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May 1, 2003


Men twice as likely to die during storms

Men are more than twice as likely to die during thunderstorms than are women, and most cases involve a vehicle or sports.

These findings from a Pitt study were presented April 28 at the Centers for Disease Control and Prevention’s Safety in Numbers meeting in Atlanta.

“We found that deaths from thunderstorm-related weather conditions center around flash floods and lightning strikes, and the victims are primarily male,” said Thomas J. Songer, assistant professor of epidemiology at Pitt’s Graduate School of Public Health and assistant professor of neurological surgery at Pitt’s School of Medicine and Center for Injury Research and Control. “In deaths from flash floods and high winds, most of the victims were in a vehicle, usually engaged in an attempt to drive through the water. With regard to lightning strikes, most of the victims were involved in sports or recreational activities, or in work-related activities at the time of death.”

Songer examined data on thunderstorm-related deaths in the United States from 1994 through 2000. Specific weather elements included thunderstorm winds, flash floods, tornadoes and lightning. Data included circumstances of death, age, gender, activity, location, work relatedness, date, time and vehicle involvement.

A total of 1,442 deaths were identified; 70 percent were males. Two-thirds occurred outside the home, and most of these occurred in males during flash floods or lightning strikes.

Specifically, the highest percentage of deaths from flash floods involved driving/transport (65 percent); from lightning involved sports/recreation (36 percent) or work (21.8 percent); from tornadoes involved outdoor activities (40 percent) or driving/transport (23 percent), and from high winds involved driving/transport (35.6 percent) or boating/fishing (23 percent).

“When a thunderstorm strikes, the best thing to do is to get into a building. But when that’s not possible, questions arise over whether to seek low or high ground; to remain in a vehicle or to get out,” said Songer. “Judging by the numbers of deaths from various weather conditions associated with thunderstorms, the proper course of action appears to depend upon what weather conditions one is facing, and where one is at the time. Lightning seeks the highest point in an area, which puts sports and recreation enthusiasts at risk during activities that involve a wide-open playing field, golf course or lake. Getting into a car is advisable, if possible. On the other hand, when near a rising body of water one should abandon one’s vehicle and seek higher ground to avoid flash floods.”


Type 1 diabetics can get ‘double diabetes,’ heart disease from insulin resistance

Insulin resistance, a condition commonly associated with the development of type 2 diabetes, is likely a major cause of heart disease in people with type 1 diabetes, according to study results published by Pitt Graduate School of Public Health (GSPH) researchers in the May 2003 issue of Diabetes Care, a journal of the American Diabetes Association.

“Heart disease is a major complication for people with diabetes, including those with type 1 diabetes, and until now there has been no clear explanation for its cause,” said principal investigator Trevor Orchard, professor in GSPH’s epidemiology department. “We now suspect that insulin resistance occurs in those with type 1 diabetes in the same way as it does in those with type 2, essentially giving these individuals double diabetes and greatly increasing their risk of heart disease.”

Insulin resistance, long associated with type 2 diabetes and a risk factor for heart disease, occurs when the body does not properly use insulin to metabolize blood glucose, or sugar. The condition results when insulin fails to enable cells to admit glucose, necessary for cells’ energy production. Glucose then builds up in the blood, and additional insulin is required. The new study suggests that this condition can occur in people who have type 1 diabetes as well.

“The good news is that not all people with type 1 diabetes are insulin resistant, and for them the risk of heart disease may not be as high,” Orchard said. “Clearly, reducing or preventing insulin resistance through exercise, weight loss and possibly medication may help people with type 1 diabetes avoid heart disease.”

The study analyzed data from the Pittsburgh Epidemiology of Diabetes Complication Study (PEDCS), a 10-year prospective investigation based on a cohort of adults with type 1, or childhood-onset, diabetes. Of the 658 subjects in PEDCS, 603 did not have heart disease at baseline and were followed for the current study.

Over the 10-year period there were 108 cardiovascular events such as angina, heart attack or death among the participants. Risk factors were lowest among those who experienced no cardiovascular events, moderate among those with angina and highest among those who died.

Insulin resistance was a risk factor that predicted all adverse events, and it was the most severe among those participants who experienced the most serious events.

To measure insulin resistance, investigators used the estimated glucose disposal rate (eGDR), a novel calculation based on waist-to-hip ratio, hypertension status and long-term blood sugar levels. Study participants with no cardiovascular events had a normal eGDR; those who experienced angina, considered a moderate event, had a lower eGDR; and those with the most severe events had the lowest eGDR.

High blood sugar itself was the only potential risk factor that did not appear to predict cardiovascular events.

“Our analyses are consistent with the hypothesis that individuals with high blood glucose develop plaques in their coronary arteries that are more fibrous than normal. That quality could have a stabilizing effect that makes the plaque less likely to rupture and cause a blood clot that would result in a heart attack,” Orchard explained. “However, any protective effect from the fibrous nature of their arterial plaque is countered by the likelihood that glucose causes more such plaques and that it will not affect the risk of atherosclerosis-related problems elsewhere in the body, where the very existence of plaque can lead to lower extremity arterial disease, which sometimes results in amputation.”

The study was supported by the National Institutes of Health.


G&PS prof awarded NASA grants

David A. Crown, an adjunct assistant professor in Pitt’s Department of Geology and Planetary Science (G&PS) and a senior scientist at the Planetary Science Institute in Tucson, Ariz., has been awarded two NASA research grants for studies in planetary geology.

Crown received a $197,571 grant from NASA’s Mars Data Analysis Program to investigate surfaces of ancient Martian volcanoes using data acquired by the Mars Global Surveyor and Mars Odyssey spacecrafts, which currently are orbiting Mars. Crown, along with assistant professor Michael S. Ramsey, also received a $150,000 grant from NASA’s Planetary Geology and Geophysics (PGG) Program for comparative studies of lava flows on the Earth, Mars, and Venus. Crown has been a principal investigator in NASA’s PGG program since 1994.


Bacteriophages may be largest unexplored reservoir of gene sequence data

The largest unexplored reservoir of gene sequence information may be contained in bacteriophages, viruses that infect bacteria, according to a paper published in the April 18 edition of Cell.

Contributing to the paper were researchers at Pitt, Albert Einstein College of Medicine, the Tuberculosis Research Center of India, and two American high schools.

Characterizing the genomes of 10 new mycobacteriophages for the study revealed an astounding number of never-before-seen genes, according to principal investigators Graham Hatfull, Roger Hendrix and Jeffrey Lawrence of Pitt’s biological sciences department and William R. Jacobs Jr., professor of microbiology and immunology and of molecular genetics and a Howard Hughes Medical Institute (HHMI) investigator at Einstein College. Hatfull is an HHMI Professor and Eberly Family Professor of Biotechnology, Hendrix is a professor of biological sciences and Lawrence is an associate professor.

The researchers found that 50 percent of the genes in the mycobacteriophages they studied had never been seen previously and that 80 percent of the remaining 50 percent had been found only on the 14 mycobacteriophages that have been sequenced to date.

Bacteriophages are the most abundant organisms on Earth, with estimates of the number of different species at 10 million trillion trillion. No genomically defined phage has been isolated more than once, and the few sequenced phage genomes are widely varied, according to the paper’s authors.

“The genomic sequences of these newly isolated mycobacteriophages suggest that the bacteriophage population as a whole is amazingly diverse,” said Hatfull. “There is some suggestion that phages could be involved in bacterial pathogenesis in ways we never imagined.”

For example, one of the phages studied contained a gene homologous to the human gene in lupus, according to Jacobs. “While we don’t yet know the function of this protein, we’re pretty confident that it will lead us to better understanding of lupus. Many autoimmune diseases have infectious origins — lupus may also.”

The researchers conducted their work with the aid of high school students from Pelham Memorial High School in Pelham, N.Y., and Greater Latrobe High School in Latrobe, Pa. Participating students, who are listed as coauthors of the paper, were part of a science educational program established by the Howard Hughes Medical Institute. In the project, the high school students gathered samples, participated in purification of the phages and isolation of DNA, and assisted in the electron microscopy.

“While much of the nuts and bolts of the sequencing was done by folks here in our genome center, the students also participated in the analysis of the DNA sequence and annotation of the genomes,” according to Hatfull. The Pittsburgh Bacteriophage Institute, one of the world’s leading centers for bacteriophage genomics and co-directed by Hatfull and Hendrix, provided the environment for student researchers.


Gene therapy may treat post-radical prostatectomy erectile dysfunction

Researchers from the University of Pittsburgh Medical Center (UPMC) have found that gene therapy may not only be a feasible, but also may be an ideal treatment for neuropathic erectile dysfunction (ED). Neuropathic ED results from damage to the nerves essential to achieving and maintaining an erection and is experienced by 79.6 percent of men who undergo radical prostatectomies.

“While radical prostatectomy can be a cure for early stage prostate cancer in a large percentage of patients, there are a number of risks and side effects that patients must consider when deciding on whether to have the surgery or not — one of those being the high likelihood of experiencing erectile dysfunction,” said Michael Chancellor, director of neurourology at UPMC and professor of urology at Pitt’s School of Medicine. “If by using gene therapy prior to surgery, we can minimize nerve damage and preserve the patient’s ability to have an erection, the patient may be less reluctant to have the potentially life-saving procedure.”

In the study, researchers injected herpes simplex virus vectors that deliver neurotrophic factors, factors that facilitate the recovery of injured nerves, into the corpus cavernosum or cavernous nerve of rats at the time of cryo-injury to the cavernous nerve. The cavernous nerve is the nerve that stimulates erection; cryo-injury has similar effects on the nerve as radical prostatectomy. After injection, they found that the viral vectors transported the neurotrophic factors to the nerve. On electrical nerve stimulation, nerve-injured rats that expressed the viral vector experienced an increase in intracavernous pressure.

Researchers hope that this concept can be translated into humans, enabling gene therapy to be used as a prophylactic treatment for men undergoing radical prostatectomy.

Radical prostatectomy is used to treat the early stages of prostate cancer by surgically removing the prostate gland and surrounding tissue. The procedure has a success rate of 70 to 85 percent. A high percentage of patients experience ED after the procedure due to injury to the peripheral nerves, including the cavernous nerve, located close to the prostate gland.

Study results were presented April 28 at the annual meeting of the American Urological Association (AUA) and are published in abstract 1179 of the AUA proceedings.

In addition to studying the use of gene therapy to treat post-radical prostatectomy ED, the Pitt team also is investigating the potential of using muscle derived stem cells to regenerate peripheral nerves often damaged by radical prostatectomy. This study is published in abstract 1256 of the AUA proceedings.


LGBP resolves or improves diabetes for most patients

According to a study presented April 24 by University of Pittsburgh Medical Center (UPMC) researchers at the American Surgical Association’s (ASA) annual meeting in Washington, D.C., 97 percent of patients who underwent laparoscopic Roux-en Y gastric bypass surgery for obesity (LGBP) had resolution or improvement of their type 2 diabetes mellitus.

The study by Philip Schauer, assistant professor of medicine at Pitt’s School of Medicine and co-director of the Minimally Invasive Surgery Center at UPMC Presbyterian, examined 1,150 patients over a five-year period following their LGBP surgeries. Of those patients in the study, 240 (21 percent) had type 2 diabetes mellitus and 192 of the 240 patients (80 percent) were available for follow-up.

The LGBP procedure involves constructing a small stomach pouch of approximately 15 millimeters (about the size of a plastic medicine cup), and bypassing a small segment of intestines by constructing a Y-shaped limb of small bowel. Patients lose weight because there is a decrease in caloric intake resulting from the reduced reservoir capacity of the small stomach pouch.

Type 2 diabetes is the most common form of diabetes, in which the body is unable to properly use the insulin that it produces. About 80 percent of people with type 2 diabetes are overweight.

“Patients with the shortest duration and mildest form of diabetes prior to surgery had quicker resolution and significantly better outcomes, suggesting that early surgical intervention is warranted to increase the likelihood of patients having a normal level of glucose in the blood,” said Schauer.


Minimally invasive esophagus surgery results in improved survival, less hospital time

Findings from the largest study to date evaluating minimally invasive esophagectomy (removal of the esophagus to treat esophageal cancer) indicate that the procedure results in lower mortality rates and shorter hospital stays compared with most open procedures.

The results of the study, conducted by James D. Luketich, associate professor of surgery and chief, Division of Thoracic Surgery, University of Pittsburgh Medical Center (UPMC) and co-director, Lung and Esophageal Cancer Program, University of Pittsburgh Cancer Institute, and Chrish Fernando, also of UPMC, were presented at the annual meeting of the American Surgical Association (ASA), April 24-26, in Washington, D.C.

Minimally invasive esophagectomy, or MIE, was evaluated in 221 patients at UPMC from June 1996 through August 2002. Average hospital stays and mortality rates were compared with similar-size studies of open methods including thoracotomy (surgical opening of the chest wall) and laparotomy (surgical opening of the abdomen), or both.

The study found that the median hospital stay was seven days for patients who underwent MIE compared with typical hospital stays in excess of 10 days for patients who underwent open procedures. The study also found that mortality occurred in 1.3 percent of the MIE cases compared with typical mortality rates of up to 5 percent or higher as reported for open procedures.

MIE is a video-assisted surgical procedure that utilizes instruments introduced into the body through very small incisions and a laparoscope, or tiny camera. Patients who are candidates for MIE undergo extensive preoperative evaluation involving laparoscopic staging, endoscopic ultrasound and CT scans to assess the extent of the disease.

“Our study demonstrates that minimally invasive esophagectomy offers results as good as, if not better than, open esophageal procedures,” said Luketich, who also is co-director of the Mark Ravitch/Leon C. Hirsch Center for Minimally Invasive Surgery at UPMC. “These results are encouraging and demonstrate that MIE can improve patient outcomes without compromising accepted standards of care.”

Luketich stressed, however, that the success of esophagectomy, whether done through standard open approaches or minimally invasively ones, largely depends on surgical expertise in the procedure and volume of procedures performed annually. He also noted that excellent results using open approaches have been reported from centers that specialize in esophagectomy.

The American Cancer Society estimates that in 2003 approximately 13,900 people will develop esophageal cancer in the United States, and 13,000 will die from the disease. It also has been noted that esophageal cancer is rapidly rising in the United States.

The only known risk factor for esophageal cancer is chronic heartburn. Esophageal cancer can develop in any part of the esophagus and often spreads to the windpipe, large blood vessels in the chest, lungs, liver and stomach. Symptoms include difficulty swallowing, weight loss, loss of appetite, coughing, hoarseness, bone pain and shortness of breath.

Co-authors for the study, in addition to Fernando, included Miguel Alvelo-Rivera, Philip Schauer, Percival O. Buenaventura, Neil A. Christie and James McCaughan, all with Pitt.

The study was sponsored by ASA member Timothy R. Billiar, professor and chairman of surgery at Pitt.

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