitting 366 is preferably formed from a polymer or other material known to those skilled in the art. The material from which catch arm 370 is formed is preferably elastic enough that arm 370 can be pressed inwardly toward groove 356.
A helical spring coil 376 is preferably disposed around a portion of inner shaft 126. Spring 376 has a proximal end and a distal end. The proximal end of spring 376 is connected to the distal end of fitting 366 and the distal end of spring 376 is connected to an anchor 378 extending from housing 352. As shown in
Numerous characteristics and advantages of the invention covered by this document have been set forth in the foregoing description. It will be understood, however, that this disclosure is, in many respects, only illustrative. Changes may be made in details, particularly in matters of shape, size, and arrangement of parts without exceeding the scope of the invention. The inventions's scope is, of course, defined in the language in which the appended claims are expressed.
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Owner name: SCIMED LIFE SYSTEMS, INC., MINNESOTA
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Owner name: SCIMED LIFE SYSTEMS, INC., MINNESOTA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:PALASIS, MARIA;BARRY, JAMES J.;REEL/FRAME:024636/0236
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Owner name: BOSTON SCIENTIFIC SCIMED, INC., MINNESOTA
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Effective date: 20041222
|21 May 2014
|Fee payment
Year of fee payment: 4


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