text:
A new option for chemoprevention of invasive breast cancer
STAR trial studied a galaxy of SERM effects
CASE Should she start a SERM?
A 55-year-old postmenopausal woman who has not had a hysterectomy completes a breast cancer risk assessment form and discovers that her estimated 5-year risk of breast cancer is 4%.
Should she consider taking a selective estrogen receptor modulator such as raloxifene or tamoxifen for chemoprevention of breast cancer?
Preliminary results from the Study of Tamoxifen and Raloxifene (STAR) trial clearly demonstrate that the osteoporosis drug raloxifene is an effective option for preventing invasive breast cancer in postmenopausal women at increased risk for breast cancer. Initial analyses of the STAR trial were released by the National Institutes of Health, April 17, 2006.
The study participants were an average of 58 years of age, and their calculated 5-year risk of developing breast cancer was 4%, as assessed by the Gail model,1 compared with the average population risk of 1.6% at age 58 years.
Equivalent results. Both raloxifene, 60 mg daily, and tamoxifen, 20 mg daily, were similarly effective in reducing the calculated breast cancer risk by about 50%. Both agents have been demonstrated to improve bone density.
Raloxifene was superior to tamoxifen on some important outcomes. For example, raloxifene was associated with 25% fewer deep venous thromboses, 35% fewer pulmonary emboli, and 36% fewer cases of endometrial cancer. Raloxifene may also cause fewer cataracts than tamoxifen.
Tamoxifen was superior to raloxifene in reducing the risk of 2 noninvasive forms of breast cancer. Tamoxifen, but not raloxifene, reduced the risk of developing ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS).
On balance, the results from the STAR trial largely confirm and strengthen previously reported results2-5 and indicate that both raloxifene and tamoxifen are effective agents for the chemoprevention of invasive breast cancer.
STAR: A productive collaboration
The STAR trial is an example of the high-quality, clinically important studies that can only be completed by the collaboration of the National Institutes of Health, hundreds of physician investigators, and the pharmaceutical industry. Almost 20,000 women were enrolled in the trial and followed for more than 4 years. Advances in medicine depend on large-scale trials that require the continuing collaboration of the government, the pharmaceutical industry, and practicing physicians.
Persistent questions
If we are to continue to develop breast cancer chemoprevention strategies, many challenges persist.
Is it prevention or treatment? One theoretical issue is: Are we really "chemopreventing" breast cancer, or are we actually treating subclinical, undiagnosed breast cancers? This question is difficult to answer with currently available diagnostic tools. Although of interest to the clinical investigator, the question is probably of little relevance to our patients.
STAR studied a galaxy of SERM effects
Women who participated in the STAR trial were postmenopausal, at least 35 years old (average 58 years), and had an increased risk of breast cancer as determined by their age, family history of breast cancer, personal medical history, age at first menstrual period, and age at first live birth.
The initial analysis is based on 19,471 women (of 19,747 enrolled) for whom complete study information was available: 9,745 in the raloxifene group and 9,726 in the tamoxifen group.
- Invasive breast cancer rates were statistically equivalent: 167 women in the raloxifene group and 163 in the tamoxifen group.
- Uterine cancers (mainly endometrial). More than half of the women enrolled in STAR had a hysterectomy. In women with a uterus, cancers developed in 36 of 4,732 women taking tamoxifen and in 23 of 4,712 women (36% fewer cases) taking raloxifene.
- Deep vein thrombosis (blood clot in a major vein) developed in 87 women taking tamoxifen and in 65 women (25% fewer cases) taking raloxifene.
- Pulmonary embolisms (blood clots in the lung) developed in 54 women taking tamoxifen and in 35 women (35% fewer cases) taking raloxifene.
- Strokes occurred in both groups at statistically equivalent rates: 53 women in the tamoxifen group and 51 in the raloxifene group had a stroke during the trial. Women at increased risk of stroke were excluded from the trial.
- Noninvasive breast cancer. While tamoxifen has been shown to reduce, by half, the incidence of lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS), raloxifene did not have an effect on these diagnoses. LCIS or DCIS developed in 57 women taking tamoxifen and in 81 women taking raloxifene. This result confirms data reported in the CORE Trial.5
What about aromatase inhibitors? Another important issue is whether aromatase inhibitors will prove superior to raloxifene and tamoxifen for chemoprevention of breast cancer in postmenopausal women.6 Evidence suggests that aromatase inhibitors are superior to tamoxifen for the prevention of disease recurrence in post-menopausal women with invasive breast cancer. It is reasonable, therefore, to expect that aromatase inhibitors might also be more effective for the chemoprevention of breast cancer. Currently planned clinical trials will answer this important question.
Can we afford chemoprevention? A critical practical issue is whether we have sufficient resources to support a nationwide breast cancer chemoprevention program. Experts estimate that as many as 9 million menopausal women in the United States are at increased risk for breast cancer. Who will identify these women and counsel them concerning the chemoprevention option? Who will prescribe and supervise chemo-prevention for these women?
Likely gynecologists, along with internists, family physicians, and oncologists will play a central role. ObGyns are experts in managing breast cancer screening using mammography. We also have experience prescribing raloxifene for osteoporosis. It would not stretch our current screening mammography practices to add the recommendation that patients perform a risk assessment using the Gail model,1 and consider chemoprevention if they are at increased risk.
CASE Consider raloxifene when uterus is intact
In the case of a 55-year-old woman with a 5-year breast cancer risk of 4%, a consideration of the risks and benefits may well lead to a recommendation to initiate chemoprevention with raloxifene. For this woman, with an intact uterus, raloxifene is likely the superior choice because of the increased risk of endometrial cancer associated with tamoxifen use.
Helpful web sites for you and your patients
The STAR trial is coordinated by the National Surgical Adjuvant Breast and Bowel Project (NSABP), a network of cancer research professionals, and is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health.
- Tools to calculate breast cancer risk
- STAR trial fact sheet NCI's STAR home page at
NSABP's Web sites at
or foundation.nsabp.org
- Q&A on STAR results
1. Gail MH, Brinton LA, Byar DP, et al. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst. 1989;81:1879-1886.
2. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90:1371-1388.
3. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 2005;97:1652-1662.
4. Cauley JA, Norton L, Lippman ME, et al. Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation. Breast Cancer Res Treat. 2001;65:125-134.
5. Martino S, Cauley JA, Barrett-Connor E, et al, for the CORE Investigators. Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst. 2004;96:1751-1761.
6. Cuzick J. Aromatase inhibitors for breast cancer prevention. J Clin Oncol. 2005;23:1636-1643.
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A multi-zone, multifinctional graft with two or more zones that have different chemical and biological characteristics is provided. The vascular conduit that has of an inner zone that is permanently non-thrombogenic and anti-proliferative, and one or more outer zones that allow for beneficial tissue in-growth and sealing of the graft to prevent leakage. The small diameter vascular conduits of the present invention containing these different zones may be fabricated from woven or knitted Dacron, extruded porous PTFE, from polyurethane polymer, or other similar materials, and the structure of these conduits so modified as to provide these different zones. One embodiment contains an inner non-thrombogenic layer and an outer thrombogenic layer, optionally containing a growth agent. A second embodiment contains a third intermediate layer having a growth agent impregnated therein.
1. A vascular graft having a lumen passing therethrough, said graft comprising:
a tubular wall structure including:
a first non-thrombogenic layer formed of a first material and forming the lumen, an interior surface of said first layer being treated with a non-thrombogenic agent, said first layer having a thickness less than 100 μm, and
a second thrombogenic layer outside said first layer and formed of a second material, an exterior surface of said second layer being treated with a thrombogenic agent, said second layer having a thickness less than 100 μm.
2. The vascular graft of
3. The vascular graft of
4. The vascular graft of
5. The vascular graft of
6. The vascular graft of
7. The vascular graft of
8. The vascular graft of
9. The vascular graft of
10. A vascular graft having a lumen passing therethrough, said graft comprising:
a tubular wall structure including:
a first non-thrombogenic layer formed of a first material and forming the lumen, an interior surface of said first layer being formed by chemically binding a non-thrombogenic agent to said first material, thereby permanently forming said first non-thrombogenic first layer, said non-thrombogenic agent having a concentration of at least 0.5 IU/cm2 as measured by an ATIII response test,
a second thrombogenic layer outside said first layer and formed of a second material, an exterior surface of said second layer being treated with a thrombogenic agent.
11. The vascular graft of
12. The vascular graft of
13. The vascular graft of
14. The vascular graft of
15. The vascular graft of
16. The vascular graft of
17. The vascular graft of
18. The vascular graft of
19. The vascular graft of
20. The vascular graft of
21. The vascular graft of
22. The vascular graft of
23. The vascular graft of
24. A vascular graft having a lumen passing therethrough, said graft comprising:
a first non-thrombogenic layer forming the lumen, said first non-thrombogenic layer having a thickness less than 100 μm,
a second growth layer outside said first layer, said second layer having a thickness in the range of 100 μm to 500 μm, and
a third thrombogenic layer outside both said first and said second layer, said third layer having a thickness less than 100 μm.
25. The vascular graft of
26. The vascular graft of
27. A vascular graft having a lumen passing therethrough, said graft comprising:
a first non-thrombogenic layer forming the lumen, said first non-thrombogenic layer formed by chemically binding a non-thrombogenic agent to a base material, thereby permanently forming said first non thrombogenic layer, and wherein said non-thrombogenic agent has a concentration of at least 0.5 IU/cm2 as measured by an ATIII response test,
a second growth layer outside said first layer, and
a third thrombogenic layer outside both said first and said second layer.
28. The vascular graft of
29. The vascular graft of
30. The vascular graft of
31. The vascular graft of
32. The vascular graft of
33. The vascular graft of
34. A vascular graft, comprising:
a tubular body having a first end, a second end, a wall, an interior surface, an exterior surface and a lumen passing therethrough, said tubular body formed of a biocompatible plastic,
said wall of said tubular body treated such that a first inner layer and a second outer layer are formed,
said first layer formed of a non-thrombogenic agent chemically bound to said biocompatible plastic on said interior surface of said tubular body, thereby inhibiting the proliferation of undesirable cells within said vascular graft, said first layer having a thickness of less than 25 μm,
said second layer formed of a thrombogenic material chemically bound to said biocompatible plastic on said exterior surface of said tubular, thereby promoting the infiltration of desirable cells into said second layer, said second layer having a thickness of less than 25 μm.
35. The vascular graft of
36. The vascular graft of
This application claims the benefit of U.S. Provisional Patent Application No. 60/120,263, filed Feb. 16, 1999.
The present invention relates to synthetic vascular grafts, and in particular, to multi-zone and multifunctional synthetic vascular grafts, thereby improving the biocompatibility and long term patency of synthetic vascular grafts.
Synthetic vascular grafts form an important therapeutic component to replace diseased arteries and thus save an important organ, limb, or in many cases, the life of the patient. Most synthetic vascular grafts are tubular structures that geometrically mimic the native blood vessel that it is meant to replace. While a natural blood vessel consists of many layers intimately joined together, synthetic vascular conduits are of a monolithic construction consisting of only one layer. These tubular structures are generally fabricated out of knitted or woven Dacron polyester yams or they are extruded polyurethane tubes or extruded PTFE tubes with defined porosities in the wall of the extruded tube. It is important to recognize that in the case of structures that are woven or knitted from Dacron polyester yam or fabricated from extruded PTFE tubes with porous walls, the porous nature of these structures is both a benefit and a detraction. The porous walls of these devices are designed to promote tissue in-growth under the proper environment, thus integrating the graft into the surrounding tissue. Studies by other investigators have resulted in currently marketed products that have a wall pore size of approximately 20 μm. The porous walls also result in blood leakage unless they are sealed. Several approaches are used to seal these grafts. One approach is to pre-clot the graft with the patient's blood. A second method uses impregnation of the graft with pure bovine collagen. The bovine collagen, which is similar to human collagen, a member of the basement membrane family of human tissue, promotes clotting and thus prevents leaks. A third method uses a topical application of the blood coagulant, thrombin, mixed with cryoprecipitate. While the primary purpose of these coatings is to seal the exterior of porous grafts, a further objective in all these methods is to improve the biocompatibility of the grafts.
All the approaches described above suffer some basic disadvantages that prevent the use of these types of coatings in fabricating small diameter synthetic grafts for replacing diseased vessels, particularly in peripheral applications below the knee and in coronary applications. While these problems also exist in larger diameter synthetic grafts such as those with internal diameter 6 mm and above, the problem is particularly acute in small diameter conduits. For the purpose of this invention, small diameter synthetic vascular conduits are defined as those with internal diameter ≦5 mm.
The specific problem associated with all the approaches described so far is their inability to maintain long-term patency of the graft. Over time the internal diameter of these grafts continues to decrease, eventually shutting off the blood flow. This phenomenon can occur in periods as short as three weeks or may occur over a period of several years. The problem occurs because the grafts prepared by the three methods described above create a reactive surface on the inner lumen of the graft, leading to several biological events including thrombosis, platelet aggregation leading to the formation of white thrombus, and proliferation of smooth muscle cells leading to intimal thickening and a reduction in the lumen diameter. The latter problem of smooth muscle cell proliferation is particularly problematic at the anastomosis site where the grafts are sutured to the native vessel.
Studies by Wagner, Tiffany, Thompson, Shultz, and Johnson of the Department of Surgery at the University of Pittsburgh, reported in Transactions, Society of Biomaterials, 1994, have shown that thrombin, topically applied to the external surface of the graft retains its activity in excess of 300 days and that this activity is resistant to both heparin and hirudin, which are potent anti-coagulants. Any migration of these thrombotic agents can have disastrous consequences by promoting thrombosis and plugging the vascular conduit being repaired.
Several approaches have been tried in an effort to maintain anti-coagulant behavior of the interior surface of the graft and ensure long-term patency. The inner surface of native blood vessels are lined with a layer of endothelial cells that maintain the surface in a non-thrombogenic state except when there is injury to the vasculature. In order to mimic this process, there has been an effort to grow endothelial cells on the surface of synthetic grafts. However, endothelial cells are expensive and difficult to grow on synthetic surfaces. Furthermore, there is no guarantee that the presence of endothelial cells will necessarily improve the patency of small caliber vascular conduits. Because collagen and fibronectin are known to promote the growth of many human cells including endothelial cells, the first attempt has been to coat the interior surface of these synthetic grafts with collagen, fibronectin, or a mixture of these two components.
For example, Sorin Biomedical of Italy markets a Dacron vascular graft that has been impregnated with bovine collagen. While this technique works for larger diameter grafts with internal diameters of ≧6 mm, this coating is unsuccessful with smaller diameter conduits. While collagen coating can and often does promote the growth of endothelial cells on the surface, it does nothing to prevent or retard intimal hyperplasia. Guidoin et al, reporting in ASAIO Journal Nov-Dec; 42, 1996, compared collagen impregnated grafts with pre-clotted grafts used as controls when implanted in canine models for periods ranging from one month to six months. While the collagen impregnated grafts showed a presence of endothelial cells on the inner lumen after a 30 day implantation, they found that the collagen impregnated grafts had a significantly higher wall thickness for most of the implantation period when compared with the pre-clotted grafts. The authors concluded that collagen impregnated polyester prosthesis cannot be recommended as small diameter blood conduits.
Clapper et al, reporting in Symposium, Society for Biomaterials, 1994, used a mixture of fibronectin and collagen to coat 4 mm ePTFE grafts with wall porosity of 20 μm. Data from 30-day implantation in canine models were reported. The authors show that 88% of the surface was covered with endothelial cells and the patency was 88%. Guidoin and his coworkers, however, have shown that the healing response with collagen coatings changes significantly after 30 days, resulting in substantial thickening of the vessel wall despite the presence of a layer of endothelial cells on the luminal surface. Therefore, the presence of endothelial cell coverage cannot be taken as evidence that this method will yield grafts with improved long-term patency.
Another method for improving the patency of small diameter vascular grafts has been the use of Dacron scaffolds implanted in the cutaneous trunci muscle of sheep to grow ovine collagenous tissue around the graft. Such a technique was described by Werkmeister et al in Transactions, Society for Biomaterials, April 1994. The use of scaffolds to grow animal tissue for human implantation is prone to poor quality control and is often expensive. Yet another method for fabricating small diameter vascular grafts involves combining two different layers of collagenous material as described by Termin et al, Transactions, Society for Biomaterials, April 1994. It is well known that composites manufactured from biological sources and used as blood conduits are prone to degradation and failure from aneurysms. Therefore this method does not offer a viable solution either. It is well known to those skilled in the art, that materials derived from animal tissue are also prone to calcification, thus significantly reducing the effectiveness of devices fabricated from such sources.
In U.S. Pat. No. 4,842,575, herein incorporated by reference, synthetic vascular grafts are impregnated with collagen. As described in earlier references, the use of collagen impregnation does not lead to improved patency of small caliber vascular conduits. In U.S. Pat. Nos. 5,643,712 and 5,880,090, herein incorporated by reference, the grafts are seeded with endothelial cells. While such coating may offer improved resistance to thrombosis, such coatings have not reduced intimal hyperplasia and thus do not guarantee improved patency of these small caliber vascular conduits. In U.S. Pat. No. 5,851,229, herein incorporated by reference, the inventors describe a bio-resorbable sealant for porous vascular grafts. The material used is a water absorbing polymer called a hydrogel. While such a coating can provide sealing action, it does not necessarily provide the needed anti-thrombogenic behavior, nor do such coatings reduce smooth muscle cell proliferation and intimal hyperplasia.
Greisler et al, Biomaterials 1996, Vol. 17, No. 3, studied the effects of impregnating ePTFE grafts, which have porous walls, with a mixture of Fibrin Glue, Acidic Fibroblast Growth Factor, and heparin on endothelial growth and intimal hyperplasia. This mixture appears to allow proliferation of endothelial cells on the luminal surface and in the presence of high concentration of heparin, reduce smooth muscle cell proliferation by 12%. While this reduction in smooth muscle cell proliferation is significant, it is not entirely sufficient for long-term patency. Greisler et al, in Surfaces in Biomaterials Symposium 1994, also examined the wash out kinetics of this mixture using 125I labeled Acidic Fibroblast Growth Factor and found that 86% of the mixture was washed out from the graft within fourteen days. By the end of 30 days, 96% of the mixture had been washed out from the graft. Thus, the effect of this approach appears to decrease exponentially with elapsed time.
Therefore, what is needed is a small diameter vascular conduit with diameters ≦5 mm and which has (i) a luminal surface that is permanently non-thrombogenic, (ii) a graft structure such that smooth muscle proliferation and consequent intimal hyperplasia is substantially reduced or eliminated, and (iii) a graft structure that allows integration of the graft into the surrounding tissue.
The present invention substantially reduces or overcomes all of the problems associated with the prior art. The invention provides a novel multi-zone, multifunctional graft with two or more zones that have different chemical and biological characteristics. The present invention further provides a graft with these characteristics where the biological and chemical properties of the different zones are substantially independent of one another. The present invention further provides a vascular conduit that has of an inner zone that is permanently non-thrombogenic and anti-proliferative, and one or more outer zones that allow for beneficial tissue in-growth and sealing of the graft to prevent leakage. The small diameter vascular conduits of the present invention containing these different zones may be fabricated from woven or knitted Dacron, extruded porous PTFE, from polyurethane polymer, or other similar materials, and the structure of these conduits so modified as to provide these different zones. One embodiment contains an inner non-thrombogenic layer and an outer thrombogenic layer, optionally containing a growth agent. A second embodiment contains a third intermediate layer having a growth agent impregnated therein.
FIG. 1 is a cross section of a graft having two active zones.
FIG. 2 is a cross section of a graft having three active zones.
The vascular graft of the present invention offers unique performance characteristics not found with products prepared by prior art methods. This is accomplished by creating two or more zones with different and substantially independent chemical and biological characteristics within the body of the graft. The vascular conduits of the present invention containing these different zones may be fabricated from any suitable material, including biocompatible plastics such as woven or knitted Dacron, extruded porous PTFE, from polyurethane polymer, or other similar materials. The material is preferably formed into a tubular structure and then treated and/or modified so as to provide these different zones.
The innermost layer or zone 12 that is in intimate contact with the blood flowing through the lumen 18 of the graft 10, also called the luminal layer, has chemical and biological properties that render the surface permanently non-thrombogenic. This layer or zone 12 is shown in FIG. 1 and FIG. 2. This is accomplished by chemically binding very high concentrations of agents that are non-thrombogenic to the base material 11 used in fabricating the graft 10. In addition, other agents are bound to the substrate material 11 in this zone 12 that prevent proliferation of undesirable cells, such as smooth muscle cells. It will be appreciated by those skilled in the art that there are likely to be therapeutic agents that provide both functions within a single biological compound that is bound to the surface. Thus, the zone 12 may contain one or more therapeutic agents chemically and permanently bound to the surface such that they prevent thrombosis and retard the proliferation of platelets and smooth muscle cells. Since the non-thrombogenic behavior of the graft surface depends on the concentration or dose of the therapeutic agent present, one key aspect of the present invention is that this agent is present in high concentrations. Since heparin obtained from animal sources is commonly used as a therapeutic agent for preventing thrombosis, one measure of a high concentration is that amount bound to surface that is in excess of 0.5 IU/cm2 (International Units/square centimeter) as measured by an ATIII response test and preferably in excess of 3.0 IU/cm2 as measured by an ATIII response test. It will be appreciated by those skilled in the art that other non-thrombogenic agents or other therapeutic agents may also be used. For example, hirudin or variations of the hirudin molecule may also be used in place of heparin as a non-thrombogenic agent. It should be noted that other agents may require different thresholds to be considered to be present in high concentrations. The thickness of the first layer or zone 12 can be ≦100 μm and preferably ≦25 μm. The first zone 12 plays a key role in preventing thrombosis and proliferation of smooth muscle cells. In this way the long-term patency of the graft 10 will be assured.
The second zone 14 consists of agents that may be chemically bound to the base material 11 of the graft, but this requirement is not mandatory. The second layer or zone 14 has as its main function, allowing infiltration of cells from the exterior environment into the wall of the graft 10 to create beneficial tissue. This can manifest itself as the growth of host collagen within the walls of the graft 10 and the potential migration of capillaries into the interstitial spaces of the graft wall 16. This is achieved by incorporating cell growth agents such as fibronectin, laminin or bovine collagen or analogs and variations of these materials in the wall of the synthetic graft 10. Some of the growth agents may also have thrombogenic properties.
The second zone 14 may also contain agents, such as thrombin, that promote thrombosis when the grafts 10 prepared according to this invention have of only two active zones 12, 14 as shown in FIG. 1 to insure that there is no leakage of blood from the graft 10 when porous materials are employed in fabricating the graft 10. In this case, the thickness of the second zone 14 also constitutes the bulk of the graft wall 16 and may be anywhere from 100 μm to 500 μm, and more preferably between 200 μm and 400 μm.
When preparing grafts 20 with three layers according to this invention, as shown in FIG. 2, an intermediate layer 22, devoid of any agents that promote thrombosis, is present. In this embodiment, the intermediate layer 22 only contains cell growth agents such as Fibronectin, Laminin, or collagen or analogs and variations of these materials in the wall 26 of the graft 10. In the three zone structure illustrated in FIG. 2, the outermost zone 24 contains a mixture of animal collagen such as bovine collagen and thrombin to promote clotting and thus seal the graft 10 and prevent blood leakage until the graft 10 is integrated into the surrounding tissue. The thickness of this outer zone 24 can be ≦100 μm and is preferably ≦25 μm.
It will be readily apparent to those skilled in the art that there may be several approaches to fabricating such a multizone, multifinctional small diameter vascular conduit as described in this invention. The following examples serve to illustrate a few of these approaches.
In one embodiment of this invention, a woven Dacron tubing of internal diameter of 3 mm and a wall thickness of 350 μm is first treated in a RF plasma reactor so as to modify the internal surface of the tubing and create a high concentration of amine groups on the surface. It will be apparent to those skilled in the art that there are several methods for creating such a high concentration of reactive amine groups. One such method uses a plasma deposited film network as described in U.S. Pat. No. 5,723,291 herein incorporated by reference. To these amine groups an anti-coagulant such as heparin containing functional groups reactive to the amines is covalently and chemically bound to the surface. Depending on the base material 11 and process used to form the layer, the material may be a coating which is chemically bonded to the base material 11 or the layer may be at least partially incorporated into the base material 11, thereby creating the first zone within the base material 11.
After attachment of the heparin to the interior surface, a water soluble polymer such as polyethylene glycol with a cell growth agent such as fibronectin is infused into the first layer of the graft structure. The fibronectin serves to allow growth of beneficial cells such as endothelial cells to grow in the area next to the anti-coagulant inner surface.
The exterior surface of the graft is coated with collagen or a mixture of collagen and thrombin to ensure that any blood seeping through the pores of the graft contact the collagen or collagen-thrombin mixture and promote clotting to seal the graft. The exterior of the graft may also be sealed with a thin coating of polymers formed in situ using peroxide initiated crosslinking of vinyl acrylates.
While the above description provides a means for fabricating a multizone, multifunctional vascular graft, it is to be understood that this description is illustrative only and not limiting of the disclosed invention. It will be appreciated that various methods to produce such a multifunctional, multizone synthetic vascular conduit will fall within the scope and spirit of this invention.
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The Hugh Jackman and Jake Gyllenhaal-starring crime thriller is being roundly praised by critics since it premiered at the Toronto Film Festival
Prisoners is by no means your average crime thriller, and maybe that's why critics are swooning over the latest project form Oscar-nominated director Denis Villeneuve (Incendies); a kidnapping-based movie that promises to leave viewers questioning their own morals as to how far they'd go to protect their child. Starring Hugh Jackman, Jake Gyllenhaal and the massively under-rated Paul Dano, the film has being widely praise since it premiered at the Toronto International Film Festival this month, with critics tipping their hats to the actors, director and everyone else involved for making one of the most memorable thrillers in years.
Jackman and Gyllenhaal star alongside each other in "an actor's duel"
The film is set in a rural American town and poses the question, 'how far would you go to protect your child?' When the unthinkable happens to Keller Dover (Jackman) when his 6-year-old daughter and her friend go missing, seemingly leaving no trail and no certain answers as to where they could be. There is one possibility as to where they could be though, and that's the dilapidated RV of neighbourhood creepy guy Alex Jones (Dano), which was seen only moments later in the same vicinity as where the two girls went missing. It's a test against time as Detective Loki (Gyllenhaal) must get to the bottom of the crime before Dover gets to Jones and makes him pay for what he may have done.
"A film that seems headed toward one conclusion, then veers toward another over 2/₂ of the fastest-moving hours I've seen in a recent movie," a thoroughly impressed Lou Lumenick of the New York Post said of the movie. Meanwhile, Claudia Puig from USA Today was keen to comment on the "complicated moral questions" the film brings up, adding that this same question is used by the director to develop "an intricate, horrifying mystery with breathtaking skill."
Check out the trailer for Prisoners
A.O. Scott of the New York Times described the film as "artful" and laden with "naturalistic credibility," commenting, "It absorbs and controls your attention with such assurance that you hold your breath for fear of distracting the people on screen, exhaling in relief or amazement at each new revelation."
Much of the praise has been evenly distributed across all fields in the film, with the acting talent on display regularly being picked up for individual praise. There "fascinating actor's duel going on," says Wall Street Journal's Joe Morgenstern, whilst the Chicago Sun-Times critic Richard Roeper described the film as "one of the most intense thrillers in recent years," that contained "the best performance of Hugh Jackman's career."
Prisoners is out wide on 27 September.
Terrence Howard (L), Jake Gyllenhaal, Maria Bello, Denis Villeneuve, Hugh Jackman, Melissa Leo and Paul Dano (R) attend the TIFF premiere


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Team Kai friends for life by Team Kai - over 2 years ago
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15 favourite cartoon characters
Dangermouse is a one-eyed white mouse who sports a fetching black eye patch. The cartoon was created in England by Cosgrove/Hall Productions and first aired in 1981 and ran until 1992. It is based on British espionage fiction - a loose parody of Mighty Mouse and Super Ted. Dangermouse's voice was done by British television actor David Jason and his trademark catchphrases were: "Good grief!", "Penfold, shush!" and "Blast!".
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As a retailer in the surf industry for the past 21 years, I have had to use multiple sources to stay informed to the news within surf. Since the inception of the Executive Edition of Shop-Eat-Surf.com, I need only one stop. Thanks for providing such a valuable tool to all of us in the industry. Shop-Eat-Surf is a must read for all of our staff at Maui Nix.- By George Karamitos, CEO, Maui Nix
There is no better publication that I am aware of that is so accurate and on top of any news and developments in our industry. I personally recommend it to many people that want to know and understand more about our industry. For the most part, shop-eat-surf.com gets the stories first. As a matter of fact, I require all the executives in our company to read it.- By Hezy Shaked, President & CEO, Tilly's
AGENDA: Last chance to register before July 8-9 show.
ISPO: Shanghai trade show runs July 2 - 4.
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- November/December holiday sales trending at a 4% increase, strongest since at least 2006
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NEW YORK, December 28, 2010 – The week leading up to Christmas Day 2010 proved to be filled with holiday cheer for retailers that posted their third week of positive sales results as consumers rushed to finish their shopping. For the week ending December 25, retail sales rose by 1.0 percent from the prior week, according to the ICSC-Goldman Sachs Weekly Chain Store Sales Index. In addition, retail sales, on a year-over-year basis, strengthened to their strongest rate since April 24, 2010 and increased by 4.8 percent.
"Consumers hurried to complete their last minute holiday-gift buying ahead of Christmas Day as many workers had additional shopping time on Christmas Eve, which was a federal holiday for many since Christmas Day fell on a Saturday," said Michael Niemira, ICSC vice president of research and chief economist. "That last-minute holiday spending lift was aided by consumers who had more money as a result of the improving economy, more time as a result of the Friday holiday and more holiday-season excitement than in many years," Niemira added.
For December ICSC Research expects industry sales will increase by approximately 3.5 percent (with a bias on the stronger side) and ICSC's November-December holiday-season sales forecast is trending approximately at 4.0 percent (or slightly above) and slated to the strongest since at least 2006.


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Making Regalia – Bustle Backboards
On this episode of Making Regalia with Juaquin Lonelodge, with special guest Willow Abrahamson, they show us how to construct a bustle backboard.
Making Regalia - Episode 7 Season 2 from CATV47 on Vimeo.
As you know, these episodes are brought to you by Cheyenne and Arapaho Television- CATV47. They don't have the big budgets like the major networks do so if you love these shows, why not throw a little change their ...
No More Spilled Beads! All Beaders Need To Order This Now!
If you've done any beading you've had it happen!
Spilled beads!
All those beautiful colors now in one big pile on the floor!
I've tried keeping them in the containers while beading, Tried dozens of different containers, but it still happens. They always end up on the floor.
Now here's the solution!
YouTube user PowWow Bling posted a review of the Beadsmith Sticky Bead Mat.
See ...
The Native Drum – Making a Handle for a Small Drum
Have you guys been keeping up with the awesome tutorials on Cheyenne and Arapaho Television (CATV47)? Last year we told you about a new show called The Native Drum with host Shawn Littlebear (Southern Cheyenne). Littlebear is a traditional drum maker who shares with us his various drum making tips and techniques.
In Episode 4 of The Native Drum, Littlebear makes a handle for a small hand drum.
Don't forget to visit http://www.catv47.com/the-native-drum.html on any ...
Ojibwe Pucker Toe Moccasin Tutorials
Sarah Agaton Howes is the latest designer to participate in Eighth Generation's Inspired Natives Project. Sarah is an Anishinaabe artist, teacher, and emerging community organizer from Fond du Lac Reservation in Minnesota. Back in 2013 she created a set of tutorial videos to make Ojibwe Pucker Toe Moccasins. Check them out and see if you're also an inspired native!
Step 1: Purchasing and Preparing Supplies
Step 2: Makizin Pattern and Cut out...
Making Regalia – Straight Dress Making
On this episode of Making Regalia with Juaquin Lonelodge, he has special guest Terra Houska. Terra introduces viewers to the fundamentals of straight dress making. The follow-up episode will show Juaquin and Terra constructing all the pieces in sequence. Stay tuned for that one!
Making Regalia - Show 5 of Season 2 - Straight Dress Making from CATV47 on Vimeo.
If you guys find this information helpful and valuable, make sure you show ...
Making Regalia – Constructing a Bustle
Making Regalia with Juaquin Lonelodge is back and this time he is tackling the bustle! Check out these two new episodes to help you with your regalia.
Episode 3 - Season 2
On this episode, Juaquin lays out the necessary elements for the construction of a small traditional bustle.
Making Regalia - Episode 3 of Season 2 from CATV47 on Vimeo.
Episode 4 - Season 2
Juaquin Lonelodge and special guest, Dwight Whitebuffalo discuss and assemble ...
Making Regalia: Dance Bells
Episode 2 of the second season of Making Regalia is out now! In this episode we have guest artist Redsky Whapeppah, demonstrating bell application for men's straight dance regalia as host Juaquin Lonelodge describes the history and significance of bells.
Making Regalia - Episode 2 of Season 2 from CATV47 on Vimeo.
Make sure you follow Making Regalia on Facebook. They appreciate the feedback and ...
Living Traditionally: Chickasaw Bead Artist Courtney Parchcorn
In this video from Chickasaw.TV, Courtney Parchcorn explains how her artwork helps her get in touch with her history, and how that understanding of where she came from helps her to succeed in the modern world.
This piece is especially meaningful to Parchcorn, "For All the Grandfathers"— which features an eagle motif symbolizing her own grandfather.
Making Regalia – How to Construct Leather Belts – Craft Tutorial
Host Juaquin Lonelodge is back for Season 2 of Making Regalia. In the first episode he shows us how to construct leather belts, which he says an absolute regalia necessity.
Making Regalia - Season 2 - Episode 1 from CATV47 on Vimeo.
You can catch Making Regalia on the FNX Network or CATV47.com Check your local listings for times.
Tutorial: How to Bead a Tobacco Bag, Lakota Style!
Benjamin Sitting Bull created a couple of tutorial videos for folks wanting to learn some Lakota beadwork. Watch as he adds beads to a small tobacco bag using a lazy stitch.
Part 2 talks about finishing the edge
And here he is with the finished product!
Thanks for sharing your knowledge with us!
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Israeli airstrike kills four children — next to a journalists' hotel
An errant airstrike today next to a journalists' hotel has led to a fresh wave of criticism against Israel. More ▸
An errant airstrike today next to a journalists' hotel has led to a fresh wave of criticism against Israel. More ▸
So far during Operation Protective Edge, Iron Dome has been a game-changer for Israel. More ▸
A rocket fired from Gaza damaged power lines in Israel that resulted in the loss of power to 70,000 Palestinians in the coastal strip. More ▸
Dozens of young men protesting Israel's actions in Gaza briefly besieged a Paris synagogue and clashed with security. More ▸
Experts say Israel's hope for a quiet border will be only temporarily achieved by its latest operation, Protective Edge. More ▸
Five Hamas operatives who infiltrated Israel by sea were killed in a gunfight with soldiers at an army base near the Gaza border, the Israeli military said. More ▸
Israel's Cabinet approved the call-up of as many as 40,000 additional combat reservists. More ▸
The Israeli government launched an operation aimed at ending rocket fire from the Gaza Strip. More ▸
Retaliating for a rocket barrage on southern Israel that destroyed a Sderot factory, Israeli airstrikes hit what Israel's military called "terror activity sites." More ▸
A Palestinian who infiltrated Israel from the Gaza Strip was caught with a hand grenade outside a southern Israeli community. More ▸
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text: 50's Inspired Personalised Glasses Case by Angel Lodge Studio £19.50$40.81€28.33$31.73 17 customer reviews(17) Made to order £18.50$38.72€26.88$30.10 delivery to United States - Receive this item 5-10 working days from dispatch International delivery available text colourtext colour (required)pink text / blue glasses green text / pink glasses red text / red glassestext colour (required)pink text / blue glasses green text / pink glasses red text / red glassestext colour (required)pink text / blue glasses green text / pink glasses red text / red glassestext colour (required)pink text / blue glasses green text / pink glasses red text / red glasses choice of textchoice of text (required)Mum'sGrandma'sPersonalised text (enter in the next box) (+ £5)choice of text (required)Mum'sGrandma'sPersonalised text (enter in the next box) (+ $10.46)choice of text (required)Mum'sGrandma'sPersonalised text (enter in the next box) (+ €7.26)choice of text (required)Mum'sGrandma'sPersonalised text (enter in the next box) (+ $8.13) personalisation text (if requested above) quantity by Angel Lodge Studio Location: S. Glamorgan, GB read seller's profile see seller's complete range more items from this seller Personalised Women's Glasses Case £19.50$40.81€28.33$31.73 Men's Newsprint Glasses Case £19.50$40.81€28.33$31.73 50's Inspired Personalised Glasses Case £19.50$40.81€28.33$31.73 Personalised Glasses Case £19.50$40.81€28.33$31.73 Personalised Applique Glasses Case £19.50$40.81€28.33$31.73 Cufflink Wallet £27$56.51€39.23$43.93 view all you may also like PRODUCT DETAILS CUSTOMER REVIEWS DELIVERY RETURNS Made in Britain can be personalised gift wrapping available ask seller a question save for later A cute, retro style, designer glasses case to keep your glasses safe and scratch free. This 50's inspired personalised glasses case is fun but practical. Perfect for someone who is always loosing their glasses. An easy to open and close design with an invisible magnetic fastening, no fiddly buttons and loops here! Beautifully hand made with attention to detail. Having it personalised makes it extra special, so a unique gift. Please write text exactly as you want it, including capital letters, apostophes etc. as it will be embroidered as you have written it. made from: 100% cotton canvas main body, cotton lining and interlining. invisible magnetic closure. dimensions: Approximate size: L18.5 x W8.5 cms Delivery: These cases are made to order and can therefore take up to a week to dispatch. product code: 126465 17 customer reviews Sun 06 Jul 2014 I thought there was supposed to be some more words on there but never mind. they're fine Fri 11 Apr 2014 Beautifully made, a perfect gift for Mother's Day, thank you! Thu 20 Feb 2014 Nice product! Mon 06 Jan 2014 Good quality Wed 01 Jan 2014 Grandma was thrilled with it. Wed 01 Jan 2014 Really lovely thank you was a great present for the two grandmothers. Wed 01 Jan 2014 Something different for a Xmas present. It was also beautifully made. Thanks. Mon 30 Dec 2013 No comment supplied. Thu 19 Dec 2013 Lovely and good quality Sun 15 Dec 2013 Fun product for a great gift idea. Sat 30 Nov 2013 Really pleased with the glasses case, excellent quality, lovely packaging and good all round service. Thu 07 Nov 2013 Thought this was a really unusualy gift for my mum, really pleased with it Wed 09 Oct 2013 Great product and speedy delivery Sun 06 Jan 2013 Perfect gift for someone Wed 28 Dec 2011 No comment supplied. Wed 28 Dec 2011 No comment supplied. Fri 16 Dec 2011 No comment supplied. see all customer reviews hide some customer reviews read about our product rating system ratings guide trusted independent customer feedbackforum excellent bad good poor This product is dispatched to you by Angel Lodge Studio. MAINLAND UK order now and receive this item on or before price Free Delivery Wednesday 15 July FREEFREEFREEFREE Two Day Delivery Friday 10 July £3.95$8.26€5.73$6.42 Express Next Day Thursday 9 July £4.95$10.36€7.19$8.05 Saturday Delivery Saturday 11 July £12.95$27.10€18.81$21.07 NON-MAINLAND UK estimated delivery price Highlands & Islands of Scotland 2-5 working daysfrom dispatch £2.75$5.75€3.99$4.47 Northern Ireland 2-5 working daysfrom dispatch £2.75$5.75€3.99$4.47 Other UK Islands 2-5 working daysfrom dispatch £4.95$10.36€7.19$8.05 INTERNATIONAL DELIVERY estimated delivery price Western Europe 2-5 working daysfrom dispatch £11.50$24.07€16.71$18.71 Rest of Europe 5-10 working daysfrom dispatch £11.50$24.07€16.71$18.71 USA & Canada 5-10 working daysfrom dispatch £18.50$38.72€26.88$30.10 Far East & Australasia 5-10 working daysfrom dispatch £19.50$40.81€28.33$31.73 Rest of the world 5-14 working daysfrom dispatch £19.50$40.81€28.33$31.73 You have 28 days, from receipt of cancellable goods, to notify the seller if you wish to cancel your order or exchange an item. Please note: goods that are personalised, bespoke or made-to-order to your specific requirements, perishable products and personal items sold with a hygiene seal (cosmetics, underwear) in instances where the seal is broken are non-refundable, unless faulty. Read more about our returns policy.Should you choose to return or exchange your order you will need to deliver the item(s) to the UK, where this seller is based. Angel Lodge Studio's return policy


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Showing Suppliers 1 - 4 of 4
Grainger Industrial Supply (2110 Products)
Address: 20 Gregory Dr. Branch 017, South Burlington, VT
Business Type: Distributor
Description: Grainger helps customers save time and money by providing them the right products to keep their facilities up and running. Grainger's customers are 2.0 million businesses and institutions in 157 countries. While each customer has a unique facility to operate and a different problem to solve, our... (more)
Allen Lumber Co.
Address: 502 North Main Street, Barre, VT
Business Type: Distributor
Bristol Woodworks
Address: 74 Many Waters Road, Bristol, VT
Business Type: Manufacturer
Moulton Custom Door of Vermont
Address: 3759 VT Route 100, Duxbury, VT
Business Type: Manufacturer


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Excellent product
I bought the BP 540 player and a LG 3d TV at the same time. The smart features are great and easy to use. The only negative is that I paid extra for 3D...Read complete review
I bought the BP 540 player and a LG 3d TV at the same time. The smart features are great and easy to use. The only negative is that I paid extra for 3D features that I don't need/appreciate, as the picture quality w/o 3D is, in my opinion, as good as 3D. To try out the 3D option, I bought a 3d movie, "The Desolation of Smaug" and enjoyed it on regular TV as much as I did on 3D. I do not have the slightest bit of buyer's remorse after 4 1/2 months of use.
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Worst BlueRay Player I've owned
I've owned 3 bluray players from a couple different companies. I bought this LG because I was hooking it up to an LG TV. the first unit would never connect to our home WiFi...Read complete review
I've owned 3 bluray players from a couple different companies. I bought this LG because I was hooking it up to an LG TV. the first unit would never connect to our home WiFi network, and about half the time wouldn't play blurays. I returned that unit in hopes I had faulty equipment. I was given a new unit, I brought it home. This unit was able to connect to the WiFi, but wasn't able to run any of the internet based apps. It couldn't even open netflixs. I tried to re connect to the WiFi network, but I was never able to establish a connection again. I've moved the unit to different TVs around the house, and I've still not been able to connect. So far this one hasn't had a problem playing blurays. I am so disappointed in the bluray player I'll likely never buy another LG product.
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Easy to set up
By chocolatelover
from Dayton, OH, USA
Comments about LG 3D Capable Blu-Ray Disc Player With Smart TV:
I love this Blu-Ray/DVD player. It is so easy to use and easy to set up too!. The picture quality is fantastic! I would whole heartedly advise this product!
Bottom Line Yes, I would recommend this to a friend
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Turns my LG TV into a smart TV
By icenfire59
from Stafford, VA, USA
I had to replace my old DVD player so after researching I choose this 3D Blu Ray. I very happy with it and the quality is great. There is a great many apps that came with it and I have many more features with this unit. The only thing I found out is it doesn't work while plug into a surge protector, this needs to be address.
(1 of 1 customers found this review helpful)
Does the Job!
By DrD
from Undisclosed
Good product, does the job, I just bought it so I can use the 3D features on my TV, haven't use the apps on the device. I just wish my magic remote was able to control more of the features, without having to switch remotes all the time.
This product has great features
By Anonymous
Easy to set up ... easy to use. Beautiful picture and sound from Blu-ray DVDs.
Awesome blu tooth capable
By Manny
from El Paso, TX, USA
Awesome wifi connectivity through existing wireless
great player!
By lumi64
from Englewood, CO, USA
I love this blu-ray player. my husband handled the set up so can't speak about that but the picture is great and haven't watched a 3D movie on it yet. all in all i love LG and am very happy with this purchase! super easy to use
Serves its purpose.
By wheeleze
Simple 3d/blueray player with all the necessary features.
Don't waste your money.
By Displeased
from Williamsburg, VA, USA
Bought this for the Wi-Fi, should have read the other reviews. Wi-Fi on this does NOT work at all. A whole 10 feet from the router, can't find the signal. Sure, HG recommends using a cable, but that isn't why I bought this. Found another brand for half the price with all the features, and it works.
Bottom Line No, I would not recommend this to a friend
By richb77
from Natalia, TX 78059, USA
great product but, I have Direct TV no 3d programing. Will switch to Dish when my contract is up. Watched AVITAR in 3D, I am sold on this product.
very sleek and quality product
By starrkat7
from Ohio, USA
This is a great product in a little package. It had a lot to offer bring a smart blu-ray you can use it to turn your TV into a smart TV without paying all that extra money!! This is super super easy to use, my five year old does it on her own. And LG is a very reliable brand!
Fill out the form below to request Better Price for this product.
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United States Environmental Services (USES)
based in Houston, TEXAS (USA)
We work safe. We work hard. We work smart. We stay current with training and technology. And we exercise good old-fashioned common sense in getting environmental maintenance and cleanup done right—safely, on time and on budget. Deep within confined industrial spaces and in the great outdoors, on highways and waterways, in business districts and along shorelines, on land ...
Terragon Environmental Technologies Inc.
based in Montréal, QUEBEC (CANADA)
Terragon develops and commercializes innovative technologies and practices needed to enable habitats to treat their waste locally and safely in order to recover valuable resources to be reused at the site where waste is generated. Terragon researches and engineers highly innovative waste treatment systems which anyone can operate safely, economically and without special ...
ISOS Group
based in San Diego, CALIFORNIA (USA)
ISOS Group is an innovative, fully integrated sustainability consultancy, serving the needs of organizations across all industries. Our team of GRI certified practitioners offers an unmatched blend of skills in sustainability reporting, external assurance of CSR, carbon reporting, third party GHG verification and stakeholder engagement. ISOS is a Global Reporting ...
H2O GmbH
based in Steinen, GERMANY
Wastewater evaporators from the experts for zero liquid discharge production (ZLD). We are the leading producer of wastewater evaporators for industrial wastewater treatment for the metal processing industry, automotive industry, aviation industry, machine building industry and many other industrial sectors. We manufacture our VACUDEST wastewater evaporators following ...
Waste Control Systems Inc
based in Phoenix, MARYLAND (USA)
Waste Control Systems has been providing products for the storage, transportation, and disposal of hazardous and radioactive materials. With our code knowledge, we are able to recommend safer usage, storage options, and the most effective waste reduction methods. The results are a safer, cleaner, and more profitable facility
BlueStream Environmental Technologies (Pty) Ltd.
based in Johannesburg, SOUTH AFRICA
BlueStream Environmental Technology has over a decade of experience in developing microbial solutions that are both economically sound and environmentally effective. BlueStream products provide a safe, easy and effective solution for challenging hydrocarbon waste problems with numerous successful applications. BlueStream has earned its reputation for excellence with ...
The Cleveland Vibrator Company
based in Cleveland, OHIO (USA)
Since 1923 Cleveland Vibrator Company has been designing, manufacturing and supplying vibratory products and offering services to meet material handling needs. Our diverse product and knowledge sets range from the precise challenges of fine powder screening to the most rugged feeder, screener and conveyor applications. In addition to our breadth of capabilities, we ...
based in Bilbao, SPAIN
FLUIDEX, Spanish Association of Fluid Handling Equipment Exporters, is a non profit making organization which main objectives are the international promotion of the spanish manufacturers in this industrial sector, and the defence of their general interests. Spanish association of manufacturers of tube & pipes, fittings, valves, pumps, compressors and other equipment for ...
ExTox Gasmess-Systeme GmbH
based in Unna, GERMANY
Planning, manufacturing, sale, installation and maintenance of gas detection systems and gas monitoring systems for combustible and toxic gases. Gas alarms for combustible gas monitoring and toxic gas monitoring.
based in Grapevine, TEXAS (USA)
ENTACT was established in 1991 in Dallas, Texas and founded on the belief that regulatory compliance, technical excellence, safe field performance, and sound business practices are all necessary to deliver outstanding projects. ENTACT is the largest national provider of environmental remediation services to the private industry and our twenty year growth has been achieved ...


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Originally written on Jocks and Stiletto Jill | Last updated 4/11/13
photo via @TeamSwish Jocks and diamond laced jewelry always seems to cause some sort of problems. The latest athlete accused of skipping out on a jewelry bill? That would be Knicks star JR Smith. Per TMZ, Smith reportedly purchased $25,000 worth of jewels back in 2010 that included; earrings, a diamond chain and two Black Jesus pendants. The black ice pendant is reportedly worth $15,000 alone. The company, Lemmerman sued Smith for the jewelry, attorney's fees and interest. Will JR never responded so the judge ruled in the company's favor and awarded them $48,000. All I want to know is where are your people EARL? At the very least have someone respond. Stuff like this generally doesn't go away if you ignore it. That's what you have lawyers and an agent for. To handle things of this nature. I bet you don't even rock your Jesus piece anymore…
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Kirk House Band
Abilene, TX
Saturday, May 11th, 2013 at 9:00pm
Full band cone on out!! #bringyasexy
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VIEWS: 22 PAGES: 6 POSTED ON: 8/8/2010 Public Domain
CLINICAL REVIEW Chronic abdominal pain in children
For the full versions of these articles see bmj.com CLINICAL REVIEW Chronic abdominal pain in children M Y Berger,1 M J Gieteling,1 M A Benninga2 1 Department of General Practice, Chronic abdominal pain is a common disorder in chil- functional gastrointestinal disorders related to Erasmus MC, University Medical dren and adolescents worldwide. It affects the child's abdominal pain.4 Center Rotterdam, PO Box 2040, wellbeing, and the costs from missed school days and 3000CA Rotterdam, Netherlands At present the Rome criteria are not useful in daily 2 use of healthcare resources are high. clinical practice. Further research is needed on their Department of Pediatric Gastroenterology and Nutrition, Children with chronic abdominal pain represent a prognostic and diagnostic value (for example, Emma Children's Hospital, heterogeneous population comprising both organic whether they discriminate between relevant patient Academic Medical Center, Amsterdam, Netherlands and functional gastrointestinal disorders. Functional groups) and on their responsiveness to different Correspondence to: M Y Berger disorders are those that cannot be explained by interventions.5-7 email@example.com structural or biochemical abnormalities. Differences in prevalence of organic disease are reported Who get's chronic abdominal pain? BMJ 2007;334:997-1002 doi: 10.1136/bmj.39189.465718.BE depending on the setting, ranging from 5% in the The prevalence of chronic abdominal pain in general population to 40% in a paediatric community based studies ranges from 0.5% to 19%,8 9 gastroenterologist practice.1 General practitioners and varies according to age and definitions used feel confident in labelling chronic abdominal pain (table 1).w1-w4 Studies that included large age ranges as an easy to manage functional disorder. After show two age peaks; the first at 4-6 years of age and minimal further testing, these children and their the second at 7-12 years of age.w2 The predominance parents can be reassured by explaining that the of girls is controversial (table 1).w1 w5-w7 8 9 symptoms are common and rarely associated with disease. However, when diagnostic uncertainty Do sexually abused children get chronic abdominal increases, pain does not resolve over time, or parents pain? are hard to reassure, extensive testing and referral Population based and clinical studies have consistently easily set in. As a consequence paediatricians suggested that a considerable number of adults with perceive chronic abdominal pain as a time consum- irritable bowel syndrome report histories of physical, ing and therapy resistant disorder. emotional, and sexual abuse.10 Little is known about the role of sexual abuse and the association with chronic What are we talking about? abdominal pain in children. In one case-control study In the late 1950s Apley and Naish introduced the term 72 abused children reported more functional disorders recurrent abdominal pain in children for pain that than did controls (48 v 26).11 In a prospective study, waxes and wanes, occurs for at least three episodes abused and non-abused boys reported comparable within three months, and is severe enough to affect rates of functional disorders; the duration of the the child's activities (box 1).2 This definition has been problems, however, was significantly longer in abused criticised for including both organic and non-organic boys than non-abused boys (table 1).12 causes. Von Bayer and Walker proposed a two stage approach to classification.3 For the first stage a child's presentation needs to be consistent with Apley's Sources and selection criteria criteria, whereas for the second stage subgroups are We used the Cochrane library to identify relevant identified on the basis of medical findings—for systematic reviews that evaluated the effectiveness of pharmaceutical, psychological, and complementary example, recurrent abdominal pain with constipation, interventions for chronic abdominal pain in children. constipation and anxiety, or no identifiable cause. Medline searches were used to find relevant systematic Both approaches are based on the concept that reviews on diagnosis and treatment of abdominal pain functional abdominal pain is a diagnosis by exclusion. in children using the keywords "abdominal pain", The suggestion arose to facilitate the diagnosis of "systematic review", "meta-analysis", "diagnosis", and functional disorders on the basis of symptoms alone. "treatment". We limited our searches to "all child". According to a model used in adults, a panel of experts Statements on prognosis of chronic abdominal pain were derived from a systematic literature search in in childhood gastrointestinal disorders subdivided Medline, Embase, and PsycINFO of prospective cohort childhood chronic abdominal pain into several well studies on the topic. We took additional references from defined categories on the basis of symptoms, the our personal files. Rome criteria (box 1). These criteria distinguish five BMJ | 12 MAY 2007 | VOLUME 334 997 CLINICAL REVIEW Do children of anxious or depressed parents get chronic respectively).13 This suggests that anxious parents, abdominal pain? worried by their child's symptoms, may respond to Both maternal and paternal anxiety in the first year of a their child in a way that strengthens the recurrence of child's life are associated with chronic abdominal pain symptoms.14 That family factors play a role was before the age of six years (odds ratio 1.53, 95% emphasised by the finding that children of a parent confidence interval 1.24 to 1.89 and 1.38, 1.12 to 1.71, with gastrointestinal problems are more likely to have chronic abdominal pain than children of a parent without such problems (odds ratio 5.3, 95% confidence Box 1 | Classification systems for abdominal pain in children interval 2.1 to 13.2; table 1).w18 Apley and Naish, 1958 Recurrent abdominal pain Why do children get chronic abdominal pain? Abdominal pain that waxes and wanes, occurs for at least three episodes within three The cause and pathogenesis of chronic abdominal pain months, and is severe enough to affect a child's activities in children is undoubtedly multifactorial and not well understood. Visceral sensation, hormonal changes, Subcommittee on chronic abdominal pain, 2005 inflammation, disturbances in gastrointestinal Chronic abdominal pain motility, psychological factors, and family dynamics Longstanding intermittent or constant abdominal pain have been suggested as contributory factors to chronic Functional in most children—that is, without objective evidence of an underlying abdominal pain of functional origin. It is known that organic disorder the brain and gut have a constant exchange of informa- Rome III criteria, 2006 tion. An example of the complex origin of functional Functional dyspepsia abdominal pain is the observation that patients who Must include all of the following*†: develop an intercurrent bacterial colitis are more likely Persistent or recurrent pain or discomfort centred in the upper abdomen (above the to develop irritable bowel syndrome if the infection umbilicus) occurs during stressful life events.15 Not relieved by defecation or associated with the onset of a change in stool frequency or stool form Biopsychosocial model of illness A biopsychosocial model provides a conceptual basis Irritable bowel syndrome for understanding and legitimising gastrointestinal Must include all of the following*†: symptoms not easily allocated to specific organic Abdominal discomfort (uncomfortable sensation not described as pain) or pain diseases, such as abdominal pain, diarrhoea, and associated with two or more of the following at least 25% of the time: constipation. In a biopsychosocial model of care, the Improved with defecation management of a child with functional abdominal pain Onset associated with a change in frequency of stool takes all related factors into account. Behavioural Onset associated with a change in form (appearance) of stool changes to cope better with the pain may therefore be as appropriate as pharmacological interventions to Functional abdominal pain modulate visceral sensitivity and motility. Must include all of the following*†: Episodic or continuous abdominal pain How is it diagnosed? Insufficient criteria for other functional gastrointestinal disorders Recently a committee of American paediatric Functional abdominal pain syndrome gastroenterologists concluded that there are no Must include functional abdominal pain at least 25% of the time and one or more of the following*†: diagnostic tools to distinguish functional abdominal Some loss of daily functioning pain from organic abdominal pain. Only the presence Additional somatic symptoms such as headache, limb pain, or difficulty in sleeping of alarm symptoms or signs increases the probability of an organic disorder and justifies further diagnostic Abdominal migraine testing.16 Alarm symptoms or signs include, but are Must include all of the following*‡: not limited to, those summarised in box 2. Children Paroxysmal episodes of intense, acute periumbilical pain that lasts for one or more with alarm symptoms need additional laboratory hours testing (erythrocyte sedimentation rate, comprehen- Intervening periods of usual health lasting weeks to months sive metabolic panel, and stool analysis) to examine The pain interferes with normal activities the possibility of organic abnormalities such as The pain is associated with two or more of the following: inflammatory bowel disease, coeliac disease, or less Anorexia prevalent abnormalities. Nausea Vomiting What is the diagnostic value of history and physical Headache examination? When alarm symptoms are not found, there is no Photophobia evidence that pain characteristics such as frequency, Pallor *No evidence of an inflammatory, anatomical, metabolic, or neoplastic process that severity, or location are able to discriminate between explains symptoms †Criteria fulfilled at least once a week for at least two months functional and organic disorders. Accompanying before diagnosis ‡Criteria fulfilled two or more times in the preceding 12 months symptoms such as headache, anorexia, nausea, constipation, or arthralgia occur as much in children 998 BMJ | 12 MAY 2007 | VOLUME 334 CLINICAL REVIEW their relation with abdominal pain is questionable. Box 2 | Alarm symptoms when a child presents with Children with Helicobacter pylori were not more likely chronic abdominal pain to have abdominal pain than children without Involuntary weight loss H pylori17 and the same was found for children with a Deceleration of linear growth lactose malabsorption. Positivity for antiendomysial Gastrointestinal blood loss antibodies, an indication of coeliac disease, was equally Significant vomiting present in children with chronic abdominal pain as Chronic severe diarrhoea controls.18 Unexplained fever Persistent right upper or right lower quadrant pain What do we know about prognosis? Family history of inflammatory bowel disease Most children with functional abdominal pain have relatively mild symptoms and are managed in primary care. For example, in Dutch general practice fewer with abdominal pain as a manifestation of a than 2% of children with functional abdominal pain functional disorder as in children with abdominal are referred to secondary care.19 pain due to an organic disorder.16 The presence of Studies that examine the prognosis of chronic recent stressful life events, anxiety, depression, abdominal pain are mainly in children referred to a or behavioural problems is not useful in distinguish- paediatrician or paediatric gastroenterologist. ing between functional and organic abdominal A recent systematic review of prospective follow-up pain.16 Studies evaluating this relation could not studies in children with chronic abdominal pain showed establish whether children became anxious or that the mean percentage of children with continuing depressed because of their abdominal pain or abdominal pain was 29.1% (95% confidence interval whether anxiety or depression triggered the pain 28.1% to 30.2%) (personal communication). Compared (table 1). with children who had no chronic abdominal pain at No studies could show that stressful life events baseline these percentages were considerably higher significantly differentiate patients with functional (odds ratio 6.28, 95% confidence interval 4.81 to 8.21). abdominal pain from other patient groups (table 1).16 The reported duration of follow-up in the studies ranged Good data evaluating the diagnostic value of from 1 to 29 years (personal communication). physical examination are lacking. Some studies suggest that children with chronic abdominal pain, and in particular girls, develop What is the diagnostic value of additional testing? irritable bowel syndrome as adults.w2 20 In addition, No studies have evaluated the usefulness of common there is evidence that children with chronic abdominal laboratory tests (complete blood cell count, pain are at risk of later emotional symptoms and erythrocyte sedimentation rate, comprehensive psychiatric disorders, particularly anxiety disorders.16 metabolic panel, urinalysis, stool parasite analysis) to distinguish between organic and functional abdominal What factors predict long term persistence of pain? pain in the absence of alarm symptoms. Evidence From the prospective follow-up studies available it that radiographic or ultrasonographic examination of seems that parental factors, rather than psychological the abdomen, oesophageal pH monitoring, or characteristics of the child, predict the persistence of endoscopy and biopsy can discriminate between abdominal pain (personal communication) (table 1). functional or organic abdominal pain is lacking or Acceptance by parents of the role of psychological insufficient.16 Whenever abnormalities are found factors in the maintenance of symptoms is strongly Table 1 | Factors related to diagnosis, incidence, and prognosis of functional abdominal pain Factors Likely to be related Inconclusive Unlikely to be related Diagnosis: Factors or findings that Alarm symptoms increase the risk of organic Helicobacter pylori and Pain characteristics such as differentiate between disease antiendomysial antibody frequency, severity, or functional and organic positivity17 are equally present in location; other functional abdominal pain children with chronic abdominal symptoms; anxiety, pain and children without depression; lactose abdominal pain malabsorption Incidence: Factorsrelated tooccurrence Age of child; parental anxiety in first year of Female sex; anxiety, depression; Family functioning; marital of functional abdominal child's life; parents with gastrointestinal stressful life event; sexual abuse status of parents pain problems; low socioeconomic status Prognosis: Factors related to No acceptance by parents that the disorder is Age; female sex; self confidence; Anxiety, depression; severity of persistence of functional functional; parental attention to child's other functional symptoms; coping pain abdominal pain discomfort; parental functional problems; style of parents; low socioeconomic stressful life event, sexual abuse status BMJ | 12 MAY 2007 | VOLUME 334 999 CLINICAL REVIEW associated with recovery.21 Recently Walker et al showed that parents' attention to children's discomfort Box 3 | Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and was associated with significantly more mention about Nutrition symptoms than when parents' behaviour was intended The term recurrent abdominal pain should be retired to distract.14 Diagnosis Children with chronic abdominal pain who experience Diagnostic triage to discriminate functional stressful life events are at risk of persistent abdominal pain. abdominal pain from organic disorders in young The presence of a depressive or anxiety disorder in people aged 4 to 18 years with chronic abdominal children with chronic abdominal pain does not, however, pain can be carried out by a general practitioner influence whether children continue to have abdominal Diagnostic triage should be carried out by means of pain (personal communication).16 assessment of alarm symptoms or signs and physical examination Can chronic abdominal pain be treated? Additional diagnostic evaluation is not required in Reassurance is the primary therapy in children with children without alarm symptoms chronic abdominal pain without alarm symptoms; a sub- Testing may be carried out to reassure children and stantial proportion of clinicians, however, prescribe their parents dietary or pharmacological interventions, including Treatment analgesics, antispasmodics, sedatives and, recently, Deal with psychological factors probiotics. Evidence for an effect of these interventions Educate the family (an important part of treatment) is based on only 12 randomised controlled trials.22-26 Focus on return to normal functioning rather than on Most studies were small and were carried out in the complete disappearance of pain children referred to paediatricians or paediatric Best prescribe drugs judiciously as part of a gastroenterologists. Children with psychiatric problems multifaceted, individualised approach, to relieve (such as anxiety or depressive disorders) and children symptoms and disability with known organic disorders and constipation were excluded from all studies (table 2). How effective are pharmacological and dietary irritable bowel syndrome were given peppermint oil interventions? capsules or placebo. Improvements on a scale showing Peppermint oil is thought to relax smooth muscle. In change in symptoms were reported in 71% of the one randomised controlled trial 42 children with children receiving peppermint oil compared with Table 2 | Effectiveness of treatments for abdominal pain in children Therapy Definition of disorder Description of trials Side effects Effectiveness Cognitive behavioural Recurrent abdominal pain Three randomised trials in 60 None reported Beneficial (family) therapy referred and 69 non-referred children compared cognitive behavioural therapy with waiting list or standard medical care Famotidine Recurrent abdominal pain and One randomised placebo Not evaluated Inconclusive dyspeptic symptoms controlled trial in 25 referred children; children showed improvement on a subjective scale but not on an objective measurement of abdominal pain Added dietary fibre Recurrent abdominal pain Two randomised placebo controlled Not evaluated Unlikely to be trials in 52 non-referred children beneficial and 40 children admitted to hospital Lactose-free diet Recurrent abdominal pain Two randomised controlled trials Not evaluated Unlikely to be comparing a lactose containing diet beneficial with a lactose-free diet in 38 children Peppermint oil Irritable bowel syndrome using One randomised placebo Not evaluated Likely to be Manning criteria controlled trial of peppermint oil for beneficial two weeks in 42 children referred to a paediatric gastroenterology centre Pizotifen Abdominal migraine using One placebo controlled crossover Drowsiness, Likely to be Rome II criteria trial of pizotifen for one month in 14 weight gain beneficial referred children Lactobacillus GG Irritable bowel syndrome using One randomised placebo Not evaluated Unlikely to be Rome II criteria controlled trial of lactobacillus GG beneficial in 50 children referred to a paediatric gastroenterology centre The effectiveness of analgesics, antispasmodics, sedatives, and antidepressants is currently unknown. 1000 BMJ | 12 MAY 2007 | VOLUME 334 CLINICAL REVIEW Gastroenterology, Hepatology, and Nutrition ONGOING RESEARCH presented recommendations for clinicians in primary What factors predict whether abdominal pain becomes and secondary care (box 3).16 chronic in children? What interventions are effective in reducing chronicity How can we improve the management of chronic of abdominal pain in children? abdominal pain? What interventions are effective in giving symptom Given the multifactorial onset of chronic abdominal relief and reducing its correlated functional disability? pain and the impact of family factors, the disorder is Do the Rome criteria predict the course of functional exceptionally suitable to be managed in general abdominal pain and the response to specific treatment in children? practice. Most knowledge about the prognosis and management of chronic abdominal pain, however, comes from studies carried out in referred children. This paradox should trigger research in primary 43% receiving placebo (relative risk 1.67, 95% care. confidence interval 0.95 to 2.93).24 A committee of American paediatric gastroenterologists concluded that peppermint oil given for two weeks might improve symptoms in children with irritable bowel syndrome.16 A patient's perspective In a placebo controlled crossover trial in 14 children I am Daphne. I am 12 years old. I have stomach-ache with abdominal migraine, the children reported fewer almost every day; the pain can just come on like that, days of pain while taking pizotifen (mean 8.21 pain free but when I am nervous—for instance, about a test paper days, 95% confidence interval 2.93 to 13.48).22 —it appears more often. Sometimes my belly contracts Available evidence is inconclusive for an effect of the with force and I have to run for the toilet, or I have to throw up, or I don't feel good at all. H2 receptor agonist famotidine on symptoms in In the beginning I often had to miss school, now I am children with functional abdominal pain. Famotidine used to it. I sit down and wait patiently; there isn't much improved dyspeptic symptoms only in a subgroup of I can do about it. I prefer to go outdoors into the fresh children with severe dyspeptic symptoms.22 24 air. I try not to get stressed, because that would upset The addition of dietary fibre is not effective (relative my stomach even more. risk 1.16, 95% confidence interval 0.47 to 2.87).23 I am a little ashamed of it. Some people find it awkward, Lactose avoidance is unlikely to improve symptoms but I am not badgered about it. Also when I don't feel of functional abdominal pain.22 24 well I will do my football training. During a training camp, I usually have diarrhoea and have to throw up, In one randomised controlled trial in children with but I go anyway. irritable bowel syndrome, abdominal pain was not I don't know where it comes from; there is no specific reduced with use of lactobacillus GG compared with reason. placebo.25 It is not that big a deal to me; I have had this for the last four years, and I feel that it's useless to get angry or sad How effective are psychological interventions? about it because what difference would it make? The biopsychosocial model suggests that functional A parent's perspective abdominal pain is related to several causes and in I am Daphne's mother. Daphne has had stomach-ache part to learnt response patterns. Cognitive since the age of seven years. The family doctor behavioural therapy is intended to intervene with prescribed laxatives but they were not effective in learnt response patterns. Three randomised relieving the pain. Subsequently Daphne was referred to a paediatrician. Blood, faeces, and urine tests controlled trials evaluated the efficacy of a cognitive revealed no abnormalities. Even endosonography behaviour programme and a cognitive behaviour and endoscopy were performed which also showed intervention for the family in the treatment of no cause for the pain. Each time we came to the recurrent abdominal pain.22 26 In one study improve- outpatient clinic Daphne had to tell her story over and ment occurred more quickly in the intervention over again. At a certain moment I thought, "What am I group than in the control group, and a larger propor- still doing here, they can not do anything anyway." So tion of children became completely pain-free. In the we stopped seeing the paediatrician. But I often still ask second study a higher rate of complete elimination of myself if there should be more behind it. I then hesitate about a second opinion. pain and lower levels of relapse were found at six and I feel so powerless when Daphne has pain or when she 12 months in the intervention group. In the third is on the toilet that long. In the beginning I was very study the intervention group reported significantly considerate and kept her from school, but at the same fewer episodes of abdominal pain immediately after time I did not want to spoil her too much, because I the intervention and after one year's follow-up; feared that then the pain would predominate. Happily significantly fewer school absences occurred in the enough she now manages quite well. As a family we intervention group.26 reckon with it but we give up nothing. We always have a toilet roll in the car and if necessary we stop on the hard shoulder. What do guidelines recommend? Daphne is a victim of heredity because both my Recently a subcommittee on chronic abdominal pain husband and I have the same trouble. of the North American Society for Pediatric BMJ | 12 MAY 2007 | VOLUME 334 1001 CLINICAL REVIEW Contributors: MYB wrote the first draft. MAB and MJG critically appraised and SUMMARY POINTS improved it. MJG interviewed the patient and translated the patients' stories. Chronic abdominal pain in children is not usually caused by MYB is guarantor. Competing interests: None declared. organic disease Diagnostic triage focuses on the assessment of alarm 1 Stordal K, Nygaard EA, Bentsen B. Organic abnormalities in recurrent symptoms by means of history and physical examination abdominal pain in children. Acta Paediatr 2001;90:638-42. Additional diagnostic evaluation is not required in children 2 Apley J, Naish N. Recurrent abdominal pains: a field survey of 1,000 school children. Arch Dis Child 1958;33:165-70. without alarm symptoms 3 Von Bayer CL, Walker LS. Children with recurrent abdominal pain: Family characteristics rather than patient characteristics issues in the selection and description of research participants. influence the chronicity of abdominal pain J Dev Behav Pediatr 1999;20:307-13. 4 Rasquin A, Di Lorenzo C, Forbes D, Guiraldes E, Hyams J, Staiano A, A specific intervention cannot be recommended owing to et al. Childhood functional gastrointestinal disorders: child/ lack of evidence of a beneficial effect adolescent. Gastroenterology 2006;130:1527-37. 5 Saps M, Di Lorenzo C. Interobserver and intraobserver reliability of the The challenge is to identify children at risk of a Rome II criteria in children. Am J Gastroenterol 2005;100:2079-82. prolonged course of pain and its correlated functional 6 Walker LS, Lipani TA, Greene JW, Caines K, Stutts J, Polk DB, et al. disability Recurrent abdominal pain: symptom subtypes based on the Rome II criteria for pediatric functional gastrointestinal disorders. J Pediatr Gastroenterol Nutr 2004;38:187-91. 7 Rowland M, Bourke B, Drumm B. Functional abdominal pain. Do the Rome criteria help the doctor or the patient? J Pediatr Gastroenterol In daily clinical practice a careful medical history Nutr 2005;41:S32-3. and thorough physical examination should be 8 Chitkara DK, Rawat DJ, Talley NJ. The epidemiology of childhood recurrent abdominal pain in Western countries: a systematic review. sufficient to recognise children with functional Am J Gastroenterol 2005;100:1868-75. abdominal pain. It should not be forgotten, however, 9 Ramchandani PG, Hotopf M, Sandhu B, Stein A and the ALSPAC study team. The epidemiology of recurrent abdominal pain from 2 to that functional abdominal pain has a great impact on 6 years of age: results of a large population-based study. a child's wellbeing and that in a considerable number Pediatrics 2005;116:46-50. of children it might persist. If time can be reserved to 10 Koloski NA, Talley NJ. Role of sexual or physical abuse in IBS. In: Camilleri M, Spiller RC, eds. Irritable bowel syndrome. Diagnosis and evaluate family coping strategies and psychosocial treatment. Oxford: WB Saunders, 2002:37-43. factors and if appropriate follow-up can be arranged, 11 Rimsza ME, Berg RA. Sexual abuse: somatic and emotional reactions. Child Abuse Neg 1988;12:201-8. ineffective use of healthcare resources might be 12 Price L, Maddocks A, Davies S, Griffiths L. Somatic and psychological prevented. problems in a cohort of sexually abused boys. A six year follow-up case-control study. Arch Dis Child 2002;86:164-7. We thank Bart Koes and Siep Thomas for their comments on the final draft. 13 Ramchandani PG, Stein A, Hotopf M, Wiles NJ; ALSPAC study team. Early parental and child predictors of recurrent abdominal pain at school age: results of a large population-based study. J Am Acad Child Adolesc Psychiatry 2006;45:729-36. 14 Walker LS, Williams SE, Smith CA, Garber J, Van Slyke DA, Lipani TA. Parent attention versus distraction: impact on symptom complaints by children with and without chronic functional abdominal pain. ADDITIONAL EDUCATIONAL RESOURCES Pain 2006;122:43-52. 15 Gwee KA, Leong YL, Graham C, McKendrick MW, Collins SM, Cochrane Library (www.cochrane.org) Walters SJ, et al. The role of psychological and biological factors in Systematic reviews and meta-analyses on the efficacy postinfective gut dysfunction. Gut 1999;44:400-6. 16 American Academy of Pediatrics Subcommittee on Chronic of treatments for chronic abdominal pain Abdominal Pain; North American Society for Pediatric Useful references Gastroenterology Hepatology, and Nutrition. Chronic abdominal pain in children. Pediatrics 2005;115:e370-81. Guthrie E, Thompson D. ABC of psychological medicine. 17 Macarthur C. Helicobacter pylori infection and childhood recurrent Abdominal pain and functional gastrointestinal abdominal pain: lack of evidence for a cause and effect relationship. disorders. BMJ 2002;325:701-3 Can J Gastroenterol 1999;13:607-10. 18 Fitzpatrick KP, Sherman PM, Ipp M, Saunders N, MacArthur C. Bass C, May S. ABC of psychological medicine. Screening for celiac disease in children with recurrent abdominal Chronic multiple functional somatic symptoms. pain. J Pediatr Gastroenterol Nutr 2001;33:250-2. BMJ 2002;325:323-6 19 Westert GP, Schellevis FG, de Bakker DH, Groenewegen PP, Mayou R, Farmer A. ABC of psychological medicine. Bensing JM, van der Zee J. Monitoring health inequalities through general practice: the second Dutch national survey of general Functional somatic symptoms and syndromes. practice. Eur J Public Health 2005;15:59-65. BMJ 2002;325:265-8 20 Walker LS, Guite JW, Duke M, Barnard JA, Greene JW. Recurrent abdominal pain: a potential precursor of irritable bowel syndrome in Talley NJ, Phung N, Kalantar JS. ABC of the upper adolescents and young adults. J Pediatr 1998;132:1010-5. gastrointestinal tract. Indigestion: when is it functional? 21 Crushell E, Rowland M, Doherty M, Gormally S, Harty S, Bourke B, BMJ 2001;323:1294-7 et al. Importance of parental conceptual model of illness in severe Information for patients recurrent abdominal pain. Pediatrics 2003;112:1368-72. 22 Weydert JA, Ball TM, Davis MF. Systematic review of treatments for International Foundation for Functional Gastrointestinal recurrent abdominal pain. Pediatrics 2003;111:e1-11. Disorders (www.aboutkidsgi.org/) 23 Huertas-Ceballos A, Macarthur C, Logan S. Dietary interventions for recurrent abdominal pain (RAP) in childhood. Cochrane Database The foundation is a non-profit organisation that tackles Syst Rev 2002;(2):CD003019. the problems associated with living with 24 Huertas-Ceballos A, Macarthur C, Logan S. Pharmacological gastrointestinal functional disorders. interventions for recurrent abdominal pain (RAP) in childhood. Cochrane Database Syst Rev 2002;(1):CD003017. Membership required 25 Bausserman M, Michail S. The use of Lactobacillus GG in irritable American College of Gastroenterology (http://gi.org/ bowel syndrome in children: a double blind randomised control trial. patients/gihealth/functionalab.asp) J Pediatr 2005;147:197-201. 26 Robins PM, Smith SM, Glutting JJ, Bishop CT. A randomised Patient information on functional abdominal pain in controlled trial of a cognitive-behavioral family intervention for children pediatric recurrent abdominal pain. J Pediatr Psychol 2005;30:397-408. 1002 BMJ | 12 MAY 2007 | VOLUME 334
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