University Times

More death risk in pneumonia with AKI

Patients hospitalized with even mild to moderate community-acquired pneumonia who develop acute kidney injury (AKI) are more likely to die after discharge than pneumonia patients whose kidneys remain healthy, according to a School of Medicine study in the February issue of Kidney International. The study also found a strong relationship between AKI and levels of inflammatory biomarkers.

Doctors have long known that sepsis, a systemic response to severe infection, can trigger abnormalities in kidney function that contribute to higher mortality rates, but the impact of AKI in people with milder infections has not been well characterized, said lead author Raghavan Murugan, a faculty member in the Department of Critical Care Medicine.

“Our study found that kidney injury was quite common among pneumonia patients whose illness course was otherwise uncomplicated,” he said. “They also had a higher risk of dying that persisted even 50 to 100 days after admission, which is surprising because most appeared stable and ready for discharge after eight days.”

The data were gathered from more than 1,800 participants with community-acquired pneumonia in the multi-center Genetic and Inflammatory Markers of Sepsis (GenIMS) study. A third of all patients were diagnosed with AKI, identified by abnormal creatinine levels or urine output, either on the first day of admission or during their hospital stays, as were a quarter of those with mild or moderate pneumonia. Also, a third of all the pneumonia patients progressed to severe sepsis, and of that group more than half developed AKI. Compared to those without kidney injury, AKI patients had longer hospital stays and a higher risk of dying at hospital discharge (11 percent compared to 1.3 percent), 90 days later (24 percent compared to 9.8 percent), and after one year (36.3 percent compared to 20.1 percent).

“The risk of kidney injury was lower in people with less severe infection,” said senior author John Kellum of critical care medicine. “But they still had longer hospital stays and a greater likelihood of dying during admission and even after discharge.”

Another key study finding is that pneumonia patients who also developed AKI had higher concentrations of biomarkers of inflammatory and blood coagulation pathways than those who did not have a kidney injury. “This suggests that the immune response in pneumonia is different in patients with AKI,” Murugan said. “It may be a bidirectional relationship. A stronger immune response might have caused AKI or the response was a consequence of AKI, or it worked both ways.

“We should try to develop prevention and treatment strategies aimed at mitigating the impact of AKI in all pneumonia patients,” he said. “Further research is needed to understand the mechanisms involved, particularly because patients continue to be at risk long after AKI and pneumonia have resolved.”

The GenIMS Study was funded by the National Institute of General Medical Sciences, GlaxoSmithKline and Diagnostic Products Corp.

Pitt co-authors of the study include Vijay Karajala-Subramanyam of medicine, Minjae Lee and Lan Kong of biostatistics and Melinda Carter, Derek C. Angus and Sachin Yende of critical care medicine.

LED lights outshine alternatives

Pitt researchers have conducted the first lifespan assessment of light-emitting diode (LED) streetlights and determined that the increasingly popular lamps strike the best balance between brightness, affordability and energy and environmental conservation when their lifespan from production to disposal is considered.

Engineers in the Mascaro Center for Sustainable Innovation based in the Swanson School of Engineering compared LED streetlights to high-pressure sodium (HPS) lamps found in most cities, metal halide lamps akin to those in stadiums, and the gas-based induction bulb, another emerging technology billed as bright and energy efficient. The team reported that while expensive, LEDs consume half the electricity, last up to five times longer  and produce more light than HPS and metal halide lamps. Induction lights proved slightly more affordable and energy efficient than LEDs, but also may have a greater environmental impact when in use.

The authors also noted that LED technology exhibits more potential for improvement and may surpass induction lamps in the future.

The City of Pittsburgh commissioned the Pitt report as it considers replacing 40,000 streetlights with LEDs. The city estimated that replacing HPS lamps with LED streetlights would save $1 million in energy costs and $700,000 in maintenance each year, while reducing annual carbon dioxide emissions by 6,818 metric tons.

Despite the civic enthusiasm for LEDs nationwide, until the Pitt study no comprehensive analysis of LED streetlights existed, said study coauthor Melissa Bilec, a faculty member in the Department of Civil and Environmental Engineering.

Bilec and fellow civil and environmental engineering faculty member Joe Marriott conducted the evaluation with Cassie Jurgens, a Pitt junior studying civil and environmental engineering and architecture; Pitt junior and industrial engineering student Eric Zatcoff, and Douglas Hartley, a mechanical engineering senior at the Georgia Institute of Technology.

The group’s life-cycle assessment for each lighting technology was created by using information from sales companies, manufacturers, government documents, lighting professionals and industry reports. The assessments catalog the environmental effect of the street lamps during their complete lifespan, from the extraction of raw materials and assembly to electricity consumption and disposal.

A chart of their key findings is available at www.pitt.edu/news2010/Streetlight-Chart.pdf.

Of the technologies studied, LEDs produced the most nega-tive environmental and health effects during manufacturing, according to the report.

Consisting of small lights embedded in circuit boards that require numerous raw materials, LEDs need considerable energy to produce and can be difficult to recycle.

On the other hand, producing LED housings composed largely of plastic and wire consumes far less energy than manufacturing aluminum-heavy HPS casings, the team reported.

LED bulbs also contain no mercury and fewer toxins, such as iodine and lead.

During a bulb’s lifetime, electricity consumption produces up to 100 times the environmental impact of manufacturing, the authors wrote. With electricity consumption converted into kilograms of carbon dioxide produced, metal halide bulbs would emit nearly 500 million kilograms of carbon dioxide during 100,000 hours of use, followed by HPS bulbs with more thans 400 million, induction bulbs with approximately 350 million and LEDs producing slightly more than 300 million kilograms. In addition, the reduced demand on coal-fired plants by LED technology would result in emissions of only two-thirds the amount of airborne toxins and particulates generated by metal halide and HPS lights.

The report also gauged the four technologies by output of nitrogen oxide and chlorofluorocarbon. In both categories, LEDs ranked the highest during the bulb-manufacturing stage but the lowest during actual use. In this final phase, metal halides produced the greatest emissions of both pollutants, the researchers found.

In the crucial area of cost, the prices of LED lights are highly inconsistent — the team estimated a range from $9.20 to $322 per fixture. But the technology’s considerably longer lifespan could mitigate the sticker shock. Based on 100,000 hours of use, LEDs did not last as long as induction bulbs, which were estimated to cost $280 per fixture, but were calculated to burn nearly three times longer than HPS lights and almost five times longer than metal halides.

As an example, 40,000 LED lamps initially could cost the city as much as $21 million versus approximately $9 million for metal halide streetlights. Yet replacing metal halides could cost as much as $44 million before the LED lamps needed a first replacement.

DNA repair observed

Repair proteins appear to efficiently scan the genome for errors by jumping like fleas between DNA molecules, sliding along the strands and perhaps pausing at suspicious spots, say researchers at Pitt, the University of Essex and the University of Vermont, who tagged the proteins with quantum dots to watch the action unfold. The findings are available in Molecular Cell.

Everyone is bombarded constantly with environmental toxins that inflict small errors in the DNA code, so a rapid repair system is essential to maintain the integrity of the sequences for proper cell function, explained pharmacology and chemical biology faculty member Bennett Van Houten, the study’s senior author.

“How this system works is an important unanswered question in this field,” said Van Houten, who also is the Richard M. Cyert Professor of Molecular Oncology and leader of the molecular and cellular cancer biology program at the University of Pittsburgh Cancer Institute (UPCI). “It has to be able to identify very small mistakes in a three-dimensional morass of gene strands. It’s akin to spotting potholes on every street all over the country and getting them fixed before the next rush hour.”

The researchers sought to unravel the mystery by tagging two repair proteins, called UvrA and UvrB, with quantum dots, which are semi-conductor nanocrystals that light up in different colors. They also stretched the usually clumped DNA into multiple “tightropes” to see the process more clearly.

They watched while UvrA proteins randomly jumped from one DNA molecule to the next, holding on to one spot for about seven seconds before hopping to another site. But when UvrA formed a complex with two UvrB molecules (UvrAB), a new and more efficient search technique emerged: the complex slid along the DNA tightrope for as long as 40 seconds before detaching itself and jumping to another molecule.

“If an E. coli bacterium had only one UvrAB complex, 13 hours would elapse before the entire genome was scanned for errors,” said lead researcher Neil M. Kad of the University of Essex. “About 40 complexes, comparable to the estimates of what occurs naturally, would be needed to scan it within the bacterium’s 20-minute doubling time.”

In addition to random jumping and sliding, the researchers also observed what they called “paused motion,” in which UvrAB’s motion seemed slower and purposeful.

Co-author David M. Warshaw of the University of Vermont said, “Paused motion could represent UvrAB complexes checking for structural abnormalities associated with DNA damage.”

The researchers are exploring the possibility that the complexes sample the shape or chemical configuration of DNA by interacting with it; an error could alter the local DNA structure, changing its handshake with the repair proteins and perhaps triggering a corrective response.

The study was funded by the National Institutes of Health, the Royal Society and UPCI.

Hong Wang of pharmacology and chemical biology and UPCI was among the paper’s co-authors.

Ancient infant sacrifice debunked

A study led by Pitt researchers finally could put to rest the millennia-old conjecture that the ancient empire of Carthage regularly sacrificed its youngest citizens. An examination of burial urns containing the remains of Carthaginian children revealed that most infants perished prenatally or very shortly after birth and were unlikely to have lived long enough to be sacrificed, according to a Feb. 17 report in Proceedings of the Library of Science (PLoS) ONE.

The findings refute claims from as early as the 3rd century BCE of systematic infant sacrifice at Carthage that remain a subject of debate among biblical scholars and archaeologists, said lead researcher Jeffrey H. Schwartz, faculty member in anthropology and history and philosophy of science and president of the World Academy of Art and Science.

Schwartz and his colleagues present the more benign interpretation that very young Punic children were cremated and interred in burial urns regardless of how they died.

“Our study emphasizes that historical scientists must consider all evidence when deciphering ancient societal behavior,” Schwartz said. “The idea of regular infant sacrifice in Carthage is not based on a study of the cremated remains, but on instances of human sacrifice reported by a few ancient chroniclers, inferred from ambiguous Carthaginian inscriptions and referenced in the Old Testament. Our results show that some children were sacrificed, but they contradict the conclusion that Carthaginians were a brutal bunch who regularly sacrificed their own children.”

Schwartz and his co-authors tested the all-sacrifice claim by examining the skeletal remains from 348 urns for developmental markers that would determine the children’s age at death. They indicated most of the children died in their first year, many at two-five months of age, and that at least 20 percent of the sample was prenatal.

The contents of the urns also dispel the possibility of mass infant sacrifice, the researchers noted. No urn contained enough skeletal material to suggest the presence of more than two complete individuals. Although many urns contained some superfluous fragments belonging to additional children, the researchers concluded that these bones remained from previous cremations.

The researchers conclude that the high incidence of prenatal and infant mortality are consistent with modern data on stillbirths, miscarriages and infant death. They write that if conditions in other ancient cities held in Carthage, young and unborn children easily could have succumbed to the diseases and sanitary shortcomings found in such cities as Rome and Pompeii.

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