Responding to a spate of deaths in clinical trials, the Food and Drug Administration yesterday issued its most severe warning possible for drugs widely used to treat anemia in kidney disease patients and cancer patients undergoing chemotherapy.

The "black box" warnings placed on the prescribing label for Amgen Inc.'s Epogen and Aranesp and Johnson & Johnson's Procrit are expected to result in more cautious dosing by doctors.

Use of the drugs has escalated as physicians have sought to improve the quality of life of anemic patients by using them to stimulate creation of energy-boosting red blood cells. Marketing by manufacturers has reinforced the trend. But the FDA said yesterday that recent clinical trials have shown treatment beyond recommended limits increases the risk of death from heart attack and stroke in kidney patients, and of tumor growth and death in some cancer patients.

The agency advised doctors to give patients the minimum dose required to reduce the need for blood transfusions. It said antianemia drugs should not be used in an attempt to improve the quality of life of cancer patients because those claims are unproven. The FDA allowed claims of lifestyle benefits to remain for kidney patients, but said it is re-examining the validity of patient questionnaires about factors used to support the claims.

Recent concerns about the potential dangers of antianemia drugs and their overuse have been heightened by Medicare reimbursement policies for kidney dialysis treatment, which provide a profit incentive for clinics to administer more Epogen.

Medicare loosened its policy last year to let clinics get paid even if patients exceed the FDA's recommended red blood cell limits. The National Kidney Foundation -- in a set of guidelines paid for by Amgen -- suggested last year that higher targets for red blood cell counts are appropriate, citing statistical studies that showed lower mortality. The foundation is revisiting those guidelines.

The new warnings would effectively reduce the red blood cell target to about 10 grams per deciliter, compared with the upper limit of 12 grams that remains on the label, and the 13 grams permitted under last year's updated Medicare policy. The warnings are advisory, and the targets are still left up to the discretion of physicians, the FDA said.

The FDA said it has alerted Medicare to its latest findings. A spokesman at Medicare, which spends about $2 billion annually on Epogen for dialysis patients, did not respond to a phone message yesterday.

Black box warnings, said Dr. Eric P. Winer, chief of the breast cancer center at Dana-Farber Cancer Institute in Boston, will likely make doctors more cautious about prescribing antianemia drugs.

"These are drugs that have been somewhat overused. I don't think it's been without some effort on the marketing end," he said. "There has been a tendency, I think, for patients, and to some extent health providers, to attribute more fatigue to anemia than deserves to be attributed."

The warnings tarnished the image of a class of drugs that was among the biopharmaceutical industry's first big triumphs and has generated billions of dollars for Amgen and Johnson & Johnson.

Aranesp, which accounted for $4.1 billion in sales last year, is Amgen's second-generation version of the drug. Epogen, its original form, generated $2.5 billion in revenue last year, most of it in federal Medicare reimbursements for its use in dialysis treatment. Amgen makes Procrit, which is identical to Epogen, and licenses Johnson & Johnson to sell it. Procrit sales last year totaled $3.1 billion.

Amgen's stock dropped 2.1 percent to $60.86 yesterday. Johnson & Johnson stock slipped 0.7 percent to $62.14.

In November, an article in New England Journal of Medicine described a clinical trial of Procrit called CHOIR that was cut short because of higher rates of death from heart attack and stroke in kidney patients receiving larger doses. The dosing regimen in the trial pushed red blood cell counts higher than is recommended by the FDA. The results echoed a study of Epogen in kidney dialysis patients that was suspended in 1996, also due to an unexpectedly high death rate during testing.

In October, a trial of Aranesp in Danish patients with head and neck cancers was halted early because of apparent increases in tumor growth. Amgen said it told the FDA about the trial immediately, but it did not alert investors, leading to an informal review disclosed last week by the Securities and Exchange Commission . News of the suspended study was not known until it was reported in February by The Cancer Letter , a trade publication in Washington.

In February, Amgen reported on another study of Aranesp in cancer patients not undergoing chemotherapy treatment, which resulted in a higher percentage of deaths. The causes of death have not been disclosed. The FDA has scheduled a May meeting of its Oncologic Drugs Advisory Committee to discuss the new data.

Mayor Frank Melton was released from jail Thursday after the Mississippi Supreme Court vacated his arrest and recused Judge Tomie Green from the case, according to court documents provided to The Associated Press.

Presiding Justice William Waller Jr. issued the orders without further comment.

Melton spoke to reporters at an impromptu news conference in front of the gates of his Jackson home after he arrived there from jail.

"It was quite a humbling experience," Melton said on Jackson news channel WAPT, noting he cleaned three bathrooms Thursday alongside other inmates.

"We're going to make this a great, great city," the 57-year-old mayor said. "I'm back on the job as of right now."

Melton had appointed Jackson City Councilman Frank Bluntson to be the city's interim mayor in an executive order late Wednesday.

The mayor turned himself in at the county jail Wednesday and was booked into the medical ward to await a hearing on whether he violated his probation on a misdemeanor weapons conviction.

Melton, who recently had heart surgery, checked himself into a hospital with chest pains a week earlier, the day Green issued a warrant for his arrest.

The mayor pleaded no-contest in November to a misdemeanor charge of carrying a pistol on a college campus and guilty to two other misdemeanor weapons violations. The plea deal spared him a felony conviction that would have forced him from office.

Melton was given a six-month suspended sentence on each count, one year of probation and fined $1,500.

Melton is a wealthy former TV executive and one-time state drug enforcement agency chief. He won a landslide election in 2005 on the promise of rooting out crime in Jackson.

He became a fixture on nightly newscasts, wearing fatigues, carrying guns and criticizing the district attorney's office for not putting away enough criminals. He cruised the inner city with police and often took troubled children back to his home in a gated community.

Separately, the mayor and his two former bodyguards are to stand trial April 23 on allegations they had roles in the use of sledge hammers to damage a building the mayor considered a drug haven.

Pataki spokesman David Catalfamo said the governor is not ruling out a possible later jump into the presidential campaign, although Pataki has lately cut back on campaign-like activities.

"I am thrilled to be joining Chadbourne," said Pataki in a news release issued by the law firm. "This is one of the great New York firms, and I look forward to participating in its growth."

Chadbourne's managing partner, Charles O'Neill, said the addition of Pataki and Cahill to the firm "will build upon Chadbourne's growing renewable energy practice."

Cahill is a former state environmental conservation commissioner. Pataki was praised by environmental groups throughout his 12 years in office, particularly for his efforts to add 1 million acres of preserve land to the state.

Pataki, who ousted Democratic Gov. Mario Cuomo in 1994, did not seek re-election last year to a fourth, four-year term.

Clifford Chance's Asian funds and private equity teams have been honoured with three separate industry awards this week.

On 28 February, the funds team was named Best Law Firm for Asset Management in 2006 by Asia Asset Management magazine.

Today, Clifford Chance's was voted Asia's Best Law Firm (Fund Formation) and Asia's Best Law Firm (Deals) for 2006 in Private Equity Online's annual poll.

"The awards reflect the firm's commitment to building the pre-eminent funds and private equity teams in Asia," said partner James Walker, who leads the firm's Asian funds practice.

"We have been working with our clients since the first funds were established in Asia, and we're delighted that they continue to choose us as their advisors today."

Private equity partner Andrew Whan has advised on many of the year's most significant deals. "It has been a record year for private equity in Asia, with the high level of activity, arrival of more global players, and increasing convergence between the hedge fund and private equity industries."

"Our leading private equity and funds teams work closely, enabling us to provide a well-matched, full life-cycle service to our clients as this convergence evolves."

Monday's agreement is only the latest joint effort by the western states. Last year, Arizona and New Mexico formed the Southwest Climate Change Initiative, and the governors of California, Oregon and Washington issued a joint statement in 2003 calling for regional action to address global warming. Elsewhere in the country, several Northeastern states have created the Regional Greenhouse Gas Initiative, to reduce carbon dioxide emissions from power plants through a regional cap-and-trade program, and some Midwestern states signed on to the Lake Michigan Air Directors Consortium, to establish a voluntary registry for companies to report their emissions-reduction efforts.

Efforts to establish national emissions limits have gained traction in Congress since the Democrats became the majority party, with at least four major proposals emerging. President Bush opposes mandatory carbon dioxide (CO2) limits but has proposed reducing emissions through the use of alternative fuels. A coalition of businesses and environmental groups has called for federal legislation, including a cap-and-trade program, to limit emissions of CO2 and other greenhouse gases. In September, California became the first US state to restrict greenhouse gas emissions when Schwarzenegger signed a bill authorizing a state board to set emissions targets for various industries.

US Attorney General Alberto Gonzales unveiled the First Freedom Project (FFP) Tuesday afternoon, a new Department of Justice initiative aimed at stricter enforcement of laws against religious discrimination and educating the public about their rights in this area. The DOJ will hold training seminars across the US in conjunction with the program, and the FFP website includes instructions on how to file a religious discrimination complaint with the DOJ. The program was prompted by a DOJ report, also released Tuesday, that describes how the DOJ's Civil Rights Division has "dramatically increased enforcement" of religious discrimination laws between 2001 and 2006.

Gonzales made the following remarks during a Wednesday meeting of the Executive Committee of the Southern Baptist Convention:

The Department of Justice has actively pursued cases involving religion not just in access to education and public facilities, but in equal access to housing, lending, and employment as well. Over the past six years, we have had many successes. We've launched scores of investigations involving religious discrimination in education and housing, a sharp and marked increase in the Justice Department's enforcement of these important federal protections. We have fought to maintain and make clear the crucial distinction between improper government speech endorsing religion and constitutionally protected private speech endorsing religion.

Why should it be permissible for an employee standing around the water cooler to declare that 'Tiger Woods is God,' but a firing offense for him to say 'Jesus is Lord'? These are the kinds of contradictions we are trying to address...

As part of our ongoing efforts to strengthen and preserve religious liberty in this country, I am unveiling today a new initiative: the First Freedom Project. Under this program, the Department will build on our extensive record of achievement in this area and commit to even greater enforcement of religious rights for all Americans.