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PubMedDate not supplied

Iowa nurses' knowledge of living wills and perceptions of patient autonomy.

The principle of patient autonomy is well recognized in the nursing profession. This study extends the exploration of patient autonomy by examining nurses' knowledge about living wills. The questions addressed in this study included the following: (1) Were Iowa nurses aware of the living will statute? (2) What sources of information did nurses use to learn about this legislation? (3) What were nurses' perceptions of patients' rights? (4) What were nurses' perceptions of nurses' role involving living wills? (5) Were living wills followed? (6) If not followed, which factors contributed to the failure to honor a living will? and (7) Which communication mechanisms were used to alert nurses to a living will? A questionnaire was mailed to 10,000 actively licensed nurses in Iowa. Approximately 3,000 Iowa nurses responded to the questionnaire regarding Iowa living wills. Seventy per cent of the nurses knew that Iowa had living will legislation. No single educational source was a predominate choice for targeted information about the living will statute. Nurses were reluctant to suggest to patients that they should consider writing a living will. Nurses were also more willing to assume a passive role of suggesting that patients talk with relatives about the need for a living will but were less likely to be suggest that a patient write a living will for future health care treatment decisions. The majority of the nurses favored the patient having some control in health care treatment decisions. Three major factors were pertinent to the failure to follow a living will: family request, treating physician's refusal, and lack of information that the living will existed. The medical record was the primary means of communication regarding a living will. To enhance patient efforts at self-determination, nurses must recognize the advance directive legislation is available in their state and the potential impact that their nursing care may have on the implementation of the document.

Adult↗

PubMed1998

Cancer mortality among Iowa farmers: recent results, time trends, and lifestyle factors (United States).

OBJECTIVES: To update the cancer mortality patterns among Iowa (United States) farmers for the years 1987-93 and compare these results with those previously reported for 1971-86 as well as relate the PMR patterns to risk-factor survey data. METHODS: We extracted usual occupation and cause of death from 88,090 Iowa death certificates for White males aged 20 and older for the years 1987-93. Proportional mortality ratios (PMR), adjusted for age, and 95 percent confidence intervals (CI) were calculated using deaths among nonfarmers to generate expected numbers. We compared lifestyle profiles for farmers and nonfarmers using male controls (n = 1,596) from a population-based case-control study conducted in Iowa from 1986-89. RESULTS: Iowa farmers had deficit PMRs for all-cause cancer mortality (PMR = 0.92, CI = 0.90-0.94) and for lung (PMR = 0.70, CI = 0.66-0.73), liver (PMR = 0.65, CI = 0.50-0.86), and other cancer sites strongly related to smoking and alcohol use. Farmers at all ages had excess deaths for cancers of the prostate (PMR = 1.26, CI = 1.19-1.33), rectum (PMR = 1.29, CI = 1.07-1.56), brain (PMR = 1.10, CI = 0.92-1.32), multiple myeloma (PMR = 1.17, CI = 0.98-1.40), non-Hodgkin's lymphoma (PMR = 1.09, CI = 0.96-1.23), and Hodgkin's disease (PMR = 1.62, CI = 1.04-2.54). Younger farmers (aged 20 to 64 years) had excess deaths for colon cancer (PMR = 1.52, CI =1.26-1.85) and skin melanoma (PMR = 1.60, CI = 1.07-2.38), while older farmers (aged 65+ years) had excess deaths for cancers of the pancreas (PMR = 1.18, CI = 1.04-1.34), lip (PMR = 1.58, CI = 0.59-4.21), and leukemia (PMR = 1.26, CI = 1.09-1.46). Since the 1970s, the PMR for stomach cancer has declined to expected values, while the PMRs for prostate, large intestine, pancreas, and Hodgkin's disease have increased; PMRs for other sites are consistent with earlier data. A survey from 1986-89 showed that farmers, compared with nonfarmers, smoked less, used less alcohol, had less formal education, and consumed more total calories, and calories from protein, fat, and meat while consuming fewer calories from fruits and vegetables. CONCLUSIONS: Iowa farmers continue to be at elevated risk of mortality due to certain cancers, and, of particular interest, the risk for prostate and colon cancer appears to be increasing since 1970.

Adult↗

PubMed2005

Survey of long-term-care facilities in Iowa for policies and practices regarding residents with methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci.

OBJECTIVES: To identify infection control policies and practices used by long-term-care facilities (LTCFs) in Iowa for residents with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE), and to estimate the prevalence of residents known to have these organisms. DESIGN: Survey. SETTING: LTCFs in Iowa from December 2002 through March 2003. RESULTS: Of the 429 LTCFs in Iowa, 331 (77%) responded to the survey. The estimated prevalence of residents known to have MRSA was 13.4 per 1,000 and that of residents known to have VRE was 2.3 per 1,000. Facilities owned by the government or those with an average of more than 86 occupied beds were more likely to have residents known to have MRSA and VRE (P = .002 and .007, respectively). Of the responding facilities, 7.3% acknowledged that they refused to accept individuals known to have MRSA and 16.9% acknowledged that they refused to accept those known to have VRE. Facilities in large communities (population, > 100,000) were least likely to deny admission to an individual known to have either MRSA or VRE (P = .05). Most facilities reported adhering to the national guidelines, but fewer than half (44.7%) of the respondents had heard of the Iowa Antibiotic Resistance Task Force's guidelines regarding residents with MRSA or VRE. CONCLUSIONS: Many LTCFs in Iowa care for residents known to have MRSA or VRE, but some refuse to admit these individuals. Infection control personnel and public health officials should work together to educate LTCF staff so that residents receive proper care and resistant organisms do not spread within this setting.

Cross Infection↗

PubMed1999

Telemedicine to Iowa's correctional facilities: initial clinical experience and assessment of program costs.

OBJECTIVE: To evaluate the costs and benefits of a prison telemedicine program for the institutions involved and to assess early provider satisfaction. MATERIALS AND METHODS: A survey of primary care and consulting providers from four prisons and an academic tertiary care facility in Iowa was conducted during the first year of telemedicine service linked with the state's correctional facilities, from March, 1997 to February, 1998. Data were evaluated from 247 completed telemedicine encounters. Cost estimates were made for (1) 1997 cost data for the 4,396 Iowa prisoners who were transported to The University of Iowa Hospitals and Clinics (UIHC) for their health care, and (2) the equipment, circuitry, and personnel costs necessary on both ends of the network to provide comparable telemedicine service to remote patients and providers. A formula for estimating the cost of implementing a telemedicine service is presented. It includes a projection for determining at what point the cost of the telemedicine visit approaches the average cost of an on-site visit (breakeven point). There was also a brief survey administered to presenting and consulting physicians to determine their overall satisfaction with the telemedicine system for diagnosis, treatment planning, and follow-up. RESULTS: The average cost to the prisons for an on-site inmate visit to the University of Iowa Hospitals and Clinics (UIHC) was $115 during our study period, from March 1997 to February 1998. Using a formula that specifies a number of fixed and variable costs for implementing telemedicine, we were able to determine that the breakeven point for Iowa's correctional facilities would require 275 teleconsultations per year, per site (total of 1,575 consultations a year). Given the higher equipment investment at the UIHC hub, the breakeven point would be around 2,000 teleconsultations annually. Cost studies did not include medical care, which is assumed to be relatively comparable for both on-site and telemedicine interactions. Overall, referring physicians expressed a higher rate of satisfaction with telemedicine than specialists (4.19 to 3.45, respectively, on a scale of 1 to 5 - 5 representing the highest ranking). Both consulting and referring physicians ranked the quality of transmission the highest among all questions regarding satisfaction with the telemedicine system. CONCLUSIONS: No one should anticipate instantaneous cost-effectiveness with telemedicine. However, with careful planning, implementing a telemedicine program can be "cost-acceptable" initially. Telemedicine ultimately becomes cost-effective as the volume of teleconsults increases.

Cost Savings↗

PubMed2005

Geographic distribution of ticks (Acari: Ixodidae) in Iowa with emphasis on Ixodes scapularis and their infection with Borrelia burgdorferi.

In Iowa, public concern regarding Lyme disease has increased markedly over the last decade. In response to these concerns, a statewide surveillance program was initiated in 1990 based on ticks received by the Department of Entomology at Iowa State University. Ticks were received from health care professionals, state government agencies, and the general public. A total of 5,343 ticks from all 99 Iowa counties were identified during the 12 years of this study. Dermacentor variabilis was the most numerous species, followed by Amblyomma americanum, and Ixodes scapularis. Dermacentor variabilis were distributed statewide, but A. americanum came primarily from southern Iowa counties. Prior to 1996, most I. scapularis came from counties along the Mississippi River. In the last 5 years, I. scapularis have been received from several counties in central and western Iowa and there is molecular evidence of infection with Borrelia burgdorferi in a substantial percentage of ticks. All I. scapularis were tested for the presence of B. burgdorferi. During the 12 years of this study, the presence of B. burgdorferi in I. scapularis varied from a low of zero percent in 1991-1995 to 18% in 1996. On average, fewer than 10% of all ticks examined per year were I. scapularis. In the 2000 tick season, the number of I. scapularis per year increased to 22% of submissions. This species further increased to 36.6% of ticks received in 2002.

Animals↗

PubMedDate not supplied

The Iowa Articulation Story. Collaboration works.

Historically, Iowa has had a majority of diploma and associate degree nursing graduates. Although educational mobility for registered nurses to obtain baccalaureate nursing degrees was available in Iowa before 1991, direct nursing education articulation did not exist. The impetus for developing a statewide nursing articulation plan to facilitate the entry of registered nurses to baccalaureate nursing programs was the result of a recommendation from the Iowa Board of Nursing's 1988 Statewide Plan for Nursing. The Iowa Articulation Plan for Nursing Education: RN to Baccalaureate, implemented in 1991, resulted from collaboration among nurse educators from all levels of nursing and nursing service representatives. The plan consists of four separate options and can be adapted for use in other parts of the country. The Iowa articulation story describes the process used and outcomes achieved when nurses collaborate to advance nursing education.

Education, Nursing, Baccalaureate↗

PubMed1997

Intrauterine growth retardation in Iowa communities with herbicide-contaminated drinking water supplies.

In a statewide survey of 856 Iowa municipal drinking water supplies in 1986-1987 the Rathbun rural water system was found to contain elevated levels of triazine herbicides. Rates of low birth weight, prematurity, and intrauterine growth retardation (IUGR) in live singleton births during the period 1984-1990 by women living in 13 communities served by the Rathbun water system were compared to other communities of similar size in the same Iowa counties. The Rathbun communities had a greater risk of IUGR than southern Iowa communities with other surface sources of drinking water (relative risk = 1.8; 95% CI = 1.3, 2.7). Multiple linear regression analyses revealed that levels of the herbicides atrazine, metolachlor, and cyanzinc were each significant predictors of community IUGR rates in southern Iowa after controlling for several potentially confounding factors including maternal smoking and socioeconomic variables. The association with IUGR was strongest for atrazine, but all three herbicides were intercorrelated and the independent contributions of each to IUGR risk could not be determined. We conclude that communities in southern Iowa with drinking water supplies contaminated with herbicides have elevated rates of IUGR compared to neighboring communities with different water supplies. Because of the limitations of the ecologic design of this study, including aggregate rather than individual measures of exposure and limited ability to control for confounding factors related to source of drinking water and risk of IUGR, a strong causal relationship between any specific water contaminant and risk of IUGR cannot yet be inferred. The association between the water supplied to the Rathbun communities and the increased risk of IUGR should be considered a preliminary finding that needs to be verified by more detailed epidemiologic studies.

Atrazine↗

PubMed1994

Rural connections. Iowa hospitals are establishing communications link to better serve rural areas.

The Sisters of Mercy Health Corporation, with 14 hospitals in Iowa, and the Mercy Health Centers of Central Iowa, with 13 hospitals in the state, believe fiber-optic technology may provide solutions to the inadequacies inherent in the rural healthcare delivery system. Since 1989, Iowa has committed more than $100 million toward the development and installation of a statewide fiber-optic communication network. The Iowa Communication Network (ICN) was originally envisioned as a means of providing voice, data, and interactive video capabilities to state government agencies, libraries, schools, and colleges. Currently, only hospitals with medical education programs are authorized to use the network, but others are expected to be allowed to soon. Realizing the potential benefits telemedicine and the ICN posed, in June 1993 the Sisters of Mercy Health Corporation and the Mercy Health Centers of Central Iowa jointly established the Midwest Rural Telemedicine Consortium (MRTC) to enhance rural residents' access to primary healthcare through integrated communications systems. The MRTC is trying to secure federal funding to conduct a demonstration project in eight hospitals. The project's goal is to determine how the use of telemedicine applications, specifically fiber-optic applications, affects access, quality, and costs in providing specialty healthcare services to rural patients.

Catholicism↗

PubMed1999

Multiple human exposures to a rabid bear cub at a petting zoo and barnwarming--Iowa, August 1999.

On August 27, 1999, a black bear cub, approximately 5-6 months old, died after several hours of acute central nervous system symptoms; preliminary test results available on August 28 indicated the bear had rabies. The bear was part of the Swenson's Wild Midwest Exotic Petting Zoo in Clermont, Iowa (northeastern Iowa). At the petting zoo, visitors fed, wrestled, and may have been nipped by the bear. The bear also was taken to an August 14 barnwarming at the Tharp barn in Holy Cross, Iowa (eastern Iowa), where it reportedly nipped people. An estimated 400 people from 10 states (Arizona, California, Florida, Illinois, Iowa, Minnesota, New Mexico, New York, Ohio, and Wisconsin) and Australia had contact with the bear cub at either the petting zoo or the barnwarming during the 28 days before its death, during which the bear may have transmitted rabies virus.

Animals↗

PubMed1975

Dietary survey of low-income, rural families in Iowa and North Carolina. III. Contribution of food groups to nutrients.

Percentage contributions of specific food groups indicated in the Basic 4 to protein, calcium, vitamin A, and ascorbic acid in one day's diets of thirty-five Iowa families and twenty-five North Carolina families are reported. All members of the families ate all meals at home. Their diets met or exceeded two-thirds of the 1968 Recommended Dietary Allowances for seven nutrients. Data were collected by the 24-hr. recall method. While the percentage contribution of the meat group to protein intake of the North Carolina families ranged from zero to 84 per cent, that of the Iowa group was from 35 to 85 per cent. The range for the percentage contribution of the milk group to calcium intake of North Carolina families was similar; however, in the Iowa group the range was from 2 to 97 per cent. The vitamin A-rich fruit and vegetable group contributed from zero to 99 per cent for the North Carolina families of vitamin A intake and from zero to 88 per cent for the Iowa group. Ascorbic acid-rich fruits and vegetables contributed from zero to 100 per cent of the ascorbic acid intake of the Iowa group and from zero to 95 per cent in North Carolina families. The results support the argument that the exclusive use of the "Daily Food Guide" or the "Basic 4" to assess nutritional intake of diets may produce biased in formation.

Ascorbic Acid↗

PubMed2001

WORKSAFE IOWA Occupational Medicine Associates Network: a university--community partnership in occupational safety and health.

The WORKSAFE IOWA Occupational Medicine Associates Network is a unique health care model for dispensing regional occupational medicine services in the state of Iowa, USA. WORKSAFE IOWA is an educational, informational, and consultation service of the College of Public Health at The University of Iowa. WORKSAFE IOWA includes a fee-for-service industrial hygiene program, the Occupational Medicine Associates Network, and educational and informational services. The Associates Network provides education, information, and consultation in exchange for an annual fee paid by each Associate to the university-based network. The Associates clinics provide comprehensive occupational medicine services to up to 1,500 clients through 66,000 annual clinic visits in their respective communities. The Associates Network has been financially self-sustaining over a period of 10 years, and has proven to provide valuable services to the community-based Associates, and to provide excellent training opportunities for the University students in several occupational safety and health disciplines.

Community Networks↗

PubMed2002

A comparison of dental caries and tooth loss for Iowa prisoners with other prison populations and dentate U.S. adults.

PURPOSE: When one compares National Health and Nutrition Examination Survey III (NHANES III) data to previous national surveys it appears that oral health in the United States has improved. The purpose of this study was to determine if this trend holds for prisoners in Iowa, specifically in regard to number of decayed teeth, number of decayed surfaces, and number of missing teeth. METHODS: This original research is a report of cross-sectional data regarding untreated decay and missing teeth. A representative sample of inmates newly admitted to the Iowa Medical Classification Center (IMCC) between June and December 1998 was selected. Oral health data were collected from records obtained as the result of dental treatment screening examinations conducted by the IMCC staff dental hygienist. Demographic data were obtained from questionnaires. The oral health status of this Iowa inmate population was compared with the status of previously studied samples of inmates throughout the nation using descriptive and parametric statistics and with dentate, noninstitutionalized U.S. adults using descriptive, non-parametric, and parametric statistics. RESULTS: Of the 174 study participants, 149 were male and 25 were female. On average, male inmates had 7.09 decayed teeth, 15.3 surfaces of decay, and 4.07 missing teeth. The female inmates averaged 5.56 teeth with untreated decay, 14.4 surfaces of decay, and 5.12 missing teeth. Findings showed that male Iowa inmates have more untreated decay than previously studied samples of inmates throughout the nation. IMCC Caucasian male inmates had 1.6 to 7.8 times as many untreated decayed teeth as previous inmates, while African American inmates showed 1.2 to 3.4 times as many untreated decayed teeth. The Iowa male inmates had fewer missing teeth than most of the inmate comparison groups. Compared with dentate, noninstitutionalized U.S. adults, the IMCC inmates, male and female combined, had 8.4 times the amount of untreated decay but similar numbers of missing teeth. CONCLUSIONS: Newly admitted male and female inmates were disparate from the general dentate U.S. adult population in terms of untreated decay. This also was found for IMCC male inmates compared to previous studies of male inmates. Inmates of both genders at IMCC did not appear to be disparate with the comparison population with regard to number of missing teeth.

Adolescent↗

PubMed1997

Iowa trial court blocks parental notification law.

The US District Court for the Southern District of Iowa issued a preliminary injunction on January 22 that prohibits enforcement of that state's parental notification requirement for young women seeking abortions. Under the law, which was passed by the Iowa legislature in March 1996, one parent of a woman under the age of 18 must be notified at least 48 hours before the procedure (see RFN V/6). Alternatively, the young woman may seek a court waiver of the mandate. Judge Ronald Longstaff found that the women's health care providers challenging the law were likely to prevail in their claim that the statute presents an unconstitutional obstacle to young women's right to choose abortion. Affirming findings made in a temporary restraining order that prevented the law from taking effect earlier in the month, Judge Longstaff held that the law would put doctors who provide emergency abortions to young women at risk of liability, a possibility that could discourage physicians from providing abortion services (see RFN VI/1). The court also found that the judicial bypass laid out in the statute failed to sufficiently protect a young woman's confidentiality or guarantee an expeditious procedure. The plaintiffs in Planned Parenthood of Greater Iowa vs. Miller are represented by Dara Klassel and Roger Evans of the Planned Parenthood Federation of America, CRLP's Priscilla Smith and Michael Erdos, Mark Lambert of Planned Parenthood of Greater Iowa, and Randall Wilson of the Iowa Civil Liberties Union.

Abortion, Induced↗

PubMed1996

District court finds proposed Iowa women's health facility does not need state approval.

On October 18, the US District Court for the Southern District of Iowa ordered the Iowa Department of Health to withdraw its demand that Planned Parenthood of Greater Iowa obtain a "certificate of need" in order to open a new facility in Davenport. Judge Charles R. Wolle found that state officials had deliberately misused the certificate of need requirement--a policy originally created to allow communities to influence health care standards at local facilities and prevent duplication of medical services--to block the clinic, which far from providing duplicative services would become the only provider of abortions in the Quad Cities. For at least 10 years, no family planning facility in Iowa has been required to obtain a certificate of need, in large part because the review standards are generally regarded as obsolete. The application process would have required Planned Parenthood to publicly disclose its sources of funding, identify the intended site of the facility, and pay a substantial fee; it would also have involved a public hearing at which members of the community could object to the clinic. The court concluded that state officials could not justify applying the requirements to a facility providing abortions when it had routinely failed to apply them to other clinics that offer the same services but do not provide abortions. Judge Wolle further ruled that the state's order for a certificate of need imposes a substantial obstacle to access to abortion that is unjustified by any government interest--and therefore unconstitutional under the standards established by the US Supreme Court in Planned Parenthood vs. Casey. Planned Parenthood Federation of America is representing the plaintiffs in Planned Parenthood of Greater Iowa vs. Atchison.

Abortion, Induced↗

PubMedDate not supplied

Attitudes of Iowa dental hygienists regarding self-regulation and practice.

PURPOSE: This study investigated Iowa dental hygienists' perceptions about education, practice, and licensure regarding issues related to self-regulation. Furthermore, it was the purpose of the study to determine if these perceptions were statistically related to membership in the American Dental Hygienists' Association (ADHA). METHODS: In October 1992, 150 Iowa dental hygienists were randomly selected to participate in a mail survey. The questionnaire included items on self-regulation, licensure, practice, supervision, delivery systems, and independent practice. Responses were analyzed by frequency distributions and the chi-square statistic. RESULTS: Ninety responses were received, representing 80% of the 112 subjects with valid Iowa addresses, but only 60% of the selected sample. Of the 36 variables analyzed, only two were statistically significantly different by ADHA membership. Thus, data were combined and reported for all respondents. The majority of Iowa dental hygienists (71.6%) believed dental hygiene was pursuing self-regulation to improve quality of care. They wanted more dental hygiene representation on licensure boards and almost 50% wanted separate boards. The majority of respondents favored control of dental hygiene practice and 70% wanted alternatives to the current dental hygiene care delivery system. Most respondents stated general supervision and independent practice would increase access to oral healthcare without increasing patients' risk of health problems. CONCLUSIONS: The majority of Iowa dental hygienists support the dental hygiene profession's goal of self-regulation. ADHA members and nonmembers have similar attitudes and opinions about dental hygiene self-regulation, licensure, delivery systems, and practice.

Attitude of Health Personnel↗

PubMed1994

Motility of isolated bowel segment Iowa model III.

The isolated bowel segment (IBS) is an amesenteric segment of bowel that is devoid of extrinsic nerves and yet is viable with motility and absorption preserved after its mesentery is completely severed. The IBS is created by initial coaptation of a loop of bowel to a host organ, such as muscle (Iowa model I), liver (Iowa model II), or intestine, and secondary severance of its mesentery several weeks later. In previous studies using Iowa models I and II, the viability, motility, and absorption of the IBS were preserved by vascular collaterals, which form across the coaptation. In rats, an IBS was created in the jejunum by initial enteroenteropexy (Iowa model III), followed by its mesenteric division five weeks later. At the second laparotomy, bipolar electrodes were implanted in the IBS and the adjacent jejunum. One week later, myoelectrical recording was performed during a fasting state. Coordinated abroad propagation of migrating motor complex (MMC) was observed in the IBS. The MMC period was 16.9 +/- 1.7 and 19.3 +/- 0.8 min in the intact bowel, and 22.8 +/- 0.8 min in the IBS (P = 0.1). After feeding, the MMC in the IBS was replaced by irregular spike burst activity similar to that observed in the intact bowel. This study concludes that the IBS Iowa model III can be used for studies of bowel physiology.

Anastomosis, Surgical↗

PubMed2004

Performance on the IOWA card task by adolescents and adults.

Performance on the Iowa Card Task (ICT) is impaired in several populations that demonstrate poor decision-making and risk-taking including patients with damage to the ventromedial prefrontal cortex. For some individuals, adolescence is a period of poor decision-making and risk-taking. Adolescence is also a period of neuroanatomic and neurochemical remodeling. There is evidence that neuropsychological functions of the prefrontal cortex change during adolescence; however, decision-making, as measured by the ICT, has not been systematically studied in adolescents over the age of 14 years. In the present study, 60 participants (30 female) in each of grades 6-12, and 60 young adults were administered the Iowa Card Task, the Wisconsin Card Sorting Task (WCST), a survey of impulsivity and excitement-seeking, and a quantity-frequency index of substance use. Results showed significant and steady improvement on the Iowa Card Task from the 6th grade to adulthood. Performance on the Iowa Card Task was not correlated with measures of impulsivity, excitement-seeking or reported individual substance use. There was one indication that poly-substance use was negatively correlated with performance on the ICT. Performance on the WCST was not significantly correlated with performance on the Iowa Card Task or any other measure. Across age, males and females had a different response pattern on the ICT. Females tended to choose cards associated with both immediate wins and with long-term outcome. Males tended to choose on the basis of long-term outcome. Results are discussed in terms of adolescent brain development and decision-making differences between males and females.

Adolescent↗

PubMed2001

Pathogenic effects of D23N Iowa mutant amyloid beta -protein.

Cerebral amyloid beta-protein angiopathy (CAA) is a key pathological feature of patients with Alzheimer's disease and certain related disorders. In these conditions the CAA is characterized by the deposition of Abeta within the cerebral vessel wall and, in severe cases, hemorrhagic stroke. Several mutations have been identified within the Abeta region of the Abeta protein precursor (AbetaPP) gene that appear to enhance the severity of CAA. We recently described a new mutation within the Abeta region (D23N) of AbetaPP that is associated with severe CAA in an Iowa kindred (Grabowski, T. J., Cho, H. S., Vonsattel, J. P. G., Rebeck, G. W., and Greenberg, S. M. (2001) Ann. Neurol. 49, 697-705). In the present study, we investigated the effect of this new D23N mutation on the processing of AbetaPP and the pathogenic properties of Abeta. Neither the D23N Iowa mutation nor the E22Q Dutch mutation affected the amyloidogenic processing of AbetaPP expressed in H4 cells. The A21G Flemish mutation, in contrast, resulted in a 2.3-fold increase in secreted Abeta peptide. We also tested synthetic wild-type and mutant Abeta40 peptides for fibrillogenesis and toxicity toward cultured human cerebrovascular smooth muscle (HCSM) cells. The E22Q Dutch, D23N Iowa, and E22Q,D23N Dutch/Iowa double mutant Abeta40 peptides rapidly assembled in solution to form fibrils, whereas wild-type and A21G Flemish Abeta40 peptides exhibited little fibril formation. Similarly, the E22Q Dutch and D23N Iowa Abeta40 peptides were found to induce robust pathologic responses in cultured HCSM cells, including elevated levels of cell-associated AbetaPP, proteolytic breakdown of smooth muscle cell alpha-actin, and cell death. Double mutant E22Q,D23N Dutch/Iowa Abeta40 was more potent than either single mutant form of Abeta in causing pathologic responses in HCSM cells. These data suggest that the different CAA mutations in AbetaPP may exert their pathogenic effects through different mechanisms. Whereas the A21G Flemish mutation appears to enhance Abeta production, the E22Q Dutch and D23N Iowa mutations enhance fibrillogenesis and the pathogenicity of Abeta toward HCSM cells.

Amino Acid Sequence↗