Indonesia confirms two more bird flu deaths

Jakarta (VNA) - The Indonesian Health Ministry on August 13 confirmed the deaths of a woman and her daughter in Bali as a results of bird flu, bringing the country's total death toll from the disease to 83.

These were the first human deaths from bird flu on the resort island, where the H5N1 virus was identified more than a year ago.

The 29-year-old woman died on August 12 and her five-year-old daughter on August 3, Bayu Krisnamurti, head of the national commission for bird flu, said.

Laboratory tests provided by the Eikman Institute and the Health Ministry confirmed the presence of H5N1 in both cases, Bayu told reporters.

ST. LOUIS — When Missouri voters approved a constitutional amendment last November protecting human embryonic stem cell research, it was viewed as a key endorsement of the research even in states with deep religious roots and strong antiabortion forces like this one.

But the expected expansion of stem cell research in Missouri has since run into political and financial roadblocks, putting the future of the research in doubt.

State lawmakers who opposed the constitutional amendment continue to fight it, introducing new bills that would bar some types of the research and suggesting that a ballot initiative to that end may lie ahead.

Although the legislative efforts have so far failed, the uncertainty has made it difficult for facilities to attract stem cell specialists, some of whom question the state’s commitment to research that supporters say could lead to treatments for diseases like Parkinson’s and cancer.

In June, a private facility in Kansas City, the Stowers Institute for Medical Research, suspended plans for a $300 million expansion, citing the “persistent negative political climate” toward embryonic stem cell research.

The founders of the institute, Jim and Virginia Stowers, had contributed $30 million to the campaign to pass the constitutional amendment.

Kevin C. Eggan, an assistant professor of molecular and cellular biology at Harvard University who works with stem cells, said he had strongly considered moving to Stowers, but had delayed his plans.

“Everybody hoped that Missouri was going to be a good test case,” Mr. Eggan said. “It was exciting to us that stem cell research was being voted in in a state which has very restrictive abortion laws. But it has turned out to be a big disappointment.”

A few months ago, the University of Missouri, in Columbia, lost some $85 million in state money for a new research facility. University officials said the facility was not intended for stem cell research, but opponents of the research blocked the financing anyway, suggesting that the constitutional amendment would make it possible down the road.

“For a bright shining moment in time, we were moving ahead as a state to protect research,” said Senator Chuck Graham, Democrat of Columbia. “But now the other side wants to walk away, not only from stem cell research, but all research. Their attitude now is, if there’s a beaker or a Petri dish involved, we’re not going to fund it.”

Representative Jim Lembke, a St. Louis Republican who said he opposed the destruction of human embryos, is among those who have proposed new legislation outlawing some elements of the research.

“As people are educated about this issue, they come around,” Mr. Lembke said.

The ballot measure that passed last fall guarantees that any federally allowed stem cell research or treatment will also be allowed in Missouri.

The question of embryonic stem cell research has usually been fought out in state legislatures, not among voters, but supporters said the Missouri legislature’s efforts to ban the research had led them to seek the statewide vote.

Only in California had voters approved a comparable measure, and Missouri was seen as offering a picture of how a more socially conservative state might respond. California’s measure was approved in 2004 and included $3 billion in financing for stem cell research. Missouri’s measure included no money.

Other factors made the Missouri vote of special importance. It became a central issue in a race here that would help decide the balance of power in the United States Senate — between Senator Jim Talent, the Republican incumbent, who opposed the amendment, and Claire McCaskill, his Democratic challenger, who supported it and ultimately won.

Though the amendment passed, the margin of 51 percent to 49 percent, a difference of 50,800 votes (out of about 2.1 million cast), was slimmer than some had predicted. It was rejected in 97 of the state’s 114 counties, secretary of state records show, gaining most of its support in the metropolitan areas of St. Louis and Kansas City.

Supporters of the amendment outspent opponents by a wide margin. Within hours of the vote, opponents said they would fight on, focusing their attention narrowly on one element of the research, known as therapeutic cloning or somatic cell nuclear transfer, in which the nucleus of a mature cell is transplanted into an egg cell, which would then produce stem cells.

The debate has come down to a fight over what constitutes “cloning.”

Supporters of the amendment say they banned human cloning, which they defined in the amendment as an act that could result in a woman’s pregnancy and the creation of a human fetus inside a woman’s uterus. Opponents say the replication of cells, regardless of implantation in the uterus, amounts to cloning.

“We think it’s a false distinction to say that a clone exists only based on geography,” said Pam Fichter, the president of Missouri Right to Life. “Look, we support ethical stem cell research, and we think cloning was misrepresented to voters. We know that a majority of Missourians oppose cloning.”

Donn Rubin, chairman of the Missouri Coalition for Lifesaving Cures, which led efforts to pass the amendment, said that reproductive cloning was what the public worried about.

“What we protect is a very promising form of medical research that involves cells in a lab dish, not something that involves pregnancy,” Mr. Rubin said.

Some scientists and academics said they had hoped that the amendment might make Missouri a new center of embryonic stem cell research, giving the state an economic boost. Instead, it may be sending forth precisely the opposite message: that the state, despite its pioneering ballot measure, has yet to figure out where it stands on stem cell research.

Mr. Lembke’s measure failed to reach the floor of the State House this spring, but the intended outcome of the research amendment has been delayed by actions like the blocking of the research building at the University of Missouri.

“Any time you have these kinds of debates, it has a statewide impact,” said Dr. Gordon H. Lamb, the university’s interim president. “It also has an impact on people who look at the state as a whole from the outside.”

Jaci Winship, the executive director of Missourians Against Human Cloning, said her group was weighing the possibility of a new initiative, perhaps as soon as next year. Members of Missouri Right to Life have been gathering names and contributions for such an effort.

Mr. Rubin’s group, meanwhile, has continued raising money, bracing, he said, for another fight.

WASHINGTON, Aug. 9 — Two small studies of the popular heartburn drugs Prilosec and Nexium found that patients who took the medicines over many years had an increased risk of sometimes fatal heart attacks and heart failure.

But officials at the Food and Drug Administration played down the heart worries, saying that other studies suggested no such risks. The F.D.A. will need another three months to complete a thorough analysis of the drugs’ safety, the officials said in an announcement on Thursday.

In the meantime, doctors and patients should continue to prescribe and use the drugs as before, the officials said.

AstraZeneca, the maker of Prilosec and Nexium, released a statement saying that it agreed with the F.D.A.’s preliminary assessment. “Therefore, patients should not change their medication in the light of the study data,” the company said.

The F.D.A.’s preliminary message is part of a new agency strategy to be far more forthcoming about possible public health risks, even ones agency officials largely dismiss.

The agency came under criticism in recent months for failing for more than a year to alert the public to studies that suggested that Avandia, a medicine prescribed for Type 2 diabetes, may increase the risks of heart attacks and angina.

Agency officials initially dismissed concerns about Avandia’s safety, but a panel of experts voted overwhelmingly on July 30 that the risks were real.

“It’s hard to know if this will play out similarly until we have completed our analyses” of Prilosec and Nexium, said Dr. Paul Seligman, the agency’s associate center director for safety policy and communication.

Concerns about Prilosec and Nexium began on May 29 when AstraZeneca sent the F.D.A. the results of a 14-year study of the treatment of reflux disease that compared patients taking Prilosec with those who underwent surgery.

Within a year of the study’s inception, patients taking Prilosec were more likely to have heart attacks, heart failure and heart-related sudden death than were those who underwent surgery. The effect continued throughout the study, the drug agency said.

A second, continuing study of Nexium found similar risks early in the trial, but this effect seemed to go away as the trial continued, the agency said.

The Prilosec study suffered from several weaknesses that could have led to a false suggestion of a risk, the agency said. Patients who underwent surgery tended to be younger and healthier than those who took Prilosec. And 14 other Prilosec studies found no heart risks, it said.

“Based on everything we know now, F.D.A.’s preliminary conclusion is that the observed difference in risk of heart attacks and other heart-related problems seen in early analyses of the two small long-term studies is not a true effect,” the agency said in a written statement.

The parallels with the Avandia situation are striking, demonstrating the difficulty of trying to assess drug safety issues.

In the case of Avandia, a combined analysis of more than three dozen short-term studies revealed a heart risk, but the drug agency largely dismissed this result when a continuing long-term trial did not find such a risk. With Prilosec, a long-term trial suggested a heart risk, but the agency dismissed the finding because 14 briefer studies were more reassuring.

Prilosec and Nexium, which are nearly identical, are part of a class of medicines known as proton pump inhibitors that resolve heartburn by reducing the stomach’s production of acid. Among the other drugs in this class are Prevacid, Protonix and Aciphex.

The F.D.A. has asked for safety data from the makers of all proton pump inhibitors. Dr. Seligman said.

The agency’s announcement about Prilosec and Nexium was the earliest public warning that it had ever made during a safety review, Dr. Seligman said.

“We were cognizant from the earliest submission about whether and how we should say something,” Dr. Seligman said.

Boston Scientific’s tortured relationship with Advanced Bionics, the high-tech implant company it acquired in 2004, is about to end.

Boston Scientific said late yesterday that it had reached an agreement to amend the original takeover terms in a deal that would return some of Advanced Bionics’ businesses to the original shareholders and to the management team led by Alfred E. Mann, 81, the billionaire inventor who founded the company.

Boston Scientific had paid $740 million to acquire Advanced Bionics, but it also had agreed to future progress payments that could have raised the total cost past $3 billion. The new deal, which is expected to close in January, will allow Boston Scientific to avoid potential future payouts that could have totaled $2.6 billion over the next six years.

The revision will also end “shared management provisions” enshrined in the original deal that had deteriorated into a battle for control in federal court. Boston Scientific lost the first round in April when a judge for the United States District Court for the Southern District of New York, Alvin K. Hellerstein, granted Mr. Mann an injunction blocking Boston Scientific from ousting him or Jeffrey P. Greiner, his co-chief executive, from day-to-day management. Boston Scientific is appealing the decision.

Boston Scientific had tried to remove the two men because it thought Advanced Bionics was moving too slowly toward profitability and paying too little attention to quality, according to testimony and documents in the court case. Quality practices had emerged as a central concern for Boston Scientific last year, after federal regulators issued a warning letter citing numerous violations at company facilities.

Under the revised deal announced yesterday, Boston Scientific will pay Mr. Mann and other former Advanced Bionics shareholders $1.15 billion to buy the division that makes pain management devices, for $650 million at closing and $500 million in March 2009. The devices include the Precision Plus spinal cord stimulators and a microstimulator being developed under the Bion name that may have a broad range of pain control applications.

Boston Scientific will sell back to an Advanced Bionics investment group the implantable hearing aid and drug pump businesses for $150 million. Mr. Greiner, who is head of Boston Scientific’s Neuromodulation Group, will resign to run the reconstituted Advanced Bionics, which will continue to be based in Valencia, Calif. Michael Onuscheck, who oversees the pain management implants, will become head of the neuromodulation operations.

“We look forward to building on our proud record of achievement in hearing health and to further developing the implantable drug pump technology,” Mr. Greiner said in the statement released by Boston Scientific.

The new arrangements will save Boston Scientific $500 million in payments that would have been due in 2008 and 2009 and a potential $2.1 billion that might have come due in future years, according to Paul Donovan, a spokesman for Boston Scientific.

Mr. Donovan said the pain management business was on track to bring in $200 million in revenue this year and to generate profits. He said the company thought that sales would climb to $250 million in 2008 with increasing profits.

“We also think there is synergy between the microelectronics in this business and our C.R.M. business,” said Mr. Donovan, referring to implantable cardiac rhythm management devices like defibrillators and pacemakers.

The new deal addresses pressing needs for Boston Scientific, which faces heavy debts from its $27 billion acquisition of Guidant last year and unexpectedly weak sales in defibrillators and coronary stents, its two largest businesses. It reduces a potential drain on cash at a time when investors have become increasingly worried about how the company will pay off the Guidant debt.

Those concerns were spotlighted last week when Boston Scientific decided not to pursue a public offering of a minority stake in its endosurgery operations, which develop devices to treat digestive, urological and gynecological disorders. That deal might have brought in up to $1 billion to reduce the debt. The company’s stock fell to five-year lows, and credit agencies cut their ratings on its bonds.

Boston Scientific’s shares rose 56 cents to close at $13.76 yesterday on the New York Stock Exchange in trading that ended before the announcement. But they fell as low as $13.20 in after-hours trading before rebounding.

“At the margin, it’s a net positive for Boston Scientific,” said Lawrence Keusch, who follows the industry for Goldman Sachs. “They keep the best components, and they are getting rid of long-term overhangs.”

Investors’ initial negative reaction may have reflected in part Boston Scientific’s forecast that the deal would require an after-tax charge against earnings of $360 million.

Though President Bush has had episodes of mild vertigo in recent weeks, they have not interfered with his work, and he is in excellent health, the White House said yesterday in releasing findings from his annual medical checkup.

The bouts of unsteadiness, which were reported as having improved, began after Mr. Bush had a viral infection in June at the Group of 8 meeting in Germany, the White House said. Such dizziness often follows viral infections, usually of the upper respiratory tract, and can last a few weeks. The symptoms may be continuous or intermittent.

Mr. Bush has sinusitis and has recovered from serous otitis media, an ear infection, in the last few days, his doctors said. The medical report said Mr. Bush, 61, was treated last August for a skin rash over his left shin attributed to Lyme disease.

The White House did not disclose the diagnosis last August because Lyme disease had not interfered with Mr. Bush’s duties, as when he temporarily turned over the powers of the presidency to Vice President Dick Cheney when he had a colonoscopy in July. Mr. Bush’s doctors described him as “fit for duty,” a standard military phrase.

Scott M. Stanzel, a White House spokesman, likened Mr. Bush’s episodes of imbalance to the feeling that can occur in someone who has just gotten off a boat.

“The president goes for lengthy bike rides on narrow trails in the woods and does not have any problems with his balance,” Mr. Stanzel said.

Mr. Bush rearranged his schedule at the Group of 8 meeting because he had a head cold and was not feeling well. The periods of unsteadiness began after that, Mr. Stanzel said.

The doctors attributed the unsteadiness to mild vestibular neuronitis in the president’s left ear. The serous otitis media was in the right ear and was first detected last Friday, but has since cleared up. The sinusitis involved the right maxillary sinus.

The findings are consistent with viral illnesses that can be followed by periods of unsteadiness for several weeks, said Dr. Michael G. Stewart, the chief of ear, nose and throat medicine at NewYork-Presbyterian/Weill Cornell hospital. Untreated Lyme disease can lead to nerve damage, often involving the eighth cranial nerve, the same one affected by vestibular neuronitis. But Mr. Bush’s doctors said they did not believe the Lyme infection was linked to his vestibular neuronitis because the skin lesion had not recurred.

The White House doctors evaluated Mr. Bush for Meniere’s disease, another inner ear ailment that can produce vertigo, hearing loss and ringing in the ears. But the doctors ruled out Meniere’s disease because Mr. Bush did not have some key signs and symptoms, the White House official said without disclosing what they were.

Dr. Richard J. Tubb, physician to the president, and Dr. Kenneth Cooper of Dallas oversaw 11 other doctors who examined Mr. Bush in sessions starting July 17.

Mr. Bush weighed 192 pounds, 4 pounds less than last year, a change he attributed to “less birthday cake.”