Month: April 2012

Two-dimensional boron has potential advantages over graphene.

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Theoretical physicist Boris Yakobson and his team at Rice University have taken an unusual approach to analyzing the possible configurations of two-dimensional sheets of boron, as reported this week in the American Chemical Society journal Nano Letters.

Treating it as Swiss cheese – in which the holes are as defining as the cheese itself – was the key concept in figuring out what atom-thin sheets of boron might look like. Those sheets, when rolled into a hollow tube, or nanotube, could have a distinct advantage over carbon nanotubes; boron nanotubes are always metallic, while the carbon atoms in a nanotubes can be arranged to form either metallic or semiconducting nanotubes. This variation in atomic arrangement — known as chirality — is one of the major hurdles to carbon nanotube processing and development.

“If I dream wildly, I like to think boron nanotubes would make a great energy-transporting quantum wire,” said Yakobson, Rice’s Karl F. Hasselmann Professor of Mechanical Engineering and Materials Science and professor of chemistry. “It would have the benefits of carbon, but without the challenge of selecting a particular symmetry.”

A boron lattice, even in just two dimensions, can have a range of configurations, Yakobson said. Fully packed, it’s a layer of atoms arranged in triangles. That’s one extreme. But take one atom out, and what was the center of six triangles becomes a hexagon. Take all such possible atoms out and the sheet looks exactly like graphene, the two-dimensional, single-atom thick form of carbon that has been all the rage in the world of chemistry and materials science for the past decade.

Between those two extremes are thousands of possible forms of pure boron in which missing atoms leave patterns of hexagonal holes.

 

“Carbon is well-defined,” said Yakobson, whose theories focus on the interactions at play among atoms as they bond and break. “Any deviation in graphene’s hexagonal form is what we call a defect, which has negative connotations.

 

“But we find there is a rich variety in two-dimensional boron,” he said. “It’s all purified – there’s no non-boron here, even though there are vacancies, empty sites. The amazing thing is that nature prefers to have it that way; Not hexagonal, where every third position is missing an atom, and not a triangular lattice. The optimum is right in the middle.”

In that most-stable middle ground, the researchers found 10 to 15 percent of the boron atoms in a lattice were missing, leaving “vacancy concentrations” in a variety of patterns.

 

Yakobson said using traditional computational methods to assess thousands of boron configurations would have cost too much and taken too long. So he and Rice research scientist Evgeni Penev applied cluster expansion, a method of calculation more commonly applied to alloys.

 

“Evgeni gave it a twist: He treated the empty spaces as the second alloy ingredient, in the same way you can’t have Swiss cheese without ‘alloyed in’ voids and real cheese. In this calculation, the holes are an equal, physical entity.”

With space as a pseudoalloy, the researchers found a range of formation energies one might employ to identify stable sheets of boron with particular vacancy concentrations. They also found that synthesized boron layers would probably be polymorphic: Each sheet could contain a jumble of patterns and still be considered pure boron.

“Polymorphic means that all these possibilities are pretty much equal, and equally likely to form,” Yakobson said.

“This is a small part of the fundamental physics,” Penev said. “The next step is to consider more practical things, like whether it can be synthesized and under what conditions.”

 

Yakobson, who in 2007 first theorized the possibility of an 80-atom boron “buckyball,” said that while boron is difficult to work with, that difficulty makes it more rewarding. “On one hand, it’s very hard to conceive a possibility or to get experimental evidence. On the other hand, the field isn’t as crowded as graphene.”

Co-authors of the paper are Rice postdoctoral researchers Somnath Bhowmick and Arta Sadrzadeh.

Source:  Rice University

 

 

Brain Freeze Might Help Solve Migraine Mysteries.

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Eager eaters know that gulping a Slurpee or inhaling a sundae can cause that brief seizing sensation known in the not-so-technical literature as “brain freeze” or “ice cream headache.”

Just what causes this common cautionary condition has remained mysterious to sufferers and scientists alike (not that the two categories need remain mutually exclusive).

A new study, presented April 22 at the Experimental Biology 2012 annual meeting in San Diego, proposes a probable answer. And it’s one that could also suggest new treatments for more serious conditions, such as migraines and traumatic brain injuries.

The findings were not easy to obtain and required 17 courageous volunteers to submit themselves to brain freeze. These healthy, self-sacrificing adults took sips of extra-cold water through a straw, which they aimed at the roof of their mouths. While their lips were sipping away, subjects’ brains were monitored via transcranial Doppler, which can sense changes in arterial blood flow. As soon as volunteers achieved and then emerged from a freeze, they alerted the researchers.

Researchers then were able to pinpoint changes in brain activity at those precise moments, comparing those signals with measurements taken under control conditions when subject sipped on room temperature water.

The team, led by Melissa Mary Blatt, of the Department of Veterans Affairs New Hersey Health Care System, found that just before brain freeze, the anterior cerebral artery opened wider and pumped extra blood to the brain. This artery is one of two in charge of bringing blood to the frontal lobes, which is also where subjects reported the greatest freeze pain. This response might be the body’s effort to keep the brain from getting too cold by supplying it with a blast of warm blood.

Tellingly, as the vessel contracted back to its normal diameter, the pain went away.

The researchers suggested that the pain might stem from the excess pressure generated by this quick burst of blood into the closed skull cavity.

A similar blood-induced pressure might also be partly responsible for migraines, traumatic brain injury headaches and others, the researchers noted. If that turns out to be the case, new treatments that prevented this quick dilation of the blood vessels could be key in turning down pain for many headache sufferers.

For the rest of us, perhaps we should try to sip, slurp and lick a bit more slowly

Source: Scinentific American.

ATA: Interdisciplinary communication necessary after thyroidectomy.

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In a statement issued by the American Thyroid Association, members of its Surgical Affairs Committee said enhanced communication and well-defined interdisciplinary care plans for patients undergoing thyroidectomy are necessary.

Sally E. Carty, MD, of the division of endocrine surgery at the University of Pittsburgh School of Medicine, and colleagues based their recommendations on findings from the 2009 ATA guidelines, besides reviewing office notes, referral letters, operative consents, operative reports, operative diagrams and artwork, and preoperative and postoperative patient education materials.

They identified essential elements of interdisciplinary communication from three distinct settings: preoperative evaluations, intraoperative findings and postoperative data, events and plans.

“A wide variety of findings from clinical examination, biochemical testing, cross-sectional and functional imaging tests, and other sources can have a major impact on postoperative risk assessment and therefore may significantly influence decision-making with regard to the role of adjuvant radioiodine ablation therapy, degree of thyrotropin suppression, and extent an frequency of follow-up evaluations,” the committee members wrote.

High-risk physical examination findings and historical features such as palpable cervical lymph node or prior neck irradiation may influence postoperative management and, therefore, should be included in preoperative evaluation, they said.

Several intraoperative details are similarly critical to the risk-stratified postoperative management, including the extent of thyroid surgery, description of gross extrathyroidal extension, completeness of surgical resection and more.

Additionally, postoperative findings such as hypocalcemia, hypothyroidism and vitamin D use are factors that may affect postoperative care.

“Although defining the roles and responsibilities of thyroid cancer care is beyond the scope of the present article, we feel sure all caregivers would agree that careful communication among the individual practitioners of a health-care environment remains of paramount importance — it is then that all practitioners and the patients themselves most benefit,” the researchers concluded.

Source: Endocrine Today.

ALPHA OMEGA: n-3 fatty acids did not reduce major CV events in patients with history of MI.

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Low doses of n-3 fatty acids given in the form of margarine spreads did not lower the risk for major cardiovascular events in patients from the ALPHA OMEGA multicenter, randomized, double blind, placebo-controlled trial.

This study, the results of which were presented at the 2010 European Society of Cardiology Congress in Stockholm, included patients (n=4,837, mean age 69 years) enrolled from April 2002 to December 2006 after experiencing myocardial infarction. The patients were randomly assigned to different margarine spreads that provided low doses of n-3 fatty acids — 400 mg per day of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) or approximately 2 g per day of alpha-linolenic acid (ALA) — or placebo. Patients were followed for 40 months.

During follow-up, 671 patients developed a major CV event. According to study results, event risk was not reduced in patients receiving EPA plus DHA or ALA vs. placebo. Researchers noted a 27% reduction (HR=0.73; 95% CI, 0.51-1.03) in major CV events in women who received ALA, as well as a 49% reduction (HR=0.51; 95% CI, 0.27-0.97) in CHD mortality in patients who received EPA plus DHA.

“In the total patient population, low doses of n-3 fatty acids were not related to major CV events,” Daan Kromhout, MD, professor of public health research at Wageningen University, The Netherlands, and researcher on the study, said in the concluding comment of his presentation. “ALA may prevent major CV events in women, which needs confirmation.”

 

 

The ALPHA OMEGA Trial investigators are to be praised for this independent, investigator-initiated, food-based trial that was conducted with limited governmental funds. The pragmatic approach of the trial has to be reinforced, specifically the fact that this is food-based, because this is a model of a serious attempt to give a scientific basis to the wide-spreading advising of the potentially or hypothetical beneficial effect of food.

The pragmatic approach of the trial, the low dose of polyunsaturated 3 fatty acids and the relatively small sample size with respect of the event occurrence do not allow us to draw firm conclusions about the effect of the n-3 polyunsaturated fatty acids in this population of post-MI patients.

– Luigi Tavazzi , MD

Scientific Director, GVM Hospitals of Care and Research,
Cotignola, Italy

Source: Endocrine Today.

 

 

New Warnings Added to Aliskiren-Containing Medications.

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The antihypertensive drug aliskiren should not be coadministered with angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) in patients with diabetes because doing so may raise risks for renal impairment, hypotension, and hyperkalemia, the FDA announced Friday. The labels of all aliskiren-containing medications will be updated to note this contraindication.

In addition, the new labels will warn against using aliskiren with ACE inhibitors or ARBs in patients with moderate-to-severe renal impairment.

These changes follow preliminary results from the placebo-controlled ALTITUDE trial, in which coadministration of the drugs was associated with increased risks for renal impairment, hypotension, and hyperkalemia. Data also suggest “a slight excess of cardiovascular events” with aliskiren, according to the FDA.

The following brand-name drugs contain aliskiren:

  • Amturnide
  • Tekturna
  • Tekturna HCT
  • Tekamlo
  • Valturna

Source: FDA MedWatch safety alert .

 

Acknowledgment of comorbidities could improve fracture prediction algorithms.

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An increased awareness of comorbidities and their impact upon fracture risk may help improve upon fracture-prediction algorithms, according to a study published in Bone.

The researchers used the multinational Global Longitudinal Study of Osteoporosis in Women (GLOW) to assess comorbidities’ effect on fracture risk, with baseline questionnaires and occasional follow-up interviews to determine any incidence of clinical fracture and comorbidities. A comorbidity index was compiled, and the impact of this index’s addition to FRAX risk factors was assessed.

According to the study abstract, 3,224 (6.1%) of 52,960 women in the GLOW study developed fractures during a 2-year period. Parkinson’s disease and multiple sclerosis indicate a higher risk of fracture than other comorbidities, the researchers noted. With the exception of hypertension, celiac disease, cancer and high cholesterol, all recorded comorbidities in the GLOW study were significantly associated with fracture risk. Heart disease, osteoarthritis and chronic obstructive pulmonary disease were major predictors of fracture.

Using a fracture prediction algorithm and adding a comorbidity index resulted in an improvement of the fracture prediction model, the authors concluded in the abstract.

Source: Endocrine Today.

 

Testosterone supplements improved breathing exercise capacity in HF patients.

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Patients with moderate to severe HF and left ventricular systolic dysfunction who used testosterone therapy experienced improvements in exercise capacity and breathing capabilities, with no increase in CV events, according to results of a meta-analysis.

“The improvement in exercise capacity was consistent across all of the studies,” Justin A. Ezekowitz, MD, researcher, professor and director of the Heart Function Clinic at University of Alberta in Edmonton, Canada, said in a press release. “Compared to patients in placebo groups, the differences were striking.”

Mustafa Toma, MD, of St. Paul’s Hospital, University of British Columbia, Canada, and colleagues designed four double blind, randomized trials (n=198 patients; 84% men; mean age, 67 years) to assess associations between testosterone therapy and increases in exercise capacity.

The four studies consisted of varying administration of testosterone. Two studies used intramuscular injections of 1 g testosterone undecanoate (Nebido, Jenahexal Pharma GmbH) and Sustanon 100. The other two studies used a transdermal patch (5-mg Androderm [Watson Labs] and 300-mcg Intrinsica [Warner Chilcott UK Limited]).

Patients participated in the 6-minute walk test (6MWT), incremental shuttle walk test (ISWT) or peak VO₂ as part of the evaluation of exercise capacity after 52 weeks of treatment.

Testosterone therapy resulted in an average increase of 54 minutes (95% CI, 43-65) in 6MWT, 46.7 minutes (95% CI, 12.6-80.9) in ISWT and 2.7 mL/kg/minute (95% CI, 2.68-2.72) in peak VO₂ vs. placebo.

The researchers said the degree of improvement found in the study is greater than ACE inhibitors, beta-blockers and cardiac resynchronization therapy, which are currently used for morbidity and mortality reduction in patients with HF.

Despite the impressive findings, the researchers said there must be additional trials to examine the various testosterone delivery methods.

Source: Endocrine Today.

 

 

Ceasing statin therapy puts patients with rheumatoid arthritis at increased risk for death.

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Patients with rheumatoid arthritis who permanently discontinue statin therapy appear to increase their risk for cardiovascular disease mortality and all-cause mortality, according to results of a study published in Arthritis Care & Research.

For the population-based longitudinal study, researchers used administrative health data to analyze mortality outcomes in 4,102 people with rheumatoid arthritis and incident statin use from 1996 to 2006. Of the 4,102, 60% were women and the mean age was 67 years. Statin discontinuation was defined as persistent nonuse for at least 3 months anytime during prescribed statin therapy. With statin discontinuation as a time dependent variable, Cox’s proportional hazard models were used. Multivariable models were adjusted for age, sex, comorbidities and risk factors for mortality, and proxy indicators of rheumatoid arthritis severity.

The researchers found that about 45% of the cohort discontinued statin therapy at least once during the 4-year follow-up period. Researchers reported 198 deaths from CVD (31% from MI and 15% from stroke) and 467 deaths overall. Statin discontinuation was found to be associated with 60% increased risk of death from CVD and 79% for deaths from all causes. The association between statin discontinuation and mortality outcomes was not modified by timing of first prescription, age, or sex (P>.29), the researchers said.

“Our study provides evidence of the harmful effects of ceasing statin therapy,” Mary De Vera, PhD, of the University of British Columbia School of Population and Public Health and Arthritis Research Centre of Canada, said in a press release. “Our study findings emphasize the importance of medication compliance in rheumatoid arthritis patients who are prescribed statins.”

Source: Endocrine Today.

 

 

GH treatment halted decline of certain cognitive skills in children with Prader-Willi syndrome.

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Growth hormone treatment in children with Prader-Willi syndrome prevented deterioration of some cognitive skills while improving abstract verbal reasoning and visuospatial skills, according to data from a randomized controlled trial.

“Before the start of GH treatment, older age had a significant negative effect on cognition. Also, untreated controls showed a deterioration of cognitive functioning. These findings indicate that cognitive functioning of untreated children with [Prader-Willi syndrome] deteriorates over time compared with healthy children. Our study shows that GH treatment prevents this deterioration,” the researchers wrote.

Elbrich P.C. Siemensma, MD, researcher for the Dutch Growth Research Foundation in the Netherlands, and colleagues designed a 2-year randomized controlled GH trial, followed by a 4-year longitudinal study on GH treatment, in 21 boys and 29 girls aged 3.5 to 14 years.

Cognitive functioning was measured every 2 years by four short forms of the Wechsler Preschool and Primary Scale of Intelligence-Revised, Dutch version (WPPSI-R) or the Wechsler Intelligence Scale for Children-Revised, Dutch version (WISC-R), depending on patient age.

Subtests in vocabulary, similarities (verbal IQ subtests), block design and picture arrangement (performance IQ subtests) of the WISC-R were used in children aged older than 7 years. For children aged younger than 7 years, picture arrangement was replaced with picture completion under the WPPSI-R.

After 4 years of GH treatment, the mean standard deviation score on the similarities (+0.4; 95% CI, –0.1 to 0.7) and block design (+0.3; 95% CI, 0.07-0.6) subtests were significantly higher than at baseline. Vocabulary subtests (P=.01) and total IQ (P=.03) were similar to baseline at 4 years.

Block design subtest scores were significantly lower among children with a maternal uniparental disomy at baseline (P=.01); however, these patients had a larger increment on this subtest during 4 years of GH treatment vs. patients with a deletion, the researchers wrote.

Higher increases in similarities (P=.04) and block design (P<.0001) were significantly associated with lower baseline scores.

The researchers wrote that their findings suggest that GH should be administered at an early age to prevent deterioration. However, older children who are lagging may benefit even more from GH treatment.

Source: Endocrine Today.

 

 

A 39-year-old. female presents with adrenal mass, hypokalemia

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A 39-year-old woman was referred for the evaluation of primary aldosterone with a history of hypertension since she was aged 17 years. She had hypokalemia over the past 4 years.

Her blood pressure was 132 mm Hg/81 mm Hg with a pulse of 83; she was taking metoprolol 50 mg twice daily, lisinopril 40 mg daily, amlodipine 10 mg daily and potassium chloride 40 mEq twice daily.

Laboratory testing showed a serum sodium 139 mmol/L; blood urea nitrogen (BUN) 10 mg/dL; creatinine 0.69 mg/dL; potassium 3 mmol/L; chloride 102 mmol/L; carbon dioxide 26.5 mmol/L; aldosterone 17 ng/dL with a plasma renin activity of 0.2 ng/mL/hour.

The serum aldosterone/plasma renin activity (PRA) ratio was elevated at 85 ng/mL/hour.

A 24-hour urine collection for aldosterone was elevated at 54.3 mcg/24 hour (reference range 2.3-21). After salt suppression (3 gm sodium chloride four times daily for 5 days), the urine aldosterone of 37.1 mcg/24 hour (reference range <5 mcg) remained elevated with a normal urinary free cortisol of 40.1 mcg/24 hour.

A CT of the abdomen with an adrenal protocol showed a normal-appearing left adrenal gland and a 2 cm × 1.9 cm right adrenal mass with low attenuation (10 Hounsfield units [HU]; Figure 1) that increased immediately after contrast infusion (27.9 HU) with a fast washout (4.1 HU) consistent with a lipid-rich adenoma.

A bilateral adrenal vein sampling was performed with continuous IV cosyntropin 50 mcg/hour. Catheters were placed in the right femoral vein and with fluoroscopic guidance to inferior vena cava (IVC), then into the right adrenal vein, right accessory hepatic vein and a right adrenal vein.

Venogram of the right adrenal vein showed multiple venous branches draping around the right adrenal mass (Figure 2).

Venous blood samples were obtained from the right and left adrenal veins and the IVC and analyzed for aldosterone and cortisol. The cortisol ratio of the right adrenal vein and the left adrenal vein were identical (see Table 1), which proves both catheters were appropriately placed and draining both adrenal glands.

With continuous cosyntropin stimulation, the aldosterone/cortisol ratio from the right adrenal vein was higher than the left adrenal vein and the IVC (Table 1). This is consistent with a right aldosteronoma.

She had an uneventful endoscopic right adrenalectomy that showed an ovoid, well-circumscribed, yellow tumor measuring 3.5 cm × 2.1 cm × 1.3 cm within the adrenal cortex, consistent with an adrenal adenoma. Postoperative she was able to stop the potassium supplements and had a normal blood pressure with only lisinopril at 20 mg daily. Laboratory testing showed potassium 4.6 mmol/L; plasma aldosterone 1 ng/dL; PRA 5.5 ng/mL/hour; and aldosterone/renin ratio of 0.2.

Clinically, primary hyperaldosteronism (PH), or Conn’s syndrome, should be considered with antihypertensive drug-resistant hypertension associated with hypokalemia. The diagnosis can be challenging but important to diagnose because, as in the patient presented in this case, the hypertension can often be cured by surgery. There are other causes of PH that should not be treated surgically, but rather medically.

PH is caused by aldosterone-producing adenomas (APAs), aldosterone-producing renin-responsive adenomas (AP-RAs), bilateral adrenal (glomerulosa) hyperplasia or idiopathic adrenal hyperplasia (IAH), primary adrenal hyperplasia (PAH) and, rarely, familial forms of PH.

Approximately 70% of PH is due to a single adrenal cortical adenoma, and most of the rest is due to bilateral IAH. It is important to distinguish between these two subtypes of PH because the treatment of adenoma is surgery, but the treatment of choice for IAH is medical therapy with aldosterone antagonists.

When PH is suspected, a random serum aldosterone and PRA should be measured (see Table 2 on next page). A ratio of aldosterone (ng/dL)/PRA (ng/mL/hour) of more than 20 to 25 has a 95% sensitivity and a 75% specificity for PH.

The next confirmatory test is a 24-hour urinary aldosterone sodium chloride loading of more than 14 mcg/day. Rarely, in difficult borderline tests, an oral IV salt-loading protocol may be performed.

After 5 days of salt loading (10-12 g of sodium chloride), a serum for an aldosterone/PRA ratio and 24-hour collection is done for aldosterone, sodium, potassium and creatinine. The creatinine confirms adequate collection, urinary sodium of more than 250 mEq/day confirms adequate sodium load and validates the other measurements. This test is rarely done because of the significant risk for hypokalemia from the sodium load.

Initial radiologic investigation in the workup of PH is high-resolution, thin-slice (2-2.5 mm) adrenal CT scanning with contrast. Aldosteronomas tend to be small and may not always be seen on CT or MRI scans.

Characteristics of a benign adrenal mass on CT include tumors smaller than 5 cm, regular margins, no necrosis, very low CT attenuation (<20 HU) and delayed contrast washout of more than 50%. The overall sensitivity is more than 90%, but there are many false-positive scans from incidentalomas, which may be found in up to 10% of the population.

Adrenal venous sampling confirms the lateralizable excess aldosterone production and distinguishes between IAH and an aldosteronoma. The accuracy of the test is more than 95% when the procedure is technically successful. The ratio of aldosterone concentrations between the right and left adrenal veins generally exceeds 10:1.

The procedure can be complicated by venous thrombosis and adrenal hemorrhage.

Stephanie L. Lee, MD, PhD, is associate professor of medicine; associate chief, section of endocrinology, diabetes and nutrition; and associate professor of medicine at the Boston Medical Center.

Source: Endocrine Today.