•    Giffords doing well after weekend surgeries: doctors
•    Doctors open breathing hole in Giffords’ throat

GoogleNews.com, FORBES.com, LOS ANGELES | Mon Jan 17, 2011  (Reuters) – The astronaut husband of Congresswoman Gabrielle Giffords said in his first television interview that his wife still faces months of recovery but is a “really, really tough woman.”
Capt. Mark Kelly, a NASA space shuttle commander who rushed to Giffords’ side after she was shot in the head during a January 8 rampage in Arizona, told ABC News that he was realistic about challenges facing his wife.
“Gabby’s got a long road ahead of her,” Kelly said in an interview set to air on the ABC News program “20/20” on Tuesday.
“We know that the recovery from these kind of injuries isn’t measured in days and weeks,” he said. “It’s more like weeks and months. And so she’s got a long, tough road ahead of her. But, you know, she’s a really, really tough woman.”
Giffords, who was struck in the head by a single bullet was upgraded from critical to serious condition on Sunday, after doctors said they had removed her from a ventilator and that the danger from brain swelling had passed.
Surgeons said during a press conference on Monday that the congresswoman was recovering well from a pair of weekend operations and could be released from the hospital to begin rehabilitation in the coming weeks.

Doctors Remove Bone Chips From Giffords Eye Socket

A poster outside of Rep. Gabrielle Giffords office in Tucson, Ariz., wishes her well Sunday, Jan. 16, 2011. Makeshift memorials have sprouted up around Tucson for the victims of the Jan. 8 shooting that killed six people and injured 13, including Giffords. (AP Photo/Susan Montoya Bryan)

By AMANDA LEE MYERS and BOB CHRISTIE

GoogleNews.com, FORBES.com, January 17, 2011, TUCSON, Ariz. — Doctors have successfully performed a surgery on Rep. Gabrielle Giffords’ eye socket to remove bone fragments as the wounded congresswoman showed more signs of improvement.

There were no complications from the surgery, and Giffords is improving so much that she was able to give her husband a back rub.

Dr. Randall Friese said Mark Kelly also told doctors he saw Giffords smile. He said sometimes people see what they want to see, but that “if he says she’s smiling, I buy it.”

Giffords still cannot speak because of a tracheotomy done so the breathing tube could be removed from her mouth.

Dr. Michael Lemole says the eye operation entailed making an incision above the eyebrow, removing bone chips to relieve pressure and reconstructing the roof of the socket.

GoogleNews.com, FORBES.com, January 17, 2011, (earlier story)TUCSON, Ariz. (AP) – U.S. Rep. Gabrielle Giffords has surmounted one hurdle after another since she was gravely wounded in the Arizona shootings. Her latest was especially significant – a condition upgrade from critical to serious.

Her doctors’ decision Sunday was yet another sign of a remarkable recovery since she was shot in the head Jan. 8 when a gunman opened fire as she met constituents in a Tucson supermarket parking lot. Six people were killed and 13 were wounded, including the congresswoman.

Giffords is now able to move around well enough that she gave Kelly a back rub from her hospital bed, he told ABC’s Diane Sawyer in an interview that will air Tuesday.

“(It is) so typical of her. She’s in the ICU. You know, gone through this traumatic injury. And she spent 10 minutes giving me a neck massage,” Kelly explained. “I keep tellin’ her. I’m like, ‘Gabby, you’re in the ICU. You know, you don’t need – you know, you don’t need to be doin’ this.’ But it’s so typical of her that no matter how bad the situation might be for her, you know, she’s lookin’ out for other people.”

The gesture seemed to comfort Giffords and shows that his wife is improving and that her spirit and their personal bond remain strong, he said.

Kelly also said he would be willing to meet with the parents of suspect Jared Loughner. Kelly, who has two teenage daughters from a previous marriage, said they have to be hurting.

Giffords had been in critical condition since the attack but doctors were positive, and at times almost giddy, in describing her progress.

She responded from the moment she arrived at the emergency room, at first just squeezing a doctor’s hand. Then she raised two fingers.

Giffords opened her unbandaged eye shortly after President Barack Obama’s bedside visit Wednesday.

Then, more milestones – which doctors said were all indicative of higher cognitive function – were achieved, all with her husband, astronaut Mark Kelly, at her side.

Kelly asked her to give him a thumbs-up if she could hear him. She did more than that. She slowly raised her left arm. By the end of the week, she had moved her legs and arms.

Finally on Sunday, doctors decided to upgrade her condition because a tracheotomy done a day earlier was uneventful, hospital spokeswoman Katie Riley said. A feeding tube was also put in Saturday, and doctors speculated that they might soon know if she could speak.

At the hospital, more than 100 people were gathered amid the sea of get-well balloons and cards when the University of Arizona put out the condition statement.

“Oh, that’s great news,” said Jean Emrick, a 50-year resident of Tucson, as a violinist played in the background.

Her eyes watering, Emrick said: “Tucson is such a special place and she represents what’s the best of southern Arizona.”

As night fell, candles at the makeshift memorial began to flicker. A mariachi band played the “The Star-Spangled Banner.”

Few people survive a bullet to the brain – just 10 percent – and some who do end up in a vegetative state. It is even more rare for people with gunshot wounds to the head to regain all of their abilities, and doctors have cautioned that the full extent of Giffords’ recovery remains uncertain.

A Test for 400 Inherited Diseases

Spotting disease: The white column in the middle of this DNA sequence chart highlights a four-letter deletion in the genome that is linked to a disorder called Lesch-Nyan syndrome. The disorder, which strikes in infancy, causes severe mental and physical problems.     Credit: Stephen Kingsmore

New technology will allow broad screening for prospective parents

MIT Technology Review, January 17, 2011, by Emily Singer  —  Researchers have developed a new test designed to simultaneously detect genetic mutations involved in more than 400 severe diseases. The test, which was shown to be highly accurate, is initially aimed at screening prospective parents for mutations linked to rare inherited disorders.

Thanks to inexpensive sequencing technology, scientists aim to offer the test for just a few hundred dollars, similar to the cost of tests currently available for detecting individual diseases or a handful of disorders.

“We want this test to become available in the same way Tay-Sachs and cystic-fibrosis testing has,” says Stephen Kingsmore, chief scientific officer of the National Center for Genome Resources and senior author on the study. Tay-Sachs, a rare inherited disorder, strikes in infancy and is typically fatal within the first few years of life. “Forty years of experience with Tay-Sachs resulted in that awful disorder becoming pretty much eradicated in North America,” he says. “This is just on a grander scale.”

The new test, which reads the sequence of about 2 million letters of DNA spread out over 7,000 different chunks, is designed to detect mutations in genes that have been linked to so-called recessive Mendelian disorders, including cystic fibrosis and Tay-Sachs. People who inherit two mutant copies of the relevant gene are guaranteed to develop the disease, while people with only one copy will not. These diseases often strike early in life with severe consequences, including severe disability and death. And while they are individually rare, together they account for about 20 percent of infant mortality.

Testing prospective parents for these mutations can help them prevent or plan for the diseases. Couples who are both carriers of mutations in a particular disease-linked gene could choose to adopt, to conduct genetic tests on in-vitro-fertilized embryos, or to do prenatal testing and terminate affected pregnancies.

While more than 1,000 genes have been linked to recessive Mendelian disorders, the tests now available to prospective parents screen for only the most common, such as cystic fibrosis, and are mainly offered to parents in high-risk groups. Ashkenazi Jews are at particular risk of carrying Tay-Sachs mutations, for example.

“To be able to screen for more than 400 rare conditions is really an important advance,” says Eric Topol, director of the Scripps Translational Science Institute, who was not involved in the study. “We don’t have anything near that today.”

The major impediment to broad genetic screening has been cost, for the kind of DNA sequencing used in most clinical diagnostic tests is very expensive. Kingsmore and collaborators took advantage of the latest sequencing technology, which can sequence much greater volumes of DNA more quickly and cheaply. This technology has already transformed genetic research, but it has been slow to make its way into medical use.

“A huge question is whether it is robust enough to be used in clinical testing in humans,” says Kingsmore. According to his findings, published Wednesday in Science Translational Medicine, the answer is yes. When compared with another technology—microarrays designed to detect specific genetic mutations—the sequencing-based approach was 99.98 percent accurate. And follow-up testing of DNA from 100 people with a known mutation was 100 percent accurate. (Kingsmore’s team actually found that a number of the original samples had been misclassified.)

The advantage of a sequencing-based test over one that uses microarrays is that the latter can detect only known mutations. Sequencing, on the other hand, can spot any variation in disease-linked genes, even if it has never been seen before. (For some diseases, a few common mutations account for most cases of the disease, but for others, many different types of mutations can disrupt the relevant gene.) A comprehensive screening test launched last year by a startup called Counsyl tests only for known mutations. That’s a problem, says Kingsmore, because “we don’t have a good catalogue of mutations for most diseases.”

To develop the new test, the team modified existing technology to select relevant portions of the genome by binding stretches of complementary DNA to the regions of interest, drawing them out of a soup of DNA. Next they used sequencing technology from Illumina to analyze the extracted DNA. Since submitting their paper, the researchers have expanded the test to scan for mutations linked to more than 600 different conditions.

Kingsmore says the test currently costs $618 to run, not including any costs associated with commercialization. He predicts the cost will drop in next the next two years. His institute, a nonprofit that developed the technology with funding from a patient-advocacy group, aims to offer it for $500, on par with current carrier screens.

“Rapid progress in sequencing makes it possible to gather the enormous amount of sequencing information at a manageable cost,” says Arthur Beaudet, chair of the department of Molecular and Human Genetics at Baylor College of Medicine, who was not involved in the study. “And it will quite likely get cheaper over time.”

The test isn’t yet available to prospective parents. Researchers are now beginning to test the technology in clinical labs, a necessary step toward getting it approved by the Food and Drug Administration. “We believe we will be able to offer it on a research basis in the summer of 2011,” says Kingsmore.

Cell invader: Immediately after injection into live mice, micelles can be seen travelling through the
bloodstream glowing green.     Credit: Science Translational Medicine

Tiny Trojan horses deliver a cancer drug to cell nuclei

MIT Technology Review, January 17, 2011, by Nora Schultz  —  A new nanodelivery system is able to sneak cancer treatments past the defenses of drug-resistant tumor cells—offering hope to many cancer patients who benefit little from existing drug treatments.

Researchers at the University of Tokyo designed small soapy clusters of molecules, called micelles, to carry drugs into tumor cells and release their cargo inside. The molecules harness the cell’s internal transport system to get close to their target—the cell’s DNA.

Releasing the drug close to a cancer cell’s nucleus appears to protect it from the cell’s self-defense mechanism. The approach slowed the growth of tumors in mice—even tumors that were completely resistant to the drug when it was administered normally. The work was published yesterday in the journal Science Translational Medicine.

“This addresses a key hurdle in cancer treatment by overcoming the limitations faced by free drugs—that is, development of resistance by cells,” says Samir Mitragotri, professor of chemical engineering at the University of California, Santa Barbara, who was not involved with the research.

Micelles were tested as a delivery system for the colorectal cancer drug oxaliplatin in mice with drug-resistant human colon cancer.

Ordinarily, oxaliplatin is injected into a patient’s bloodstream, and from there it enters the cytoplasm of tumor cells by way of small gaps or channels in the cell membrane. Only about 5 to 10 percent of the drug particles make it to the cell’s nucleus, but those that do attach themselves to the DNA and disrupt its function, eventually killing the cancer cell. Once colorectal cancer has begun to metastasize, however, within nine months it develops defense proteins in its cytoplasm that inactivate oxaliplatin.

The micelles penetrate the cell membrane in a different way, entering the cell through a process called endocytosis. Small sections of the cell membrane pinch off and form bubble-like vesicles that engulf the micelles. These membrane-enclosed sacks travel along the cell’s internal transport system until they approach the nucleus. As the micelles get closer to the cell nucleus the chemistry inside the vesicles gradually becomes more acidic, the better to digest their cargo into small nutrient particles.

As conditions become more acidic, the molecules of the micelles, which have self-assembled around the drug molecules, lose their ability to stick together and release the drug molecules.

“Micelles work as nanoscaled Trojan horses to efficiently deliver a drug into the nucleus of drug-resistant cancer cells,” says lead author Kazunori Kataoka, a professor in the Department of Materials Engineering and Bioengineering at the University of Tokyo.

This drug-delivery mechanism slowed tumor growth by approximately 75 percent compared with tumors treated with regular oxaliplatin.

By equipping each micelle component with a green fluorescent tag at the surface and a red fluorescent tag that faces the core, the researchers were able to track their progress through cells with fluorescent video microscopy and film when and where the micelles delivered their payload.

Katakoka’s colleague Nobuhiro Nishiyama, says the micelles are more responsive than any other known drug carrier to the chemical conditions at the target site inside a cell.

Omid Farokhzad of the Laboratory of Nanomedicine and Biomaterials at Harvard Medical School says that without this kind of subcellular targeting system, drugs delivered by nanocarriers are not necessarily more effective. “Nanocarrier engineering really needs to become more sophisticated, and people will look to this work as a landmark study for how you can engineer the system to target subcellular compartments,” Farokhzad says