I’m currently at 39,000 feet on my way to NY to have a fun weekend with my daughter. I slipped a few medical journals into my carry-on to review so that I could find an article to share in my weekly newsletter. The seat is cramped, the cabin is crowded, most of my fellow passengers are sleeping….I passed over articles on multiple therapies for tuberculosis (too much coughing going on around me), sepsis and organ failure, as well as AIDs – defining cancers (too depressing)…Each subject is critical to the progress of medicine and I did read up on them, but for this newsletter I selected an article in JAMA titled ” Genital Shedding of Herpes Simplex Among Symptomatic and Asymptomatic Persons with HSV-2 Infection”.
So here it is…answering the question: do individuals who don’t know they have genital herpes shed the virus (and hence can spread it to a partner) to the same extent as those that have recurrent lesions (and are aware of their diagnosis)?

A quick herpes review: Genital herpes (HSV-2) is unfortunately, extremely prevalent. Over half a billion people worldwide have the virus and it is estimated that 23.6 million persons aged 15 to 49 become infected annually. In the US, 16% of adults have had it as evidenced by the fact that they have antibodies to HSV-2, but only 10 to 25 % of persons with this “everlasting infection” know that they harbor it. As a result, individuals who don’t know they have had herpes spread most of the HSV-2 infections. The risk of sexual transmission doesn’t correlate with recognition of symptoms but is correlated with silent viral mucosal shedding (and obviously, sexual contact with a partner).

Researchers at the University of Washington enrolled participants who were 18 and older in this herpes study for the published study. They advertised for participants through word of mouth at the university, newspaper ads (and promises of payment), tested many and in the end found 498 individuals who had antibodies to herpes 2. They then divided them into 2 groups: those who were symptomatic (had a clinical history of genital herpes) and those who were not (never knew that they had a lesion, their diagnosis was made with the herpes antibody blood test). Each person then self-collected swabs of their genital secretions for at least 30 days. (The swabs were examined by quantitative polymerase chain reaction for HSV DNA…I had to add that for the purists.)

The results showed that those who had symptomatic genital lesions were twice as likely to shed the virus and 3 times more likely to develop lesions than those who were, on initial testing, asymptomatic. However in those with no symptoms, genital HSV shedding did occur on 10% of days, and almost all of it was subclinical (i.e. the person did not recognize a lesion). There was a similar shedding rate between men and women; which means that men can have sub-clinical shedding on normal appearing genital skin. (There goes the adage, look before you engage…)
What they also found was that many of those who were initially asymptomatic begin to recognize recurrent herpes once they had received the diagnosis through their blood tests. They may have felt that what they had in the past was just a mild irritation or itch and ignored it, now they didn’t.

I have frequently been the doctor who sees a patient with “something down there” and either through direct culture and/or a blood test have made the diagnosis of herpes. Often the first statement posed by my now horrified patient is “he never told me”, or “was he with someone else?” Neither may be correct…the partner may not have known that he (or she) had acquired herpes in the past, or the woman with the “new” herpes infection may have had it all along and only now has become aware of a clinical lesion. (Perhaps brought on by illness, stress or diminished immunity.)

It certainly would be helpful to have universal herpes 2- antibody testing. But this is not currently a part of “routine” blood tests, nor is it financially feasible. The best protection will continue to be the use of condoms. For those who have been diagnosed with herpes, daily prophylactic use of the antiviral medications such as Valtrex or acyclovir should decrease shedding as well as recurrent lesions. So far that’s the best advice that’s offered by the experts. Somewhat depressing at 39,000 feet (or for that matter at sea level)!

Over the years many of my patients have come in with the happy announcement that their home pregnancy test was positive, but then voice their concern: ” I drank (wine, beer, the hard stuff) before I knew I was pregnant. Does this mean that I damaged the pregnancy? Should I worry?” (This is LA, some were already planning the preschool, grade school, high school and ivy league school that the 7 week old fetus would eventually be attending and worry that her or his chances were ruined!)

Fetal alcohol syndrome has been recognized for over a century. (It obviously has been around for as long as fermented beverages have been consumed; although when I watch all those television series about 16th century nobility, the males seem to be imbibing while the erstwhile maids, women and even princesses and queens are rarely portrayed sipping wine or mead. Considering the absence of birth control, some must have been pregnant.) Full blown fetal alcohol syndrome is pretty hard to miss: it manifests as low set ears, facial changes small chin and jaw, small head circumference, joint contractures, cardiac defect, varying degrees of mental retardation, behavioral abnormalities, hyperactivity and developmental delays. This array of fetal malformations can vary but, in general, has been associated with alcohol abuse (5 or more drinks a day) that continues throughout the pregnancy. So, could a mere drink or two a week in the first trimester do harm?

This question was addressed in a study published in a 2010 British Journal of Obstetrics and Gynecology and recently reviewed in the journal titled Obstetrical and Gynecologic Survey. (The latter allows me to catch up on the myriad articles published in my field.) The article detailed a prospective study of 2900 pregnancies in Australia (where I guess alcohol is readily available) between 1989 and 1999. A 14-year follow up of the children born to the women allowed the researchers to ascertain if alcohol had been harmful to the children’s behavior and development.

During various times in their pregnancy, the women were asked if they were or had been abstaining from all alcohol or occasionally drank (up to one standard drink per week), drank lightly (2-6 standard drinks per week), moderately (7-10 standard drinks per week) or heavily (11 or more standard drinks per week). The children from their pregnancies were then studied at birth and at 2, 5, 8, 10 and 14 years. The researchers also tried to correct for variables that could influence a child’s behavior, such as maternal age and education, the occurrence of stressful events during the pregnancy, maternal smoking and the presence of the father in the home as well as family income.

The results were somewhat surprising: In this analysis, the offspring of women who drank 2 to 6 or 7 to 10 drinks per week during the first 3 months of pregnancy did not have behavior problems up to the age of 14, and in fact had better behavioral scores than the offspring of mothers who did not drink at all!
The author of the review article points out that fetal susceptibility to alcohol is now known to be partially dependent on how rapidly alcohol is metabolized by the mother. Those who metabolize it more slowly have a higher peak blood alcohol level for a longer time than “fast metabolizes”. Alcohol breakdown (not that of the drinker, but that of the intoxicant) is dependent on possessing certain alleles (or genes), called ADH1B2 and ADH1B3. (Of note ADH1B3 has a high frequency among African Americans; unfortunately, the Australian study did not report the race of their participants.) But then how many women know their alcohol allele status? So although the allele data is interesting, it probably won’t help most women’s concerns regarding their alcohol consumption, especially in early pregnancy.

Bottom line: There are many factors that influence fetal susceptibility to alcohol, and it’s certainly best to “play it safe” and just not drink during pregnancy. But the current study allows physicians to continue reassuring their patients that have drunk less than 11 drinks per week in their first trimester that this was unlikely to have caused adverse fetal affects. And I have to add…. no one can guarantee the “right” school admission

In addition to my usual Friday website article, I felt it was necessary to address the recent JAMA article on estrogen-only therapy (in women who have had a hysterectomy.) The women were followed and results have just been published years after the Women’s Health Initiative (WHI) was stopped. The American Menopause Society (NAMS) said it best and hence I am simply forwarding the message that appeared on their website in response to this article. Once more, their conclusions reinforce the fact that estrogen (without a progestin) did not increase, but actually decreased breast cancer, in follow-up of over 10 years. Premarin (CEE) therapy was found to be beneficial vis a vis heart disease, colorectal cancer and overall, all-cause mortality for women under the age of 70 but appeared to lose its benefits and indeed worsen mortality rates after the age of 70. So here is the data and the NAMS conclusion:

Brief summary of the article: The final results of the Women’s Health Initiative Estrogen-Alone Trial, reflecting a median of 6 years of treatment and an average of 10.7 years of follow-up, are published in this article. The long-term follow-up and post-stopping findings for this trial have not been previously reported. The authors examined health outcomes in 10,739 women with prior hysterectomy, comparing those randomized to receive CEE treatment versus placebo. The median duration of adherence (taking >80% of study pills) to CEE was 3.5 years.

The main outcomes were CHD and invasive breast cancer. In addition, a global index of risks and benefits included CHD, stroke, pulmonary embolism, breast cancer, colorectal cancer, hip fracture, and death.

Results: For the overall study population, there was a significantly reduced risk of invasive breast cancer among women randomized to CEE versus placebo over the 10.7 years of follow-up (23% reduction; HR 0.77; 95% CI, 0.62-0.95). Risk reductions were similar in the treatment and post-stopping periods. In the overall study population, there was no significant effect of CEE on CHD, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality. However, younger women (ages 50-59 at enrollment) tended to have much more favorable outcomes on CEE than the older women for CHD, heart attack, colorectal cancer, all-cause mortality, and the global index. For heart disease endpoints, risks were 40% to 50% lower with CEE than placebo in women ages 50 to 59 but were higher with CEE than placebo in women ages 70 to 79. For example, for every 10,000 women per year taking CEE, there were 12 fewer heart attacks, 13 fewer deaths, and 18 fewer adverse events for women ages 50 to 59. In contrast, for every 10,000 women per year ages 70 to 79, there were 16 extra heart attacks, 19 extra deaths, and 48 extra adverse events for women taking CEE (P values for interaction by age were statistically significant).

Conclusions: In this randomized trial, conjugated equine estrogens (CEE) use was associated with a decreased risk of invasive breast cancer and much more favorable results for coronary heart disease (CHD), all-cause mortality, and several other outcomes in younger than in older women. Overall, the observed pattern provides more support for the “timing hypothesis.” The findings highlight the differences between estrogen alone and estrogen plus progestin in terms of breast cancer risk and other chronic disease outcomes, as well as important differences by age group. Whether the reduction in breast cancer risk with CEE alone will apply to all women at menopause and to estradiol or other formulations of estrogen, and whether it will persist with longer-term estrogen use, remains unknown.

In the midst of our horror about the earthquake, tsunami and nuclear reactor disasters in Japan and concerns about the latter’s impact on the air, ocean and life forms, I thought that the timing of the article in the March issue of The New England Journal of Medicine was intriguing. It brought up another less immediate but valid concern, that of the effect of coal on our food and risk of disease.  (I hope that those of you reading this article acknowledge coal’s impact on climate change and the ecologic repercussions that are, in themselves, a disaster). The NEJM article was titled “Mercury Exposure and Risk of Cardiovascular Disease in Two U.S. Cohorts.”

A quick review: as we use coal for power, we contaminate our atmosphere with mercury. This then returns to the oceans of the earth and is incorporated into plankton where it is converted into organic methylmercury. The latter is stored in the fat of fish. As larger fish eat smaller fish, their levels of methylmercury go up. We then eat the fish and the methylmercury gets into our bodies (and is also stored in our fat). Chronic, low-level methylmercury exposure can cause neurodevelopment delay in infants. It’s currently recommended that women of childbearing age, pregnant or nursing mothers, and infants and young children eat no more than 2 servings of fish per week and also limit their intake of certain species of fish that are especially high in mercury. The worst culprits are the ones on the top of the fish eating food chain: shark, swordfish, king mackerel, and tilefish. Then to complicate matters, fish from streams and rivers in areas that have high mercury pollution may also be less than safe, especially if consumed regularly. (For information on mercury pollution check http://www.epa.gov/mercury/advisories.htm.)

For adults, the main health concern regarding chronic low levels of methylmercury (not high, toxic ones) is the risk for cardiovascular damage and disease. Government agencies, the Institute of Medicine and (I assume) the rest of us want to know if mercury exposure is correlated with cardiovascular disease.

There has been robust research that shows that fish consumption is heart healthy; indeed, fish intake has been shown to be inversely associated with the risk of coronary heart disease, especially fatal heart attack and stroke. So what is a fish eating person (like myself, who does not eat meat) to do?

Researchers from Harvard, the University of Washington, and the University of Missouri studied mercury exposure in 2 large groups of individuals. The first was comprised of male physicians followed from 1986 in the Health Professionals Follow-up Study (don’t get me started on my gender protests regarding this study) and the second was through the Nurses Health Study (as you may guess, all female) in which the nurses were followed from 1976. The two studies totaled 51,529 men and 121,700 women.
And here is where it gets really interesting… Their toenail clippings were stored! (I read this, believe it or not, while getting a pedicure and wondered if I should save my own toe nail clippings for research.) Apparently concentrations of mercury and selenium in toenails have been found to be excellent biomarkers of usual methylmercury and selenium exposure. The researchers wanted to check selenium (which we get from consuming plants grown on selenium –rich soil) because this trace element provides protection against mercury toxicity in some experimental studies.

They identified 3427 participants with cardiovascular disease and matched them to controls who were the same age, sex, race and smoking status. They also had information on their fish consumption and lifestyle habits. Their toenail mercury and selenium concentrations were assessed by (and I’m sure you will get this) the use of neutron-activation analysis. The usual complicated statistical analysis (actually called a multivariate analysis) was done and demonstrated that participants with higher mercury exposures did not have a higher risk of cardiovascular disease nor did selenium concentrations make a difference in the results.
The authors concluded that their findings “provide no support for clinically relevant adverse affects of typical levels of dietary methylmercury exposure on cardiovascular disease in U.S. adults”. They went on to state that the absence of an association “should not alter ongoing public health and policy efforts to reduce mercury contamination in fish and the environment.”

Bottom line: Most of us can continue to eat the “right” fish for our heart’s sake, but women who are pregnant or may become pregnant, or who are breast feeding should limit their fish consumption. Now, we can start worrying about the impact of radiation on those fish…

I just had to report on this study, I love its title… InCHIANTI (Yes, Chianti, as in wine…but it had nothing to do with alcohol consumption.  I do have to assume, however, that because the study was carried out in the Chianti area of Tuscany, the participants and perhaps the researchers consumed their share.) Joking aside, this was a study that examined the impact of Vitamin D levels on depression in a population of adults over 65 who lived in Tuscany. (No novel or movie there…)

InCHIANTI stands for Invecchaire in Chianti, or aging in the Chianti area. Nine hundred and fifty four participants (531 women and 423 men) aged 65 or older were followed for 6 years. A special questionnaire called the Center for Epidemiological Studies-Depression Scale (the acronym is CES-D) was used to assess depressive symptoms at baseline and at 3-and 6-year follow-up. The CES-D contains 20 questions which are scored (a point for each “depressed answer); the higher the points, the more likely the person is clinically depressed. This is considered an excellent scale to measure depression in older adults. The blood level of Vitamin D (measured as 25(OH) D) at baseline and 3 and 6 years later was measured at the same time that the CES-D was administered to the participants.  The study results were published in the Journal of Clinical Endocrinologic Metabolism.

Although you may not want to know the numbers (you can skip to the next paragraph), the researchers found that the women with Vitamin D levels lower than 50 nanomoles per liter) when compared with those with higher initial levels of D, had greater increases in depression scores (2.1 and 2.2 points) at 3-and 6-year follow-up.

A lower baseline blood level of Vitamin D in women was associated with a significant higher risk of developing depression during the follow-up. This was not seen to the same extent in men.

The authors point out that low Vitamin D levels become very prevalent in older individuals due to reduced sunlight exposure from decreased outdoor activity and reduced vitamin dietary intake. In older adults, Vitamin D deficiency has been linked to fractures, poor physical activity, frailty and loss of muscle mass and strength. Those with low D levels are more likely to require nursing home admission and suffer from chronic diseases including osteoporosis, diabetes and cardiovascular disease.  Whether the low Vitamin D levels in this population of women was truly a causal factor for depression or the diseases associated with the low D levels made the women depressed is not clear. Nor do we have data that lets us state that increasing Vitamin D levels will help halt these depressing disorders.

Bottom line: Low Vitamin D is associated with depression in older women in Tuscany….and if it happens there, it can happen anywhere. It may pay to hedge our aging bets by maintaining adequate Vitamin D levels. This is where I suggest supplements, for most of us, 1,000 units of Vitamin D should get us there

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