Day: 02/01/2012

Side Effects of Bone Marrow and Stem Cell Transplantation.

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Although it is an effective treatment for several types of cancer, bone marrow and stem cell transplantation—like other cancer treatments—can cause side effects. The types and intensity of side effects vary from person to person and with the type of transplant, the person’s health, and other factors.

Doctors and scientists are continually working to identify treatment methods that have fewer side effects. Your health care team will work with you to ease or prevent any side effects that occur. This is called symptom management or supportive care. Be sure to talk with your health care team about any symptoms you experience, including new symptoms or a change in symptoms.

Side effects of bone marrow and stem cell transplantation include the following.

Infection

We live in a world surrounded by living microscopic organisms, including bacteria, viruses, and fungi. Many of these are beneficial, but some are dangerous, even for people with a healthy immune system. The chemotherapy and/or radiation therapy given before stem cell transplantation weakens the patient’s immune system, lowering the body’s defenses against these organisms. Stem cell recipients are, therefore, especially vulnerable to infection during this early period of treatment.

One common misconception is that the greatest risk of early infection comes from outside the patient’s own body—from visitors, foods, and other sources. However, this is not true. Most infections that occur during the first few weeks of a transplant are due to organisms that are already in the patient’s body, hiding in places such as the lung, sinuses, skin, and the intestines. They cause infection during a period of low immunity. Fortunately, most of these infections are relatively easy to treat with modern antibiotics. The reduced immunity of the early transplant period lasts about two weeks, after which the immune system is back to near full-fighting strength and can keep most common germs at bay without the help of medications. This is true for both autologous (AUTO) and allogeneic (ALLO) transplant recipients.

However, a risk of serious infection remains for recipients of ALLO transplants beyond the first month. This risk occurs because ALLO transplant recipients are given anti-rejection drugs (medications that suppress the immune system to prevent the body from rejecting the donor’s stem cells). The risk of infection increases when more anti-rejection drugs are needed.

Graft-versus-host disease

Patients who have an ALLO transplant (which uses stem cells from another person) are at risk of developing a unique type of post-transplant illness called graft-versus-host disease (GVHD). It occurs when the transplanted stem cells recognize the patient’s body as foreign and attack it, causing inflammation. GVHD ranges from mild to life-threatening. AUTO transplant recipients do not face this risk.

Fortunately, donor stem cells that are 100% matched to those of the patient rarely cause this problem, and doctors have medications that can prevent the development of GVHD; every patient receives these preventive anti-rejection medications. However, if the donor is less than a perfect match, or in rare cases when the match is 100%, GVHD can develop and make the patient ill. When this happens, the patient is given more anti-rejection medicines to treat the GVHD, but this increases the risk of infection.

GVHD is a double-edged sword, potentially helping or hurting the patient. At its worst, it can be fatal. However, in moderation, GVHD can be lifesaving because the transplanted cells have the ability to recognize and kill resistant cancer cells that may have escaped the chemotherapy and/or radiation treatment. Therefore, mild GVHD can ultimately lead to the cure of the patient. In fact, this is the primary way that ALLO transplantation cures cancers like leukemia.

There are two types of GVHD, both of which can occur with varying degrees of severity:

Acute GVHD (AGVHD). This form of the disease typically occurs within the first three months after an ALLO transplant, typically affecting the skin, intestines, and liver. Patients develop rashes, diarrhea, and jaundice (yellowing of the skin and the whites of the eyes) as each organ system is affected. Treatment consists of medications that block T cells (a type of white blood cell that helps the body’s immune system fight infection).

Chronic GVHD (CGHVD). This form typically occurs more than three months after an ALLO transplant, and it can last a few months or a lifetime. It may be clinically “silent,” producing no symptoms and requiring no specific therapy. Or it may become a source of medical problems needing regular medical attention and treatment. Symptoms may be mild (including dry eyes, dry mouth, and blood test abnormalities that indicate a slightly irritated liver) or more severe (including loss of skin elasticity, known as scleroderma; muscle and joint pains; weight loss; and difficulty breathing).

Doctors try to prevent severe GVHD from occurring. This is best accomplished by finding stem cells that best match those of the patient and by using preventive drugs during the first three to six months after the transplant.

Other common side effects

In addition to infection and GVHD, other side effects may occur during a transplant, often related to the destruction of the original bone marrow, the chemotherapy, or the radiation therapy. These include fatigue, mouth sores, sore throat, diarrhea, nausea and vomiting, low blood count, loss of hair, changes in skin pigmentation, rash, cataracts, sexual side effects, and infertility. The type, quantity, and severity of side effects often vary from patient to patient, depending on the patient’s health, the amount of previous treatment, and the type of transplant received. These side effects can usually be managed through medication and go away over time.

Almost any part of the body has the potential to be affected in some way by the transplant process. Doctors will monitor a patient’s recovery using a variety of tests, including those for the liver, kidneys, lungs, heart, and other organs. There is a risk of some permanent side effects from a bone marrow transplant, including infertility (the inability to have children) and cataracts (a clouding of the lens of the eye). Talk with your doctors about the possible short-term and long-term effects you may experience before having a bone marrow transplant, as compared with the risks and benefits of other available treatment options.

Source:Cancer.net

 

 

Mom’s Love Good for Child’s Brain.

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School-age children whose mothers nurtured them early in life have brains with a larger hippocampus, a key structure important to learning, memory and response to stress.

The new research, by child psychiatrists and neuroscientists at Washington University School of Medicine in St. Louis, is the first to show that changes in this critical region of children’s brain anatomy are linked to a mother’s nurturing.

Their research is published online in the Proceedings of the National Academy of Sciences Early Edition.

“This study validates something that seems to be intuitive, which is just how important nurturing parents are to creating adaptive human beings,” says lead author Joan L. Luby, MD, professor of child psychiatry. “I think the public health implications suggest that we should pay more attention to parents’ nurturing, and we should do what we can as a society to foster these skills because clearly nurturing has a very, very big impact on later development.”

The brain-imaging study involved children ages 7 to 10 who had participated in an earlier study of preschool depression that Luby and her colleagues began about a decade ago. That study involved children, ages 3 to 6, who had symptoms of depression, other psychiatric disorders or were mentally healthy with no known psychiatric problems.

As part of the initial study, the children were closely observed and videotaped interacting with a parent, almost always a mother, as the parent was completing a required task, and the child was asked to wait to open an attractive gift. How much or how little the parent was able to support and nurture the child in this stressful circumstance — which was designed to approximate the stresses of daily parenting — was evaluated by raters who knew nothing about the child’s health or the parent’s temperament.

“It’s very objective,” Luby says. “Whether a parent was considered a nurturer was not based on that parent’s own self-assessment. Rather, it was based on their behavior and the extent to which they nurtured their child under these challenging conditions.”

The study didn’t observe parents and children in their homes or repeat stressful exercises, but other studies of child development have used similar methods as valid measurements of whether parents tend to be nurturers when they interact with their children.

For the current study, the researchers conducted brain scans on 92 of the children who had had symptoms of depression or were mentally healthy when they were studied as preschoolers. The imaging revealed that children without depression who had been nurtured had a hippocampus almost 10 percent larger than children whose mothers were not as nurturing.

“For years studies have underscored the importance of an early, nurturing environment for good, healthy outcomes for children,” Luby says. “But most of those studies have looked at psychosocial factors or school performance. This study, to my knowledge, is the first that actually shows an anatomical change in the brain, which really provides validation for the very large body of early childhood development literature that had been highlighting the importance of early parenting and nurturing. Having a hippocampus that’s almost 10 percent larger just provides concrete evidence of nurturing’s powerful effect.”

Luby says the smaller volumes in depressed children might be expected because studies in adults have shown the same results. What did surprise her was that nurturing made such a big difference in mentally healthy children.

“We found a very strong relationship between maternal nurturing and the size of the hippocampus in the healthy children,” she says.

Although 95 percent of the parents whose nurturing skills were evaluated during the earlier study were biological mothers, the researchers say that the effects of nurturing on the brain are likely to be the same for any primary caregiver — whether they are fathers, grandparents or adoptive parents.

The fact that the researchers found a larger hippocampus in the healthy children who were nurtured is striking, Luby says, because the hippocampus is such an important brain structure.

When the body faces stresses, the brain activates the autonomic nervous system, an involuntary system of nerves that controls the release of stress hormones. Those hormones help us cope with stress by increasing the heart rate and helping the body adapt. The hippocampus is the main brain structure involved in that response. It’s also key in learning and memory, and larger volumes would suggest a link to improved performance in school, among other things.

Past animal studies have indicated that a nurturing mother can influence brain development, and many studies in human children have identified improvements in school performance and healthier development in children raised in a nurturing environment. But until now, there has not been solid evidence linking a nurturing parent to changes in brain anatomy in children.

“Studies in rats have shown that maternal nurturance, specifically in the form of licking, produces changes in genes that then produce changes in receptors that increase the size of the hippocampus,” Luby says. “That phenomenon has been replicated in primates, but it hasn’t really been clear whether the same thing happens in humans. Our study suggests a clear link between nurturing and the size of the hippocampus.”

She says educators who work with families who have young children may improve school performance and child development by not only teaching parents to work on particular tasks with their children but by showing parents how to work with their children.

“Parents should be taught how to nurture and support their children,” Luby says. “Those are very important elements in healthy development.”

 

Source:NIH

 

Give Your Kids a Smoke-Free Childhood.

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According to the U.S. Surgeon General, there is no safe level of exposure to secondhand smoke. Even brief moments around smoke can be harmful to a person’s health. Exposure to secondhand smoke is especially unsafe for infants and children because their bodies and lungs are still developing and growing. Yet, more than half of all young children in the United States are exposed to secondhand smoke.

What is secondhand smoke?

Secondhand smoke refers to both the smoke exhaled from a smoker’s lungs and the smoke from a burning cigarette, cigar, or pipe. When a non-smoker inhales (breathes in) secondhand smoke, it is called passive smoking or involuntary smoking.

Inhaling secondhand smoke is like you are actually smoking. Many of the harmful substances in tobacco stay in the air; if you inhale them, they go into your lungs and bloodstream. Secondhand smoke is a poisonous cocktail of hundreds of chemicals proven to harm human health, including more than 60 substances known to cause cancer, such as lead, carbon monoxide, arsenic, ammonia, formaldehyde, and a type of cyanide.

Health risks to children from secondhand smoke

Research shows that secondhand smoke increases children’s risk of a variety of health problems. In fact, the U.S. Surgeon General has stated that secondhand smoke causes premature death and disease in children and adults who do not smoke. For children, secondhand smoke exposure raises the risk of the following conditions:

  • Ear infections
  • Asthma attacks
  • Lung infections, such as bronchitis and pneumonia
  • Coughing and wheezing
  • Sudden Infant Death Syndrome (SIDS)
  • Heart disease
  • Cancer

Ongoing research continues to find additional links between secondhand smoke and children’s well-being, including evidence of links to mental health issues and problems with children’s ability to learn.

Protecting your children from secondhand smoke

The only way to fully protect children from secondhand smoke is to make sure they are not around people who are smoking, especially indoors. Strategies like opening windows, using a fan, or turning on an air conditioner do not work. This is why many states have banned smoking in restaurants and other public buildings.

Here are some ways you can protect your family from secondhand smoke:

  • Keep your home and car smoke-free. This includes making sure family, friends, and visitors never smoke inside your house or vehicle.
  • Make sure the places where your child spends time—such as daycare, school, or after-school programs—do not allow smoking.
  • Ask caregivers and relatives not to smoke around your children.
  • Keep your family away from places that allow smoking inside. For instance, eat in restaurants that are smoke-free. Non-smoking sections do not protect from secondhand smoke.
  • If you are pregnant, avoid being around people who are smoking.
  • If you smoke, consider quitting. In addition to the potential effects on your children, smoking is harming your own health. Quitting can be difficult, but there are many resources to help you, including talking with your doctor about how to quit smoking.

Keeping your children away from secondhand smoke may have the added benefit of preventing your children from becoming smokers themselves. One study showed that children of smokers are less likely to start smoking if their parents routinely sit in smoke-free areas of public places. Not smoking in the home also helps prevent teen smoking, the study found.

Source:Cancer.net

 

A Novel Cause of Food Poisoning — Something’s Fishy.

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A recently described marine parasite, acquired through ingestion of raw fish, was identified as the cause of several foodborne illness outbreaks in Japan.

Outbreaks of an unidentified foodborne illness associated with the consumption of raw fish, but of unknown etiology, have increased in Japan during the past decade. Symptoms — vomiting and diarrhea — typically begin 2 to 20 hours after ingestion of the fish and last about 24 hours. Researchers in Japan recently conducted an investigation of cases reported in that country from 2008 to 2010.

Epidemiologic analysis involving >1300 affected individuals from 24 municipalities implicated a single fish species — Paralichthys olivaceus, the olive flounder — as the food vector. Microscopic examination of P. olivaceus muscle from farm-cultured fish and from remnants of meals ingested by patients revealed six-valved spores consistent with a myxosporan of the family Kudoidae. Genetic analysis implicated Kudoa septempunctata, a parasite recently identified as a new species after its isolation from P. olivaceus muscle. In animal-infection experiments, spores obtained from the farmed-fish and outbreak samples caused diarrhea in suckling mice and emesis in house musk shrews.

Comment: Consumption of raw fish in the forms of sushi and sashimi originated in Japan but has become popular worldwide. Wild fish harbor a variety of parasites, many of which are not macroscopically visible. Aquaculture facilitates transfer of parasites and other disease-causing agents among fish, and the international trade in farmed fish can easily spread such agents worldwide. K. septempunctata has already been detected in olive flounder imported to Japan from Korea,; spread to other countries is a certainty.

Source: Journal Watch Infectious Diseases

1 Million Birth Control Pill Packs Recalled.

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Pregnancy Risk With Lo/Ovral-28, Generic Norgestrel/Ethinyl Estradiol

Pfizer has recalled 1 million packs of Lo/Ovral-28 and generic norgestrel/ethinyl estradiol birth control pills.

The pills, which must be taken in the correct sequence, may be mixed up. Women using the products risk pregnancy and should consult their doctors.

Although the pills are made and packaged by Pfizer, they are sold by Akrimax Rx Products and carry the Akrimax name on their labels.

The recall includes 14 lots of brand-name birth control pills and 14 lots of generic birth control pills distributed across the U.S.

The pills come in blister packs of 28 pills from which each dose must be taken in sequence. A Pfizer investigation found that some packs have the wrong number of pills, and the pills may be out of order.

Each pack normally contains 21 white pills with an active ingredient and seven pink pills that are inert. But women who take inert pills on days they should be taking active ones may not get the contraceptive effect they want, and should be aware of the signs of early pregnancy.

Other than pregnancy, the recalled pills have no health risks other than those usual for the product.

Pfizer has corrected the error. Meanwhile, the following product lots are being recalled:

 

NDC Product Lot Expiration Configuration/Count
24090-801-84 LO/OVRAL® 28 E15678 08/31/2013 6 Pilpacks® of 28 tablets each
24090-801-84 LO/OVRAL® 28 E15679 08/31/2013 6 Pilpacks® of 28 tablets each
24090-801-84 LO/OVRAL® 28 E15686 08/31/2013 6 Pilpacks® of 28 tablets each
24090-801-84 LO/OVRAL® 28 E15687 01/31/2014 6 Pilpacks® of 28 tablets each
24090-801-84 LO/OVRAL® 28 E15690 01/31/2014 6 Pilpacks® of 28 tablets each
24090-801-84 LO/OVRAL® 28 E15698 01/31/2014 6 Pilpacks® of 28 tablets each
24090-801-84 LO/OVRAL® 28 E15700 02/28/2014 6 Pilpacks® of 28 tablets each
24090-801-84 LO/OVRAL® 28 E80434 07/31/2013 6 Pilpacks® of 28 tablets each
24090-801-84 LO/OVRAL® 28 E80438 08/31/2013 6 Pilpacks® of 28 tablets each
24090-801-84 LO/OVRAL® 28 F36908 02/28/2014 6 Pilpacks® of 28 tablets each
24090-801-84 LO/OVRAL® 28 F36909 02/28/2014 6 Pilpacks® of 28 tablets each
24090-801-84 LO/OVRAL® 28 F43915 03/31/2014 6 Pilpacks® of 28 tablets each
24090-801-84 LO/OVRAL® 28 F43926 03/31/2014 6 Pilpacks® of 28 tablets each
24090-801-84 LO/OVRAL® 28 F43927 03/31/2014 6 Pilpacks® of 28 tablets each
24090-961-84 Norgestrel 0.3 mg/Ethinyl Estradiol 0.03 mg E15677 08/31/2013 6 Pilpacks® of 28 tablets each
24090-961-84 Norgestrel 0.3 mg/Ethinyl Estradiol 0.03 mg E15704 01/31/2014 6 Pilpacks® of 28 tablets each
24090-961-84 Norgestrel 0.3 mg/Ethinyl Estradiol 0.03 mg E15706 01/31/2014 6 Pilpacks® of 28 tablets each
24090-961-84 Norgestrel 0.3 mg/Ethinyl Estradiol 0.03 mg E80440 08/31/2013 6 Pilpacks® of 28 tablets each
24090-961-84 Norgestrel 0.3 mg/Ethinyl Estradiol 0.03 mg F16388 01/31/2014 6 Pilpacks® of 28 tablets each
24090-961-84 Norgestrel 0.3 mg/Ethinyl Estradiol 0.03 mg F16390 02/28/2014 6 Pilpacks® of 28 tablets each
24090-961-84 Norgestrel 0.3 mg/Ethinyl Estradiol 0.03 mg F22132 02/28/2014 6 Pilpacks® of 28 tablets each
24090-961-84 Norgestrel 0.3 mg/Ethinyl Estradiol 0.03 mg F31330 02/28/2014 6 Pilpacks® of 28 tablets each
24090-961-84 Norgestrel 0.3 mg/Ethinyl Estradiol 0.03 mg F36911 03/31/2014 6 Pilpacks® of 28 tablets each
24090-961-84 Norgestrel 0.3 mg/Ethinyl Estradiol 0.03 mg F36913 03/31/2014 6 Pilpacks® of 28 tablets each
24090-961-84 Norgestrel 0.3 mg/Ethinyl Estradiol 0.03 mg F43924 03/31/2014 6 Pilpacks® of 28 tablets each
24090-961-84 Norgestrel 0.3 mg/Ethinyl Estradiol 0.03 mg F43925 03/31/2014 6 Pilpacks® of 28 tablets each
24090-961-84 Norgestrel 0.3 mg/Ethinyl Estradiol 0.03 mg F43934 03/31/2014 6 Pilpacks® of 28 tablets each
24090-961-84 Norgestrel 0.3 mg/Ethinyl Estradiol 0.03 mg F53238 03/31/2014 6 Pilpacks® of 28 tablets each

 

Women who have used the products should notify their doctors and return the products to their pharmacies.

Source:webMD

Incidence, prevalence, and survival of chronic pancreatitis: a population-based study.

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Population-based data on chronic pancreatitis (CP) in the United States are scarce. We determined incidence, prevalence, and survival of CP in Olmsted County, MN.
METHODS: Using Mayo Clinic Rochester`s Medical Diagnostic Index followed by a detailed chart review, we identified 106 incident CP cases from 1977 to 2006 (89 clinical cases, 17 diagnosed only at autopsy); CP was defined by previously published Mayo Clinic criteria. We calculated age- and sex-adjusted incidence (for each decade) and prevalence rate (1 January 2006) per 100,000 population (adjusted to 2000 US White population). We compared the observed survival rate for patients with expected survival for age- and sex-matched Minnesota White population.
RESULTS: Median age at diagnosis of CP was 58 years, 56% were male, and 51% had alcoholic CP. The overall (clinical cases or diagnosed only at autopsy) age- and sex-adjusted incidence was 4.05/100,000 person-years (95% confidence interval (CI) 3.27-4.83). The incidence rate for clinical cases increased significantly from 2.94/100,000 during 1977-1986 to 4.35/100,000 person-years during 1997-2006 (P<0.05) because of an increase in the incidence of alcoholic CP. There were 51 prevalent CP cases on 1 January 2006 (57% male, 53% alcoholic). The age- and sex-adjusted prevalence rate per 100,000 population was 41.76 (95% CI 30.21-53.32). At last follow-up, 50 patients were alive. Survival among CP patients was significantly lower than age- and sex-specific expected survival in Minnesota White population (P<0.001).
CONCLUSIONS: Incidence and prevalence of CP are low, and approximately 50% are alcohol related. The incidence of CP cases diagnosed during life is increasing. Survival of CP patients is lower than in the Minnesota White population.

Source:AJG

 

 

Tranexamic acid for upper gastrointestinal bleeding.

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Tranexamic acid reduces haemorrhage through its antifibrinolytic effects. In a previous version of the present review, we found that tranexamic acid may reduce mortality. The present review includes updated searches of randomised trials on tranexamic acid versus placebo, cimetidine or lansoprazole.
OBJECTIVES: To assess the effects of tranexamic acid for upper gastrointestinal bleeding. SEARCH
METHODS: Electronic searches (The Cochrane Library, MEDLINE, EMBASE, Science Citation Index) and manual searches were combined. The last search update was in October 2011.
SELECTION CRITERIA: Trials in which patients with upper gastrointestinal bleeding were randomised to receive either tranexamic acid or placebo, or any anti-ulcer drug, were included.
DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. All-cause mortality was the primary outcome measure. Random-effects model meta-analyses were performed and results presented as relative risks (RR) with 95% confidence intervals (CI). Subgroup, sensitivity, regression and sequential analyses were performed to analyse sources of intertrial heterogeneity and the robustness of the overall result.
MAIN RESULTS: Seven double blind randomised trials on tranexamic acid versus placebo, cimetidine, or lanzoprazole were included. One trial offered endoscopic treatment to all patients that were randomised. Random-effects model meta-analysis found that tranexmic acid reduced mortality compared with placebo (41 of 829 versus 68 of 825 patients; RR: 0.61, 95% CI 0.42 to 0.89). The beneficial effect was not confirmed in subgroup analysis stratified for the quality of bias control, in worst case scenario analyses (in which 21% of the randomised patients were excluded), or in sequential analyses. No significant differences were found between tranexamic acid and placebo on bleeding, surgery, or transfusion requirements. No clear effects of tranexamic acid were identified in trials using endoscopic therapy or in the trials comparing tranexamic acid with cimetidine or lansoprazole. In the tranexamic acid group, five cases of serious thromboembolic events occurred (myocardial infarction, pulmonary embolism, and cerebral infarction). Overall, the number of patients with any thrombotic event was not significantly increased in the tranexamic acid group (RR 1.87, 95% CI 0.60 to 5.85).
AUTHORS’ CONCLUSIONS: Considering the internal and external validity of the evidence, tranexamic acid cannot be recommended for routine use. Additional trials in which tranexamic acid is used in combination with the currently recommended interventions are required.

Source:Cochrane library.

 

Randomized trial of dual antibody induction therapy with steroid avoidance in renal transplantation.

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Given our previous experience using dual-induction therapy with antithymocyte globulin (ATG)/daclizumab (Dac) (each with fewer doses than if used alone), we chose to compare two distinct dual-induction strategies.
METHODS: Single-center, open-label randomized trial of 200 primary kidney transplant recipients was performed: (group I, n=100) ATG/Dac (3 ATG, 2 Dac doses) versus (group II, n=100) ATG/alemtuzumab (1 dose each), with maintenance consisting of reduced tacrolimus dosing (rTd), enteric-coated mycophenolate sodium (EC-MPS), and early corticosteroid withdrawal. One half of standard EC-MPS dosing was targeted in group II to avoid severe leukopenia previously seen with alemtuzumab. The goal in both arms was to achieve rapid and effective lymphocyte depletion while simultaneously allowing reduced maintenance immunosuppression. Primary endpoint was the incidence of biopsy-proven acute rejection (BPAR).
RESULTS: With median follow-up of 38 months, there were no differences in BPAR rates: 14 of 100 vs. 13 of 100 (including borderline) and 10 of 100 vs. 9 of 100 (excluding borderline) in groups I and II, respectively (nonsignificant). Actuarial patient/graft survival at 48 months was 96%/91% in group I vs. 92%/83% in group II (N.S.). Mean estimated glomerular filtration rate (+/-standard error) at 36 months was 72.1+/-3.3 vs. 67.5+/-3.3 in groups I and II (N.S.). Greater incidence of leukopenia occurred in group II at month 1 only (P=0.002). Percentages having EC-MPS withheld/discontinued due to leukopenia, gastrointestinal symptoms, and infection were 12 of 100, 7 of 100, and 0 of 100 in group I vs. 19 of 100, 0 of 100, and 2 of 100 in group II, respectively (P=0.01). Rates of new onset diabetes mellitus after transplantation and infections were equally low in both groups (no lymphoproliferative disorders were observed).
CONCLUSIONS: These two distinct dual-induction therapies with rTd, EC-MPS, and planned early corticosteroid withdrawal resulted in favorable rates of BPAR and all secondary outcomes.

Source:Transplantation.

Flu Researcher Ron Fouchier: ‘It’s a Pity That It Has to Come to This’

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In a statement posted today on the Web sites of Nature and Science, a group of 39 influenza researchers announced a 2-month moratorium on studies that make the avian influenza strain H5N1 more transmissible between mammals. The moratorium is intended to allow time for an international debate about this type of research, which some people say has the potential to help bioterrorists.

ScienceInsider talked to Ron Fouchier of Erasmus MC in Rotterdam, the Netherlands, who carried out one of the two studies that triggered the international debate. (His paper is under review at Science.) Fouchier’s answers have been translated from Dutch and edited for clarity and brevity.

Q: Who took the initiative for this announcement?

R.F.: The initiative came from Adolfo Sastre-García [an influenza researcher at Mount Sinai Medical Center in New York City who has a grant from the National Institute of Allergy and Infectious Diseases (NIAID) that funded Fouchier’s study], Yoshihiro Kawaoka [whose H5N1 study, in press at Nature, has also been reviewed by the U.S. National Science Advisory Board for Biosecurity (NSABB)], and myself. We discussed it with a group of about 10 scientists who are doing similar studies themselves; then we asked another 30 or so influenza researchers who are not working on these studies but who could do them, if they wanted to sign. They all agreed wholeheartedly. So it’s not a Fouchier show. It’s an initiative that is supported very broadly.

Q: Why did you take this step now?

R.F.: We were advised by various organizations, and of course we’ve followed the press coverage and the political debates. We had the impression, based partly on advice from third parties, that it would be sensible to announce a moratorium.

Q: Which third parties?

R.F.: The organizations that fund our research, but also governments that we are talking to. So much is happening at the moment that it makes sense to take a break, to give the infectious diseases field time to think this over and talk about how to handle this kind of research in the future. This research offers opportunities and challenges, and governments and organizations need time to react.

Q: Are you doing this because if you don’t, governments might move to halt the research?

R.F.: The debate is so controversial that we can’t rule that out. We’d rather have everybody take a breather to reflect carefully on how to handle this.

Q: But have you received clear signals that there might be a ban of some sort?

R.F.: We don’t have clear signals that something is about to happen, but you see the signals in the press, from experts and advisers, and those signals reach governments as well. We see articles from Michael Osterholm [director of the Center for Infectious Disease Research and Policy at the University of Minnesota, and an influenza expert], and from people like Laurie Garrett, the Pulitzer Prize winning author [and a Senior Fellow for Global Health at the Council on Foreign Relations]. And then there are the biosecurity experts at the University of Pittsburgh, like Thomas Inglesby. … And [smallpox eradication leader] D. A. Henderson has been very vocal . All of these people can have quite an impact on the White House and elsewhere.

Q: How do you feel about the moratorium yourself?

R.F.: It’s a pity that it has to come to this. I would have preferred if this hadn’t caused so much controversy, but it has happened and we can’t change that. So I think it’s the right step to make. It’s comparable to what happened in 1975 at the Asilomar conference. But I think that was driven more by the scientists themselves; this time it’s mostly the public controversies that drive it.

Q: Do you have ideas about how the debate about these studies should be organized and who should participate?

R.F.: I think there has to be a whole series of debates. A couple are on the rails already. As we say in our statement, a meeting will be organized in the next couple of weeks, which I hope will include participation of the World Health Organization (WHO) and the U.S. government. The [American Society for Microbiology] has organized a plenary session at its biodefense meeting next month. The New York Academy of Sciences has a meeting as well. People need to talk, and infectious diseases specialists need to take the microphone and explain why this research is important and how you can do it safely.

Q: Has the scale of the controversy surprised you? Had you expected this when you first discussed the study at a meeting in Malta in September?

R.F.: When we presented this, of course we expected that there would be some commotion, and that we would have to explain to the public and the press why we’re doing this and how you can do it safely.

I think we have done that very well in the Netherlands. We were very proactive; before we submitted the paper for publication we informed all the relevant authorities, so they knew what was happening and had the time to prepare, and when the story started making the rounds in the U.S. media, we spent 3 days talking to newspapers, TV, and radio. And that nipped the debate in the bud. In the U.S., this hasn’t happened. And the people who are the most vocal in the press are the biosecurity experts. It’s a pity that so few people from the flu field have jumped in front of the cameras, especially in the U.S.

Q: Did the NSABB recommendations take you by surprise?

R.F.: Absolutely. This was something that was unprecedented, and something I wasn’t counting on at all.

NSABB has said that the risks outweigh the benefits, and now many people are saying: In that case, you shouldn’t do this research at all. That’s a very logical response. But the infectious disease community doesn’t agree with NSABB on this. What NSABB should explain better is what the risks are exactly. How much bioterrorism have we seen in the past? What are the chances that bioterrorists will recreate these viruses? And is it really true that publication of this research would give bioterrorists or rogue nations an advantage? That’s what I would like to hear from the NSABB.

Q: You think it doesn’t give them an advantage?

R.F.: No. Because bioterrorists can’t make this virus, it’s too complex, you need a lot of expertise. And rogue nations that do have the capacity to do this don’t need our information. So I don’t think they will benefit from this information at all. Meanwhile, NSABB gives very little credit to the public health benefits, while the entire influenza community is crying just how important that is. For them the balance between risk and benefit is very different than for NSABB.

Q: But NSABB has several infectious disease researchers among its members, including Osterholm, who’s an influenza expert himself. And they hired Robert Webster, a flu researcher at St. Jude Children’s Research Hospital in Memphis, as a special adviser.

R.F.: The question is whether that was enough, or whether they should have asked more influenza experts. If they had asked somebody like Peter Palese of Mount Sinai School of Medicine, you would have had a very different answer. If you read his piece in Nature—I think he was totally right.

Osterholm, in his article [published yesterday with Henderson] in Science, has a very fatalistic attitude. He says countries in Asia, Africa, and the Middle East are unable to do surveillance, so they don’t need the data from our paper. That’s too fatalistic. It would be better to say: How can we help those countries set up a decent surveillance system? Osterholm also says that the data make no difference for vaccine development. That’s really based on nothing. So if that is the influenza expert within NSABB, I’d like to see someone with a more positive attitude.

Q: How will the moratorium affect research at your own lab?

R.F.: We were of course working to find out exactly which mutations cause the virus to become transmissible by aerosol. That is going to stop now; we were almost done with that, but not quite. We were working to find out which biological properties of the virus are associated with the mutations that we have found. The biological properties of the virus are really more important than the mutations themselves.

Q: What biological properties are you referring to?

R.F.: In a paper in Current Opinion in Virology, we said we thought there were a number of things that might make an avian influenza virus transmissible between mammals. At the time, that was purely hypothetical. We said the virus probably has to do better in the upper respiratory tract than deep inside the lungs; it must bind to certain mammalian receptors; it has to reproduce in large amounts, to increase chances of transmission; it has to be stable in small droplets, and so on.

Now that we have these mutations, we can look at each of these steps to see if they occur. And you will see that for each step, there are multiple options, more possible mutations than just the ones we have found so far. So that’s very important.

Something else that has to happen is evaluating existing vaccines and antiviral drugs. Until now, we only have looked in vitro whether these virus’s characteristics match existing vaccine strains, and whether the virus is sensitive to antiviral drugs. We haven’t tried it in our animal model yet.

Q: You also want to repeat the experiments with more H5N1 strains?

R.F.: Yes. We did this with one genetic lineage of the H5N1 virus. The question is whether all lineages can become aerosol-transmissible. If they can’t, if it’s just this lineage, perhaps you can focus on the region where it came from and try to stop H5N1 outbreaks there to prevent a pandemic. If it can happen everywhere, you’ve got to work everywhere.

Q: Would you also like to do similar studies in other avian influenza strains, such as H7N7?

R.F.: That is certainly something we’d like to do in the long run. But that has a much lower priority because we’re not seeing H7N7 outbreaks at the moment, and we’re definitely not going to do that anytime soon; I don’t think that would be wise.

Q: Have you had requests from other labs to share the virus you have created?

R.F.: Not explicitly. Everybody understands that this is not the right time to ask.

Q: But if they did ask, what would you do?

R.F.: I have an agreement with our funder, the NIAID, that if such requests were made, I will discuss it with them. So I can’t decide that on my own.

Q: Andrew Pekosz recently told Science that a moratorium would be especially harmful for the young scientists who do the actual lab work. Do you see that as a problem?

R.F.: I think that that is a small problem compared to the other issues. I have a postdoc here, Sander Herfst, who has worked on this extremely hard for 4 years and for whom a terrific breakthrough in his career is on hold. But those are individual cases. I think the repercussions of the NSABB recommendations for the life sciences are much more important. If we get very strict new guidelines for prescreening proposals, I think that could hobble the life sciences for years.

Q: In a policy forum you co-authored and which was published yesterday on Science‘s Web site, you suggest that you cannot promise to always keep the key details from your paper secret. Under what circumstances would you decide to reveal them?

R.F.: Well, Science and we have said that we’re going to try to adhere to NSABB’s recommendations. The U.S. government is now searching for a mechanism to share the key details with people who have a legitimate need to see them, but this is far from easy; there are all kinds of legal issues. So what that mechanism will look like and whom that information can be shared with is very unclear.

Meanwhile, WHO has said: This research is super-important, but it’s just as important that the data are shared, or it could mean the end of the Pandemic Influenza Preparedness Framework. And rightly so, because that framework is very important for surveillance systems. Suppose it would collapse if for whatever reason the manuscript couldn’t be shared with certain people. Then we’ll have to talk to the U.S. government and WHO. That could happen. Again, you will have to weigh benefits and risks.

Also, as researchers, we work very closely with people in Indonesia. It would be very unwise for us not to share our results with our close collaborators.

Q: So if those researchers weren’t approved to make use of the sharing mechanism …

R.F.: I don’t know who will be at the controls of that mechanism, and what the arguments would be for denying access to certain people. But if the result is that I can’t share details with my collaborators, then I have a problem. That kind of situation can arise. So we’re giving the American government and the NSABB the chance to set up a mechanism, and we are waiting what they come up with. But we cannot say now that we will never share that information.

Q: When do you think you will know more about that mechanism and the publication of your paper?

R.F.: The previous deadline was the end of January, but from what I have heard, the U.S. government has asked for a 4-week extension. So I think it will be late February.

Q: Are you in touch with Yoshihiro Kawaoka?

R.F.: On a daily basis.

Q: You have been all over the press while he has remained completely silent. Wouldn’t you have preferred to make the case for these studies together?

R.F.: We both made a conscious choice to do what we did. I feel I have a responsibility to defend my point of view and to answer those media calls. And of course I made that decision when I decided to go to Malta. He hasn’t talked about his work at a meeting, so what he has done is still under wraps in that paper at Nature. And I can understand his decision; he has two labs to run, one in Japan and one in the U.S. Frankly, the last 3 months I have done nothing but politics, press, and things like that. I don’t have time for my science anymore.

Source:Science Now.

 

Stem Cells Build a Better Rat Penis.

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Men in need of penis reconstruction could soon enjoy the benefits of a special ingredient: stem cells. A new study in rats shows that lacing a penis graft with adult stem cells yields better healing and sexual function than using the graft alone. The finding may point the way to improved treatments for a variety of human penile impairments.

Men with penis injuries, deformities, or severe Peyronie’s disease—which causes excessive scarring that can curve or shrink the penis—sometimes need surgery to reconstruct their genitalia and restore their sexual function. Many receive a graft made of their own tissue, cadaver tissue, or pig intestines, but the surgery can cause complications, including erectile dysfunction.

Wayne Hellstrom, a urologic surgeon at Tulane University School of Medicine in New Orleans, Louisiana, who regularly treats men with Peyronie’s disease and other penile problems, wanted to offer his patients a surgical intervention with fewer side effects. So he teamed up with colleagues in California and China to build a better penis graft.

The team seeded pig intestine grafts with adult stem cells taken from fat tissue in rats. Because rats don’t develop Peyronie’s disease, the researchers had to induce scarring by making incisions in the rodent penises. They then operated on the scarred rats, removing part of the scar tissue and supplanting it with a graft, as is done in patients with severe Peyronie’s disease. Eight rats received the stem cell-laced grafts; another eight got the grafts sans stem cells. A third group had a “sham” surgery that didn’t involve a graft, and a control group didn’t undergo surgery at all.

Eight weeks later, when the rats had recovered from surgery, the researchers examined the rodents’ penises. They found that rats with stem cell-laden grafts had less scarring and better erectile responses, as measured by the animals’ reactions to electric stimulation, than did those with stem cell-free grafts. The rodents’ erections were comparable in rigidity, blood flow, and response time to those in the “sham” and control rats. Cells from the penises with stem cell-laced grafts contained more neuronal and endothelial NOS, enzymes that help trigger and maintain erections. They also had more VEGF, a growth factor whose functions include stimulating new blood vessel development.

The results, published online today in the Proceedings of the National Academy of Sciences, suggest that lacing the grafts with stem cells enhances blood flow and boosts the production of molecules that make and maintain erections, all of which makes for a better penis reconstruction.

“We were really excited and surprised that stem cells can create this much improvement,” says Tulane urologist Asim Abdel-Mageed, a co-author of the study.

“This is an excellent study, with lots of clinical implications,” says Trinity Bivalacqua, a urologist at the Johns Hopkins Medical Institutions in Baltimore, Maryland. But he notes that the method applies only to reconstructions, not to cases where a surgeon may need to build a new penis from scratch. And although the technique works well in rats, “this doesn’t always translate to humans,” Bivalacqua says.

Hellstrom and colleagues plan to test the method in primates next and then eventually in people. “Peyronie’s affects 3% to 9% of adult males and causes a lot of psychological distress,” Hellstrom says. “If we can improve what we have now, it seems like the logical thing to do.”

Source:Science Now.