Dental caries, or tooth decay, continues to be the most prevalent infectious disease in the world, presenting significant public health challenges and socio-economic consequences. It leads to the loss of the hard tissues of the tooth, followed by inflammation and necrosis of the subjacent dental pulp. In the U.S. alone, over 20 million dental restorations are placed each year, with failure rates of up to 60%. Hence, there exists a critical need for better biologic therapeutics to restore the damaged dentin-pulp complex to its original form and function. However, progress in this area has been slow compared with that in other fields of regenerative medicine.

Tissue-engineering strategies directed at mimicking the natural extracellular matrix have utilized synthetic and non-synthetic scaffolds to direct cell differentiation and matrix mineralization (in the case of bone). The most promising among the new generation of delivery systems are synthetic peptide hydrogels, which provide a nanostructured matrix highly similar to natural matrix. Short peptides can be designed to self-assemble into nanofibers, form macroscopic gels, and entrap living cells. With single amino acids as building blocks, the resulting materials are non-toxic, non-inflammatory, and biodegradable. The modular concept allows for high control over the system and, at the same time, makes it extremely versatile.

Speaking during the 86th General Session of the International Association for Dental Research, a team of investigators from Baylor College of Dentistry (Dallas), the University of Regensburg (Germany), and Rice University (Houston) presented its preliminary data describing the results of studies on hydrogels made of peptide amphiphiles, where a short peptide sequence is attached to a fatty acid, which provides the driving force for self-assembly. However, they recently applied a different design concept, where the self-assembly of peptide chains is achieved without attaching a hydrophobic tail. Based on their design, the chains can include bioactive peptide sequences for cell adhesion, binding of growth factors, or other biological molecules with therapeutic potential. Hence, multidomain peptide hydrogels represent a novel and highly versatile material offering a higher degree of control over nanofiber architecture and better chemical functionality.

The overarching goal of this research is to utilize these multidomain peptides as a biomimetic scaffold, along with dental stem cell therapy, to provide a natural 3D environment that can control and direct the differentiation and function of dental stem cells for the targeted regeneration of the dentin-pulp complex.

This work is highly translational and innovative, since it capitalizes on a new and previously untested material with novel properties for the regeneration of the dentin-pulp complex. Importantly, the results will provide the foundation for developing multidomain peptide scaffolds as novel therapeutics for the regeneration of the dentin-pulp complex.

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About the International Association for Dental Research

The International Association for Dental Research (IADR) is a non-profit organization with more than 10,800 individual members worldwide, dedicated to: (1) advancing research and increasing knowledge to improve oral health, (2) supporting the oral health research community, and (3) facilitating the communication and application of research findings for the improvement of oral health worldwide.

To learn more about the IADR, visit iadr/.

This is a summary of an abstract entitled “Novel Hydrogel Systems for Dentin Regeneration”, by R.N. D’Souza et al., of the Baylor College of Dentistry (Dallas), presented at the 86th General Session of the International Association for Dental Research.

Source: Linda Hemphill

International & American Association for Dental Research

More than a quarter of cancer survivors who still smoke have not been advised to quit smoking by their health care providers in the last year, according to a study published by researchers at Fox Chase Cancer Center in the current issue of the Journal of General Internal Medicine. The findings suggest that health care providers – from doctors to dentists to nurses – are missing an opportunity to make a dramatic difference in the quality of life of their patients.

“While smoking cessation is difficult, it can play an important role in increasing cancer survivors’ quality of life,” says the paper’s lead author Elliot Coups, Ph.D., former associate member of Fox Chase Cancer Center’s faculty and a participant in the Fox Chase Keystone Program in Cancer Risk and Prevention. “Time and again, studies have shown that people really do listen to what is said at the doctor’s office in regards to smoking, so health care providers need to take advantage of this teachable moment.”

According to Coups, an associate professor of medicine at UMDNJ-Robert Wood Johnson Medical School, who recently joined the Division of Public Health Science at The Cancer Institute of New Jersey, the harmful effects of smoking have an important impact on cancer survivors. Smoking is known to adversely affect survivors’ quality of life, lower their projected life-spans, and to increase their risk for cardiovascular disease, as well as second, unrelated cancers.

“With improvements in cancer medicine, we are seeing a growing population of cancer survivors who are returning to their primary physicians with their unique medical issues,” says Carolyn Heckman, Ph.D., assistant professor at Fox Chase Cancer Center and a co-author of the study. “Smoking cessation, in particular, needs to be addressed at every visit with a health care provider.”

Coups and his colleagues drew the data for this study from 1,825 participants in the 2005 National Health Interview Survey conducted by the National Center for Health Statistics. The participants were survivors of an array of cancers, including cervical, colon, breast, melanoma, uterine and prostate cancer.

Nearly all of those surveyed reported visiting a health care provider within the previous year. Among the 18 percent of cancer survivors who reported currently smoking, nearly 65 percent indicated they wanted to quit smoking and 40 percent had tried to quit within the last year. The study found that when survivors try to quit smoking they, unfortunately, tend not to use evidence-based behavioral treatments or pharmacotherapies (such as nicotine patches or gum), which is consistent with the general population of smokers.

“This survey cannot tell us why these people did not get the help quitting that they needed or why some survivors didn’t receive smoking cessation advice from their health care providers,” Coups says. “Yet it should serve as encouragement to health care providers to talk about smoking with their cancer survivor patients, and not to assume that another provider is taking care of the problem. Survivors especially need guidance in using evidence-based smoking cessation treatments.”

Funding for this research comes from grants from the National Cancer Institute.

Source:
Greg Lester

Fox Chase Cancer Center

The ability of blood
tests to precisely measure very low doses of anti-rejection drugs in kidney
transplant patients may make a significant difference in assuring long-term
viability and survival, according to research presented at the
American Association for Clinical Chemistry (AACC) annual meeting.

The current thinking in transplant medicine favors reducing doses of
tacrolimus and other immune-suppressive drugs as much as possible after
kidney-transplant procedures. “Even though we are succeeding in preventing
organ rejection, we haven’t made much progress to improve long-term
survival,” said Sudarshan Hebbar, M.D., senior medical director, Abbott
Diagnostics. “Unfortunately, most kidney transplant patients will go back
on dialysis in eight to ten years, in part because the anti-rejection drugs
can be toxic to the kidneys.”

Dr. Hebbar added that kidney-transplant patients have high incidence of
heart attacks and other cardiovascular disorders from long-term effects of
renal disease. Therefore, minimizing drug toxicity over time is considered
one way to help improve long-term graft survival and preserve quality of
life for transplant patients.

To minimize long-term toxicity of transplant medications, physicians
frequently aim to taper down doses of immunosuppressive drugs to as low a
level as possible without risking rejection. “Successful low-dose regimens
of tacrolimus and other anti-rejection medications require highly precise,
ultra-sensitive drug-monitoring assays,” said Daniel Levine, Ph.D.,
director of the clinical laboratory, Iris and B. Gerald Cantor Clinical
Research Laboratory at The Rogosin Institute in New York City.

Dr. Levine emphasized the importance of using an accurate and precise
test to monitor patients on low-dose treatment regimens. “At low doses,
even the slightest variation in blood-level readings could be devastating
to transplant patients. The consequence for the laboratory is twofold: it
must have accurate, precise testing for immunosuppressive drugs, and
tacrolimus tests that are accurate to 4 ng/mL are no longer adequate,” he
explained.

Dr. Levine reported results of his studies evaluating the performance
of the Abbott ARCHITECT assay for tacrolimus, the most widely used
immunosuppressant drug. He said the usual dosing range for the medication
is between 2 and 15 ng/mL, with lower doses preferred. “The challenge for
the laboratory, therefore, is to assure with the utmost confidence to the
physician that a tacrolimus blood level of 3 ng/mL is exactly right and not
5,” Levine said.

In the trials, the Abbott ARCHITECT tacrolimus assay was accurate and
precise at low levels and showed consistent results. “The functional
sensitivity in our hands was 0.9 ng/mL, exceeding the package insert claim
of 2 ng/mL. We are fully confident the ARCHITECT tacrolimus assay meets our
requirement for low-level tacrolimus monitoring,” Levine said.

“The ARCHITECT tacrolimus assay is the only automated transplant
monitoring test that meets international standards for low-level
monitoring,” according to Dr. Hebbar.

The ARCHITECT tacrolimus assay is used for the quantitative
determination of tacrolimus in human whole blood, as an aid in managing
liver and kidney transplant patients receiving tacrolimus therapy.

About the ARCHITECT Family

With its extensive menu of diagnostic tests, user-friendly software and
advanced sample management capabilities, the ARCHITECT family and the
currently marketed flagship analyzer, ARCHITECT(R) ci8200(R), meet the
needs of today’s diagnostics laboratory by enhancing workflow and
productivity. ARCHITECT instruments are designed with laboratory-focused
features such as the capability to prioritize emergency tests, the ability
to use common reagents among platforms and sample monitoring. These
features not only minimize training, but also reduce inventory costs and
sample contamination potential, leading to better results for laboratories,
physicians and, ultimately, patients.

About Abbott’s Diagnostics Businesses

Abbott is a global leader in in vitro diagnostics and offers a broad
range of innovative instrument systems and tests for hospitals, reference
labs, molecular labs, blood banks, physician offices and clinics. With more
than 65,000 institutional customers in more than 100 countries, Abbott’s
diagnostic products offer customers automation, convenience, bedside
testing, cost effectiveness and flexibility. Abbott has helped transform
the practice of medical diagnosis from an art to a science through the
company’s commitment to improving patient care and lowering costs. Abbott’s
history is filled with examples of first-of-a-kind diagnostic products and
significant technological and research advancements.

About Abbott

Abbott is a global, broad-based health care company devoted to the
discovery, development, manufacture and marketing of pharmaceuticals and
medical products, including nutritionals, devices and diagnostics. The
company employs more than 68,000 people and markets its products in more
than 130 countries.

Abbott
abbott

Men who smoke cigarettes run an increased risk of experiencing erectile dysfunction, and the more cigarettes smoked, the greater the risk, according to a study by Tulane University researchers published in the American Journal of Epidemiology.

A team of researchers led by Jiang He, Professor of Epidemiology at the Tulane University School of Public Health and Tropical Medicine, examined the association between cigarette smoking and erectile dysfunction in a 2000-2001 study in China involving 7,684 men. The researchers used questionnaires to assess the status of cigarette smoking and erectile dysfunction. Those surveyed were men between the ages of 35-74 who did not have vascular disease.

The team found that there was a significant statistical link between the number of cigarettes that men smoked and the likelihood they would experience erectile dysfunction. The association between smoking and erectile dysfunction was even stronger in participants with diabetes. An estimated 22.7 percent of erectile dysfunction cases among Chinese men might be attributable to cigarette smoking, says the study.

Although erectile dysfunction is not a life-threatening condition, it compromises well-being and quality of life. The Tulane study results suggest that smoking prevention should be an important approach for reducing the risk of erectile dysfunction.

###

Source: Arthur Nead

Tulane University

As expected, the… President’s Council on Bioethics on Thursday released a report outlining possible ways to move forward with embryonic stem cell research without “upsetting ethical concerns” by describing methods for producing stem cells without destroying human embryos, Reuters reports. The report was released while Congress is considering whether to loosen federal restrictions on the research (Fox, Reuters, 5/12). President Bush’s embryonic stem cell policy — which he announced on Aug. 9, 2001 — limits federally funded embryonic stem cell research to stem cell lines created on or before that date. Critics of Bush’s policy have said that the embryonic stem cell lines available for federal funding are not biologically diverse, are contaminated with nonhuman material and are useless for research into possible cures for degenerative diseases (Kaiser Daily Reproductive Health Report, 5/12). “Much of the ethical controversy over stem cells derives from the fact that, until now, the only way to obtain human pluripotent stem cell lines has been to derive them from living human embryos by a process that necessarily destroys the embryos,” the report says, adding, “If a way could be found to derive such stem cell lines without creating and destroying human embryos, a good deal of that ethical controversy would subside” (Reuters, 5/12).

Report Details
The 18-member council — which comprises bioethicists, researchers, legal experts and others — suggested four alternatives to current stem cell research techniques that create an embryo through cloning or use an embryo discarded from fertility clinics, the Washington Post reports. “Stem cells might be obtainable from dead embryos; from living embryos, by nondestructive biopsy; from bioengineered embryo-like artifacts; and from reprogrammed adult somatic cells,” the report says (Washington Post, 5/13). However, the report concludes that two of the alternatives — taking cells from living embryos through nondestructive biopsy and from bioengineered embryo-like artifacts — still could be viewed as “ethically problematic,” the New York Times reports. Of the remaining alternatives, the idea for using cells from a dead embryo evolved from the fact that some embryos created in fertility treatments stop undergoing cell division and are considered dead. Although this sometimes happens because the embryo has damaged cells, which would be unusable, the council said it might be possible to salvage viable stem cells from these embryos. The second method deemed ethically acceptable is to take stem cells from reprogrammed adult somatic cells, an idea derived from the technique used for cloning animals, according to the Times. When the nucleus from an adult cell is inserted into an unfertilized egg, the egg can make the nucleus return to an “embryonic state,” the Times reports. The council recommends finding the underlying factors, possibly chemical signals, that are responsible for this change and using them to convert adult cells into stem cells.

Council Disagreement
Two of the three research scientists on the council have “vigorously rejected” the report’s recommendations, the Times reports (Wade, New York Times, 5/13). Michael Gazzaniga, a professor of neurology at Dartmouth College, in a rebuttal to the council report said the proposed alternatives are “high-risk gambles” and evade the question as to whether the United States should endorse embryonic stem cell research as it currently is done or whether the country will “remain hostage to the arbitrary views of those with certain beliefs about the nature of life and its origins” (Kaiser Daily Reproductive Health Report, 5/12). Janet Rowley, a cell biologist at the University of Chicago, said it is “totally baffling” to let healthy embryos die instead of using them to help other patients. The “sharp division” between scientists and bioethicists on the council is “unusual,” the Times reports. Council Chair Leon Kass said the council has a more balanced perspective, with more members who are “pro-life” than past councils, and that it is “more representative of the nation as whole.” He added, “I’m proud of this council in that we were by design created to reflect the deeper differences in American society and, without papering over those differences, we have found a way to move the discussion forward” (New York Times, 5/13).

Alternatives Potential, Next Steps
“It remains to be seen whether any of these proposals will succeed scientifically, and more discussion is surely required on some of the ethical issues we have identified,” the report says. Sean Tipton, a spokesperson for the American Society for Reproductive Medicine and the Coalition for the Advancement of Medical Research, said, “We would agree that you ought to pursue all the alternatives. But we think scientific merit ought to drive those decisions.” He added that research using live human embryos still holds “the most promise” for developing cures for some diseases, according to Reuters (Reuters, 5/12). However, some scientists “are impatient to start research,” and several of the council’s proposed alternatives could “take many years to be explored,” according to the Times. Rowley said it would be the “height of folly” to allow “healthy surplus embryos” to be discarded, the Times reports (New York Times, 5/13).

House Legislation To Receive Vote
House Majority Leader Tom DeLay (R-Texas) on Thursday said the chamber will vote before the August recess on legislation (HR 810) that would loosen federal restrictions on human embryonic stem cell research, CQ HealthBeat reports. The measure would allow researchers to receive federal funding for the study of embryonic stem cells derived from embryos created for fertility treatments and willingly donated by patients. Under the measure, patients could not be compensated for embryo donation and would have to have full knowledge of how the donated embryos would be used (CQ HealthBeat, 5/12). The legislation would not allow federal funding for embryonic stem cell research on stem cell lines or embryos created expressly for research purposes (Kaiser Daily Reproductive Health Report, 5/12). DeLay said the vote on the bill would come “sooner rather than later.” The legislation has nearly 200 co-sponsors, according to CQ HealthBeat (CQ HealthBeat, 5/12).

“Reprinted with permission from kaisernetwork kaisernetwork. You can view the entire Kaiser Daily Reproductive Health Report, search the archives, or sign up for email delivery at www.kaisernetwork/dailyreports/repro The Kaiser Daily Reproductive Health 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.

Treatment of hypertension has proven to reduce cardiovascular risk substantially, but a large proportion of people with hypertension in the general population are not even diagnosed or treated. As a risk factor for stroke, ischemic brain lesions and silent brain infarcts, general atherosclerosis, myocardial infarction and cardiovascular morbidity, hypertension may also be a risk factor for dementia related to cerebrovascular disease. After a stroke event dementia occurs in up to 25% of patients above age 70.

Dementia: a growing public health challenge

Characterized by significant decline in memory and other cognitive abilities, dementia is a major cause of disability and mortality, and causes a high burden of suffering for patients and their families. Due to an aging population and the tragic effects of dementia, this age-related disease represents a growing medical, social, and economic problem. It is one of the most common diseases in the elderly, with crude prevalence rates between 5.9-9.4% for subjects aged over 65 in the European Union (Berr et al., 2005). Dementia drastically affects daily life and everyday personal activities. Often the disease is associated with behavioural symptoms, personality change and numerous clinical complications, increasing the risk for urinary incontinence, hip fracture, and – most markedly – dependence on nursing care. Thus, it is not surprising that the costs of care for patients with dementia are immense.

The two most common causes of dementia are AlzheimerВґs disease (AD) and vascular dementia. AD accounts for 50-70% of all cases of dementia, about 20-30% have either vascular dementia or a combination of vascular dementia and AD (Boustani et al., 2003). In older patients, the brain lesions associated with each dementia type often occur together. AD and vascular brain lesions interact in important ways to impair cognition, suggesting common pathways of the two neurological diseases. In the absence of effective therapies (in terms of disease modification), it is essential that all potentially reversible causes of dementia be fully investigated.

Dementia is one of the major challenges of the 21st century due to the enormous burden these disorders impose on health care systems.

Dementia: searching for a breakthrough

Today there is tremendous interest in developing effective treatments that will interfere with some step in the etiologic process or even prevent the clinical onset of dementia. With regard to AD, the sequence of the molecular and cellular events leading to progressive cognitive decline and the steps that are most amenable to intervention have been discussed controversially, but now there is substantial agreement that certain biochemical changes in the brain occur many years or decades before clinical symptoms. However, no effective prevention measures can be recommended so far.

Advancing age is the major risk factor for dementia, with a doubling of risk every five years after the age of 65 (Jorm et al., 1987; Kawas, 2003). During the last decade, evidence has accumulated that high blood pressure may be a risk factor for both AD and vascular dementia, independent of the presence of cerebrovascular disease. Several longitudinal studies suggest an association between AD and previous hypertension. In addition, observational studies indicate that the use of antihypertensive drugs may reduce the incidence of AD and dementia. Conversely, no study reports that antihypertension treatment increases the risk for dementia.

Treatment of hypertension might be a key factor in the prevention of dementia and cognitive decline.

Dementia: risk and antihypertensive treatment

Most trials of antihypertensive treatment in relation to dementia and cognitive decline have been accomplished as part of large trials where dementia is of secondary interest alongside the primary investigation of cardiovascular outcomes. So far five hypertension trials including in total approximately 22.600 patients have reported on dementia or cognitive function in association with antihypertensive treatment:
SHEP: Systolic Hypertension in the Elderly Program evaluating the effects of antihypertensive treatment using a diuretic (chlorthalidon)

MCR: Medical Research Council’s Treatment Trial of Hypertension using a beta-blocker (atenolol) or a diuretic (hydrochlorthiazide)

Syst-Eur: The Systolic Hypertension in Europe Study using a calcium-channel blocker (nitrendipine)

SCOPE: The Study on Cognition and Prognosis in the Elderly using an angiotensin II type 1 (AT1) receptor blocker (candesartan cilexetil)

PROGRESS: Perindopril Protection against Recurrent Stroke Study using an ACE-inhibitor (perindopril) and a diuretic (indapamide)

These trials observed significant reductions in cardiovascular outcomes, but only one study (Syst-Eur) reported a significantly reduced incidence of dementia under antihypertensive treatment. Regarding other cognitive outcomes, two studies reported a reduction of 11-19% for ‘significant cognitive decline’. Only one study (PROGRESS) showed a significantly lesser decline in cognitive function under antihypertensive treatment compared to placebo, while the other studies observed no differences between the groups in different cognitive tests. No study reported a higher risk for dementia or cognitive decline in the groups treated with antihypertensive drugs.

With regard to subanalyses of these data, the PROGRESS study showed that dementia in combination with recurrent stroke was reduced by 34%. SCOPE found that cognitive function declined significantly less under antihypertensive treatment among patients with mild cognitive dysfunction (compared to controls). In SHEP, antihypertensive treatment reduced incidence of dementia if drop-outs were assigned a prevalence of 20-30% of dementia.

Dementia prevention: is there hope for the future?

The seemingly scanty findings from these trials could give rise to pessimism regarding the possibilities for dementia prevention. However, there are several methodological shortcomings that might explain some of the results and need to be considered in subsequent trials in order to achieve sound results:
Changes in cognitive function may better be detected when the majority of patients does not score close to the maximum in cognitive tests (exclude Вґceiling effectВґ).

Generally, studies should include patients with a higher short-term risk of developing dementia (e.g. old patients, patients with other risk factors, patients with poor cognitive performance at study entry).

Sufficient test-sensitivity should be ensured to detect cognitive changes over time.

Follow-up has to be at least 5 years to detect an effect of antihypertensive treatment on AlzheimerВґs disease. All hypertension trials so far have only measured short-term effects of antihypertensive treatment.

In order to detect and substantiate an effect of antihypertensive treatment on dementia risk, patients have to be observed for more than 5 years.
Selective attrition should be considered if missed cognitive assessments differ between treatment and placebo groups: SHEP study data e.g. revealed that the placebo group had more missed assessments than the treatment group. In addition, patients with missed assessments had more cardiovascular events during the study period. Thus an assumption was made that 20-30% of those with missed assessments were cognitively impaired, and consequently antihypertensive treatment was shown to reduce the risk of cognitive impairment.

Dementia prevention should also be investigated in younger patients: Even if risk factors are treated, it might be too late to achieve a prevention effect in those ages in which trials have been conducted so far. Strikingly, consistent associations between low blood pressure and Alzheimer’s disease (AD) have been reported, with decreasing blood pressure in the years preceding AD onset. Thus patients with high blood pressure enrolled in hypertension trials might in fact have a decreased short-term risk for dementia, and those who develop dementia in these trials may have other characteristics than dementia in general.

The influence of dementia risk factors has to be clarified with regard to their roles in early, mid and late life, and relative to disease onset. In any case, early treatment of hypertension is essential.

Clinical implications

According to observational studies, antihypertensive treatment is related to a reduced risk of Alzheimer’s disease (AD).

Primary prevention trials published so far have yielded first hints for the prevention of dementia by antihypertensive treatment. Due to these findings the following clinical considerations should be taken into account:

Most of the individuals with hypertension or dementia are not detected. For the prevention of cardiovascular disease the detection and treatment of hypertension, irrespective of whether it prevents dementia or not, is of eminent importance. Convincing study data clearly show that antihypertensive treatment reduces the cardiovascular risk, even among very old people.

Furthermore, it is vital to diagnose cognitive impairment in individuals with hypertension as it may have implications for patient compliance.

Detection and treatment of hypertension in patients with dementia including AlzheimerВґs disease (AD) is important, as prevention of stroke and silent cerebrovascular disease may slow down the course of cognitive decline in AD.

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This release is available in Spanish.

Presented at the 21st Congress of the European College of Neuropsychopharmacology 2008, Barcelona, Spain

References
Berr C, Wancata J, Ritchie K. Prevalence of dementia in the elderly in Europe. European Neuropsychopharmacology 2005;15:463-471

Boustani M, Peterson B, Harris R, et al. Screening for Dementia. Systematic Evidence Review No. 20. Rockville, MD: Agency for Healthcare Research and Quality, June 2003

Jorm AF, Korten AE, Henderson AS. The prevalence of dementia: a quantitative integration of the literature. Acta Psychiatr Scand 1987;76:465-479

Kawas CH. Early AlzheimerВґs disease. N Engl J Med 2003;349:1056-1063

Skoog I, Gustafson D. Update on hypertension and Alzheimer’s Disease. Neurological Research 2006;28:605-611

Skoog I, Lithell H, Hansson L, Elmfeldt D, Hofman A, Olofsson B, Trenkwalder P, Zanchetti A, for the SCOPE Study Group. Effect of baseline cognitive function on cognitive and cardiovascular outcomes: Study on COgnition and Prognosis in the Elderly (SCOPE) – a randomized double-blind trial. Am J Hypertens. 2005;18:1052-1059

Correspondence:
Professor Ingmar Skoog, M.D., Ph.D.
Neuropsychiatric Epidemiology Unit,
Institute of Neuroscience and Physiology,
Sahlgrenska Academy,
Göteborg University, Sweden

Source: Sonja Mak

European College of Neuropsychopharmacology

Saudi Arabia’s warning to elderly Muslims, pregnant women and children against undertaking Hajj/Umrah pilgrimage this year in view of rapidly spreading swine flu worldwide sent a shock wave amongst Muslim community in Britain.

However Health Experts from Association of British Hujjaj a National Hajj specific organisation UK offer their support to the precautionary measures taken by Kingdom of Saudi Arabia and strongly urge elderly, pregnant women and children from UK to defer their pilgrimage until the availability of the Swine flu vaccine. British pilgrims have always been at high risk of infections due to the crowded conditions at ceremonies, accommodation sites and on public transport. Therefore pilgrims must follow the guidelines issued by the authorities and they should be vaccinated against the Swine Flu virus once this vaccine is available at least two weeks before their departure to perform pilgrimage.

Association of British Hujjaj also urge British Muslims community that they should be aware of symptoms of the swine flu disease and in case of fever, cough or shortness of breath, headache, sore throat, tiredness, aching muscles, chills, sneezing, runny nose or loss of appetite they should stay at home, call your GP and do not go into your GP surgery or emergency departments unless you are advised to do so, because you might spread the illness to others.

People are reminded to use clean tissues to cover their mouth and nose when they cough and sneeze and bin the tissues after use and also wash their hands with soap and hot water and this good hygiene practice should also be implemented while they are performing the pilgrimage.

“Take the swine flu threat seriously, be safe than sorry and contact your doctor before travelling” said the Health Experts in their joint statement.

Source
Association of British Hujjaj (Pilgrims) UK (A.B.H)

While the American Stroke Association reports that stroke is the third leading cause of death and one of the top causes of disability in the United States, young adults showing signs of suffering a stroke are sometimes misdiagnosed in hospital emergency rooms, preventing them from receiving early effective treatment that can prevent serious damage.

Performing magnetic resonance imaging sooner on younger stroke patients entering emergency rooms can lower the rate of misdiagnosis and lead to faster appropriate treatment, according to a team of Wayne State University School of Medicine and Wayne State University Physician Group neurologists.

The Wayne State University-Detroit Medical Center Stroke Program team presented its findings during the American Heart Association/American Stroke Association’s International Stroke Conference 2011 in Los Angeles, Calif.

In “Early Performance of MRI is Associated with Lower Rate of Stroke Misdiagnosis in Young Adults,” the team examined the cases of 77 patients with a mean age of 37.9 years who reported to an emergency room displaying stroke symptoms. Of those cases, 14.5 percent of the patients were initially misdiagnosed.

The chances of a misdiagnosis decreased if physicians performed an MRI of the patient within 48 hours. The likelihood of a misdiagnosis increased as the age of the patients decreased. The study concluded that early performance of an MRI leads to greater accuracy of a stroke diagnosis in young adults brought to emergency rooms, and patients younger than 35 years of age are at greater risk of being misdiagnosed when exhibiting stroke symptoms. However, if a patient demonstrating stroke symptoms arrived via ambulance, there was a lower rate of misdiagnosis. The team hypothesized that arrival by ambulance may increase an emergency room staff’s perception of the gravity of the patient’s condition.

“Accurate diagnosis of stroke on initial presentation in young adults can reduce the number of patients who have continued paralysis and continued speech problems,” said Seemant Chaturvedi, M.D., professor of Neurology and director of the WSU-DMC Stroke Program. “We have seen several young patients who presented to emergency rooms with stroke-like symptoms within three to six hours of symptom onset, and these patients did not get proper treatment due to misdiagnosis. The first hours are really critical.”

“Part of the problem is that the emergency room staff may not be thinking ‘stroke’ when the patient is younger,” Dr. Chaturvedi said. “Physicians must realize that a stroke is the sudden onset of these symptoms.” Patients arriving with “seemingly trivial symptoms like vertigo and nausea” should be assessed meticulously, he said.

Delay can be costly. After 48 to 72 hours, there are no major interventions available to improve stroke outcome, he said.

Intravenous delivery of the clot-dissolving agent tissue plasminogen activator is the only U.S. government-approved treatment for acute stroke. The drug must be administered within three hours of symptom onset to reduce permanent disability.

The findings build on the team’s 2009 study in which members reviewed seven years worth of data covering 57 patients between the ages of 16 and 50. The patients were enrolled in the Young Stroke Registry at the Comprehensive Stroke Center at the WSU School of Medicine. Four males and three females (average age 34) in the study were misdiagnosed with migraine headaches, vertigo, alcohol intoxication or other conditions. They were discharged from the emergency room, but later were found to have suffered a stroke.

Other team members who conducted the study include Pratik Bhattacharya, M.D., M.P.H.; Nandakumar Nagaraja, M.D.; Kumar Rajamani, M.D.; Ramesh Madhavan, M.D., D.M.; and Sunitha Santhakumar, M.D., all members of the Wayne State University Department of Neurology and the Wayne State University Physician Group.

Source:
Julie O’Connor
Wayne State University – Office of the Vice President for Research

Data presented at the APA Annual Meeting on Vanda Pharmaceuticals Inc.’s (NASDAQ: VNDA) investigational drug candidate, iloperidone, included its 4-week, short-term Phase III trial, as well as a pooled analysis of three long-term, 52-week trials, studying the efficacy and safety of iloperidone. Iloperidone is a 5HT2/D2 antagonist (“atypical”) antipsychotic currently under review by the U.S. Food and Drug Administration (FDA) for the treatment of schizophrenia. Additional data were presented identifying genetic markers that may help predict response to iloperidone, which Vanda believes could lead to unique, individualized treatment for schizophrenia. These data were presented at the 161st American Psychiatric Association (APA) Annual Meeting in Washington, D.C.

“The data from the clinical trials studying the efficacy and safety of iloperidone suggest that iloperidone could be a useful long-term treatment option for people with schizophrenia,” said Peter Weiden, M.D., Director of the Psychosis Program of the Department of Psychiatry at the University of Illinois at Chicago and one of the leading experts on adverse events of antipsychotic medications.

The data presented are part of the New Drug Application (NDA) submitted and currently under review by the FDA and demonstrate that iloperidone is effective in the short-term treatment of schizophrenia and that iloperidone is non-inferior to haloperidol in long-term maintenance measured as time to relapse over 52 weeks. In these trials, iloperidone showed short- and long-term safety with respect to movement disorders and metabolic effects, including extrapyramidal symptoms (EPS) and akathisia, as well as blood glucose, body weight and lipid profiles.

Schizophrenia is a chronic, severe and disabling disorder that affects approximately one percent of Americans. A high degree of treatment dissatisfaction remains among patients with schizophrenia and the physicians who treat them. The recent CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study, conducted by the National Institute of Mental Health (NIMH) and reported in the New England Journal of Medicine, evaluated several antipsychotic medications and revealed that 74 percent of patients taking antipsychotics discontinued treatment within 18 months, primarily because of insufficient efficacy and tolerability issues.*

Iloperidone’s Efficacy Profile

In data presented on a 4-week Phase III trial, iloperidone (24 mg/day) was more effective than placebo in the short-term treatment of acutely exacerbated schizophrenia, providing relief across both positive and negative symptom domains. Iloperidone showed significantly greater improvement than placebo in Positive and Negative Symptom Scale Total (PANSS-T) scores, as did ziprasidone (-12.0; p=0.006 for iloperidone vs. placebo and -12.3; p=0.012 for ziprasidone vs. placebo); these improvements were seen in both the mean PANSS Negative (PANSS-N), PANSS Positive (PANSS-P) subscales. Additionally, Brief Psychiatric Rating Scale (BPRS) scores improved significantly with iloperidone (-7.4; p=0.013) and ziprasidone (-7.2; p=0.042) versus placebo; and Clinical Global Impression Severity (CGI-S) scores also significantly improved with iloperidone (-0.65; p=0.007) and ziprasidone (-0.67; p=0.013) versus placebo.

In data presented from three prospective, 52-week Phase III trials comparing a dose range of iloperidone (4-16 mg/day given BID, n=981) to haloperidol (5-20 mg/day given BID, n=300), iloperidone was statistically non-inferior to haloperidol in time to relapse (89.8 days with iloperidone vs. 101.8 days with haloperidol; p=0.764). Additionally, the three trials found similar relapse rates and improvements in Clinical Global Impression of Change (CGI-C) and PANSS-T scores.

Iloperidone’s Safety Profile

Data presented from a 4-week Phase III trial demonstrated that rates of worsened Barnes Akathisia Scale (BAS) total score was similar between iloperidone and placebo (8.3% vs. 11.6%; p=0.302) but significantly higher with ziprasidone versus placebo (26.0% vs. 11.6%; p

Approximately 60 million people across the globe have chronic kidney disease, and many will need dialysis or a transplant. Breakthrough research published in the Journal of the American Society Nephrology (JASN) indicates that patients’ own kidney cells can be gathered and reprogrammed. Reprogramming patients’ kidney cells could mean that in the future, fewer patients with kidney disease would require complicated, expensive procedures that affect their quality of life.

In the first study, Sharon Ricardo, PhD (Monash University, in Clayton, Australia) and her colleagues took cells from an individual’s kidney and coaxed them to become progenitor cells, allowing the immature cells to form any type in the kidney. Specifically, they inserted several key reprogramming genes into the renal cells that made them capable of forming other cells.

In a second study, Miguel Esteban, MD, PhD (Chinese Academy of Sciences, in Guangzhou, China) and his colleagues found that kidney cells collected from a patient’s urine can also be reprogrammed in this way. Using cells from urine allows a technology easy to implement in a clinic setting. Even better, the urine cells could be frozen and later thawed before they were manipulated.

If researchers can expand the reprogrammed cells – called induced pluripotent stem cells (iPSCs) – and return them to the patient, these IPSCs may restore the health and vitality of the kidneys. In addition to providing a potentially curative therapy for patients, the breakthroughs might also help investigators to study the causes of kidney disease and to screen new drugs that could be used to treat them.

In an accompanying editorial, Ian Rogers, PhD (Mount Sinai Hospital, in Toronto, Ontario, Canada) noted that “together, these two articles demonstrate the feasibility of using kidney cells as a source of iPSCs, and efficient production of adult iPSCs from urine means that cells can be collected at any time.”

Just as exciting, the ease of collection and high frequency of reprogramming described in these articles may help improve future therapies in many other areas of medicine.

Notes:

Dr. Ricardo’s co-authors include Bi Song, Jonathan Niclis, Maliha Alikhan, Samy Sakkal, Aude Sylvain, Andrew Laslett, Claude Bernard (Monash University, in Clayton, Australia); and Peter Kerr, (Monash Medical Centre, Australia, in Clayton, Australia).

Dr. Esteban’s co-authors include Ting Zhou, Christina Benda, Yinghua Huang, Xingyan Li, Yanhua Li, Xiangpeng Guo, Guokun Cao, Shen Chen, Duanqing Pei (Chinese Academy of Sciences, in Guangzhou, China); Sarah Duzinger (University of Natural Resources and Life Sciences); Lili Hao, Jiayan Wu (Chinese Academy of Sciences, Beijing, China); Yau-Chi Chan, Kwong-Man Ng, Jenny Cy Ho, Hung-Fat Tse (University of Hong Kong, Pokfulam, in Hong Kong, HKSAR, China); Matthias Wieser (University of Natural Resources and Life Sciences and Austrian Center for Industrial Biotechnology (ACIB), in Vienna, Austria); Heinz Redl (Austrian Cluster for Tissue Regeneration, Vienna, Austria); and Johannes Grillari, Regina Grillari-Voglauer ( University of Natural Resources and Life Sciences and Evercyte GmbH, in Vienna, Austria).

Disclosures: The authors reported no financial disclosures.

The articles: “Generation of Induced Pluripotent Stem Cells from Human Kidney Mesangial Cells” and “Generation of Induced Pluripotent Stem Cells from Urine,” and the editorial: “Induced Pluripotent Stem Cells from Human Kidney,” are available online.

Source:
Adrienne Lea

American Society of Nephrology