text:
Intralumenal drug eluting prosthesis
A prosthesis for insertion into a lumen to limit restenosis of the lumen. The prosthesis carries restenosis-limiting drugs which elute after the device is positioned in the lumen.
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1. Field of the Invention
This invention related to methods for lessening restenosis of body lumens, and to prosthesis for delivering drugs to treat said restenosis.
2. Description of the Related Art
Restenosis is defined as the reclosure of a previously stenosed ans subsequently dilated peripheral or coronary vessel. It occurs at a rate of 20-50% for these procedures and is dependent on a number of clinical and morphological variables. Restenosis may begin shortly following an angioplasty procedure, but usually ceases at the end of approximately six (6) months. There is not a current therapeutic procedure that has been proven to significantly reduce this restenosis rate.
A recent technology that has been developed that assesses the problem of restenosis is intravascular stents. Stents are typically metallic devices that are permanently implanted (expanded) in coronary and peripheral vessels. The goal of these stents is to provide a long-term "scaffolding" or support for the diseased (stenosed) vessels. The theory being, if you can support the vessel from the inside, the vessel will not close down or restenose. Unfortunately, initial data from clinical stent implants indicates that these metallic structures are not very successful in reducing restenosis.
Pharmacologic (biochemical) attempts have been made to reduce the rate of restenosis. All of these attempts have dealt with the systemic delivery of drugs via oral, intravascular or intramuscular introduction. Little, if any success has been achieved with this systemic approach.
For drug delivery, it has been recognized for a long period of time that pills and injections may not be the best mode of administration. It is very difficult with these types of administration to obtain constant drug delivery. Patient noncompliance with instructions is also a problem. Through repeated does, these drugs often cycle through concentration peaks and valleys, resulting in time periods of toxicity and ineffectiveness. Thus, localized drug treatment is warranted.SUMMARY OF THE INVENTION
The invention provides prostheses which may be inserted into a lumen of a body and fixed to the lumen wall adjacent an area needing treatment. Most typically, the lumen will be part of the vascular system which may be subject to restenosis following angioplasty. However, the methods and devices of the invention are also suited to treatment of any body lumen, including the vas deferens, ducts of the gallbladder, prostate gland, trachea, bronchus and liver or any other lumen of the body where medication cannot be applied without a surgical procedure. The invention applies to acute and chronic closure or reclosure of body lumens.
The prostheses of the invention include at least one drug which will release from the device at a controlled rate to supply the drug where needed without the overkill of systemic delivery. The prostheses include means for fixing the device in the lumen where desired. The prostheses may be completely biodegradable or may be bioabsorbable in whole or incorporated into the lumen wall as a result of tissue over growth, i.e., endothelialization. Alternatively, the prostheses may be biostable in which case the drug is diffused out from the biostable materials in which it is incorporated.
The prosthesis comprises a generally flexible tubular body which is fixed against the lumen wails by a mechanical action. The device should not cause an appreciable reduction in the lumen cross-section where inserted. Conventional stent designs which provide an expansion of the vessel are suitable, though not required. In all cases, the prostheses of the invention require the presence of an elutable drug compounded to the prosthesis itself. With conventional metal stents, the invention requires a drug-carrying coating overlying at least a portion of the metal.
The drugs in the prosthesis may be of any type which would be useful in treating the lumen. In order to prevent restenosis in blood vessels, migration and subsequent proliferation of smooth muscle cells must be checked. Platelet aggregation and adhesion can be controlled with antiplatelets and anticoagulants. Growth factor and receptor blockers and antagonists may be used to limit the normal repair response.
The current invention contemplates the usage of any prosthesis which elutes drugs locally to treat a lumen in need of repair. Controlled release, via a bioabsorbable polymer, offers to maintain the drug level within the desired therapeutic range for the duration of the treatment. When "stent" is referred to herein, it may include the classical definition of stents as they are used in intravascular applications. "Stent" used herein also includes any prothesis which may be inserted and held where desired in a lumen. It includes, but is not limited to, structures such as those shown and described in U.S. Pat. No. 4,886,062 to Wiktor.BRIEF DESCRIPTION OF THE DRAWINGS
A detailed description of the invention is hereafter described with specific reference being made to the drawings in which:
FIG. 1 is a greatly enlarged side view of an intralumenal drug-eluting prosthesis of the invention;
FIG. 2 is a greatly enlarged side view of an alternative embodiment to the prosthesis of FIG. 1;
FIG. 3A is a greatly enlarged fragment of the embodiment of FIG. 1;
FIG. 3B is a greatly enlarged fragment of the embodiment of FIG. 1 in which two layers of polymers are present, each having a different drug;
FIG. 4 is a greatly enlarged fragment of the embodiment of FIG. 2;
FIG. 5 is a greatly enlarged microscopic fragmentary detail of drug shown eluting form the porous structure of a filament or filament coating in a prosthesis into tissue or the vessel lumen;
FIG. 6 is a greatly enlarged cross-section of a blood vessel showing plaque profile immediately post-balloon catheter dilation procedure;
FIG. 7 is a greatly enlarged cross-section of the subject of FIG. 6 at a later date showing restenosis;
FIG. 8 is a greatly enlarged cross-section of a blood vessel showing plaque-prosthesis profile immediately post-prosthesis implant procedure;
FIG. 9 is a greatly enlarged cross-section of the subject of FIG. 8 after ingrowth has occurred;
FIG. 10 is a greatly enlarged fragmentary perspective view of a blood vessel wall and prosthesis filament of FIGS. 1 and 3 immediately after implantation;
FIG. 11 is a greatly enlarged fragmentary perspective view of the subject of FIG. 10 after about one month;
FIG. 12 is a greatly enlarged fragment of a loose weave of prosthesis filaments;
FIG. 13 is a greatly enlarged fragment of a coated metal filament in a loose weave;
FIG. 14 is a greatly enlarged fragment of a melted junction weave of prosthesis filaments in a loose weave;
FIG. 15 is a greatly enlarged fragment of a kinked junction wave of prosthesis filaments;
FIG. 16 is a greatly enlarged fragment of multistrand weave of prosthesis filaments; and
FIG. 17 is a alternative embodiment to FIG. 16, in which strands are not woven.
FIG. 18 is a partial sectional view of a catheter for delivery of the prosthesis of the present invention.
FIG. 19a-19i are sectional views of the deployment of the prosthesis by the catheter of FIG. 18.DESCRIPTION OF THE PREFERRED EMBODIMENTS
In the discussion above, a very simple definition of restenosis was given. As a complement to this definition, there are several more clinical definitions. Several of these definitions are listed below:
1. Reduction of minimal luminal diameter to less than 50% of the normal lumen diameter.
2. Loss of at least 50% of the initial gain achieved in angioplasty.
3. Decrease of at least 30% in the lumen diameter compared to post-angioplasty result.
4. A return to within 10% of the pre-angioplasty diameter stenosis.
5. An immediate post angioplasty diameter stenosis of less than 50% that increases to 70% or greater at follow-up.
6. Deterioration of 0.72 mm in minimal luminal diameter or greater from post-angioplasty to follow-up.
7. As for 6, but with a deterioration of 0.5 mm.
These definitions are sued by cardiologists to angiographically define restenosis.
Several hypotheses exist on why and how restenosis occurs. The current, most widely accepted explanation is that restenosis is a natural healing process in response to the arterial injury that occurs during all types of angioplasty procedures. This very complex healing process results in intimal hyperplasia, more specifically migration and proliferation of medial smooth muscle cells (SMC). The problem associated with this arterial healing process is that in some instances, it does not shut off. The artery continues to "heal" until it becomes occluded. It should be noted that restenosis is not a re-deposition of the plaque-like cholesterol material that originally occluded the artery.
The following is a possible scenario for restenosis according to the vessel healing hypothesis. Successful angioplasty of stenotic lesions produces cracking of the plaque, dissection into the media, denudation and destruction of endothelial cells, exposure of thrombogenic collagen, released tissue thromboplastin, and an increased loss of prostacyclin production. All of these lead to the aggregation of active platelets.
FIGS. 6 and 7 show a typical vessel 30 in cross-section after angioplasty procedures showing the interior 32 of the lumen. In FIG. 6 the interior of the lumen is rough and includes intimal flaps 34. Damage causes healing with deposition of platelets, fibrin formation and proliferation of neointima 37 which as shown in FIG. 7 significantly reduces the interior of the lumen.
Activated platelets release several mitogens including platelet derived growth factor (PDGF), epidermal growth factor, and transforming growth factor. PDGF has both mitogenic and chemotactic properties and thus, may induce both mitigation of SMC from the medial layer to the intimal layer as well as proliferation (Intimal hyperplasia). PDGF causes SMC proliferation by binding to specific PDGF receptors. Once the PDGF is bound to the receptors, deoxyribose nucleic acid (DNA) synthesis occurs and new cells are replicated. Minor endothelial injury may cause platelet adhesion and activation with the resultant release of PDGF. Thus, even the deposition of a monolayer of platelets may be sufficient to induce SMC proliferation.
Deeper arterial injury which is sometimes associated with complex stenotic lesions leads to more extensive platelet deposition and activation which may cause an even greater availability of the mitogenic factors. Thus, increased SMC proliferation and intimal hyperplasia. Arterial injury from angioplasty may result in release of PDGF-like compounds from not only platelets but also macrophages, monocytes, endothelial cells, or SMC's themselves.
Activated SMC from human atheroma or following experimental arterial injury secrete PDGF-like molecules which appears to lead to self perpetuation of SMC proliferation by the release of their own PDGF-like substances. Thus, any or all of the cells which can secrete PDGF relate substances (platelets, macrophages, monocytes, endothelia, and smooth muscle cells) may contribute to the cascading effect of restenosis after angioplasty.
The previous restenosis scenario resulted from normal angioplasty procedures. During balloon angioplasty if the balloon is undersized or not totally inflated and the plaque cracking and extensive endothelial denudation does not occur the lesion could still restenose. Rheologic factors contribute as well to the interaction between platelets and the arterial wall. Residual stenosis, resulting from inadequate balloon expansion, produces a high local shear rate and enhances platelet deposition and activation. These stenoses may be important as a stimulus for some proliferation through enhanced platelet deposition and secretion of growth factors. This hypothesis correlates with the increased incidence of restenosis in patients with high-grade residual stenoses or transtenotic gradients.
Prevention of Restenosis
In order to prevent restenosis, one must stop the proliferation of smooth muscle cells. As stated earlier, this is a biochemical process which cannot be treated mechanically. Several hypothesis exist on how to biochemically stop restenosis. Some of which are:
1. Reduce the adhesion and aggregation of the platelets at the arterial injury site.
2. Block the expression of the growth factors and their receptors.
3. Develop competitive antagonists of the above growth factors.
4. Interfere with the receptor signaling in the responsive cell.
5. Find a "natural" inhibitor of smooth muscle proliferation.
Item #1 is directly related to the formation of thrombus, a major problem with all types of angioplasty procedures. Items #2, #3 and #4 are closely related. They deal with blocking restenosis during the massive cell migration and replication cycle. Unlike item #1, these items address the growth factors that are produced from sources other than platelets. Item #5 is listed to address the question; Why don't 50-80% of the people undergoing angioplasty restenose? There may be some type of natural inhibitor that these people produce that stops the proliferation of smooth muscle cells.
There are at least two (2) different ways to prevent the adhesion and aggregation of platelets. One method is to use an antiplatelet and another is to use an anticoagulant.
Antiplatelet drugs include such as aspirin and dipyridamole. Aspirin is classified as an analgesic, antipyretic, anti-inflammatory, antiplatelet drug. It has been clinically tested and proven to reduce the risk of sudden death and/or non-fatal reinfarction in post myocardial infarction (heart attack) patients. The proposed mechanism of how aspirin works, relates directly to the platelets. It somehow blocks the platelets, restricting coagulation. This prevents the cascading platelet aggregation found in thrombus and subsequently restenosis. Aspirin is therefore a possible restenosis inhibitor. Dipyridamole is a drug similar to aspirin, in that is has anti-platelet characteristics. Dipyridamole is also classified as a coronary vasodilator. It increases coronary blood flow by primary selective dilatation of the coronary arteries without altering systemic blood pressure or blood flow in peripheral arteries. These vasodilation characteristics are thought to be possibly beneficial for restenosis prevention.
Anticoagulant drugs include Heparin, Coumadin, Protamine, and Hirudin. Heparin is the most common anticoagulant used today. Heparin, in one form or another, is used in virtually every angioplasty procedure performed. All four (4) of these drugs function as an anticoagulant by preventing the production of thrombin, a binding agent which causes blood to clot. This too, may reduce the cascading effect of platelet aggregation at the lesion site, thus possibly reducing restenosis. The use of Protamine in the presence of Heparin causes the Protamine to function as a Heparin antagonist, blocking the effect of the Heparin. Protamine, however, used alone, acts as an anticoagulant. Hirudin is singled out because it is not normally found in the human body. Hirudin is a drug that is found in the salivary glands of leeches. It is a very concentrated anticoagulant that functions in a similar manner as Heparin, Coumadin, and Protamine.
There are several types of drugs that interrupt cell replication. Antimitotics (cytotoxic agents) work directly to prevent cell mitosis (replication), whereas antimetabolites prevent deoxyribose nucleic acid (DNA) synthesis, thus preventing replication. The action of the antimitotics and antimetabolites are similar, they can be grouped into one category. This category will be known as the anti-replicate drugs.
Anti-replicate drugs include among others: Methotrexate, Colchicine, Azathioprine, Vincristine, VinBlastine, Fluorouracil, Adriamycin, and Mutamycin. The target systemic molarity desired with methotrexate is on the order of 10.sup.-6 M with a range of between 10.sup.-3 to 10.sup.-8 Molar. Locally, the molarity of the drug may be highly variable, which is one of the great disadvantages in systemic administration of the drug. When drugs are delivered locally via the prosthesis of the invention, they may be at therapeutic levels at the diseased site while at the lower limits of detectability in the bloodstream. So little drug is required for effective local treatment of a lumen that the drug may not be detectable in blood samples.
Anti-inflammatory drugs such as glucocorticoids (e.g., dexamethasone, betamethasone) can also be useful to locally suppress inflammation caused by injury to luminal tissue during angioplasty.
If the restenosis process ranges from shortly after injury to about four to six months later, then the generalized elution rates contemplated are such that the drug should ideally start to be released immediately after the prosthesis is secured to the lumen wall to lessen cell proliferation. The drug should then continue to elute for up to about four to six months in total.
Complex systems of drugs may be carried by the prosthesis. An anticoagulant or antiplatelet may be included in the outermost surface of the device in order to elute off very quickly for the first several days. Antiinflammatories and antireplicates can be formulated into the device to continue to elute later, when in contact with non-blood cells after neointima overgrowth has surrounded the device. This usually occurs in about two weeks. The drug elution rate does not need to be uniform, and may be tailored to fit the need of the patient.
Prosthesis (Stent) Design
The current invention contemplates the usage of any prosthesis which elutes drugs locally to treat a lumen in need of repair. When "stent" is referred to herein, it may include the classical definition of stents as they are used in intravascular applications. "Stent" used herein also includes any prosthesis which may be inserted and held where desired in a lumen.
FIGS. 1 through 17 show features of some of the prostheses which may be used to carry and elute restenosis limiting-drugs.
The current preferred stent 10 configuration consists of a single filar, monofilament braided mesh design as shown in FIG. 1. There are sixteen (16) filaments 12, eight (8) of which are wound in one helical direction, and the remaining eight (8) which are wound in the opposite direction. The stent 10 is self-expanding to a predetermined diameter. The profile (diameter) of the stent 10 can be easily reduced by pulling the stent 10 longitudinally. In this reduced profile configuration, the stent 10 can be loaded into a catheter for delivery into the vessel.
The stent 20 shown in FIGS. 2 and 4 is a metallic malleable design which may be forced against a lumen wall by a balloon catheter which fixes it into position. The exterior surface of the metal filaments 22 would include a coating 14 with a drug-eluting polymer described previously. The polymer may be biostable or bioabsorbable. If biostable, the drug would diffuse out of the polymer.
The variations of design shown in the embodiments of FIGS. 1 and 2 show that the prosthesis of the invention must be secured against a lumen wall and must carry a drug-eluting polymer.
There are many variables in the design of stent 10. The angle (.alpha.) of the filaments 12 is a major variable. The angle .alpha. can vary from 0 degrees to 180 degrees. The design in the Figures is based on an angle in the 60 degree to 90 degree range.
There are many options for fabricating the drug eluting stents. One option is to have all sixteen (16) filaments be drug eluting. Or, you could have any number of filaments up to sixteen (16) degrade and elute drugs. Another option is to have a multi-filar stent. Instead of a single filament braided into the stent, it is possible to have two (2), three (3), or even four (4) strands 16 braided to form a filament 12 as shown in FIG. 16. This would create a stent with much greater expansile force, but also have much more material in the surface area. This is a common trade-off in stent design. Similar to the single-filar design, the multi-filar form shown in FIG. 16 could have varying numbers of strands 16 that are drug eluting. FIGS. 16 and 17 show that the multi-filar design may be braided or unbraided. One (1), two (2), three (3), or four (4) of the filaments could be impregnated with a drug and biodegradably elute. Alternatively, the polymer may be biostable which allows for diffusion of the drug without degradation.
The stent 10 of FIG. 1 consists of a wound braided mesh which is self-expanding to a predetermined diameter and whose profile diameter can be greatly reduced for catheter introduction. The radial expansile force increases with diameter to the point of the self-expanded diameter limit, at which point the angle between the filaments and the longitudinal axis is a maximum. FIGS. 12 and 15 show alternative construction techniques to alter the radial expansive force. FIG. 12 shows the filaments 12 being woven without any connection. FIG. 13 is similar except the filament 22 is formed with a metal core 16 and a coating 14. In FIG. 14 the individual filaments 12 are shown with a bonded juncture 18. The bonding at the juncture 18 prevents the individual filaments 12 from sliding relative to each other, which improves the radial strength. The mechanically kinked junction 19 shown in FIG. 15 also limits the sliding of the filaments to change the radial strength. A heated platen press may be pressed against the wound stent while still on the forming mandrel to form the kinks. Higher temperatures may be used to form the melted junctures 18.
The devices may be made more visible under fluoroscopy and x-ray by incorporating radiopaque materials into marker band 24 to the individual filaments 12 at the ends of the stent 10 as shown in FIG. 1. Such marker bands could help to locate the stent and assure proper placement and patency.
Bioabsorbable Prosthesis (Stent) Materials
Controlled release, via a bioabsorbable polymer, offers to maintain the drug level within the desired therapeutic range for the duration of the treatment. In the case of stents, the prosthesis materials will maintain vessel support for at least two weeks or until incorporated into the vessel wall even with bioabsorbable, biodegradable polymer constructions.
Several polymeric compounds that are known to be bioabsorbable and hypothetically have the ability to be drug impregnated may be useful in prosthesis formation herein. These compounds include: poly-1-lactic acid/polyglycolic acid, polyanhydride, and polyphosphate ester. A brief description of each is given below.
Poly-1-lactic acid/polyglycolic acid has been used for many years in the area of bioabsorbable sutures. It is currently available in many forms, i.e., crystals, fibers, blocks, plates, etc. These compounds degrade into non-toxic lactic and glycolic acids. There are, however, several problems with this compound. The degradation artifacts (lactic acid and glycolic acid) are slightly acidic. The acidity causes minor inflammation in the tissues as the polymer degrades. This same inflammation could be very detrimental in coronary and peripheral arteries, i.e., vessel occlusion. Another problem associated with this polymer is the ability to control and predict the degradation behavior. It is not possible for the biochemist to safely predict degradation time. This could be very detrimental for a drug delivery device.
Another compound which could be used are the polyanhydrides. They are currently being used with several chemotherapy drugs for the treatment of cancerous tumors. These drugs are compounded into the polymer which is molded into a cube-like structure and surgically implanted at the tumor site.
Polyanhydrides have weaknesses in their mechanical properties, due to low molecular weights. This drawback makes them difficult to process into a filament form. Also, polyanhydrides have poor solubility, making characterization and fabrication difficult.
The compound which is preferred is a polyphosphate ester. Polyphosphate ester is a compound such as that disclosed in U.S. Pat. Nos. 5,176,907; 5,194,581; and 5,656,765 issued to Leong which are incorporated herein by reference. Similar to the polyanhydrides, polyphoshate ester is being researched for the sole purpose of drug delivery. Unlike the polyanhydrides, the polyphosphate esters have high molecular weights (600,000 average), yielding attractive mechanical properties. This high molecular weight leads to transparency, and film and fiber properties. It has also been observed that the phosphorous-carbon-oxygen plasticizing effect, which lowers the glass transition temperature, makes the polymer desirable for fabrication.
The basic structure of polyphosphate ester monomer is shown below. ##STR1## where P corresponds to Phosphorous, O corresponds to Oxygen,
and R and R1 are functional groups.
Reaction with water leads to the breakdown of this compound into monomeric phosphates (phosphoric acid) and diols (see below). ##STR2## It is the hydrolytic instability of the phosphorous ester bond which makes this polymer attractive for controlled drug release applications. A wide range of controllable degradation rates can be obtained by adjusting the hydrophobicities of the backbones of the polymers and yet assure biodegradability.
The functional side groups allow for the chemical linkage of drug molecules to the polymer. This is shown below. ##STR3##
The drug may also be incorporated into the backbone of the polymer. ##STR4##
In summary, the highly hydrolytically reactive phosphorous ester bond, the favorable physical properties, and the versatile chemical structure make the polyphosphate esters a superior drug delivery system for a prosthesis.
FIGS. 3A and 3B show that the filaments 12 may be made from one or several layers of polymer. In FIG. 3A only a single polymer is present to carry the drugs. In FIG. 3B a second layer of polymer 15 is shown. That layer 15 may be a simple barrier which limits diffusion of drugs in the polymer 14. In that event, the smaller molecules could elute out immediately, while larger compounds would not elute until later when the layer 15 has biodegraded. Alternatively, layer 15 may include a different drug incorporated therein from that found in layer 14. The barrier coating 15 could be as simple as a silicone or polyurethane.
The prosthesis is inserted into the lumen wherever needed as per the usual procedure for stents. The device is fixed into place either by radial expansion in devices such as shown in FIG. 1 or are deformed by a balloon catheter in the case of devices in accordance with FIG. 2.
FIGS. 8 through 11 show the placement and effects of the drug-eluting prosthesis of the invention. The prosthesis tacks up any intimal flaps and tears caused by any prior ballooning. The initial deposition of platelets and subsequent thrombus formation 38 is controlled and minimized by the stent design and the elution which limits platelet aggregation and other immediate repair responses described previously. Localized thrombus formations in the areas of cracked and roughened plaques and newly exposed underlying collagen and fibro-muscular tissues is also decreased. This results in limited but quick neointima formation 40 and intimal proliferation over individual stent filaments progressing to mature endothelial lining. Long term significant restenosis is therefore limited. Elution of the anti-replicates along or in conjunction with the initial elution of anti-coagulants can also limit the extent of the restenosis which occurs in the natural healing process.
In yet another embodiment of the invention, a purely polymeric prosthesis such as that having the configuration shown in FIG. 1 can be combined with an expandable metal stent to provide additional support for the prosthesis. This can be important since preferred bioabsorbable polymeric materials for the prosthesis may have insufficient resilience to expand an occluded body lumen or to maintain its expansion. By including a metal stent within the lumen of the polymeric prosthesis, the polymeric prosthesis is effectively held against the wall of the body lumen by the strength of the metal stent. In a most preferred aspect of this embodiment, the metal stent is only temporarily implanted so that only the bioabsorbable prosthesis remains implanted in the body lumen on a long term basis. This can be accomplished by including a polymeric stent body and a metal stent body on the distal end of a catheter designed to expand and release the stents. Both of the stent bodies have a number of support elements which make up an open-ended, radially expandable self-supporting tubular structure. In the polymeric stent structure, a bioabsorbable polymeric element (such as a filment made from a bioabsorbable polymer) having drugs incorporated therein can be attached to the support elements of the body so that at least a portion of the bioabsorbable element is exposed at the exterior surface of the polymeric stent body. The stents are arranged on the distal end of the catheter such that the catheter can provide remote, transluminal deployment of the stents, with the metal stent inside the polymeric stent, from an entry point into a selected portion of the body lumen to be treated and also remote actuation of an expansion mechanism from the proximal end of the catheter. The expansion mechanism (e.g. a balloon or the like if the metal stent is made of malleable metal for balloon expansion or a release mechanism if the metal stent is a self-expanding stent made from a resilient metal) is one capable of providing radial expansion of the metal stent body to bring the metal stent into supporting contact with the polymeric stent body and also to press the polymeric stent body so that it expands radially into contact with the wall of the body lumen. This will bring the bioabsorbable element into supporting contact with a body lumen at an interior portion of the body lumen to be treated and will position the bioabsorbable element to deliver drugs to the body lumen. Following the expansion of the stents into luminal contact, the balloon (if the expansion device is a balloon) can be deflated which allows luminal flow to be restored. After the stents have been in place for a predetermined period of time, the metal stent can be removed to leave only the polymeric stent (and its drug delivery component) in position in the body lumen. This can be accomplished, for example, by radially contracting the metal stent and then withdrawing it from the body lumen or by unwinding the metal stent a bit at a time as it is withdrawn from the body lumen.
Referring now to specific embodiments shown in the drawings, one possible configuration for a polymeric prosthesis supported by a metal stent is that of the prosthesis shown in FIG. 1 supported by a metal stent having a configuration such as that taught in U.S. Pat. No. 4,886,062 to Wiktor which is incorporated herein by reference. These devices may be combined by simply placing the polymeric prosthesis over the metal stent and balloon; introducing the prosthesis, stent, and balloon into the body lumen as a unit until it reaches the desired point for expansion; inflating the balloon to radially expand the prosthesis and stent into contact with the body lumen; and removing the balloon. In such an embodiment, the metal stent would be permanently implanted with the polymeric prosthesis. Another embodiment of this concept is shown in FIGS. 18 and 19a-19i in which the metal stent is only implanted for a limited period of time and then removed. Referring now to FIGS. 18 and 19a-19i, a catheter assembly 50 includes a hub assembly 52 at a proximal end, an inflatable balloon 54, a metal stent 56 and a polymeric prosthesis 58 at a distal end and a sheath 60 extending from the proximal to the distal end. The metal stent 56 is crimped onto the balloon 54 and includes an elongated lead 62 extending to the proximal end of the catheter assembly 50 where it includes an enlarged portion 64 to enable an operator to securely grip the lead 62. Distal to the balloon 54 is the polymeric prosthesis 58 which is constrained from radial self-expansion by the sheath 60. In operation, a guidewire 66 is inserted into the body lumen 68 and through the point of occlusion 70. The catheter assembly 50 is then passed into the lumen 68 on the guidewire 66 until the prosthesis 58 is positioned at the point of the occlusion 70. The sheath 60 is then drawn back, thereby allowing the prosthesis 58 to be pushed out of the sheath 60 by the leading edge of the balloon assembly where it radially self-expands into luminal contact. The balloon 54 and stent 56 are then advanced out of the sheath 60 as a unit and into the open center of the prosthesis 58. The balloon 54 is then inflated to expand the metal stent 56, the prosthesis 58 and the occlusion 70. The balloon 54 is then deflated and withdrawn from the metal stent 56 and prosthesis 58, leaving the metal stent 56 inside the prosthesis 58 in support of the prosthesis 58 and the occlusion 70. If the body lumen 68 is a blood vessel, blood flow is restored by deflating the balloon 54. If desired, the balloon 54 can then be withdrawn entirely from the sheath 60 and also, if desired, the sheath 60 and guidewire 66 can be withdrawn. However, it is preferred to leave the balloon 54, sheath 60 and guidewire 66 in place in order to provide support for the lead 62 and to avoid entangling the lead 62 with the catheter lumen or guidewire 66 as they are withdrawn. If the balloon 54 or guidewire 66 are to be withdrawn, it may be preferable to modify the sheath 60 by providing a separate lumen in the sheath 60 or another location in the catheter assembly 50 for the lead 62. After a desired period of time which allows the prosthesis to achieve a stable support for the lumen, the lead 62 is pulled at the proximal end of the catheter assembly 50, thereby causing the metal stent 56 to unwind and be taken up into the sheath 60. The metal stent chosen for use in this method should include no edges or ends which can snag the prosthesis 58 and pull it from its intended position in the body lumen 68. The sheath is then withdrawn, leaving the prosthesis 58 in place in the lumen 68.
This completes the description of the preferred and alternate embodiments of the invention. Those skilled in the art may recognize other equivalents to the specific embodiments described herein which equivalents are intended to be encompassed by the claims attached hereto.
1. A device for local intralumenal administration of drugs comprising:
- (a) a body including a plurality of support elements forming a open-ended, radially expandable, self-supporting tubular structure having an interior surface and an exterior surface, the tubular structure including as support elements a plurality of helical elements, each of which is wound in a helix configuration along a center line of the tubular body as a common axis, said helical elements wound in opposing helical directions such that the tubular body is variable in radial diameter under axial movement of opposite ends of the body relative to each other;
- (b) a flexible, polymeric filament attached to the support elements of the body, at least a portion of the filament exposed at an exterior surface of the tubular body;
- (c) a drug compounded into the polymeric filament such that the drug is delivered to the body lumen when the tubular body is radially expanded into contact with the portion of the body lumen to be treated; and
- (d) a radially expandable stent of malleable metal in supporting contact with the tubular structure.
2. A device for local intralumenal administration of drugs comprising:
- (a) a body including a plurality of support elements forming a open-ended, radially expandable, self-supporting tubular structure having an interior surface and an exterior surface, the tubular structure including as support elements a plurality of helical elements, each of which is wound in a helix configuration along a center line of the tubular body as a common axis, said helical elements wound in opposing helical directions such that the tubular body is variable in radial diameter under axial movement of opposite ends of the body relative to each other;
- (b) a flexible, polymeric filament attached to the support elements of the body, at least a portion of the filament exposed at an exterior surface of the tubular body;
- (c) a drug compounded into the polymeric filament such that the drug is delivered to the body lumen when the tubular body is radially expanded into contact with the portion of the body lumen to be treated; and
- (d) a radially expandable stent of resilient metal in supporting contact with the tubular structure.
3. A device for local intralumenal administration of drugs comprising:
- (a) a body including a plurality of bioabsorbable polymeric elements forming an open-ended, radially expandable tubular structure having an interior surface and an exterior surface, the tubular structure including a plurality of elements joined together such that the tubular body is variable in radial diameter;
- (b) a flexible, bioabsorbable polymeric filament attached to the elements of the body such that at least a portion of the filament is exposed at an exterior surface of the tubular body;
- (c) a drug compounded into the polymeric filament such that the drug is delivered to the body lumen when the tubular body is radially expanded into contact with the portion of the body lumen to be treated; and
- (d) a radially expandable metal stent in supporting contact with the tubular body.
4. The device of claim 3 also comprising a barrier coating of polymeric material on the drug-containing filament to limit the rate of drug elution.
5. The device of claim 3 wherein the drug is selected from the group consisting of antiplatelet drugs, anticoagulant drugs, anti-inflammatory drugs, antireplicate drugs and combinations of said drugs.
6. The device of claim 3 wherein the stent is a radially expandable stent of malleable metal.
7. The device of claim 3 wherein the stent is a radially expandable stent of resilient metal.
8. The device of claim 3 wherein the elements of the tubular body are joined together by weaving and wherein the flexible, polymeric filament is woven into the support elements of the tubular body.
9. The device of claim 3 wherein the polymeric filament is attached to the elements of the tubular body by a bonded juncture.
|April 1972
|April 27, 1982
|March 17, 1987
|April 7, 1987
|July 7, 1987
|April 26, 1988
|October 3, 1989
|October 10, 1989
|December 12, 1989
|May 8, 1990
|July 31, 1990
|February 5, 1991
|Kaplan et al.
|May 14, 1991
|May 28, 1991
|Fox, Jr.
|July 2, 1991
|September 10, 1991
|October 1, 1991
|October 22, 1991
|October 29, 1991
|November 5, 1991
|April 7, 1992
|October 6, 1992
|October 6, 1992
|November 24, 1992
|December 15, 1992
|May 25, 1993
|August 10, 1993
|February 1, 1994
|Schwartz et al.
|April 19, 1994
|November 22, 1994
|Andersen et al.
|January 24, 1995
|Scott et al.
|August 22, 1995
|August 22, 1995
|Schwartz et al.
|November 7, 1995
|Buscemi et al.
|March 19, 1996
|Buscemi et al.
|August 13, 1996
|Wolff et al.
|September 3, 1996
|Buscemi et al.
|January 7, 1997
|Schwartz et al.
|May 13, 1997
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|July 1, 1997
|Myler et al.
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|October 7, 1997
|Sahatjian et al.
|March 1990
|August 1985
|November 1983
|April 1989
Type: Grant
Filed: Dec 4, 1996
Date of Patent: Dec 22, 1998
Assignee: Medtronic, Inc. (Minneapolis, MN)
Inventors: Rodney G. Wolff (Minnetonka Beach, MN), Vincent W. Hull (Ham Lake, MN)
Primary Examiner: Debra S. Brittingham
Attorneys: Daniel W. Latham, Harold R. Patton
Application Number: 8/759,197
International Classification: A61F 206;


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A contemporary personalised typography print in grey and green. Megan Claire's aim is to stand out from the crowd with her distinctive designs and clever thinking. She creates contemporary and personalised cards, prints and gift tags. Each one is designed, drawn and finished individually by Megan Claire using high quality materials. These selected items will make a truly special gift when you personalise your chosen item with a special message. Follow these three simple steps and you'll receive your personalised item within 14 days of ordering. How to personalise your product table.cq-sizeguidetable {width:100%; border-collapse: collapse; text-align:left; font-family: Arial; font-size:12px; border-bottom:1px solid #f4f2ec; margin-top:10px;padding-bottom:1px;}table.cq-sizeguidetable th {border-width: 0px;padding: 8px;background-color:#dedbd2;}table.cq-sizeguidetable td {border-width: 0px;padding: 8px;border-style: none;}table.cq-sizeguidetable td:first-child {font-weight:bold;}.cq-sizeguidetable tr:nth-child(odd){background-color: #f4f2ec;} 1. Place your order 2. Think of 12 things about Dad or what he likes. For the best layout, try to use a variation of sentence lengths. 3. Email your personalisation details directly to firstname.lastname@example.com within three day after placing an order* including your name, order number and contact details. If you are purchasing this as a gift and do not wish the recipient to be contacted, please ensure that you put your own contact details for this order 4. If you are ordering a print, you'll receive a mock up preview of your personalised product via email Refund policy This item is made to your specification and so is excluded from our usual returns policy. Find out more. This does not affect your statutory rights You may be contacted by the supplier about your order. Please note: the text will be smaller over a certain number of characters
H35.5 x W27.5cm

subset: commoncrawl


text:
Steve & Tracy Koss
Sutton West Coast Realty
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Mockups are a great way to show off your designs without having to make the product so that you can list multiple items in your shop quickly! Digital mockups make it easy to see how your design will look once made. Saves time on editing photos and money for props and backdrops.
If you struggle with product photography this is a great option for you.
Simply download the high resolution JPEG and add your digital design.
Purchase includes:
Zip file containing: 1 JPEG file in high resolution and Seller's Copyright Policy
Compatible with Silhouette Studio, Cricut Design Space, Scan N Cut, Adobe Illustrator and other cutting and design programs
So Fontsy Standard Commercial Use License


text:
Short version: there are going to be Divergent e-shorts!
Four of them!
And they will be about…drumroll, please…
(See what I did there?)
And the first one will be out on September 24th!
Long version: when my publisher approached me hoping that I would be able to write some extra Divergent content from them, I considered a few options for what I might write about, or whose perspective I might choose. Over time it became clear to me that the character I was most interested in exploring further was Four. Two reasons: first, I know his perspective is the one a lot of you are interested in reading (I get asked if I'm going to write anything else from his perspective all the time!), and hey, you're my readers and I like to write things you want to read; second, I was excited by the idea of expanding my own understanding of him, the way I did when I rewrote the knife-throwing scene from his perspective for the Free Four e-short.
For me, Four has never just been Tris's love interest or a way for sexual tension to enter the story. He has always been a whole person with a history that affects him (and Tris) in significant ways, and a co-mover of the plot along with Tris. These stories are helping me to delve into his character in a way I never have before, and to build up parts of the world that Tris never experienced due to her limited perspective. Interestingly enough, they also affected the content of Allegiant, giving me more to draw from—awesome, right?
These stories will be longer than Free Four (Four's retelling of the knife-throwing scene, which was only thirteen pages), and the first one will be out on September 24th. You can learn more official info here, too. And of course, I'll keep you informed of the other stories as information becomes available, too.


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Chicago, IL (SportsNetwork.com) - Jonathan Toews scored, Corey Crawford had 34 saves and the Chicago Blackhawks beat the St. Louis Blues 2-0 Monday in Game 3 of the Western Conference quarterfinals. After a pair of overtime losses in St. Louis, the Blackhawks got their first win in the best-of-seven series with Game 4 on tap for Wednesday in Chicago. "That was a big win for us but we have to keep the same mentality," said Crawford. "Just because we came here and got the first one at home doesn't mean it's going to be easy. We have to be prepared to work even harder and keep the same good feelings we had in this game." Crawford had 15 saves in the first period, eight in the second and made his 11th save of the third period on an Alex Pietrangelo shot that was re-directed in the final minute. It was Crawford's third career postseason shutout. Toews scored 4:10 into the game and Marcus Kruger added an empty-netter to seal the win. Both teams were missing top players. Blackhawks defenseman Brent Seabrook began serving his three-game suspension for the check that knocked David Backes out of Game 2 on Saturday and led to Vladimir Tarasenko's tying goal for the Blues with 6.4 seconds remaining. Backes was also out after Seabrook drove his shoulder into the Blues captain's face, sending him head-first into the corner boards. After Tarasenko tied Game 2, Barret Jackman scored 5:50 into overtime to give St. Louis a 2-0 series lead. The Blues won Game 1 in a similar hear-stopping fashion after Jaden Schwartz scored with 1:45 left in regulation and Alexander Steen won it 26 seconds into the third overtime, the longest game in franchise history. Both games ended 4-3. Now, the Blues are hoping to avoid a repeat of last year, when they posted a pair of 2-1 wins over Los Angeles in the first round, then lost the next four games. "We knew this was going to be a long series," said Blues coach Ken Hitchcock. "We really played hard and played well and did a lot of things we needed to do to win the game, but you have to give their goalie credit. He was good." Ryan Miller stopped 23 of the 24 shots he faced in this one, only letting Toews' drive from the top of the right circle get past him. Toews took the shot with Blues defenseman Kevin Shattenkirk in front of him, and it squeaked through Miller's legs. "After that I feel like I competed an battled," said Miller. "There are going to be moments where things aren't going to go your way, you just have to keep moving forward." Later, with St. Louis making a late push, Crawford was able to get his glove on Pietrangelo's re-directed shot from the right side, knocking it down. "He saw everything," said Toews. It was the Blues' last good chance before Kruger sealed the Chicago win with his empty-net goal with 20 seconds left. Game Notes Duncan Keith, Sheldon Brookbank, Brandon Saad and Michal Handzus each had an assist for Chicago. It was Saad's second assist of the series ... Chicago was 0-for-4 on the power play and St. Louis went 0-for-3.
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Boston-area rock fans already know the Adam Ezra Group is one of the region's hottest acts, with a reputation for galvanizing live shows and smart songwriting. But they've also always kept a relentless touring schedule, all over the country, and this summer is no exception, with the band hitting the road around the first of July.
But first they have a little date on Boston Harbor, headlining Sunday afternoon's Rock and Blues Cruise, which leaves from the World Trade Center terminal at 3 p.m. Tonight (Friday) they're going to be opening for Willie Nelson and Allison Krauss, at the Meadowbrook Pavilion in Gilford, N.H. Later this summer, after their national tour, the AEG headlines the free concert series from Project Arts in Plymouth, on August 27.
Inquiring minds wanted to know, first of all, how the heck the AEG managed to secure four dates in Montana, July 2-5, starting in Glasgow, Montana and ending at the exotic sounding Zebra Lounge in Bozeman on the fifth. A Boston band with that much fan appeal in the Great Sky State?
Ezra laughed good naturedly, and assured us the band had toured all over the West for as long as they could, and in fact there were rock fans out there along with the mountain lions.
"First off, we have a booking agent who did a wonderful job," said Ezra from his new apartment in Chelsea. "Every year we have tried to trek out west, because we love that area, and have had some incredible shows in Colorado, for instance. This time, the first offer we got was for the Yellowstone Festival on July 4. That seemed like a really fun way to celebrate the Fourth, so we agreed to that. Last year we had played Glasgow, which is way up by the Canadian border, so we told them we'd be coming through if they were interested again. Eventually we filled in our week with those four dates."
"In the indie music world we work in, you play anywhere and everywhere you can," Ezra added. "I'm still thrilled people want us to play anywhere, and I've been at this for about fifteen years. This is really the first time in my career that we have more calls than we can handle. I'm still amazed people pay us to play music. We take as many dates as we can make, and it feels incredibly good, and gratifying, to have so many people wanting us to play for them."
Longtime AEG fans know Ezra is a Wayland native who went to Colgate, where he spent most of his spare time playing lacrosse. It was only after college that he began exploring music, and also bouncing around the country, working various jobs and honing his musical chops. Ezra's debut recording was a solo CD in 2000, but a few years later he had crafted his vision into a band, where his infectious, rhythmically pulsating style captured fans almost immediately.
The AEG includes Ezra on acoustic guitar and vocals, Corinna Smith on fiddle, Francis Hickey on bass, Josh Gold on keyboards, Alex Martin on drums, and the percussionist known as Turtle. Ezra's songs tend to be compelling vignettes, often with a humorous twist, but just as often with subtle reminders that we're all in this together. Critics have compared his music to the Dave Matthews Band, both for his acoustic guitar/frontman role and for the tendency to jam out, but the anthemic quality of many Ezra songs also prompt comparisons to Bruce Springsteen.
When we heard AEG perform last fall, at the release party for their "Better Than Bootleg: Vol. 1" live record, a couple of Ezra's more folk-rock tunes reminded us of Jackson Browne, and one evoked the best of Harry Chapin. He also proved he can sing a cathartic soul song with the best of them that night. The bottom line is AEG's music uses a wide palette, but it's always a warm and lively dance-rock concoction.
"Oh, my God, when people compare me to Bruce Springsteen," Ezra exclaimed. "That is the most validating thing for a songwriter like me to hear. Bruce is an incredible writer, who's created an incredible legacy in the musical world. I don't know if I deserve that comparison, but I am honored for sure if I can."
"I'm also a big fan of Dave Matthews, who is a unique writer himself," said Ezra. "It is rare when someone with such a simple approach can connect so powerfully. I love the Dave Matthews Band comparisons because they also place such an emphasis on their live shows."
While a casual listener might suspect Ezra crafts his story-songs with words initially, it's just the opposite.
"I write a lot of songs, a lot of different ways," Ezra noted. "The process varies, but the music always comes first. usually I'll be noodling on my guitar, or more often recently on my piano, and whatever feeling the music brings out inspires the concept of the song. In that sense, when I'm coming up with the words, I'm trying to figure out what the song is already about. I flesh it out and see where the song will take me. But the lyrics always tend to flow in afterwards, when the music is set."
"I look at songwriting like puzzle-solving," Ezra added. "If I know where the emotion is in the music, then I can determine where the song wants to go. And I bring a lot of music to the table for the rest of the band, and they add whole new elements to them."
Like many bands with sterling live show reputations, the AEG faces the challenge of re-creating that magic on record. That's part of the reason for the "Better Than Bootleg" live CD last year, intended as the first in a continuing series.
"It is very difficult to capture the feel of our live concerts on record," said Ezra. "I write a lot of songs, and we play a ton of different songs, and we always felt we never had a record that did justice to our live show. What we've done is have Josh Gold training as a recording engineer, along with his keyboard work. The idea is to turn our touring operation into almost a mobile studio, with the aim of releasing content, content, content. Every show is a different experience, and we feel it is very cool to offer fans as much music to consume as possible."
Again, longtime AEG fans know that the merchandise table at live shows offers CDs for whatever price the buyer feels is fair. Getting their music out to the public is AEG's primary aim.
"Better Than Bootleg-Vol. 1" was intended as the first of a series," Ezra explained. "We're setting up our tour infrastructure so that we can release live music once or twice a year, and coordinate it with our studio albums too. Releasing an album used to be a big deal, but now with websites, Twitter accounts and so on, you can get the word out almost instantly. Our policy of 'pay whatever you want' has been hugely rewarding for us--people like it, and our music gets out."
"It's been a really slow game, one show, even one fan, at a time," Ezra summed up. "It has been a long road to get where we are, but I don't regret the path we took. It's been very inspiring to see it grow, and our fans interacting. This cruise of Boston Harbor will be a great way to kick off the summer for all of us."


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As Kelly Weaver walks through the halls of the Alexander Leigh Center for Autism in Crystal Lake (alexanderleighcenterforautism.com), she beams with pride.
"We started with one student in my basement back in 2007," says Weaver, the center's executive director. "Now we have 27 students ages 3 to 15. In August we started our first freshman high school program, which was very exciting."
Weaver's passion for providing autistic students with comprehensive care is deeply personal. Her only child, Gillian, born in 1998, "descended into//?// autism" at 15 months, she said.
"I'd gone through seven years of infertility and tried to get pregnant — then we have this beautiful, fabulous baby, and she was going to be different than we anticipated," Weaver recalls. "There wasn't a lot of information on autism at that time, so I Googled it. There was nothing but horrible things online. I sort of threw myself across the bed and threw up a couple of times. At that time autism rates were 1 in 5,000. Today the CDC rate is 1 in 88. We have a pandemic going on."
As Weaver tried to learn more about having a child with autism, tragedy struck her family in several ways: She discovered she had ovarian cancer, and her husband, Kevin, was diagnosed with a brain tumor.
"He passed away eight months after his diagnosis, when Gillian was 4," she says. "It was a very challenging part of my life."
After the death of her husband, Weaver realized the public school system wasn't meeting her daughter's needs, so she focused all of her energy on creating a center for children with autism.
"My friend Dorie (Hoevel) — we both have children with autism — so we sat down one night and tried to map out a plan of where our kids were going to go for treatment," she says. "We thought, 'If we were in charge, what would it look like?' We started with a sheet of paper. Her (child's name) is Zachary Alexander and mine is Gillian Leigh, which is how we got the name of our school — Alexander Leigh. We named it after our kids, so we constantly remember every time we walk in the door what we are working for."
The following is an edited version of our conversation.
Q: How's Gillian doing now?
A: She's 14 and in the freshman class here at the center. She's talking. She can read. She does all kinds of things in the community. She lost her "severe" diagnosis about a year ago, which was a big "to do." In the public school Gillian didn't speak and didn't read, so to have her read a story or say, "Hi, Mom!" when I walk through the door or "Love you, Mom," those kinds of things are pretty spectacular. And the blessings just keep coming. This has certainly been challenging, but it's never been hard. I go out on the floor and watch the kids and see them do something that's really cool, and I'm quickly reminded of why I'm doing this.
Q: What makes your autism center so unique?
A: Our school runs differently because I'm a parent with a child with autism. Not a lot of schools have parents who have developed (the curriculum). … This model allows us to evoke more change. It's more personal. It's more intense, but parents can come and grow. We are a therapeutic day school, so we offer several types of therapies depending on the child's needs. We're also a nonprofit, so we have fundraisers and accept donations so we can continue to grow. The ultimate goal is functional independence and to be able to integrate these children back into public schools. The earlier we get the students, the better that chance is. … Early intervention is really important for development of all kids, not just kids with autism. We're learning the most up until 8 or 9 years of age.
Q: What advice would you give to a parent who may be dealing with similar challenges?
A: You have to trust your gut. I knew in my gut that there was something not quite right about an occupational therapist (who) was assigned to my daughter's case who had never met a child with autism, let alone worked with them. … So I started searching for therapists who were at the top of their game in treating children with autism. And if I were to be really honest with myself, I knew something wasn't quite right with Gillian when she was a year old. … As a parent, usually what holds us back is our fear. We're afraid to learn the truth.
There is so much focus on perfection in this day and age. … You can either feel your child is slowing you down and has changed what you thought your life was going to look like, or you can choose to be an autistic family. Once that shift is made, you really begin to see the families thrive.
Q: As a society, are we making enough strides treating kids with autism?
A: Yes and no. My daughter was in the first wave of autism, so certainly the kids who are diagnosed now have more resources available. The scary component is going forward: Services completely drop off, so that's why we're working so hard to get the high school classes and a transitional plan for adult living. Because if you think about it, in 30 years we're going to have a population where one out of 88 adults will be autistic. That means at any given time in Wal-Mart there's going to be one to two adults with autism in there. Many folks with autism are not able to live independently as of yet, and there's nothing planned for that, so it's very frightening actually.
Q: What keeps you going, given the challenges you've faced?
A: I really can say that I know that I'm living my purpose. ... Something good always comes out of every situation. It's always up to us to be patient and trust the process to find out what that is.
Drawing inspiration
We asked Kelly Weaver how she keeps facing the challenges life throws her way.
"Swimming in my own lane," she says. "Not looking back and not looking to the side. And really taking my responsibilities seriously."
Twitter @jenweigel


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HP is taking its networking fight with Cisco Systems out of the data center and into corporate campuses and branch offices.
Cisco has made a fortune – maybe several fortunes – selling multiple-tiered Layer 2/3 networks that span data centers, campuses, and branch offices, and the company's rivals are trying to flatten and simplify those networks to steal business away from a Cisco that has been distracted by its entry into the server and consumer markets. The Networking division of IT giant Hewlett-Packard, bolstered by its acquisition of 3Com, is one of the Cisco rivals that wants to take a piece out of Cisco's hide. Or rather, fabric.
At the Interop networking trade show in Las Vegas today, HP is announcing a new lineup of A Series campus core switches that hook into its recently upgraded line of E Series modular access switches and wireless access points to create a campus-wide fabric that is, say HP executives, flatter and cheaper than the way Cisco wants customers to build their networks.
"There's too many layers," Mike Nielsen, director of solution marketing at HP Networking, tells El Reg. "There are three layers in the data center network because Cisco told us to do it that way. There are three layers in the campus network, and that's too many."
The big complaint is the three tiers of the network: the core switching, the distribution tier, and the access layer. Sometimes you need those three tiers, but sometimes you do not. According to research by HP, there is about $1.5bn in "stranded capital" globally wasted in the distribution tier and maybe another $1bn in the access tier that is the result of bad network design for campus networks.
To help flatten out the networks, HP has cooked up the A10500 core campus switch, which allows customers to get rid of the distribution tier, hooking the A10500 core switch directly into the E5400 and E8200 access switches to build out a campus network.
HP's A10500 Series campus core switches
There are three A10500 models, and they borrow technologies that are used in HP's A12500 data center core switches and the A7500 line of campus switches. The A10504 is the entry machine, and the A10508 and A10508-V are the big bad boxes that mount the networking I/O modules either horizontally or vertically in the chassis.
The A10508 has a backplane that packs 5.75Tb/sec of bandwidth and has 1.28Tb/sec of switching capacity; it has a packet-forwarding rate of 960 million packets per second. It comes with two engine slots, four vertical fabric module slots (in the back of the chassis), and four horizontal I/O line cards (in the front). It can be configured with up to 192 Gigabit Ethernet ports or up to 64 10 Gigabit Ethernet ports. The machine has three 2,500 watt power supplies plus one spare in a standard configuration. The 10GE modules come in 4, 8, or 16 port flavors using XFP or SFP+ cabling, or 24 and 48 port variants using XFP or SFP cabling.
The A10508 and 10508-V basically double up the networking capacity. These boxes have two engine cards and have a backplane that delivers 11.52Tb/sec of bandwidth, 2.56Tb/sec of switching capacity, and 1.92 billion packets per second of forwarding capacity. The bigger A10500 core campus switches have four fabric slots, just like the smaller model, but have eight line cards for a maximum of 384 Gigabit ports and 128 10GE ports. This unit also has five 2,500 watt power supplies plus a spare.
HP says that the port-to-port latency on the A10500 core switches is around 3 microseconds. You can gang up to four of the A10500 chassis together (burning some of the ports for interconnection) to create a 1,440 "super core" switch. And the switch chassis have enough bandwidth that they can support future 40GE and 100GE line cards, when they become available.
Nielsen says that the A10500 has 3.7 times the 10GE port density of Cisco's Catalyst 6509 core switch in full-on configurations, and offers 75 per cent lower latency and 3.5 times the switching capacity. And the E5406 access switch, which is paired with the A10500, offers sub-3 microsecond latency – 90 per cent lower than Cisco's Catalyst 4506 access switches – with 128 per cent higher port density and 35 per cent lower energy consumption.
HP will start shipping the A10500 core campus switches in the second half of this year. Pricing was not announced.
In March, HP rolled out three E-Series wireless access points, which complete the network picture. These wireless access points pack two radios and offer 450Mb/sec of bandwidth, which is three times what you get on a typical home Wi-Fi router and 50 per cent better than the typical enterprise-class access point, according to Roger Sands, director of wireless networking at HP. These wireless access points were developed by HP ahead of the 3Com acquisition, by the way, and the company is cooking up devices that provide 600Mb/sec of bandwidth in the future.
HP's wireless access points
The E Multi Service Module (MSM) 430 is a dual-radio access point with two spatial streams. It costs $699. The MSM460 and MSM466 each have two radios, but have three spatial streams for better wireless fidelity; they cost $999. The MSM430 runs at 300Mb/sec with two streams while the MSM460 and MSM466 run at 450Mb/sec with three streams. The MSM430 and MSM460 share the same packaging (on the bottom in the picture), while the MSM466 (shown on top) has ports to plug into a number of different antenna options and operates both radios in the 5GHz band. The MSM430 and MSM460 each have one radio running at 2.4GHz and the other running at 5GHz.
In addition to the new core campus switches and wireless access points, HP is rolling out Intelligent Management Center 5.0, a tool that comes from 3Com that is used to monitor and manage HP's own networking gear as well as that of Cisco and other networking equipment makers. More importantly, says Nielsen – who used to work for Cisco – HP is offering one tool where Cisco has 28 different tools spanning its products. IMC 5.0 federates network management and server orchestration and converges both physical and virtual network management, all from the Holy Grail of a single pane of glass.
IMC can manage wired and wireless networks from the core to the access layer, and it can be used to initiate virtual machine migrations by hooking into hypervisors and their APIs or it can watch a virtual server move and then make sure that its network follows along with it reactively. With IMC 5.1, which will be available by the end of the year, the tool is being integrated with HP's VirtualConnect virtualized network fabric and switching for its BladeSystem blade servers, so it can work in concert with that blade machine's automated server provisioning.
IMC 5.0 supports 2,600 different networking devices across 35 different manufacturers – and over 1,000 of those devices that it can manage have a Cisco brand slapped on them. "A lot of people start out buying IMC and then only later buy HP networking devices," says Nielsen. This is probably the kind of thing that will get new HP president and CEO Leo Apotheker giggling while rubbing his hands together. IMC 5.0 costs $6,995.
In addition to the new core switches and updated IMC software, HP is rolling out reference architectures for fabrics in the data center, which HP calls FlexFabric, and is gearing up to do the same for campus-wide networks (FlexCampus) and branch offices (FlexBranch). The idea is to have one set of software tools to manage physical and virtual networks across data centers, campuses, and branch offices while at the same time flattening out networks by eliminating the distribution tier wherever possible.
"We think we are the most credible alternative to Cisco in the market today," says Nielsen. "We are the challenger and we think we have a better way to do things." ®
Sponsored: Webcast: Discover and secure all of your attack surface


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My Craft Corner
Oh, hello there! So happy you're here to check out my crafty nook! You might be surprised that I don't have a craft room or studio. Actually, I haven't had a craft room in years, but that hasn't stopped me from making. Today I'm going to walk you through my creative space, shelf by shelf. If you're without a craft space, that's DEFINITELY OK! You can pack so much into one 3 tiered bookshelf (see below) if need be.
No room for a bookshelf in your home? That's fine too. You can always grab a craft cart or even a plastic storage bin that you can slide under your bed.
Ok, so lets get into these shelves...
(Top to bottom, left to right)Top
-Crepe paper (LOVE using this stuff for making pocket letter embellishments.)
-Journaling cards, embellished pocket mail cards, ATC size-precut cardstock
-Sizzix BigShot (seriously the BEST diecutting machine out there!)
First Shelf
--Reset Girl A5 Ballerina Planner (See my 2017 planner setup)
--Happy Binder, Target Dollar Spot binder (How to Make a Happy Binder aka Junk Journal)
--Kate Spade wallet (too big for my current purse, so I just put it here cause it matches!)
--Heidi Swapp personal memory planner
--Cream Recollections personal planner (first collection)
--Websters Color Crush Travelers Notebook in Rose Gold, similar (Check out some of my creative journaling layouts!)
--Beige Storage box (different mini accordion folders with die cuts, stickers, ephemera, etc.)
--Clear Document holder (scraps of patterned cardstock)
--Striped file folder organizer (digital paper, printables, Pocket Letter® printables)
Second Shelf
--First organizer (Bakers twine, ribbon, twine, embroidery floss, gold thread, cotton cord)
--Middle organizer (Scissors, pens, watercolor brush pens, watercolor brushes, adhesive, Tim Holtz Tiny Attacher, Tombow Dual Brush Pens for handlettering, Sizzix Die Brush, white ink pens, Calligraphy Set, pencils, odds & ends)
--Last organizer (Doilies, envelopes, bags, thank you cards, blank card and envelope sets)
Third Shelf
--Craft Tools Bin (Ranger Heat Tool, hot glue gun, Martha Stewart mini Scoring Board, Angora Watercolor Palette, notebooks, journals, watercolor pad, long-reach stapler for DIY notebooks, paper cutter/trimmer)
--Mambi Striped Organizer (stamps, acrylic blocks, embossing powders, stamp pads)
--Sticker Bin (alpha stickers, Etsy shop stickers, Tim Holtz phrase stickers, planner stickers, Sizzix stickers, David Tutera for Sizzix planner stickers)
Not pictured
-I have my e-cutter (Sizzix Eclips 2) off to the side on the floor. Ha! I still don't know where to put it, but I hope to purchase a desk really soon.
-I have a train makeup case full of washi tape! It's on the bottom shelf of my coffee table.
Now that I've shared my craft space, tell me about yours! Do you have a whole room to yourself? Do you have a bookshelf like me? Let me know. I LOVE hearing from you!
*This post contains affiliate links. That means I might receive a commission from any purchases you make using one of these links. This doesn't cost you a thing and helps me out! Also just wanted to mention that there's absolutely NO PRESSURE to buy anything. Ever! This is just something I do in case you're interested in any of the products you see. Happy browsing!
2 lovely comments
I generally reply by email, unless you are a No-Comment-Reply Blogger.
Thank you for making my day!


text: Watch and be seen - what would be a city like Vienna without its ''Schanigärten''? Enjoy moments of leisure and watch the colorful life on Vienna's most beautiful pedestrian zone in our open-air café. The elegant café is located right in front of the Hotel on the exquisite shopping street Kärntner Straße. Opened from mid-March to mid-October it is the perfect place to pause for some pleasant moments and enjoy the bustling activity of downtown Vienna.


text:
Officials say a multi-million dollar traffic system upgrade is on track and on budget.
Officials say a multi-million dollar traffic system upgrade is on track and on budget.
Anthony Prinz, transportation services administrator for the City of Jacksonville, said the project will upgrade the 10- to 15-year-old technology operating the area�s traffic system.
The project consists of updating 90 traffic signals, placing about 50 closed-circuit cameras that will let staff monitor congestion and other traffic problems � and nine message boards in congestion-prone areas to warn motorists of delays with enough advance to allow for detours.
�This is probably the most cost-effective investment in a roadway system like Jacksonville�s,� Prinz said.
He said a project such as the Jacksonville Parkway that will stretch from the end of the Jacksonville Bypass at Marine Boulevard to Western Boulevard Extension, primarily impacts one part of Onslow County and costs $28 million. The signal project, estimated to cost $5 million, will affect every driver in the community, he said.
�When you can invest $5 million and change every traffic signal in the city, that�s a lot of bang for your buck,� he said.
The current �unintelligent system� doesn�t allow for special circumstances, such as holidays or wrecks, Prinz said, but the new system would allow for more flexibility.
For example, specialized signal timing would be possible when area Marines are released for a long weekend or holiday, causing less congestion on N.C. 24.
The project is a cooperative effort with the Federal Highway Commission, N.C. Department of Transportation and City of Jacksonville with the commission and DOT paying the first $5 million of the project and the city paying the costs of anything after that. Camp Lejeune was also involved in the planning process to make sure the system can support base-related traffic patterns, though the systems are not connected. Prinz said that ideally the system would communicate with the traffic system aboard Camp Lejeune once both systems have up-to-date technology.
Once the project is complete, the City of Jacksonville will maintain the traffic system. They are currently working to hire a traffic signal system engineer who will be responsible for operating and optimizing signal timing and responding to incidents such as wrecks and coordinating the traffic signal with first responders. Currently there are two maintenance technicians who are helping with the project�s construction, and a third will be hired next year.
While Prinz was unsure how much the positions would cost the city, he did say that the N.C. DOT will help fund system maintenance and operation, including staff and equipment. For example, the engineer position will be 98-percent funded by the N.C. DOT, he said.
The engineer�s office will be in the new Department of Public Safety, next door to the E-911 center, Prinz said. That office will receive all the traffic data from the new system, including the cameras and message boards.
�Who better to maintain the system than people who live here and work here on a daily basis?� he asked.
According to Prinz, the construction of the message boards will begin in the next month; and staff plans to begin testing the new system toward the end of the year. Monitoring and troubleshooting is expected to be complete by next summer when the system would be turned over to the City of Jacksonville for maintenance.
Amanda Hickey is the government reporter at The Daily News. She can be reached at firstname.lastname@example.com.


text:
A federal judge in Pittsburgh has dismissed a lawsuit filed by four people who bought tickets to the February 2011 Super Bowl in Dallas, but had to watch the game on TV because the seats weren't properly installed in time for the game.
U.S. District Judge David Cercone dismissed the fraud claim saying the people who bought the tickets can't prove that the National Football League and the Dallas Cowboys -- whose brand-new stadium hosted the game between the Green Bay Packers and Pittsburgh Steelers -- intended to defraud anyone.
The judge says the case is a contract dispute, but that the ticket holders can't pursue it in federal court because the combined valued of the tickets, travel and hotel costs doesn't exceed $75,000.
The latest news from around North Texas.
A separate trial for hundreds of other ticket holders is scheduled in Dallas in October.


text:
About Us
The Vanderbilt Institute for Global Health's Student Advisory Council is comprised of graduate and undergraduate students from various schools across the university. The purpose of the Student Advisory Council is to bring together diverse students interested in global health with the goal of fostering cross-disciplinary student networking and collaboration. Members of the Student Advisory Council are responsible for bringing the student perspective to the institute, especially with regards to student opportunities and experiences.


text:
A Developer.com Site
An Eweek.com Site
how can i use 'append' clause in spool file to keep my existing spool file and add to it whenever i re-login
Try this:
OCP DBA 7.3, 8, 8i, 9i, 10g, 11g
OCA PL/SQL Developer
Oracle ACE Director
My website: oracle-base.com
My blog: oracle-base.com/blog
hi tim
its not working in that way also as iam using oracle 9i
i write this in glogin.sql file:
column l_date new_value l_date noprint
select to_char(sysdate,'DDMONYYYY') l_date from dual;
spool c:\sqllog\log_&&l_date append
and when i login to my sql it gives following error:
Illegal spool file name: "c:\sqllog\log_14FEB2006 append" (bad character: ' ')
is there any other way. i don't want to overwrite the previous data in my spool file that was created very first time i logged to my SQL.
no, cant do that, 9i doesnt support appending to a spool file
You could create a sequence and use that in the file name OR use sys_context('USERENV','SESSIONID') - either way every logon will have a unique file name. eg:
select to_char(sysdate,'DDMONYYYY')||'_'||sys_context('USERENV','SESSIONID') l_date from dual;
"The power of instruction is seldom of much efficacy except in those happy dispositions where it is almost superfluous" - Gibbon, quoted by R.P.Feynman
And yet another idea. If you're on UNIX create an alias in your .profile for sqlplus:
alias sqlplus='sqlplus /nolog 2>&1 | tee -a mysqlplus.log
I believe this should work
alias sqlplus='sqlplus /nolog 2>&1 | tee -a mysqlplus.log
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text:
Nobex Radio Companion goes global with v 22.214.171.124. Nobex announced that it will add over 1000 worldwide
stations bringing its total station selection to over 2000. Nobex will be adding 17 countries, including
Mexico, Brazil, France, and Spain. Local stations are free, but to tune in to the international stations you
need the premiere package, which is $19.99 a year or $3.99 a month.
Don't see a station you like? Submit it by clicking here.
Pick up Nobex by pointing you Blackberry browser here.


text:
Post rny throw up
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Recent Status Updates
For 5 months I've been telling the doctor's that there is a stricture in my esophagus. "We need to run more test, figure this out, doesn't seem like you have a stricture. Let us be the doctors, you do not have a medical degree". And the likes.· 0 replies
The test came back today.
I have a stricture in my esophagus. Thinking about putting an M.D on my mail box.
- This update has no replies.
Finally two weeks off! Going on vacation this night!· 2 replies
Went to the hospital's clinical nutritionist today, and she told me to eat more oats and try healthy cereals. I am so glad that someone has given me "permission" to eat grain. I have a stressful relationship with grains😬· 4 replies
I felt the same way about sandwiches. The dietician said I was being too strict with myself about them and that I should try to reintroduce them. I "can" or more like allow myself them now and it hasnt affected me too much now that Im trying to hold a stable weight. Not to mention, I can just cut them out again if I want to lose weight again.
I hear you. I was happy when I could add some grains too. I added multi grain rice crackers which I use to carry avocado, hummus & liverwurst (poor man's pate lol) for my snacks. I was already eating rolled oats for breakfast about 3/4 days a week but now have it most days. The grains help with regulating the bowels & also help with eradicating that slightly gaunt, hollow look weight loss leaves on our faces. Yay!
I feel the issue with grain is that it is so undecided. Some people treat it like the devil. Others pile on grain. I am not talking about eating fine white baking flour with a spoon. But oats, one of the healthiest things that can be eaten in the world. I should be allowed to eat it - but it is a metal blockage for me were I wonder is bad or is it good for me, like really?
I haven't eaten much bread for years, but sometimes it would be nice to just make a sandwich, easy and guilt free without having to cook something.
I didn't think I had lost a significant of weight either the past 2 months, but it turns out I lost 11 kgs for 10 weeks 😮 She straight out said to me "the weight is just falling off you, and you need to eat more, you will benefit from grains". Never in my life has someone said to me until the past 2-3 months "eat more"😂
I swear I eat more now than I did most days when I was overweight - only ate one or two meals a day. Now it's three meals & three snacks. I ate rolled oats throughout my weight loss though then a serve lasted three or four days now it's two days. It does get so confusing: you shouldn't eat this then oh yes you can eat that. I think moderation is the key in everything for us now. Rolled oats, a small slice of bread or crackers a couple of times a week should be ok as long as they're nutritious multigrains. It's not like eating a whole packet of biscuits or a full loaf of bread in one go. Add one multi/whole grain to your diet & see how you go.


text: This news item expired on 1/15/2013, so the information below could be outdated or incorrect. Weight of the Nation Event Everyone is invited to participate in the Weight of the Nation event on January 15 beginning at 5:30 p.m. at the UNC Asheville Sherrill Center, Mountain View Room. In the United States, two-thirds of all adults and almost one third of our children are overweight or obese. North Carolina is the 14th most obese state in the nation. The Weight of the Nation event aims to present a solution and encourage conversation about the problem we all know exists by bringing together people from all parts of the WNC community. Registration is from 5:30 - 6 p.m., with opening remarks at 6 p.m. Snow date set for same time and location on Tuesday, February 5. Register for free at ashevillechamber.org/event/weight-nation. To learn more about this movement, check out the HBO documentary. For more information or general questions - contact Margarita Gonzalez at firstname.lastname@example.com or (828) 775-7079. Media questions - contact Virginia Maziarka at firstname.lastname@example.com or (828) 210-9603. Table: News Item Documents File NameSizeTypeDate & Time Added Weight of the Nation Event Flyer 432 KB 01/02/2013 1:25 PM


text:
Warm up in these incredibly comfortable open-bottom sweatpants. Made from cotton/poly fleece, they feature an elastic waist. Great for teams, but perfect for just hanging out. No drawcord on youth sweatpants.
Every order is custom printed and personalized to your needs direct from our production facility in Detroit, MI. Items are typically completed within 5 business days and then require additional shipping time to reach your location. Bulk orders of 12 or more items will take 7-10 business days for production.


text:
Both Havelock and West Craven had a lot on the line in Friday�s Coastal Conference Boys� Basketball Tournament Championship.
VANCEBORO � Both Havelock and West Craven had a lot on the line in Friday�s Coastal Conference Boys� Basketball Tournament Championship.
Havelock was trying to win its first title in recent memory, while West Craven was aiming to repeat as champs, and truly finish the conference season and postseason undefeated.
In a hard-fought battle, West Craven was a smidgen tougher by outlasting the Rams, 72-64.
Josh Cuthbertson scored 32 points, 16 in the third quarter alone, and snatched 12 rebounds.
He also passed Kinston and North Carolina legend Jerry Stackhouse in North Carolina high school career points.
�The whole team has to step up and they did tonight,� West Craven coach Bryan Goehring said.
�We�ve been through a ton of close-game situations that have prepared us for tonight. The defensive intensity picked up in the second half."
The Eagles led, 52-48, after three quarters, and iced it away with converted free throws and in-your-face defense that forced Havelock turnovers.
�My guys played as hard as they could tonight and with their (West Craven�s) athleticism, we came up just short against them again," Havelock coach Bill Fryczynski said.
�I can�t remember the last time we lost two in a row, so going into the playoffs as conference runner-up, and playing in the game for the first time since nobody knows when, I�m very proud of the guys this year.�
Demetres Abrams added 20 points to the Eagles� tally and Tyrone Brown just missed a double-double with nine points and nine rebounds.
The Rams were led by Matt Prichard�s 15 points, while David Carter added 14, Zack Bruns 13 and Pharoh Cooper put up 11.
�It just feels great to be conference champs again as a senior,� Josh Cuthbertson said.
�Havelock came to play tonight and we knew they would, but my guys stepped up and wanted it a bit more. It makes me feel great as a star player because I know I can�t do it by myself.�
The Eagles and Rams both will have home playoff games Monday, as the 3-A state tournament gets underway.
West Craven (72) - Josh Cuthbertson 32, Demetres Abrams 20, Tyrone Brown 9, Zac Cuthbertson 4, Anthony Oates 4, Andrew Reid 2, Kylikke Green 1.
Havelock (64) - Matt Prichard 15, D.J. Carter 14, Zack Bruns 13, Pharoh Cooper 11, Kyran Bowman 7, Shondel Granison 4.
Jordan Honeycutt can be reached at 252-635-5670 or at email@example.com. Follow Jordan on Twitter @JHONEYnbsj29


text:
MadView3D 0.4.1: Cross-Platform 3D Model Viewer
0 Members and 1 Guest are viewing this topic.
Javascript Library for GPGPUWebCLGL is a free Javascript library for general purpose computing using WebGL. It uses a code style like WebCL to handle the operations and then translate to WebGL code. The library is not 100% the same as the future WebCL specification nor has all its advantages, but it is already very usable.


text:
Product Information
The KTX 3 electrical element offers adjustable temperature levels ranging from 30°C to 60° in steps of 1°C. An electronic temperature sensor guarantees precise temperature control. The device displays the current set temperature level and indicates the status of the heating cycle or standby state. It also has an easy interface for controller programming. The KTX 3 utilises the Terma-Split System allowing disconnection of the heating element (Terma Split) from the controller..
- Colour: Chrome
- Watts: 300W
- In the event of a power failure, the electrical elements remember the previous setting (last setting used) enabling collaboration with external timers and intelligent building systems.
- Equipped with an easy to read LCD display with clock
- KTX is equipped with frost protection (ANTIFREEZE )
- A function that allows a controlled temperature and drying time, after which the heater will return back to its previous state.
- A 24-hour timer allows you to program up to 4 intervals for heating at a pre-selected temperature or to switch between heating and power off states.
- Supplied with a 2 years warranty
Item Code:


text:
The Acumen of Dedicated Security Analysts
Psicurity analysts extensively assess and document networks to identify and mitigate risk. The quality of our documentation and focus on customer relationships facilitates consensus among executives, managers, and staff who are working together to improve security.
Countless products are meant to defend networks, and detect vulnerabilities. But, no product replaces dedicated security analysts.


text:
This is very much a noob question, and for that I apologize.
I want to make a dialog in visual c++ 2008. Apparently I must use the "MFC Wizard". When I click new project, this does not come up as one of the options
So, how do I add custom dialogs to vc++2008 project?


text:
- you must be a cook and somehow remain a cook
- you must have 99% of turns taken or better
- you must be able to speak english fluently
- you must have a sense of humor
- you must want to kick ass in team games with 300spartans
- you must embrace your awesome rank and put fear into your enemies
- you must be open minded
- you must participate in team chat
- you must be willing to try new game types especially freestyle
- you should be over 18
Q: What do you see when the Pillsbury Doughboy bends over? A: Doughnuts!
Q: What did the baker say to the hot girl? A: I'll put a bun in your oven!
Q: What happened when the baker's wife came home early? A: She caught her husband Masterbaking.
Q: Why are bread jokes always funny? A: Because they never get mold!


text:
Vermont Association of Naturopathic Physicians
"The highest ideal of cure is the rapid, gentle and permanent restoration of health…in the shortest, most reliable, and least disadvantageous way, according to clearly realizable principles." —Dr. Samuel Hahnemann, 1842.
Welcome to the official website of the Vermont Association of Naturopathic Physicians (VANP). The VANP is comprised of Naturopathic Physiciains trained at one of the accredited four year medical schools throughout Canada and the U.S.
Through this site you can find a physician near you who is trained to provide the finest in complementary and alternative medicine, learn more about Naturopathic medicine, support our organization and find links to related fields.
This website has been generously sponsored by the following companies which support Naturopathic medicine:
Looking to purchase for the VANP Pharmacology Review webinars by Dr. Paul Anderson? Click here


text:
Event Organiser: Travel Bulletin
Date(s): 06/07/2020
Time: 6:00 pm - 9:30 pm
Venue Address:
Bristol Marriott City Centre
2 Lower Castle Street
United Kingdom
Event Website: link
Add to your Outlook Calendar
Travel Bulletin hosts the UK travel trade's most educational and enjoyable travel agent training showcases.
Over the past 9 years we have hosted a series of destination and themed showcases, bringing a range of key suppliers and learning opportunities to our travel agent readers.
Attending agents continually feedback to us on the wealth of product knowledge they have gained at our showcases.
But it's not all work, work, work…we also lay on some generous hospitality in the form of delicious hot food and drink, live entertainment and an unbeatable range of prizes.
At each showcase, a sizeable proportion of agents have walked away with some stellar prizes including: luxury resort stays, hampers, return flights, fam trip places, shopping vouchers and much much more…!
What do other agents think …???
"An excellent event, thank you. I thought the variety of suppliers was excellent and despite having just 8 minutes, all got their key points across and the opportunity to continue to chat at dinner was superb. Thank you for all the time and effort put in to provide such a great event."
Alistair, Dorking Travel
"Thanks Jeanette, I did enjoy the evening and event – well run, good atmosphere and you (Matt etc) looked after us well. I liked the 'speed dating' style table hopping with the Suppliers. Excellent material and appreciated the food, drinks vouchers (two would have been fine, not 4!) and of course the venue."
Ian Bisset, Travel Counsellors
To confirm your teams places, call us on: 0207 834 6661 or email: email@example.com
See you soon, Hannah, Ashweenee, Alice, Jeanette, Simon, Matt, Sarah, Bill and Tim.