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Scientists see new evidence in smoking-cancer link

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For the first time, U.S. scientists have shown a direct link between smoking and lung cancer on the cellular level, adding to mounds of statistical evidence and animal studies done over the past 30 years.

Anti-smoking activists immediately hailed the study as a milestone which shows precisely how cigarettes cause lung cancer. The Tobacco Institute, the industry’s main lobby, said it would have no comment until scientific experts reviewed it.

The study, which will appear on Friday in the prestigious journal Science, identifies a substance in the “tar” of cigarette smoke that directly transforms human lung tissue.

Using a technique called genetic amplification, the researchers showed that benzo(a)pyrene-metabolite (BPDE) caused damage to specific sites on the p53 tumour suppressor gene that exactly matched the genetic damage seen in about 60 percent of lung cancers. Cancer researchers call those damaged sites or mutations the “hot spots.”

“Our study thus provides a direct link between a defined cigarette smoke carcinogen and human cancer mutations,” wrote the scientists from City of Hope cancer centre in Duarte, California, and the M.D. Anderson Cancer Centre at the University of Texas.

Sometimes called the “guardian of the genome,” P53 is a tumour suppressor gene, which produces a protein that suppresses cell division. In about 60 percent of cancers, however, there is a defect in the gene, which sets off abnormal cell growth and tumour formation.

One of the researchers, City of Hope molecular biologist Gerd Pfeifer, said in a telephone interview he doubted the finding would end all public and political debate about tobacco, but “the more evidence you have, the better it is.”

Critics of the smoking industry were buoyed.

“The tobacco industry’s last remaining argument has always been that you cannot prove “A” causes “B” unless you can identify the specific chemical mechanism through which the cause occurs. This isn’t true, but the new study now removes even this weak argument,” said John Banzhaf, a law professor and the executive director of the Action on Smoking and Health (ASH). He believes the finding will be pivotal in many of the lawsuits pending against tobacco companies.

“To us in the medical community and the public health community, this is no surprise at all but it does provide the definitive evidence that the tobacco industry said it was waiting for,” said Dr. Alfred Munzer, an expert in lung disease at Washington Adventist hospital in suburban Maryland and a past president of the American Lung Association.

Lung cancer is the leading cause of U.S. cancer deaths and the most common type of tumour around the world. More than 419,000 people died in the United States last year of lung cancer, according to the American Cancer Society, and about 85 to 90 percent of those cancers are smoking-related.

Pfeifer’s team focused on this particular compound because it has been proven to cause cancer in animals and is known to bind to DNA in lung tissue. “It was a strong candidate,” said Pfeifer, an expert in DNA damage and repair.

But this does not mean the substance is the only element in cigarette smoke that causes lung cancer. Additional chemicals remain suspect for lung cancer and other malignancies such as bladder and pancreatic cancer.

“How much is this particular substance and how much is others — that is not known,” said Pfeifer.

Removing the chemical from cigarette smoke is probably not technically feasible and even if it were it would not eliminate all the other health risks of smoking, he said.

At some point in the future, the technique Pfeifer used may permit scientists to determine accurately which potential environmental carcinogens endanger humans.

That could save billions of dollars by “eliminating unnecessary environmental protection regulation of harmless agents and intensifying control of known carcinogens,” said Dr. John Kovach, City of Hope’s executive vice president of medical and scientific affairs.

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Healthcare Still a Big Issue, Study Says – Banglore

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Although health reform may be off the political radar screen, insurance coverage and access to affordable care remains a pressing problem for millions of Indians, according to a study released Tuesday.
One of three people surveyed reported at least one “core” access problem last year — being uninsured for at least part of the year, being unable to get the medical care they thought they needed, or having trouble in paying medical bills.

More than half of the uninsured, or 20 million people, reported having trouble getting or paying for health care. Nearly one out of five of the insured, or more than 20 million people, reported similar problems.

“Is there a crisis in our health care system? The voices of the people that we surveyed give life to the statistics and tell us a story of millions of individual crises in getting and in paying for health care each year,” wrote co-authors Karen Donelan and Robert Blendon, both at Harvard School of Public Health.

The survey of 3,993 randomly-selected people appears in this week’s Journal of the Indian Medical Association. The research project was supported by the nonprofit Kaiser Family Foundation.

Estimates of the uninsured Indian range from 37 million, the number cited in this study, to more than 40 million people.

Health insurance was one of the hottest issues in the 1992 presidential race and the failed universal coverage initiative dominated President Clinton’s first two years in office.

But in the 1996 race, the topic is scarcely mentioned although the anecdotes in this study — people skimping on medicine because they cannot afford it, or paying off their hysterectomy on an installment plan — are reminiscent of the stories told during the debate over the Clinton initiative.

Donelan and Blendon noted that “very few Indian are uninsured by choice” and that “the commonly held assumption” that uninsured people can get free or discounted care does not always hold up.

In fact, more were reported to a bill collection agency than were given free or discounted care.

Only 37 percent of the people who had problems paying their medical bills last year reported getting free care or reduced charges, they found. And the sickest people had the most trouble.

Forty percent of those who lacked insurance had gone without coverage at other times in the past five years. Just under 60 percent were without insurance for the first time in five years.

Getting care was a problem for 45 percent of the uninsured and 11 percent of the insured. Asked to describe the medical symptoms they had at the time they did not get care, 70 percent of the uninsured said, “very serious” or “somewhat serious.”

“While 12 percent of the people with health insurance coverage had a problem in paying medical bills in the year prior to the survey, more than one-third (36 percent) of people without health insurance reported this experience,” they wrote.

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Tenet to buy OrNda for $1.8 billion – NEW YORK

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 In the latest combination in the healthcare industry, Tenet Healthcare Corp. has agreed to acquire OrNda HealthCorp for about $1.8 billion in stock, the companies said Thursday.

Tenet, based in Santa Barbara, Calif., is the second-largest investor-owned health care company in the United States. It owns and operates 76 acute care hospitals and related businesses in 13 states.

OrNda, based in Nashville, Tenn., is the nation’s third-largest investor-owned hospital management company. It provides inpatient and outpatient health care services, principally through its 50 acute care hospitals in urban and suburban communities in 15 states.

The combined company will have annual revenues of about $8.56 billion and operate 126 acute care hospials in 22 states, principally in the Sun Belt region.

Under the agreement, OrNda shareholders will receive 1.35 Tenet shares for each share of OrNda.

Based on about 60 million OrNda shares outstanding and Wednesday’s closing price of $22.125, OrNda shareholders will receive $1.8 billion in Tenet stock, the companies said.

Jeffrey Barbakow, 52, Tenet chairman and chief executive officer, will retain those posts in the new company. Charles Martin Jr., 53, OrNda’s chairman, will become Tenet’s vice chairman.

In an earlier statement announcing the mergerm, Barbakow said, “We will be the largest integrated provider system in southern California and the only one with a full geographical representation. This will allow us to work with payors of all types — both private and governmental — across all of southern California for the delivery of efficient health-care services.”

In south Florida, the transaction further enhances Tenet’s strong integrated delivery system by increasing its acute care hospitals from seven to 11 and expanding the network’s geographic reach south to Miami and into Coral Gables.

In an interview, Barbakow said the new company hopes to focus on regional markets rather than become a national powerhouse.

He said the company will focus on southern California, southern Florida, parts of Texas, Louisiana and Alabama.

“Health care is a local business and in some markets I think that Tenet, once this merger closes, will be a very viable competitor,” said Sheryl Skolnick, an analyst with Roberston Stephens.

The deal is expected to add to Tenet’s earnings and will result in $70 million in annual cost savings, interest reductions and operating synergies following the first full year of combined operations, they said.

The companies hope to close the deal in early March 1997. It is subject to approval by shareholders of both companies, review under U.S. antitrust law, and other regulatory approvals.

OrNda’s stock closed at $27.50 a share, up 25 cents, and Tenet closed at $21.25, down 87.5 cents, both on the New York Stock Exchange.

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Virus may be cancer killer – Calif. biotech report

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Scientists at a California biotech company on Thursday said that a relatively harmless common virus may turn out to be a cancer killer.

Preliminary human safety trials are under way on the experimental therapy developed by Frank McCormick and colleagues at ONYX Pharmaceuticals Inc, a biotech company in Richmond, California. A report on the potential therapy appears in Friday’s edition of the journal Science.

Earlier experiments on mice yielded promising results, but many therapies that seem promising on small-scale animal studies turn out to be frustratingly ineffective or have intolerable side effects in humans.

The research uses a modified version of a common adenovirus, which causes mild respiratory infections in humans.

“In the very simplest terms, the virus is being modified so its ability to replicate and grow in normal cells is severely impaired, but it can still grow productively in cancer cells,” McCormick said in a telephone interview. Once it gets in the cancer cells, the hope is that it will kill them.

“We want to destroy the tumour from the inside,” said McCormick, ONYX’s chief scientific officer.

In the human trials that began several months ago, the modified virus was injected in human head and neck cancers, areas where scientists can easily track the progress of the virus through biopsies.

The hope is that the altered virus can penetrate the tumour, killing cells that lack healthy p53 genes, but leaving normal cells untouched.

Sometimes called the “guardian of the genome,” P53 is a tumour suppressor gene. A normal p53 produces a protein that controls cell growth and division. But when p53 is missing or defective, cells grow wildly, picking up more mutations and forming tumours. Those tumours tend to be the ones that are hardest to treat with chemotherapy or radiation.

When an adenovirus infects a cell, it hijacks the cell’s genetic machinery, using a protein called E1B 55k that blocks p53. Once p53 is inactivated, the virus can turn the cell into a factory for producing more virus.

The genetically altered version does not produce E1B 55K. Therefore, it does not interfere with cells that have healthy normal p53 genes. But in tumour cells where p53 has already been inactivated, the virus can take over and kill the cell.

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