Source: Massachusetts General Hospital  –  This small device contains about 80,000 microscopic pillars that can trap cancer cells in the blood. It was used in a study involving 55 cancer patients.


Brilliant Concept:

A “Blood Biopsy”, by Gregory Mone, April 5, 2010 — Cancer patients could soon benefit from a new screening device that can pick out and analyze rare tumor cells from standard blood samples, according to a report today in Science Translational Medicine. The device, which is the size of a business card, could be an alternative to surgery, offering a noninvasive way of monitoring whether tumors are spreading to other parts of the body. All it would require is the prick of a needle.

“The concept is a blood biopsy,” explains Massachusetts General Hospital mechanical engineer Shannon Stott, the study’s lead author. “The question is, can we just take a simple blood sample and get the same type of information that we would get if we did a surgical biopsy?”

The target cells, known as circulating tumor cells, or CTCs, are most likely shed into the bloodstream by existing tumors. Even if a tumor is removed, these cells can seed a new location, causing the cancer to spread. Not all of them are necessarily harmful, Stott tells AOL News. “But some population of the cells may have the potential to find a new place to take root,” she says.

Scientists have long been working to develop a technology that can pick out these cells, but the technical challenges are significant. An FDA-approved technology called CellSearch uses a multistep process to analyze blood for CTCs, but Stott says her device is more sensitive, registering much higher numbers of the fragile cells, and that it could be used to gather more valuable information.

In the new study, Stott and her colleagues used their business-card-sized device to analyze blood samples from 55 prostate cancer patients. The device has nearly 80,000 microposts, or pillars, each of which is coated with an antibody that effectively traps target cancer cells. When the scientists run a volume of blood through it, the CTCs stick to these pillars. The rest of the blood is then washed away, leaving only the target cells for analysis.

Even though these cells can be as rare as one in 10 billion, Stott says the device was able to capture hundreds of them per milliliter of blood. The scientists were also able to study the health of the CTCs — whether they were ready to die off or poised to divide and spread.

Stott and her colleagues tested samples of each patient’s blood taken before prostate-removal surgery, and follow-ups collected after intervals of 24 hours, nine days and three months had elapsed. Many of the patients had little or no CTCs at the start, and with others, their levels dropped immediately after the surgery.

But for one subset, Stott says, the rare cells stuck around through that three-month follow-up. “What we’re going to do now is continue to track these patients for the next two years to see if there’s any meaning,” she says. “Is that a sign of a more invasive prostate cancer?”

Though the current work focuses on prostate cancer, Stott says the technology is applicable to many other forms of the disease — citing breast cancer and lung cancer as two additional possibilities. She says the group hopes to develop a faster, more efficient plug-and-play version of the device for wider clinical use.

As science and global capitalism gallop forward, they kick up difficult questions about emotional attachment.,, by Arlie Hochschild, April 5, 2010  –  The auto-rickshaw driver honks his way through the dusty chaos of Anand, Gujarat, India, swerving around motorbikes, grunting trucks, and ancient large-wheeled bullock-carts packed with bags of fodder. Both sides of the street are lined with plastic trash and small piles of garbage on which untethered cows feed. The driver turns off the pavement onto a narrow, pitted dirt road, slows to circumvent a pair of black and white spotted goats, and stops outside a dusty courtyard. To one side stands a modest white building with a sign that reads, in English and Gujarati, “Akanksha Clinic.”

Two dozen dainty Indian women’s sandals, toes pointed forward, are lined along the front porch. For it is with bare feet that one enters a clinic housing what may be the world’s largest group of gestational surrogates — women who rent their wombs to incubate the fertilized eggs from clients from around the globe. Since India declared commercial surrogacy legal in 2002, some 350 assisted reproductive technology (ART) clinics have opened their doors. Surrogacy is now a burgeoning part of India’s medical tourism industry, which is slated to add $2 billion to the nation’s gross domestic product by 2012. Advertisements describe India as a “global doctor” offering First World skill at Third World prices, short waits, privacy, and — important in the case of surrogacy — absence of red tape. To encourage this lucrative trend, the Indian government gives tax breaks to private hospitals treating overseas patients and lowers import duties on medical supplies.

In his 2007 book, Supercapitalism , Robert B. Reich argues that while industrial and clerical jobs could be outsourced to cheaper labor pools abroad, service jobs would stay in America. But Reich didn’t count on First World clients flying to the global South to find low-cost retirement care or reproductive services. The Akanksha clinic is just one point on an ever-widening two-lane global highway that connects poor nations in the Southern Hemisphere to rich nations in the Northern Hemisphere, and poorer countries of Eastern Europe to richer ones in the West. A Filipina nanny heads north to care for an American child. A Sri Lankan maid cleans a house in Singapore. A Ukrainian nurse’s aide carries lunch trays in a Swedish hospital. Marx’s iconic male, stationary industrial worker has been replaced by a new icon: the female, mobile service worker.

We have grown used to the idea of a migrant worker caring for our children and even to the idea of hopping an overseas flight for surgery. As global service work grows increasingly personal, surrogacy is the latest expression of this trend. Nowadays, a wealthy person can purchase it all — the egg, the sperm, and time in the womb. “A childless couple gains a child. A poor woman earns money. What could be the problem?” asks Dr. Nayna Patel, Akanksha’s founder and director.

But despite Patel’s view of commercial surrogacy as a straightforward equation, it’s far more complicated for both the surrogates and the genetic parents. Like nannies or nurses, surrogates perform “emotional labor” to suppress feelings that could interfere with doing their job. Parents must decide how close they are willing (or able) to get to the woman who will give birth to their child.

As science and global capitalism gallop forward, they kick up difficult questions about emotional attachment. What, if anything, is too sacred to sell?


I follow a kindly embryologist, Harsha Bhadarka, to an upstairs office of the clinic to talk with two surrogates whom I will call Geeta and Saroj. (Aditya Ghosh, a journalist with the Hindustan Times, has kindly offered to join me.) The room is small, and the two surrogate mothers enter the room nodding shyly. Both live on the second floor of the clinic, but most of its 24 residents live in one of two hostels for the duration of their pregnancy. The women are brought nutritious food on tin trays, injected with iron (a common deficiency), and supervised away from prying in-laws, curious older children, and lonely husbands with whom they are allowed no visits home or sex.

Geeta, a 22-year-old, light-skinned, green-eyed beauty, is the mother of three daughters, one of whom is sitting quietly and wide-eyed on her lap. To be accepted as a surrogate, Akanksha requires a woman to be a healthy, married mother. As one doctor explains, “If she has children of her own, she’ll be less tempted to attach herself to the baby.”

“How did you decide to become a surrogate?” I ask.

“It was my husband’s idea,” Geeta replies. “He makes pav bhaji [a vegetable dish] during the day and serves food in the evening [at a street-side fast-food shop]. He heard about surrogacy from a customer at his shop, a Muslim like us. The man told my husband, ‘It’s a good thing to do,’ and then I came to madam [Dr. Patel] and offered to try. We can’t live on my husband’s earnings, and we had no hope of educating our daughters.”

Geeta says she has only briefly met the parents whose genes her baby carries. “They’re from far away. I don’t know where,” she says. “They’re Caucasian, so the baby will come out white.” The money she has been promised, including a monthly stipend to cover vitamins and medications, is wired to a bank account that Patel has opened in Geeta’s name. “I keep myself from getting too attached,” she says. “Whenever I start to think about the baby inside me, I turn my attention to my own daughter. Here she is.” She bounces the child on her lap. “That way, I manage.”

Seated next to Geeta is Saroj, a heavy-set, dark woman with intense, curious eyes, and, after a while, an easy smile. Like other Hindu surrogates at Akanksha, she wears sindoor (a red powder applied to the part in her hair) and mangalsutra (a necklace with a gold pendant), both symbols of marriage. She is, she tells us, the mother of three children and the wife of a vegetable street vendor. She gave birth to a surrogate child a year and three months ago and is waiting to see if a second implantation has taken. The genetic parents are from Bangalore, India. (It is estimated that half the clients seeking surrogacy from Indian ART clinics are Indian and the other half, foreign. Of the foreign clients, roughly half are American.) Saroj, too, knows almost nothing about her clients. “They came, saw me, and left,” she says.

Given her husband’s wages, 1,260 rupees (or $25) a month, Saroj turned to surrogacy so she could move to a rain-proof house and feed her family well. Yet she faced the dilemma of all rural surrogates: being suspected of adultery — a cause for shunning or worse. I ask the women whether the money they earn has improved their social standing. For the first time the two women laugh out loud and talk to each other excitedly. “My father-in-law is dead, and my mother-in-law lives separately from us, and at first I hid it from her,” Saroj says. “But when she found out, she said she felt blessed to have a daughter-in-law like me because I’ve given more money to the family than her son could. But some friends ask me why I am putting myself through all this. I tell them, ‘It’s my own choice.'”

Since Dr. Patel began offering surrogacy services in 2004, 232 surrogates have given birth at Akanksha. A 2007 study of 42 Akanksha surrogates found that nearly half described themselves as housewives and the rest were a mix of domestic, service, and manual laborers. Hindu, Muslim, and Christian, most had seventh- to 12th-grade educations, six were illiterate, and one — who turned to surrogacy to pay for a small son’s heart surgery — had a bachelor’s degree. Each surrogate negotiates a different sum: One surrogate carrying twins for an Indian couple discovered she was being paid less (about $3,600) than a surrogate in the next bed who was carrying one baby for an American couple for about $5,600.

Observers fear that a lack of regulation could spark a price war for surrogacy — Thailand underselling India, Cambodia underselling Thailand, and so on — with countries slowly undercutting fees and legal protections for surrogates along the way. It could happen. Right now international surrogacy is a highly complex legal patchwork. Surrogacy is banned in China and much of Europe. It is legal but regulated in New Zealand and Great Britain. Only 17 of the United States have laws on the books; it is legal in Florida and banned in New York.

In India, commercial surrogacy is legal but unregulated, although a 135-page regulatory law, long in the works, will be sent to Parliament later this year. Even if the law is passed, however, some argue it would do little to improve life for women such as Geeta and Saroj. For example, it specifies that the doctor, not the surrogate, has the right to decide on any “fetal reduction” (an abortion). Moreover, most Indian federal laws are considered “advisory” to powerful state governments, and courts — where a failure to enforce such laws might be challenged — are backlogged for years, often decades. Dr. B.N. Chakravarty, the Calcutta-based chair of the surrogacy law drafting committee, says that the growth of the industry is “inevitable,” but it needs regulating. Even if the law were written to protect surrogates and then actually enforced, it would do nothing to address the crushing poverty that often presses Indian women to “choose” surrogacy in the first place.

For N.B. Sarojini, director of the Delhi-based Sama Resource Group for Women and Health, a nonprofit feminist research institute, the problem is one of distorted priorities. “The ART clinics are posing themselves as the answer to an illusory ‘crisis’ of infertility,” she says. “Two decades back, a couple might consider themselves ‘infertile’ after trying for five years to conceive. Then it moved to four years. Now couples rush to ARTs after one or two. Why not put the cultural spotlight on alternatives? Why not urge childless women to adopt orphans? And what, after all, is wrong with remaining childless?”

But Dr. Patel, a striking woman in an emerald green sari and with black hair flowing down her back, sees for-profit surrogacy as a “win-win” for the clinic, the surrogate, and the genetic parents. She also sees no problem with running the clinic like a business, seeking to increase inventory, safeguard quality, and improve efficiency. That means producing more babies, monitoring surrogates’ diet and sexual contact, and assuring a smooth, emotion-free exchange of baby for money. (For every dollar that goes to the surrogates, observers estimate, three go to the clinic.) In Akanksha’s hostel, women sleep on cots, nine to a room, for nine months. Their young children sleep with them; older children do not stay in the hostel. The women exercise inside the hostel, rarely leaving it and then only with permission. Patel also advises surrogates to limit contact with clients. Staying detached from the genetic parents, she says, helps surrogate mothers give up their babies and get on with their lives — and maybe with the next surrogacy. This ideal of the de-personalized pregnancy is eerily reminiscent of Aldous Huxley’s 1932 dystopian novel Brave New World , in which babies are emotionlessly mass-produced in the Central London Hatchery.

Patel’s business may seem coldly efficient, but it also has a touch of Mother Teresa. Akanksha residents are offered daily English classes and weekly lessons in computer use. Patel arranges for film screenings and gives out school backpacks and pencil boxes to surrogates’ children. She hopes to attract donations from grateful clients to help pay children’s school fees as well. “For me this is a mission,” Patel says.

In light of appalling government neglect of a population totally untouched by India’s recent economic boom, this charity sounds wonderful. But is it wonderful enough to cancel out concerns about the factory?


After leaving Anand, I head to Dr. Nandita Palshetkar’s office in Mumbai. With Alifiya Khan, another journalist from the Hindustan Times, I meet with Leela, a lively 28-year-old who gave birth to a baby for Indian clients about six months ago. Like Geeta and Saroj, Leela had been desperate for money, but her experience of pregnancy was utterly different. On the day I meet her, she is dressed in a pink sari, hair drawn back from her olive-skinned face into a long black braid. She leans forward, smiling broadly, eager to talk about her baby, his genetic parents, and her feelings about being a surrogate mother.

At age 20, Leela married a fellow worker at a Mumbai-based company canteen. “I didn’t know he was alcoholic until after we married,” she says. “My husband ran up a $7,000 debt with the moneylender who sent agents to pressure him to repay it. … We couldn’t stop the moneylender from hounding us. I decided to act. I heard from my sister-in-law that I could get money for donating my eggs, and I did that twice. When I came back to do it a third time, madam [Dr. Palshetkar] told me I could earn more as a surrogate.”

Was she able to pay off the debt? Leela lowers her head: “Half of it.”

She ate better food during her paid pregnancy than during her other pregnancies and delivered the baby in a better hospital than the one where she delivered her own children. Unlike others I spoke with, Leela openly bonded with her baby. “I am the baby’s real mother,” she says. “I carried him. I felt him kick. I prayed for him. At seven months I held a celebration for him. I saw his legs and hands on the sonogram. I suffered the pain of birth.”

The baby’s genetic parents, Indians from a nearby affluent suburb, kindly reached out to Leela. The genetic mother “sees me as her little sister, and I see her as my big sister,” Leela says. “They check in with me every month, even now, and call me the baby’s ‘auntie.’ They asked if I wanted to see the baby. I said ‘yes’ and they brought him to my house, but I was disappointed to see he was long and fair, not like me. Still, to this day, I feel I have three children.” A friendship of sorts arose between the two mothers, although Leela’s doctor, like Patel, discouraged it. “I deleted their phone number from my list because madam told me it’s not a good thing to keep contact for long,” she says.

In a November 2008 New York Times Magazine article titled “Her Body, My Baby,” American journalist Alex Kuczynski describes searching through profiles of available surrogates. “None were living in poverty,” she writes. Cathy, the woman she eventually chose to carry her son, was a college-educated substitute teacher, a gifted pianist, and fellow fan of Barack Obama. They shared a land, a language, a level of education, a political bent — coming together to create a baby didn’t seem like such a giant leap. But when the surrogate and genetic mother come from different corners of the globe — when one is an Indian woman who bails monsoon rains from her mud-floor hut and the other is an American woman who drives an SUV and vacations at ski resorts — the gap is more like a chasm. And as one childless American friend (rendered infertile through a defective Dalkon Shield intrauterine device) told me, “If I had hired a surrogate, I’m not sure how close I’d want to be to her. How open can you keep your heart when it’s broken? Sometimes it’s better not to touch unhealed wounds.” A code of detachment seems almost necessary to circumvent the divide.

But detachment isn’t so easy in practice. Even if you can separate the genetic parents from the surrogate, you cannot separate the surrogate from her womb. One surrogate mother told the sociologist Amrita Pande, “It’s my blood, even if it’s their genes.” Psychologists tell us that a baby in utero recognizes the sound of its mother’s voice. Surrogates I spoke with seemed to be struggling to detach. One said, “I try to think of my womb as a carrier.” Another said, “I try not to think about it.” Is the bond between mother and child fixed by nature or is it a culturally inspired fantasy we yearn to be true?

I asked Dr. Chakravarty if he thought that some children born of surrogacy would one day fly to India in search of their “womb mothers.” (The proposed regulation requires parents to reveal to an inquiring child the fact of surrogacy, though not the identity of the surrogate.) “Yes,” he said. But chances are such an 18-year-old would not find her womb mother. Instead, she might come to realize she had been made a whole person by uniting parts drawn from tragically unequal worlds.

In a larger sense, so are we all. Person to person, family to family, the First World is linked to the Third World through the food we eat, the clothes we wear, and the care we receive. That Filipina nanny who cares for an American child leaves her own children in the care of her mother and another nanny. In turn, that nanny leaves her younger children in the care of an eldest daughter. First World genetic parents pay a Third World woman to carry their embryo. The surrogate’s husband cares for their older children. The worlds of rich and poor are invisibly bound through chains of care.

Before we leave the Akanksha clinic in Anand, the gentle embryologist, Bhadarka, remains across the table from Aditya and me after Geeta and Saroj have left the room. I ask Bhadarka if the clinic offers psychological counseling to the surrogates. “We explain the scientific process,” she answers, “and they already know what they’re getting into.” Then she moves her hands across the table and adds softly, “In the end, a mother is a mother, isn’t that true? In the birthing room there is the surrogate, the doctor, the nurse, the nurse’s aide, and often the genetic mother. Sometimes we all cry.”

This story originally appeared in The American Prospect.


Arlie Hochschild’s most recent books are The Commercialization of Intimate Life and (co-edited with Barbara Ehrenreich) Global Woman: Nannies, Maids and Sex Workers in the New Economy., by Zosia Chustecka, April 5, 2010 — New results showing that dutasteride (Avodart, GlaxoSmithKline) reduces the risk for prostate cancer have propelled the subject of chemoprevention for prostate cancer into the spotlight once again.

But the latest results do not convince an expert who has spoken out against this approach in the past; he does so again in an editorial accompanying the study in the March 31 issue of the New England Journal of Medicine.

The study, known as Reduction by Dutasteride of Prostate Cancer Events (REDUCE), was conducted in men considered to be at a high risk for prostate cancer because of their age (50 to 75 years of age), an elevated level of prostate-specific antigen (PSA), or because they had already had a prostate biopsy because of suspicion of prostate cancer.

Over the course of 4 years, significantly fewer prostate cancers were detected in men taking dutasteride than in those taking placebo, representing a relative risk reduction of 22.8% (P < .001).

The researchers, headed by Gerald Andriole, MD, chief of urologic surgery at Washington University School of Medicine in St. Louis, Missouri, conclude that dutasteride “may be considered as a treatment option for men who are at high risk of prostate cancer.”

The data from this trial, which was sponsored by the manufacturer of dutasteride, have been submitted for approval for the indication of prostate cancer risk reduction, Dr. Andriole told Medscape Oncology. Currently, dutasteride is marketed for use in benign prostatic hyperplasia.

Nothing New?

Editorialist Patrick Walsh, MD, from the James Buchanan Brady Urological Institute at Johns Hopkins Medical Institutions in Baltimore, Maryland, told Medscape Oncology that the new data on dutasteride are similar to what has been seen with finasteride (Proscar, Merck & Co), and he believes that neither drug should be prescribed for the chemoprevention of prostate cancer.

“Dutasteride and finasteride do not prevent prostate cancer, but merely temporarily shrink tumors that have a low potential for being lethal,” Dr. Walsh writes in his editorial.

The use of these drugs for prevention may be somewhat risky.

“Furthermore, the use of these drugs for prevention may be somewhat risky,” he warned.

These drugs suppress PSA levels, Dr. Walsh told Medscape Oncology. This is “worrisome,” he explained, because a decrease in PSA might convince men that the drug is preventing prostate cancer and lull them into a false sense of security that could delay a diagnosis “until they have disease that is difficult to cure,” he said.

“Major Distinction” Between Findings

Dr. Andriole agreed that the broad results for the 2 drugs are similar — dutasteride was shown to reduce the risk for prostate cancer by 23%, which is close to the 25% reduction seen with finasteride.

But there is a “major distinction” between the 2 drugs in the findings of high-grade tumors, he told Medscape Oncology.

This has been a major concern with the finasteride data. The 7-year Prostate Cancer Prevention Trial found a reduction in low-grade tumors, but at the same time found an increase in high-grade tumors in the drug group over the placebo group. However, later analyses suggested that the effect of finasteride that reduced the size of the prostate made these high-grade tumors easier to find, rather than increasing their incidence.

In the just-published REDUCE trial, Dr. Andriole said there was “no increase in high-grade tumors in the raw data.”

Although the numbers show a significant increase in high-grade tumors in the dutasteride group, compared with the placebo group (12 vs 1; P = .003), Dr. Andriole asserted that this imbalance can be explained by the men in the placebo group being excluded from the trial if their first biopsy found a tumor. If those men had remained in the study and been biopsied again a few years later, some of their tumors “likely would have been upgraded,” he explained, and this would have resulted in the number of high-grade tumors in the 2 groups being comparable. “This so-called tumor upgrading has been observed in other studies,” he said, adding that this point is elaborated upon in the discussion section of their paper.

Dr. Andriole also noted that if the mathematical modeling that was applied to the finasteride data was applied to the dutasteride data, it would actually show a statistically significant 38% reduction in the risk for high-grade tumors. This is not detailed in their paper, but is explained in a supplementary appendix, he said.

Recommended for Men at High Risk

Dr. Andriole told Medscape Oncology that he recommends prescribing dutasteride to men who are at high risk for prostate cancer (because of elevated levels of PSA, such as in this trial, or because of a family history of the disease). “This drug can reduce the man’s chance of being overdiagnosed and overtreated for prostate cancer,” he added.

In addition, he believes that the benefits of reducing the risk for prostate cancer and the improvement seen in outcomes related to benign prostatic hyperplasia outweigh the risk for adverse effects, which include sexual dysfunction and, in this trial, heart failure.

The sexual adverse effects, which include erectile dysfunction (reported in 9% of men taking dutasteride and in 5.7% of men taking placebo; P < .001), are reversible, Dr. Andriole said, and if they do appear, the drug can be discontinued, he added. Heart failure (reported in 0.7% of men taking dutasteride and in 0.4% of men taking placebo; P = .03) has not been reported as an adverse effect with these drugs, he noted. He suspects that the cases seen in this trial are related to the concomitant use of alpha blockers, although he admitted that this is “speculation.”

Use Recommended by ASCO and AUA

The American Society of Clinical Oncology (ASCO) and the American Urological Association (AUA) jointly recommended the use of both dutasteride and finasteride in asymptomatic men to reduce the risk for prostate cancer in new guidelines issued in February 2009.

However, to date there has been little use of these drugs for this indication, several experts have told Medscape Oncology in previous interviews. This is an off-label use at present; both drugs are marketed for benign prostatic hypertrophy (finasteride is also marketed for male pattern baldness).

Dr. Andriole agreed that there has been little use of finasteride for reducing the risk for prostate cancer, and believes that this stems from concern over the high-grade tumor findings. He believes that the new data on dutasteride will “lay that anxiety to rest,” and that these latest data will lead to an increase in the use of dutasteride for this indication.

Expert Discourages Use for Prevention

Dr. Walsh is firmly opposed to the use of these drugs for prostate cancer risk reduction. He has spoken out against finasteride in comments made in response to an article about the drug preventing cancer that made the front page of the New York Times (June 15, 2008).

“I am very concerned about encouraging patients and general physicians to use this drug,” he wrote in the winter 2009 issue of Prostate Cancer Discovery. He notes finasteride does not prevent prostate cancer, “it just prevents men from knowing they have it!”

“First, it has no primary effect in reducing the number of men who will have a positive biopsy,” he writes. “Second, men will believe that it prevents cancer, will be pleased that their PSA levels fall, and will not understand the potential danger of undiagnosed high-grade disease.”

Dr. Walsh told Medscape Oncology that the comments he made about finasteride at that time apply equally to dutasteride.

“[REDUCE] showed that there was a 23% reduction in low-grade tumors that the patients would never have known they had,” he said. “Does this sound like an indication to take a pill with sexual side effects that costs $4 a day?”

In his editorial, Dr. Walsh reviews previous studies on finasteride and the latest study on dutasteride. He points out that neither drug “significantly reduced the risk of prostate cancer among men who were followed closely and who underwent a biopsy because of an elevated PSA level (corrected for the effect of the drug) or an abnormal digital rectal examination.” He adds that, “unfortunately, this is the setting that would be used for prevention.”

But this approach “will continue to be pushed because of financial interests,” he told Medscape Oncology. The clinical trials have been huge and the companies involved “must have spent a ton of money on it,” he noted.

The REDUCE trial was supported by GlaxoSmithKline, manufacturer of dutasteride, and 4 of the coauthors are employees of the company. Dr. Andriole reports receiving consulting or advisory fees from GlaxoSmithKline and 8 other pharmaceutical companies; several coauthors report receiving consulting, advisory, or lecture fees from GlaxoSmithKline. Details are in the paper. Dr. Walsh has disclosed no relevant financial relationships.

N Engl J Med. 2010;363;1192-1202, 1237-1238.

Press Release…………..U.S. Department of Health and Human Services


National Cancer Institute (NCI)

April 5, 2010  –  In a new study in mice, scientists have compensated for mutations in the Brca1 gene that can lead to cancer by deleting a second gene, which then lessens the probability of cancer. Mice Brca1-associated mammary tumors have significant similarities to human BRCA1- associated (BReast CAncer 1, early onset) breast cancer in regard to tumor aggressiveness, high incidence, mutations and genetic instability. The study, led by scientists at National Cancer Institute (NCI), part of the National Institutes of Health, and their colleagues, appeared online April 1, 2010 and in print April 16, 2010, in the journal Cell.

In humans, mutations in the BRCA1 gene increase the risk of breast, ovarian, and other cancers by impairing an important pathway for the repair of damaged DNA. Lead investigator Andre Nussenzweig, Ph.D., head of the Molecular Recombination Section of NCI’s Experimental Immunology Branch, and his colleagues found that when a gene known as 53BP1 was also defective, the formation of the mammary tumors that normally develop in Brca1 mutant mice was suppressed. Moreover, they found that inactivation of 53BP1 restored the DNA repair function that is lost when Brac1is mutated.

The protein produced by the Brca1 gene participates in an important DNA repair pathway called homologous recombination (HR). This pathway is used to repair a type of DNA damage called replication-associated chromosome breaks, which develop spontaneously when cells divide. When HR is defective, whether through Brca1 mutations or mutations in other genes whose products are involved in this pathway, cells must rely on alternative DNA repair pathways. These other pathways are more error-prone, or mutagenic, than HR, and they can lead to the formation of abnormal and unstable chromosome structures. The resulting genomic instability increases the risk of tumor development.

Women who carry a harmful mutation in the BRCA1 gene have up to an 85 percent lifetime risk of developing breast cancer, and up to a 40 percent lifetime risk of developing ovarian cancer. To date, there are no effective or targeted therapies that overcome the breast cancer susceptibility caused by mutations in BRCA1. “Promoting HR by using drugs that inhibit toxic pathways for DNA repair could greatly reduce the development of breast and ovarian cancer in women with BRCA1 mutations,” said Nussenzweig.

The team used a strain of mice, originally developed by NIH researchers, that have a defective Brca1 gene. These mice frequently develop mammary tumors, which are similar to human breast cancers. Nussenzweig and colleagues found when the mice also were lacking the function of a protein called 53BP1, mammary tumor formation was largely suppressed.

To investigate the molecular basis by which the loss of 53BP1 suppressed Brca1-associated mammary tumor formation, the researchers undertook a series of experiments using mouse cells grown in culture. These experiments showed that it was possible to restore HR to Brca1-deficient cells by inactivation of the gene 53BP1.

Further analysis led to a model in which both Brca1 and 53BP1 are capable of binding to replication-associated chromosome breaks. According to this model, when both proteins are present, Brca1 displaces 53BP1, the HR machinery has full access to the breaks, and HR proceeds. In Brca1-deficient cells, the binding of 53BP1 to the site of DNA damage interferes with the activity of HR proteins. Consequently, the damage is instead repaired by an alternative mutagenic pathway that promotes cancer. When 53BP1 is absent, Brca1 is not needed to displace it. Therefore, HR can take place normally when both proteins are missing.

“Our results show that the choice of pathway used to repair DNA damage determines whether the repair is error-free or error-prone. This opens the possibility of using drugs to inhibit mutagenic DNA repair pathways and promote error-free DNA repair,” said Nussenzweig.

The study also suggests that BRCA1-deficient tumors may become resistant to chemotherapy by acquiring additional mutations in certain DNA repair proteins, but that such resistance may one day be overcome by drugs developed to affect pathway choice, according the researchers.

NIH investigators from the National Heart, Lung and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases also participated in the study, as well as colleagues from Beckman Research Institute of City of Hope, Duarte, Calif.; Rockefeller University, New York City; and the Spanish National Cancer Research Centre, Madrid, Spain.


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Nussenzweig A, et al. 53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks. Cell, April 16, 2010.  DOI 10.1016/j.cell.2010.03.012.



This NIH News Release is available online at:


Hospital Therapy…………..Source: Flickr, by Alison Gandey, April 5, 2010 — For the first time in more than a decade, an American Society of Anesthesiologists taskforce has updated its chronic pain guidelines.

The new recommendations are designed to help clinicians who treat pain. The objectives are to optimize pain control, enhance physical and psychological well-being, and minimize adverse outcomes.

Richard Rosenquist, MD, from the University of Iowa Hospital, Iowa City, led the 12-member taskforce of anesthesiologists in both private and academic practice from various parts of the United States. The group also worked with members of the American Society of Regional Anesthesia and Pain Medicine.

The new guidelines appear in the April issue of Anesthesiology.

The recommendations apply to patients with chronic noncancer, neuropathic, somatic, or visceral pain. The taskforce focused on interventional diagnostic procedures including diagnostic joint block, nerve block, and neuraxial opioid trials.

Focus on Interventional Diagnostic Procedures

The team agreed that findings from the patient history, physical examination, and diagnostic evaluation should be combined to provide an individualized treatment plan focused on optimizing the risk-to-benefit ratio. Treatment should progress from a lesser to greater degree of invasiveness.

“Whenever possible,” the taskforce reports, “direct and ongoing contact should be made and maintained with the other physicians caring for the patient to ensure optimal care.”

The new guidelines advocate for multimodal interventions for patients with chronic pain. The taskforce suggests that a long-term approach that includes periodic follow-up evaluations should be developed and implemented as part of the overall treatment strategy. In addition, when available, multidisciplinary programs may be used.

The new guidelines detail

  • ablative techniques,
  • acupuncture,
  • blocks,
  • botulinum toxin,
  • electrical nerve stimulation,
  • epidural steroids,
  • intrathecal drug therapies,
  • minimally invasive spinal procedures,
  • pharmacologic management,
  • physical therapy,
  • psychological treatment, and
  • trigger point injections.

The taskforce defines chronic pain as pain of any etiology not directly related to neoplastic involvement associated with a medical condition or extending in duration beyond the expected temporal boundary of tissue injury and normal healing and adversely affecting the function or well-being of the individual.

Drugs for chronic pain include anticonvulsants, antidepressants, benzodiazepines, N-methyl-D-aspartate receptor antagonists, nonsterioidal anti-inflammatories, opioid therapy, skeletal muscle relaxants, and topical agents. The taskforce discusses each in detail and recommends strategies for monitoring and managing adverse effects and patient compliance.

The new guidelines cover a range of advances not included in the initial version published in 1997. As a result, the number of pages has more than doubled in the new publication. The complete guidelines are available online.

Financial disclosures for the 12 members of the American Society of Anesthesiologists taskforce were not provided.

Anesthesiology. 2010;112:810-833.

But Your Inner Chocolate Police Need to be On Patrol (Heartwire),, by Lisa Nainggolan  –  April 5, 2010 (Nuthetal, Germany) — The largest observational study so far to examine the association between chocolate consumption and risk of cardiovascular disease has found that those who ate the most chocolate–around 7.5 g per day–had a 39% lower risk of MI and stroke than individuals who ate almost no chocolate (1.7 g per day) [1].

Lead author Dr Brian Buijsse (German Institute of Human Nutrition, Nuthetal, Germany) told heartwire : “This shows that habitual consumption of chocolate is related to a lower risk of heart disease and stroke that is partly explained by blood-pressure reduction. The risk reduction is stronger for stroke than for MI, which is logical because it appears that chocolate and cocoa have a pronounced effect on BP, and BP is a higher risk factor for stroke than for MI.” Buijsse and colleagues report their findings online March 31, 2010 in the European Heart Journal.

However, Buijsse cautions that only small amounts of chocolate were associated with the benefits and it is too early to give recommendations on chocolate consumption: “Maybe it’s a boring message, but it’s a little too early to come up with recommendations, because chocolate contains so many calories and sugar, and obesity is already an epidemic. We have to be careful.” However, he added, that if people did want to treat themselves, they would be better off choosing small amounts of chocolate, preferably dark chocolate, over other sweet snacks. “We know it is the cocoa content in chocolate that is important, so the higher the cocoa content, the better.”

Dr Steffen Desch (University of Leipzig, Heart Center, Germany), who was not involved with this study but who has performed research on the effects of chocolate on blood pressure, told heartwire : “This is an interesting study that adds to the growing body of evidence that flavanol-rich chocolate might be associated with health benefits. Several epidemiological studies (including the Zuphten Elderly Study, by the same first author) and even more physiological trials have been published before.”

“What is missing now is a large-scale randomized trial of flavanol-rich chocolate versus control. The most reasonable end point would probably be the change in blood pressure between groups.” However, Desch added, “the major problems in designing such a study are the lack of funding and finding an appropriate control substance. To the best of my knowledge, there is no commercially available flavanol-free chocolate that offers the distinct bitter taste and dark color inherent to cocoa-rich chocolate.”

Biggest Chocolate Consumers Had Lowest Blood Pressure

Buijsse and colleagues followed 19 357 people, aged between 35 and 65, who were participants in the Potsdam arm of the European Prospective Investigation into Cancer (EPIC). They received medical checks, including blood pressure and height and weight measurements at the start of the study (1994–1998), and they also answered questions about their diet, lifestyle, and health, including how frequently they ate 50-g bars of chocolate.

The research was conducted before the health benefits of chocolate and cocoa were recognized, so no differentiation was made between milk, dark, and white chocolate in the study. But in a subset analysis of 1568 participants later asked to recall their chocolate intake over a 24-hour period, 57% ate milk chocolate, 24% dark chocolate, and 2% white chocolate.

Participants were divided into quartiles according to their level of chocolate consumption. Those in the top quartile, eating around 7.5 g of chocolate a day, had blood pressure that was about 1 mm Hg (systolic) and 0.9 mm Hg (diastolic) lower than those in the bottom quartile.

In follow-up questionnaires, sent out every two or three years until December 2006, the participants were asked whether they had had a heart attack or stroke, information that was subsequently verified by medical records from general physicians or hospitals. Death certificates from those who had died were also used to identify MIs and strokes.

“Our hypothesis was that because chocolate appears to have a pronounced effect on blood pressure, chocolate consumption would lower the risk of strokes and heart attacks, with a stronger effect being seen for stroke,” explained Buijsse.

Those Eating Most Chocolate Had Half the Risk of Stroke

During the eight years, there were 166 MIs (24 fatal) and 136 strokes (12 fatal); people in the top quartile had a 27% reduced risk of MI and nearly half the risk (48%) of stroke, compared with those in the lowest quartile. The relative risk of the combined outcome of MI and stroke for top vs bottom quartile was 0.61 (p=0.014).

The researchers found that lower baseline blood pressure explained 12% of the reduced risk of the combined outcome, but even after taking this into account, those in the top quartile still had their risk reduced by a third (32%) compared with those in the bottom quartile over the duration of the study.

To put this in terms of absolute risk, Buijsse said if people in the group eating the least amount of chocolate increased their chocolate intake by 6 g a day, 85 fewer heart attacks and strokes per 10 000 people could be expected to occur over a period of about 10 years.

He says it appears that flavanols in chocolate are responsible for the beneficial effects, causing the release of nitric oxide, which contributes to lower BP and improves platelet function.

Dr Frank Ruschitzka (University Hospital, Zurich, Switzerland) agrees. He said in a European Society of Cardiology statement [2]: “Basic science has demonstrated quite convincingly that dark chocolate particularly, with a cocoa content of at least 70%, reduces oxidative stress and improves vascular and platelet function.”

Only Small Amounts of Chocolate Beneficial; Don’t Eat Too Much

Buissje said this work builds on his earlier small trial–the Zuphten Elderly Study–performed in 500 men in Holland, which showed that chocolate consumption lowered overall cardiovascular mortality. “Due to the small size of this study, we were not able to differentiate between stroke and MI in this, but now we are able to look at stroke and MI separately, so it’s a nice addition,” he notes.

And the findings are in line with an intervention study that showed that eating around 6 g of chocolate a day–one small square of a 100-g bar–might lower CV disease risk, he says. “So the effects are achieved with very small amounts.”  

British Heart Foundation dietician Victoria Taylor made the same point: “It’s important to read the small print with this study. The amount consumed on average by even the highest consumers was about one square of chocolate a day or half a small chocolate Easter egg in a week, so the benefits were associated with a fairly small amount of chocolate.

“Some people will be tempted to eat more than one square; however, chocolate has high amounts of calories and saturated fat . . . two of the key risk factors for heart disease,” she noted in a statement.

Ruschitzka similarly urged caution: “Before you rush to add dark chocolate to your diet, be aware that 100 g of dark chocolate contains roughly 500 calories. As such, you may want to subtract an equivalent amount of calories, by cutting back on other foods, to avoid weight gain.”, by Nadia Arumugam  –  Long gone are the days when chocolate bars came in three simple varieties; white, milk and dark. Nowadays additions like chili, green tea, bacon and manna crystal barely raise an eyebrow as shoppers hustle past the chic chi candy displays in gourmet grocery stores. So what do you do when you want to cause a stir in the over saturated chocolate world? You go back to basics. Rather than innovating with outlandish flavorings, Dubai based chocolate company Al Nassma replaced the oh-so-passe cow’s milk with camel’s milk from camels raised on its own farm. 3,000 camels later and ten months since the company started selling its unique chocolates locally in Dubai, Al Nassma has decided that the rest of the world is finally ready for its camel confections.

“We aim to be the Godiva of the Middle East,” said the Company’s general manager, Martin Van Almsick as reported by Reuters. But with plans to open a store in Japan and to expand into Europe and the US, it’s also counting on the adventurous palates of the intrepid international gourmand to ensure the chocolate has more than just a fleeting novelty value. As for how the chocolate actually tastes, there’s no word from Van Almsick. The website is also suspiciously barren of any useful information. Al Nassma is a “refreshing ocean wind that at certain times brings the coolness of the ocean to the desert plains. Now this phenomenon lends itself to another, equally refreshing feat, the first and finest camel milk chocolate”, is all it offers. The cynic might wonder whether they are trying to hide something. Apparently, camel milk has a stronger, more pungent flavor and aroma than cow’s milk, resembling goat’s milk. Still the potentially  funky taste  might be worth it if you can pick up a box of camel shaped chocolates that actually has camel in it. After all, when was the last time you ate a chocolate Easter bunny that was actually made of bunny milk?

Jesting aside, this isn’t to say that Al Nassma isn’t on to something special after all. Camel milk certainly has its advocates. Not only is it reputed to have significantly more vitamin C, iron and potassium than standard cow’s milk but it’s also considerably lower in fat. And there’s more; clinical analysis of camel’s milk has shown it to be 40 per cent lower in cholesterol than cow’s milk. When combined with sugar and all the magic involved in chocolate making, however, it’s doubtful that these health benefits still apply.

But we may not be all that far away from being able to pick up a carton of unadulterated camel juice from our local bodegas. Certainly not if camel milk fanatic Millie Hinkle has anything to do with it. Just a couple of days ago, The Wall Street Journal Online ran a story on the trials and tribulations of Hinkle’s endeavor in trying to market camel milk in the US. Hinkle first tried camel milk in the UAE 10 years ago and soon became obsessed with the “other” white stuff. Hinkle is working with a large camel dairy in the Middle East who will help to start a camel dairy in the U.S. Aside from the challenges in getting the milk approved from the FDA, there’s another, perhaps even more trying and potentially dangerous problem that Hinkle faces. Camels don’t like to be milked. “Camels can be cantankerous and persuading them to give up their milk can be part chore, part art. Camel experts say the animals are often ticklish around their udders and, without proper training, might lie down in the middle of being milked,” reports the WSJ.

The Wall Street Journal,, by Lauren Etter, RALEIGH, N.C. — Millie Hinkle first tasted camel milk in the United Arab Emirates about 10 years ago. She had no idea the salty drink, still warm from the camel and served in an ornate bowl with a side of walnuts, would become an obsession.

“It has taken over my life,” said the 57-year-old practitioner of natural medicine as she cruised down a tree-lined road here in her white SUV emblazoned with a camel.

In some countries, camel milk is called “liquid gold” for its healing and nutritional qualities. But camel dairy is not widely available in the U.S., in part because the animals don’t like to be milked. Lauren Etter reports from Raleigh, North Carolina.

Ms. Hinkle has drained her savings, slashed the number of hours she spends at her day job and started a company called Camel Milk USA. Her goal is to bring the milk, reputed to have healing and aphrodisiac powers, to the U.S. where it’s been hard to get mainly because camels weren’t listed in rules governing the sale of milk.

In April, Ms. Hinkle won initial approval from the National Conference on Interstate Milk Shipments, a nonprofit group, to market the milk. Now, she’s awaiting approval from the U.S. Food and Drug Administration on some final details.

But there are several humps to overcome before camel milk is widely available in the U.S. For starters, there aren’t many camels here. Those that are mainly work in circuses or live in zoos.

Another challenge: Camels don’t much like to be milked. Camels can be cantankerous and persuading them to give up their milk can be part chore, part art. Camel experts say the animals are often ticklish around their udders and, without proper training, might lie down in the middle of being milked.

Camel milk is a centuries-old staple for nomadic tribes across the Middle East and Africa. It is also drunk by elderly men to enhance virility; by the sick to treat a variety of ailments; and by those who believe it has magical properties.

Camels feed at North Carolina‘s Ferncroft Farms, which is working with Millie Hinkle, proprietor of Camel Milk USA.

Ms. Hinkle said she’s working with a large camel dairy in the Middle East that is interested in helping start a camel dairy in the U.S. She declined to name the dairy.

Most camel milking is still done by hand, but some modern dairies have gotten into the game. A dairy in Dubai called Emirates Industries for Camel Milk & Products sells camel-milk chocolate and camel milk under the brand “Camelicious.” The milk comes in flavors including saffron and date.

The Camelicious dairy, opened in 2006, uses mechanized milking technology and trains camels to walk into the milking parlor. When the dairy first started, “the Bedouins said, ‘No way will the animals enter that milking parlor,'” said Peter Nagy, the Hungarian farm manager there.

He and his wife, both veterinarians, solved the problem, he said, but “I cannot explain exactly how this was done.” Mr. Nagy credits training by his wife: “A woman has a sixth sense” that allows her to “know how the animals feel.”

Today, the Camelicious dairy has more than 1,500 camels. They are taken by the Bedouins on one-hour walks daily through the desert in a caravan formation. The dairy is working to develop higher-yielding milking camels. An average milking camel produces about two gallons of milk a day, Mr. Nagy said. Dairy cows produce around seven gallons a day.

In a 2006 report, the United Nations recommended camel milk as an area for Middle East economic development, saying that $10 billion in global sales “would be entirely within the realm of possibility.”

Ms. Hinkle, who dons flowing white pantsuits and dangly gold earrings, sometimes tears up when talking about her quest. “I have to try to do what I can to help the most people,” she said. “And for me this is it.”

She said she was interested in becoming a physician as a young woman, but after being “poisoned” by lawn pesticides decided instead to study natural medicine. She opened her own clinic about 20 years ago in Raleigh, called Natural Health Resource Center. Here, from a second-floor office, she says she fields emails and calls from people who want camel milk as a health remedy and immigrants who crave the drink.

She gets a phone call almost every week from Abdirizak Mohamuod, a Somalian man in Minnesota who sells dried fruits and ethnic food. He says he has at least 70,000 Somalian customers in Minnesota who would buy it. “We would like to get the milk as soon as possible,” he said.

Ms. Hinkle got her first taste of camel milk in the late 1990s while on a trip to the United Arab Emirates with her husband, who was then working for the state of North Carolina. As guests at the home of a member of the royal family, she recalls they were shown a lush backyard filled with racing camels and treated to fresh camel milk.

“I liked it OK,” she said. But “it was one taste, and I never thought of it again.”

Until three years ago. Her curiosity was piqued after reading about the benefits of camel’s milk in an alternative-health magazine.

Camel milk has three times as much vitamin C as cow’s milk and contains high amounts of iron, unsaturated fatty acids and B vitamins, according to the United Nation’s Food and Agriculture Organization. Proponents tout it as an aid for everything from diabetes to autism. A biomedical research company in Belgium, called Ablynx, has been working on developing drugs based on antibodies found in camels and llamas, called nanobodies.

When Ms. Hinkle tried to buy camel milk in the U.S., she couldn’t find any, which she found frustrating. “As I read more about camel milk, I thought ‘I gotta get it here.'”

Her drive sent her before the National Conference on Interstate Milk Shipments, a nonprofit, industry-backed group formed in 1946 that oversees drafting of certain regulations that are then sent for FDA approval. She put together a proposal asking for camels to be included under the milk rules. The FDA recently gave tentative approval to cover camels, as well as reindeer, llamas, moose and donkeys under the rules.

An FDA spokesman said, “We wanted to improve the science basis in the definition” of milk coming from hooved mammals to include “species that may not have ‘true hooves,'” such as camels.

Now, Ms. Hinkle is working to get FDA approval of a series of tests required to ensure the quality of camel milk. To do that, she needed samples. Larry Seibel, an animal breeder just north of Raleigh who specializes in white and spotted camels, agreed to help.

On a recent day, Mr. Seibel’s wooded 85-acre reserve, called Ferncroft Farms, was abuzz with peacocks, munchkin cats, French bulldogs and a zebra. One of his 40 camels, named Martha, had recently given birth, providing a perfect milking opportunity since a camel tends to give up milk only with its baby nearby.

Martha, standing nearly 6 feet tall at the hump, moaned and kicked around hay in her barn. Her baby hungrily suckled her udders as a farmhand tiptoed around her and started milking.

Mr. Seibel petted Martha and cooed, “Good girl.” Finally, Martha squirted her milk, which resembled a cappuccino, into a glass jar.

“Mission accomplished,” said Ms. Hinkle.