1999

Aging
How Physicians View Hormone
Replacement Therapy
Seniors at Risk
Biologic Rhythms and Aging

Cancer
Hormonal Steroids and Ovarian Cancer
A Molecular Approach to Tumors and
Infectious Diseases

Children
Immunizing Children in Low Income Families
Humane Circumcision

Dental
Baby Bottle Tooth Decay
Measuring Dental Care Quality

Innovative Programs
Sharing Good Ideas About Women's Health Care
Does a Health Plan Benefit Help Smokers Quit?
Hepatitis C: Making a Critical Difference

Mental Health
Mental Health Research : A Progress Update
A New Approach to Managing Depression

Technology
A New Tool for Breathing Emergencies
Mechanical Ventilation: A Double-Edged Sword
Itching and Burn Wounds
Plastic and Reconstructive Surgery
Finding Measles-Like Illness

Research Update
Lifelong Treatment of HIV Infection
Antibiotics and Bacterial Resistance
Tear Proteins and Dry Eye
Continuity of Care and Diabetes

Hormone replacement therapy (HRT) for post-menopausal women is controversial. HRT can decrease menopausal symptoms and protect against osteoporosis, coronary heart disease and possibly Alzheimer's disease. However, it may increase the risk of breast cancer and endometrial cancer. Women who already have heart disease may also be at greater risk for cardiac events with HRT.

How much do physicians counsel women about HRT? A survey was sent to HealthPartners physicians from three specialties - gynecology, family practice, and internal medicine. Each physician was asked to assess the risks and benefits of HRT, describe their prescribing philosophies, and identify possible barriers to counseling.

Virtually all respondents said the prevention of osteoporosis and cardiovascular conditions are the greatest benefits of HRT. Gynecologists and women physicians were the most likely to believe that HRT might prevent Alzheimer's disease. Physicians in family practice and internal medicine were the most concerned about thromboembolism.

The survey indicated that patients, rather than their providers, tend to initiate discussions about HRT. The physicians described two primary barriers to counseling: lack of time and limited knowledge. These findings suggest both that women patients could benefit from alternate resources for education about HRT and that physicians need to be kept updated about new and sometimes conflicting information on HRT.

Research Team
Cheri J. Rolnick, PhD, MPH, Mary E. Kelley, BA; Terese A. DeFor, MS, Richard A. Kopher, MD, Renee B. Compo, NP

Funding
Wyeth-Ayerst Laboratories

Related Publications
Rolnick SJ, Fortman KJ, Bloom FB. Monographs: Advancing Women's Health: Health Plan's Innovative Programs in Mid-life Women's Health Issues, Breast Cancer, Domestic Violence and Obsetrics and Pregnancy Care. New York: American Association of Health Plan (AAHP), The Commission on Women's Health Columbia University, June 1998.

Rolnick SJ, Owens B, Botta R, Sathe L, Hawkins R, Cooper L, Kelley M, Gustafson D. Computerized information and support for patients with breast cancer or HIV infection. Nursing Outlook 1999;47:78-83.

Rolnick SJ, Kopher RA, Compo RB, Kelley ME, DeFor T. Provider attitudes and self-reported behaviors related to hormone replacement therapy. Menopause, 1999. (In Press).

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Individuals aged 65 and older are the fastest growing segment of society and as a group are the largest consumers of health care. What factors predict which seniors are most at-risk of being hospitalized? In 1995, over 11,000 senior members at HealthPartners completed a brief survey that covered psychological and social factors, physical health status, and basic demographics. The survey data were matched with electronic medical records two years later to see which factors were associated with hospital admissions and length of hospital stay. The most important predictors of hospital admissions were poor self-perceived health, using high numbers of medications, advanced age, male gender, decreased functional status, and having been recently widowed. Among seniors admitted to the hospital, those who have functional problems, take a large number of medications, live alone, and are male tend to have the longest hospital stays.

Research Team
Robin R. Whitebird, PhD, Michael J. Goodman, PhD

Funding
HealthPartners Research Foundation

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Biologic rhythms are found in all living matter - from a single cell to a human being - and these rhythms affect most bodily functions. Rhythms may last minutes, hours, days, or even months. Circadian rhythms, for instance, occur about once every 24 hours. Other rhythms vary according to the seasons.

Good health depends on maintaining these rhythms - that is, maintaining the appropriate sequence of physiologic events. Disturbances in biologic rhythms due to aging are thought to alter the normal sequence of events in tissues and organs and lead to some of the deficiencies and chronic disorders that are associated with aging.

Researchers at HealthPartners, in collaboration with the Institute of Endocrinology of the Romanian Academy of Medical Sciences, investigated biologic rhythms throughout the human lifespan. More than 1000 subjects participated in the research, ranging from children to people age 100 and over, and included both healthy individuals and those with various diseases, some of which are associated with aging.

The findings indicate that the elderly do experience characteristic changes in biologic functioning. A notable change is a decrease in the length of certain circadian rhythms. Some functions, like blood pressure, shift from a circadian to a 12-hour frequency, while other cardiovascular functions, such as the heart rate, remain at a 24-hour frequency.

One especially striking change in the aged is their decrease in melatonin. This hormone is secreted during darkness and sleep and gives humans information about their environmental light-dark cycle. Another change is a shift of urine excretion from daytime to nighttime, which accounts for some of the sleep disturbances found in elderly of both sexes.

The thyroid gland, which regulates metabolism, is also impaired in the aged. The gland shows a delayed response to thyroid-stimulating pituitary hormone and does not increase its function in response to cold weather, an adaptation normally present in younger people.

These findings help to better define the characteristic changes in biologic rhythms of aging, some of which may be responsible for the disturbances experienced during old age.

Research Team
HealthPartners Research Team: Erhard Haus, MD, PhD, David J. Lakatua, MD, Linda Sackett-Lundeen, MT (ASCP). Institute of Endocrinology: Romanian Academy of Science, Bucharest, Romania: G.Y. Nicolau, PhD, C.I. Parker

Funding
Ramsey Foundation, Department of Pathology-Regions Hospital, Romanian Academy of Sciences

Related Publications
Touitou Y, Haus E, editors. Biologic Rhythms in Clinical and Laboratory Medicine. Berlin Heidelberg: Springer-Verlag. 1994 Special Edition:730.

Nicolau GY, Haus E.: Chronobiology of the hypothalamic- pituitary-thyroid
(HPT) axis. In: Touito, Y, Hau, E, editors. Biologic Rhythms in Clinical and Laboratory Medicine. Hedelberg: Springer-Verlag, 1994 Special Edition:330-347.

Haus E, Touitou Y: Chronobiology of development and aging. In: Redfern, Lemmer, editors. Handbook of Experimental Pharmacology: Physiology and Pharmacology of Biologic Rhythms. Heidelberg: Springer-Verlang, 1997:95-134.

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Findings from a number of studies suggest steroid hormones may play a role in the growth and development of ovarian cancers. Cancer researchers within the Department of Obstetrics and Gynecology are investigating the role of three steroid hormones in the growth and development of ovarian tumors: estrogens, androgens, and progestins. The researchers at HealthPartners, in collaboration with research groups in Canada and Italy, are also studying the role of steroid hormones in lung and prostate tumors.

These studies have found that some types of ovarian tumors are unaffected by estrogens, androgens, or progestins. Other tumor types not only react to these steroids but can actually generate their own steroid hormones, independently of the woman's endocrine glands.

Findings from this research program may help to determine what mechanisms cause steroid actions within tumors. This research should also improve the ability to detect ovarian tumors, predict tumor behavior and response to treatment, and devise new approaches to controlling tumor growth.

Research Team
Charles H. Blomquist, PhD, Dennis G. Bealka, MD, Paul H. Lima, MS, Denise M. Ramsey, MLT

Funding
HealthPartners Research Foundation and the Regions Hospital Foundation.

Related Publications
Blomquist CH, Leung BS, Beaudoin C, Poirier D, Tremblay Y. Intracellular regulation of 17b-hydroxysteroid dehydrogenase type 2 catalytic activity in A431 cells. J. Endocrinol 1997;153:453-464.

Blomquist C, Bealka D, Tuli-Puri S, McGinley D, Posalaky Z, Lakatua D. Kinetic evidence of 17b-hydroxysteroid dehydrogenase (17-HSD) type 1 but not 17-HSD type 2 in a human ovarian endometrioid adenocarcinoma positive for estrogen, progesterone and androgen receptor. Scientific paper presented at the Endocrine Society Annual Meeting, New Orleans, LA, June 24-27, 1998.

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How do tumors form? What makes them grow and escape normal body control? These unanswered questions are being addressed by research at the Molecular Pathology Laboratory.

One project is investigating uterine leiomyoma, a benign tumor affecting more than 20% of women over the age of 30 and leading to about 200,000 hysterectomies annually in the United States. Methods from molecular biology, such as DNA sequencing, are being used to study genetic differences between normal uterine tissue and leiomyoma. The purpose of this project is to identify the genes that control leiomyoma growth. Understanding the basis of the transformation is necessary for new diagnostic methods and better approaches to therapy.

HealthPartners researchers are also working to devise and evaluate a new molecular biology approach to differentiate among among mycobacterias, organisms that cause tuberculosis and other less known infectious diseases. Through this approach, the lab can detect small genetic variations in the makeup of mycobacteria and use them to identify some of the species of this large family.

These studies use pathological material to answer basic questions about the development of tumors and to test new diagnostic methods in infectious diseases.

Research Team
David J. Lakatua, MD; Douglas Olson, MD, Corina A. Pambuccian, MD, MS

Funding
HealthPartners Research Foundation

Related Publications
Siembieda SP, Olson DA, Lakatua DJ. Detection of Mycobacterium avium and intracellularae using species specific primers. Biotechnology Winter Symposia, February,1994.

Olson DA, Siembieda SP, Lakatua DJ. Immunoglobulin heavy chain rearrangement in Hodgkin's lymphoma using the polymerase chain reaction. Biotechnology Winter Symposia, February, 1994.

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One of the most effective preventive health strategies is to immunize infants and children against certain common, infectious diseases. Unfortunately, children in impoverished families often do not receive the appropriate series of vaccinations. At HealthPartners, immunization has been lower in the Prepaid Medical Assistance Program (PMAP), a government-supported program that serves low income families.

A research project, using chart reviews, focus groups with parents and interviews with clinic staff, identified five potential methods for improving the rate of immunizations in this population. First, reminder systems need to be implemented to prompt parents when their child needs a vaccination. Second, a clinic notation system should be developed to assure that children get appropriate immunizations when they visit the clinic for any reason - to avoid "missed opportunities." Third, parents could benefit from education on immunizations, well childcare visits, and how to use the medical system more efficiently. Fourth, vaccinations need to be started on time, before three months of age. Finally, a community-based immunization registry would help keep track of immunizations even when patients go to more than one clinic.

Research Team
HealthPartners Research Team: Peter G. Harper, MD MPH, Jim Nordin MD MPH, David Griffin MD, Stephanie Molliconi, Mary Bursek, Kathie Culhane-Pera, MD. Center for Asian Studies: Yer Moua. Park Nicollet: Renner Anderson MD.

Funding
Center for Health Promotion-HealthPartners and HealthPartners Research Foundation

Related Publications
Anderson R, Kind E. Improving childhood immunization rates. The Bulletin 1994;38(2)

Carlin E, Carlson R, Nordin JD. Using continuous quality improvement tools to improve pediatric immunization rates. Jt Comm J Qual Improv 1996;22(4):277-88.

Harper PG, Madlon-Kay DJ, Luxenberg MG, Tempest R. A clinic system to improve preschool vaccinations in a low socioeconomic population. Arch of Ped and Adol Med 1997 December;151:1220-23

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Neonatal circumcision is the most common surgical procedure done on males during childhood. Currently there are nearly 1,200,000 circumcisions performed annually in the United States. When done without the benefit of analgesia, this procedure is stressful and painful. If parents ask that their infant sons be circumcised, it is a pediatrician's obligation to perform this operation in the most humane way possible.

HealthPartners pediatricians have been carrying out newborn circumcisions under local anesthesia since 1986. More than 10,000 procedures have been completed in the past 12 years, without any significant complications. Hundreds of other pediatricians and family practitioners have learned this technique from HealthPartners' pediatricians. In a series of publications since 1988, the HealthPartners' research team has demonstrated the safety and efficacy of the dorsal penile nerve block (DPNB). Consequently, other comfort measures have been recommended to make this common operation more humane for infants and their families.

At the request of the American Academy of Pediatrics, a training film on DPNB has been developed for sharing with the 40,000 pediatricians nationally who subscribe to Pediatrics in Review. The article is in CD-ROM format to allow both text and video to be reviewed on a home or office computer. The goal of the publication is to make local anesthesia the standard practice in infant circumcision. In March 1999, a special taskforce at the American Academy of Pediatrics recommended local anesthesia for all infants who are to be circumcised.

Research Team
HealthPartners: Lawrence M. Condon, MD, Howard J. Stang, MD, Leonard W. Snellman, MD

Funding
Ross Laboratories and American Academy of Pediatrics

Related Publications
Stang HJ, Snellman LW, Condon LM, et al. Beyond dorsal penile nerve block: a more humane circumcision. Pediatrics 1997;101:e3.

Condon LM, Stang HJ, Snellman LW. Humane circumcision. Pediatr Rev
(serial on CD-Rom) 1998;19:1-2.

Stang HJ, Snellman LW. Circumcision Practice Patterns in the United States. Pediatrics (serial online) 1998;101(6):e5.

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Despite recent declines in caries, otherwise known as "cavities" or "tooth decay," certain segments of the population have an especially high risk for dental problems. For example, children under the age of three can develop a type of early childhood caries known as "baby bottle tooth decay." This type of caries is often destructive and may require treatment in the operating room under general anesthesia. Moreover, children with baby bottle tooth decay are at increased risk for developing caries in their permanent teeth. Dental researchers at HealthPartners are evaluating a screening tool for identifying infants at high risk for baby bottle tooth decay and are also testing the effectiveness of two chemo-therapeutic agents in arresting early potential tooth decay.

Research Team
HealthPartners Research Team: Susan Hahn-Hamamoto, DDS, James Hilton, DDS, Paul Walker, DDS, MS. University of Minnesota Dental School: Thomas Beckman, DDS, MS, Jim Hodges, PhD. Private practice: Pamela Erickson, DDS, PhD.

Funding
HealthPartners Research Foundation

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How can health plans monitor the quality of their dental care and make sure that patients at high risk for dental disease receive appropriate interventions? The HealthPartners Dental Group and Research Foundation collaborated with other dental researchers on a project to develop indicators of quality in dental care. An expert panel was convened, representing dental plans, purchasers, and dental providers. This panel proposed a set of quality of care measures, which were modeled on quality indicators in medical care. HealthPartners served as a pilot site to test these new indicators. The tests showed that the indicators are reasonably reliable and the information is routinely available in dental charts.

Dental plan purchasers are beginning to pay attention to issues of quality. This project will help provide objective information to describe quality of care in a dental plan - a dental health "report card." The research will also be useful to dentists, helping to target preventive treatment to the population at highest risk.

Research Team
University of North Carolina: James Bader, DDS, MPH, Daniel Shugars, DDS. Center for Health Research: Kaiser Permanente Northwest: B. Alex White, DDS, DrPH. HealthPartners Research Team: Brad Rindal, DDS, Michael Goodman, PhD, Stephanie Klohs, William Rush, PhD

Funding
Agency for Health Care Policy and Research, HS09453

Related Publications
Bader JD; Shugars DA; White BA; Rindal, DB. Evaluation of Audit-Based performance Measures for Dental Care Plans. Journal of Public Health Dentistry 1999. (In Press).

Bader J; Shugars D; White BA, Rindal DB. Development of Effectiveness of Care and Use of Services Measures for Dental Care Plans. Journal of Public Health Dentistry 1999. (In Press).

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What are the best programs in women's health care? The American Association of Health Plans, in collaboration with researchers at HealthPartners Research Foundation, recently completed a project to identify innovative and exemplary programs in four areas: pregnancy/birth, breast cancer, midlife women's health issues, and domestic violence. The purpose of this project was to share the best ideas about women's health care with other health plans.

Health plans around the country submitted information on their best and most innovative programs. A Women's Health Task Force reviewed and evaluated these programs and selected four model programs in each area. HealthPartners programs in two areas-domestic violence and midlife women-were identified as exemplary.

Here are a few examples of programs that were selected:

· A health plan in Florida offers a neonatal program to identify high-risk mothers-to-be and provides regular and extensive follow-up, including supportive telephone calls by nurses.
· A program in California matches newly diagnosed breast cancer patients with breast cancer survivors who serve as "buddies" and help new patients gain access to community resources.
· An HMO in rural Pennsylvania has launched an outreach initiative to provide state-of-the-art treatments for osteoporosis, by disseminating practice guidelines to physicians and educational materials to midlife women.
· A program in Massachusetts trains physicians and other health care providers to help survivors of domestic violence.

Monographs on each area were distributed to health plans around the nation.

Research Team
HealthPartners Research Team: Kristine K. Fortman, MA, Sharon J. Rolnick, PhD, MPH. American Association of Health Plans: Felicia Bloom, MHS

Funding
The Commonwealth Fund

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Every year, 50% of people who smoke try to quit. For most, the effort is unsuccessful. Beginning last year, HealthPartners and Blue Cross Blue Shield of Minnesota included tobacco cessation products in their covered benefits for members. The benefit covers the cost of nicotine gum, the nicotine patch and bupropion (brand name ZybanTM).

HealthPartners and Blue Cross are evaluating the impact of having this benefit. Does the benefit encourage patients to try to quit? Are physicians more likely to talk to their patients about quitting? The study involves a survey of 3,200 members from the two health plans who smoke cigarettes. Currently, there is no published evidence that expanding insurance coverage for tobacco cessation aids will facilitate these changes.

Research Team
HealthPartners Research Team: Raymond Boyle, PhD; Leif I. Solberg, MD; Sandra Sandell, PhD; Michael Maciosek, PhD; FeiFei Wei, PhD; Teri DeFor; Matt Malloy; HealthPartners Research Foundation Survey Center Staff. Blue Cross and Blue Shield of Minnesota: Sanne Magnan, MD,PhD, Carolyn Link Carlson, Lark Arrichiello. Veterans Administration Medical Center: Anne Joseph, MD. Minnesota Department of Human Services: Gestur Davidson, PhD

Funding
The Robert Wood Johnson Foundation, Addressing Tobacco in Managed Care Program

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Hepatitis C, a blood borne disease that damages the liver, is emerging as a major public health threat. First identified only ten years ago, hepatitis C is estimated to affect 4,000,000 Americans and lead to over 10,000 deaths each year.

HealthPartners Research Foundation and Integrated Therapeutics Group collaborated on the first research demonstration project to develop and evaluate a management protocol for hepatitis C in an HMO.

The first component of the project was to educate clinicians and HMO members. Over 1,000 health care professionals attended lunch-and-learn programs, entitled "Hepatitis C: You Can Make a Critical Difference." Almost all participants rated these programs as "excellent" or "good," while pre-tests and post-tests documented significant improvement in knowledge. In addition, all primary care physicians on staff in HealthPartners clinics received "Facts-at-a-Glance," a guideline for diagnosis and treatment. An informational article describing risk factors was included in a publication distributed to all members.

The second challenge was to find a method for identifying members who are at-risk for hepatitis C. This was accomplished by using the electronic HMO database to identify patients with conditions that have been found to be risk factors for hepatitis, such as a history of liver problems or drug abuse. A sample of 1,380 members participated in anonymous screening for hepatitis C. The sample included a potentially at-risk group and a control sample. Eleven participants tested positive for hepatitis C, less than one percent of the sample. Participants in the at-risk group were ten times more likely to test positive than those in the control group.

This research demonstration project provides a model for addressing a critical public health problem in an HMO. An extensive educational outreach effort was accomplished within a short period of time. In addition, the project demonstrates that it is feasible to identify at-risk members for targeted screening using HMO electronic data.

Research Team
HealthPartners Research Team: Lucy Rose Fischer, PhD, Principal Investigator, Kathleen Conboy, RN, BSN; Brita Hedblom, BS; John Butler, MD. Integrated Therapeutics Group: Dawn Tope, RN, MS; Elon Ronberg, MA; DeNae Shewmake

Funding
Integrated Therapeutics Group, the health management division of Schering-Plough, Inc.

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MENTAL HEALTH
Mental Health Research: A Progress Update

In the year 2000, approximately 2,000,000 Americans will suffer from schizophrenia. An additional 2,000,000 will have bipolar (manic-depressive) mood disorder. Tenfold more will experience depression or incapacitating anxiety. These serious mental illnesses often hit people in their late teens or early twenties, thus disrupting the completion of education, the initiation of careers, and the bonding of adult social relationships. Ten percent of people with serious mental illness end their life in suicide. After a century of study, we still do not fully understand the causes of these illnesses and we have no cures. HealthPartners Division of Behavioral Health is using several strategies to work toward better understanding and treatment of mental illness. Current areas of research include:

Psychopharmacology
Medications remain the mainstay of treating serious mental illness. Ongoing research focuses on the safety and efficacy of multiple new therapeutic agents for illnesses ranging from mood and anxiety disorders to schizophrenia, attention deficit disorder, and dementia. One of the longest sustained efforts is the investigation of Galantamine in the treatment of Alzheimer's Disease. Double-blinded trials show improved cognitive function with Galantamine, while individuals receiving placebo display declines in function.

Neuropathology
Research in this area utilizes a collection of autopsy brain samples and focuses on a search for abnormalities in a part of the brain called the hippocampus. Preliminary results show a reduced number and disorganized structure of a group of cells called pyramidal cells in people who had schizophrenia and other severe psychoses. It is hypothesized that this area of the brain is a final common pathway for psychotic symptoms.

Suicide
Suicide is the ninth most common cause of death among adults and the third most common cause of death among children and adolescents. Researchers at HealthPartners are designing an epidemiological study of suicide in Minnesota. By far the greatest rates of suicide are in elderly men living in rural communities. Strategies will be developed to bring preventative efforts to these high-risk populations and communities.

Victims of Torture
Researchers are investigating the outcomes of various treatments for people from around the world who have been subjected to political and military torture.

Eye tracking
The researchers are in their final year of a 5-year project looking at abnormal eye movements in people with schizophrenia and in their first-degree relatives. It is hypothesized that these well-documented abnormalities of smooth pursuit eye movements may be a marker for the genetic factor(s) that contribute to the development of schizophrenia. Results to date have identified a subset of individuals with schizophrenia who have eye tracking abnormalities which are also present in 50% of their first degree relatives.

Research Team
HealthPartners Research Team: Ronald Landbloom, MD, Elizabeth Reeve, MD, Jim Roerig, PharmD, Craig Vine, MD, Daniel Hanson, MD, PhD, June White, James Jarranson, MD, Joan Manthis, Stephanie Zumbolo, Melissa Chawla. University of Minnesota, Department of Psychology: William Grove, PhD, Bill Iocona, PhD

Funding
National Institute of Mental Health, National Alliance for Research on Schizophrenia and Depression, Janssen Pharmaceutica

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Depression is a profoundly disabling medical condition. Patients with serious depression often have difficulty sleeping, eating, working, or relating to family and friends. It is also a very common disorder, affecting 5 to 15% of patients who come to primary care clinics.

Although there are new and effective treatments, depression tends to be a chronic health problem and is difficult to manage. One large challenge is providing adequate continuity of care. A new project at HealthPartners Research Foundation is applying quality improvement techniques to improve the system for managing depression care. The basic premise of the DIAMOND Project is that "Depression Is A MaNageable Disorder." The goal of this project is to assure that all patients with depression receive good follow-up and follow-through care. Follow-up care means that there is a care plan to address a chronic problem at the appropriate level. Follow-through means that the care does not stop at a single office visit but that contact is maintained with patients over time. A key feature of this initiative is to provide telephone support from nurse care managers to patients with depression.

Three primary care clinics at HealthPartners are testing the DIAMOND improvement initiative. A before-survey was conducted in these clinics prior to implementing the new system of follow-up and follow-through care. The survey found that patients with depression are rarely given written information on depression, and that there is almost no ongoing system for telephone follow-up care. An after-survey will be conducted when the new care system has been implemented to assess if there is a change in the system of care, and if this improves outcomes for patients with depression.

Research Team
Leif I. Solberg, MD, Lucy Rose Fischer, PhD, Kathleen Conboy, RN, Thomson Davis, PhD, David Alter, PhD, Macaran Baird, MD, Steven Lucas, MD, Richard Heinrich, MD

Funding
MacArthur Foundation

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In emergencies, patients often require the insertion of an endotracheal (breathing) tube. Unfortunately, emergencies don't always occur in settings where X-ray is available to confirm the tube's correct placement. To ensure proper breathing, the tube must be inserted correctly. If placed too deep, oxygen will be delivered to only one lung.

A study conducted in the Emergency Department at HealthPartners was designed to find another method, besides X-ray, to determine if an endotracheal tube was placed too deep. The study tested a device used to measure exhaled carbon dioxide levels. To test the effectiveness of this device, the carbon dioxide measure was compared to results from a chest X-ray and physician assessment based on lung sounds, chest rise, and the amount of oxygen in the blood.

The study found that patients whose endotracheal tubes were ventilating only one lung showed significant drops in monitored carbon dioxide levels, while those ventilating both lungs did not drop significantly. A drop of 7mm/hg or more always predicted that the tube was too deep.

Based on the study findings, the Emergency Department plans to begin using this device with trauma patients, children, and patients whose tubes are inserted before they arrive at the hospital.

Research Team
David Hale, MD, PhD, Carson Harris, MD, Paul Jewett, MD

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Conditions such as pneumonia, severe infection, trauma, shock, blood transfusion, and drug overdose can precipitate Adult Respiratory Distress Syndrome (ARDS). The hallmark of ARDS is disruption of the normal boundaries between the blood vessels and airspace of the lungs, leading to flooding of airspace and stiff, airless lungs. ARDS afflicts thousands of patients every year. Although mortality has fallen in recent years, over 30% still die. Victims surviving the first three days after the diagnosis of ARDS frequently succumb to its complications later in their hospitalization. Moreover, those who survive have long hospital stays and require significant rehabilitation.

Mechanical ventilation is a cornerstone in the management of ARDS. Unfortunately, traditional approaches to mechanical ventilation can cause injury to the lungs. Researchers in the Pulmonary Medicine Department are developing techniques to "protect" the lung from injury. They also are investigating the role of ventilator settings and inflammatory mediators in worsening lung injury, as well as the physics underlying mechanical ventilation and lung injury.

This research should lead to a better understanding of the mechanisms of ventilator induced lung injury and ARDS. The ultimate goal is to provide better care and improve patient outcomes.

Research Team
John J. Marini, MD, Avi Nahum, MD, PhD; Laurel A. Wright, MD; Alexander B. Adams, RRT, MPH, John R. Hotchkiss, MD, David J. Dries, MSE, MD

Funding
HealthPartners Research Foundation; National Institutes of Health; American Heart Association

Related Publications
Nahum A, Ravenscraft SA, Adams AB, Marini JJ. Distal effects of tracheal gas insufflation: changes with catheter position and oleic acid lung injury. J. Appl Physiol 1996 Sept;81(3):1121-1127.

Crooke, PS, Head JD, Marini JJ, Hotchkiss JR. Patient-Ventilator Interaction: A General Model for Non-passive Mechanical Ventilation. International Mathematics Association Journal 1998 December; 15:321-337.

Wright L,Youngblood M, Adams AB, Hotchkiss JR, Stone M, Marini JJ. Effects of Frequency (f), mean airway pressure (mPaw), and inspiratory time fraction (Ti) on ventilator induced lung injury (VILI). Am J Resp Crit Care Med 1999;159:A478.

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When patients with healed deep burns return to the Burn Center at Regions Hospital, they are usually asked, "Do you itch?" Itching is a normal symptom of wound healing. However, itch that continues for many months interferes with work, leisure, and sleep, and creates serious problems for patients' quality of life.

New treatments have increased the survival for victims of major burn injuries. However, problems with scarring and persistent burn would itch, which does not respond to anti-histamine therapy, remain to be solved.

Anti-histamine drugs, which usually control itching, seldom eliminate itching associated with deep burn wounds. This failure of anti-histamines therapy suggests that persistent burn wound itch involves another mechanism.

Researchers at the Burn Center are attempting to discover a better therapy for burn wound itching by studying tissue biopsy specimens. A "laser confocal scanning microscope" gives three-dimensional images of nerve fibers and leukocytes that invade the wound tissue. The images show that healed deep burn wounds have few nerve fibers and contain a high number of eosinophilic leukocytes. These observations suggest that the itch sensation must arise around the margin of the wound, where nerve tissue is still preserved and that eosinophils may release unusual itch-producing factors.

Over the next year, the Burn Center will be testing experimental anti-itch therapies. One of these agents is a topical preparation of Dapsone, a drug that has been used in oral form by dermatologists for decades to treat an itchy, blistering skin disease that is also resistant to anti-histamine therapy.

These studies may significantly help patients recover from the debilitating effects of the itch component of healing burn wounds.

Research Team
Robert D. Nelson, PhD, Jody M. Rood, RN, Lynn D. Solem, MD; David H. Ahrenholz, MD; Kathy J. Schwartz, OTR; Barbara M. Moudry, RN; Wanda I. Melendez, BS

Related Publications
Nelson RD, Moudry BM, Hordinsky MK, Ahrenholz DH, Solem LD. Innervation and vascularization of grafted human burn wounds: Application of fluorescence confocal microscopy. Presented at Annual Meeting of the American Burn Association, 1995.

Debol SM, Herron MJ, Nelson RD. Anti-inflammatory action of dapsone: inhibition of neutrophil adherence is associated with inhibition of chemoattractant-induced signal transduction. J Leukocyte Biol 1997;62:727-36.

Nelson RD, Herron MJ, Ahrenholz, DH, Solem LD. Burn wound pruritus: A role for substance P and eosinophils? Presented at Annual Meeting of the American Burn Association, 1998.

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Researchers in the Department of Plastic and Reconstructive Surgery are involved in a wide array of projects on reconstructive surgery following trauma and cancer surgery.

One area of research has involved resolving controversies in the treatment of patients with facial trauma. Several studies are attempting to determine which are the best diagnostic tests and treatments for jaw fractures. Other studies assess how age, gender, and racial background affect the treatment of injuries to the eye and the bony structures around the eye. Most recently, a new diagnostic tool was adapted to help clinicians determine if patients with trauma to the area around the eye need surgery.

There is continuing controversy about the best method for breast reconstruction after mastectomy. A new research project will assess patient satisfaction following breast reconstruction. Particular focus will be on which type of breast reconstruction has produced the best aesthetic and functional result for patients who have undergone bilateral or unilateral mastectomy. Results of this research will help to educate clinicians and provide answers for patients dealing with this very difficult disease.

Research Team
Warren Schubert, MD, Adam Lokeh, MD, Ian Wilson, MD

Funding
Ramsey Foundation, AO North America, Department of Plastic and Reconstructive Surgery, Regions Hospital

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Measles is now very uncommon. Fewer than half of practicing physicians in this country have ever seen patients with this disease. Finding and counting new cases of measles is a problem. A passive surveillance system, relying on physicians to report cases, almost always results in substantial under-reporting.

Researchers at HealthPartners have tested a new method for identifying cases of measles-like illness. Their project used databases on patients enrolled in HealthPartners' clinics from 1994 through 1998. There were multiple sources of data, including electronically recorded physician notes, x-ray reports, and claims databases.

In order to identify as many cases as possible, the researchers used a broad range of diagnosis codes to indicate measles-like illnesses. They also used a variety of word search strategies. As a first step, nearly 6,000,000 records in the database were searched and 1,770 cases were identified by diagnosis codes as possible measles. In the next phase, 184 of these cases were further classified as possible measles cases by using a word search through physician notes. From this subset, 35 were classified as having a measles-like illness - that is, "febrile rash illness with cough or conjunctivitis, occurring simultaneously."

This project demonstrated that it is feasible to search for incidences of a rare condition. Out of almost 6,000,000 physician visits, 35 cases were reliably identified as measles-like illness. The search technology developed for this project can readily be used in a number of other surveillance settings.

Research Team
HealthPartners Research Team: James Nordin, MD, MPH, Feifei Wei, PhD, William Rush, PhD, Mary Kelley. Centers for Disease Control and Prevention: Rafael Harpaz, MD, MPH

Funding
Centers for Disease Control and Prevention, in affiliation with the American Association of Health Plans

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The health and well being of many HIV infected persons has improved dramatically in the last few years because of new combination therapies. In the United States, the death rate from AIDS has declined by 80%. Today there are 18 anti-retroviral medications that are FDA approved for the treatment of HIV infection. Combinations of two to four of these medications, called Highly Activate Anti-Retroviral Therapy (HAART), are prescribed for HIV infected persons. The prescribing of HAART has significantly reduced the amount of HIV virus circulating in the bloodstream, subsequently decreasing the incidence of immune deficiency-related illnesses and infections that were routinely seen a decade ago.

The remarkable reduction of HIV in the bloodstream of patients treated with HAART raised hope of a "cure" or complete elimination of the virus from the body. However, recent findings show that the levels of HIV in the lymph system are very high. Complete elimination of the virus would require about 70 years of therapy, even with no resistance and strict medication compliance. Clinicians now realize that HIV infection tends to be a chronic, life-long condition and treatment can span many decades.

With life-long therapy, complications and side effects to the therapies can be a serious, even life threatening, problem. The HIV clinic at HealthPartners discovered that hyperlipidemia (increased blood cholesterol) is often associated with a group of AIDS drugs called protease inhibitors. The researchers then investigated the impact of lipid-lowering agents to counteract hyperlipidemia. Their research to date has determined that lipid-lowering agents may be given safely and effectively while treating HIV infection.

The HIV program at HealthPartners is also participating in a national study to test a vaccine - the Vaxgen AIDSVAX. This vaccine is intended for non-HIV-infected persons who are sexually active with an HIV-infected person. The success of a vaccine would have a powerful impact on prevention here and throughout the world.

Research Team
Keith Henry, MD, Holly Melroe, RN, NP, MSN, Ray Nelson, RN, Ellen Kane, RN, Betty Bordenave, RN, Jessica Kopaczewski, BS, Jane Simpson, BS

Collaborating Organizations in the AIDS Research Consortium of the Twin Cities (ARCTIC)
Hennepin County Medical Center: Ron Schut, MD, Marsha Meredith, RN. Park Nicollet: Hal Martin, MD, Renee St. Jacque, RN. St. Paul Ramsey Health Department: Jo Ellen Nietcke, RN

Funding
Agouron Pharmaceuticals, VaxGen, Roxane, Bristol Myers Squibb, Chiron, Abbott, Roche, Glaxo-Welcome, Merck, Dupont

Related Publications
Henry K, Melroe H, Huebsch J, Kopaczewski J. Atorvastatin and gemfibrozil for protease-inhibitor related lipid abnormalities. Lancet 1998;352:1031-1032.

Zhang A, Schuler T, Cavert W, Notermans D, Gebhard K, Henry K. Reversibility of the pathological changes in the follicular dendritic cell network with treatment of HIV-1 infection. Proceedings of the National Academy of Science 1999;96(9):5169-5172.

Melroe H, Kopaczewski J, Henry K, Huebsch J. Intervention for hyperlipidemia associated with protease inhibitors. Journal of the Association of Nurses in AIDS Care 1999;10(4):20-34.

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Antibiotic resistance poses a tremendous threat in the battle against infectious diseases. As bacterial resistance diminishes the arsenal of effective antibiotics, researchers are challenged to develop new antibiotics. Limiting the use of currently available antibiotics is also critical to prevent the development of even more bacterial resistance.

Before new antibiotics can be introduced into the patient population, drug developers must prove they are both effective and safe. Researchers at HealthPartners use in vitro systems to test the effectiveness of new antibiotics and investigate dosing strategies. Glass vessels, plastic tubing, and mechanical pumps are utilized to create a dynamic environment that simulates interactions of antibiotic and bacteria in the human body. These laboratory studies provide critical data on appropriate dosage to maximize the anti-microbial effect and minimize the development of resistance. Ongoing laboratory projects also are investigating how bacteria become resistant to antibiotics.

Research Team
John C. Rotschafer, PharmD, Laurie Baeker Hovde, MT, David H. Wright, Pharm.D, Gigi H. Brown, PharmD., Marnie L. Peterson, PharmD.

Funding
Bayer Corportation, The R.W. Johnson Pharmaceutical Research Institute, Pfizer Inc., Society of Infectious Disease Pharmacists, American College of Clinical Pharmacy

Related Publications
Peterson ML, Hovde LB, Wright DH, Hoang AD, Rotschafer J., Pharmacodynamic outcome parameters as predictors for fluoroquinolones in the treatment of anaerobic infections. Scientific presentation at the American Society for Microbiology 98th General Meeting, Atlanta, GA, May 17-21, 1998.

Wright DH, Peterson ML, Hovde LB, Brown GH, Rotschafer JC. Comparison of ciprofloxacin and levofloxacin to commonly used antibiotics in the treatment of Streptococcus pneumoniae and other common bacterial respiratory tract pathogens. Scientific presentation at the Interscience Conference on Antimicrobial Agents and Chemotherapy 38th Annual Meeting, San Diego, CA, September 24-27, 1998.

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Dry eye is an uncomfortable and debilitating condition in which one's natural tears do not adequately nourish and lubricate the eye. This condition can damage the surface of the eye. Either insufficient tear secretion or excess tear evaporation causes dry eye.

Normal tears contain a complex mixture of salts and proteins in an aqueous base and are covered by a thin, oily film that slows water evaporation. Secretions from tear glands continually replenish tear fluid.

The Ophthalmology Research Laboratory at HealthPartners is studying the basic biology of lacrimal glands, the aqueous tear secretion glands. Molecular biology techniques are used to learn about proteins produced by normal lacrimal glands and secreted in tears. The team has identified new proteins that, though present in small amounts, may be crucial for tears to lubricate effectively.

These proteins, called lipases, are enzymes that act on lipids, the oily molecules that slow evaporation and stabilize the tear film. These enzymes may be required in the tears to process tear lipids. The research suggests that there may be complex interactions among the different types of molecules within tears.

Studying the function of tear glands in maintaining eye health should lead to a better understanding of the causes of dry eye and other ocular diseases.

Research Team
Susann G. Remington, PhD, J. Daniel Nelson, MD

Funding
HealthPartners Research Foundation

Related Publications
Nelson JD. Diagnosis of Keratoconjunctivitis Sicca. Int. Ophthalmol Clin 1994;34:37-56.

Remington SG, Lima PH Lima, Nelson JD. Pancreatic lipase-related protein 1 mRNA in female mouse lacrimal gland.. Invest Ophthalmol Vis Sci 1999;40:1081-1090.

Remington SG, Nelson JD. A novel lipase-related mRNA in lacrimal glands. Invest Ophthalmol Vis Sci 1999;40:S537.

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Thorough care for diabetes requires ongoing visits with a physician and regular glycosylated hemoglobin tests to monitor potential symptoms or problems. Diabetic patients receiving comprehensive and ongoing care tend to be more successful at controlling their blood glucose levels and self care practices than patients with a less intensive level of care.

A recent survey of diabetic patients at HealthPartners found that patients who have a regular provider of care use more preventative services and receive a more intensive level of care than patients without a regular provider. Patients with a regular provider also show greater improvement in glycosylated hemoglobin levels. The results of this study underscore the importance of continuity of care for patients with diabetes.

Research Team
HealthPartners Research Team: Patrick O'Connor, MD, William Rush, PhD, Michael Goodman, PhD, Linda Cherney, MPH, RD, Leif Solberg, MD. Minnesota Department of Health: Donald Bishop, PhD, Jay Desai, MPH, Laurel Reger, MBA.

Funding
Centers for Disease Control and Prevention, HealthPartners, HealthPartners Research Foundation

Related Publication
O'Connor PJ, Desai J, Rush WA, Cherney LM, Solberg LI, Bishop DB. Is having a regular provider of diabetes care related to intensity of care and glycemic control? J Fam Pract 1998;47:290-297.

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