In experiments with mice, researchers have found that the body’s immune system can use a surprisingly common molecule to recognize prostate tumors. The molecule comes from a protein found in all cells of the body; however, immune cells appear to respond to it only when it is present on the surface of cells within a tumor.

Understanding how this protein, known as histone H4, signals the immune system to respond to malignant cells may help researchers refine immunotherapy strategies that harness the body’s own immune system to fight tumors. Some types of immunotherapy are already being tested in patients, but many questions remain unanswered. In particular, researchers want to know if tumor cells display molecular signposts that tell the immune system, “I’m a cancer cell, destroy me.”

Howard Hughes Medical Institute investigator James P. Allison and his team report finding one such signpost in prostate tumors in mice. The finding points toward possible improvements in immunotherapy.

“We know very little about how the immune system responds to tumors, especially early tumors,” said Allison, director of the Ludwig Center for Cancer Immunotherapy at Memorial Sloan-Kettering Cancer Center in New York. “Is the tumor at that stage invisible, or can immune cells detect it? And if they can detect it, can they mount a response? Those are the two big questions.”

Allison’s research, published in the January 11, 2008, issue of Science, found that immune cells can, in fact, detect prostate cancer, at least in lab mice. However, the immune system mounts only a feeble attack against the tumor.

But the signpost Allison’s team identified might make revving up that feeble response much easier.

The strategy relies on a specific type of immune system cell called a killer T cell. Each of these cells bristles with thousands of receptors that recognize molecules that do not belong in the body. When a T cell recognizes a foreign molecule, it tries to destroy the cell carrying it. The T cell then replicates, making copies that also latch onto the same foreign molecule.

In 1982, while at the University of Texas at Austin, Allison discovered T cell antigen receptors, the fork-like proteins that recognize the molecular signals on invading cells. Each T cell has a different receptor as determined by genetics and a random process. There are trillions of different T cell receptors possible, a number greater than the number of cells in the human body.

In normal tissue, the distribution of receptors found on T cells is random. That is, a batch of T cells will have a range of receptors, with none being more common than the others.

But in the new work, one of Allison’s colleagues, Peter Savage, discovered that the cancerous prostate glands of mice harbored many T cells carrying a specific receptor. That meant that a single T cell had recognized the malignancy and had replicated.

Savage found the overrepresented receptor in 15 of 20 mice with prostate cancer. “That told us something was going on,” said Allison. “You don’t see this in normal mice.”

At this point, the team knew that the immune system of the mice was recognizing a particular signpost of malignancy. But they had no idea what the signpost was.

“The obvious question was, ‘What are these T cells seeing?’” said Allison. “And that’s when the hard work started.”

The team chopped up tumor cells in a dish and mixed them with antigen presenting cells and T cells carrying the receptor they had identified. The T cells switched on, which “showed we had really gotten the right receptor,” said Allison. However, during control experiments, the team also found that nearly any type of tissue, if it was chopped up, would activate the T cells.

“This started some head scratching,” said Allison. Because if every tissue activated the T cells, it meant that the signpost was not specific to the cancer cells.

The mystery deepened when mice were engineered to produce T cells that carried only the receptor of interest. Those cells did not attack every tissue. They only attacked – albeit feebly – the prostate tumors. It was a conundrum.

Returning to their experiments in the lab dish, the team decided to focus on specific parts of the tumor cells. They soon discovered that only molecules from the nucleus activated their T cells.

“This was really a surprise, because normally, nuclear proteins don’t get fed onto the cell surface,” said Allison. And in living animals, T cells only recognize molecules on the surface of other cells – they can’t peer deep into the nucleus.

The team then searched for particular nuclear proteins that activated the T cells. They eventually struck on histone H4. As the wrapper that sheaths the DNA inside all cells, histones are abundant in the nucleus. The finding explained why the normal cells, when chopped up, had activated the T cells – their histones were being exposed.

The team had identified the molecular signpost that activated the T cells, but they had also landed on another big question – how do the histones rise to the surface of the tumor cells. “Every cell has a ton of histone, and we just don’t know why the tumor cells put it on their surface,” said Allison.

The team is now examining the blood of patients with prostate and other cancers to see if people, like mice, carry T cells sensitive to histone. If so, “then we can take those cells out and try to activate them,” said Allison. “Those cells already recognize the tumor. If we can mobilize them, maybe it will have a therapeutic effect.”

Allison and his colleagues are also conducting studies to determine whether the presence of histone H4-reactive T cells in the blood could be used as a diagnostic marker for the early detection of prostate cancer.

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Source: Jennifer Michalowski

Howard Hughes Medical Institute Continue reading →

Adolescents with suicidal thoughts and elevated depression had stronger and faster reduction of symptoms when treated with family therapy than with standard treatment in the community. Researchers from The Children’s Hospital of Philadelphia reported these findings this month in the Journal of the American Academy of Child and Adolescent Psychiatry.

Suicide is the third leading cause of death in American adolescents, accounting for more than 1,300 deaths in youths between the ages of 12 and 18 in 2005. An additional one million teens attempt suicide each year, leading to high emotional and financial costs to families and the health care system. Unfortunately, very few treatment studies have focused on this vulnerable age group or identified treatments with proven results.

In this study, Attachment-based Family Therapy (ABFT), found that patients with severe suicidal thinking were at least four times more likely to have no suicide thinking at the end of the treatment or three months after treatment, than patients treated in the community. Patients in ABFT also showed a more rapid decrease in depression symptoms and were retained in treatment longer than in community care, even with additional supports provided by the study. This is the first treatment study for teen suicidal ideation to show robust and statistically significant improvement over treatment as usual.

“Most treatment models mainly work with the adolescents alone, helping them to learn new coping and problem solving strategies,” says study leader Guy S. Diamond, Ph.D., director of the Center for Family Intervention Science at the Children’s Hospital of Philadelphia. “But adolescents are highly influenced by their parents. Family conflict, chaos, and strife can contribute to youth suicide, while at the same time family love, trust, and communication can buffer against it. This therapy aims to resolve family conflicts and promote family strengths so that the appropriate bond of attachment can protect youth from self harm.”

The researchers studied 66 children between the ages of 12 and 17 who presented in primary care or emergency rooms with severe suicidal thinking and depressive symptoms. The average age was 15, about three quarters were African American and 83 percent were female. Parent participation was required.

“Parents are not viewed as the problem, but as the curative medicine,” Diamond says. “They are the key to keeping lines of communication open in order to monitor against suicidal behavioral. And while no treatment is perfect for all patients, helping any family through a youth’s suicide crisis is important.”

Diamond says his team’s future studies will focus on a broader population of patients, stronger comparison treatments, and long term outcomes to better assess treatment benefits.

A grant from the Centers for Disease Control and Prevention supported this research. Diamond’s co-authors were Gregory Brown, Ph.D. from the University of Pennsylvania; Matthew B. Wintersteen, Ph.D., from Thomas Jefferson University; Robert Gallop, Ph.D., from West Chester University; and Gary M. Diamond, Ph.D., from Ben-Gurion University of Negev, Israel; Karni Shelef, Ph.D., of Achva Academic College of Israel; and Suzanne Levy, Ph.D., from Children’s Hospital.

About The Children’s Hospital of Philadelphia: The Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children’s Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 441-bed hospital recognition as a leading advocate for children and adolescents.

Source: The Children’s Hospital of Philadelphia Continue reading →

Cord blood stem cells can be collected only once – immediately following birth. This means that the number of genetically unique cord blood stem cells is limited to the quantity obtained at this single point in time. To allow for multiple uses and also to increase their capacity for transplantation in adolescents and adults, researchers are developing methods to stimulate stem cells to divide and increase in number while retaining their primitive state. This process is known as stem cell expansion.

Stem cell expansion is an important tool both for improving transplant outcomes and enabling individuals to use their own cord blood samples for more than one treatment. This is particularly important given advances in regenerative medicine – the science of using the body’s own cells to repair or replace damaged tissues and organs – which will likely increase the number of diseases that cord blood stem cells are able to treat as a result.

While expanded stem cells are not yet approved for medical use in humans, several expansion studies and clinical trials are underway. An emerging number of expansion techniques succeeding in vitro and in animal models suggest that one or many of these methods will eventually be available.

In fact, published research indicates that cord blood stem cells can be successfully expanded with reproducible results. In one study, researchers isolated primitive embryonic-like stem cells from cord blood and expanded the number of stem cells in culture 389-fold.1 In another study, researchers expanded the number of stem cells in culture up to 723-fold by isolating stem cells from cord blood using cell surface markers. 2

According to the National Marrow Donor Program (NMDP), more than 6,000 men, women and children are searching the NMDP registry on any given day. Expanding the volume of stem cells available in a cord blood unit would allow even more patients to be treated, including adults. It would also allow those families who have privately banked their cord blood stem cells to use them for multiple treatments and even potentially donate a portion of their cord blood sample to patients in need.

Leading Researchers are Evaluating Expanded Cord Blood Stem Cells
in Human Patients

The use of expanded cord blood stem cells in humans is currently being assessed in a number of clinical trials.

In November, the Gamida Cell/Teva Joint Venture announced that the first patient in its international, multi-center trial received a transplant of stem/progenitor cord blood stem cells in combination with non-expanded cells from the same unit. The trial will assess the efficacy and safety of expanded cord blood transplantation as a treatment for hematological malignancies, including leukemia and lymphoma. 3

Below are three additional clinical studies that show the applicability of stem cell expansion in human cord blood transplants:

- At Hackensack University Medical Center in Hackensack, New Jersey, two adults with chronic myelogenous leukemia exhibited rapid engraftment after receiving expanded cord blood transplants. These results show the promising role cell expansion may hold in adult transplantation. 4

- Thirty-seven patients with blood or breast cancer received expanded cord blood transplants in a study at the University of Colorado. This trial demonstrates the feasibility and safety of using expanded cord blood stem cells to treat patients with high-risk malignancies. 5

- Investigators at Duke University Medical Center administered cord blood stem cells expanded by the Aastrom Replicell System (developed by Aastrom Biosciences) to 27 patients with malignant and nonmalignant disorders. The recipients exhibited durable long-term engraftment and demonstrated the safety of this cell expansion technique for
clinical use. 6

The increasing number of institutions that are actively pursuing these new technologies is an indication of the scientific importance of stem cell expansion. The positive results seen in studies thus far suggest that expansion technologies may be available to more patients in the future.

References

1. McGuckin et al. Production of stem cells with embryonic characteristics from human umbilical cord blood. Cell Prolif. 2005;38:245-255.

2. Yao CL, et al. Characterization of serum-free ex vivo-expanded hematopoietic stem cells derived from human umbilical cord blood CD133+ cells. Stem Cells and Development. 2006;15:70-78.

3. First Patient Undergoes Expanded Cord Blood Transplant in the ExCell Registration Study of StemEx® for Leukemia and Lymphoma.
Available at: home.businesswire/portal/site/google/index.jsp? ndmViewId=news_view&newsId=20071106005916&newsLang=en.

4. Pecora AL, et al. Prompt and durable engraftment in two older patients with high risk chronic myelogenous leukemia (CML) using ex vivo expanded and unmanipulated umbilical cord blood. Bone Marrow Transplantation. 2000;25:797-799.

5. Shpall E, et al. Transplantation of ex vivo expanded cord blood. Biology of Blood and Marrow Transplantation. 2002;8:368-376.

6. Jaroscak J, et al. Augmentation of umbilical cord blood (UCB) transplantation with ex vivo expanded UCB cells: Results of a phase I trial using the Aastrom Replicell system. Blood. 2003;101:5061-5067.

7. Ohishi K, varnum-Finney B, and Bernstein I. Delta-1 enhances marrow and thymus repopulating ability of human CD34+CD38-cord blood cells. The Journal of Clinical Investigation. 2002;110(8):1165-1174

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The latest data from groundbreaking human clinical trials of the effectiveness of continuous glucose monitors (CGM) show that the primary determinant of improvements in achieving better diabetes control is regular use of monitors – six days per week or more – rather than the age of patients, and that benefits continue well past the time when people with type 1 diabetes begin using the devices – including experiencing fewer low blood sugar emergencies.

The findings of two studies from the major multi-center trial funded by the Juvenile Diabetes Research Foundation were published online by the journal Diabetes Care (available here). The first showed that regular use of CGM devices is the principal factor in achieving better diabetes control, rather than the age of people using the monitors, or other demographic, clinical, or psychosocial factors. The second showed that people using CGM to help manage their disease were able to sustain good diabetes control; and just as important, that continued strong control came while actually lowering the incidence of hypoglycemia – dangerous low-blood-sugar incidents that can occur with tightly managed type1 diabetes.

“Based on these results and previous JDRF CGM trials published over the past 12 months, we know that these devices can help people get in control of their diabetes, help people already managing their disease maintain good control, and help people stay in control over an extended period of time, while lowering their risk for hypoglycemia,” said Dr. William V. Tamborlane, of Yale University, a co-chair of the JDRF funded study.

Research has shown that good blood sugar control is a key factor in reducing the risk of the devastating long-term complications of the disease, such as blindness and kidney disease – but that the fear of low blood sugar emergencies often prevents many people from achieving tight control, and remains a constant concern for those who manage their diabetes well. The landmark Diabetes Control and Complications Trial (DCCT) showed that with intensive insulin therapy, excellent blood glucose control was obtained, but at the expense of a considerable increase in hypoglycemia. Today, the JDRF study has shown that, with CGM, hypoglycemia can be reduced while maintaining excellent blood sugar control over an extended period of time.

The JDRF CGM study was a randomized and controlled trial involving 451 adults and children ranging in age from 8 to 72-years-old at 10 sites, including the Atlanta Diabetes Associates, the Joslin Diabetes Center, Kaiser Permanente Southern California, Nemours Children’s Clinic – Jacksonville, FL, the Lucile Packard Children’s Hospital at Stanford University, the Barbara Davis Center for Childhood Diabetes at the University of Colorado Denver, the University of Iowa, the University of Washington, and Yale University, and coordinated by the Jaeb Center for Health Research in Tampa, Florida. Three age groups were analyzed separately: 8 to 14 years of age, 15 to 24 years of age, and 25 years of age or older.

People with diabetes try to maintain their blood sugar levels between 70 mg/dL and 180 mg/dL. When blood sugar becomes very low, people can become confused, lethargic, and even slip into a coma or die. Very high blood sugars can also be dangerous. And long-term, lack of control increases the risk of developing devastating complications, including eye, kidney, nerve, and heart disease. One measure of control is HbA1c, which measures long-term blood sugar management; standards of good control are generally below 7% for adults, and below 7.5% to 8% for children, depending on age. Based on the DCCT findings,.with respect to worsening of eye disease, a 10% decrease in HbA1c (7.2% vs. 8%) is associated with a 40% decrease in progression

According to one Diabetes Care paper (Factors Predictive of Use and of Benefit from CGM in Type 1 Diabetes), in the first six months of theJDRF trial, more frequent CGM use was associated with a greater reductions in HbA1c levels – a finding that was present in all age groups using the devices. Successful use of the devices was defined as an average of six days or more per week.

In each age group, patients averaging at least six days per week of CGM use had substantially greater improvements in HbA1c compared with those who used the devices less often.

According to the Jaeb Center’s Dr. Roy W. Beck, the initial findings published from the JDRF CGM trials in the New England Journal of Medicine in October 2008, had noted that improvements in diabetes control for participants in the trial were most significant among those in the 25 and older age group; children, teenagers and young adults saw less dramatic improvements. However, he pointed out, the findings published in Diabetes Care, looking at those same trial results in a different way, show that after adjusting for the frequency of CGM use, the association of age group with improvements in HbA1c was no longer significant – in other words, participants in the trial in all age groups, from children through adults, who used CGM devices six days per week or more saw similar levels of improvement in their diabetes control. In addition, the study found that regular use of blood glucose testing prior to beginning CGM therapy was an excellent predictor of regular CGM use and thus of improvement in glucose control.

The second study published in Diabetes Care (Sustained Benefit of Continuous Glucose Monitoring on HbA1c, Glucose Profiles, and Hypoglycemia in Adults with Type 1 Diabetes) showed that CGM use had long-term impact: people who began the trial with HbA1c levels at 7% or above saw a reduction in HbA1c mainly in the first eight weeks of the study, and then remained relatively stable through the next 44 weeks; and for participants who began the trials with an HbA1c below 7%, they remained within that target range over the entire 12 months of the study.

“In this six-month extension to the trial, we found that most adults continued to use CGM almost every day, and had sustained benefits in diabetes control as measured by HbA1c levels and the amount of time blood sugar was in the target range,” said Dr. Aaron Kowalski, Program Director for Metabolic Control at JDRF. “These benefits persisted despite less intensive follow-up over the second half of the trial than the first, which was designed to approximate usual clinical practice.”

He noted that just as important as the persistence of control that CGM devices helped patients achieve was the remarkably low rate of severe hypoglycemic events during the second six months of the study. Severe hypoglycemic events – which required the assistance of another person or medical professional – were experienced by 10% of the study participants during the first six months of the trial, but only by 4% in the second six months. The rate of severe hypoglycemic events fell from 21.8 events per 100 person-years during the first six months to 7.1 events per 100 person-years during the second six months. The rate was not associated with the HbA1c level of the trial participants at the time the study began.

According to Dr. Tamborlane, an investigator in both the JDRF CGM Trial and DCCT trials, the rate of severe hypoglycemia in people using CGM devices during the second six months of the JDRF trial was markedly lower than in the Diabetes Control and Complications Trial intensive treatment group – seven hypoglycemia events compared with 62 in the DCCT trial – even though the mean HbA1c of JDRF trial participants at 6.8% was lower than the DCCT trial participants’ level of 7.1%.

“Plus, the total absence of severe hypoglycemia during the second six months of the study in the participants who began the trial with an HbA1c below 7% is particularly striking, especially since these subjects were able to maintain a mean HbA1c of 6.4%,” Dr. Tamborlane said.

These studies are the third and fourth publications resulting from JDRF’s groundbreaking CGM trials, established to clinically assess the benefits of CGM devices in helping people with type 1 diabetes manage their disease more effectively. In addition to results published last fall in The New England Journal of Medicine, results were published in May in Diabetes Care, showing that people with type 1 diabetes who have already been successful in achieving recommended blood sugar goals (below 7%) can further benefit from using continuous glucose monitoring (CGM) devices, while experiencing less hypoglycemia.

JDRF has actively shared the results of the CGM trial with health insurance plans, and as a result many of the nation’s leading plans including Aetna, Cigna, Kaiser Permanente, United Healthcare, and Wellpoint now cover CGM for patients with type 1 diabetes. In addition, due to the JDRF trial, CGM is now included in national standards of care for type 1 diabetes, making doctors more likely to prescribe them for patients.

More information on the JDRF CGM Trials, and on the Artificial Pancreas Project, is available online at artificialpancreas.

About Type 1 Diabetes


Type 1 diabetes is an autoimmune disease that affects children, adolescents, and adults, in which the immune system attacks cells in the pancreas that produce insulin, a hormone that enables people to convert food into energy. People with type 1 diabetes are dependent on insulin for the rest of their life. But insulin is not a cure, and people with diabetes are at significant risk for a wide range of serious complications, including heart disease, blindness and kidney disease. As many as 3 million people in the U.S. have type 1 diabetes.

Source:
Joana Casas

Juvenile Diabetes Research Foundation International Continue reading →

The first five years of a child’s life are filled with a wide range of psychological, emotional, and physical changes that can be exciting but overwhelming. But this doesn’t have to be a time of confusion or uncertainty. In its new book, “The Wonder Years”, The American Academy of Pediatrics (AAP) offers the information parents need to help their children flourish during these formative years.

“The Wonder Years” features more than 500 full-color photographs, diagrams, illustrations, and timelines. The book is uniquely arranged by developmental milestones and the related skills that children learn in each area-instead of just chronologically by child’s age-to give caregivers the bigger picture of what to expect, how to foster their child’s progress, and how to make the most of this amazing time. It includes the most up-to-date findings on child development in the following chapters:

- Movement – Everything from the early stages of head movement to sitting, crawling and eventually, walking are covered, complete with activities to foster your child’s athletic abilities.

- Fine motor skills – When will you know if your child is right or left handed? When do they first start to reach for objects? These and other topics-as well as how to encourage the artist in your child are explained in-depth.

- Sensory development – The five senses and the development at all stages-responding to one’s own name, developing taste preferences, and distinguishing between colors to name a few-are discussed.

- Mental growth – Here’s a “behind the scenes look” at your child’s brain and how this important organ affects everything.

- Social and emotional growth – From bonding and colic, to playing make-believe and developing attachments with other children, caregivers are given a comprehensive overview of their child’s emotional health.

- Bowel and bladder development – Parents are given the answers to tell when their child is ready to toilet train and how to help them in this physical-and emotional-milestone.

“The Wonder Years” also includes fun parent-child activities to boost emotional and mental growth-such as how to foster the artist in your child and games beyond peek-a-boo. The book indicates to caregivers when help may be needed in a certain area of development, along with advice on how to consult a specialist when concerns do arise. From heredity, gender, and environmental surroundings, “The Wonder Years” details the multitude of factors that can affect all aspects of a child’s development.

The book is edited by Tanya Remer Altmann, MD, FAAP, a pediatrician in private practice and clinical instructor at the University of California, Los Angeles. It is available on aap and in bookstores.

American Academy of Pediatrics (AAP)

141 Northwest Point Blvd, PO Box 927

Elk Grove Village, IL 60009-0927

United States
aap/ Continue reading →

The North Dakota Department of Health is providing guidance for the
public and physicians regarding swine flu.

While no cases have been identified in North Dakota at this time, as of April 26, 2009, 40 cases
of swine flu have been confirmed in the United States, according to the U.S. Centers for Disease
Control and Prevention (CDC). The confirmed cases are in California, Kansas, New York City,
Ohio and Texas. The cases appear to be mild; only one person was hospitalized, and at this time,
all the known cases in the U.S. have recovered. Mexico also is experiencing an outbreak with an
undetermined amount of cases there.

“This is a situation we are paying close attention to,” said State Health Officer Terry Dwelle,
M.D. “We have sent information to physicians, hospitals and local public health units asking
them to increase surveillance for the disease. We’re asking the general public to follow
guidelines just like during a regular flu season to help reduce the spread of the disease.”

The Department of Health offers these recommendations:

- As always, if you are sick you should stay home from work or school to avoid spreading
the infection to others.

- Cover your mouth and nose with a tissue when coughing or sneezing. It may prevent those
around you from getting sick.

- Avoid close contact with people who are coughing or otherwise appear ill.

- Avoid touching your eyes, nose and mouth. Germs are often spread when a person touches
something that is contaminated with germs and then touches his or her eyes, nose, or
mouth.

- Wash hands frequently.

- People experiencing cough, fever and fatigue, possibly along with diarrhea and vomiting
should contact their doctor. If you have recently traveled to an area with confirmed cases,
make sure your doctor knows your travel history.

- The CDC is recommending that any non-essential travel to Mexico be cancelled. For
updated travel restriction information, visit cdc/swineflu. Look for “Travel
Notices.”

Swine flu viruses are not transmitted by food and a person cannot get swine flu from eating pork
products. Drugs called antivirals can reduce the severity of the disease if taken early. North
Dakota does have a stockpile of antivirals if needed.

“The Department of Health has plans in place to respond to public health emergencies,” said
Dwelle. “We are watching this situation closely and have resources ready if we need them. It’s
also important for the public to pay attention and to follow guidelines given from our department
and their local public health unit.”

Source
North Dakota Department of Health
Further information on Swine Flu

See a Map Of H1N1 Outbreaks
See our Mexico Swine Flu Blog Continue reading →

By the time they are adults, men and women have distinctive attitudes about the roles women should play in society, but little is known about how these views develop. A Penn State study tracked youth’s attitudes for most of the school age and adolescent years and found varying patterns of change according to gender, birth order, parent’s influences and other factors.

“We charted the course of gender attitudes over time, and studied characteristics of families and family members that helped to shape the way youth’s attitudes changed over time,” says Dr. Ann Crouter, Penn State professor of human development and family studies and lead author of the study which is published in the current issue of the journal Child Development.

“Several different patterns of change emerged, suggesting that there is no single course of gender attitude development from middle childhood through adolescence. Instead, change patterns were different for girls versus boys, for firstborns versus secondborns, for youth with a sister versus a brother, and for youth with parents who had more versus less traditional attitudes,” added Crouter, also director, Social Science Research Institute and of the Children, Youth, and Families Consortium, both at Penn State.

Other authors are Shawn D. Whiteman, assistant professor, child development and family studies, Purdue University; and Susan McHale, professor of human development and family studies, and D. Wayne Osgood, professor of crime, law justice and sociology, both at Penn State.

This study was the first longitudinal study to track youth’s gender attitudes over a long period of time, specifically from about ages 7 to 19. The research focused on a sample of 201 two-parent, predominantly White, working and middle class families who were first interviewed when the firstborn child in the family was about 10 years old and the secondborn child was about 7 and a half years old. Two siblings and their mothers and fathers were interviewed at home every year for 9 years, until firstborns were about 19 and secondborns were about 16.5 years old.

During each home interview, family members rated the traditionality of their gender attitudes, describing how much they agreed with statements like: “Sons in a family should be given more help to go to college than daughters;” or “In general, the father should have greater authority than the mother in making decisions about raising children.”

Most youth became less traditional over time, but the attitudes of firstborn boys with brothers and traditional parent were the most traditional to begin with, and became more traditional over time, the researchers write. Similarly, girls and secondborn boys who had parents with more traditional attitudes and brothers did not become as nontraditional over time as other offspring, suggesting that having traditional parents and a brother is a potent combination that supports the development of traditionality in gender role attitudes.

“Patterns for firstborns and secondborns were somewhat different, with secondborns tending to become less traditional in middle childhood but endorsing more traditional attitudes again beginning at about age 15,” Crouter notes. “We speculated that peers may be an important influence on secondborns.”

In society at large, attitudes about gender roles are gradually becoming less traditional and more egalitarian, but the researchers found that even in the face of this widespread shift, there are individuals who are staunchly conservative about the roles of women and men. The findings suggest that gender attitudes take shape across childhood and adolescence, and that the cues youth take about attitudes come, at least in part, from experiences with parents and siblings.

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This research was supported by a grant from the National Institute for Child Health and Human Development.

Contact: Vicki Fong

Penn State Continue reading →

When your body cranks up the heat, it’s a sign that something’s wrong-and a fever is designed to help fight off the infection. But turning up the temperature can have a down side: in about one in 25 infants or small children, high fever can trigger fever-induced (febrile) seizures. While the seizures themselves are generally harmless, a prolonged fever resulting from infection or heatstroke of over 108??F (42??C) can eventually lead to respiratory distress, cognitive dysfunction, brain damage or death.

New research by scientists at the University of Toronto Mississauga and Queen’s University has shown that genetic variation in the foraging gene results in different tolerance for heat stress, and demonstrates how the use of specific drugs can replicate this effect in fruit flies and locusts. While the findings are at an early stage, the researchers suggest that since this genetic pathway is found in other organisms, it could lead to ways to rapidly protect the brain from extremely high fevers in mammals, including humans. The new study appears in the Aug. 22 issue of the journal PLoS ONE (Public Library of Science ONE).

“Our research suggests that manipulation of a single gene or genetic pathway will be sufficient to rapidly protect the nervous system from damage due to extreme heat stress,” says senior researcher, Professor Marla B. Sokolowski, who holds a Canada Research Chair in Genetics.

In their research, post-doctoral fellow Ken Dawson-Scully and Sokolowski demonstrate that the foraging gene, responsible for a protein called PKG, protects against heat-induced neural failure in fruit flies and locusts. When they increased the temperature by 5??C per minute (starting from 22??C and rising to 42??C), they found that fruit flies with a lower level of PKG experienced neural failure at much higher temperatures than those with higher levels of PKG.

Using drugs that interact with the PKG molecule, the researchers showed it is possible to induce an extremely rapid protection of neural function during heat stress. Queen’s biologists Gary Armstrong and Mel Robertson exposed locusts to increasing heat while monitoring the neural circuit that controls breathing. At approximately 30??C (about three minutes before expected neural failure), the researchers injected the locusts with a PKG inhibitor. Compared to locusts who received a placebo injection, the treated locusts showed a rapid and significant protection of their neural circuitry.

“During heat trauma to the brain, there exists a window of opportunity between the time of occurrence of neural dysfunction and eventual brain damage or death,” says Dawson-Scully. “Manipulation of the PKG pathway during this period should increase an individual’s chance of survival.”

The research was supported by the Heart and Stroke Foundation of Canada, the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada.

utoronto Continue reading →

UroToday – Men with clinical stage T3 prostate cancer (CaP) are often found to have locally advanced or regional disease. As such, radiotherapy with androgen deprivation is most commonly employed. Dr. Carver and colleagues at Memorial Sloan Kettering Cancer Center reviewed the outcomes of 176 men who had radical prostatectomy (RP) for stage T3 CaP. Their report appears in the August, 2006 issue of the Journal of Urology.

Men included in the study underwent RP between 1983 and 2003. Clinical staging was provided by the attending surgeon. Neoadjuvant hormonal therapy (NHT) was given to 64/176 men and the remainder had RP as monotherapy. No participant received adjuvant hormonal therapy. Biochemical recurrence (BCR) was defined as a PSA >0.2ng/ml. Clinical and pathologic data was obtained and analyzed.

Men treated with NHT had higher mean pretreatment PSA levels and a greater incidence of clinical seminal vesicle invasion. Downstaging to a pathologically organ confined tumor occurred in 24% of men who had RP as monotherapy and in 41% of men who had NHT. Positive surgical margins occurred in 24% of men who had RP as monotherapy and in 31% of men who had NHT. BCR was found in 84/176 (48%) at a mean time of 4.6 years after surgery. The 10-year probability of freedom from BCR for men with PSA levels 20ng/ml was 68%, 50%, and 20%, respectively. NHT was not a predictor of BCR.

Salvage radiotherapy was given to 10% of men at BCR. Of the 84 men with a BCR, 65 (77%) were treated with androgen deprivation at a median time of 1.4 years after surgery. After initiation of androgen deprivation, 69% achieved an undetectable PSA nadir level. 26/65 men (40%) had progression to hormone refractory disease. The overall probability of freedom from clinical failure at 5 and 10 years was 86% and 76%, respectively. At a median follow-up of 6.4 years, 82% of men are alive, 11% died of CaP, and 7% died of other causes. The overall probability of death from CaP at 5, 10, and 15 years after RP was 6%, 15%, and 24%, respectively. Fifty-two percent of men who had RP for clinical stage T3 disease were free of disease recurrence.

Christopher P. Evans, M.D.
J Urol 2006;176:564-8.
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Members of the… Senate Health, Education, Labor and Pensions Committee on Thursday during a confirmation hearing for Lester Crawford, the nominee for FDA commissioner, likely will focus on his tenure as acting agency commissioner at a time when FDA “was plagued by drug safety problems,” CQ HealthBeat reports (CQ HealthBeat, 3/16). Crawford has served as acting commissioner or deputy commissioner of FDA for the past three years. President Bush in 2001 considered Crawford for the position of FDA commissioner before he nominated Mark McClellan, now current CMS administrator. Crawford, who has served as FDA acting commissioner since McClellan left the position last March, has focus on expedited approvals of new medications, protection of the U.S. food and prescription drug supply from terrorist attacks and improvement of prescription drug manufacturing and safety. Crawford has said that he opposes the legalization of prescription drug reimportation from other nations (Kaiser Daily Health Policy Report, 2/15). According to CQ HealthBeat, the most “significant questions” at the hearing likely will focus on how FDA addressed safety issues related to COX-2 inhibitors, reports that antidepressants could increase the incidence of suicidal thoughts in children and an unexpected flu vaccine shortage last year. Committee Democrats also likely will ask questions related to prescription drug reimportation, CQ HealthBeat reports (CQ HealthBeat, 3/16).

Criticism, Support
Republicans support Crawford’s confirmation as FDA commissioner, but some Democrats and consumer advocates are “questioning President Bush’s choice,” the AP/Las Vegas Sun reports (Freking, AP/Las Vegas Sun, 3/16). A spokesperson for Sen. Edward Kennedy (D-Mass.) said that the ability of FDA to protect the health and safety of U.S. residents “has been called into question in recent years,” adding, “We have a responsibility to seriously examine issues such as drug safety and give Dr. Crawford the opportunity to provide explanations” (CQ HealthBeat, 3/16). Consumers Union, the Consumer Federation of America and the U.S. Public Interest Research Group have questioned whether Crawford has the “willingness to act in the best interest of consumers” (AP/Las Vegas Sun, 3/16). Sidney Wolfe, director of the Health Research Group at Public Citizen, said, “Crawford has been and will be one of the worst commissioners that there has been.” However, according to the New York Times, Crawford has “guided the agency through one of its most difficult periods in decades” and likely will receive many “‘it-could-have-been-worse’ endorsements” (Harris, New York Times, 3/17). Senate Majority Leader Bill Frist (R-Tenn.) said, “Dr. Crawford’s eminently qualified to handle the challenges and responsibilities of keeping our nation’s food and drug supply safe and secure.” Jeff Trewhitt, a spokesperson for the Pharmaceutical Research and Manufacturers of America, which supports confirmation for Crawford, added, “Crawford knows the agency, and he knows it well. He responds to crises quickly and with quiet efficiency.” (AP/Las Vegas Sun, 3/16).

Broadcast Coverage
NPR’s “Morning Edition” on Thursday reported on the confirmation hearing for Crawford. The segment includes comments from Crawford; Wolfe; and Dr. Raymond Woosley, director of the University of Arizona C-Path Institute, which works with FDA to expedite prescription drug development and approval (Silberner, “Morning Edition,” NPR, 5/17).

The complete segment is available online in RealPlayer.

“Reprinted with permission from kaisernetwork kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved. Continue reading →