The Urge to Itch

Here's the link to the abstract for a new article about the genetics of Familial Primary Localized Cutaneous Amyloidosis. Amyloidosis can be primary or secondary, systemic or localized. In this case, the article discusses primary amyloidosis (it is not the result of another condition) that is localized to the skin (internal organs are spared). This disease can be divided into lichenoid, macular, and nodular appearances, but all consist of amyloid (a protein) deposits in the skin that are very itchy. The treatment is to decrease the itchiness via topical steroids, antihistamines, and light therapy and in certain cases, to remove or destroy the deposits. There is no treatment for the mechanism of the disease, only symptom mitigation.

The most interesting part of this article is the new information on the mechanism of itchy skin. The Oncostatin M Receptor beta is mutated in FPLCA. It is used as a building block for Oncostatin M type II receptors and interleukin-31 receptors. With the mutations, the two cytokines, Oncostatin M and IL-31, are ineffective. This may be the cause for itching. Further research needs to be done on other itchy skin disorders and see if they too have a defect in this pathway.

Anti-aging creams?

Here's an article on ingredients to look for in "anti-aging" or "anti-wrinkle" products. The review is meant to identify products that help with skin surface regularity, deep wrinkles, and dyspigmentation.

I can't access the full article right now, but will update...

MRSA: to decolonize or not to decolonize?

Although the Dutch system of "search and destroy" has given the Netherlands one of the lowest rates of MRSA colonization and infection, testing everyone in a hospital for MRSA and subsequently treating is not generally recommended. Numerous studies have advocated colonization screening and mupirocin decolonization for outbreaks, but it has not been proven to reduce infections in endemic areas. This study from Kauffman, et al is widely cited and makes a few key points:
1) reduction of MRSA colonization is not necessarily correlated to reduction of MRSA infection in facilities without high infection rates
2) mupirocin resistance is increasing with prolonged use
3) intranasal mupirocin is only an effective decolonizer if all other colonized areas of the body are treated with mupirocin as well

Mupirocin is widely used, especially in dermatology, for recurrent superficial infections and wound healing in high-risk individuals. It will be interesting to follow the trend of mupirocin resistance amongst strains of MRSA. Mupirocin is by far the most effective agent in decolonization although new medications are under review. There are two types of mupirocin resistance, high-level (plasmid-mediated) and low-level (still mupirocin susceptible at the commonly used dosage). High-level resistance is most concerning and was shown to increase with widespread mupirocin use in the above study.

Kauffman CA, Bradley SF, Terpenning MS. Methicillin-resistant Staphylococcus aureus in long-term care facilities. Infect Control Hosp Epidemiol. 1990;11:600–603.

Scott and White to test all patients for MRSA

Now here's an interesting piece of news! Scott & White hospitals in Round Rock and Temple, TX are going to start testing all patients for MRSA colonization through nasal cultures. This will surely provide some interesting epidemiological data, but the bigger question is, what will they do with this information? Are they going to try to treat everyone who is colonized? Study after study does not recommend this unless the patient has recurring infections. This is going to be an important question in the coming years, should asymptomatic MRSA carriers be treated? The Netherlands maintains one of the world's lowest MRSA colonization and infection rates by screening for MRSA upon hospital admission and subsequently treating all colonizers. Does the US have the resources for this? Also, with mupirocin-resistant MRSA emergence, is it a waste of resources to treat patients who are asymptomatic? And would treatment involve just topical antibiotics? Antiseptic washes? Oral antibiotics? I'm eager to see how this information is handled and if hospital MRSA infection rates are decreased.

New type of tattoo ink

Laser tattoo removal is when the pigmented ink in the skin absorbs energy from the laser, breaks down, and is resorbed by the body's immune system. This requires a certain wavelength to target a certain color at a certain depth in the skin. Also, the energy should not be so much as to damage the surrounding skin. Some colors are easier to remove than others, and tattoos that are more skillfully applied at an even depth across the skin are easier to remove as well.

Freedom-2 is an interesting, relatively new product that allows for easier tattoo removal. Instead of the multiple laser treatments and incomplete removal, Freedom-2 advertises tattoo removal after just one laser treatment. They do this by using a biodegradable ink that is microencapsulated. These microcapsules are what make up the tattoo. When a laser's energy is applied to the capsules, they burst, releasing the biodegradable ink. This is assuming it is easier to burst open the capsule than it is to heat and destroy normal ink. Also, it should be easier for the body to dispose of the biodegradable ink than the normal ink.

It is featured as one of Time magazine's best new inventions, and is really a clever idea. However, keep in mind that this product is not FDA-regulated and has not been thoroughly studied in the literature. The material used for encapsulating is not listed on their web page, but it is always a risk that you may have an allergy to the product.

Exercising makes wounds heal faster

At least according to this study. It is a pretty straight forward look at wound size in a sedentary versus exercise group of mice. The exercise did not have a statistically significant effect on wound healing in young mice, but did in older mice. TNF alpha, monocyte chemoattractant, and keratinocyte chemoattractant were all decreased with exercise. These mainly cause inflammation at the wound site. From this data, it can be inferred that exercising reduces inflammation in the skin, which speeds up wound healing in mice. We'll see how this translates to humans, but it's an interesting study overall.

Why is the nose the most common site of BCCs?

A study out of Australia attempts to explain why basal cell carcinomas are most commonly found on the sides of the nose. Here is the news article I found. It seems like a reasonable theory that our curved eyeballs would reflect UV rays onto the side of our noses, making skin cancer more common there than on other parts of our face that are equally exposed to sunlight. Also, the medial canthus (inner corner of the eye) is a common place to see skin cancers, but looks like it is pretty well-shadowed to direct sun. According to this study, it receives a focused ray of UV radiation reflecting from the eye, which might explain its susceptibility to BCCs. The study uses models to show how 60-100% of UV radiation is reflected from the eye surface and where this reflected radiation is eventually absorbed, helping to explain why some areas of the face are more likely to get skin cancers.

Now we need a study discussing the effects of wearing sunglasses on the distribution of skin cancers as the flatter lenses should prevent as much reflection onto the face.

Birt B, Cowling I, Coyne S, Michael G. The effect of the eye's surface topography on the total irradiance of ultraviolet radiation on the inner canthus. J Photochem Photobiol B. 2007 Apr 2;87(1):27-36

Birt B, Cowling I, Coyne S. UVR reflections at the surface of the eye. J Photochem Photobiol B. 2004 Dec 2;77(1-3):71-7.

National Hairdressers Day

Hairdressers are particularly prone to hand dermatitis, and today seems like a great day to discuss why. The constant wet and dry of their hands drys the skin and weakens its protective barrier. With the addition of the large number of irritating chemicals and the possibility of developing allergies to other chemicals, hairdressers have pretty beaten up hands.

PPD (paraphenylendiamine) in black hair dye and glycerol monothioglycolate in hair perming solutions are two allergens that hair dressers come ac. People are exposed to them and over time can become sensitized. This means that the immune system recognizes the chemical as an allergen and mounts an immune response to it upon subsequent exposures.

PPD is also used in "black henna". Henna is naturally green and has not been reported as an allergen before. However, PPD is used to blacken the color, so someone can become sensitized to PPD without having used hair dye. This web page has a great picture of allergic contact dermatitis to black henna (PPD).

Vinyl gloves are effective at preventing PPD sensitization, but not glycerol monothioglycolate sensitization. How do you treat allergic contact dermatitis? Avoidance is the only way to prevent it. And topical steroids can be used to help current lesions heal.

Take home points:
1. Black hair dye, black henna tattoos, and perming solutions contain common allergens
2. People can become allergic to something with repeated exposure over time


Redlick F, DeKoven J. Allergic contact dermatitis to paraphenylendiamine in hair dye after sensitization from black henna tattoos: a report of 6 cases. CMAJ. 2007 Feb 13;176(4):445-6.

Fisher AA. Management of hairdressers sensitized to hair dyes or permanent wave solutions. Cutis. 1989 Apr;43(4):316-8.

CA MRSA in dermatology

Community-acquired methicillin Staphylococcus aureus (CA MRSA) is a relatively recent infection (the last decade). It is particularly relevant to dermatologists as these bacterial strains present most commonly as skin or soft tissue infections. With the recent media blitz surrounding MRSA, it is difficult to discern the medical facts from the news reports. The American Academy of Dermatology has some valuable Talking Points and FAQs that are useful to both patients and healthcare professionals alike.

Mineral makeup

I've heard lots of patients extol the virtues of mineral makeup, and from what I have seen, it appears to be very effective as a natural-appearing foundation. It is pretty amazing how well it covers up patchy skin pigmentation or redness on the face, but still looks natural. And as of yet, I have not seen any irritant or allergic contact reactions to the makeup. It's claim to fame is that it is almost solely made of finely pulverized natural minerals and does not contain fillers and preservatives. Since the fillers and preservatives are common allergens and irritants, the pure mineral makeup could be safer for sensitive skin. However, there is no regulatory body certifying the purity of this makeup so it is up to the consumer to check ingredients. There are lots of companies out there (as evidenced by a simple Google search), and it is difficult to know which ones are better and safer. As with sunscreens, there is concern over the safety of nanoparticles being applied to the skin as there would likely be increased absorption. The absorption of topical powdered minerals has not been studied, so I cannot comment on this either way. One of these weekends, I'm going to explore the makeup counters at the mall and see what sorts of products are out there and what ingredients they use...

I've been away

I've been away for a couple months doing rotations at other medical schools and have fallen behind on my posts. Many are in the works and I just haven't had time to read all the journal articles before posting. Now that I'm back, look for the daily posts.

Smallpox vaccine and eczema

This article discusses how the newest smallpox vaccine has been approved for testing in patients with eczema or atopic dermatitis.

Between 1 and 6 percent of patients vaccinated with the original smallpox vaccine had eczema vaccinatum (EV), where the live virus vaccine actually caused a smallpox infection. The mortality rate for EV is 1%. This article explains why people with atopic dermatitis may have this response. The vaccine is administered via the lower epidermis, which has proven to have the best immune response. Individuals with atopic dermatitis have an altered epidermis that does not produce the same quantity of anti viral and anti bacterial proteins. Further, with the dermatitis, there is an exagerrated Th2 response, but Th1 cells are the primary cell-mediated immune cells. Basically, patients with atopic dermatitis could not safely be vaccinated with the original vaccine. In fact, exposure to someone who was vaccinated was enough to give some patients EV. Because over 50% of the population has eczema or comes in direct contact with someone who does, it is an important step for a vaccine to reduce the risk of EV.

Engler RJ, Kenner J, Leung DY. Smallpox vaccination: Risk considerations for patients with atopic dermatitis. J Allergy Clin Immunol. 2002 Sep;110(3):357-65.

Sweaty palms... treatment with surgery

If iontophoresis and botox are not treating the hyperhidrosis, the effected area of skin can be excised (usually only used for axillae), denervated with a sympathectomy, or liposuction can be performed to remove the sweat glands at the dermal/subcutaneous border (usually only used in axillae). The surgeries should only have to be done once, but are significantly more involved than the prior treatments discussed. The article in the Canadian literature referenced yesterday has a nice discussion about when to use which treatment. And Emedicine has a good summary of the surgical procedures.

Boni R. Tumescent suction curettage in the treatment of axillary hyperhidrosis: experience in 63 patients. Dermatology 2006; 213:215– 217.

Sweaty palms... treatment with botox

Botulinum toxin A blocks the release of the neurotransmitter acetylcholine at the neuromuscular junction. This toxin, which is produced by the Clostridium botulinum bacteria, inhibits the stimulation of muscular cells, including those surrounding eccrine sweat glands. Blocking the secretion of sweat glands in this way has proven to be an effective treatment usually lasting 3-4 months. It does, however, require multiple injections. With 1.5 cm standard spacing, my palms would need about 50 injections each.

Solish N, Bertucci V, Dansereau A, Hong HC, Lynde C, Lupin M, Smith KC, Storwick G; Canadian Hyperhidrosis Advisory Committee. A comprehensive approach to the recognition, diagnosis, and severity-based treatment of focal hyperhidrosis: recommendations of the Canadian Hyperhidrosis Advisory Committee. Dermatol Surg. 2007 Aug;33(8):908-23.

Sweaty palms... treatment with iontophoresis

Finding studies proving the efficacy of iontophoresis for hyperhidrosis was not as difficult as figuring out how iontophoresis works. The hands and feet are placed in a water bath and a direct electric current is run through it. This is a popular treatment if topical aluminum salts have failed. Iontophoresis is also used to help with the cutaneous absorption of drugs.

This article (and others following it) have related the accumulation of hydrogen ions in the sweat glands to secretory damage. With the electric current, water becomes acidified and the ions more easily penetrate the skin because of the current. They collect in the sweat glands and damage them. It takes multiple treatments for hyperhidrosis treatment, as after one treatment, there was only a mild decrease in activity with choline stimulation.

Sato K, Timm DE, Sato F, Templeton EA, Meletiou DS, Toyomoto T, Soos G, Sato SK. Generation and transit pathway of H+ is critical for inhibition of palmar sweating by iontophoresis in water. J Appl Physiol. 1993 Nov;75(5):2258-64.

Sweaty palms

Hyperhidrosis is excess sweating via the eccrine glands beyond what is required for thermal regulation. There are various guidelines for how much sweat produced over a certain body area is normal, but clinically no one uses these. The guidelines are used more for research than for actually diagnosing the condition. The loose definition for hyperhidrosis is excess sweating that interferes with daily activities.

Today I was just going to discuss different causes of excess sweating and the quality of life implications. Over the next couple days I'll discuss two of the treatments.

Emedicine has a great article if you are interested in details. I thought hyperhidrosis would have more information on the internet, but most of what I found were ads for various treatments.

Localized essential hyperhidrosis usually presents in childhood or adolescence as localized excess eccrine sweat production of the palms, soles, and/or axillae. The exact cause is unknown, but it is believed to be triggered by overactive sympathetic innervation causing excessive stimulation of the glands. Palms and soles sweating is not associated with heat, but more so with anxiety, so the excess sweating should stop when the patient is asleep or sedated. Generalized excess sweating may be caused by systemic disease and should be further investigated. The Emedicine article has a list of disorders under the "Causes" subheading that can present with localized or generalized excessive sweating.

I helped treat a patient with hyperhidrosis of the palms and soles, and it was interesting to hear her perspective on how this has affected her life. She doesn't like to shake hands and can't wear shoes without socks. The thing she was most looking forward to after her treatment was to wear dress shoes! Although her disorder is completely benign, the quality of life implications can be socially debilitating. A friend of mine has trouble with yoga because of her sweaty soles, and people with axillary hyperhidrosis suffer from embarrassing sweat stains. Depending on a person's age and occupation, the effects of hyperhidrosis can vary in severity.

First line treatment is topical aluminum salts (used in anti-perspirants), which are drying to the skin.

Aamir Haider and Nowell Solish. Focal hyperhidrosis: diagnosis and management.
Can. Med. Assoc. J. 2005 172: 9.

UV protection from windows Part 2

I did some more research on UV protection of windows since I got stuck on window films the last time I posted about this.

I found a great review article discussing the photoprotective properties of glass and what is being done to increase broad spectrum UV protection.

Tuchinda C, Srivannaboon S, Lim HW. Photoprotection by window glass, automobile glass, and sunglasses.J Am Acad Dermatol. 2006 May;54(5):845-54.

I wish that everyone could have a copy of this article, as it has some useful tables, but here's my attempt at summarizing it.

Clear glass allows almost full (90%) visible light transmission and blocks about 30% of solar heat and 20% of UV radiation. Depending on the use of the glass (commercial v. residential) and how much visible light transmission is desired, different methods of fortifying clear glass are available. Here are some properties of glass and how they affect light transmission.

1. Thickness - minimal effect on light transmission
2. Double-glazing - moderate reduction in UV and heat radiation without sacrificing much visible light transmission
3. Tinting - more effective than double-glazing in UV and heat radiation, but sacrifices visible light transmission
4. Reflective coating - significant reduction of visible light, UV, and solar heat transmission
5. Low emissivity glass (coating of microscopically thin, transparent layers of silver between layers of antireflective metal oxide coatings) - significant reduction of UV and heat radiation without sacrificing much visible light transmission
6. Laminated glass (bonding two pieces of glass together with polyvinyl butyral) - dramatic reduction of UV radiation but only moderate reduction of solar heat while retaining good visible light transmission
7. UV-blocking coating - dramatic UV reduction with minimal solar heat and visible light transmission reduction

According to this article, using double glazed glass, where one piece is low-e glass and the other has the UV-blocking coat offers the best UV and heat insulation without sacrificing visible light and can block up to 99.9% of UV transmission. The thing to remember is that UV blocking is not uniform over all wavelengths. It is easier to block shorter wavelengths than longer ones. So the 0.1% of UV transmitted will not be a cross section of UV wavelengths, but will be predominantly UVA1 (long wavelength) waves.

According to this report from the government, a ten-window house can spend $75 more per window ($750) to get a more efficient frame with low-e double glazed glass instead of plain clear glass. The energy savings per year for heating/cooling are estimated at $319 per year. In less than 2.5 years, the energy savings would make up for the increased cost, not to mention the sun protection benefits. With housing design including more windows, the sun protection factor cannot be discounted.

New psoriasis drug in the news

The World Congress of Dermatology met this past week in Argentina, and this story made international news. It is about the new biologic drug used to treat psoriasis, Ustekinumab. I found this study detailing its mechanism of action

Reddy M, Davis C, Wong J, Marsters P, Pendley C, Prabhakar U. Modulation of CLA, IL-12R, CD40L, and IL-2Ralpha expression and inhibition of IL-12- and IL-23-induced cytokine secretion by CNTO 1275. Cell Immunol. 2007 May;247(1):1-11.

This drug works by targeting IL-12 and IL-23. Current medications such as Adalimumab (Humira), Etanercept (Enbrel), Efalizumab (Raptiva), and Infliximab (Remicade) work similarly by targeting other types of cell messangers. All but Efalizumab work by blocking TNF alpha, an inflammation-causing mediator. Efalizumab binds to CD11a and prevents T cell functioning. Because psoriasis is mediated by T cells, these biologic drugs can work. Further, IL-12 is one of the key mediators in T cell activation.

Part of the problem with the current biologics is that they are extremely expensive (which I'm sure Ustekinumab will be also), and they require weekly injections or infusions. This new drug promises to only require monthly self injections, which is far more convenient and less painful than the weekly administrations. It should also help reduce cost compared to a drug like remicade, which requires infusions at specialty pharmacies or a hospital.

Do eyebrows grow back?

According to this study

Fezza JP, Klippenstein KA, Wesley RE. Cilia regrowth of shaven eyebrows. Arch Facial Plast Surg. 1999 Jul-Sep;1(3):223-4.

eyebrow regrowth after complete shaving is possible. Five brave patients had one eyebrow shaven and within 4 months all but one had full regrowth. The fifth patient required an extra couple months for full regrowth. Because of the small sample size, no conclusions can be drawn as to the implications for widespread eyebrow shaving. However, this should debunk the commonly held myth that eyebrows don't grow back.

Ultraviolet-C rays

We don't hear much about UVC rays in the popular media or in the literature with relation to skin damage. This is because UVC is blocked by the ozone layer and has not been a significant player in skin damage. Most journal articles discussing UVC address its germicidal properties and use in laboratory research. But as the ozone layer continues to thin, UVC damage will become more significant in the pathogenesis of skin disease.

UV protection from windows

There are a two questions I want to address in this posting:

1. How much UV radiation to normal windows block?

Normal glass is good at filtering out lower wavelength UV waves (UVB), but UVA waves predominantly transmit through the glass.

2. Do the UV films and special UV windows actually make a difference?

In this study, the UV film added to the auto glass had a significant reduction in cytotoxicity compared to normal glass. The plain glass offered 29% protection while glass and film together offered 93% protection. This includes longer wavelength UVA. But this study only measured the resultant effects on cells and did not actually measure which and how much UV radiation went through the glass, making it difficult to draw conclusions about UVA v. UVB protection from the film.

Bernstein EF, Schwartz M, Viehmeyer R, Arocena MS, Sambuco CP, Ksenzenko SM. Measurement of protection afforded by ultraviolet-absorbing window film using an in vitro model of photodamage.Lasers Surg Med. 2006 Apr;38(4):337-42.

The Skin Cancer Foundation has a list of recommended window films for UV protection. I haven't been able to figure out how they chose these window films. On 3M's website, they say that all of their films listed here block 99.90% of UV radiation, but again, no details.

According to

Edlich RF, Winters KL, Cox MJ, Becker DG, Horowitz JH, Nichter LS, Britt LD, Long WB, Edlic EC.Use of UV-protective windows and window films to aid in the prevention of skin cancer. J Long Term Eff Med Implants. 2004;14(5):415-30.

the International Window Film Association offers certifications for certain levels of UV protection, but after checking out their website, I couldn't find any detailed standards.

And this article

J.A. Johnson and R.M. Fusaro, Broad-spectrum photoprotection: the roles of tinted auto windows, sunscreens and browning agents in the diagnosis and treatment of photosensitivity, Dermatology 185 (1992), pp. 237–241.

is able to correlate visible light transmitted to UV light transmitted. Basically concluding that the less visible light transmitted, the broader spectrum of UV protection available.

Basically it's hard to tell which window tints are better than others, but it is safe to assume that darker tints will block more UV radiation.

Psoriasis... is it contagious?

Today, my first day of a Pediatric Dermatology rotation, I was struck by the significant lack of public awareness about psoriasis. Almost 1 in 50 people have psoriasis. 125 million people worldwide have this condition, and everyone must know someone (if not a few someones) with psoriasis. Yet two patients came in on the same day requesting notes for their teachers stating that their skin condition is not contagious. If there is any way to make a shy adolescent who has so much psoriasis that he wears a baseball cap, long pants, and long sleeve shirts in the Texas heat any more uncomfortable, it is to imply that other kids may not be safe around him. The teacher did not trust either of these students' or their parents' retelling of the diagnoses. These kids know what they have because they are reminded with every pill they take and every ointment they use, not to mention the physical discomfort they endure.

I read this article talking about a drug-company sponsored public health website with a great section onpsoriasis. It is well done and informative. There are many other great websites out there with reliable information, including the National Psoriasis Foundation. I hope you take a few minutes to learn a little more about psoriasis.

Is tanning ever good for you? (Neonatal jaundice)

It is not uncommon for neonates to have high bilirubin levels, causing jaundice. This is because their livers are still immature and are not able to process heme at full capacity quite yet (decreased uptake and conjugation of bilirubin) and they have a higher red blood cell turnover rate than adults. The bilirubin deposits in the epithelium, causing the yellow tint in their eyes and skin. This could lead to more serious depositions in the nervous system, and possibly kerincterus.

The number one therapy is phototherapy, with blue, white, or green lights. Blue is best absorbed by the yellow bilirubin and helps metabolize it to water-soluble lumirubin, which can then be excreted. Green has a longer wavelength and may be better for protein-bound bilirubin. Phototherapy causes a systemic reduction in bilirubin levels.

Dennery PA, Seidman DS, Stevenson DK. Neonatal hyperbilirubinemia. N Engl J Med. 2001;344 :581 –590

Is tanning ever good for you? (Psoriasis and eczema)

UV light has anti-inflammatory effects that can help control both psoriasis and atopic dermatitis. This treatment is used in both children and adults and is thought to be particularly effective for acute onset conditions. PUVA, UVB, and narrow-band UVB have all been used. PUVA requires the ingestion of a psoralen pill before treatment, which increases photosensitivity to UVA waves. Narrow band UVB is thought to have fewer side effects than normal UVB treatment.

There are lots of studies on the effectiveness of PUVA and UVB for psoriasis and eczema treatments. But this study discusses the mechanism of action of PUVA v, NB-UVB v cyclosporin.

Erkin G, Ugur Y, Gurer CK, Asan E, Korkusuz P, Sahin S, Kolemen F. Effect of PUVA, narrow-band UVB and cyclosporin on inflammatory cells of the psoriatic plaque.
J Cutan Pathol. 2007 Mar;34(3):213-9.


- PUVA is the only treatment that decreased Langerhans cells (CD1a+) in the epidermis
- All 3 treatments decreased T lymphocytes (CD4+ and CD8+)
- All 3 treatments reduced expression of CD86, an inflammatory stimulator

Is tanning ever good for you? (Acne)

Narrow band blue light (420 nm) has anti-inflammatory effects on acne. It is less useful for comedonal acne, where inflammation is less prevalent. The light attacks the heme metabolism mechanism of Propionibacterium acnes, therefore killing the bacteria. This study showed the antinflammatory effects of the blue light also. There was reduced staining of IL-1alpha and ICAM-1, both indicators of an inflammatory response. And with the addition of low-dose narrow band-UVB (312 nm), the results were even better.

Shnitkind E, Yaping E, Geen S, Shalita AR, Lee WL. Anti-inflammatory properties of narrow-band blue light. J Drugs Dermatol. 2006 Jul-Aug;5(7):605-10.