Side Effects of Laser Treatment of Nevus of Ota

Lasers have revolutionized the treatment of nevus of Ota and other dermal melanocytoses. The Q-switched ruby (694 nm), Q-switched alexandrite (755 nm), and Q-switched Nd:YAG (1064 nm) lasers have all been shown to effectively treat nevus of Ota. As with many new treatments, adverse effects accompany the benefits, and this long-term, large study from a Japanese hospital proves that these treatments are no exception.
More than 400 patients with nevus of Ota were treated over 16 years; 101 of these patients were treated with the Q-switched ruby laser and evaluated 1 year after the last treatment. Long-standing hypopigmentation was the most common side effect, affecting almost 17 percent of patients. Almost 6 percent of patients had hyperpigmentation. One patient whose nevus of Ota had cleared completely developed a recurrence.
Comment: Rates of clearing nevus of Ota with the Q-switched ruby and other short-pulsed lasers approach 100 percent. Although recurrences are very uncommon, side effects -- unfortunately -- are not. Hyperpigmentation was relatively rare and most often temporary, but hypopigmentation was relatively common and permanent in almost 17 percent of patients. Given the similar wavelength and the resulting similarity in melanin-absorption spectra, it is likely that the Q-switched alexandrite laser would produce the same kind of pigmentary side effects as the ruby laser. Q-switched Nd:YAG lasers, however, are less likely to produce such changes, because at 1064 nm, their light is less well absorbed by melanin pigment. Only long-term evaluation of the other Q-switched lasers will determine their actual side-effect profiles, but theoretical analysis leads to the prediction that the Nd:YAG laser will become the laser of choice for this condition.

Timothy Brown - Man "cured" AIDS

Inspired by the only person ever to be cured of HIV, the International AIDS Society has launched a new research strategy aimed at ridding patients of the deadly virus.
When Timothy Brown took the stage, awe descended over delegates gathered at the 2012 International Cord Blood Symposium in San Francisco last month. It is not, after all, everyday they are addressed by someone sounique: Brown is the only person in the world to have been apparently cured of HIV infection. A donor for a 2007 haemopoietic stem cell transplant to treat his leukaemia was also carefully chosen to confer a rare genetic mutation, which protects those with it from contracting HIV.The natural mutation-a short deletion in both copies of the CCR5 gene-is present in less than 1% of the population. Also known as the Berlin patient after the Berlin-based clinical team that treated him, he made headlines around the world when details of his case were published in February, 2009. Brown is now both free of leukaemia and HIV. "After 5 years without HIV medications, I still have no trace of HIV in my body", he tells the audience. "[And] I have been poked and biopsied from head to toe."
Brown's case has energised HIV researchers and helped inspire a new global scientific strategy aimed at finding an HIV cure for the 34 million people infected with the virus worldwide (the strategy does not cover the development of a prophylactic vaccine or preventive approaches). Unveiled on July 19 by a working group of the International AIDS Society (IAS) ahead of the 2012 International AIDS Conference in Washington, DC, USA (July 22-27), Towards an HIV Cure, aims to provide a road map for scientists, governments, funders, and industry to get the job done.
"There is widespread acceptance that we need a fundamentally different way of approaching HIV infection", says Steven Deeks, an HIV researcher at the University of California, San Franciso, USA, who co-chairs the working group, along with IAS President Françoise Barré-Sinoussi who co-discovered HIV. Right now, Deeks explains, there are more than 20 antiretroviral drugs that are quite good at suppressing the virus and can grant decades of healthy life. But there are "limitations to the approach". In order for the drugs to work people have to take them every day, they have side-effects, are expensive, and access is not universal. "The Berlin patient...demonstrated to the field that a cure, which most people thought was impossible, could be done."
The new strategy outlines seven main priorities for research straddling basic, translational, and clinical science (panel) if either a "sterilising cure", which permanently removes the virus, or a "functional cure", which controls it for years without drugs, is to be found. It also outlines several potential routes for the eradication of HIV: use of aggressive drug regimens; early initiation of antiretroviral therapy (ART); use of virus-purging agents; enhancement of anti-HIV immunity; better understanding of basic HIV science; modification of host genetics; and use of HIV-specific killing agents.The report also highlights ethical challenges of the work, including the problem of undertaking clinical trials when the effectiveness of ART means that there is little benefit to volunteers from participating.
Panel
Seven main priority areas for research into an HIV cure *Cellular and viral mechanisms involved in HIV persistence at a molecular level *Anatomical compartments and cellular sources of HIV reservoirs *Immune activation and dysfunction in the presence of antiretroviral therapy *Natural models of HIV/simian immunodeficiency virus control *Assays to measure persistent infection *Therapeutic and immunological approaches for eliminating persistent HIV infection *Enhancement of immune response to control viral replication
A particular focus is on developing drugs to kill the infected cells. "One of the major barriers to a cure is that the virus persists [during long-term ART] in this latent state", says Deeks. A theoretical approach to a cure could be a four part assault. A drug like vorinostat, which causes the latent virus to be expressed, along with an anti-inflammatory drug to diminish the number of infectable cells, a therapeutic vaccine to enhance the capacity of the immune system to kill those infected cells that are now making virus, and intensified ART to prevent any new cells from becoming infected.
But it is "impossible to guess" how far away that is, says Deeks.Scientists still have much to learn first about the basic biology of HIV including, for example, how the virus persists during long-term ART and how the so-called "elite controllers"-the small group of people who, unlike those with the double CCR5 mutation, acquire the infection but can control it-actually do so. Deeks says that research in this area might reveal a mechanism to allow any patient with HIV to become an elite controller.
Also highlighted in the strategy is gene therapy for HIV, which consists of taking cells from the patient, altering them so that they contain the CCR5 mutation and then expanding the number and re-infusing them into the patient with the hope that they will work as well as a naturally occurring CCR5 mutation.Yet the most immediate hope for a cure in the clinic likely lies in the stem cell transplantation approach used on Brown. "The second patient who is going to be truly cured is probably going to be somebody who gets another stem cell transplant of some kind or another", says Deeks.
Unfortunately, however, the expensive technique is applicable to very few patients with HIV: those with haematological malignancies that require a stem cell transplant, though there is some interest in also possibly using it for the few patients who do not respond to ART. For most patients with HIV, for whom antiretroviral drugs prolong life for many decades, it simply is not worth undergoing a risky transplant procedure, making the technique unsuitable for mass application. "If you want to change the global nature of this epidemic, then you are going to need something that is going to be applicable to everybody-and that is probably going to have to be through other mechanisms", says Deeks.
Yet questions about scalability are not stopping transplant scientists from pushing the frontiers. Following Brown's appearance, delegates at the Cord Blood Symposium heard how transplants from stem cells derived from umbilical cord blood could be the next step in curing patients who have HIV and a haematological malignancy.
Leading the discussion was Lawrence Petz, the chief medical officer at the cord blood therapeutics company, StemCyte. "Since [Brown's] transplant was so successful why hasn't it been done again for other patients?" Petz asks. The answer is that Brown was extremely lucky: it is hard enough in the case of normal stem cell transplants to find a donor who is immunologically compatible with the recipient, and even more difficult if that donor also needs to have a double copy of a rare CCR5 mutation. The Berlin team, led by Gero Hütter, has failed to repeat its success not for want of trying but because it has not proved possible to find a donor who is the right match.
Petz's solution is to do the same transplant with stem cells from cryopreserved cord blood. Because cord blood stem cells are regarded as naive, the compatibility between the donor and the patient does not have to be as exact. For a given patient, it is easier to find a suitable cord blood unit with the CCR5 mutation. StemCyte began collaborations with cord blood banks worldwide to systematically screen samples for the CCR5 mutation in 2011. Thus far, of the 17 000 samples screened, it has found 102. The plan is to screen another 30 000 samples in the hope of the inventory reaching at least 300. That is the number, Petz predicts, at which it will be possible to find a good match for about 28% of adult Caucasian patients and 74% for children with a standard cell dose. And, notes Petz, the chance could rise to 82% and 86%, respectively, if the cell dose is lowered by combining stem cells from a half-matched family member to provide a bridge while the cord blood stem cells engraft.
This May, another patient with both HIV and leukaemia underwent a stem cell transplant in the Netherlands using cord blood stem cells from a unit with a double CCR5 mutation. It is too early to know if it has worked yet and there could be additional complications for patients with HIV/AIDS, says Jürgen Kuball of the UMC Utrecht team overseeing the research, but he expects to be able to say more in December (a similar transplant due to take place in Spain in June was aborted because of inadequate viability of the stem cells in the cord blood). If successful, the Utrecht patient would be the second after Brown to be cured of HIV.
Meanwhile, the new cure strategy is problematic for some researchers. Daniel Halperin, an HIV prevention and behaviour change expert at the University of North Carolina at Chapel Hill, worries the focus on only two options-medication with ART or a cure-could lead people to think that other, preventive approaches, which have been shown to work in the real world and require vastly less money, are not as important. "If you talk a lot about a cure and you get all this hype and excitement going it could make it harder for behaviour change to happen on the ground", he told The Lancet.
Other experts, however, see it as a milestone. This is the first consortium to lay out a pathway for a cure, says Bruce Walker, an HIV researcher at Harvard University and director of the Ragon Institute in Massachusetts-a collaboration which is working to accelerate the discovery of an HIV/AIDS vaccine. There are still many unknowns and challenges, but stating the goal is the "first step" towards achieving it. "We have to set a high bar for ourselves", he says. "And once we figure out how to [cure the virus] we can turn our attention to doing it in a way that is going to be cheaper and more deliverable."

What is metastatic cancer (Definition)

Metastatic cancer is a cancer that has spread from the part of the body where it started (the primary site) to other parts of the body. When cancer cells break away from a tumor, they can travel to other areas of the body through either the bloodstream or the lymph system (a collection of vessels that carry fluid and immune system cells).

The Lymph System

If the cells travel through the lymph system, they may end up in the lymph nodes (small, bean-sized collections of immune cells) or spread to other organs. If the cells travel through the bloodstream they can go to any part of the body. Most often, the cancer cells break off and travel in the bloodstream. Many of these cells die, but some settle in a new area, begin to grow, and form new tumors. This spread of cancer to a new part of the body is called metastasis.
In order for cancer cells to spread to new parts of the body, they have to go through several changes. They have to be able to break away from the original tumor and enter the bloodstream or lymph system, which can carry them to another part of the body. At some point they need to attach to the wall of a blood or lymph vessel and move through it into a new organ. They then need to be able to grow and thrive in their new location. All the while, they need to be able to avoid attacks from the body's immune system. Going through all these steps means the cells that start new tumors may no longer be exactly the same as the ones in the tumor they started in. This may make treatment more difficult.
Even when cancer has spread to a new area, it is still named after the part of the body where it started. For example, if prostate cancer spreads to the bones, it is still called prostate cancer (not bone cancer). Likewise, breast cancer that has spread to the lungs it is still called breast cancer, not lung cancer.
Sometimes the metastatic tumors have already begun to grow when the cancer is first found and diagnosed. And in some cases, a metastasis may be found before the original (primary) tumor is found. If a cancer has already spread to many places before it is found, it may be hard to figure out where it started. If this happens the cancer is called cancer of unknown primary.