Shape matters

Unlocking the keys to H. pylori’s helical structure may lead to better antibiotic drugs for diseases from ulcers and stomach cancer to diarrhea and cholera

SEATTLE — May 27, 2010 — The bacterium Helicobacter pylori, which lives in the human stomach and is associated with ulcers and gastric cancer, is shaped like a corkscrew, or helix. For years researchers have hypothesized that the bacterium’s twisty shape is what enables it to survive – and thrive – within the stomach’s acid-drenched environment, but until now they have had no proof.

For the first time, researchers at Fred Hutchinson Cancer Research Center have found that, at least when it comes to H. pylori’s ability to colonize the stomach, shape indeed matters. Microbiologist Nina Salama, Ph.D., and colleagues report their findings May 28 in Cell.

Salama and colleagues are the first to demonstrate that the bug’s helical shape helps it set up shop in the protective gelatin-like mucus that coats the stomach. Such bacterial colonization – present in up to half of the world’s population – causes chronic inflammation that is linked to a variety of stomach disorders, from chronic gastritis and duodenitis to ulcers and cancer.

“By understanding how the bug colonizes the stomach, we can think about targeting therapy to prevent infection in the first place,” said Salama, the paper’s corresponding author and an associate member of the Human Biology Division at the Hutchinson Center. The paper’s first author, Laura K. Sycuro, Ph.D., conducted this work while a student in the University of Washington/Fred Hutchinson Cancer Research Center Molecular and Cellular Biology graduate program. She is now a postdoctoral research associate in the Hutchinson Center’s Clinical Research Division.

Specifically, the researchers discovered a group of four proteins that are responsible for generating H. pylori’s characteristic curvature. Using a mouse model, they found that laboratory-engineered mutant strains of H. pylori that are deficient in these proteins fail to twist properly and, consequently, are unable to colonize the stomach.

“Having these mutant strains in hand allowed us to test whether the helical shape is important for H. pylori infection, and it is,” Salama said. “All of our mutants had trouble colonizing the stomach and were out-competed by normal, helical-shaped bugs.” Interestingly and somewhat puzzlingly, the H. pylori mutants retained their ability to propel themselves through a thick, mucus-like gel in a petri dish even though they were unable to establish infection in stomach colonization experiments.

The researchers also discovered a novel mechanism by which these proteins drive the organism’s shape, in essence acting like wire cutters on a chain-link fence to strategically snip certain sections, or crosslinks, of the bacterium’s mesh-like cell wall.  “The crosslinks preserve the structural integrity of the bacterial wall, but if certain links are cleaved or relaxed by these proteins, it allows the rod shape to twist into a helix,” Salama said.

Mutant forms of H. pylori that lack these proteins are misshapen, ranging from rods to crescents, which hampers their ability to bore through or colonize the stomach lining.

“We found that the bacteria that lost their normal shape did not infect well, and so we know that if we inhibit normal shape we can slash infection rates,” Salama said.

Other disease-inducing bacteria that have these proteins include Vibrio cholerae, a comma-shaped bug that causes cholera, and the curved to helical rod-shaped Campylobacter jejuni, which is the leading cause of bacterial diarrhea in developed countries.

“The fact that we found proteins that act on the cell wall of H. pylori that seem to be important for bacterial survival and that these proteins are found in other pathogens with similar shapes makes them a possible drug target for a number of bacterial diseases,” she said.

H. pylori is contagious, but its exact transmission route is unknown. While more than 80 percent of those infected will remain asymptomatic, an estimated 10 percent to 15 percent will develop related diseases such as ulcers and/or stomach cancer. About 70 percent of stomach cancers are associated with H. pylori infection.

The current treatment for H. pylori infection in those diagnosed with peptic ulcers is a combination of proton-pump inhibitors to reduce gastric acid secretion paired with antibiotics to eradicate the bug. The treatment is not always effective, however, due to the prevalence of antibiotic resistance.

“H. pylori infection is hard to treat. There are no vaccines. Right now the only treatment is eradication therapy, and we are running out of tricks because of resistance to essentially all current antibiotics,” Salama said.

The bug was first characterized in the early 1980s by Australian researchers Barry J. Marshall and Robin Warren, who in 2005 received the Nobel Prize in physiology or medicine for their discovery. Prior to their finding, the prevailing theory was that most stomach ulcers and gastritis were caused by spicy food or stress.

In addition to helical rods or spirals, bacterial species come in a wide variety of highly conserved shapes that range from spheres and rods to crescents and stars. They can be found on and within animals and plants – and indeed wherever life exists, from deep in the Earth’s crust to the oceans and forests – and they play a key role in regulating the environment. In humans, which harbor 10 times more bacterial cells than human cells, bacteria not only cause diseases ranging from strep throat to pneumonia, but they also perform a host of helpful duties, from aiding digestion to making vitamins that the human body alone cannot produce.

“We are a consortium. We depend on them as they depend on us,” Salama said.

source: Fred hutinson’s cancer center

Is Early Balding Linked to Prostate Cancer?

Study Suggests Men Who Are Bald at Young Age May Have Risk for Prostate Cancer?
man inspecting hairline in mirror

Feb. 15, 2011 — Men who start to go bald by age 20 may have an increased risk for developing prostate cancer later in life, a study suggests.

Prostate cancer patients in the study were twice as likely to report that they began to lose their hair by this age as men who did not have the disease.

The findings appear to contradict research published last spring, which found early baldness to be protective against prostate cancer. But that study contradicted even earlier research suggesting just the opposite.

Cancer experts tell WebMD that the evidence linking baldness to prostate cancer remains inconclusive.

“This really just shows how much we don’t know,” American Cancer Society Director of Prostate and Colorectal Cancers Durado D. Brooks, MD, tells WebMD.

“Even if this research is corroborated, the message is not clear,” he explains. “If you are a 20-year-old man and you are balding, the most that can be said based on this latest study is that you might develop prostate cancer in 40 years.”

Losing Hair Early in Life

In the new study, published Tuesday in the Annals of Oncology, researchers found no evidence that specific patterns of hair loss were more closely linked to prostate cancer than others. The study also failed to show an association between early hair loss and the diagnosis of prostate cancer earlier in life.

The association between hair loss and prostate cancer was also not seen in men who reported that they began losing their hair at age 30 or 40.

“All that we can really say from this research is that men who are balding at age 20 appear to have an increased risk for prostate cancer,” radiation oncologist and study researcher Michael Yassa, MD, tells WebMD. “These other associations may exist, but we were not able to show them.”

About one in four men with male pattern baldness starts to lose his hair before age of 21 and two out of three will experience some hair thinning by age 35, according to the American Hair Loss Association.

Known medically as androgenic alopecia, male pattern baldness is caused by both genetics and hormones, but the specific relationship between the two is not completely understood.

It is believed that the androgen dihydrotesterone (DHT), which is a product of the male hormone testosterone, is produced in high amounts in genetically susceptible men. At these high levels DHT appears to cause the hair follicles to shrink over time, causing the hair to become weak and, eventually, stop growing.

DHT has also been implicated in the development and growth of prostate cancer.

The drug Propecia blocks the conversion of testosterone to DHT. Several widely publicized studies also suggest that it may prevent prostate cancer in high-risk men.

In an effort to better understand the DHT connection, Yassa and colleagues from France’s European Georges Pompidou Hospital asked close to 400 prostate cancer patients and around 400 men without the disease about their balding history.

A total of 37 participants with a history of prostate cancer  and 14 participants without reported some degree of balding by the age of 20, including receding hairline and/or thinning of the hair on top of the head.

Yassa says the research could help identify men who might benefit from prostate cancer screening.

“There is a huge debate right now about who should be screened and whether screening is appropriate for the general population,” he says, adding that men with early balding may be good candidates for screening.

But Brooks is not convinced.

“There is really nothing here that should alter the recommendation of the American Cancer Society and other groups that men should learn all they can about the potential risks and benefits of prostate cancer screening and then make a decision about whether or not to be screened,” he says.

American Cancer Society Chief Medical Officer Otis Brawley, MD, agrees.

“We have not moved beyond speculation at this point,” he tells WebMD. “There is no reason for bald men to obsess about this.”

source: webMD

Poor Sleep May Worsen RA Symptoms

Link Found Between Poor Sleep Quality and Greater Risk of Pain for Rheumatoid Arthritis Patients
senior man awake in bed

Feb. 16, 2011 — People with rheumatoid arthritis (RA) who don’t sleep well face significant risks of greater functional disability due to pain and fatigue symptoms associated with poor sleep quality, a new study shows.

Researchers at the University of Pittsburgh studied the relationship between sleep quality and functional disability in 162 patients with rheumatoid arthritis. All patients had been diagnosed with RA for at least two years; their average age was 58.5 and 76% were female.

In addition, each participant had rheumatoid arthritis on average for 14 years. Data were drawn from patient questionnaires on sleep quality, depression, and overall health. Patients provided information concerning fatigue, depression, severity of pain, and functional disability.

RA Questionnaire

Results derived from the questionnaire showed that 61% of participants were poor sleepers; 33% reported pain that disturbed their sleep at least three times per week.

“The primary finding of our study is that poor sleep quality is associated with greater functional disability among patients with [rheumatoid arthritis] and this relationship may be explained by pain severity and fatigue,” says study researcher Faith S. Luyster, PhD, in a news release. Luyster is a research assistant at the University of Pittsburgh School of Medicine.

“These results highlight the importance of addressing sleep complaints among patients with [rheumatoid arthritis],” she says. “By treating sleep problems, either pharmacologically or behaviorally, symptoms and activity limitations associated with [rheumatoid arthritis] may be reduced.”

The researchers say their findings are consistent with other evidence that suggests that disruption of sleep may lower the threshold for pain, and also worsen it, in otherwise healthy adults.

The study is published in the Feb. 15 issue of the Journal of Clinical Sleep Medicine.

Rheumatoid arthritis is an inflammatory disease that affects about 1.3 million adults in the U.S., causing pain, swelling, stiffness, and loss of function in joints. People with RA have long reported problems with sleep.

Disability from joint disease in people with rheumatoid arthritis may limit their ability to walk, groom themselves, and write, and can be further affected by fatigue, pain, and depression.

Pain, Fatigue, and Depression

The researchers say it’s possible that disability may affect depression, pain severity, and fatigue, which affect sleep quality, but also possible that sleep quality may worsen pain and fatigue and increase risks of depression.

“Not sleeping well at night can contribute to greater pain sensitivity and fatigue during the day, which in turn can limit patient’s ability to engage in activities of daily living and discretionary activities,” Luyster says in the news release.

“Addressing sleep problems via pharmacological or behavioral interventions may have a critical impact on the health and lives of patients” with rheumatoid arthritis, the researchers write.

The researchers also say more study is needed to determine whether improving sleep quality can reduce pain, depressive symptoms, fatigue, and disability in people with rheumatoid arthritis.

source: webMD

Vaccination against Chlamydia Genital Infection Utilizing the Murine C. muridarum Model{triangledown}

Chlamydia trachomatis genital infection is a worldwide public health problem, and considerable effort has been expended on developing an efficacious vaccine. The murine model of C. muridarum genital infection has been extremely useful for identification of protective immune responses and in vaccine development. Although a number of immunogenic antigens have been assessed for their ability to induce protection, the majority of studies have utilized the whole organism, the major outer membrane protein (MOMP), or the chlamydial protease-like activity factor (CPAF). These antigens, alone and in combination with a variety of immunostimulatory adjuvants, have induced various levels of protection against infectious challenge, ranging from minimal to nearly sterilizing immunity. Understanding of the mechanisms of natural infection-based immunity and advances in adjuvant biology have resulted in studies that are increasingly successful, but a vaccine licensed for use in humans has not yet been brought to fruition. Here we review immunity to chlamydial genital infection and vaccine development using the C. muridarum model.

source: journal of vaccine and immunology

Hot flashes may signal breast cancer protection

the more frequent and severe the menopausal symptoms, the lower the cancer risk

Women who have experienced hot flashes and other symptoms of menopause may have a 50 percent lower risk of developing the most common forms of breast cancer than postmenopausal women who have never had such symptoms, according to a recent study by Hutchinson Center researchers.

The results of the study—the first to examine the relationship between menopausal symptoms and breast cancer risk—were published online ahead of the February print issue of Cancer Epidemiology Biomarkers & Prevention.

The protective effect appeared to increase along with the number and severity of hot flashes—also known as hot flushes, according to senior author Dr. Chris Li, a breast cancer epidemiologist in the Public Health Sciences Division.

“In particular we found that women who experienced more intense hot flushes—the kind that woke them up at night—had a particularly low risk of breast cancer,” he said.

Breasts may benefit from decreased estrogen

Li and PHS colleagues, including Drs. Kathi Malone and Janet Daling, suspected a link between menopause misery and decreased breast cancer risk because hormones such as estrogen and progesterone play an important role in the development of most breast cancers, and reductions in these hormones caused by gradual cessation of ovarian function can impact the frequency and severity of menopausal symptoms.

“Since menopausal symptoms occur as hormone levels fluctuate and drop, we hypothesized that women who experienced symptoms such as hot flushes and night sweats—particularly frequent and severe symptoms—might have a lower risk of breast cancer due to decreased estrogen levels,” he said.

Indeed, the researchers found a 40 percent to 60 percent reduction in the risk of invasive ductal and invasive lobular carcinoma—the two most common types of breast cancer—among women who experienced hot flashes and other symptoms. The association between such symptoms and decreased cancer risk did not change even after the researchers accounted for other factors known to boost breast cancer risk, such as obesity and use of hormone replacement therapy.

For the study, which was funded by the National Cancer Institute, Li and colleagues interviewed 1,437 postmenopausal Seattle-area women, 988 of whom had been previously diagnosed with breast cancer and 449 of whom had not, who served as a comparison group. The women were surveyed about perimenopausal and menopausal symptoms ranging from hot flashes, night sweats and insomnia to vaginal dryness, irregular or heavy menstrual bleeding, depression and anxiety.

“While menopausal symptoms can certainly have a negative impact on quality of life, our study suggests that there may be a silver lining if the reduction in breast cancer risk is confirmed in future studies,” Li said. “If these findings are confirmed, they have the potential to improve our understanding of the causes of breast cancer and improve approaches to preventing this disease.”

source: Fred Hutchinson Cancer Research Center

Terbutaline Should Not Be Used for Prolonged Preterm Labor

The FDA is adding a boxed warning to the injectable bronchodilator medication terbutaline to caution against using the drug off-label for prevention or prolonged treatment (longer than 48 to 72 hours) of preterm labor in pregnant women. The FDA is also warning against using the oral form of the drug for these purposes because it is not proven to be effective and has a similar risk profile.

The agency has received postmarketing reports of serious adverse reactions in women who were given the drug for obstetric uses. The reactions include increased heart rate, cardiac arrhythmias, pulmonary edema, myocardial ischemia, hypokalemia, hyperglycemia, and death.

The FDA concludes that “the risk of serious adverse events outweighs any potential benefit to pregnant women.”

source: FDA MedWatch alert

Fighting tumors with tumors

Researchers at The Rogosin Institute have used cancer cell–containing agarose beads to inhibit tumor proliferation in animals.1 Although the strategy sounds counterintuitive, the macrobeads already are in an investigator-sponsored Phase II trial in patients with pancreatic cancer, advanced colorectal cancer or refractory prostate cancer.

Previous work had shown that the growth of solid tumors is characterized by progressive slowing of the rate of growth as the tumor increases in size, suggesting that growth might be inhibited by molecules signaling the presence of tumor mass.2, 3

Rogosin’s Barry Smith and his team hypothesized that this negative feedback could be harnessed to fight cancer if the same effect could be recreated through controlled exposure to a tumor—for example, to tumor cells encapsulated in an artificial matrix.

Smith is director of Rogosin, a professor of clinical surgery at Weill Cornell Medical College and an attending physician at New York-Presbyterian Hospital.

The researchers set out to test this hypothesis by growing mouse renal adenocarcinoma (RENCA) cells in agarose and then coating them with agarose to produce macrobeads that were 6–8 mm in diameter.

Within one week after encapsulation, 99% of the tumor cells underwent apoptosis. The remaining tumor cells represented several subpopulations.

These surviving cells formed large, metabolically active tumor colonies that could be maintained in the 3D culture indefinitely, with little increase in total cell number or colony volume but with continuous individual cellular turnover. Although tumor cells were proliferating, they exhibited automatic growth inhibition as the encapsulated tumor reached its ultimate mass in the macrobead.

Further studies showed that the cells displayed stem cell markers, had increased gene expression in pathways associated with stem cells and, when released from the 3D matrix after three years of encapsulation, could still proliferate and form tumors.

To discover what signals the encapsulated tumor cells were using for growth regulation, the team used mass spectroscopy to identify around 750 proteins and peptides in macrobead culture media. At least 10 of these proteins were highly conserved across species and known to have tumor inhibitory properties.

Thus, the researchers postulated that, in vivo, the inhibitory proteins could be released by the beads into the abdominal fluid and then the bloodstream, where they would be transported to a tumor and possibly regulate its growth.

They put their hypothesis to the test in mice that had 2,500 RENCA cells implanted under the renal capsule, which surrounds the kidney. Using this mouse model of renal cancer, intraperitoneal implantation of the macrobeads led to smaller tumors than implantation of empty macrobeads (p<0.05).

The researchers also tested the macrobeads in dogs and cats in the end stages of various naturally occurring cancers. The beads improved disease in 39 of 51 animals without evident impairment of their immune systems. One cat with gastrointestinal lymphoma lived for three years after receiving five macrobead implants, and a cat with mammary carcinoma lived for eight years after receiving four implants. Each received about 200 beads at each implant site.

In 11 dogs with prostate cancer, the macrobeads increased median survival to 177 days compared with an expected survival of <50 days for no treatment.

Based on these data, Smith’s team believes the macrobead effect to be neither species- nor tumor-specific.

The team published its findings in Cancer Research and included scientists from Cornell University, Columbia University, New York-Presbyterian Hospital, The Rockefeller University, The Ohio State University, Bob Evans Farms Inc., the Veterinary Oncology & Hematology Center and the Gerald P. Murphy Cancer Foundation.

Richmond Prehn, professor emeritus of pathology at the University of Washington and one of the original proponents of the idea that tumor growth could be inhibited by tumor mass,2 thought the effect of multiple inhibition components from the macrobead to slow tumor growth was “exciting indeed.”

He added that it was “very surprising that the presumably relatively small number of encapsulated tumor cells had such profound effects on the much larger tumor target in the in vivo experiments.”

Indeed, he said those data could imply that the “confined cells were putting out unexpectedly large amounts of inhibition components.”

“There are actually significant changes of up to 100-fold in the amounts of particular proteins and/or peptides that are released by the cells in the macrobeads,” Smith said. “In addition to the possibility of larger amounts of particular molecules being released, there is also the possibility that one or more of the released factors are triggering a cascade of events that help to produce part of the effect.”

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The maturation of a macrobead

Olga Garkavenko, head of molecular diagnostics at Living Cell Technologies Ltd., said the findings illustrate “the unique aspect of cellular therapy—the synergistic effect of multiple components as opposed to the action of just a single agent.”

She said the technology described in the paper might be a good tool for tumor regulation research and for in vitro testing of proposed antitumor therapeutics because the cell population of the macrobeads seems to represent a cancer stem cell niche of sorts. Because cancer stem cells are believed to be responsible for enabling the perpetuation of tumors, the macrobeads could be used to test therapeutics that, to be optimally effective, would have to show activity against such cells.

Garkavenko did say that using the macrobeads as a therapeutic “might be a bit premature. It would be very useful to show the data on long-term tracking of tumor cells from macrobeads in experiments” to ensure that the cancerous xenocells do not survive in the host if they somehow escape from the macrobeads.

Previous work has shown that porcine cells can survive for years in a nonimmunosupressed patient after extracorporeal pig spleen perfusion.4

“Cell-based therapies offer more physiologic control, far less toxicity than pharmacologic approaches and when embedded can take the form of therapeutic units that can be stored, used immediately and assayed for function prior to implantation.”

Elazer Edelman
Pervasis Therapeutics Inc.

Smith acknowledged that there is a very small possibility of microchimerism—the survival of a xenocell in the recipient’s bloodstream. However, he told SciBX that “the mechanical barriers of the agarose shell, immunologic—xenogeneic—barriers of the host and macrobead growth-controlling signals in bloodstream all work to prevent cross-species seeding and propagation of unencapsulated cells. In fact, in our veterinary study of cats and dogs, no evidence of any surviving mouse cancer cells outside the macrobead is found for periods of up to 3–5 years post-implant.”

In a Phase I trial in cancer patients, intraperitoneal implants of about 8–16 macrobeads per kilogram per patient were safe. Because the agarose beads are well tolerated by the body, there is no need to remove them. The human abdomen could hold as many as 15 implants without a problem.

The ongoing Phase II trial is enrolling patients with pancreatic cancer, advanced colorectal cancer or refractory prostate cancer and is measuring tumor response rate, time to progression, quality of life and tumor markers.

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The macrobead core

The Rogosin team is not the only one using macrobeads in cancer. An endothelial cell–containing macrobead was described at the beginning of the year in Science Translational Medicine by researchers from the Massachusetts Institute of Technology, The University of Texas at Austin, the Boston University School of Medicine and Harvard Medical School.5

These researchers, led by Elazer Edelman, showed that endothelial cells encapsulated in gelatin matrices decreased tumor growth and invasiveness in mice. Pervasis Therapeutics Inc. is developing the implant technology to treat solid tumors in conjunction with surgical resection.

Edelman is a professor of health sciences and technology at MIT, professor of medicine at Harvard Medical School and a coronary care unit cardiologist at Brigham and Women’s Hospital. He is also a cofounder and director of Pervasis and member of the scientific advisory board.

Although the technology might appear to be potentially safer because it uses endothelial cells instead of cancer cells, researchers interviewed by SciBX wanted to see next steps showing whether the cross talk occurring between the encapsulated endothelial cells and the host tumor cells could cause the transformation of the endothelial cells.6

Smith said, “There seem to be similarities between the two macrobead systems with multiple factors being secreted that act on multiple pathways to inhibit growth. Inhibiting a single pathway does not appear to be enough to inhibit cancer cell growth.”

“It is possible,” he continued, “that endothelial cells are having some effect in our model given that the RENCA cells are passaged through mice and such vasculature cells could be encapsulated in the RENCA macrobeads. However, I don’t see that Edelman’s system selects for stem cells.”

Edelman believes that the idea of using cells as paracrine regulators is gaining momentum. “Cell-based therapies offer more physiologic control, far less toxicity than pharmacologic approaches and when embedded can take the form of therapeutic units that can be stored, used immediately and assayed for function prior to implantation,” he said.

He added that “what is most exciting is that we and others have used these approaches effectively with mature, progenitor and stem cells.”

Rogosin has exclusively licensed its macrobead IP to the Metromedia Bio-Science LLC unit of Metromedia Co.

Metromedia Co., the privately held broadcast and telecommunications company run by billionaire John Kluge until his death in September, is financially backing the studies.

Metromedia Bio-Science has put $50 million into the cancer project and intends to funnel the bulk of any revenue from the treatment, should it reach the market, into Kluge’s charitable foundation.

source: sciencevx

Venous Interventions in Children

Advanced medical treatment options have improved pediatric survival but often require invasive vascular procedures or venous access. These procedures increase the risk for thromboembolism in children, and there has been a corresponding increase in the reported incidence of deep venous thrombosis and postthrombotic syndrome in the pediatric population. Percutaneous venous interventions using catheter-directed therapy (CDT), like mechanical thrombectomy and infusion thrombolysis, have been used much less frequently in children, even though they have shown good results in adults. A multidisciplinary team including pediatric hematology, interventional radiology, and intensive care unit is suggested for management of venous thrombosis in children. Indications and contraindications for CDT in children are similar to adults. Mechanical thrombectomy and infusion thrombolysis are some of the more commonly performed treatments. CDT in children requires adapting to patient size and locally available equipment. Ultrasound guidance for access, “cork” technique, appropriate dosing of tissue plasminogen activator for infusion/pharmacomechanical thrombolysis, and simultaneous administration of heparin, plasminogen (fresh frozen plasma), and deficient coagulation factors are some of the important variations of CDT technique in children. Postprocedure monitoring is very important for successful thrombolysis. Retrievable inferior vena cava filters are increasingly being used in children as well, for prophylaxis against pulmonary embolism (PE) if there is a significant risk of PE with/without contraindications to anticoagulation.

source: science direct

Automated vs. Manual BP Monitoring for Systolic Hypertension

Automated blood pressure monitoring was more accurate.

Office manual blood pressure (BP) monitoring is fraught with problems, including variable BP measuring skills among healthcare workers, “white-coat hypertension,” and digit preference (readings ending in “0”). In this trial, Canadian investigators randomized 67 primary care practices to use either ongoing manual office BP monitoring (control) or automated office BP monitoring using the BpTRU device (intervention; after the BpTRU cuff is positioned properly, the patient is left alone, and the device automatically takes five BP readings and displays an average). Awake ambulatory BP monitoring was the gold standard.

Overall, 555 patients with systolic hypertension participated in the study. Compared with manual office BP readings, automated office BP readings correlated more strongly with ambulatory BP monitoring. For example, the mean manual office systolic BP after enrollment was 6.5 mm Hg higher than ambulatory BP, whereas mean automated office systolic BP was only 2.3 mm Hg higher than ambulatory BP; this difference was significant. For diastolic BP, mean automated and manual office measurements were both about 4 mm Hg higher than ambulatory measurements. Another striking finding was a fall in automated systolic BP while the patient rested in the exam room: Mean systolic BP fell from 147 to 133 mm Hg during a 10-minute period.

Comment: Automated BP monitoring (with multiple readings taken while the patient is resting) is more accurate than manual BP monitoring in primary care patients with systolic hypertension. The results have obvious clinical implications, such as limiting unnecessary treatment. Indeed, several years ago, my institution systematically eliminated manual BP monitoring in favor of automated BP monitoring.

Paul S. Mueller, MD, MPH, FACP

Published in Journal Watch General Medicine February 17, 2011