University Times

Urological research presented

New study results from School of Medicine researchers were presented in May at the annual meeting of the American Urological Association.

They include:

• Botox yields lasting prostate relief

Injecting botulinum toxin A, or Botox, into the prostate gland of men with enlarged prostate eased symptoms and improved quality of life up to a year after the procedure, according to researchers at Pitt’s School of Medicine and at the Chang Gung University Medical College, Taiwan.

Michael B. Chancellor, senior author of the study and professor of urology and gynecology at the School of Medicine, said enlarged prostate is “a challenging disease to live with because it causes frequent and difficult urination. Unfortunately, common treatments also are problematic because they carry some risk of serious side effects, such as impotence. Our results are encouraging because they indicate that Botox could represent a simple, safe and effective treatment.”

The 37 study participants, diagnosed with symptomatic benign prostatic hyperplasia (BPH) that did not respond to standard medical treatment, received injections of Botox directly into their prostate glands. Up to one year post-injection, 27 of these patients, or 73 percent, experienced a 30 percent improvement in urinary tract symptoms and quality of life. Patients did not experience any significant side effects.

According to Yao-Chi Chuang, principal investigator of the study from Chang Gung University, Botox reduces the size of the prostate gland through a cellular process called apoptosis, in which the prostate cells die in a programmed manner. This reduction in size can improve urine flow and decrease residual urine left in the bladder.

Naoki Yoshimura of Pitt’s School of Medicine was among other researchers involved with the study.

• Stem cell injections treat incontinence

Women with stress urinary incontinence (SUI) who were treated using muscle-derived stem cell injections to strengthen their sphincter muscles experienced long-term improvements, according to researchers at Pitt and the Sunnybrook Health Sciences Centre in Toronto. The study, which followed patients for more than a year, suggests that the approach is safe, improves patients’ quality of life and may be an effective treatment.

Women with SUI involuntarily leak urine during activities that put pressure on the bladder, such as running, coughing, sneezing or laughing. Stress incontinence is caused by childbirth, menopause or pelvic surgery.

Michael B. Chancellor, the study’s senior author and professor at the School of Medicine, said: “We’re demonstrating for the first time that we may be able to offer people with SUI a long-term and minimally invasive treatment option.”

In the study, researchers took biopsies of skeletal muscle tissue from eight female patients and isolated and expanded the stem cells from the tissue in culture. Patients received injections of the muscle-derived stem cells into the area surrounding the urethra.

Five of the eight women in the study reported improvement in bladder control and quality of life with no serious short- or long-term adverse effects one year after the initial treatment.

Janet Erickson and Wendy Leng of the medical school contributed to the study.

• Green tea may fight bladder inflammation

Herbal agents could be used to treat inflammatory bladder diseases, according to a study that found that components of green tea protected bladder cells from damage in culture.

Green tea, reported to have many health benefits, is comprised of catechins — plant metabolites that provide it with many anti-oxidative properties.

Pitt’s Michael B. Chancellor said: “These results indicate herbal supplements from green tea could be a treatment option for various bladder conditions that are caused by injury or inflammation.”

In the study, normal and cancerous bladder cells were exposed to two major catechin components of green tea, epigallocatechin gallate (EGCG) and epicatechin gallate (ECG). Both protected cell lines significantly from exposure to hydrogen peroxide, which damages or kills cells. The concentrations of EGCG and ECG used in the study were at levels that could be achieved through dietary intake.

Co-investigators were Shelby Morrisroe, Christian Coyle, Brian Phillips, William de Groat and Naoki Yoshimura, all of the School of Medicine.

The study was funded by the Fishbein Family CURE-IC Program.

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New matter, a polariton superfluid, created at Pitt

Pitt physicists have demonstrated a new form of matter that melds the characteristics of lasers with those of the world’s best electrical conductors. The work introduces a new method of moving energy from one point to another as well as a low-energy means of producing a laser-like light beam.

The researchers and their collaborators at the Bell Labs of Alcatel-Lucent detailed the process in the May 18 issue of the journal Science.

The new state is a solid filled with a collection of energy particles known as polaritons that have been trapped and slowed, explained lead investigator David Snoke, associate professor of physics and astronomy, who worked with Pitt graduate students Ryan Balili and Vincent Hartwell on the project.

Using specially designed optical structures with nanometer-thick layers that allow polaritons to move freely inside the solid, Snoke and his colleagues captured the polaritons in the form of a superfluid. (In superfluids and in their solid counterparts, superconductors, matter consolidates to act as a single energy wave rather than as individual particles. In superconductors, this allows for the perfect flow of electricity.)

In the new state of matter, which can be called a polariton superfluid, the wave behavior leads to a pure light beam that is similar to that from a laser but much more energy efficient.

Traditional superfluids and superconductors require extremely low temperatures (approximately -280 and -450 degrees Fahrenheit, respectively); the polariton superfluid is more stable at higher temperatures and may be capable of being demonstrated at room temperature soon.

Pitt’s research builds on current efforts in physics laboratories around the world to create materials that mix the characteristics of superconductors and lasers.

Snoke’s work provides a new method to trap and manipulate the energy particles. Applied to technology, this technique could provide new ways of controlled transfer of optical signals through solid matter.

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Nation’s first beating heart transplant done at UPMC

Kenneth R. McCurry, an assistant professor of surgery in the Division of Cardiothoracic Surgery at the School of Medicine, performed the nation’s first beating heart transplant last month at UPMC.

The heart, which was protected by its own nutrients and blood supply supported by an investigational organ preservation device, was transplanted successfully into a 47-year-old man with congestive heart failure and pulmonary hypertension.

The donated heart was maintained in a beating state on the investigational Organ Care System (OCS) for two hours and 45 minutes.

The recipient was discharged from the hospital April 30.

McCurry, director of cardiopulmonary transplantation at UPMC’s Heart, Lung and Esophageal Surgery Institute, is principal investigator of the PROCEED Trial at UPMC. The study is evaluating the safety and efficacy of the OCS for heart transplants.

The OCS is designed to maintain donor hearts in a beating, functioning state during transportation from the donor to the recipient’s hospital. After removal from the donor, the heart is placed into the OCS, where it is revived immediately to a beating state, perfused with oxygen and nutrient-rich blood and maintained at the appropriate temperature.

The current standard of preserving an organ for transplantation is cold preservation, in which the organ initially is perfused with a cold solution and packed in sterile ice. The organ is without blood or oxygen, which may cause injury to the transplanted organ or possible rejection.

“By maintaining the organ in near perfect physiologic state, the OCS will reduce injury and help extend the life of these organs, which also will improve patient outcomes with less rejection and shorter length of ICU and hospital stay,” said McCurry.

In April the U.S. Food and Drug Administration approved the pilot phase trial at UPMC, Brigham and Women’s Hospital in Boston, the UCLA Medical Center in Los Angeles, the University of Chicago Hospitals Cardiac Center and the Cleveland Clinic Heart and Vascular Institute.

Results of a similar European trial using the OCS were reported at the annual meeting of the International Society of Heart Lung Transplantation last month. That trial showed success with the device in 20 heart transplants with 30-day graft and patient survival at 100 percent.

Co-investigators at UPMC were Robert Kormos, Yoshiya Toyoda, Christian Bermudez and Diana Zaldonis, all from the Department of Surgery.

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Gleevec study funded

University of Pittsburgh Cancer Institute researchers have received $25,000 to better understand and improve a common treatment for gastrointestinal cancer. The grant comes from the GIST Cancer Research Fund — a patient-driven organization that funds research on gastrointestinal stromal tumors, or GISTs.

The award supports the research of Anette Duensing, a research assistant professor of pathology in the School of Medicine. Duensing and her colleagues are examining the mechanisms of action of Gleevec, a treatment for GIST that, although initially effective, does not stop tumors from growing long-term and does not work in about 15 percent of patients.

Duensing’s lab is examining how cells respond to the treatment. She has identified a novel protein that appears to influence tumor cell response to Gleevec and is manipulating levels of this protein in GIST cells in an attempt to destroy tumor cells faster and more effectively.

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Soldiers benefit from sports medicine

Advances in sports medicine science designed for the athletic field are being applied to the battlefield to help protect American soldiers from injury.

Funded by a $2.75 million grant from the Department of Defense to UPMC, the new Injury Prevention and Performance Enhancement (IPPE) Laboratory at Fort Campbell, Ky., is operated by researchers from the Pitt/UPMC Neuromuscular Research Laboratory (NMRL).

NMRL scientists have been studying research data involving athletes’ body positioning and neuromuscular control as it relates to injury.

The IPPE lab is one of two components of a larger DoD initiative to create a Wounded Warrior Rehabilitation Center that will include a return-to-readiness physical therapy and athletic training program to rehabilitate injured soldiers.

The lab will allow researchers to identify injury risk factors for more than 900 air assault soldiers in the U.S. Army’s 101st Airborne Division. Researchers will study injury patterns, causes and risk factors. For example, knee and ankle injuries in this soldier population have been linked to awkward and dangerous landing positions during parachuting, fast-roping and rappelling. Intense climbing, pulling and overhead activity can alter shoulder mechanics over time, leading to injuries.

Using biomechanical modeling techniques and equipment, such as a motion monitor electromagnetic tracking device, researchers can study precise physical movement patterns, forces, joint angles and range of motion on test subjects while they perform task simulations. Intervention exercises will be designed to improve specific muscle strength, flexibility, joint position, balance and neuromuscular control to prevent injury.

Potentially the first in a network of similar facilities proposed throughout the military, the lab’s data will be used to develop training and conditioning programs for injury prevention and performance enhancement.

The IPPE lab director is NMRL director Scott Lephart, who also is an associate professor of orthopaedic surgery, holds an appointment in the School of Health and Rehabilitation Sciences and serves as chair of the Department of Sports Medicine and Nutrition.

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UPMC docs study new heart pump

Doctors at UPMC have begun a study using an investigational cardiac device, the VentrAssist Left Ventricular Assist System (LVAD), to see whether it can be used safely and effectively in patients with end-stage heart failure.

The study, funded by Ventracor, aims to enroll a total of 30 patients at nine centers in the United States.

Five patients at UPMC have received the device so far, and one has received a heart transplant after waiting for nearly three months on LVAD.

The experimental pump is implanted in patients with end-stage heart failure to assist the heart. It draws blood from the left ventricle and returns it to the aorta, working in tandem with the heart.

The titanium pump is lighter than older pumps, weighing just over a half-pound, compared to five pounds. In addition, its centrifugal design allows it to respond to exercise more like the natural heart.

While this device is approved only for use in the study, there are a limited number of LVADs that are approved commercially for a bridge to heart transplant, but they can be large and cumbersome. Patients must be tethered to machines that severely limit their activity.

The researchers hope that the VentrAssist LVAD investigational study will help reduce the load on the patient’s heart while awaiting a transplant and improve blood flow, circulation and overall quality of life.

In some cases, the patients with earlier model LVADs demonstrated recovery of their own heart and could be weaned off the LVAD without needing a heart transplant. It is not known yet whether the VentrAssist LVAD will have the same effect. A parallel U.S. clinical trial will look at the safety and feasibility of the VentrAssist LVAD as an alternative to transplantation.

“The VentrAssist LVAD presents us with a third-generation mechanical solution for end-stage congestive heart failure that approaches the goal of minimal interference with a patient’s life,” said Robert Kormos, co-director of heart transplantation, director of the artificial heart program and medical director of the McGowan Institute for Regenerative Medicine. “In a subsequent study, we will focus on support for transplant candidates as well as permanent use for those who do not qualify for heart transplantation, hopefully demonstrating its advantages over previous technology.”

Other Pitt investigators involved are Michael Siegenthaler, Jeffrey Teuteberg, Linda Cadaret, Michael Mathier, Dennis MacNamara, Kenneth McCurry and Mary Amanda Dew, all of the School of Medicine.

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