Every 5°C rise in maximum temperature pushes up the rate of hospital admissions for serious injuries among children, reveals one of the largest studies of its kind published online in Emergency Medicine Journal.

Conversely, each 5° C drop in the minimum daily temperature boosts adult admissions for serious injury by more than 3%, while snow prompts an 8% rise, the research shows.

The authors base their findings on the patterns of hospital treatment for both adults and children in 21 emergency care units across England, belonging to the Trauma Audit and research Network (TARN), between 1996 and 2006.

Any patient requiring hospital admission for more than three days, a transfer to another hospital or critical care, or who subsequently died after being injured, was included in the analysis in a bid to see if clear temporal patterns emerged, which were linked to prevailing weather conditions.

These criteria applied to just under 60,000 patients, whose average age was 48 (adults) and 10 (children). The data analysis indicated strong seasonal trends.

Among adults, every 5°C rise in maximum daily temperature and each additional two hours of sunshine increased the admission rate for serious injury by just under 2%.

But an even stronger pattern was seen among admissions for children, with equivalent temperature rises prompting a 10% increase in admissions and extra sunshine a 6% increase.

The authors calculate that the rate of children’s admissions between the months of April and September may be up to 50% higher than average.

At the other end of the scale, each 5°C drop in the minimum daily temperature boosted adult admissions for serious injury by more than 3%, while snow prompted an 8% rise.

Admissions peaked at weekends.

“The results of this extensive study, covering many trauma units of varying size and location over an extensive period of time, show strong and intuitively convincing relationships between recorded weather and trauma admissions,” say the authors.

They conclude that this analysis could be used to predict daily admission rates, and therefore staffing levels and the planning of other resources.

Notes

Emergency Medicine Journal is one of more than 30 specialist titles published by BMJ Group.

Source:

British Medical Journal

Senator Orrin Hatch (R-Utah) on Wednesday joined a group of House Republicans to support a bill… (HR 810) that would loosen federal restrictions on human embryonic stem cell research and predicted that Congress will pass the legislation, the Salt Lake Tribune reports (Gehrke, Salt Lake Tribune, 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. The House legislation 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. The legislation would not allow federal funding for embryonic stem cell research on stem cell lines or embryos created expressly for research purposes. Rep. Michael Castle (R-Del.), who is the primary sponsor of the measure, in March after meeting with House Speaker Dennis Hastert (R-Ill.), Majority Whip Roy Blunt (R-Ohio) and Chief Deputy Majority Whip Eric Cantor (R-Va.) said that the leaders concluded that the House should move forward in some way on the current legislation or something similar to it (Kaiser Daily Reproductive Health Report, 3/25).

Hatch Comments
Hatch, who is an abortion-rights opponent, said that the House bill is a “critical first step” toward loosening the embryonic stem cell policy, CQ HealthBeat reports (CQ HealthBeat, 5/11). Although Hatch in the Senate has co-sponsored a “more expansive” bill (S 876) to loosen the embryonic stem cell research restrictions, he said the House legislation is “an ingenious approach to break through the logjam” on the issue, according to CQ Today (Schuler, CQ Today, 5/11). “I come to this issue as a proud right-to-life senator,” Hatch said, adding, “I do believe, very strongly, that it is possible to be both antiabortion and pro-embryonic stem cell research. I believe that pro-life means caring for the living as well” (Salt Lake Tribune, 5/12). Castle said that the measure “expands (the research) within Bush’s ethical guidelines” while eliminating the date restriction set down in Bush’s executive order (CQ Today, 5/11).

Prospects, Ad Campaign
Rep. Charlie Bass (R-N.H.) said that more than 200 House members already have committed to voting for the bill, according to the Tribune (Salt Lake Tribune, 5/12). Some House members used their votes on the federal budget “as leverage” to get a commitment from House leaders for a floor vote on the embryonic stem cell research bill, and the vote could come next week, according to Roll Call (Kondracke, Roll Call, 5/12). Hatch said there are currently about 60 votes for the House bill in the Senate. He added that he has had discussions with Senate Majority Leader Bill Frist (R-Tenn.) about scheduling a floor vote, according to the Tribune. “If we can pass this in the House, I really believe we can pass it in the Senate,” Hatch said (Salt Lake Tribune, 5/12). However, Bush has “resisted” change to his policy and has not said whether he would veto the House measure if it passed both chambers, according to CQ Today (CQ Today, 5/11). Hatch said that Bush would be under pressure from the scientific and medical communities to sign the bill, according to the Tribune (Salt Lake Tribune, 5/12). House Republican moderates on Wednesday announced an advertisement campaign to support the bill. The campaign will highlight former first lady Nancy Reagan’s support for loosening restrictions on embryonic stem cell research (CQ Today, 5/11). Print ads are scheduled to appear this week in Roll Call and The Hill, and television ads will be shown on national cable television stations in a few weeks, according to the Washington Times (Washington Times, 5/12).

Ethics Panel Report
The President’s Council on Bioethics on Thursday is scheduled to release a report that was intended to outline possible ways to make embryonic stem cell research less controversial by describing methods for producing stem cells without destroying human embryos, but the council could not reach any unanimous recommendations, according to the Chicago Tribune. The council’s disagreements over the new and “in some cases strange” methods proposed by members shows “how difficult it can be to bring together opposing viewpoints” on the issue, according to the Tribune. One proposal by council member William Hurlbut, a Stanford University bioethicist, would use cloning technology to produce an “embryo-like” group of cells from which stem cells could be extracted, according to the Tribune. Supporters of the approach say that the group of cells would “not be an actual human embryo” but would still produce stem cells for research, according to the Tribune. However, while opponents say such an approach would be “well-intentioned,” it still could “violate the sanctity of human life,” according to the Tribune. The council rejected a proposal to obtain stem cells by removing single cells from living embryos being used in fertility treatments. The technique would not require the destruction of embryos but could put the embryos “at risk,” which the council called “an unacceptable trade-off,” according to the Tribune. 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” (Manier, Chicago Tribune, 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.

Scientists at Schepens Eye Research Institute have discovered what chemical in the eye triggers the dormant capacity of certain non-neuronal cells to transform into progenitor cells, a stem-like cell that can generate new retinal cells. The discovery, published in the March issue of Investigative Ophthalmology and Visual Science (IOVS), offers new hope to victims of diseases that harm the retina, such as macular degeneration and retinitis pigmentosa.

“This study is very significant. It means it might be possible to turn on the eye’s own resources to regenerate damaged retinas, without the need for transplanting outside retinal tissue or stem cells,” says Dr. Dong Feng Chen, associate scientist at Schepens Eye Research Institute and Harvard Medical School, and the principal investigator of the study. “If our next steps work in animal disease models, we believe that clinical testing could happen fairly quickly.”

Scientists have long been aware of MГјller cells (which exist in great abundance in the eye) and have generally assumed that they were responsible for keeping retinal tissue protected and clear of debris. In recent years, however, researchers have reported that these cells sometimes exhibit progenitor cell behavior and re-enter the cell cycle (dividing and differentiating into other type of cells). Progenitor cells are similar to stem cells but are more mature and are more limited in the number of cells types they can become.

But until this study, scientists have not understood what triggers the transformation. In their study, Chen and her team observed that when the naturally occurring chemicals known as glutamate and aminoadipate (which is a derivative of glutamate) were injected into the eye, the MГјller cells began to divide and proliferate. Not certain if these chemicals directly signaled the transformation, they tested them in the laboratory and in mice.

They added each chemical separately to cultures of pure MГјller cells and injected each into the space below the retina in healthy mice. In both cases, the cells became progenitor cells and then changed into retinal cells. And with aminoadipate, the newly minted retinal cells migrated to where they might be needed in the retina and turned into desirable cell types. Specifically, they showed that by injecting the chemical below the retina, the cells give rise to new photoreceptors – the type of cells that are lost in retinitis pigmentosa or macular degeneration, as a result, leading to blindness.

The team’s next step will be to test this process in animals that have been bred to have diseases that mimic macular degeneration and retinitis pigmentosa. The goal would be to learn if damaged retinas regenerate and vision improves. The team will likely use just aminoadipate because it only binds with MГјller cells without the side effects of glutamate, which can actually harm retina cells in large doses.

“We believe that a drug created from the chemical aminoadipate or a similar compound has great potential for healing damaged retinas,” says Chen.

###

Other authors of the study include:

Masumi Takeda 1,2,3
Akira Takamiya 1,2,3
Jian-wei Jiao 1,2
Kin-Sang Cho 1,2
Simon G. Trevino 1
Takahiko Matsuda 4
Dong F. Chen 1,2

1 The Schepens Eye Research Institute, Boston, Massachusetts

2 Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts

3 Department of Ophthalmology, Asahikawa Medical College, Asahikawa, Japan

4 Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts.

Schepens Eye Research Institute is an affiliate of Harvard Medical School and the largest independent eye research institute in the nation.

Source: Patti Jacobs

Schepens Eye Research Institute

It’s an unfortunate fact backed by studies of former professional football and soccer players: injury to joint cartilage escalates the risk of developing of osteoarthritis (OA). However, why this occurs – the details of how joint cartilage cells respond to acute trauma and how this response leads to progressive cartilage degradation – remains open to investigation.

To shed further light on this issue of intense research interest, an international team of rheumatologists and biotechnologists conducted a microarray screening of adult human joint cartilage subjected to injury. Led by Dr. Francesco Dell’Accio, a Clinician Scientist Fellow of the Arthritis Research Campaign, the team reported in the May issue of Arthritis & Rheumatism the full-genome characterization of the moleculer response of adult human articular cartilage to mechanical injury.

The gene expression profile of cartilage explants 24 hours after mechanical injury was compared to that of uninjured control explants using microarray technology. The explants were obtained either from uninvolved cartilage areas of knees affected by OA or from healthy cartilage from one individual who underwent a limb amputation following a road traffic accident. The expression of selected genes was then confirmed using real time PCR and immunohistochemistry.

In the injured samples, a total of 690 genes were significantly either up- or downregulated at least 2-fold compared with expression in the uninjured samples. Significant clusters included genes associated with cell signaling, wound healing, and skeletal development, as well as genes previously found to be differentially expressed in OA cartilage. Members of the WNT, TGFОІ, and FGF family of signalling molecules were included in the regulated gene list. A targeted analysis of the Wnt signaling pathway in injured cartilage revealed up-regulation of the ligand Wnt-16, down-regulation of the secreted inhibitor FRZB, nuclear accumulation of ОІ-catenin, and upregulation of several known WNT target genes supporting net activation of this signalling pathway. Wnt-16 and ОІ-catenin were barely detectable in preserved cartilage from OA joints but dramatically up-regulated in areas of the same joint with moderate to severe OA damage.

This study indicates that several genes encoding signalling molecules are regulated following cartilage injury in adult individuals. Although it is tempting to speculate that some of these genes represent a reparative response, Dr Dell’Accio stresses that at the moment we do not know whether such phenomena are supporting repair (hence representing potential therapeutic tools) or even play a role in the progression of damage (hence potential therapeutic targets). Hence further investigation is needed “to optimally target the respective pathways to promote joint surface cartilage defect repair or to stop further joint surface breakdown, thereby preventing the development of posttraumatic OA.”

In a related editorial, Dr. Tonia L. Vincent and Dr. Jeremy Saklatva of Imperial College London raise the question of whether the response of cartilage to injury is relevant to osteoarthritis. As they argue, the findings of Dr. Dell’Accio and his colleagues suggest that Wnt activity may be important in OA, possibly driving bone changes in disease, such as osteophyte formation, but not necessarily directly injury-regulated. Yet, as they also note, studies devoted to unraveling the link between joint injury and OA risk are leading the way toward a better understanding of the tissue processes and the signaling pathways activated in disease. “Further investigation into the pathways revealed in this injury microarray is likely to be highly informative,” Dr. Vincent states.

###

Article: “Identification of the Molecular Response of Articular Cartilage to Injury, by Microarray Screening: Wnt-16 Expression and Signaling After Injury and in Osteoarthritis,” Francesco Dell’Accio, Cosimo De Bari, Noha M. Eltawil, Paul Vanhummelen, and Costantino Pitzalis, Arthritis & Rheumatism, May 2008; 58:5 pp. 1410-1421.

Editorial: “Is the Response of Cartilage to Injury Relevant to Osteoarthritis,” Tonia L. Vincent and Jeremy Saklatvala, Arthritis & Rheumatism, May 2008; 58:5 pp. 1207-1210.

Source: Sean Wagner

Wiley-Blackwell

The toxic gas formaldehyde is contained in building materials including carpeting, curtains, plywood, and adhesives. As it is emitted from these sources, it deteriorates the air quality, which can lead to “multiple chemical sensitivity” and “sick building syndrome”, medical conditions with symptoms such as allergies, asthma, and headaches. The prevalence of formaldehyde and other volatile organic compounds (VOC) is greater in new construction.

Researchers are studying the ability of plants to reduce formaldehyde levels in the air. A study led by Kwang Jin Kim of Korea’s National Horticultural Research Institute compared the absorption rate of two types of houseplants. The results of the experiment on Weeping Fig (Ficus benjamina) and Fatsia japonica, an evergreen shrub, were published in the Journal of American Society for Horticultural Science.

During the study, equal amounts of formaldehyde were pumped into containers holding each type of plant in three configurations: whole, roots-only with the leafy portion cut off, and aerial-only, with the below-ground portion sealed off, leaving the stem and leaves exposed.

The results showed the combined total of aerial-only and roots-only portions was similar to the amount removed by whole plants. Complete plants removed approximately 80% of the formaldehyde within 4 hours. Control chambers pumped with the same amount of formaldehyde, but not containing any plant parts, decreased by 7.3% during the day and 6.9% overnight within 5 hours. As the length of exposure increased, the amount of absorption decreased, which appeared to be due to the reduced concentration of the gas.

Aerial parts of reduced more formaldehyde during the day than at night. This suggests the role played by stomata, tiny slits on the surface of the leaves that are only open during the day. The portion of formaldehyde that was reduced during the night was most likely absorbed through a thin film on the plant’s surface known as the cuticle. Root zones of ficus removed similar amounts between night and day. However, japonica root zones removed more formaldehyde at night.

Researchers consider microorganisms living among the soil and root system to be a major contributor to the reduction. Japonica were planted in larger pots than the ficus, which may account for the lower night reduction rate of the latter. More knowledge of the contributions of microorganisms is cited by the study to be important in further understanding the air purifying potential of plants.

###

The complete study and abstract are available on the ASHS J. Amer. Soc. Hort. Sci. electronic journal web site: journal.ashspublications/cgi/content/abstract/133/4/521

Founded in 1903, the American Society for Horticultural Science (ASHS) is the largest organization dedicated to advancing all facets of horticultural research, education, and application. More information at ashs

Source: Michael W. Neff

American Society for Horticultural Science

University of Utah researchers used data from Portuguese water dogs – the breed of President Barack Obama’s dog Bo – to help find a gene that gives some dogs curly hair and others long, wavy hair.

It was part of a National Institutes of Health (NIH) study – published online Thursday, Aug. 27 by the journal Science – showing that variations in only three genes account for the seven major types of coat seen in purebred dogs. The findings also point the way toward understanding complex human diseases caused by multiple genes.

“We were part of a team that found three genes that control 90 percent of the seven coat types that characterize different breeds of purebred dogs,” says K. Gordon Lark, one of 20 co-authors of the study and a distinguished professor emeritus of biology at the University of Utah.

“We helped identify the gene that controls curly or wavy coats,” adds study co-author Kevin Chase, a University of Utah research specialist in biology.

The study’s first author is Edouard Cadieu, and its senior author is Elaine Ostrander, both of the National Human Genome Research Institute in Bethesda, Md. Other authors came from that institute, which is part of NIH, and from the University of California’s Davis and Los Angeles campuses, Cornell University in Ithaca, N.Y., and Affymetrix Corp., in Santa Clara, Calif.

The study showed that combinations of various forms of only three genes – named RSPO2, FGF5 and KRT71 – account for seven major coat types in purebred dogs.

By analyzing more than 1,000 dogs from 80 domestic breeds, the researchers found that RSPO2 is the gene associated with whether or not a dog has a moustache and large eyebrows (known together as “furnishings”); FGF5 is linked to whether a dog’s fur is long or short; and KRT71 determines if the hair is curly or wavy.

Mutant Genes and the Well-Dressed Dog

All purebred dogs have the three genes, but the presence or absence of mutant, variant forms of those genes – rather than the ancestral forms inherited from wolves – determines coat types:
Short-haired dogs like basset hounds have none of the variant genes, just the ancestral form of each gene.

Wire-haired dogs such as Australian terriers have the variant form of only the RSPO2 gene.

Dogs with wiry and curly hair – airedale terriers, for example – have variants of both RSPO2 and KRT71 genes.

Long-haired dogs like golden retrievers have a variant form of the FGF5 gene.

Long-haired dogs with furnishings, such as the bearded collie, have variant forms of FGF5 and RSPO2.

Curly haired dogs such as Irish water spaniels have the variant forms of the FGF5 and KRT71 genes.

Curly haired dogs with furnishings – such as the bichon frise breed and some Portuguese water dogs, including President Obama’s dog Bo – have the variant form of all three genes.

Portuguese water dogs come in both curly haired and wavy haired varieties, depending on what form of the KRT71 gene they have. Chase says wavy haired Portuguese water dogs fit in the new study’s long hair with furnishings category.

Chase says breeders characterized First Dog Bo as curly with furnishings, while Lark’s Portuguese water dog, Mopsa, has wavy hair, even though she appears pretty curly. Chase notes that the KRT71 gene really controls the extent of curl, not curl versus no curl

What about the fur characteristics of mutts? Because mutts are not part of a closed breeding population like each breed of purebred dog, it’s difficult to separate the genetic contributors to their traits, Chase says.

“We don’t know enough about the genetics of mutts,” Lark adds.

From Portuguese Water Dogs to Human Disease

Chase and Lark assisted the NIH research by sharing data on Portuguese water dogs, which they have studied for years.

“Our contribution to this paper is data collected on the Portuguese water dog that indicated that keratin genes controlled the amount of curliness,” Lark says. “Our data plus other data from the Ostrander group narrowed this down to KRT71.”

KRT71 carries the code that produces keratin 71, a structural protein in hair.

Even though he and Chase studied the genetics of curliness stemming from KRT71, Lark says the other two genes involved in determining dog coat types are more interesting in the sense that they produce proteins that regulate a variety of processes in living organisms, not just the kind of coat a dog has. That makes them relevant to diseases of dogs and humans.

“Dogs share many diseases and other traits with humans,” Lark says. “That’s why they were used for many decades so extensively for pharmaceutical and medical-physiological-biochemical testing. Not surprisingly they share much of their genome [genetic blueprint] with humans also.”

Lark says a dog bred for a desired trait may end up, years later, more vulnerable to cancer, immune disorders or other diseases of aging, and thus have a shorter life span.

“Ultimately the most important part of this paper – mostly the work of Ostrander’s group – is that we will be able to get glimpses of how major regulatory genes interact with other genes to change the functioning of an animal in a way that does not kill it, but that may eventually compromise its longevity or its functioning as it ages,” Lark says.

Earlier studies involving Ostrander and Lark revealed genetic variations that make small dogs small and account for longevity in dogs.

A Pup for a President and a Geneticist

Lark, once a soybean geneticist, has run a long-term dog genetics research effort known as the Georgie Project, after Georgie, a stray Portuguese water dog he adopted in 1986. Georgie died in 1996, and when Lark sought a replacement, a breeder sent him Mopsa – now 13 years old – and nagged him to study the breed’s genetics.

Lark and Chase learned that the breed was ideal for genetics research because all Portuguese water dogs descended from a small group of “founders” and could help the search for genes responsible for complex traits – including human diseases caused by multiple interacting genes.

Portuguese water dogs gained publicity earlier this year when President Obama fulfilled his promise to get a dog for his daughters by obtaining Bo, a Portuguese water dog, reportedly as a gift from U.S. Sen. Edward Kennedy, D-Mass.

“As a supporter of Obama, I feel glad that he has a good dog,” Lark says. “He has good taste and a good dog.”

The portion of the new study conducted at the University of Utah was funded by NIH’s National Institute of General Medical Sciences, the Judith L. Chiara Charitable Fund and the Nestle Purina PetCare Co.

Source:
Lee Siegel

University of Utah

The Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending approval of Zypadhera (olanzapine powder and solvent for prolonged release suspension for injection, also known as olanzapine long-acting injection) for maintenance treatment of adult patients with schizophrenia sufficiently stabilized during acute treatment with oral olanzapine, Eli Lilly and Company (LLY) announced.

The opinion issued by the CHMP will need to be ratified by the European Commission before the new indication is considered approved. The Commission usually makes a decision within two to three months of a CHMP recommendation.

Olanzapine long-acting injection is an investigational formulation that combines olanzapine, an atypical antipsychotic, with pamoic acid resulting in a salt that sustains the delivery of olanzapine for a period of up to four weeks. Long-acting injectables have been associated with improved treatment for patients who struggle with adherence to oral medications.(i)

“Because of the chronic and severe nature of schizophrenia, persistent challenges with adherence and the limited number of depot formulations available, we believe that olanzapine long-acting injection has the potential to become a valuable treatment option for patients,” said David McDonnell, M.D., clinical research physician at Lilly.

The CHMP opinion was based on a comprehensive data package comprising eight studies, involving 2,054 patients, including a double-blind, placebo- controlled, fixed-dose study (HGJZ)(ii); a double-blind, oral olanzapine- controlled, fixed-dose study (HGKA)(iii); and six open-label studies(iv). In these trials, olanzapine long-acting injection (LAI) was found to be similar to olanzapine oral in terms of rate of symptom exacerbation and showed a similar safety profile as the oral formulation with the exception of injection-related events, including olanzapine LAI Post-Injection Syndrome. (v) Additionally, the trials showed that olanzapine long-acting injection (LAI) separated from placebo as measured by total PANSS score reduction over 8 weeks of treatment, and a drug effect that was observed as early as one week from the first injection.(vi); olanzapine long-acting injection was studied as a once every-four week and a once every-two week injection, without the need for oral antipsychotic supplementation.

As of August 31, 2008, across all clinical trials, olanzapine LAI Post- Injection Syndrome events, including a range of symptoms of sedation (from mild in severity to unconsciousness) and/or delirium (including confusion, disorientation, agitation, anxiety and other cognitive impairment), have been seen in 0.07 percent of injections and 1.4 percent of patients, all of whom have recovered fully. (vii)

As part of the marketing authorization, Lilly has proposed a comprehensive risk minimization plan for identifying and managing olanzapine LAI Post- Injection Syndrome. The plan includes a requirement for a post-injection observation period described in the product labeling, and an extensive healthcare provider training and educational program.

Earlier this month, Zypadhera was approved for use in New Zealand. Independent regulatory reviews of olanzapine LAI applications for schizophrenia are ongoing in the United States, Canada, Australia and other countries.

About Long-acting Injectable Antipsychotic Medications

The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines state that poor or partial treatment compliance is a major problem in the long-term treatment of schizophrenia. Depot formulations should be considered as a treatment option when a patient expresses a preference for such treatment due to convenience or if it is determined that a depot formulation is necessary to help with compliance.(viii)

Long-acting antipsychotic formulations have been associated with improved treatment adherence and reduced treatment failures.(ix) By administering long- acting medications, healthcare professionals know when patients have received their medication and can immediately detect non-adherence when a patient fails to return for a scheduled injection.* Different from both oral and injected short-acting formulations, long-acting formulations of antipsychotics allow for stable concentrations of the active drug to remain at a therapeutic range for an extended period of time.(xi)

About Schizophrenia

Schizophrenia is a severe and debilitating illness with such symptoms as delusions (false beliefs that cannot be corrected by reason), hallucinations (usually in the form of non-existent voices or visions), disorganized speech and severe disorganized or catatonic behavior. These signs and symptoms are associated with marked social or occupational dysfunction. Features of schizophrenia consist of characteristic signs and symptoms that have been present for a significant portion of time during a one-month period, with some signs of the disorder persisting for at least six months.(xii) In addition to these symptoms, patients with schizophrenia are at greater risk for medical comorbidities than the general population.

About Olanzapine

Since olanzapine was introduced in 1996, it has been prescribed to more than 26 million people worldwide. Olanzapine is not recommended for use in patients under 18 years of age.

In Europe, olanzapine is indicated for schizophrenia and in clinical trials, it has shown to be effective in maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response. It also is indicated for the treatment of moderate to severe manic episodes and, in those patients whose manic episode has responded to olanzapine treatment, it is indicated for the prevention of recurrence in patients with bipolar disorder.

SAFETY INFORMATION

Hyperglycaemia and/or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma has been reported rarely, including some fatal cases. In some cases, a prior increase in body weight has been reported, which may be a predisposing factor. Appropriate clinical monitoring is advisable, particularly in diabetic patients and in patients with risk factors for diabetes mellitus for which regular glucose control is recommended.

Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebo-controlled clinical trials. Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline. Lipid alterations should be managed as clinically appropriate, particularly in dyslipidemic patients and in patients with risk factors for the development of lipids disorders.

The proportion of patients who had adverse, clinically significant changes in weight gain, glucose, total/LDL/HDL cholesterol or triglycerides increased over time. In adult patients who completed 9-12 months of therapy, the rate of increase in mean blood glucose slowed after approximately 4-6 months.

As with all antipsychotic medications, a rare and potentially fatal condition known as Neuroleptic Malignant Syndrome (NMS) has been reported rarely with olanzapine. If signs and symptoms appear, immediate discontinuation is recommended. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure.

Also, as with all antipsychotic treatment, prescribing should be consistent with the need to minimize Tardive Dyskinesia (TD). The risk of developing TD increases as the duration of treatment. If signs and symptoms of TD are observed a dose reduction or discontinuation should be considered and it should be noted that the symptoms can temporally deteriorate or even rise after discontinuation.

Other potentially serious adverse events include low blood pressure, seizures, elevated prolactin levels, elevated liver enzymes, thromobembolism, neutopenia, sweating, insomnia, tremor, anxiety, nausea, or vomiting.

Olanzapine should not be used in patients who have a hypersensitivity to the drug nor those with narrow angle glaucoma. It should not be used to treat dementia-related psychosis and/or behavioural disturbances because of an observed increase in death and cerebrovascular accident. It should also not be used in the treatment of dopamine agonist associated psychosis in patients with Parkinson’s disease.

The most frequently (seen in >/= 1% of patients ) reported adverse reactions associated with the use of olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, cholesterol, glucose and triglyceride levels, glucosuria, increased appetite, dizziness, akathisia, parkinsonism, dyskinesia, orthostatic hypotension, anticholinergic effects, transient asymptomatic elevations of hepatic transaminases, rash, asthenia, fatigue and oedema.

About Lilly

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers – through medicines and information – for some of the world’s most urgent medical needs. Additional information about Lilly is available at lilly

P-LLY

This press release contains forward-looking statements about the safety and efficacy of olanzapine long acting injection (LAI) and reflects Lilly’s current beliefs. However, as with any investigational pharmaceutical product, there are substantial risks and uncertainties in the process of research, development, regulatory milestones and commercialization. There is no guarantee that olanzapine LAI will be approved for the treatment of schizophrenia or that if approved, it will be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly’s filings with the United States Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.

References

i. Maxine X. Patel and Anthony S. David. Why aren’t depot antipsychotics prescribed more often and what can be done about it? Advances in Psychiatric Treatment (2005) 11: 203-211.

ii. Lauriello J., Lambert T., Andersen S., Lin D., Taylor C.C., McDonnell D. Olanzapine Long-Acting Injection: An 8-Week Double-Blind, Randomized, Placebo-Controlled Study in Acutely-Ill Patients with Schizophrenia. Journal of Clinical Psychiatry. May 2008.

iii. Detke H., McDonnell D., Kane J., Naber D., Sethuraman G., Lin D. Olanzapine Long-Acting Injection for the Maintenance Treatment of

Schizophrenia: A 24-Week, Randomized, Double-Blind Trial. Data presented at Schizophrenia International Research Society Meeting. June 21-25, 2008.

iv. McDonnell D., Andersen S., Detke H., Watson S. 160-week interim results from an open-label extension trial of olanzapine long-acting injection. Data presented at Schizophrenia International Research Society Meeting. June 21-25, 2008.

v. Detke H., McDonnell D., Kane J., Naber D., Sethuraman G., Lin D. Olanzapine Long-Acting Injection for the Maintenance Treatment of Schizophrenia: A 24-Week, Randomized, Double-Blind Trial. Data presented at Schizophrenia International Research Society Meeting. June 21-25, 2008.

vi. Lauriello J., Lambert T., Andersen S., Lin D., Taylor C.C., McDonnell D. Olanzapine Long-Acting Injection: An 8-Week Double-Blind, Randomized, Placebo-Controlled Study in Acutely-Ill Patients with Schizophrenia. Journal of Clinical Psychiatry. May 2008.

vii. McDonnell D., Sorsaburu S., Brunner E., Detke H., Andersen S., Bergstrom R., Mitchell M., Ogle K., Watson S., Corya S. Post-Injection Delirium/Sedation Syndrome Observed with Olanzapine Long-Acting Injection. Data Presented at European College of Neuropsychopharmacolgy Meeting. August 30-September 3, 2008.

viii. Falkai P., Wobrock T., Lieberman J., Glenthoj B.,Gattaz W.F., Moller H.J & WFSBP Task Force On Treatment Guidelines For Schizophrenia. The World Journal of Biological Psychiatry, 2006; 7(1): 5/40

ix. Maxine X. Patel and Anthony S. David. Why aren’t depot antipsychotics prescribed more often and what can be done about it? Advances in Psychiatric Treatment (2005) 11: 203-211.

x. Kane J.M et al. Guidelines for depot antipsychotic treatment in schizophrenia. European Neuropsychopharmacology, Volume 8, Number 1, 1 February 1998, pp. 55-66(12). p. 58.

xi. Maxine X. Patel and Anthony S. David. Why aren’t depot antipsychotics prescribed more often and what can be done about it? Advances in Psychiatric Treatment (2005) 11: 203-211.

xii. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, fourth edition, 2000, pp. 298.

Eli Lilly and Company

lilly

Research has officially begun in the largest study ever conducted to measure levels of various gases and airborne pollutants emitted from poultry, dairy and swine facilities across the nation.

Led by Purdue University, the 2.5-year, $14.6 million study will measure levels of hydrogen sulfide, particulate matter and ammonia, among other chemicals, released from livestock facilities. Measurements have begun in locations throughout the country and by midsummer will be under way at all 20 study sites in eight states.

“This study will give us a wealth of much-needed scientific information about livestock-generated air pollution,” said Al Heber, the Purdue professor of agricultural and biological engineering who leads the study. “There has never been a study this comprehensive or long-term.”

The “National Air Emission Monitoring Study,” conducted under the advisement of the U.S. Environmental Protection Agency, will record two continuous years of emission data at concentrated animal feeding operations. These comprise barns and manure storage units like lagoons.

Using advanced measurement tools and methods, this study will fill gaps in EPA’s database, Heber said, since little quantitative research has been done on these emissions.

Researchers also will measure emissions from open-air sources like dairy corrals and manure basins and lagoons. Specialized sensors, including lasers and reflectors, will measure levels of hydrogen sulfide and ammonia released.

“This data will help us be able to estimate the quantity of emissions given a farm’s activities and number of animals,” said Richard Grant, a professor of agronomy and a principal investigator in the study. He said the study would help develop an “emissions-estimating methodology.”

In addition to the large amount of data that will be gathered, Heber said the study will establish infrastructure that should later allow researchers to test different abatement strategies to improve downwind air quality.

“For example, if we put hogs on certain diets, we can significantly reduce ammonia emissions,” Heber said. “These experiments are needed to develop real solutions in the field.”

Other studies have shown that levels of emissions vary by temperature and time of day, factors that can be considered in developing better air-emission controls, Heber said. Many of the producers whose farms are being monitored in the study have indicated receptiveness to follow-up studies on such mitigation strategies, he said.

Two other principal investigators from Purdue include Teng Lim and Jiqin Ni, and Bill Bogan is the study’s operations manager.

Purdue will collaborate with 11 researchers from seven different universities in the study. These include Frank Mitloehner and Ruihong Zhang from University of California-Davis; Curt Gooch from Cornell University; Steve Hoff, Jacek Koziel and Jay Harmon from Iowa State University; Larry Jacobson from University of Minnesota; Wayne Robarge and Lingjuan Wang from North Carolina State University; Ken Casey from Texas A&M University’s Agricultural Experiment Station; and Pius Ndegwa from Washington State University-Pullman.

This study is funded by the Agricultural Air Research Council, a non-profit organization that receives its funds from livestock industry groups, and will be overseen by the EPA Office of Air Quality Planning and Standards.

Writer: Douglas M Main

purdue.edu

UroToday – In the online edition of the Journal of Clinical Oncology, Dr. Douglas McNeel and associates report a phase I/IIa trial of a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with stage D0 prostate cancer (CaP). PAP is a prostate tumor antigen that can elicit an immunologic antigen-specific CD8+ T cell response. The vaccine, pTVG-HP, is a plasmid DNA encoding the full length human PAP cDNA downstream of a eukaryotic promoter.

Study patients included those with a rising PSA after primary therapy (stage D0). The design was single institution, with a dose escalation; level 1 to 100ug, level 2 to 500ug and level 3 to 1,500ug. Dose-limiting toxicity was defined as adverse events higher than grade 2. The maximum tolerated dose (MTD) was the dose level preceding a level at which more than one DLT was observed, or the 1,500ug level in the absence of DLTs. Patients were treated 6 times at 14-day intervals with the vaccine co-administered with 200ug granulocyte-macrophage colony-stimulating factor. The vaccine was delivered intradermally on the arm in two to three divided administrations. Blood tests including PSA were performed monthly. Autologous antigen-presenting cells were prepared by culturing tissue flask-adherent peripheral blood mononuclear cells (PBMNC) in the presence of 20ng/ml recombinant human granulocyte-macrophage colony-stimulating factor and 10ng/ml recombinant human IL-4 for 6 days. T cells were sorted and cultured with dendritic cells plus PAP protein, PSA protein, and tetanus toxoid. Cells were transferred to immunospot plates coated with anti-IFNпЃ§ capture antibody. T-cell response was determined by BrdU incorporation assay with flow cytometric evaluation.

The patient cohort consisted of 22 men and no adverse events higher than grade 2 occurred, so 9 patients were accrued at the 3 dose escalation levels and an additional 13 men at the 1,500ug dose level. Induction of PAP-specific IFNпЃ§-secreting CD8+ T cells was the primary response. Three of 22 men had evidence of a response to PAP, one in each treatment dose group. Two of 22 patients had a CD8+ IFNпЃ§-secreting response to tetanus toxoid. Six of 22 men had a 3-fold or higher increase in CD8+ proliferative T-cells. No patient had either a complete PSA response or a PSA decline greater than 50%. However, the median PSADT increased from 6.5 months pre-treatment to 8.5 months on-treatment to 9.3 months post-treatment.

McNeel DG, Dunphy EJ, Davies JG, Frye TP, Johnson LE, Staab MJ, Horvath DL, Straus J, Alberti D, Marnocha R, Liu G, Eickhoff JC, Wilding G

J Clin Oncol. 2009 Jul 27. Epub ahead of print
doi:10.1200/JCO.2008.19.9968

UroToday Contributing Editor Christopher P. Evans, MD, FACS

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Crux Biomedical®Inc. announced that it has successfully enrolled the first patient in its Retrieve 2 pivotal U.S. IDE trial. The trial will evaluate the safety and efficacy of Crux’s new Vena Cava Filter (VCF). The Crux VCF is a retrievable, implantable filter which is designed to trap blood clots that can lead to a potentially fatal pulmonary embolism (PE). It is the first VCF to be developed that is bidirectional and thus permits insertion or retrieval from either the femoral or jugular veins.

The implant was performed by Jon Hupp, a vascular surgeon at Anne Arundel Medical Center, located in Annapolis, Maryland. “Current retrievable filters either require short term removal or seem to have an unacceptable frequency of migration or fracture issues. Hopefully, the Crux filter will improve on this situation. There are a large number of patients who could benefit from such a device,” Dr. Hupp explained. Crux’s Retrieve 2 study is being conducted at 18 sites in the United States.

Vena cava filters were originally designed as a permanent implant only. Subsequent design improvements have provided physicians with the option to retrieve the filter once a patient is no longer at risk of a PE. Presently in the United States, over 50% of vena cava filters implanted are designed for retrieval at a later date. However, currently cleared vena cava filters are associated with a variety of complications. These complications present challenges to the physician when attempting to retrieve the device. The Crux VCF design will prevent filter tilt and associated challenges in retrieval. “Physicians are very enthusiastic with our bidirectional design and the additional choices that it will provide in delivery and retrieval of the implant,” stated Mel Schatz, CEO of Crux Biomedical.

Vena cava filters were first introduced in the 1960s and have become an important tool to reduce the occurrence of a PE. There are an estimated 200,000 deaths per year attributed to PE in the United States. The CDC and the American Public Health Association have indicated that the deaths due to PE exceed the combined mortality per annum in the U.S. attributed to breast cancer, AIDS and traffic accidents.

Crux Biomedical was founded in 2004 by Dr. Thomas Fogarty and specializes in minimally invasive medical implants. It is headquartered in Menlo Park, California and is funded by Alloy Ventures and Emergent Medical Partners.

Source: Crux Biomedical Inc