Posted: April 24th, 2011 | Author: admin | Filed under: HIV | Comments Off
The two-hundred-year history of vaccination has generated only one success story against a sexually transmitted pathogen: the hepatitis B vaccine. This program was put in action during the early 1990s. It looked good at the outset but is already showing signs of trouble. Hepatitis B, like HIV, can generate variation quickly through mutation. Recent data indicate that a massive hepatitis B vaccination program in Taiwan is causing the virus to evolve around the vaccine.Why have vaccines not been as successfully applied against sexually transmitted pathogens as against other kinds of pathogens? Each sexually transmitted pathogen has its own story, but there are some general reasons that the standard approach to vaccination is not particularly effective against venereal diseases.Sexually transmitted pathogens are the beneficiaries of several psychological idiosyncrasies. First there is morality. People have little control over whether they will inhale air laden with viruses, whether a mosquito will get lucky, or whether some of their food has been contaminated because of neglected hand washing. But people are supposed to have some control over whether they engage in sex. Treating syphilis with an antibiotic is remedying a past moral lapse, but vaccinating people against syphilis can be seen as encouraging immoral behavior. Allocating money for the development of venereal vaccines can be politically risky for the same reason.There is also the immunological problem. Sexually transmitted pathogens have to be able to avoid destruction by the immune system, and vaccines rely on the immune system to destroy sexually transmitted pathogens. This is the problem that seems to be making the hepatitis B vaccine program show hairline cracks. Hepatitis B stays ahead of the immune system by mutating its form. If the vaccine primes the immune system to combat one form of the virus, the door is left open to another form.Vaccines against cancer have generated much hope but little success in the way of disease control. If most cancers turn out to be caused by viruses, all of this might change. Consider cervical cancer. Once cervical cancer became recognized as an infectious disease, new opportunities arose. The papillomavirus that causes this cancer offers several distinct antigens that would not have been available as immunological targets if the cancer had been caused solely by mutations. Even with vi-rally caused cancer there is the problem of getting the immune system to knock out a lump of the body’s own cells, but at least there is a chance that the cells are hanging the virus’s body parts as a kill me sign for the immune system. Cells infected with the most deadly forms of papillomavirus do seem to post such signs using parts of the E6 and E7 proteins; and cells that were engineered to express these proteins were destroyed by the cytotoxic T cells that would need to be mustered to take care of these cells in the body. There is still the problem of killing a big lump of cells from the outside. Once the lump gets too big, no amount of immunological activity may be sufficient. But the immunological action triggered by an E6 or E7 vaccine may work much earlier in the course of infection, long before a distinct lump is seen.If such a vaccine does act against infected cells, it could have a much greater long-term punch than its developers suspect. The E6 and E7 proteins are the ones that sabotage the cell’s ability to control its division. A vaccine derived from them would therefore be a virulence antigen vaccine that might provide an extra evolutionary punch by tipping the competitive balance in favor of the papillomaviruses without the damaging form of these proteins. These mild strains of papillomavirus would then be left to generate additional protection against the harmful strains by triggering immunity to antigens that the mild arid harmful strains share.AIDS vaccines present a different set of problems and opportunities. On the positive side, the infected cells are not cloistered inside tumors. On the negative side, the virus is so mutation prone that a vaccine that would protect against all variants is probably unattainable. Still, the virulence antigen strategy may provide substantial protection if it is used early in the infection as a therapeutic vaccine. This kind of usage requires that the most damaging forms of HIV’s proteins be identified and used in the vaccine. When these forms then arise by mutation, they may be quickly knocked out before they have a chance to gain a foothold. The protein HIV uses to attach to and enter cells, for example, typically changes during the course of infection, allowing HIV increasingly to enter and damage the helper T cells. This change is critical because these T cells tend to be far more important to the orchestration of the immune response than are the other cells HIV infects when it does not have this altered form. If the altered form of this protein was used in a vaccine early during infection, the more damaging viruses might be controlled longer because the immune system would be ready for them when they arose. In this case the normal immunity generated by the less damaging HIV in the body is supplemented by a vaccine-induced immunity that specifically suppresses the more damaging form. The more of the harmful forms that could be included in such a therapeutic virulence antigen vaccine, the longer the delay in the breakdown of the immune system.*63\225\2*
Posted: April 14th, 2011 | Author: admin | Filed under: Healthy bones Osteoporosis Rheumatic | Comments Off
Over the course of your life, you go through four phases of bone development. For the first part of your life, you build bone. You then have a relatively short plateau phase, when you’re maintaining the bone mass you’ve built up at basically peak levels. As you age, resorption overtakes formation, giving you a third phase, this one of bone loss. The fourth stage is also one of loss, but with the additional complication of formation and deposition slowing down (as well as breakdown picking up).Throughout infancy and childhood and into young adulthood, your bones are growing longer, wider, and thicker, and getting denser (phase one). Adolescence is a particularly busy time for your bones, as the sex hormones that drive puberty also spur bone growth. Half of all bone is made during the teen years. Even after you stop growing taller (and your bones stop growing longer), bone mass still increases as long as formation stays ahead of resorption. By the time you are 20, 90 percent of your bone mass is set. You still build, slowly, for a few more years, and reach peak bone density in your mid to late 20s. You generally stay there for about a decade (phase two).But by age 35 or so, you start phase three. Just about everyone begins to experience a slow decline in bone mass—0.5 to 1 percent a year—as resorption proceeds faster than deposition. For women, there is a drastic increase in the rate of bone loss for the first five to ten years after menopause—jumping to 3 to 5 percent lost each year—because of the decrease in estrogen (for women not taking hormone replacement therapy) and progesterone. Postmenopausal osteoporosis shows up in women between the ages of 50 and 65, generally. It is no surprise that the fracture rate accelerates greatly ten to fifteen years after menopause.Women who undergo surgical menopause (having their ovaries removed) lose twice as much bone as other women at menopause, because even after menopause the ovary produces a small amount of estrogen, along with other hormones important to bone health. Women who have a hysterectomy but keep their ovaries also lose bone at an accelerated rate (though not as quickly as women with no ovaries), probably because the uterus makes vitamin D, which is necessary for healthy bones. Rapid bone loss may begin a year or two before your period actually stops, especially in the spine (and other trabecular bone). In fact, the rate of hip fractures rises dramatically for women in their early 40s, well before the average age of menopause. Over a third of premenopausal women lose bone faster than even the expected rate of loss, and for them, taking action is particularly important.Men, too, have an acceleration in bone loss, but not until much later, around ages 60 to 65, probably connected to the decrease in testosterone. Without additional complications, they never lose as much as women do in menopause, but still, losing 1 percent of bone mass a year really adds up.Eventually, the rate of loss slows again (for women) to about 1 percent a year throughout the rest of their lives, putting men and women on an equal footing by that point. But now you have an additional problem (phase four): your rate of bone formation is slowing down too, so you have more to contend with than just overenthusiastic bone breakdown. We absorb less calcium as we get older and make less vitamin D, meaning that bodies have less in the way of raw material to work with in building bone. On top of that, the older we get, the poorer our overall diets tend to be, for a variety of reasons. Combined with lower than optimal levels of hormones, low bone density becomes a serious risk.Over an average lifetime, a woman loses 30 to 40 percent of her total bone mass, and a man about 20 to 30 percent. By age 80, many women have lost two-thirds of their skeletons. Because trabecular (spongy) bone is softer to begin with, most bone loss begins there. Loss in the spine begins as early as the 20s. Cortical bone is denser to begin with, and loss there generally doesn’t occur at all until after age 50. Overall, more trabecular bone than cortical bone is lost. In the years just after menopause when the most bone is lost, women lose about 10 percent of their cortical mass and 25 percent of their trabecular bone mass, before the rate of loss slows again, and end up with a lifetime decrease of about 35 percent of cortical bone and 50 percent of trabecular. It is the dramatic decrease in trabecular bone (predominant in the spine) that causes women to shrink—losing up to 6 inches of height by the time they are 80. Men lose about 25 percent of the total of both kinds of bone over their lifetimes.After bone loss starts, each decade increases your risk of fracture about one and a half times. A high rate of bone turnover puts you at increased risk regardless of your bone density, and low bone density most certainly ups your risk. The younger you are when your bone loss begins or quickens, the higher your risk of fractures will be later in life. That’s just another way to say it’s never too early to start on the 6-Week Bone Density Program. It is also never too late.*16\228\2*
Posted: April 4th, 2011 | Author: admin | Filed under: Epilepsy | Comments Off
Ambulatory monitoring is usually performed with a small tape cassette worn on the belt and attached by small wires to EEG electrodes pasted to the scalp. These cassettes can record EEG for twenty-four hours without a change in the tape. When the person wearing the monitor has an “episode,” or feels the warning of an episode, he can push a button; a mark will then be made on the cassette tape. For children it is important to have an observer record the time on the machine and also any suspected or unusual behaviors, data to be correlated later with any abnormalities appearing on the recorded EEG.Reading twenty-four hours worth of EEG paper would be cumbersome and time-consuming, but the tapes can be played at sixty times the normal speed with the technician or doctor listening for the characteristic sounds of seizures. If such abnormalities are heard, the tape is slowed down and the EEG tracings displayed on a videoscreen for further analysis. This then becomes an efficient method of screening for EEG abnormalities and seizures.While ambulatory monitoring permits recognition of major brain wave abnormalities, such as generalized spike-wave seizures, it is not, however, precise enough for pre-surgical evaluations. There are also a few additional drawbacks and limitations to the ambulatory monitoring test. Because the child being monitored is usually at home, and because it is not uncommon for one or more of the electrodes to become loose or unglued without anyone knowing, the monitoring may yield less than accurate reports. It may be impossible to interpret any episodes that occur if not all of the electrodes are working. True to Murphy’s Law, it is invariably the critical electrode that malfunctions.It may be difficult to tell what is a seizure and what isn’t. If the tape is scanned rapidly, brief events may be missed unless they have been identified earlier by the child or the observer. That is why it is so important for an accurate diary to be maintained during the recording. Also, if events are occurring infrequently, they may not occur at all while the child is being monitored. Thus, ambulatory monitoring is impractical for assessing rare events. Ambulatory monitoring is not for everyone; in selected cases, however, it can be useful.*86\208\8*