Day: 01/12/2012

Catheter-Directed Thrombolysis Reduces Long-Term Sequelae After Proximal Deep Venous Thrombosis.

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The technique has potential to reduce chronic discomfort and disability substantially.

Anticoagulation after lower-extremity deep venous thrombosis (DVT) can prevent thrombus extension, embolization, recurrence, and death, but does not prevent common chronic sequelae such as edema, pain, hyperpigmentation, and skin breakdown (collectively known as postthrombotic syndrome [PTS]). Systemic thrombolysis can prevent PTS but increases bleeding risk. In catheter-directed thrombolysis (CDT), a catheter with side-holes is embedded in the thrombus and releases a thrombolytic agent over several days.

Investigators in Norway randomized 209 adults with first-time iliofemoral DVT to conventional treatment with heparin and warfarin or to conventional treatment plus CDT. CDT patients underwent venography to determine the extent of thrombus, followed by catheter insertion (usually into the popliteal vein). Use of additional modalities, such as angioplasty and stents, was permitted at the discretion of the treating physicians. Patients in both groups were advised to use knee-high compression stockings for 2 years.

At 6 months, prevalence of iliofemoral patency was significantly higher (66% vs. 47%) in CDT patients, and PTS occurred with equal frequency (about 30%) in both groups. After 24 months, however, prevalence of PTS was significantly lower (41% vs. 56%) in patients who underwent CDT. Three major and 17 other bleeding complications occurred in the CDT group; none were life-threatening.

Comment: Despite some methodologic weaknesses, this unblinded study adds important data to an otherwise sparse evidence base for CDT and suggests that this technique can substantially reduce chronic discomfort and disability after DVT. For now, however, American College of Chest Physicians guidelines recommend CDT only for “selected patients with extensive acute proximal DVT.”

Source: Journal Watch General Medicine

 

Cold winters caused by warmer summers, research suggests

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Scientists have offered up a convincing explanation for the harsh winters recently experienced in the Northern Hemisphere; increasing temperatures and melting ice in the Arctic regions creating more snowfall in the autumn months at lower latitudes.

Their findings may throw light on specific weather incidents such as the extremely harsh Florida winter of 2010 which ended up killing a host of tropical creatures, as well as the chaos-causing snow that fell on the UK in December 2010.

Published today, Friday 13 January, in IOP Publishing’s journal Environmental Research Letters, this new research suggests that the trend of increasingly cold winters over the past two decades could be explained by warmer temperatures in the autumn having a marked effect on normal weather patterns, causing temperatures to plummet in the following winter.

The strongest winter cooling trends were observed in the eastern United States, southern Canada and much of northern Eurasia, which the researchers, based at Atmospheric and Environmental Research (AER), the University of Massachusetts and the University of Alaska Fairbanks, believe cannot be entirely explained by the natural variability of the climate system.

Their results showed strong warming throughout July, August and September in the Arctic, which continued through the autumn and, according to their observational data, appeared to enhance the melting of sea ice.

This warmer atmosphere, combined with melting sea ice, allows the Arctic atmosphere to hold more moisture and increases the likelihood of precipitation over more southern areas such as Eurasia, which, in the freezing temperatures, would fall as snow. Indeed, the researchers’ observations showed that the average snow coverage in Eurasia has increased over the past two decades.

They believe the increased snow cover has an intricate effect on the Arctic Oscillation – an atmospheric pressure pattern in the mid- to high-latitudes – causing it to remain in the “negative phase”.

In the “negative phase”, high pressure resides over the Arctic region, pushing colder air into mid-latitude regions, such as the United States and northern Canada, and giving the observed colder winters.

The lead author of the study, Judah Cohen, said: “In my mind there is no doubt that the globe is getting warmer and this will favour warmer temperatures in all seasons and in all locations; however, I do think that the increasing trend in snow cover has led to regional cooling as discussed in the paper and I see no reason why this won’t continue into the near future. Also if it continues to get much warmer in the fall, precipitation that currently falls as snow will fall as rain instead, eliminating the winter cooling.”

It is also deduced that one of the main reasons conventional climate models fail to pick up on this observed winter cooling is their failure to account for the variability of snow cover, which, as demonstrated in this study, can greatly improve the accuracy of seasonal, and lengthier, forecasts.

“We show in the paper how using the snow cover in a seasonal forecast can provide a more skilful or accurate forecast. Without correctly simulating the coupling of winter climate patterns and the variability of snow fall, the models currently used by Government centres miss an important influence on winter and will therefore continue to be deficient in predicting winter weather on seasonal time scales, and even longer decadal time scales,” continued Cohen.

Source:Nature/ Environmental Research Letters.

What Will It Take to Eliminate Pediatric HIV? Reaching WHO Target Rates of Mother-to-Child HIV Transmission in Zimbabwe: A Model-Based Analysis.

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A woman who is infected with HIV can pass the virus to her baby during pregnancy, labor and delivery, or breastfeeding—mother-to-child HIV transmission (MTCT). Without treatment, up to 30% of babies born to HIV-infected women will become infected with HIV during pregnancy or at delivery, and a further 5%–20% will become infected through breastfeeding. In 2009, around 400,000 children under 15 years of age became infected with HIV, mainly through MTCT—90% of these MTCT infections occurred in Africa.

In addition to preventing HIV infection among prospective parents and avoiding unwanted pregnancies among HIV-positive women, effective prevention of MTCT (PMTCT) requires preventing the transmission of HIV from infected mothers to their infants during pregnancy, labor, delivery, and breastfeeding.

In 2010, the World Health Organization (WHO) published new guidelines for PMTCT based on combination antiretroviral therapy for women with advanced HIV disease, and two options for countries to select for women with less advanced disease. Option A includes zidovudine (ZDV) during pregnancy and single-dose nevirapine (sdNVP) at delivery, followed by daily nevirapine syrup for infants throughout the duration of breastfeeding; Option B includes maternal triple-drug ARV regimens throughout pregnancy and breastfeeding. However, WHO estimates that only 53% of pregnant women worldwide received any antiretroviral medicines for PMTCT in 2009.

Why Was This Study Done?

As in many sub-Saharan African countries where prolonged breastfeeding is common, and necessary to improve child health, Zimbabwe is implementing the 2010 WHO guidelines with Option A. However, because of the challenges of enrolling and retaining women in PMTCT programs, the effectiveness of this strategy is unknown. Therefore in this study, the researchers used a model to calculate the level of PMTCT uptake in Zimbabwe, the PMTCT drug regimens, and the duration of breastfeeding that would be necessary to reach the WHO goal of an MTCT risk below 5%.

What Did the Researchers Do and Find?

The researchers used a validated computer simulation model developed for analyzing the cost-effectiveness of preventing AIDS complications to measure risk of infant HIV transmission at the time of weaning, the HIV infection risk at 4–6 weeks of age, infant survival at two years of age, and 2-year HIV-free survival. The researchers used four scenarios of PMTCT uptake and linked the models to two populations of pregnant and breastfeeding women (mean age, 24 years) in Zimbabwe, and then analyzed the combinations of the factors necessary to reach MTCT risks less than 5%.

At baseline, the researchers found that the 2008 National PMTCT Program in Zimbabwe led to a projected 12-month MTCT risk of 20.3%. The projected risk in 2009 was 18.0% because of improved uptake. The estimated MTCT risk with Option A at 56% uptake (2009 levels) was 14.4% and with Option B was 13.4%. However, even with greatly increased uptake, such as 95% levels, the researchers found that projected transmission risks would exceed the WHO goal of less than 5% MTCT, and that the MTCT risk would fall below 5% at the 95% uptake level only if the lowest transmission risks were used for each drug regimen, or if breastfeeding duration were shortened.

What Do These Findings Mean?

These findings show that the planned implementation of the 2010 WHO PMTCT guidelines with Option A in Zimbabwe could substantially reduce infant HIV infection risk compared to the 2009 national program with sdNVP. Furthermore, in order to reach a MTCT risk of less than 5%, a national program based on either Option A or Option B will also need to include strategies to improve access to PMTCT services (to almost 100% uptake), retain women in care, and support medication adherence throughout pregnancy and breastfeeding. These findings from a resource-limited country with high HIV prevalence and prolonged breastfeeding may be useful for other countries in sub-Saharan Africa.

Source:PLOS

 

 

 

 

Long-Term Survival in a Large Cohort of Patients with Venous Thrombosis: Incidence and Predictors.

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The term venous thrombosis describes the clinical situation—more common during pregnancy, after surgery, or serious illness—in which a blood clot lodges in a vein. One specific type, which is more serious, involves the clot forming in a major vein in the lower leg and thigh and is termed a deep venous thrombosis. The clot can block blood flow and cause swelling and pain, but more seriously, can break off and move through the bloodstream, causing an embolism. An embolism can get stuck in the brain (and cause a stroke), lungs (and cause a pulmonary embolism), heart (to cause a heart attack), and/or other areas of the body, leading to severe damage.

Venous thrombosis is known to be associated with considerable short-term morbidity and mortality: the mortality rate after venous thrombosis is about 20% within one year and studies to date have suggested that the mortality rate is two to four times higher for patients with pulmonary embolism, of whom 10%–20% die within three months after the event. Many factors are associated with venous thrombosis, and the underlying cause of the thrombosis affects survival; for example, those with thrombotic events provoked by surgery or trauma have a lower mortality risk than patients with thrombosis caused by malignancy. Furthermore, about 10%–20% of patients who have had a venous thrombosis develop a recurrence within five years and up to 50% develop post-thrombotic syndrome—long-term swelling, pain, and changes in skin color.

Why Was This Study Done?

It is currently unknown whether the poor prognosis associated with venous thrombosis is limited to the months following the thrombotic event, or persists for years afterwards. So in this study, the researchers sought to answer this question by analyzing the long-term survival in a large cohort of patients who had experienced a first venous thrombosis and who were all followed for up to eight years.

What Did the Researchers Do and Find?

The researchers used the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis study (MEGA study), which was a case-control study involving 4,965 consecutive patients aged 18 to 70 years who were objectively diagnosed with a deep venous thrombosis or pulmonary embolism and recruited from six anticoagulation clinics in the Netherlands between March 1999 and September 2004. The control group consisted of partners of patients (n = 3,297) and a random control group matched on age and sex (n = 3,000). The researchers obtained causes of death from the Central Bureau of Statistics and for the observation period (30 days after the venous thrombosis, to either death or end of follow-up between February 2007 and May 2009) compared cause-specific death rates of the patients to those of the general Dutch population. The researchers devised specialist survival models (called Kaplan-Meier life-tables) and calculated standardized mortality ratios (SMRs—the ratio of the observed number of deaths over the number of deaths expected) to estimate relative rates of all cause mortality by type of the initial thrombosis and the underlying cause.

Using these methods, the researchers found that the overall mortality rate in patients with thrombosis was substantially greater than in the control group (22.7 per 1,000 person-years compared to 4.7 per 1,000 person-years). Apart from malignancies, the researchers found that the main causes of death were diseases of the circulatory and respiratory system. Patients with venous thrombosis and malignancy had the highest risk of mortality: 55% died during follow-up. Patients with venous thrombosis without malignancy had an overall 2-fold increased risk of mortality compared to the control group and this risk was comparable for patients with different forms of thrombosis (such as deep venous thrombosis and pulmonary embolus). According to the researchers’ calculations, the relative risk of death was highest during the first three years after thrombosis, but for those with thrombosis of unknown cause, the risk of death increased by two-fold up to eight years after the thrombosis. Furthermore, the researchers found that the highly increased risk of death for those with pulmonary embolism is mainly only for the first month as long-term survival is similar to that of patients with a deep venous thrombosis.

What Do These Findings Mean?

These findings show that patients who have experienced a venous thrombosis for the first time have an increased risk of death, which may last up to eight years after the event. These findings have important clinical implications and suggest that long-term clinical follow-up could be beneficial in patients who have experienced a venous thrombosis for the first time.

Source:PLOS

 

 

 

 

Emergency Planning for People with Cancer .

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People with cancer have specific medical needs, especially during active treatment and in the time after treatment. These needs may become serious in the event of a natural or man-made disaster, such as tornadoes, earthquakes, hurricanes, floods, outbreaks of disease (such as the flu or measles), and terrorist attacks. Even if such an event is unlikely where you live, it is important to be prepared. This article will help you and your family plan for emergency situations.

Here are some tips to help you and your family prepare for an emergency:

Make a Plan

During a disaster, electricity, gas, water, and telephone services may be interrupted. Roads may be closed and emergency services that are especially important for people with cancer, such as ambulance and hospitals, may be unavailable. When making a plan, it is important to consider how these outages might affect you.

  • Develop your plan with your oncologist. Talk to him or her about what you need to do to manage your cancer during emergencies. For example, what are your options if you cannot get to a scheduled radiation treatment or to the clinic for chemotherapy?
  • Talk with your family about different disasters that could occur and how the person with cancer could be affected. Write down a few solutions for coping with each scenario.
  • Choose a place where everyone will meet during a disaster.
  • Identify a friend or a relative for everyone to communicate with in case you and your loved ones are separated or cannot get to the meeting place. This person can also be a back-up for any important information you may need, such as phone numbers for your doctor or pharmacy.
  • Don’t forget to brainstorm specific needs, such as evacuation transportation assistance or help coordinating medical appointments during and after a disaster.

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Be Ready To Stay or To Go

Depending on the type of disaster, you may be asked to evacuate (leave your house), or you may be asked to “shelter in place” (stay home). It is important to be ready for both. Contact your local American Red Cross chapter or public health department for information about how best to prepare to either evacuate or shelter in place and to learn about your community’s warning signals for natural disasters or public health emergencies—what they sound like and what you should do when you hear them.

Evacuate

Gather and keep supplies in a waterproof “go bag” that you can grab if you need to quickly leave. A “go bag” can be a backpack, tote bag, or even a small container that is easily carried.

In addition to basic supplies, such as water and blankets, your “go bag” should include any cancer medications and supportive care items.

Know where or who you will stay with if you need to be evacuated and be sure to consider areas that are convenient for the person with cancer. For example, if you will stay at a shelter, make a list of shelters in your area, including ones that have special medical facilities or ones that accept service animals. If you know in advance that you or your loved one will need assistance with evacuation transportation, make a list of transport services in your area that are available to help.

Shelter in Place

During other disasters, you may be asked to “shelter in place.” In this scenario, you will need enough water, food, medication, and other supplies, such as a first-aid kit, to survive on your own until help is available.

Water: Each day a person needs to drink at least 2 quarts (a half gallon) of water. Plan on an additional half-gallon of water per person to prepare food and for personal hygiene. If the person with cancer is taking medication that makes them extra thirsty, plan on having more water. Have enough water for at least three days.

Food: Stock up on foods that you eat regularly and that don’t need a refrigerator, such as energy bars, peanut butter, crackers, and canned fruit (don’t forget a can opener). Talk with your doctor about any vitamin, mineral, or protein supplement to help you get the nutrition you need. Have enough food for at least three days.

Medication: Make sure you have enough medication for at least one week, including any cancer medication and other medications for pain, nausea, and other side effects of cancer treatment. If it is not possible to have a week-long supply of medications and supplies, keep as much as possible on hand and talk with your pharmacist or doctor about what else you should do to prepare. For example, if the electricity goes out for a long time, it will be difficult to keep medications refrigerated.

Other supplies: Make a first-aid kit to treat basic injuries, such as cuts or burns. Many people with cancer are at high risk of developing an infection. To protect yourself or your loved one, include sanitizing supplies in your first-aid kit, such as antiseptic spray, peroxide, or alcohol. If you or your loved ones have a central venous catheter, or an intravenous line to receive treatment, include extra dressings and supplies in your kit.

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Keep Important Medication Information Together

Work with your doctor to summarize your medical history, including information about your cancer diagnosis and treatment, in a simple document. Include your current medications and dosages, current and recent treatments, and other dietary and health needs.

In addition to your medical history, keep a copy of other important documents related to your cancer treatment and care, including:

  • Pathology reports
  • Lab reports
  • Imaging results
  • Names, addresses, phone numbers, and fax numbers of all the doctors who are treating you or your loved one
  • Insurance information

Source:Cancer.net

Pap Test—What to Expect

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A  Pap test, also called a Pap smear, detects cervical cancer and can also find early changes in the cells of a woman’s cervix that, if left untreated, could turn into cancer. It is most often used as a screening test for cervical cancer in women who have no symptoms, typically done at the same time as a gynecologic checkup.

A Pap test involves gathering a sample of cells from the cervix. The sample is placed on a glass slide and sent to a laboratory for examination under a microscope by a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease). The pathologist can identify abnormal cells, which may be precancerous or cancerous. If the Pap test finds an abnormality, it is most commonly related to treatable, precancerous cellular changes, rather than cervical cancer.

The medical team

A Pap test is typically performed in a doctor’s office by a gynecologist, a medical doctor who specializes in treating diseases of the female reproductive organs. Pap tests are also sometimes performed by other health care professionals, including physician assistants and nurse practitioners. If your gynecologist is a man, a female assistant or nurse will be in the room during the Pap test.

If the results of the Pap test indicate cancer, an oncologist (a doctor who specializes in cancer) will treat the cervical cancer.

Questions to ask your doctor before the Pap test

Before having a Pap test, consider asking your doctor the following questions:

  • Who will perform my Pap test?
  • When will I get the test results?
  • Who will explain the results to me?
  • What happens if the test results are abnormal or unclear?
  • What further tests will be necessary if the test results indicate cancer?
  • After this test, when should I have my next Pap test?

Preparing for the procedure

To ensure that the Pap test results are as clear as possible, do not have sexual intercourse for two to three days before the test. In addition, do not use tampons, birth-control foams, vaginal medicines, douches, or vaginal creams or powders for two to three days before the test; these products may wash away abnormal cells.

The best time to schedule your Pap test is at least five days after the end of your menstrual period. A Pap test can be done during your menstrual period, but it is better to schedule the test at another time.

During the procedure

A Pap test is performed during a pelvic examination in a private room in your health care professional’s office. It takes only a few minutes. The test can be uncomfortable, but it is not usually painful. Emptying your bladder before the examination and taking deep breaths and relaxing your muscles during the procedure may make it more comfortable.

When you arrive for your examination, your health care professional may ask you some basic questions related to the test, including the following:

  • Are you pregnant?
  • Do you use birth control?
  • What medications have you recently taken?
  • Do you smoke?
  • When was your last menstrual period, and how long did it last?
  • Do you have any problems or symptoms, including itching, redness, or sores?
  • Have you had surgery or other procedures on your reproductive organs?
  • Have you ever had abnormal results from a previous Pap test?

When you are ready for your examination, you will remove your clothes below the waist, lie on your back on an examination table, and cover your waist and legs with a sheet. In addition, you will raise your feet and put your heels in stirrups at the end of the table, allowing your knees to relax to the sides. You can keep your socks on to keep your feet warm.

Next, the health care professional performing the examination will gently insert a lubricated plastic or metal instrument, called a speculum, into your vagina. This tool slowly spreads apart the vaginal walls. This may cause some slight discomfort.

After a visual inspection of the cervix (the part of the uterus that opens to the vagina), the health care professional will use a cotton swab, a spatula, or a cervical brush to gather cells from two places on the cervix: the ectocervix (the part closest to the vagina) and the endocervix (the part next to the body of the uterus). This area is called the transition zone, and it is where cervical cancers develop. As the cells are collected, you may feel pulling or pressure.

The health care professional will smear the cells onto a glass microscope slide or put the cells into a container and send the sample to a pathologist for evaluation.

Once the Pap test is complete, your health care professional will complete the pelvic examination. He or she will put two lubricated, gloved fingers inside your vagina, using the other hand to feel from the outside for any lumps or tenderness in other reproductive organs, including your fallopian tubes, ovaries, and uterus.

After the procedure

You may have a small amount of vaginal bleeding after your Pap test. However, tell your doctor if you have excessive bleeding. You can resume your normal activities immediately after the test.

Although the Pap test is an excellent screening tool, it is not perfect. Thus, sometimes the results are normal even when there are abnormal cervical cells present; this is called a “false negative” test result. That is why regular screening is important; talk with your doctor about how often you should have a Pap test. Research shows that almost all cervical abnormalities can be found with regular screening and treated before they become cancerous.

Source:Cancer.net

 

 

 

 

 

 

St Judes’s newsletter:January

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Gene therapy achieves early success against hemophilia B

St. Jude researchers have developed a treatment that offers hope to patients with the bleeding disorder hemophilia B. In a recent clinical trial conducted at the University College London (UCL), symptoms improved significantly in hemophilia B patients following a single gene therapy treatment.

The findings mark the first proof that gene therapy can safely reduce disabling, painful bleeding episodes in patients with the blood disorder. Results of the Phase I study appeared in the New England Journal of Medicine.

Hemophilia B is caused by an inherited mistake in the gene for making a protein called Factor IX, which is essential for normal blood clotting. Previous efforts to ease hemophilia B symptoms by introducing a correct copy of the gene had been unsuccessful. The current study used a harmless virus as the vector to deliver the Factor IX gene along with additional genetic material into each patient’s liver. The vector used in the study was produced at the Good Manufacturing Practices facility on the St. Jude campus. The approach was jointly pioneered by St. Jude and UCL, initially in the lab of study co-author Arthur Nienhuis, MD, of St. Jude Hematology.

As is often the case with experimental therapies, this study was conducted in adults to ensure the treatment was safe and effective. Plans are to include children in future trials. Because they have not yet experienced the joint damage and other complications of the disease, children undergoing gene therapy will likely benefit even more than adults do.

“These results are highly encouraging and support continued research. More patients are scheduled to be enrolled in future trials scheduled to begin later this year,” said the study’s senior author, Andrew Davidoff, MD, St. Jude Surgery chair.

 

In-house screening reduces stroke risk

Gail Fortner, RN, uses an ultrasound to measure blood flow in arteries leading to a child’s brain. The procedure, known as transcranial Doppler (TCD) ultrasound, is the most effective tool for predicting primary stroke in patients with sickle cell anemia.

Gail Fortner uses ultrasoundSickle cell patients at St. Jude undergo annual TCD screenings at their regular clinic visits. Most sickle cell centers require patients to go to radiology or neurology appointments to have the test done.

With the knowledge obtained from TCD screenings and the treatment offered to those considered to be at high-risk for strokes, clinicians are able to prevent stroke in many children with sickle cell anemia.

“Today, 99 percent of our high-risk patients ages 2 to 16 are screened for stroke. In published data from other institutions, that number is from 49 to 58 percent,” Fortner said.

She and Beth McCarville, MD, Radiological Sciences, are training Brazilian and Jamaican physicians who will be collaborating with St. Jude and Baylor College of Medicine on a future multicenter trial. This will be the first NIH-funded international sickle cell disease clinical trial and the latest example of the hospital’s collaboration on research that helps to improve the quality of life for sickle cell patients.

 

Molecule serves as key in some protein interactions

St. Jude structural biologists Brenda Schulman, PhD, Daniel Scott, PhD, and Julie Monda have identified a mechanism that facilitates some protein interactions that are workhorses of cells. In the process, they have also found a potential new cancer drug development target.

Brenda Schulman, PhD, Daniel Scott, PhD, and Julie MondaThe discovery involves a chemical known as an acetyl group. About 40 to 80 percent of human proteins have this chemical added to the amino acid at one end of the protein during a process known as N-terminal acetylation. Although it has long been recognized that proteins are N-terminally acetylated, until now it was unknown how that process could serve specific functions.

The researchers showed that much like a key must fit precisely to work a lock, the acetylated end of one enzyme fits perfectly into a deep pocket on the surface of another protein. The connection helps accelerate the activity of a protein complex that is involved in regulating cell division and that has been linked to cancer. The research appeared in the journal Science.

The findings have potential implications for drug discovery and for understanding basic mechanisms governing the interaction of possibly thousands of proteins, said Schulman, who is also a Howard Hughes Medical Institute investigator.

“The work presents a major new concept in protein-protein interactions,” she said. “This raises the question of whether similar ‘keys’ on thousands of different proteins also unlock doors to allow them to function.”

Brain tumor research yields new treatment options

St. Jude investigators have pioneered a new approach to drug development and have identified dozens of potential new treatments for ependymoma, a rare tumor of the brain and spine.

The new system combines the latest drug screening technology with the first accurate laboratory model of the tumor.

Using the method, researchers have identified new and existing drugs as possible ependymoma treatment candidates. The drugs were identified by screening 5,303 existing medicines, natural products and other compounds for activity against the tumor, which affects children and adults.

The list of candidate drugs included 5-fluorouracil (5-FU), which has been widely used to treat adult cancers but has not been formally tested against ependymoma.

Based on study results, St. Jude is now planning a clinical trial of 5-FU in young ependymoma patients, said senior author Richard Gilbertson, MD, PhD, Comprehensive Cancer Center director.

The work was published recently in the scientific journal Cancer Cell.

Researchers hope to use the same system to expand chemotherapy options for patients with other cancers. Rather than waiting years for clinical trial results, this system promises to take just months to provide key information about a drug’s effectiveness and optimal administration.

 

Study addresses survivors’ neuromuscular problems

Kirsten Ness, PhD, of St. Jude Epidemiology and Cancer Control, is principal investigator of research that is spurring efforts to address the neuromuscular problems of some cancer survivors.

Kirsten Ness, PhDIn a study recently published in the journal Cancer, Ness and her colleagues found that high doses of two drugs widely used to treat children with acute lymphoblastic leukemia (ALL) left nearly half of adult survivors in their mid-30s with walking, balance and other limitations typical of someone decades older.

The study is the first to document the association between high doses of methotrexate and the muscle, joint and nerve problems that affect some long-term survivors of childhood ALL. Adult survivors whose treatment included high cumulative doses of the drug vincristine were also identified as being at increased risk of reduced ankle flexibility, reduced leg strength and difficulty walking.

The information was collected as part of the St. Jude LIFE study that provides ongoing clinical follow-up to thousands of St. Jude cancer survivors.

“These survivors do not complain of pain or numbness, but many have evidence of a mild motor neuropathy that affects their ability to walk and leaves them at risk for a variety of problems later in life,” Ness said.

Simple stretching and strengthening exercises may help ease the problems, she added.

 

Nasal flu vaccine safe for young cancer patients

New St. Jude research demonstrates that both the flu shot and the nasal vaccine are safe for use in young cancer patients. The finding is important because the influenza virus poses a severe risk to cancer patients with immune systems weakened by their disease and treatment. Flu can also cause life-threatening illness and delay chemotherapy.

The new findings will not change recommendations that pediatric cancer patients receive flu shots, which deliver a vaccine made from killed flu viruses, rather than nasal vaccines, which use a different form of influenza virus to trigger a protective immune response. But the research should ease any lingering concerns that pediatric cancer patients will contract flu following direct or indirect exposure to the nasal vaccine.

The vaccine, which is marketed as FluMist, uses live, but weakened flu virus to trigger protection.

The study is the largest yet to compare the safety of the two flu vaccines. Patricia Flynn, MD, Infectious Diseases, was senior author of a paper on this topic, which appeared in the Journal of Infectious Diseases.

 
Cover of inaugural issue of Promise magazine

Let us eat cake

Both Promise magazine and St. Jude Children’s Research Hospital are celebrating anniversaries. This is the 50th issue of Promise, which was launched in 1998. This year, the hospital also celebrates a monumental milestone—five decades of finding cures and saving children. Look for a special issue marking the hospital’s anniversary in April of this year…and go ahead: Celebrate!

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Outreach program is national model

A marquee outreach program developed at St. Jude is a national model for raising awareness about sickle cell disease, the world’s most prevalent genetic disorder.

Approximately one in 12 African Americans has sickle cell trait. Sickle cell disease is also prevalent among those of Caribbean, Latin American, Mediterranean or Middle Eastern descent.

The Know Your Sickle Status program, or K.Y.S.S., provides free educational programs and screenings to families affected by sickle cell trait and sickle cell disease. K.Y.S.S. offers awareness education to at-risk populations, particularly teenagers and young adults.

“If one parent has sickle cell trait and the other parent has sickle cell trait or any other abnormal hemoglobin trait, the couple has a one-in-four chance of having a child with sickle cell disease. That’s why it is important for people to know their status,” said Yvonne Carroll, RN, director of Patient Services in St. Jude Hematology.

Coordinated by Charlotte Hoyle of Hematology, the peer education component of K.Y.S.S. targets African-American teenagers and young adults who are at risk for having children with sickle cell disease. St. Jude has one of the largest sickle cell centers in the country. Approximately 800 patients, from infants to teenagers, are treated at the center.

To access sickle cell resources and materials at St. Jude, visit www.stjude.org/sicklecell.

 

Hormone research may lead to more targeted drug development

Research led by St. Jude scientists advances a strategy for taming the side effects and enhancing the benefits of steroids and other medications that work by disrupting the activity of certain hormones.

The approach relies on a small molecule developed at St. Jude. In this study, scientists showed that a compound known as SJ-AK selectively blocked the activity of genes in a cell signaling pathway regulated by thyroid hormone. SJ-AK also affected cells growing in the laboratory, reducing cell proliferation as well as the production and secretion of a growth hormone regulated by thyroid hormone.

The research appeared in the journal ACS Chemical Biology.

The findings raise hope that compounds like SJ-AK will lead to drugs with more tailored effects by selectively controlling signaling pathways that switch genes on and off.

“This study offers the first evidence that it is possible to shut down a portion of the signaling network activated by a particular hormone,” said the study’s senior author, R. Kiplin Guy, PhD, chair of Chemical Biology and Therapeutics at St. Jude.

Such selectivity could lead to a new generation of medications with greater effectiveness and fewer side effects. The new treatments could include steroids that fight leukemia or suppress the inflammation associated with autoimmune disorders without affecting metabolism or bone strength.

Source: St Judes’s newsletter

Subclinical Atrial Fibrillation Seems Associated with Increased Stroke Risk .

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Subclinical episodes of atrial fibrillation (AF) predict a significantly increased risk for stroke, according to an international study in the New England Journal of Medicine.

Researchers recruited some 2600 patients aged 65 and over who’d just received a pacemaker or an implantable cardioverter-defibrillator. None had previous episodes of clinical AF. By 3 months, the devices detected subclinical episodes of AF (a heart rate of 190 or more per minute and lasting longer than 6 minutes) in about 10% of patients. Over a mean follow-up of 2.5 years, those with subclinical AF had more than twice the risk for ischemic stroke or systemic embolism as those without subclinical AF.

Asked to comment, Journal Watch Cardiology‘s Dr. Mark Link writes: “Although the current findings are by no means definitive for guiding anticoagulation decisions, they do support taking device-documented subclinical AF seriously. If an asymptomatic patient’s CHADS2 score is high and subclinical episodes are frequent or prolonged, I would consider anticoagulation.”

source:NEJM

Worm seeks worm: Researchers find chemical cues driving aggregation in nematodes.

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Scientists have long seen evidence of social behavior among many species of animals, both on the earth and in the sea. Dolphins frolic together, lions live in packs, and hornets construct nests that can house a large number of the insects. And, right under our feet, it appears that nematodes—also known as roundworms—are having their own little gatherings in the soil. Until recently, it was unknown how the worms communicate to one another when it’s time to come together. Now, however, researchers from the California Institute of Technology (Caltech) and the Boyce Thompson Institute at Cornell University have identified, for the first time, the chemical signals that promote aggregation.

“We now have an expanded view of a very fundamental type of communication, which is recognizing other members of the same species and getting together with them,” says Jagan Srinivasan, a senior research fellow in biology at Caltech and lead author of the study detailing this process, which was published in the January issue of PLoS Biology.

The researchers looked at the lab-friendly Caenorhabditis elegans worm—a relatively safe version of the phylum, whose parasitic cousins include hookworms, whipworms, and trichinas, which cause trichinosis—to gather data.

According to Paul Sternberg, Thomas Hunt Morgan Professor of Biology at Caltech and a corresponding author on the paper, nearly 25 percent of the world’s human population is infected with some type of parasitic nematode; animals and plants can fall prey to the nasty worms, too. Since nematode parasites live inside a host and attack it internally, knowing how the worms communicate via chemicals could be very important to the fields of biomedicine and agriculture.

“One of the ways to eradicate them would be to have some sort of a chemical that can attract them in order to kill them more efficiently,” explains Srinivasan.

Sternberg and Srinivasan are not new to the idea of chemical signaling among C. elegans. In 2008, their research showed how the worms secrete chemicals as a sexual attractant. This time, they worked to find chemical cues that control the social behavior of aggregation. What they found is a complex “language,” in which the worms combine different chemicals into compounds, building a molecular library of signals that regulate behavior. They did this by testing a previously identified family of chemicals in mutant worms—made to not produce the chemicals on their own—to measure the behavioral effects of the different chemical combinations.

“We’re starting to get a hold on the chemical ‘alphabet’ that makes up these words, which have different meanings in different social contexts,” says Srinivasan. “It’s a modular code that tells us that within the physiology of the organism, there is a lot going on in terms of how the environment is interpreted and read out for social communication.”

For example, one class of chemicals the researchers found encourages worm-to-worm company, while a different class of compounds being expressed at the same time keeps other worms away. This suggests that the worms release different amounts of each compound based on what each worm is trying to communicate. If the worm is starting a new colony, it probably just wants a certain number of worms around to find and share food—too many and the colony may not thrive. However, if there is a big piece of fruit, the worm may call on a large group to help access the food source.

“The amazing thing here is that for one chemical, if it’s modified even just a little bit, the meaning is changed,” says Sternberg, who is also an investigator with the Howard Hughes Medical Institute. “That’s what makes it more like a language. If I say a Chinese word, and my intonation is wrong, the word has a different meaning.”

Next, the team will explore whether or not the same chemical compounds are made by other nematodes. They will also work to figure out how the worms’ nervous system senses and sorts the different compounds.

“Understanding the worm’s language is just a first step,” says Srinivasan. “We hope that by learning more about how social recognition occurs in the worm nervous system, we can eventually provide insights into how the human brain encodes social information, too.”

Source:PLoS Biology.

 

 

 

Frequent red meat eaters at higher risk of stroke.

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A high-protein diet might benefit health in some ways, but depending on what kind of protein a person consumes, it could raise their stroke risk too, suggests a large new study that finds eating lots of red meat ups the likelihood of having a stroke while poultry lowers it.

“The main message from this paper is that the type of protein or the protein package is really important for the risk of stroke. We have to consider protein in the context of the foods,” said Dr. Frank Hu, a professor at the Harvard School of Public Health and one of the authors of the study.

He and his colleagues collected data from two massive health surveys that tracked tens of thousands of men and women from roughly middle age to their senior and elderly years.

Over 20-some years of the study, nearly 1,400 men and more than 2,600 women had a stroke.

Caused by a blood clot or a burst blood vessel that stops blood flow to the brain, stroke is the third most common cause of death in the United States. Twenty-six out of every 1,000 people in the U.S. have experienced a stroke, according to the Centers for Disease Control and Prevention, and about 800,000 die of stroke each year.

To see what influence different types of dietary protein have on stroke risk, the researchers divided up the people in the study based on how much red meat, poultry, fish, dairy and other sources of protein they typically ate each day.

Men who ate more than two servings of red meat each day — which was at the high end of the meat eaters — had a 28 percent increased risk of stroke compared to men who averaged about a third of a serving of red meat each day, the low end of the red meat eaters.

The researchers considered a serving of red meat as four to six ounces of beef or a hamburger patty.

Women who ate nearly two servings of red meat a day had a 19 percent higher risk of stroke than women who ate less than half a serving each day.

A 19 percent increase in stroke risk means that instead of 26 out of every 1,000 people having a stroke, 31 out of every 1,000 people would have one.

The researchers also looked at the change in stroke risk that would come with substituting different forms of protein for one daily serving of red meat: swapping in one serving a day of poultry lowered stroke risk by 27 percent, a serving of nuts or fish was linked to a 17 percent drop in risk and a serving of dairy dropped the risk by 10 to 11 percent.

Dr. Adam Bernstein, the lead author of the study and a researcher at the Cleveland Clinic, said he was not surprised to see that red meat eaters suffer more strokes.

“We’ve also done work on red meat and diabetes and red meat and coronary heart disease. So it makes sense that these cardio-metabolic diseases are grouped together,” Bernstein told Reuters Health.

An earlier study, led by Susanna Larsson at the Karolinska Institute in Stockholm, Sweden, also found that eating red meat had a link to stroke risk (see Reuters Health story of December 31, 2010).

What was new in the current study, Larsson said, was that frequent poultry eaters showed a lowered risk of stroke.

People who ate the most chicken or turkey each day — about a half serving for women and three-quarters of a serving for men — had a 13 percent reduced risk of stroke compared to those who ate barely more than a serving a day.

One serving was considered four ounces.

“I do not think that poultry has been considered as a protein source that might lower the risk of stroke. This is new,” Larsson told Reuters Health in an email.

Also surprising in the study was that fish seemed to offer no protection against stroke.

Larsson pointed out that earlier work has found fewer strokes among groups who eat fish often.

It’s possible that the benefits of fish depend on how it’s served, Bernstein said.

“There’s a lot of variation in how people cook and prepare fish, and we couldn’t get down to that level,” he said.

The researchers didn’t prove that beef is to blame for the increased number of strokes, but Bernstein said it could be that the fat and iron in red meat play a role.

Larsson said the findings support current recommendations to limit how much red meat people eat, and to opt for chicken and fish instead.

Source:Stroke.