Month: September 2010

Genome maps could help predict risk of breast cancer

Posted by

0


The discovery raises the hope of personalized preventive treatments for women susceptible to post-menopausal breast cancer.

The new research is among the first to link the cumulative effects of variations in several genes to a woman’s risk of breast and uterine cancer. Individually, the single-letter variations – single-nucleotide polymorphisms (SNPs) – had little impact.

Researchers from Singapore, Sweden and Finland linked 121 SNPs within 15 genes to women’s risk of developing oestrogen receptor (ER)-positive tumours. The variations are in a section of DNA close to a gene responsible for processing oestrogen.

The new associations were found in two different cancers and two different populations, suggesting the findings were not random chance events.

Dr Edison Liu – a lead scientist on the study – commented that each single-letter variation adds only a little to breast cancer risk but that risk increases for women who inherit several harmful SNPs.

It’s like being dealt a bad hand in a poker game,’ he said, adding that ‘this risk is greatly affected by other non-genetic factors like a woman’s reproductive history’ – increasing the complexity of the search for genetic factors.

Dr Liu said it’s unlikely large changes in a single gene would completely explain a woman’s risk. ‘Families carrying major perturbations in the oestrogen receptor or in the genes metabolising oestrogens would most likely die out over generations’, he suggested; therefore, only variations with small effects continue to be inherited.

‘We’re now looking at whether we can produce a model of genetic susceptibility that can explain some of the risk of ER-positive breast cancer,’ Dr Liu added. The model could be used to identify women who would benefit from treatments to reduce their lifetime exposure to oestrogen, such as aromatase inhibitors (drugs that block the conversion of other hormones into oestrogen).

ADHD Identified as a Genetic Disorder

Posted by

0


Subtle abnormalities in chromosomal structure are significantly more frequent among people with attention-deficit/hyperactivity disorder than in controls, according to a Lancet study.

Researchers performed genome-wide analyses in 350 British children with ADHD and 1000 controls. Abnormalities (called copy-number variants) larger than 500 kilobases occurred with twice the frequency in ADHD. Among subjects with ADHD and intellectual disability, the frequency was almost six times as great. The abnormalities were centered on a location in chromosome 16 that is also linked to autism and schizophrenia. The findings were confirmed in a separate cohort of Icelanders.

The authors say their findings refute the idea that ADHD “is purely a social construct.”

Asked to comment, Dr. Barbara Geller of Journal Watch Psychiatry said: “These findings, and recent work on both structural and functional imaging differences between ADHD and neurodevelopmentally healthy controls will, hopefully, soon lead to specific biological tests for clinical use.”

Rotarix Label Has New Warning About Risk for Bowel Abnormality

Posted by

0


The US Food and Drug Administration (FDA) has revised the label of the rotavirus vaccine Rotarix (GlaxoSmithKline) to warn of a small increased risk for intussusception that was reported in a Mexican study, the agency announced yesterday.

A potentially life-threatening condition, intussusception occurs when 1 portion of the intestine telescopes into another. This anomaly, which can develop in the absence of vaccination, may lead to internal bleeding, an intestinal hole, and abdominal infection. The annual rate of spontaneous intussusception — and subsequent hospitalization — is roughly 34 in 100,000 healthy young infants and children, the FDA stated.

Symptoms, which usually develop suddenly, include fussiness, frequent vomiting, diarrhea or stools containing blood or mucus, and severe belly pain, cramping, and swelling.

Preliminary results from a postmarketing study of Rotarix in Mexico suggest that there is an increased risk for intussusception in the 31 days after the first dose, with a relative risk of 1.8, according to the agency. Most cases occurred during the first 7 days after the first dose.

Extrapolated to the United States, these results would represent up to 4 additional hospitalizations due to intussusception per 100,000 infants within 31 days of the first Rotarix dose. The agency noted that the annual background rate of intussusception in Mexico — between 60 and 90 per 100,000 children — is higher than that in the United States.

The FDA said it would review the final results from the Mexican study when they become available in 2011. It noted that GlaxoSmithKline is conducting a postmarketing study of Rotarix and intussusception in the United States.

In 1999, the rotavirus vaccine RotaShield was withdrawn from the market after studies suggested an elevated risk for intussusception on the order of 9 additional cases per 100,000 infants. No increased risk for this bowel condition emerged in clinical trials for both Rotarix and another rotavirus vaccine, RotaTeq (Merck), but the agency nevertheless has monitored the 2 vaccines for this potential problem.

The postmarketing study in Mexico did not examine RotaTeq, and it is not undergoing a label revision. The FDA said it has uncovered no evidence of an increased risk for intussusception with RotaTeq, but it will continue to study the issue.

Kounis syndrome

Posted by

0


Cevik C et al. – Kounis syndrome is potentially a life–threatening medical emergency with both a severe allergic reaction and acute coronary syndrome. Most of the information about this syndrome has come from the case reports. The management of these patients may be challenging for clinicians, and unfortunately guidelines have not been established yet. In this article, the authors review the current guidelines of acute coronary syndromes and anaphylaxis along with the published cases with Kounis syndrome secondary to beta–lactam antibiotics.

Quantum computers move a step closer

Posted by

0


Successes at entangling three-circuit systems brighten the prospects for solid-state quantum computing.

Eugenie Samuel Reich

Quantum computing has made another advance along the path from theorists’ darling to working device.

A circuit of four superconducting qubits. Scientists have succeeded in entangling three of these.M. NEELEY

The concept depends on entanglement, a strange phenomenon in which the quantum states of spatially separated systems, called ‘qubits’, become intrinsically linked. The entanglement of two or more qubits sets up a ‘superposition’ of states in which calculations can run in parallel — in principle allowing a quantum computer to race through problems that it would take a classical computer eons to solve.

Such a quantum machine would require hundreds or even thousands of entangled qubits. The maximum reached so far is 12, but some of the systems that researchers are working with, including those depending on the spins of ions, may be hard to scale up. In this issue of Nature, two research groups1 report progress on an alternative approach: entangling qubits made from superconducting circuits, a technology that is amenable to manufacture on electronic chips. “Superconducting qubits are one of the better candidates for building a quantum computer,” says Daniel Gottesman, a quantum researcher at the Perimeter Institute in Waterloo, Canada.

The teams have achieved three-qubit entanglement in such a system, which is significant because three is the minimum number needed for quantum error correction — an essential attribute if quantum computers are ever to become practical. A quantum computer is susceptible to flipping its bits and losing information. Measuring bits to check their values part way through a computation would destroy the superposition. But entangling each bit with two extra bits makes it possible to check two of those bits for errors while allowing the calculation to go forwards in the third.

To construct their qubits, a team led by Rob Schoelkopf of Yale University in New Haven, Connecticut, used superconducting aluminium wires cooled to within a degree of absolute zero. The circuits were linked so that voltage and current oscillations flowing through each one would influence the others, and the entanglement was generated with a sequence of microwave bursts that changed the states of the circuits. The result was a kind of entanglement called a Greenberger–Horne–Zeilinger (GHZ) state, in which the three qubits are in a superposition of all being zero, and all being one.

A second group, led by John Martinis of the University of California, Santa Barbara, also succeeded in creating the GHZ state, as well as a ‘W state’, in which the superposed states feature one qubit with a value of one and the other two with a zero. Neither group has used their three entangled bits to run quantum error correction yet. But Schoelkopf emphasizes that his group has already run another type of algorithm using two-qubit entanglement3. He adds that a future challenge will be finding a way to lengthen the lifetime of the qubits, which lose their information within about 100 operations.

Emanuel Knill, an expert in quantum information science at the National Institute of Standards and Technology in Boulder, Colorado, isn’t sold on the approach, noting that it will be difficult to control multiple qubits from outside a refrigerator. But he says he’s happy to see that both groups prepared their quantum states with decent fidelities, meaning that the states are a good match to those the researchers intended to create. “The challenge,” he says, “is to scale up the number of gates and qubits.”

source:Nature

Split cornea transplantation allows use of one cornea for 2 recipients

Posted by

0


Splitting a single cornea for transplantation into two recipients can reduce the donor shortage and the costs of corneal transplantation surgery, researchers from Germany report in the August 17th Ophthalmology online.

“Our short-term results using split cornea transplantation technique show great promise,” Dr. Ludwig M. Heindl from Friedrich-Alexander University Erlangen-Nurnberg told Reuters Health by email. “The visual results for the patients are at least equal” to results of penetrating keratoplasty.

Dr. Heindl and colleagues describe their initial experience with 12 consecutive split donor corneas. Each was split for same-day transplantation into a patient with a keratoconus (in combination with deep anterior lamellar keratoplasty, or DALK) and a patient with Fuchs’ endothelial dystrophy (in combination with Descemet’s membrane endothelial keratoplasty, or DMEK).

In two eyes, accidental macroperforation of Descemet’s membrane required conversion to penetrating keratoplasty, but split donor cornea preparation was performed successfully in all 10 of the remaining cases.

In the 10 eyes with successful DALK, mean best spectacle-corrected visual acuity (BSCVA) improved from 20/131 to 20/35, mean spherical equivalent improved from -3.5 diopters (D) to -1.4 D, and mean refractive astigmatism decreased from 2.6 D to 1.3 D.

Similarly, in the 10 eyes treated with DMEK, mean BSCVA improved from 20/100 to 20/31. Mean spherical equivalent changed only slightly from 0.5 to 0.6 D, as did mean refractive astigmatism (from 0.5 to 0.6 D).

In the 2 eyes for which penetrating keratoplasty was necessary during DALK, BSCVA averaged 20/50, mean spherical equivalent was -0.3, and mean refractive astigmatism was 0.3 D.

The authors point out that in this small study, the use of split cornea transplantation saved a total of 10 donor corneas.

“Now, we are implementing split cornea transplantation in our clinical routine treating patients with anterior and posterior corneal diseases,” Dr. Heindl said. “Further aims include enlarging the spectrum of diagnoses applicable for the split cornea approach and extending the time between the DALK and DMEK procedure.”

He added that he and his colleagues hope to make split transplantation — already common with liver transplants — a routine procedure in ophthalmology as well.

Vascular Risk Reduction in Patients with Ehlers-Danlos Syndrome

Posted by

0



In a randomized trial, celiprolol, an inexpensive, well-tolerated drug, decreased incidence of arterial rupture or dissection.

Ehlers-Danlos syndrome arises from defects in type III collagen, causing skin hyperelasticity and fragility and joint hypermobility. Fatal complications, which occur at a median age of 40–50, can include mitral valve prolapse and spontaneous rupture of large- and medium-sized arteries. Although propranolol is known to lower rates of aortic dilatation and death in Marfan syndrome, the preventive role of beta-blockers in Ehlers-Danlos syndrome is unknown. Celiprolol, a β1-adrenoceptor antagonist with partial β2-adrenoceptor agonist action, has been used for hypertension in various countries since 1989 but is currently unavailable in the U.S. In an open-label trial with blinded assessment of clinical events, investigators in France and Belgium randomized 53 patients with clinical vascular Ehlers-Danlos syndrome (33 of whom had mutations of COL3A1) to celiprolol (uptitrated by 100 mg every 6 months to a maximum of 400 mg twice daily) or no beta-blocker treatment for 5 years. Most patients were normotensive at baseline. All but two celiprolol recipients achieved the maximum dosage.

After a mean follow-up of 47 months, the trial was stopped early because the rate of the primary endpoint, arterial rupture or dissection, was significantly lower in celiprolol recipients than in controls (20% vs. 50%; hazard ratio, 0.36; 95% confidence interval, 0.15–0.88). Blood pressure levels and heart rates did not differ significantly between the two groups. Only one patient discontinued celiprolol because of fatigue.

Comment: These findings suggest that celiprolol can prevent life-threatening complications of vascular Ehlers-Danlos syndrome. Although more data are needed to elucidate how celiprolol exerts its therapeutic effect independently of a hemodynamic effect, an editorialist notes that beta-blockers seem to suppress transforming growth factor β (TGFβ) expression, which might decrease matrix turnover and stabilize aneurysms in these patients. The possible role of other drugs that block TGFβ (e.g., angiotensin-receptor blockers) in vascular Ehlers-Danlos syndrome remains to be determined.

Published in Journal Watch Cardiology September 29, 2010

XMRV Researchers Discuss the State of the Science

Posted by

0


XMRV virus particles seen by transmission electron microscopy. (Image courtesy of University of Utah Health Sciences Public Affairs) XMRV virus particles seen by transmission electron microscopy. (Image courtesy of University of Utah Health Sciences Public Affairs.)

More than 200 researchers from around the world met this month to discuss XMRV, a recently discovered retrovirus that has been linked to prostate cancer and chronic fatigue syndrome in some but not all studies. The striking discrepancies in results among researchers—with some groups consistently finding the virus in patient samples and others not—led to discussions about how to gather basic information about the virus and advance the science.

Everyone who attended the international workshop, held September 7–8 on the NIH campus, agreed that XMRV can infect humans. The virus (xenotropic murine leukemia virus-related virus) was initially discovered in prostate tumors in 2005 and subsequently reported to be present in some patients with chronic fatigue syndrome.

Although XMRV may well be detectable in some prostate cancer and chronic fatigue syndrome patients, there is currently no evidence that the virus causes disease in people. “We don’t know that XMRV causes any human disease,” said Dr. Robert Silverman of the Cleveland Clinic, who was part of the research team that discovered the virus in prostate tumors.

His colleague, Dr. Eric Klein, also a discoverer of XMRV, discussed the possibility that viruses may play a role in prostate cancer as they do in some other cancers. If XMRV were a cause of prostate cancer, then the virus could be a biological marker for identifying specific types of disease as well as a basis for developing a vaccine against the virus, he said.

“What We Know”

NIH Director Dr. Francis Collins noted in his introductory remarks that the science on XMRV was at “a very important juncture.” He stressed that proving an association between a virus and a disease is not the same as proving causation. Urging participants to approach presentations with a healthy skepticism, he said that the workshop would be a chance to discuss “what we know and what we don’t know.”

The workshop included presentations by researchers who have found the virus in patient samples and others who have not. Talks were often followed by questions about the methods used in the experiments and strategies for developing more consistent results across laboratories.

“The good thing about the meeting was that it got people talking to each other who hadn’t had an opportunity to do so, and these exchanges will help us set up collaborations and sharing of techniques and samples,” said Dr. John Coffin of Tufts University, one of the organizers. “I don’t think anyone changed their minds [about the role of the virus in disease], but it was a big step toward helping to get all these discrepancies resolved. It was also helpful to have interactions between scientists and people outside the scientific community, such as advocates.”

Among the potential explanations for why only some groups have found the virus were the selection of patients for the studies, where the patients lived, and laboratory methods, such as how the samples were collected, handled, and processed.

Possible Contamination

Contamination of patient samples by mouse DNA could also play a role in positive results, some researchers said. Mouse cells contain hundreds of DNA sequences that are similar but not identical to XMRV. Contamination is a particular concern because today’s genetic tools are capable of detecting trace amounts of DNA or RNA from mouse viruses or tissues in patient samples.

To make this point, Dr. Coffin showed a picture of his swimming pool and proposed a thought experiment. He said that if a single drop of mouse blood were added to the pool and allowed to mix well, DNA from virus-related sequences in the mouse cells could be detected in a 1 mL sample of water (20 drops) with the tools commonly used to search for XMRV. “That’s how sensitive the tools are today,” he said.

Dr. Ila Singh of the University of Utah agreed that contamination from mice can occur very easily in the lab and urged researchers to be “ultra careful.” Her group recently reported that XMRV was present in malignant prostate cells and was more commonly found in men with aggressive tumors.

“The discrepancies may come down to the tests, or assays, being used, as well as the storage and processing of samples,” said Dr. Stuart LeGrice of NCI-Frederick, one of the organizers. “With this meeting, the groundwork has been laid for focusing on the role of contamination and whether handling and processing play a role in results.”

Some participants also called for creating reference samples that researchers could use to evaluate how well tools detect XMRV. This could include positive samples from patients as well as appropriate negative controls. As one participant said, the field urgently needs a protocol that would give researchers concordant results—regardless of whether those results are positive or negative.

“I suspect that until we have the technological details sorted out we won’t be able to address the more interesting ideas” about whether the virus is involved in human disease, said Dr. Jonathan Stoye of the National Institute for Medical Research, UK, another member of the organizing committee.

Conflicting Results

Researchers from the Baylor College of Medicine were among those who presented positive results. Bryan Danielson and his colleagues detected XMRV in 32 of 144 patients (22 percent) with prostate cancer from the southern United States. The virus was present in both normal and prostate tumor tissue, which suggests that infection may precede the onset of cancer, the researchers said.

But another study failed to detect the virus in nearly 800 cases of prostate cancer. Dr. Karen Sfanos of Johns Hopkins University and her colleagues had used two different methods (PCR and immunohistochemistry) to look for XMRV.

“We don’t see the virus in prostate cancer,” said Dr. Alan Rein of NCI-Frederick, who co-led the study with Dr. Angelo M. DeMarzo of Johns Hopkins. “Once we can detect the virus, then we can think about its effects on humans. But first we have to show that the virus is there.”

Reliable, reproducible assays are absolutely essential for moving the field forward, said Dr. Donald Blair of NCI’s Division of Cancer Biology. “The meeting focused people’s attention on the need to collaborate and get to the bottom of why results differ and to understand the biological implications of these differences.”

Dr. Coffin predicted that standard assays for detecting the virus in patient samples should be available within a year. “I’m optimistic,” he said.

With so many scientists working on XMRV, the field could answer basic questions about the virus within months, said Dr. Collins, the NIH director. “Now is a great time to have this meeting, and people should be questioning the data,” he added. “That’s what we’re taught to do as scientists.”

source:NCI

Swimming Pool Chemicals May Carry Cancer Risk

Posted by

0


goggles floating on water surface

Sept. 13, 2010 — Swimming in indoor pools may result in respiratory effects and induce DNA damage that could lead to cancer, according to new research that examined the impact of byproducts of pool disinfection.

But the researchers emphasize they are not suggesting anyone get out of the pool. “We do not say stop swimming,” says researcher Manolis Kogevinas, MD, PhD, professor of epidemiology at the Centre for Research in Environmental Epidemiology in Barcelona. “We should keep a clear message that swimmers should keep swimming.”

The research findings, he tells WebMD, are a message to the industry that ”the positive effects of swimming could be increased by reducing the chemicals.”

Industry experts and pool researchers agree. “It’s good that research is being done in this area,” says Thomas Lachocki, CEO of the National Swimming Pool Foundation, an educational nonprofit organization based in Colorado Springs, Colo.  The research is published online in the journal Environmental Health Perspectives.

Swimming and Health Risks: A Closer Look

”We have been doing research on chemicals in water — not swimming pools [specifically] — for quite some time,” Kogevinas says. More recently, he and his colleagues have focused more intently on indoor swimming pool water. “Chemicals are produced when you put chlorine in water,” he says. Chlorine reacts, for instance, to urine, cosmetics, and other substances typically found in swimming pools.

The researchers wanted to characterize these disinfection byproducts, or DBPs, in an indoor pool environment. Other studies have linked DBP exposure in drinking water to a risk of bladder cancer and other problems.

In the first of three new studies published in the journal, the researchers evaluated 49 healthy adults after they swam for 40 minutes in an indoor chlorinated pool, looking for biomarkers linked to cancer.

“What we found is by analyzing blood samples and urine samples, we have an increase in risk markers related to cancer,” Kogevinas tells WebMD.

Exposure to the pool water was associated with a five-fold increase in one of the markers, he says. But that does not mean swimmers are doomed to get cancer, he stresses.

“This doesn’t mean at all that swimmers have a five times increased cancer risk,” he says. “It simply means that after swimming for 40 minutes in a chlorinated pool, you get an increase in this marker in the blood that in other studies has been associated with future cancer risk.”

Swimming and Respiratory Effects

In a second study, Kogevinas and his colleagues focused on respiratory effects of exposure to indoor pool water.

“We compared markers of lung injury before and after swimming,” he says, evaluating 48 swimmers this time, from the same group as in the first study.

They found changes in just one blood marker, a slight increase in one known as CC16. The increase, the researchers say, is due to the exercise itself in addition to the DBP exposure.

”Some studies have suggested a link with swimming and asthma,” Kogevinas says. “We found [only] one of many [respiratory] biomarkers [had] a small increase.”

In a third study, the researchers looked at water and air samples from two indoor pools. “We shipped them to the EPA [U.S. Environmental Protection Agency],” Kogevinas says.  They found more than 100 DBPs in the pool water, some not identified before.

”Many are the same chemicals we find in tap water,” he tells WebMD.  “Some have been identified in experimental studies, animal studies, to be harmful.”

The bottom line? “Pool water is not worse or better than tap water,” he says, when it comes to byproducts. Only in the pool, he adds, “swimmers get a massive dose.”

Swimming Pools and Health Risks: Second Views

Experts from the swimming pool industry say research is crucial. “It’s important we find ways to reduce exposure to potentially hazardous chemicals in pools,” Lachocki says.

Even so, he calls the three studies “limited” because of some shortcomings. He wanted more information on how the pools studied were managed and what standards were used to keep the pools maintained.

“The question is, were the pools studied on the end of the spectrum of fabulously well taken care of, or not so fabulously?” he says.

The conclusion of the research that the pool water is no more hazardous than drinking water doesn’t tell people if that is representative of most pools or just the ones studied, Lachocki says.

Another limitation is the small number of swimmers studied, he says.

What’s a Swimmer to Do?

Lachocki agrees that no one should give up swimming as a result of the research. “Swimming continues to be ideal for an aging population and for a sedentary population,” he says.

People who swim in indoor pools can check out the pool first, he tells WebMD. Ask, for instance, if the pool has certified operators, which means they have had training in how best to disinfect a pool.

His foundation trains certified operators. “There should be a certificate on the wall, showing the people who operate the pool are certified.”

Swimmers can buy test strips, widely available at pool supply stores, and test the water themselves, he says. Swimmers can also ask the pool operators to show them the maintenance records proving the pool is maintained properly, he says.

Kogevinas suggests that people who swim in indoor pools follow rules, such as not urinating in the pool and showering before swimming.

Assessing an Imaging Technique in Bladder Cancer

Posted by

0


Fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography showed promise for detecting malignancy after routine CT or MRI findings were unclear.

The limitations of computed tomography (CT) and magnetic resonance imaging (MRI) of the pelvis make radiographic assessment of patients with muscle-invasive bladder cancer problematic. Clinical staging — defined ultimately by pathologic evaluation of the bladder after cystectomy — has shown that understaging and overstaging are common when imaging (typically CT), cystoscopic exams, and pathology findings from transurethral resection of bladder tumor are used.

To date, the case has not been strong for routine use of fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) as an imaging technique in bladder cancer. The clinical value of FDG-PET/CT has shown greater promise, prompting investigators to prospectively evaluate the sensitivity and specificity of this technique for identifying metastatic lesions in 57 patients with bladder cancer. Patients had undergone initial imaging with either CT or MRI. All FDG-PET/CT findings were classified as true positive or negative or false positive or negative. Follow-up imaging or biopsy was used to confirm the presence or absence of metastatic disease.

In an organ-based analysis of 135 lesions in 47 patients, FDG-PET/CT had a sensitivity of 87% and a specificity of 88%; in a patient-based analysis, the sensitivity was 81% and the specificity was 94%. Pre- and postimaging surveys by 53 of the managing clinicians showed that they altered their planned management in 36 patients (68%) because of the FDG-PET/CT findings; for example, the findings made them consider biopsy unnecessary in 11 patients (21%). Subsequent review of medical records revealed that the altered management was appropriate in 34 of the 36 patients. In the other two patients, false-negative FDG-PET/CT results led to an attempt at curative surgery in one patient and a delay in systemic chemotherapy for metastatic disease in the other.

Comment: The authors note that their specificity and sensitivity values are consistent with FDG-PET/CT findings in other major epithelial cancers. They recommend additional studies to better assess the clinical value and to permit formal cost analysis. Of note, FDG-PET/CT seems to be useful when findings from routine CT or MRI imaging are unclear, not when used as a standard study for initial assessment of patients with advanced disease.

Published in Journal Watch Oncology and Hematology September 28, 2010