Discovery of Ovarian Cancer Gene Gives Hope

A specific gene, located on the 11th chromosome, has been found to be associated with aggressive ovarian cancer.

According to the American Cancer Society, ovarian cancer will be diagnosed in an estimated 22,220 women in 2005. More than 16,000 women will die from the condition annually. The disease is nebulous at onset presenting minimal or no symptoms. Unfortunately, roughly 80 percent of ovarian cancer cases are diagnosed in later stages when the five-year survival rate is only about 30 percent.

In the study, headed by Tian-Li Wang of Johns Hopkins University School of Medicine, seven unique ovarian cancer tissue samples were examined using a technique called digital karotyping. The researchers discovered a gene, called Rsf-1, that was overproduced or amplified on chromosome 11 in 13.2 percent of all types of aggressive ovarian cancers, but not in any of the lower-grade forms of the cancer.

"The gene is a 'candidate' oncogene," said Wang. "An oncogene is a gene that will trigger cell growth abnormally, so if you block this you can inhibit cancer cell growth."

Researchers have discovered oncogenes for other forms of cancer and have used the knowledge to develop targeted or specialized chemotherapy interventions to specifically address the overexpressed gene and inhibit growth of the cancer. A classic example is the development of the breast cancer antibody Herceptin, targeted for the HER2/neu gene.

Clinicians view the discovery as good news and an outgrowth of the rapidly expanding field of biotechnology. "This is very hopeful news and raises the possibility of vastly improved treatment of this disease. There is still a long way to go from finding a gene to raising a drug that proves useful against it, but new technologies have made it a much speedier process."


Johns Hopkins Psychiatrists Suggest Alternative Treatments for Alzheimer's

Peter V. Rabins, M.D., M.P.H., and Constantine G. Lyketsos, M.D., M.H.S., professors of psychiatry at The Johns Hopkins University School of Medicine, cautioned that clinicians should consider both the risks and benefits for patients suffering from dementia, such as Alzheimer's disease, and when possible delay prescribing so-called second-generation antipsychotic medications for patients who exhibit psychotic symptoms or aggression.

A study published at JAMA reviewed all available published and unpublished randomized placebo-controlled, parallel-group, clinical trials of the second-generation antipsychotic drugs marketed in the United States to treat patients with dementia.

They concluded that the patients taking second-generation antipsychotic medications were 1.5 times more likely to die than patients taking a placebo.

"These results," said Rabins, "do not suggest that first-generation antipsychotic drugs like haloperidol and chlorpromazine, introduced in the 1950s, are safer alternatives to second-generation drugs."

"We do not believe the findings contraindicate the use of antipsychotics for patients with dementia who have psychotic symptoms and agitation, but rather that they change the risk-benefit analysis such that antipsychotics should be used only when the patient's symptoms present an identifiable
risk to the patient or to others," Rabins said.

Rabins said antipsychotics should not be used when other treatments are available and the risk of harm or significant distress is low. He said a range of alternative treatments, including behavioral interventions and antidepressants, have proven to be effective in some cases.

He noted the possibility that higher death and illness rates might exist among frail individuals exposed to other classes of drugs, but the absence of long-term data limits the ability to study this question.

"We look forward to international efforts to improve long-term monitoring for adverse events," Rabins said, "and for research into the important questions raised by this study."


NEWS FROM HOME

Reconstructive Surgery for Hopkins Medical Campus

Johns Hopkins Medicine plans to break ground on two new hospital towers on Orleans Street, beginning a $1.2 billion overhaul that could eventually raze nine buildings and a parking garage on its East Baltimore Medical Campus.

Demolition will likely begin this month on the Broadway garage on Jefferson Street to make way for the towers, which will share a lobby and consolidate many services now provided in the buildings slated for demolition, said Gary M. Stephenson, a spokesman for Hopkins.

One tower will house a 530,000-square-foot Children's and Maternal Health Hospital, providing the state's only dedicated pediatric trauma center. The building will include 205 inpatient beds; 10 children's operating rooms; and outpatient care for oncology, psychiatry and the Pediatric Clinical Research Unit, among other services.

The second will bring an 830,000-square-foot Cardiovascular and Critical Care Tower, two floors of which will be occupied by the Johns Hopkins Heart Institute, a new entity that will integrate Hopkins' various cardiac services. The tower will provide 320 beds, 14 endoscopy and bronchoscopy rooms and a full complement of radiology equipment.

Half of all the campus' hospital beds are in buildings erected before 1963 and ill-equipped to handle the electrical power needed for modern health technologies. Outdated power plants operate at full capacity and the buildings need costly ventilation, heating and air-conditioning upgrades.

The Joint Commission on Accreditation of Healthcare Organizations has also stressed a need for single-patient rooms, which decrease the chance of patients spreading disease.

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Experts Highlight Strategies to Raise "Good" HDL Cholesterol

Cardiology experts at Johns Hopkins have issued interim guidelines for physicians on how best to treat low levels of HDL cholesterol, the so-called good cholesterol, which helps keep arteries clear from the buildup of LDL cholesterol, the so-called bad cholesterol.

The Hopkins researchers report that existing strategies to prevent heart disease have not addressed the best means to raise HDL cholesterol and instead have focused heavily on lowering LDL cholesterol, which leads to plaque formation and narrowing of the arteries that can cause heart attack.

"We have reached a turning point in the prevention of coronary heart disease from an emphasis during the last 15 years on lowering LDL cholesterol levels to an emphasis in the next decade on raising levels of HDL cholesterol," says article lead author and cardiologist Roger Blumenthal, M.D.

Blumenthal notes that every single milligram per deciliter increase in HDL cholesterol lowers a person's risk of suffering a fatal heart attack by about 3 percent. Low levels of HDL cholesterol are known to increase overall risk of dying from heart disease and, specifically, to increase risk of arteries narrowing again after angioplasty surgery to clear them.

Using a recent patient case study from Hopkins involving a 41-year-old man with low levels of HDL cholesterol (28 milligrams per deciliter), the researchers reviewed how over a period of three years his HDL levels were raised to above normal by modifying his lifestyle risk factors. These modifications included making sure the patient engaged in regular exercise, ceased smoking, assumed control over his weight as measured by body mass index, limited alcohol intake, and monitored dietary fat intake. The patient lost nearly 50 pounds while undergoing treatment.

To raise HDL cholesterol levels, the researchers recommend a regular exercise program of brisk aerobic exercise for 30 minutes, several times per week, if not every day.

Quitting smoking, they point out, provides an average increase in HDL levels of 4 milligrams per deciliter. Aids such as drug therapy, nicotine replacement products and counseling can help patients quit.

Weight control is also highlighted as critical to raising HDL levels, with the researchers noting that every kilogram of weight lost raises a patient's HDL levels by an average 0.35 milligrams per deciliter.

Mild to moderate consumption of alcohol, no more than one to two drinks per day, they say, has been shown beneficial in raising HDL levels by an average of 4 milligrams per deciliter, irrespective of type of alcohol consumed.

For dietary control, the researchers recommend a diet low in saturated fat and rich in the polyunsaturated fatty acids found in foods such as oils (olive, canola, soy and flaxseed), nuts (almonds, peanuts, walnuts and pecans), and cold-water fish (salmon and mackerel), and shellfish. Consumption of carbohydrates, they say, should be restricted because high glycemic products, such as processed cereals and breads, are associated with lower HDL levels.

Funding support for the researchers was provided by the Maryland Athletic Club & Wellness Center Charitable Foundation in Lutherville, Md.


Digital Mammography Better at Finding Cancer in Younger Women

A study of 42,760 women at 33 sites across the United States and Canada, including Johns Hopkins, found that digital mammography is better than standard X-ray mammography at locating cancer in young women and those with dense breast.

The study, one of the largest breast cancer screening studies ever performed, was conducted by the American College of Radiology, funded by the National Cancer Institute, and reported September 16, 2005 in a special online publication of the New England Journal of Medicine.

Digital mammography detected up to 28% more cancers than X-ray mammography in women 50 and younger, premenopausal and perimenopausal women, and women with dense breasts, according to the American College of Radiology Imaging Network (ACRIN) Digital Mammographic Imaging Screening Trial (DMIST). However, the ACRIN results showed no difference between digital and film (X-ray) mammography in detecting breast cancer for the general population of women.

Nagi Khouri, M.D., director of breast imaging at Johns Hopkins Medicine and the principal investigator for the Hopkins site of the study, says its conclusions have important implications for women. "There is a large percentage of women for whom we can now demonstrate that digital mammography is the preferred modality," he said.


INTERNATIONAL NEWS

For Two Girls, a Chance to Lead Separate Lives

They have never been able to sleep apart, sit upright or see each other face to face. Yet if an operation by a team of doctors from India and the US is successful, two 10-year-old Indian girls joined at the head will finally be able to lead separate lives.

Benjamin Carson, director of pediatric neurosurgery at Johns Hopkins Children's Centre, in Baltimore, Maryland, who is leading the medical team, said the procedure was possible after studying an angiogram of the brains of the twins and consulting doctors at the Indraprastha Apollo hospital in New Delhi. The pioneering US neurosurgeon was flown in after Abu Dhabi's crown prince, Mohammed bin Zayed Al-Nahyan, said he would pay for any operation. He had read about the twins in a newspaper.

Dr. Carson said the operation would be complex but "if everything goes the way we plan, I expect they will both be alive".

The Indian twins share a blood drainage vessel in the brain - a concern for doctors. Dr. Carson said that at each stage of the operation there was a 20% chance of failure, but that without the operation the twins would face a lifetime of procedures.

The problem with the girls, Farah and Saba, is that Farah has two kidneys and Saba has none, so Farah's body has to carry her sister's functions. "What we are seeing is evidence of cardiac malfunction in Farah because she is carrying her sister. That will get worse with time," said Carson.

Conjoined twins originate from a single fertilized egg, so they are always identical and of the same sex. The number of twins joined at the skull worldwide is believed to be between 10 and 20. "Eventually I want to reach a point where all separations like this will become routine," Carson points out.

The operation will be a first for India, where there has been a rapid expansion of western-style private hospitals in city centres. "We can both learn something from each other. Our team of 20 doctors will be there working with Dr Carson's group. It will be a joint effort," said Anupam Sibal, director of medical services at Indraprastha Apollo hospital.


NEWS FROM HOME (...continued)

Hopkins' two new towers will have only single-patient rooms, Stephenson said. "In many cases, it's easier to replace the facilities than to try to renovate. It's much more cost effective."

Once built, likely by late 2008, the Critical Care and Children's and Maternal towers "will form a new main entrance to the hospital accessible from Orleans Street."

Other additions could also bring new research buildings and renovated housing for medical students.

"It's not only going to be a new hospital for now, but a hospital for the future," Stephenson said.


NEW ON THE WEB

The new Annual Report for Fiscal Year 2005 is now available at the Johns Hopkins Medicine International website. There you will find everything you always wanted to know about Johns Hopkins Medicine International, with emphasis on the activities of our last fiscal year.

To view the 2005 Annual Report or to download a copy of the PDF file, visit our website: www.jhintl.net.

Exercise Stress Testing Helps Identify People at Risk of Developing Coronary Heart Disease

Performing cardiac stress tests that measure exercise capacity and heart rate recovery can improve dramatically on existing techniques that predict who is most likely to suffer a heart attack or die from coronary heart disease (CHD), the leading cause of death in the United States.

A Johns Hopkins team reports that 90 percent of men and women with no early signs of CHD who, nevertheless, died from it had had below average results from their cardiac stress tests conducted 10 to 20 years earlier.

The team's analysis showed these asymptomatic people were two to four times more likely to die from CHD within 10 to 20 years than people with average or better-than-average stress test results.

These exercise stress tests are easy to perform, lasting less than 20 minutes and requiring only that a person walk on a treadmill at progressively higher speeds and inclines every three minutes until they become markedly fatigued. During the test, people are hooked up to a heart monitor.

"This is the strongest evidence to date that selective use of cardiac stress testing improves prediction of who is really at high risk of suffering a fatal heart attack," says senior study author and cardiologist Roger S. Blumenthal, M.D.

At 10 medical centers across the United States, study participants were given a physical examination, and had blood tests performed. Each participant also underwent cardiac stress testing, which included stress testing for exercise capacity and heart rate recovery, plus any changes in the heart's electrical signaling that are typical of decreased blood flow to the heart muscle.

Cardiac stress testing is used to gauge how well the heart works when it has to pump harder and use more oxygen, for example, while walking on a treadmill. The exercise, sustained for five to 10 minutes, mimics the strain placed on the heart when arteries are blocked or narrowed.

During stress testing, a person's breathing, blood pressure and heart rate are monitored while the intensity of their exercising is slowly increased to see how their heart responds. The amount, in number of beats per minute that the heart rate drops two minutes after exercise stops, is also recorded to determine heart rate recovery.

Using tables that take into account a person's age, gender and weight, the results can be compared against average scores to see if a person is below, at or above the norm. There is very little risk of harm associated with the testing because participants are closely monitored.

"Cardiac stress testing could significantly improve our abilities to find and aggressively treat people so that they are much less likely to suffer a heart attack," says the study's lead author, cardiologist Samia Mora, M.D., M.H.S.

Funding for the study was provided by the Maryland Athletic Club Charitable Foundation in Lutherville, Md.


Emphasis on Improved Care, Faster Access Shortens Hospital Stays

Physicians at The Johns Hopkins Hospital have disproved the notion that longer hospital stays mean better care. On a recently established program the goal is to improve patient care and cut down on wait times. According to statistics released by the hospital, the program has led to a 4 percent decrease in the overall amount of time patients have to spend in any one of the hospital's 850 acute-care beds.

"Our results show that there is room for improvement in the way large teaching hospitals deliver high-quality care and that they can provide more of it without long wait times and to the better satisfaction of the patients we serve," says JHH physician in chief Myron Weisfeldt, M.D. "Our next step is to strengthen this program as part of the management culture within Hopkins and to see if other hospitals can adopt our efforts to form the basis of a national program."

"The amount of time a patient stays at the hospital is a tough judgment call that requires more than medical training; it requires constant questioning and review of how we manage a large hospital, practice medicine and treat our patients," says kidney specialist Paul Scheel Jr., M.D., vice chairman of medicine at Johns Hopkins.

Taking cues from best practices and management review systems already in place in the airline industry and at NASA, the Johns Hopkins team set out to do a step-by-step analysis of how hospital services, such as tests and
treatments, are managed as patients move among them.

The Johns Hopkins data was compared to those of other hospitals by using scores available from a well-known U.S. actuarial firm that has for decades calculated average lengths of stay for hundreds of hospital procedures and diagnoses. The team not only interviewed physicians whose patients stayed longer than anticipated but also reviewed the patients' files in search of common sources of delay in delivery of care.

Interviews with cardiologists revealed a nagging problem of one-day or two-day waits for ultrasound results, which are needed to update a patient's condition before discharge. In response, the Department of Radiology agreed to a policy of "same-day" discharge service for ultrasound procedures and revised its lab hours when necessary to accommodate the workload. The radiology department went even further, altering its consultation schedule to fit demand and alleviate backlogs and moving to a seven-day-per-week schedule for elective, or non-emergency, cases.

The most dramatic example was applied to patients needing intravenous infusions because they were experiencing organ rejection after transplantation, or as part of their treatment for lupus. The Johns Hopkins team established an outpatient intravenous center, allowing patients to go home after one or two days before having to return to the hospital as outpatients for their remaining infusions.

According to Johns Hopkins' chief of surgery, Julie Freischlag, M.D., "Heading home from the hospital after a traumatic illness is a very emotional time for patients and their families. It is a major step in recovery for any patient to leave the hospital, a place where they have grown to feel safe and secure.

"Linking quality of patient care to efficient lengths of stay was a learning process for everyone involved," says neurosurgeon Henry Brem, M.D., professor and director of neurosurgery at Johns Hopkins. "But it was not until we looked at the numbers that we realized we really could do more with less, especially delays."