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New Hope For a Cancer Vaccine

"Extreme remedies are very appropriate for extreme diseases"

-- Hippocrates

Researchers at the University of Pennsylvania Medical Center have devised a method to transform common white blood cells into rare dendritic cells that boost the immune system's cancer-fighting forces. In test-tube cultures, the modified cells have already shown their ability to activate T cells within one week.  

Penn investigators collaborated with a team from the National Cancer Institute in this ongoing research. The next step is to demonstrate that the dendritic cells can induce a clinically useful and safe response in the bodies of cancer patients.  

"Our procedure could be used to produce vaccines against cancers, including breast, colon, and melanoma," said Brian J. Czerniecki, MD, PhD, assistant professor of surgery in Penn's School of Medicine. Although vaccines are typically thought of as a preventive treatment--administered to patients before contracting a disease--most cancer vaccines are designed to spur the immune system into attacking existing tumors.  

Dendritic cells play a leading role in generating an immune response. Until recently, cancer vaccines have used additives called adjuvants to mobilize dendritic cells. Now they can generate them directly.  

Czerniecki told ScienceNow that he is very much encouraged by the dataon the vaccine. The procedure "is very much more potent than other cancer vaccines," he said.  

Reports began October 9.

The Lancet (London)

The Journal of the American Medical Association

ScienceNow

Pittsburgh Post Gazette

Explaining Carbon Monoxide Poisoning

Researchers at the University of Pennsylvania Medical Center have discovered a novel biochemical mechanism for carbon monoxide poisoning that may someday lead to new clinical approaches for treating carbon monoxide poisoning.  

The classic explanation for CO's poisonous action is that it binds to hemoglobin molecules in the blood, impairing oxygen delivery to the body's cells. Eventually cells essentially suffocate and die. "This traditional view explains the mechanism of carbon-monoxide toxicity in only a small fraction of all people exposed to it," said Stephen R. Thom, MD, PhD, associate professor of emergency medicine and chief of hyperbaric medicine at Penn's Institute for Environmental Medicine. "The vast number of patients we see clearly don't fit this traditional explanation. Science falls down in terms of what we see in day-to-day practice."  

Thom and his colleagues have identified a mechanism that provides an alternative explanation for CO toxicity. "We found that carbon monoxide binds to the same sites on heme proteins as nitric oxide," Thom said. Nitric oxide is a naturally occurring vasodilator and gaseous signaling molecule. An excess of NO, however, is deleterious to brain cells and other tissues.  

"We have identified how CO can damage cells at levels that are relevant to real-world situations," said Thom in The Lancet. Thom said he hoped that the study's findings will convince physicians who tenaciously hold onto the classic explanation for carbon monoxide toxicity that there is more than one way to explain CO poisoning.  

Reports began October 4.

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Sniffing Out Infections

In the "olden" days, doctors were accustomed to detecting various medical problems by using their sense of smell. In today's world of high technology, this practice has fallen by the wayside. Now, University of Pennsylvania Medical Center researcher C. William Hanson III, MD, associate professor of anesthesia, has found that aroma-analysis machines like those used in the beverage, food, and perfume industries, can detect the presence of pulmonary infection. He presented the "electronic nose" at the annual meeting of the American Society of Anesthesiologists in October.  

"We've found that the aroma-analysis device can be used as a tool to diagnose lung infections sooner, faster, non-invasively, and at a fraction of the cost of current diagnostic techniques," Hanson said.  

Hanson began his research by borrowing an aroma-sensing machine from a company called AromaScan. He and his colleagues tested 19 ICU patients who had recently undergone heart surgery. Ten patients were thought to be uninfected, and the nine others had known lung yeast infections. After the machine analyzed samples of their breath, its sensors gave different readings for the infected patients.  

"There's a lot of work that needs to be done yet," Hanson said in The Philadelphia Inquirer. But, he added, "I think that this approach to diagnosing diseases is a potential gold mine."  

Reports began October 6.

MSNBC

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Skin-Sparing Mastectomy

Traditionally, women facing surgery because of breast cancer were treated with either mastectomy or lumpectomy. But even the less invasive lumpectomy procedure tends to leave the breast with an unusual appearance, and the radiation therapy that usually follows tends to shrink the breast.  

Now, a new technique that combines the expertise of cancer surgeons and plastic surgeons offers many women an alternative. Called "skin-sparing mastectomy," the surgery involves excising the breast tissue through an opening made by removing only the nipple and surrounding areola. This leaves the breast "skin envelope," and eliminates the need for totally removing the breast. The skin envelope is filled in by using tissue from the patient's abdomen and/or back, resulting in a breast that has virtually the same shape and sensation as the woman's opposite breast.  

"Appearance-wise, we are really close," said Louis Bucky, MD, assistant professor of surgery and a plastic surgeon at Penn's Center for Human Appearance, on WPVI-TV6's Action News. "I would say that in a bra, nobody can tell the difference, or in a bathing suit or an evening gown." Douglas Fraker, MD, associate professor of surgery and chief of the division of surgical oncology, said that the appropriateness of the surgery depends on the patient. "Patients who are opting toward mastectomy rather than lumpectomy and radiation for whatever reason are candidates," Fraker said. "Also, patients who have larger lesions and smaller breasts, those who have ductal carcinoma--which is a non-invasive cancer which may present extensively, yet localized in the breast and is not treatable by lumpectomy surgery--and those patients who are fearful of or cannot be subjected to radiation treatment which traditionally follows lumpectomy surgery are appropriate choices."  

Reports began October 3.

Reuters

The Philadelphia Inquirer

WCAU-10

Better Results with AIDS Cocktail

According to two papers published in The New England Journal of Medicine in early September, a three-drug combination of antiretroviral therapy suppresses viral load in HIV-positive patients and improves clinical outcomes.  

The first report was based on a government study conducted at 40 sites, including the University of Pennsylvania Medical Center, that found that patients who received an "AIDS cocktail"--combining the drug Crixivan with the AIDS drugs AZT and 3TC--fared better than those didn't receive all three drugs simultaneously.  

The second study, based on a study conducted at Beth Israel Deaconess in Boston examined the outcome of patients on a similar three-drug combination, with similar results.  

"The study shows that the regimen with Crixivan can keep people alive longer and keep them healthier," commented Stephen Gluckman, MD, associate professor of medicine and an investigator on the government study, in an interview with WCAU-TV10's News 10.  

The government study showed that the AIDS cocktail cut the progression of the disease in half, and lowered the death rate. The level of HIV in the blood of patients taking the drugs was reduced to undetectable levels. But this does not mean the patients are cured.  

"The virus can live in many other places, many other tissues, particularly the lymph nodes, and merely getting it out of the blood doesn't get it out of these other tissues."  

Reports began September 10.

Weight Watchers

Town & Country

Talking About Depression

Depression affects about 17.6 million Americans a year. No matter the source, most depression can be treated successfully. But only about a third of sufferers seek help. To raise consciousness about the affliction, two prominent University of Pennsylvania Medical Center experts recently discussed the subject in articles that appeared in popular women's magazines.  

Thomas A. Wadden, PhD, professor of psychology in psychiatry and director of Penn's Weight and Eating Disorders Program, recently had a lengthy "Q & A" session with Weight Watchers magazine. When asked how depression differs from an "off" mood, Wadden explained, "Depression is a severe disturbance in mood that disrupts the individual's daily functioning. Depression affects your mood, your behavior, your thinking." Symptoms of depression include sadness and an inability to enjoy things that used to give pleasure. Wadden commented that although there is no clear evidence that depression is more common in obese people, it does appear that more obese people suffer from dysthymia--a low grade depression characterized by sad feelings, but without sleep and appetite disturbances or suicidal thoughts.  

Ira Katz, MD, PhD, professor of psychiatry, spoke on the subject of depression after age 70 in Town & Country magazine. "Everyone who works with older people is amazed by their ability to cope with disease, loss, disability--as long as they're not depressed." Treating late-life depression is a medical necessity. Many antidepressants are available that can help, but Katz said that treatment is not limited to drugs. "Eight to twelve weeks of cognitive behavioral therapy, interpersonal therapy, or problem-solving therapy can make a big difference," he added.

The articles appeared in the September issues.

Ladies' Home Journal

The Patient Who Changed a Career

Ladies' Home Journal had a specific story angle in mind: Ask "top docs" to describe their toughest, most memorable patients--the ones who taught them the most about medicine and compassion. Barbara Weber, MD, associate professor of medicine and genetics and director of Penn's Breast Cancer Program, was one of three physicians highlighted.  

Weber told the story of a patient she treated for breast cancer several years ago who had a very strong family history of the disease. Although the gene for hereditary breast cancer had not been isolated at the time, Weber and her research team "had learned enough to predict which family members were likely to carry it by looking at their DNA." This particular patient's family was under study: each family member had given his or her blood. Weber and her team were able to identify each member who had the gene--but they were not permitted at that time to reveal the information obtained from ongoing research.  

One day the patient came in for a visit with her younger sister, who so farhad not developed the disease. The sister mentioned to Weber that was preparing to have a prophylactic double mastectomy. The information startled Weber. She remembered that the study information showed that this sister did not have the gene.  

"My heart raced as I thought back to the laboratory tests on Susan's family," said Weber. "I excused myself and left the examination room." She immediately tried to contact a colleague to ask for advice, but could not reach him. A quick decision was needed, and it was clear to Weber what she had to do. "Cancel the surgery," she told her patient's sister.  

"I really didn't have a choice that day I agonized over whether to tell [the sister] the results of her test. ... I couldn't have lived with myself if I'd kept silent and let her have an operation she didn't need."  

The article appeared in the October issue.

Hospital and Healthcare News

WPVI-TV6

A Breath Test to Detect Ulcers

A new breath test that can detect the presence of active Helicobacter pylori in patients with gastrointestinal symptoms associated with peptic and gastric ulcers is now available at the University of Pennsylvania Medical Center. The test, called the Carbon-13 urea breath test (C-13 UBT), was approved by the Food and Drug Administration in 1996. At present, Penn's gastroenterology division is the only facility in the Philadelphia area to offer the test.  

Previously, the only accurate way to detect the presence of active H. pylori infection was an endoscopic biopsy. In the Delaware Valley, approximately 30 to 35 percent of the population are infected with the bacteria, although most never develop major problems. "The endoscopic biopsy, while the gold standard for H. pylori detection, is uncomfortable for the patients, takes more time, and costs much more to perform than the C-13 UBT," said Metz in Hospital and Healthcare News.  

The C-13 UBT, developed by Meretek of Houston, takes about 45 minutes to perform. The patient fasts before the test, and then drinks a clear tasteless solution. Breath samples are collected before and after the liquid is taken. The samples are analyzed by the lab, and results are available in three days. The test detects urease, which is produced in large amounts by H. pylori.  

Reports began in July.

Phildelphia Business Journal

Teaching Compassion

When Alicia M. Conill, MD, assistant professor of medicine, began her career as a physician, she used to ponder whether medical students could be taught compassion. What she found was that compassion is something that is most easily learned firsthand. And because she was struck with a disease--multiple sclerosis--she became an unwitting student.  

Conill joined the Division of General Medicine at the University of Pennsylvania Medical Center in 1987, teaching and handing a caseload that soon included 3,000 patients. It was a year later that Conill was diagnosed with the disease.  

Multiple sclerosis is a chronic illness that causes progressive weakness in the limbs. As Conill's disease progressed, she eventually had to give up seeing patients regularly. Her whole life changed. Now Conill runs intensive workshops for Penn's medical students to teach them what everyday life is like for disabled patients.  

In October, Conill was named was named a "Health Care Hero" by Philadelphia Business Journal. "The health system unfortunately is not conducive to helping people with uncertainty," Conill said. "There are a lot of issues that we as physicians don't think about. We don't learn enough as physicians to make patients' lives better."  

In Conill's 26-hour workshop, students are assigned to two groups. They either play the part of a disabled person, or of the caregiver of a disabled person. The disabled group uses props to stimulate disabilities--a plastic bottle cap worn in the mouth simulates a speech impedient; dark glasses smeared with Vaseline simulate blindness. Caregivers are required to stay with their charges around the clock, to provide assistance in moving them, and to offer toileting and feeding assistance. Students in both groups finish the workshop with a deeper understanding. "It's a very sobering thing when you can say to a patients, 'I can imagine what you are going through.'"  

The article appeared in the October 10-16 issue.

Modern Healthcare

David Shulkin Named Modern Healthcare "Up & Comer"

David Shulkin, MD, chief quality officer of the University of Pennsylvania Health System and chief medical officer at the Hospital of the University of Pennsylvania and Presbyterian Medical Center, has been named one of the top healthcare leaders nationwide in the Modern Healthcare magazine annual Up & Comers awards. Each year Modern Healthcare selects healthcare executives across all sectors to recognize as Up & Comers. Shulkin was the only healthcare executive named in Pennsylvania and one of two physicians nationwide. He is responsible for medical affairs, graduate medical education, social work, community health, quality assessment, and disease management within the University of Pennsylvania Health System.  

Among his many accomplishments, Shulkin has developed a system for the hospitals to collect standardized clinical data and a compatible case management system to introduce best clinical practices that can ensure high quality delivery of care.  

The article appeared September 15.

The Philadelphia Daily News

A Columnist Recieves a Heart Transplant

One evening in June, he was enjoying dinner and a movie with his wife. But upon returning home, things started to go awry. What Philadelphia Daily News columnist Rick Selvin initially thought was indigestion turned out to be a heart attack that landed him in the Hospital of the University of Pennsylvania.  

Selvin recalled his experiences at HUP in a lengthy feature that appeared in the Philadelphia Daily News. After a triple bypass operation, Selvin became a patient on Founders 8 as he waited for a heart transplant. There he made friends quickly with the "competition"-- the other patients awaiting hearts.  

Selvin spoke highly of HUP, giving it the nickname "Club MEDicine." "Breakfast in bed, 24-hour room service and, ahem, really good drugs." He added, "The nurses are angels of mercy who make my day-to-day existence bearable and sometimes enjoyable. They maintain a sense of humor and a confidence that decreases my apprehension by double-digit percentages." One of Selvin's biggest disappointments at being hospitalized was having to miss the Philadelphia Folk Festival for the first time in 35 years. A fellow patient felt similarly--he had been going to the festival for 20 years. An idea dawned on them--maybe the festival could be brought to them. With the help of the "hospital brass" and a festival publicist, it was arranged. Two acts from the festival came to perform for patients, family, friends, and staff. The event was covered by WPVI-TV6. Selvin hoped that the publicity generated by the show at HUP would draw attention to the need for donor organs.  

Shortly before the article was published, Selvin received a donor heart. He is now recuperating.  

The article appeared September 12.