Medical Front Page

NASHVILLE, TN – Vanderbilt researchers have discovered a rare, but important risk posed by the antibiotic azithromycin, commonly called a “Z-pack.” The study found a 2.5-fold higher risk of death from cardiovascular death in the first five days of taking azithromycin when compared with another common antibiotic or no antibiotics at all.

Wayne A. Ray, Ph.D., professor of Preventive Medicine, and C. Michael Stein, M.B.Ch.B., the Dan May Chair in Medicine and professor of Pharmacology, collaborated on the research published in an edition of the New England Journal of Medicine.

Azithromycin, commonly called a “Z-pack” is one of the most popular treatments for bacterial sinus infections and bronchitis. Although it was previously considered to carry little to no cardiac risk, the researchers noted well-documented reports in the published literature as FDA database reports linking azithromycin with serious arrhythmias. Based on this evidence, the Vanderbilt researchers sought to examine cardiovascular deaths in patients who were taking the antibiotic.

Tennessee Medicaid (TennCare) patient records were examined from 1992 to 2006.

The researchers took many steps in this large, observational, population-based study to rule out other reasons for the increase in cardiovascular deaths in patients taking azithromycin. About 348,000 recorded prescriptions of azithromycin were compared with millions of similar records from people who were not treated with antibiotics or were treated with other antibiotics. The primary comparison was with amoxicillin, an antibiotic that is considered to be heart safe and is used in similar clinical circumstances as azithromycin.

While the absolute number of deaths was quite low, relative to amoxicillin, there were about 47 more deaths per million courses of therapy in those taking the azithromycin. That risk increased to 245 additional cardiovascular deaths per million in patients already known to have a high risk for heart problems.

The researchers emphasized that the decision to prescribe any antibiotic requires careful balancing of both potential benefits and risks. This calculation must consider the severity of the infection, the susceptibility of the organism, the availability of alternative antibiotics and adverse effects.

“We believe this study adds important information on the risk profile for azithromycin,” said Ray. “For patients with elevated cardiovascular risk and infections for which there are alternative antibiotics, the cardiovascular effects of azithromycin may be an important clinical consideration.”

- MFP Wire Services
- 05-17-2012

BETHESDA, MD – Melanoma is the most deadly form of skin cancer, estimated by the National Cancer Institute to afflict more than 70,000 people in the United States annually and the incidence rate continues to rise. In a study published online in Genome Research, researchers have identified a previously unknown non-coding RNA that plays an important role in the biology of melanoma, a finding that could lead to a new target for therapy.

Most skin cancers are nonmelanomas, arising from cells other than melanocytes (the melanin-producing cells that are responsible for a suntan). Melanomas, skin cancers that arise from melanocytes, are less common but more dangerous because they can migrate deep into the skin to find blood and lymphatic vessels that help the tumor cells to grow and spread to other parts of the body.

Oncogenes are genes that have the potential to cause cancer, and are often mutated in tumor cells, including melanomas. Mutations in the oncogene BRAF are present in more than 70% of melanomas, and the vast majority of BRAF mutants are a single mutant form, BRAFV600E. Inhibitors of BRAFV600E used in the clinic can induce tumor regression, but patients eventually relapse.

In order to better understand the biology of oncogenic BRAF and identify new targets for therapy, researchers are investigating the RNA world of cancer. RNAs are the messenger molecules that the cell primarily uses to transmit the information stored in the DNA sequence, and translate it into functional proteins. However, about 50% of transcribed RNAs actually code for no proteins at all, but many RNAs may still have critical regulatory roles to play.

In this report, a team of researchers led by Drs. Ross Flockhart and Paul Khavari of the Stanford University School of Medicine has delved into the RNA world of BRAFV600E melanomas by sequencing and analyzing the RNA “transcriptome” of patient samples. They looked for RNA transcripts, including those that may never have been characterized before, that are rewired by BRAFV600E and may be relevant to melanoma.

“By digging deeper than ever before, we found more than 100 genes encoding long non-coding RNAs that are dramatically altered by BRAFV600E,” said Flockhart. Long non-coding RNAs (lncRNAs) are garnering significant interest, as these molecules have been implicated in diverse cellular functions, but the role of lncRNAs in cancer is not well understood. Of the lncRNAs altered by BRAFV600E, Flockhart and colleagues homed in on a previously uncharacterized lncRNA gene that is recurrently and highly induced in melanomas, called BANCR. “Increased activation of the novel gene we discovered does not seem to be an isolated event,” Flockhart noted. “It will be interesting to investigate if this is also the case in other cancers.”

To test what role BANCR might be playing in melanoma, the team found that by turning off BANCR in the cancer cell by a technique called knockdown, the ability of the melanoma cells to migrate in a cell culture experiment was impaired. This indicates that BANCR is required for full migratory capacity in melanoma, and could be a potential target for therapy.

The authors explained that their work illustrates the power of RNA sequencing to study a cancer such as melanoma and identify a previously unknown regulator of disease progression. As studies such as this paint a more complete picture of cancer biology, we will have a better understanding of how tumors evade drugs, and how previously unknown players such as BANCR could be new targets for treatment.

- MFP Wire Services
- 05-16-2012

STOCKHOLM, SWEDEN – Women are more likely to suffer post-traumatic stress than men after leaving an intensive care unit, finds a new study published in BioMed Central’s open access journal Critical Care. However, psychological and physical ‘follow-up’ can reduce both this and post-intensive care unit depression.

Patients in the intensive care unit often suffer post-traumatic stress, anxiety, or depression due, not only to the illness or trauma that put them there, but to the very nature of the intensive care unit and life-saving treatment. As a result, follow-up schemes have been put in to place to help alleviate these psychological problems. Researchers from the Karolinska University Hospital Solna and the Karolinska Institutet compared patient’s recovery from 2006, before a follow-up scheme was started, with that of patients in 2007 and 2008.

The scheme consisted of non-compulsory meetings at three, six and 12 months after being discharged from intensive care unit with a nurse, physician and a physiotherapist, revisiting the intensive care unit, and in severe cases being referred to a psychiatric unit for further therapy.

Before the use of the follow-up scheme women had much higher scores on the Impact Event Scale, which measures post-traumatic stress, than men. For women, after the introduction of follow-up, these scores were significantly reduced. However, the scheme had no effect on the Impact Event Scale score of men.

Dr Peter Sackey, who led this study, explained, “In general, for the same event, women are twice as likely to suffer post-traumatic stress disorder, recover more slowly, and are more prone to suffer long-term effects. We found this was also true in intensive care unit survivors. The women with the highest Impact Event Scale scores were the ones who were most helped by the follow-up scheme. While it is not clear whether the scheme only helps patients at severe risk of PTSD, it does mean that these people have access to the treatment they need.”

- MFP Wire Services
- 05-15-2012