Heparin Investigation – Latest Baxter Update

10 17 15'

Written by admin

Comments Off on Heparin Investigation – Latest Baxter Update

Baxter is providing an update on several
advances related to the investigation into recent heparin adverse reactions
associated with the company’s U.S. vial-based heparin products, which have
since been recalled.

I. Baxter confirms that the contaminant identified in the company’s
U.S. heparin vial products is hypersulfated chondroitin sulfate.

Baxter scientists have provided information to the U.S. Food and Drug
Administration (FDA) that confirms the presence of hypersulfated chondroitin
sulfate in the heparin Active Pharmaceutical Ingredient (API) that was used in
Baxter’s vial-based heparin products in the U.S., which the company fully
recalled.

Chondroitin sulfate is a molecule that occurs naturally and is a major component
of cartilage – the tough, connective tissue that cushions the joints. Chondroitin
sulfate is a common, biologically derived material that is sold in oral form as a
dietary supplement. The substance we found in the affected lots of heparin API
is not a naturally occurring substance, but the hypersulfated version of
chondroitin sulfate, which means that it has been chemically modified, resulting
in a more heparin-like molecule.

This finding is consistent with last week’s update stating that the unknown
material appeared to be a highly sulfated glycosaminoglycan-like (GAG-like)
material. While heparin-like, the material is structurally different from naturallyoccurring
heparin. The hypersulfated chondroitin sulfate has approximately the
same molecular weight as heparin and is similar in other ways, which is why
standard testing did not detect its presence.

II. Baxter scientists have detected the contaminant in crude heparin,
which indicates that the material is introduced in the supply chain
before it reaches the API manufacturer (SPL).

Baxter has collaborated with FDA in the development of sophisticated analytical
procedures, using capillary electrophoresis and nuclear magnetic resonance
spectroscopy technology. Baxter has also applied these sophisticated analytical
procedures to test the crude heparin material, which comes from consolidators,
and has detected the peak in some crude material lots. Consolidators and
workshops handle the crude material used in the manufacture of the heparin API,
and Baxter will continue to seek access to consolidators and workshops that
supply SPL in an effort to understand how hypersulfated chondroitin sulfate was
introduced.

“The hypersulfated chondrointin sulfate is not only found in the active
pharmaceutical ingredient (API) we use to make our heparin, but in the crude
material used to make the API,” said Norbert Riedel, Ph.D., Baxter’s corporate
vice president and chief scientific officer. “That means that this contaminant was
very likely introduced at the workshop or consolidator level, before it reached our
API supplier and definitely before it reached Baxter.”

“We’re at a critical juncture in the investigation and further progress can be
accelerated with the cooperation of the consolidators and workshops,” said
Riedel.

III. Baxter is working on establishing causality between the contaminant
and adverse reactions; tests underway.

While a causal link has not been established, the increase in adverse events has
been associated with lots of the product containing this substance.

To confirm a causal link, the same allergic response must be reproduced in a test
environment. Considering that a very narrow population of patients
(approximately one per 10,000 doses) had an allergic reaction, developing a way
to mimic the clinical environment is difficult.

Baxter has already conducted a number of biologic tests, trying to determine
whether the contaminated API causes allergic reactions.

“So far we have not been able to trigger allergic responses in biologic tests,” said
Riedel. “Given that the rate of reactions associated with the recalled heparin
were reported in approximately one per 10,000 doses, recreating this reaction is
statistically challenging,” he said.

Baxter is continuing its efforts to determine if there is a link between the
contaminant and adverse reactions, using additional advanced tests.

“The remaining questions are how and why hypersulfated chondroitin sulfate was
introduced into heparin crude materials, and whether or not causality can be
established,” said Riedel.

IV. No fatalities have been confirmed by medical evidence to be caused
by allergic reactions to Baxter heparin.

At this point in time, neither Baxter nor the U.S. Food and Drug Administration
(FDA) has confirmed that allergic reactions to Baxter’s heparin have caused any
fatalities. The company determined that there are four cases in which patients
received Baxter heparin and suffered an allergic-type reaction to heparin that
may have contributed to the adverse outcome, though there is not yet enough
medical data available to draw a firm conclusion that the allergic reaction caused
the death. In each of these cases, the patient had multiple, complex medical
conditions. In three of these four cases, patients had either undergone, or were
in the process of undergoing, invasive cardiac surgery. The company has
received approximately 600 heparin-related adverse reaction reports to date.

Baxter International Inc.
baxter

Category:

Uncategorized

Tagged with:

Share it:

Clot Risk From HRT Pills And Patches

10 16 15'

Written by admin

Comments Off on Clot Risk From HRT Pills And Patches

“HRT pills DOUBLE the risk of getting blood clots – but patches are safer, say experts,” reads the headline in the Daily Mail. It reports on research that has investigated the risk of blood clots from two different forms of hormone replacement therapy (HRT). The newspaper says, “One million women are currently taking HRT, with an estimated three out of four using pills.”

The findings come from a review of 17 studies of women taking HRT. It is already well known that HRT is a risk factor for blood clots, but this new study provides valuable evidence about the size of the risk and gives some idea of the difference between using patches or pills. However, women taking HRT should not be overly alarmed; the actual risk is still relatively small. It is too early to conclude that patches are safer than pills as there were a smaller number of studies which looked at their use. Much further research, preferably randomised trials of patches compared with pills, will be needed to confirm whether HRT patches are safer.

Where did the story come from?

Marianne Canonico and colleagues from Inserm Cardiovascular Epidemiology Section and Université Paris-Sud, Villejuif Cedex, France and the University of Glasgow carried out this research. Individual researchers received funding from Inserm, Assistance Publique des Hopitaux de Paris and the University of Glasgow. It was published in the peer-reviewed British Medical Journal.

What kind of scientific study was this?

This was a systematic review and meta-analysis in which the researchers combined results from several studies; some were observational studies and some randomised controlled trials. These studies looked at the risk of venous thromboembolism (a blood clot in the vein, either in the location that it was formed – thrombosis – or that has travelled to another vein in the body – embolism) in women taking hormone replacement therapy.

The researchers carried out a search of the electronic database Medline, for all English language studies published between 1974 and 2007 that included any keywords relating to HRT (e.g. oestrogen replacement or oestrogen therapy) in combination with those relating to venous thromboembolism. Each of the identified observational or experimental study types was assessed for study quality. If the study was considered suitable for inclusion, the researchers collected the relevant information on the type of HRT used (e.g. the type of hormones used, route of administration and duration of treatment) and the characteristics of venous thromboembolism (e.g. deep vein thrombosis or pulmonary embolism, how it was diagnosed, whether there was another suspected cause).

The data from the observational studies and the randomised trials was combined separately and the researchers carried out statistical tests to see whether there were any significant differences between the methods and results of the individual studies that may affect the reliability of the combined results.

What were the results of the study?

The initial search identified 1,890 articles which were filtered to give a final seven case-control studies (four of which involved HRT patches as well as tablets), nine randomised controlled trials and one cohort study. All of the studies were considered to be of high quality, with most of them investigating a first episode of venous thromboembolism that did not have any identified provoking risk factors (idiopathic).

All individual studies apart from one found a consistent trend for increased risk of venous thromboembolism with use of HRT. The combined results of the eight observational studies (the case-control studies and the cohort study) found that oral HRT significantly increased risk of thromboembolism by 2.5 times compared with placebo. The nine randomised controlled trials also found significant risk from oral HRT, but the size of the risk was slightly less, at 2.1 times. However, the four observational studies investigating HRT given via a patch found that, although there was still a trend for increased risk versus placebo, this was not significant.

The researchers then carried out a separate analysis of the trials to look at other characteristics of HRT use that may affect risk. They found that previous use of HRT did not significantly increase risk compared with first time users. There was no difference in the size of risk whether oestrogen was used alone or in combination with progestogen. However, the length of therapy seemed to have an effect, with use of HRT for less than one year significantly increasing the risk by four times, compared with a double increased risk for women who used HRT for more than one year. They also found that was an even greater risk if women had an additional genetic condition that increases their blood’s tendency to clot, or if they were overweight.

What interpretations did the researchers draw from these results?

The researchers conclude that “current use of oral oestrogen increases the risk of venous thromboembolism by twofold to threefold” and this may be even greater during the first year of use or in women with other risk factors. They say that HRT given via a patch may be safer but that further research is needed.

What does the NHS Knowledge Service make of this study?

Hormone therapy is already well-recognised as one of the risk factors for venous blood clots, but this new study provides valuable evidence about the size of the risks and gives some idea of the difference between patches and pills. However, there are several limitations, which should be considered:

– It should not be assumed from this research that it is unsafe to take HRT in pill form while patches are safe. Only four observational studies followed women using HRT patches while eight observational studies and nine randomised controlled trials – the most reliable research method – investigated oral HRT. Although the combined results of the four observational studies of HRT patches did not find significantly increased risk of venous thromboembolism, many more studies, ideally randomised controlled trials, will be needed to confirm that this is the case.

– The HRT used in the studies differed in terms of the type of oestrogen used, the dose and whether or not it was combined with a progestogen hormone (although the researchers did not find this that this affected the risk). Trials were also of different lengths and used different populations of women, e.g. postmenopausal women with a healthy uterus or women who had undergone hysterectomy. These things may all affect venous thromboembolism risk. In addition, it is unclear what other risk factors women may have had (besides weight and the clotting disorders, which the researchers considered) and whether these differed between trials.

– The actual size of the risk from oral HRT remains small. The researchers say that while one thromboembolism could be expected in 1,000 woman of this age over a year, an additional 1.5 would be expected to be seen in 1,000 women taking oral HRT for one year. These absolute risks are comparable to those seen in other studies of oral HRT but cannot be compared with any risks calculated for women using patches because no significant increase in risk was demonstrated for HRT patches.

– Only one electronic database was used and while Medline is a reliable source citing a large quantity of published research, some studies may have been missed that could have been identified through other search methods.

– Not all of the studies were identified to study venous thromboembolism as a primary outcome; in several it was a secondary outcome as part of studies that were designed to investigate the incidence of other things, e.g. coronary heart disease or stroke. The use of secondary outcomes for meta-analysis may also affect the reliability of the results.

An accompanying editorial in the British Medical Journal suggests that while waiting for the results of further trials, healthy menopausal women aged 50-59 should be reassured that the risk of thromboembolism when taking HRT is low and that the risks may be lower with lower doses of hormones. Women with previous venous thromboembolism or a mutation affecting prothrombin should be offered alternatives to oestrogen.

Links to the headlines

Oral HRT clots risk. Daily Mirror, May 23 2008
HRT pills ‘blood clot risk link’. BBC News, May 23 2008
HRT pills higher blood clot risk than patches. The Daily Telegraph, May 23 2008

This news comes from NHS Choices

Category:

Uncategorized

Tagged with:

Share it:

Test For Tumor Suppressor P53 Is Needed To Prescreen Patients For Blood Cancer Drugs

10 15 15'

Written by admin

Comments Off on Test For Tumor Suppressor P53 Is Needed To Prescreen Patients For Blood Cancer Drugs

Researchers at the University of Pennsylvania Schools of Medicine and Veterinary Medicine have determined a way to pre-screen cancer patients to see if they are suitable candidates for proteasome inhibitors, a promising class of anti-cancer drugs. They propose to test for p53, a well-known tumor-suppressor protein that is broken down by cellular machinery called proteasomes. This study appears online in the journal Blood, in advance of print publication in June 2007.

In cancer patients whose tumors do not produce p53, proteasome inhibitors might be ineffective. This patient group could be spared unnecessary treatment with possible harmful side effects. On the other hand, proteasome inhibitors are highly effective against lymphomas that do have the ability to produce p53.

“Proteasomes resemble paper shredders they break down proteins such as p53 into smaller pieces,” says senior author Andrei Thomas-Tikhonenko, PhD, Associate Professor of Pathology. “A proteosome inhibitor effectively jams the shredder so that p53 is not immediately broken down.”

In this study, the research team used a mutant strain of mice in which p53 activity can be switched on and off. “In principle, tumors in these mice could be obliterated by turning p53 back on,” says Thomas-Tikhonenko. “The problem was that a protein called MDM2 sent p53 into the teeth of the proteasome shredder.” The proteasome inhibitor bortezomib (Velcade®) causes this jamming process and restores p53 function. However, if p53 was inactivated in the mice, bortezomib treatment failed to kill tumors. Similar effects were seen with cell lines derived from human Burkitt’s lymphomas. When implanted into mice, these lymphoma cells were highly sensitive to the proteasome inhibitor, but as soon as p53 was removed, the inhibitor had no effect.

“These findings have important implications for clinical practice,” Thomas Tikhonenko adds. “Bortezomib is approved by the Food and Drug Administration for the treatment of multiple myeloma, another cancer of lymphoid cells. Yet, only a fraction of multiple myeloma patients respond to the drug.”

The researchers speculate that responsive myelomas are the ones retaining the p53 protein, which gets stabilized during treatment and triggers self-destruction of cancerous cells. “If confirmed experimentally, our hypothesis will serve to pre-select patients with the best chances of success those with p53 and spare the rest those without p53 the severe side effects of bortezomib therapy,” explains Thomas-Tikhonenko.

There are two ways, suggest the researchers, to test for p53 production in cancer patients. First, if MDM2 is expressed at abnormally high levels, it is a good indicator that p53 is constantly being made. Second, genetic tests can also be conducted to see if the malignant cells still have the gene for p53 or if the portion of the chromosome on which p53 is found has been deleted.

In addition to Thomas-Tikhonenko, Duonan Yu and Martin Carroll, both from Penn, were co authors. The National Institutes of Health and the Commonwealth of Pennsylvania Health Research Formula Fund provided funding for this research.

PENN Medicine is a $2.9 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System.

Penn’s School of Medicine is ranked #2 in the nation for receipt of NIH research funds; and ranked #3 in the nation in U.S. News & World Report’s most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System includes three hospitals, all of which have received numerous national patient-care honors [Hospital of the University of Pennsylvania; Pennsylvania Hospital, the nation’s first hospital; and Penn Presbyterian Medical Center]; a faculty practice; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.

University of Pennsylvania School of Medicine
3600 Market St., Ste 240
Philadelphia, PA 19104
United States
med.upenn/

View drug information on Velcade.

Category:

Uncategorized

Tagged with:

Share it:

Making Clot-Buster Safer By Blocking Toxic Effects

10 14 15'

Written by admin

Comments Off on Making Clot-Buster Safer By Blocking Toxic Effects

Since the introduction of the life-saving clot-busting drug tPA more than a decade ago, evidence has been accumulating that tPA (tissue-type plasminogen activator) can be a double-edged sword for a brain affected by stroke. Although it remains the only FDA-approved treatment for acute stroke, tPA can also contribute to inflammation and brain cell damage.

Scientists at Emory University School of Medicine are testing strategies for blocking LRP1, a molecule that appears to transmit inflammation signals triggered by tPA. They have found that in mice, genetically removing LRP1 from certain brain cells called microglia softens tPA’s impact on the brain.

The results, published online this week by the American Journal of Pathology, suggest that blocking tPA’s toxic effects could make it safer and allow doctors to use it more often on patients experiencing a stroke.

“tPA is a protein released naturally by the body in response to a blood clot,” says Manuel Yepes, MD, PhD, assistant professor of neurology at Emory University School of Medicine. “But it’s clearly not just lysing the clot.”

Doctors in community hospitals can often be reluctant to administer tPA to patients who appear to be having a stroke, Yepes says. One reason is that tPA has been shown to increase the risk of bleeding in the brain, he says.

Researchers have shown that tPA treatment increases the permeability of the blood-brain barrier, and that it can cross from the blood vessels into the brain tissue, generating inflammation. tPA targets cells called microglia, which are similar to white blood cells of the immune system, although they live in the brain.

“Our strategy was to show that by blocking LRP1, you can prevent the inflammatory response to tPA,” Yepes says. “This can be done either genetically, by deleting LRP1, or perhaps pharmacologically.”

Yepes and his colleagues are now testing a natural inhibitor of LRP1 called RAP in the laboratory. Co-treating or even pre-treating stroke patients with RAP might soften tPA’s effects.

Researchers had previously been unable to examine the effects of deleting LRP1, a protein involved in transporting cholesterol and other molecules around the brain, because mice completely lacking the gene die in the womb.

Yepes and his colleagues collaborated with Dudley Strickland, PhD, professor of surgery and physiology at University of Maryland School of Medicine, who provided mice deficient in LRP1 in macrophages (white blood cells) and microglia only.

The authors showed that the genetically altered mice have half the number of activated microglia in the brain after treatment with tPA. In addition, the volume of brain tissue damaged by a simulated stroke was cut in half in the genetically altered mice.

The first author of the paper is postdoctoral fellow Chen Zhang, PhD.

The research was funded by the National Institutes of Health.

Reference: Zhang C, An J, Strickland DK, Yepes M: The Low-Density Lipoprotein Receptor-Related Protein 1 Mediates Tissue-Type Plasminogen Activator-Induced Microglial Activation in the Ischemic Brain. Am J Pathol 2009 174: 586-594.

The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include schools of medicine, nursing, and public health; the Yerkes National Primate Research Center; the Emory Winship Cancer Institute; and Emory Healthcare, the largest, most comprehensive health system in Georgia. The Woodruff Health Sciences Center has a $2.3 billion budget, 17,000 employees, 2,300 full-time and 1,900 affiliated faculty, 4,300 students and trainees, and a $4.9 billion economic impact on metro Atlanta.

Source: Jennifer Johnson

Emory University

Category:

Uncategorized

Tagged with:

Share it:

Cytopia Nominates JAK2 Clinical Candidate For Myeloproliferative Disorders – Clinical Study To Commence Late This Year

10 13 15'

Written by admin

Comments Off on Cytopia Nominates JAK2 Clinical Candidate For Myeloproliferative Disorders – Clinical Study To Commence Late This Year

Cytopia Limited (ASX:CYT) has selected CYT387, a selective and potent JAK2 inhibitor, for formal preclinical development to treat myeloproliferative disorders (MPDs). This follows extensive laboratory experimentation and includes the recent demonstration of activity in an in-vivo model of myeloproliferative disease.

Myeloproliferative disorders are a group of diseases including myelofibrosis, polycythemia vera (PV) and essential thrombocythemia (ET) that affect over 150,000 patients in the USA and more than twice that worldwide. Over 95% of PV cases and over 50% of ET and primary and secondary myelofibrosis cases are believed to be caused by a mutation in the JAK2 kinase enzyme. This renders the kinase permanently active and leads to the overproduction of particular blood cells.

No effective treatments exist for these diseases and untreated progressive disease can lead to leukemia or myelofibrosis.

CYT387 possesses an excellent selectivity profile against a large panel of kinases and other pharmacological targets. It also has excellent pharmacokinetics including oral bioavailability and in preclinical models has a promising safety profile.

CYT387 has also recently shown utility in a well-validated in-vivo model of myeloproliferative disorders in studies in the laboratory of clinical hematologist Michael Deininger MD PhD at Oregon Health and Science University, USA. Results showed a profound resolution of clinical symptoms of MPDs in mice that were dosed orally.

Dr Deininger said, “We are highly encouraged by Cytopia’s compound in this model of myeloproliferative disease which clearly indicates significant amelioration of symptoms and disease remission. The favourable data from this animal model augers well for activity of the compound in the clinic.”

The compound will now be progressed into formal preclinical studies including IND-enabling toxicology studies. This program will lead to the submission of an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA) in the fourth quarter of 2008. The preclinical development program has already been considered by the FDA in pre-IND reviews, including a face-to-face meeting with FDA reviewers last month.

“The accumulated data for CYT387 clearly indicates that this compound has an excellent potency and safety profile for the treatment of patients with MPDs. We are aggressively progressing this compound through formal preclinical studies with the aim of beginning clinical trials by the end of this year,” said Mr. Andrew Macdonald, CEO of Cytopia.

About JAK2

The discovery of a specific single activating mutation in the JAK2 enzyme in MPDs in 2005 has focused attention on developing a therapy for these diseases through selective inhibition of JAK2. To successfully address these chronic diseases with a JAK2 inhibitor, the specificity and resultant tolerability profile is a key element of the product profile required for a “best in class” inhibitor.

CYT387 is a specific JAK2 inhibitor with excellent potential for safe and efficacious chronic human dosing. It has been derived from Cytopia’s knowledge of basic biology of JAK kinases, a strong structural biology program that has delivered multiple co-crystal structures of JAK2 complexed with inhibitors, and the subsequent development of an extensive chemical library of JAK2 inhibitors through an integrated computational and medicinal chemistry platform.

Cytopia is developing a suite of JAK2 inhibitors for multiple indications including the treatment of certain cancers, particularly lymphomas and solid tumours where JAK2 has been shown to be up-regulated, and for cardiovascular diseases such as pulmonary hypertension.

About Cytopia

Cytopia Ltd is an Australian biotechnology company focused on the discovery and development of new drugs to treat cancer. Cytopia conducts its research and development via subsidiaries based in Melbourne, Australia and New York and specializes in discovering new molecules that can inhibit enzymes known as kinases, an exciting new class of drugs.

cytopia.au

Category:

Uncategorized

Tagged with:

Share it:

Successful Treatment For Mice With Beta-Thalassemia

10 12 15'

Written by admin

Comments Off on Successful Treatment For Mice With Beta-Thalassemia

Beta-thalassemia is an inherited blood disorder that results in chronic anemia. A major complication of the condition is iron overload, which damages organs such as the liver and heart. The iron overload has been linked to low levels of the protein hepcidin, a negative regulator of intestinal iron absorption and iron recycling.

A team of researchers, led by Stefano Rivella, at Weill Cornell Medical College, New York, has now shown that increasing the concentration of hepcidin in beta-thalassemic mice limits iron overload and markedly reduces their anemia. They therefore suggest that therapeutic approaches that increase hepcidin levels in patients with beta-thalassemia could be therapeutic, limiting iron overload and mitigating anemia.

In an accompanying commentary, Mark Fleming and Thomas Bartnikas, at Children’s Hospital Boston, discuss these data and suggest that modulating hepcidin levels could be a new approach to treating a multitude of diseases associated with iron overload or deficiency.

TITLE: Hepcidin as a therapeutic tool to limit iron overload and improve anemia in beta-thalassemic mice

ACCOMPANYING COMMENTARY TITLE: A tincture of hepcidin cures all: the potential for hepcidin therapeutics

Source:
Karen Honey

Journal of Clinical Investigation

Category:

Uncategorized

Tagged with:

Share it:

Early Diagnosis Of Neurodegenerative Disease On The Horizon

10 11 15'

Written by admin

Comments Off on Early Diagnosis Of Neurodegenerative Disease On The Horizon

A new blood test that can give an early diagnosis of neurodegenerative disease and distinguish between Parkinson’s and Alzheimer’s disease could be launched this summer, reports Marina Murphy in SCI’s Chemistry & Industry magazine.

Manufacturer, Oklahoma-based proteomics company, Power3 Medical Products, said it plans to sell the test, NuroPro, which would be the first diagnostic test for neurodegenerative diseases on the market, in Greece by Q3 with further plans for it to go on the US market by late Q3 or Q4.”

“There is currently no diagnostic test for any neurodegenerative disease on the market – diagnoses are currently based solely on a clinical diagnosis of symptoms,” said chief executive, Steve Rash.

Power3 has identified and patented several blood proteins(1) associated with neurodegenerative disease. The test NuroPro measures a suite of 59 protein biomarkers, the relative levels of which, they say, can help distinguish between Parkinson’s, Alzheimer’s and Lou Gehrig’s disease or tell whether a patient is disease free. The test is highly accurate with a specificity and sensitivity in the high 90s, according to Rash.

Although the test has been welcomed by Kieran Breen, director of research at the Parkinson’s Disease Society, as being particularly useful for monitoring the progression of disease and assessing the effectiveness of drugs, he urged caution saying: “While the test seems promising, larger studies need to be conducted before it can be confirmed as being helpful in making a diagnosis.”

Susan Sorensen, head of research at the UK Alzheimer’s Society said: “There are 700,000 people living with dementia in the UK, 62 per cent have Alzheimer’s disease and this will rise to more than a million in less than 20 years. An effective blood test would present those diagnosed and their families with an opportunity to prepare for the impact of this devastating illness and make crucial decisions about their future.

“The method, known as proteomics, involves analysing proteins in the blood although it remains unclear which group of proteins gives the definitive signs of Alzheimer’s disease… Some suggest Alzheimer’s, for example, is too complex to be identified in this way.”

Two clinical validation studies are currently underway at the Cleo Roberts Center of Clinical Research in Arizona, US, and the Research Institute of Thessaly in Greece.

1 Expert Review of Proteomics 2008, 5(1), 1-8; Biochemical and Biophysical Research Communications 2006, 342, 1034-1039

Source: Meral Nugent

Society of Chemical Industry

Category:

Uncategorized

Tagged with:

Share it:

New Study Demonstrates Ready-To-Use Cardene® I.V. More Effective Than Labetalol For Immediate Control Of Blood Pressure In Emergency Room Patients

10 10 15'

Written by admin

Comments Off on New Study Demonstrates Ready-To-Use Cardene® I.V. More Effective Than Labetalol For Immediate Control Of Blood Pressure In Emergency Room Patients

Results from the CLUE study, a head-to-head comparison between Ready-to-Use Cardene® I.V. (nicardipine) and labetalol in the emergency room, showed that Ready-to-Use Cardene I.V. lowers acutely elevated blood pressure more effectively than labetalol. These data were presented at the annual meeting of the American College of Emergency Physicians (ACEP) in Las Vegas, Nevada.

“The CLUE study is important for emergency room physicians because these findings demonstrate that using nicardipine instead of labetalol is more effective at controlling blood pressure in hypertensive patients”

“The CLUE study is important for emergency room physicians because these findings demonstrate that using nicardipine instead of labetalol is more effective at controlling blood pressure in hypertensive patients,” says Frank Peacock, M.D. of the Cleveland Clinic, the study’s lead investigator. “When physicians need to rapidly lower blood pressure, nicardipine is faster than labetalol. In this study, patients treated with nicardipine were approximately three times more likely to reach the target blood pressure range within 30 minutes than those treated with labetalol.”

A sudden, sustained rise in blood pressure is abnormal and may cause irreversible damage to the kidneys, heart, brain, or other organs. The longer the blood pressure remains high, the greater the risk of organ damage. It is believed that a rapid, smooth reduction of the elevated blood pressure to a target range may improve patient outcomes.1-4

A variety of agents may be used to treat high blood pressure in an emergency room setting. However, there have been few randomized studies comparing the relative benefits and risks of different antihypertensives, and there is little standardization of treatment regimens. Consequently, the choice of which agent to use in a particular patient may be determined by convenience alone. Only recently has nicardipine become available in Ready-to-Use bags which can be kept at the point-of-care and immediately available to treat the patient presenting with a hypertensive emergency.

“It is important to provide physicians with evidence-based guidance regarding the safe and effective lowering of blood pressure into a predefined target range,” says Graham May, M.D., Chief Medical Officer for EKR Therapeutics, the company that developed and markets Ready-to-Use Cardene® I.V. “This is especially true in the emergency room where prompt control of high blood pressure may reduce the severity of a heart attack or stroke.”

About the CLUE Study5

Methods: Eligible patients had to have two systolic blood pressure (BP) readings >180 mmHg measured at least 10 minutes apart, and no contraindications to either nicardipine (NIC) or labetalol (LAB). Before randomization, the emergency room physician specified a desired target systolic BP for the patient. This pressure ± 20 mmHg was called the Target Systolic Blood Pressure Range (TSBPR). NIC was started at an infusion rate of 5 mg/hr, and titrated upwards every five minutes by 2.5 mg/hr until the TSBPR was achieved, or a maximum rate of 15 mg/hr was reached; once in the target range, the NIC infusion rate was decreased to 3 mg/hr. LAB was first administered as a 20 mg bolus over two minutes, with 20, 40, or 80 mg boluses repeated every 10 minutes until the TSBPR was achieved, or a maximum of 300 mg had been given. The active treatment phase of the study was 30 minutes.

Results: CLUE enrolled 226 patients, 52.7% female, 76.4% African American, with a mean age of 52.6±14.6 y. On admission, 143 (63.3%) patients (NIC 71, LAB 72) had symptoms or signs suggesting end organ damage. There were no significant between-treatment differences in mean entry systolic BP (213.4±21.8 mmHg), diastolic BP (116.8±17.97 mmHg), demographic characteristics, or laboratory parameters, except that NIC patients were more likely to be diabetic (34.4% vs. 21.7%, p=0.032), or have hyperlipidemia (43.4% vs. 27.9%, p=0.017), and there were more past smokers [67.2% vs. 49.1%, p=0.006] and current smokers [42.2% vs. 27.3%, p=0.018] in the LAB group.

110 patients were randomized to NIC, 116 to LAB. After 30 minutes, more NIC than LAB patients had achieved the TSBPR (91.7 vs. 82.5%, p=0.039). BP was recorded every five minutes during the study period (a total of 6 measures) and more NIC than LAB patients had 5 and 6 readings within the TSBPR (47.3% vs. 32.8%, p=0.026). Adverse events were rare in either treatment group. The mean heart rate in LAB patients was slower than in NIC patients at all time points after the start of treatment (p

Category:

Uncategorized

Tagged with:

Share it:

A Fast Magnetic Fix For Sepsis?

10 09 15'

Written by admin

Comments Off on A Fast Magnetic Fix For Sepsis?

Sepsis, an infection of the blood, can quickly overwhelm the body’s defenses and is responsible for more than 200,000 deaths per year in the U.S. alone. Premature newborns and people with weakened immune systems are especially vulnerable. Since most existing treatments are ineffective, researchers in the Vascular Biology Program at Children’s Hospital Boston have come up with a first line of defense — using magnetism to quickly pull pathogens out of the blood.

Their blood-cleansing device, developed by Chong Wing Yung, PhD, a researcher in the laboratory of Don Ingber, MD, PhD, is described in the journal Lab on a Chip. (The article can be accessed at rsc/publishing/journals/LC/article.asp?doi=B816986A, and is scheduled for formal online publication on April 13).

The system they envision will work like this: The patient’s blood is drawn, and tiny magnetic beads, pre-coated with antibodies against specific pathogens (such as the fungus Candida albicans) are added. The blood is then run through a microfluidic system in which two liquid flow streams run side by side without mixing — one containing blood, the other a saline-based collection fluid. The beads bind to the pathogens, and a magnet then pulls them (along with the pathogens) into the collection fluid, which is ultimately discarded, while the cleansed blood in reintroduced into the patient.

Tested with contaminated human blood, a device with four parallel collection modules achieved over 80 percent clearance of fungi in a single pass, at a flow rate and separation efficiency that would be viable for clinical applications. Yung and Ingber estimate that a scaled-up system with hundreds of channels could cleanse the blood of an infant within several hours.

“This blood-cleansing microdevice offers a potentially new weapon to fight pathogens in septic infants and adults, that works simply by removing the source of the infection and thereby enhancing the patient’s response to existing antibiotics,” says Ingber.

Yung, Ingber and physicians Mark Puder, MD, PhD, and Jay Wilson, MD from the Department of Surgery at Children’s Hospital Boston, with collaborators from Draper Laboratories, recently won a $500,000 grant from the Center for Integration of Medicine and Innovative Technology (CIMIT) to further the work. The next phase will be to test the device in an animal model.

The study was funded by CIMIT, with additional resources from Harvard University’s Center for Nanoscale Systems (CNS) and the National Nanotechnology Infrastructure Network (NNIN) initiative. The article can be accessed at: rsc/publishing/journals/LC/article.asp?doi=B816986A.

Children’s Hospital Boston is home to the world’s largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 11 members of the Institute of Medicine and 13 members of the Howard Hughes Medical Institute comprise Children’s research community. Founded as a 20-bed hospital for children, Children’s Hospital Boston today is a 397-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children’s also is the primary pediatric teaching affiliate of Harvard Medical School.

Children’s Hospital Boston
120 Brookline Ave., 2nd Fl.
Boston
MA 02115
United States
childrenshospital

Category:

Uncategorized

Tagged with:

Share it:

How Significant Is The Bleeding Toxicity After External Beam Radiotherapy For Prostate Cancer Patients On Anticoagulation Therapy?

10 08 15'

Written by admin

Comments Off on How Significant Is The Bleeding Toxicity After External Beam Radiotherapy For Prostate Cancer Patients On Anticoagulation Therapy?

– Prostate cancer is the most common cancer among men, especially in elderly men. Since these men often also have cardiovascular diseases that require anticoagulation therapy, it is not uncommon for prostate cancer patients to be on anticoagulants, such as Coumadin and Plavix.

External beam radiotherapy is one of the standard treatment options for localized prostate cancer, and it may be the preferred choice for older patients with significant comorbid illnesses. Despite the tremendous advances in delivery of radiation recently, rectal bleeding remains a common and potentially serious toxicity of radiation. We investigated the prevalence and severity of bleeding toxicity from prostate cancer radiotherapy among patients who are on Coumadin or Plavix.

As expected, the use of Coumadin or Plavix led to a significant increase in Grade 3 or 4 bleeding toxicity after radiotherapy. The 4-year risk of serious bleeding toxicity was 16% in patients on anticoagulants, compared to less than 4% in the other patients not on any anticoagulants. On multivariate analysis, use of anticoagulants was the only significant variable associated with serious bleeding. Among the patients on anticoagulants, higher dose of radiation and previous TURP were associated with bleeding toxicity.

Interestingly, intensity-modulated radiotherapy (IMRT), which usually allows more conformal radiation delivery and sparing of more normal tissue, was associated with worse bleeding toxicity. While IMRT generally limits the amount of normal tissue exposed to high doses of radiation, it can lead to small areas receiving higher maximal dose. In other words, hot spots can be hotter, especially with certain radiation optimizing algorithms. With more recent treatment planning software, this drawback may be mitigated.

Due to the substantial risk of serious bleeding, caution must be exercised when treating patients on anticoagulation with radiation. It warrants special consideration when determining the optimal radiation dose, target volume, and limiting dose constraints. With further advancement of radiation therapy, including high-precision stereotactic radiotherapy and real-time target localization, we may be able to deliver radiation more safely to patients on anticoagulation. Furthermore, in place of external beam radiotherapy, prostate brachytherapy with radioactive seeds may reduce the amount of rectum exposed to high doses of radiation and may represent another important treatment option for these patients.

Kevin S. Choe, MD, PhD as part of Beyond the Abstract on

– the only urology website with original content global urology key opinion leaders actively engaged in clinical practice. To access the latest urology news releases from , go to:

Copyright © 2009 –

View drug information on Plavix.

Category:

Uncategorized

Tagged with:

Share it:

Tag Cloud