STUDY: Bextra has been associated with serious allergic reactions

JOURNAL: FDA and drugmaker Pharmacia

AUTHORS: FDA

ABSTRACT: The US Food and Drug Administration (FDA) and drugmaker Pharmacia are advising doctors that the firm's COX-2 inhibitor valdecoxib (Bextra) has been associated with serious allergic reactions and should not be prescribed to patients allergic to sulfa.

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COMMENTARY: In a notice issued on Friday, the FDA said it has received post-marketing reports regarding various allergic events, including skin and anaphylactoid reactions.

Although the events were rare, some patients required hospitalization, the FDA added.

The FDA said the Bextra label has been updated to reflect the new case reports and contraindication.

On November 13, according to the FDA, Pharmacia sent similar letters to healthcare professionals, advising them of the post-marketing reports and new warnings that will be included on the updated label.

In a copy of the letter posted on the agency's Web site, Pharmacia said these cases occurred in patients with and without a history of allergic-type reactions to sulfonamides and included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis and erythema multiforme.

The company said the label would be updated to carry two separate warnings for the skin and anaphylactoid reactions, as well as a section to outline the post-marketing experience. According to the label included in the Pharmacia letter, an estimate of the frequency was not possible because the reactions were voluntarily reported from a population of uncertain size.

STUDY: Rat study hints one drink a day during pregnancy may be dangerous

JOURNAL: Alcoholism: Clinical and Experimental Research, 26, 1752 - 1758

AUTHORS: Daniel Savage

ABSTRACT: A new animal study hints that even a little alcohol during pregnancy may affect a baby's brain. A group of adult rats flunked a navigation test1. Their mothers had consumed quantities of alcohol while pregnant that were analogous to one drink a day for a human during the first six months.

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COMMENTARY: Britain's Royal College of Obstetricians and Gynaecologists advises pregnant women to limit their daily alcohol intake to one small glass of wine or beer or a measure of spirits. This is to reduce the risk of fetal alcohol syndrome - the learning and behavioural difficulties seen in children whose mothers drank heavily throughout pregnancy.

The rodent research, carried out by Daniel Savage and colleagues from the University of New Mexico Medical School, suggests that there may be more subtle effects of low-level alcohol intake that become obvious only later in life, as more complex tasks are taken on.

"Behavioural deficits appeared in rats that are relevant to humans," says psychologist Charles Goodlett of Indiana University-Purdue University, Indianapolis. But, he warns, "there is an enormous step between the gestation periods of rats and humans, so we must be careful about extrapolating the data too much".

Savage and his colleagues also found altered levels of glutamate in their rats. Levels of this key messenger molecule were one-third lower than normal in the hippocampus, the brain region that is responsible for learning and memory.

So how much alcohol is safe? "We really don't know the magic number," says Savage. "In the absence of definitive information, it is better to abstain," he says. "Why take a chance?

"Neurologist Michael Charness at Harvard Medical School agrees. "For every kid with fetal alcohol syndrome, there are another ten who have been exposed to alcohol, have no obvious physical defects but do have cognitive problems." The rat results are striking and not entirely surprising, he says.

STUDY: A shorter course of radiation therapy (RT) achieved the same results as the longer

JOURNAL: J Natl Cancer Inst. 2002;94(15): 1114-1115, 1143-1150

AUTHORS: Timothy Whelan

ABSTRACT: A shorter course of radiation therapy (RT) achieved the same results as the longer, now standard, course of RT for women with clean margins at the time of lumpectomy for breast cancer, according to the results of a randomized trial published in the Journal of the National Cancer Institute.

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COMMENTARY: "A shorter fractionation schedule will lessen the burden of treatment for women, many of whom may also receive adjuvant chemotherapy, and will have important quality-of-life benefits with respect to convenience and less time away from home and work," write Timothy Whelan, BM, BCh, MSc, from the Hamilton Regional Cancer Centre in Ontario, Canada, and colleagues.

In this study, 1,234 women who had undergone lumpectomy for invasive breast cancers without lymph node metastases were randomized to receive either a shorter or longer course of whole breast radiation. The fractionation schedule was 42.5 Gy in 16 fractions over 22 days in the short treatment group, or 50 Gy in 25 fractions over 35 days in the long treatment group. Median follow-up was 59 months.

At five years, local recurrence-free survival was 97.2% in the short group and 96.8% in the long group (absolute difference, 0.4%; 95% confidence interval, -1.5% to 2.4%). There was no difference in disease-free or overall survival. The proportion of patients with excellent or good global cosmetic outcome was similar in both groups, and was greater than 76% at three years and at five years.

In an accompanying editorial, Carolyn I. Sartor, MD, and Joel E. Tepper, MD, of the University of North Carolina School of Medicine in Chapel Hill, ask whether this study sets a new standard for adjuvant radiation for early-stage breast cancer. Newer technologies such as brachytherapy may allow even more convenient, less invasive therapies without compromising long-term outcome.

However, they caution against extrapolating the good outcomes in this study beyond a select group with small tumors completely resected with clean margins.

"In carefully selected patients, use of shorter, less expensive, and more convenient radiotherapeutic approaches can produce excellent local control of breast cancer with acceptable cosmesis," they write. "It is premature to generalize these results beyond the categories of patients actually treated in the trial, but, with further technologic and biologic advances, perhaps we can ultimately do even 'less.' "

STUDY: A supplement of probiotics increases the effectiveness of conventional antibiotic therapy for H pylori.

JOURNAL: Alimentary Pharmacology & Therapeutics (2002;16:1669–75).

AUTHORS:

ABSTRACT: Taking a supplement of “friendly bacteria” (probiotics) increases the effectiveness of conventional antibiotic therapy in eradicating Helicobacter pylori (H. pylori), the organism that causes peptic ulcers.

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COMMENTARY: H. pylori is an organism that can infect the lining of the stomach. Infection with this organism is an important contributing factor to gastric and duodenal ulcers, and may also increase the risk of developing stomach cancer.

H. pylori is a persistent bug that can be difficult to eradicate. Research has determined that the most reliable way to kill this organism is by using three drugs simultaneously for a week: two antibiotics and a medication that blocks the production of stomach acid. However, as many as 50% of individuals given this triple-therapy regimen experience side effects including nausea, vomiting, diarrhea, a metallic taste, or allergic reactions. Some people are unable to complete the therapy because of these side effects.

In the new study, 160 people infected with H. pylori were randomly assigned to receive a triple-therapy regimen (lansoprazole, amoxicillin, and clarithromycin) for one week, or the same triple therapy combined with five weeks of a daily yogurt supplement that contained live lactobacilli and bifidobacteria.

Eight weeks after the triple therapy, participants were tested for the presence or absence of H. pylori in their stomach. The eradication rate was significantly higher among those who received yogurt than among those given triple therapy alone (91% vs. 78%). However, when only those who completed the full seven days of triple therapy were considered, eradication rates were similar (93.5% for the yogurt group, 89% for triple therapy alone).

That finding suggests that the main benefit of the yogurt was to help people tolerate triple therapy better and to complete the full week of treatment.

Other natural treatments may be potentially helpful in eradicating H. pylori infection; these include garlic, mastic gum, vitamin C, and certain essential fatty acids.

However, most of the studies that support the use of these treatments have been done in test tubes, and there is little evidence that these natural remedies can kill H. pylori in infected people. At present, conventional triple therapy—perhaps combined with probiotics—appears to be the most effective regimen for eradicating the ulcer bug.

STUDY: Farmers want the corn blocked until tests can determine whether it caused some hogs and cattle in Midwestern states to become infertile.

JOURNAL:

AUTHORS:

ABSTRACT: Farmers and an environmental group worry that a biotech corn suspected of containing toxic mold could contaminate the food supply, prompting them to ask Agriculture Secretary Ann Veneman to keep it off the market.

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COMMENTARY: They want the corn blocked until tests can determine whether it caused some hogs and cattle in Midwestern states to become infertile.

Agriculture Department researchers suspected some Iowa cattle and hogs became sterile after eating the potentially moldy corn. An environmental group, Friends of the Earth, has sent letters to Veneman urging her to hold it from the market for more testing.

Larry Bohlem, a spokesman for the group, said farmers in Minnesota, Michigan and Iowa who have had problems with the corn produced by Garst Seed Co. don't want to discuss it publicly.

"They're kind of afraid because they're afraid to lose the value of their corn," he said Tuesday.

Bohlem said the agencies that regulate grain, including the Agriculture Department and the Food and Drug Administration, have failed to act quickly. He said he is concerned the grain will end up in tacos and tortilla chips.

That would be a replay of a scare that occurred two years ago when Aventis' StarLink corn, which wasn't approved for human consumption, was found in the food supply. Recovery efforts cost the food and farming industry billions of dollars.

Maria Bynum, spokeswoman for the Agriculture Department, said the potentially moldy corn is the FDA's responsibility to investigate. FDA officials said they were looking into the matter.

The corn is a variety known as Bt corn, genetically designed so it won't contain molds. Initial tests have indicated, however, that it contains the mold fusarium, which can sicken animals and humans. Researchers for the USDA's Agricultural Research Service have said, though, that a biological chemical compound may be to blame.

Scientists were alerted to the problem by Jerry Rosman, a farmer who operates Rolling R Farms in Harlan, Iowa. He told them he believed the corn was the root of his problems when reproductivity in his hog herd dropped from 90 percent to 20 percent from October

2000 to August 2001.

Officials with the Slater, Iowa-based Garst Seed said they've conducted their own investigation but nothing seemed amiss.

"We are confident that corn seed has not caused the problems he has experienced," company spokesman Jeff Lacina said in a statement. "The hybrids that Mr. Rosman purchased have been widely grown for several years and no one else who has grown them has reported similar experiences to us."

Rosman said his sows appeared to be pregnant but produced no litters. He destroyed the herd, he said, but notified the Agriculture Department when he discovered four of his neighbors had similar problems. His cattle also were showing a decrease in reproductivity, he said.

The corn "was the common denominator" in all the cases, Rosman said.

Scientists began testing Rosman's corn last fall but had to stop this summer because of a court battle between Rosman and his father over dividing the farm's assets. To settle the dispute, a district court judge in Shelby County, Iowa, ordered the corn sold and the cattle, which also auctioned, Rosman said.

"That's the wrinkle in this. Otherwise, this wouldn't be an issue, and this corn would be in my control and the livestock would be in my control and we'd just hang onto it for research," he said.

Rosman hopes Veneman's office will hold the corn.

Although the corn was sold, publicity about the grain led the elevators that bought it to reject it.

Rosman's case has drawn attention from farmers in surrounding states. He said nearly a dozen Midwestern farmers and some veterinarians have come forward, saying they saw reproductivity drop in hog and cattle herds because of the grain.