Adult asthma patients using inhaled steroids such as the brand names Beclovent, Pulmicort and Flovent had on average three fewer severe asthma flare-ups each year compared to patients using inhaled cromolyn, sold under the brand name Intal.

Patients taking the steroids also scored significantly higher on tests of lung function and used their "rescue" inhalers less often than those taking cromolyn, say James Guevara, M.D., of the University of Pennsylvania School of Medicine and colleagues.

The findings were similar for children, Guevara and colleagues add, saying that their review supports recent consensus in the medical community that favors inhaled corticosteroids as a first-choice treatment for asthma.

"To our knowledge, this is the first systematic review comparing the effects of cromolyn to the gold standard, inhaled steroids," Guevara said.

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The consensus still leaves room for cromolyn treatment, according to William Storms, M.D., an allergist at the University of Colorado Health Sciences Center and director of the William Storms Allergy Clinic in Colorado Springs.

"Any expert would agree that inhaled corticosteroids are preferred first-line therapy for treatment of persistent asthma, which requires daily therapy. But we also will agree with the NIH [National Institutes of Health] asthma guidelines, which state that cromolyn and other drugs are alternative therapies," Storms said.

Cromolyn, or sodium cromoglycate, and inhaled corticosteroids both block the action of certain inflammatory cells in the lungs. Physicians recommend both types of medication for persistent asthma, but individual studies disagree about which type of medication works best, the reviewers found.

"The safety of sodium cromoglycate has been well established, but the effectiveness of sodium cromoglycate in controlling asthma symptoms may be limited," Guevara said, adding that the lack of effective control might be one reason cromolyn has fallen out of favor compared to inhaled corticosteroids since the 1990s.

Cromolyn’s manufacturer has changed several times during the past two decades, which may also explain why the drug’s popularity has waned, Storms said. The succession of companies "did not spend one dollar in research in the past 20 years to study cromolyn. All of the data are old and most are forgotten," he said.

The Cochrane reviewers examined 17 studies involving 1279 children and eight studies involving 321 adults with asthma. They found no differences in serious side effects between those using the steroids and those using cromolyn, but acknowledge that adverse effects were reported inconsistently.

Guevara and colleagues conclude that inhaled corticosteroids were superior to cromolyn regardless of the severity of the asthma. They suggest the results are so decisive that future studies comparing the two types of drugs "may not be warranted."

Storms said some patients may still prefer to stay away from inhaled corticosteroids.

"We need to examine the total patient and treat the patient, not the disease. When I tell patients I am suggesting they take an ICS [inhaled corticosteroid], many of them get that wide-eyed gaze because of the word ‘steroid.’ Then I discuss the fact that ICS are inhaled and not systemic but many patients would still prefer to try something else, if possible. That something else could be cromolyn," he says.

Lead author A. McGarry Houghton, M.D., assistant professor, Division of Pulmonary, Allergy and Critical Care Medicine, Pitt School of Medicine, said that prior to this discovery scientists thought that the enzyme, called macrophage elastase, matrix metalloproteinase-12 or MMP-12, which is produced in excess in smokers, didn’t do anything but degrade the lung’s elastic fibers, thereby contributing to the tissue destruction of emphysema.

"But we found that mice that didn’t have the gene to make this enzyme could not clear bacteria well and were more likely to die of infection," he explained. "They couldn’t make this small protein, which kills bacteria by poking holes in cell membranes." The findings were described today in Nature.

"While not the initial purpose of this study, finding novel antimicrobial mechanisms is extremely important," said senior author Steven D. Shapiro, M.D., Jack D. Myers Professor and chair of the Department of Medicine, Pitt School of Medicine, whose research teams cloned the MMP-12 gene almost 20 years ago and conducted the work that showed its role in emphysema. "Many microorganisms have adapted to circumvent our current and stagnant arsenal of antibiotics. We must find new weapons so that we don’t fall back to the public health problems we had prior to penicillin."

MMP-12 is stored in macrophages, the cells that swallow up invading bacteria. When Staphylococcus aureus was injected into the tail vein of healthy and MMP-12-deficient mice, the two-week mortality rate was about the same. However, the amount of bacteria was much greater in the lungs of MMP-12-deficient mice. In models of pneumonia and peritonitis, MMP-12-deficient mice were much less likely to survive the infection. Macrophages are present in very high numbers in the lungs and the peritoneum, which is the lining of the abdomen.

"Our experiments also showed that while the MMP-12-deficient macrophages were able to ingest bacteria, they couldn’t kill them," Dr. Houghton said. "The intracellular bacteria level escalated rather than diminished."

The researchers then looked for what gave MMP-12 its antibacterial properties. While the portion of the enzyme that catalyzes, or speeds up, chemical reactions degrades lung tissue in emphysema, its tail is the portion that kills microbes. Protein fragments were tested to identify a chain of 20 amino acids that could kill Staph aureus in culture dishes. A computer-generated 3-dimensional model of the enzyme’s tail, including the 20-amino acid chain, revealed there were only a few exposed places permitting interaction with bacterial surfaces, and that one of those loops had a protrusion containing a sequence of four amino acids, called KDEK, that is not present in any other enzymes of the MMP class.

"Humans, mice, rats and rabbits all have that special sequence and structure in MMP-12, but not in other MMPs," Dr. Houghton noted. He and his colleagues synthesized chains nearly identical to the 20-amino acid sequence but substituted other segments for KDEK, and found that both the sequence and the loop structure was necessary to kill bacteria.

The team plans to study whether the same part of the enzyme is able to kill viruses and fungi, and whether there are any connections between MMP-12′s roles in emphysema and infection defense.

Study co-authors include William O. Hartzell, M.D., formerly of Brigham and Women’s Hospital, Boston; F. Xavier Gomis-Ruth, Ph.D., Molecular Biology Institute of Barcelona, Spain; and Clinton S. Robbins, Ph.D., postdoctoral fellow, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine.

The research was supported by grants from the National Institutes of Health and Spanish and European public agencies.

Researchers at the Mount Sinai School of Medicine, New York, briefly and reversibly disrupted the blood-brain barrier in laboratory rats and generated protein/DNA complexes that passed through the disrupted barrier. This research, the first step in treating diseases of the central nervous system, was discussed today at the annual meeting of the Pediatric Academic Societies in New Orleans, May 1-5. For interviews during the meeting, contact the press room at (504) 670-8502 or 670-8508.
Researchers' Institutional Contact: Bud Perron (212) 843-8068 perrorubenstein

The two improved areas are linked to kidney disease and coronary heart disease, respectively, in patients with type 2 diabetes. The Centers for Disease Control estimates that 18 million Americans have diabetes, with more than 90 percent being type 2 cases.

The study’s findings, published in the August issue of the Journal of Nutrition, surprisingly exceeded the expectations of participating scientists at the University of Illinois at Urbana-Champaign and suggest that more widespread testing is warranted.

“The number of type 2 diabetics is increasing to epidemic proportions, with the disease being found in younger and younger individuals everyday,” said Sandra R. Teixeira, who had pursued the research as the focus of her doctoral work at Illinois. “As a result, the rate also increases tremendously for diabetic complications, which include diabetic kidney disease and cardiovascular disease.”

The human findings confirmed those of a study published a year earlier using mice, said Teixeira, now a researcher focusing on type 2 diabetes for the Novartis Institutes for Biomedical Research in Cambridge, Mass.

“Our most remarkable result was that soy protein added to the diet, compared to animal source protein, in this case casein, resulted in a significant reduction in the amount of protein in the urine,” said John Erdman, a professor of nutrition in both the U. of I. College of Medicine and College of Agricultural, Consumer and Environmental Sciences. “Patients eating casein actually had an increase of urine protein levels.”

Participants of the study were men ranging in age from 53 to 73 who were recruited at the Veterans Affairs Illiana Health Care System (formerly known as the Danville Veterans Administration Medical Center) in Danville, Ill. Veterans diagnosed with diabetic nephropathy (kidney disease) took part in the study, but over the course of three seven-month study periods several had to be dropped because of changes in medications. Data from the remaining 14 men were used for statistical analysis.

The men consumed pre-measured amounts, based on each man’s weight, of either vanilla flavored isolated soy protein made from soybeans or casein, an animal-based protein. They were supposed to have substituted 50 percent of their daily protein intake with the pre-measured powders, but instead they consumed the powders as part of additional dishes or drinks in their diet.

“Our hypothesis was that we could slow down or maintain the same protein levels in the urine by introducing soy protein,” said Lea Ann Carson, a research dietitian in the department of food science and human nutrition at Illinois. “We actually had a reduction.”

Those consuming the soy protein had a 9.5 percent reduction in the excretion of urinary albumin, an undesired buildup of globular protein indicative of worsening kidney function. Participants eating casein had an 11.1 percent increase of urinary albumin. A common treatment for diabetic kidney disease has been a reduction in protein in the diet.

In Teixeira’s earlier study of type 2 diabetic mice, casein consumption had increased protein levels in the urine, while soy protein only prevented the levels from worsening.

Levels of HDL, often referred to as good cholesterol, were improved by 4.3 percent in the human study, but overall cholesterol ratios improved only slightly. HDL dropped just slightly in the men who consumed casein.

“The results suggest that a dietary modification as easy to implement as consuming soy-protein-rich foods may help to prevent diabetic kidney disease in addition to improving blood-lipid profile,” Teixeira said. “This is quite important in light of the growing diabetic population, and larger trials are warranted to confirm the findings.”

Why the soy protein worked as it did is not known, but Erdman theorizes that isoflavones, estrogen-like components in soy, may play a role because they are thought to have improved blood lipids in earlier soy studies. Another possibility, he said, is the elevated level of serum arginine, a chemical precursor to nitrogen oxide that dilates arteries, that was observed in the men. Arginine may improve blood flow in the kidney, he said.

The study, despite focusing on just 14 participants, “is probably the strongest one done so far from the numbers of subjects and length of time, because it involved an intervention program designed for type 2 diabetes,” said Erdman, who last year was elected to the Institute of Medicine of the National Academies.

Co-authors of the study, in addition to Teixeira, Carson and Erdman, were Kelly A. Tappenden, a professor of food science and human nutrition; Mukund Prabhudesai, a professor of internal medicine in the department of pathology in the College of Medicine; Dr. William P. Marshall, head of the department of internal medicine in the College of Medicine and chief of medicine service for the Veterans Affairs Illiana Health Care System; and Richard Jones, a physician’s assistant at the VA facility.

Protein Technologies International, the Illinois Council for Agricultural Research, a Fulbright Program fellowship to Teixeira and the Foundation for Science and Technology in Portugal supported the research.

According to Creighton researchers, noninhaled, intranasal carbon dioxide (CO2) may offer a new, effective and safe treatment for many SAR sufferers. The study will be reported in an upcoming issue of the Journal of Allergy & Clinical Immunology.

“These findings indicate that noninhaled, intranasal carbon dioxide is very promising as a safe and effective treatment to provide rapid relief for seasonal allergic rhinitis. With the exception of a burning/stinging sensation when the carbon dioxide is first administered, there appears to be no significant side effects with this technique.

“It could be a good alternative for people who don’t want to take intranasal steroids,” said Thomas B. Casale, M.D., principal investigator and chief of Creighton School of Medicine’s Division of Allergy/Immunology.

Currently, there are no treatments available that provide truly rapid relief of SAR symptoms and can be used safely long-term, he added.

In the Creighton study, patients receiving CO2 reported a significant and rapid improvement in congestion, sneezing and other nasal symptoms – within 10 minutes and lasting at least 24 hours – over those taking a placebo (plain air). The CO2 group also reported some, although not statistically significant, improvement in non-nasal symptoms such as watery and itchy eyes.

Within 30 minutes of treatment, 50 percent of those taking CO2 reported more than a 50 percent improvement in nasal symptoms, compared to 27.6 percent of the placebo group.

The Creighton study involved 89 subjects, 18 to 75 years of age, who had at least a two-year history of seasonal allergies requiring pharmacotherapy. Sixty received CO2 and 29 received plain air.

The patients took the gases intranasally twice – once for each nostril – within an interval of less than five minutes for a total dose of about 1,200 milliliters. They avoided inhaling the gas by breathing through the mouth, allowing the gas to flow in one nostril, pass through the nose and sinus cavities, and pass out the other nostril.

The use of intranasal noninhaled CO2 has already proven effective in treating migraines, although it is not yet approved by the U.S. Food and Drug Administration for that use. Allergic rhinitis is triggered by some of the same mechanisms as migraines.

Casale noted that, despite currently available treatments, a significant proportion of patients with allergic rhinitis continue to suffer symptoms that impair their quality of life and can lead to other conditions such as asthma. The medical costs associated with SAR are estimated at $6 billion annually in the United States alone, he said.

For some time, medical practice guidelines have been ambiguous about whether vancomycin or so-called B-lactam antibiotics like penicillin or cephalosporins was the more appropriate therapy for treating patients admitted for cellulitis. If left untreated and infection spreads, cellulitis could become life threatening.

The Henry Ford study found that 226 patients treated intravenously with vancomycin between December 2005 and October 2008 fared better and were discharged on average one day earlier than 199 patients treated intravenously with the B-lactam antibiotics.

The study is being presented Oct. 23 at the 48th annual meeting of the Infectious Diseases Society of America Oct. 21-24 in Vancouver.

"We believe vancomycin is the better treatment option for managing patients hospitalized with cellulitis," says Hiren Pokharna, M.D., an Infectious Diseases fellow at Henry Ford Hospital and the study’s lead author.

With MRSA skin and soft tissue infections increasing, researchers sought to compare the two groups of antibiotics commonly used for treating hospitalized patients with cellulitis. The common bacterial skin infection is caused by many types of bacteria including staphylococcus and streptococcus. Symptoms include redness, swelling, tenderness and pain.

MRSA strains have proven resistant to common antibiotics like penicillin and other drugs. However, they have been shown to be susceptible to vancomycin.

The study was funded by Henry Ford Hospital.

Viktoria Mayr and colleagues from Innsbruck Medical University collaborated with colleagues from other institutions in Austria to analyse the cause of death in 3700 patients admitted to intensive care units (ICU’s). They analysed the causes of death in the ICU, in the hospital after discharge from the ICU, and one year after admission to the ICU.

Mayr et al.’s results show that 47% of patients who died in the ICU died of multiple organ dysfunction. Acute and chronic multiple organ dysfunction were much more common causes of death in the ICU than single organ failure. In addition, patients with central nervous system failure had a 16.07% increased risk of dying while in the ICU and patients with cardiovascular failure had an almost 12% risk of dying — these were the main risk factors for death while in the ICU. Mayr et al.’s results also show that malignant tumour disease caused over a third of hospital deaths in patients who had been discharged from the ICU, and one year after admission to the ICU. Exacerbation of chronic cardiovascular disease caused 19.4% of deaths after discharge from the ICU and it is the second most frequent cause of death both after discharge from the ICU and one year after admission to the ICU.

Article: Causes of death and determinants of outcome in critically ill patients Viktoria D Mayr, Martin W Duenser, Veronika Greil, Stefan Jochberger, Guenter Luckner, Hanno Ulmer, Barbara E Friesenecker, Jukka Takala and Walter R Hasibeder Critical Care 2006, in press.

The Task Force is an independent panel of experts sponsored by the Agency for Healthcare Research and Quality (AHRQ). The recommendations, which are published in the September 17 Annals of Internal Medicine, mark the first time the Task Force has called for routine osteoporosis screening.

For women who live to be 85, approximately 50 percent will have an osteoporosis-related fracture during their lives; 25 percent of these women will develop an abnormality of the spine; and 15 percent will fracture their hip. While no clinical studies have been done to assess the effectiveness of screening in reducing osteoporotic fractures, there is ample evidence that bone density testing can adequately identify women who could benefit from treatment. A new class of drugs called bisphosphonates has proved effective at reducing the risk of fracture in women with low bone density, leading the Task Force to believe that screening can be beneficial.

“As the number of people in our country over 65 continues to grow, osteoporosis screening is taking on a new importance,” said Health and Human Services Secretary Tommy G. Thompson.

“The evidence shows that the risk for osteoporosis and fractures increases with age, and the means are now available to detect low bone density and treat it,” said Heidi D. Nelson, M.D., M.P.H., of the Evidence-based Practice Center at Oregon Health & Science University. Nelson led the evidence review along with Mark Helfand, M.D., M.P.H., and a team of researchers at OHSU.

One variable for physicians to consider is that several technologies are available to measure bone density. Dual-energy X-ray absorptiometry, known as DEXA, is considered the best because it is the most extensively validated test against fracture outcomes. Published studies consistently show that the probability of receiving a diagnosis of osteoporosis depends on the choice of technology and site of the test (forearm, hip, heel, etc.). The optimal frequency of testing is unclear, but intervals of two to five years are most consistent with current understanding of the tests.

The benefits of screening large segments of the population for osteoporosis are tempered by harms of testing. Potential harms may arise from inaccuracies and misinterpretations of bone density tests. False positives could lead to inappropriate treatment and false negatives could lead to missed treatment opportunities. Costs of tests and treatment are also factors to consider when screening. Also, fear and anxiety often accompany a diagnosis of osteoporosis, just as with any medical ailment.

The U.S. Preventive Services Task Force, the leading independent panel of private-sector experts in prevention and primary care, conducts rigorous, impartial assessments of all the scientific evidence for a broad range of preventive services. Its recommendations are considered the gold standard for clinical preventive services

Once the embargo lifts at 2 p.m., P.D.T. on Sept. 16, the Task Force recommendations and materials for clinicians will be available on the Web at ahrq/clinic/3rduspstf/osteoporosis/.

The IAEA is helping to raise awareness of threats, through training in radiation protection related to medical uses of X-ray imaging systems.

The issue of radiation protection for medical personnel is particularly acute in the case of lengthy angioplasty and other cardiac interventions performed under X-ray fluoroscopic guidance. The procedure can cause extensive radiation exposure to cardiologists that could lead to cataracts, alongside other longer term health risks. Fluoroscopy provides X-ray images of a patient that physicians can view on a display screen or monitor in real time.

The IAEA is helping the medical community to address this problem through a major international initiative aimed at training cardiologists and other medical professionals in radiation protection. This September in Latin America, the IAEA is organizing a study to test the eyes of interventional cardiologists participating in a regional medical conference. The Cardiology Conference is organized by the Latin American Society of Interventional Cardiologists (SOLACI) in Bogota, Colombia.

The study is being led by a team of experts, including Prof. Eliseo Vano, Radiology Department of the Complutense University of Madrid; Prof. Norman Kleiman, Columbia University, New York; local ophthalmologists from Bogota; and Mr. Raul Ramirez of the IAEA Department of Technical Cooperation. The initiative is part of an International Action Plan on the radiological protection of patients spearheaded by the IAEA.

"In the meeting of Latin American cardiologists, we will offer participants the possibility to have their eye tested for early changes of radiation effect that may lead to cataract in future years," says Professor Eliseo Vano. "This will allow us to assess retrospectively what radiation dose these cardiologists received, and then correlate the data with changes in their lens. Hopefully, this will help them protect themselves better in the future and reduce further radiation in their eyes while maintaining the clinical load."

The IAEA´s Dr. Madan Rehani, a Radiation Safety Specialist, underscores the importance and timeliness of raising awareness of the issue within the medical community. Proper use of tools for radiation protection – like protective screens or barriers – can prevent problems.

"We started training courses for cardiologists in 2004 and so far cardiologists from more than 50 countries have been trained in radiation protection," he says. In addition, training material, on computer diskette and in printed publications, is being distributed via the IAEA website pages on the radiation protection of patients.

As part of additional outreach, Dr. Rehani says the IAEA is working with professional societies of cardiologists in many parts of the world. A network of Asian cardiologists in radiation protection has been created, and SOLACI has expressed interest in incorporating radiation protection lectures in their conferences.

The September meeting will take place in Bogota, Colombia, from 24-26 September, under the leadership of Dr. Dario Echeverri, Vice-President of SOLACI.

Stroke is the leading cause of serious long-term disability and the third leading cause of death in the United States. Responding to the need for improvements in acute stroke care, the Brain Attack Coalition (BAC) published recommendations for the establishment of primary stroke centers in 2000, and in 2003 the Joint Commission began certifying stroke centers based on these recommendations, according to background information in the article. Now, nearly 700 of the 5,000 acute care hospitals in the United States are Joint Commission-certified stroke centers, with some states establishing their own designation programs using the BAC core criteria. "Despite widespread support for the stroke center concept, there is limited empirical evidence demonstrating that admission to a stroke center is associated with lower mortality," the authors write.

Ying Xian, M.D., Ph.D., of the Duke Clinical Research Institute, Durham, N.C., and colleagues conducted a study to evaluate the association between admission to stroke centers for acute ischemic stroke and the rate of death. Using data from the New York Statewide Planning and Research Cooperative System, the researchers compared mortality for patients admitted with acute ischemic stroke (n = 30,947) between 2005 and 2006 at designated stroke centers and nondesignated hospitals. Patients were followed up for mortality for 1 year after hospitalization through 2007. To assess whether the findings were specific to stroke, the researchers also compared mortality for patients admitted with gastrointestinal hemorrhage (n = 39,409) or heart attack (n = 40,024) at designated stroke centers and nondesignated hospitals.

Among the patients with acute ischemic stroke, 49.4 percent (n = 15,297) were admitted to designated stroke centers (n=104) and 50.6 percent to non-designated hospitals. The overall 30-day all-cause mortality rate was 10.1 percent for patients admitted to designated stroke centers and 12.5 percent for patients admitted to nondesignated hospitals, with analysis indicating that admission to a designated stroke center hospital was associated with a 2.5 percent absolute reduction in 30-day all-cause mortality. Use of thrombolytic therapy (dissolving blood clots) was 4.8 percent for patients admitted at designated stroke centers and 1.7 percent for patients admitted at nondesignated hospitals (adjusted difference in use, 2.2 percent). Among patients surviving to hospital discharge, there was no difference in rates of 30-day all-cause readmission and discharge to a skilled nursing facility.

"Differences in mortality also were observed at 1-day, 7-day, and 1-year follow-up. The outcome differences were specific for stroke, as stroke centers and nondesignated hospitals had similar 30-day all-cause mortality rates among those with gastrointestinal hemorrhage or acute myocardial infarction," the authors write.

"Even though the differences in outcomes between stroke centers and nondesignated hospitals were modest, our study suggests that the implementation and establishment of a BAC-recommended stroke system of care was associated with improvement in some outcomes for patients with acute ischemic stroke."

In an accompanying editorial, Mark J. Alberts, M.D., of the Stroke Program, Northwestern University School of Medicine, Chicago, comments on the future of acute stroke care.

"A multitiered system of stroke care is developing, with the comprehensive stroke center (CSC) at the top of the pyramid, the primary stroke center (PSC) in the middle, and the acute stroke ready hospital (ASRH) at the base. Within a geographical region, a small number of CSCs would provide care for patients with the most complicated stroke cases; a larger number of PSCs would provide care for the patients with typical, uncomplicated cases; and the ASRH would provide initial screening and triage and begin acute care for patients in a rural, small urban, or suburban setting. Emergency medical services personnel would perform initial screening and triage and would transport patients with a clearly defined stroke to the closest stroke center facility. Using telemedicine technologies, hospital personnel could communicate and transfer patients to the facility with the most appropriate level of care. Many states and guidelines now support and even mandate the diversion of patients suspected of having a stroke to the nearest stroke center facility."