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PubMed1994

Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands.

BACKGROUND: Cancer has long been recognized to have a familial component. Elevated risks for cancers at the same site for relatives of cancer probands have been reported for both common cancers and a number of the rarer cancer sites. For a particular cancer site, however, the estimated risks to relatives have varied considerably depending on criteria for selection of probands, how cancers were determined in relatives, and overall study design. Not surprisingly, the estimated risks of other cancers in relatives of probands with cancer at a given site have been subject to even more variation. PURPOSE: The aim of this study was to use the Utah Population Database resource to systematically study familial clustering of 28 distinct cancer site definitions among first-degree relatives (parents, siblings, and off-spring) of cancer probands. METHODS: We estimated familial relative risks from the Utah Population Database by identifying all cases of cancer in these first-degree relatives. These observed values were compared with those expected based on cohort-specific internal rates calculated from 399,786 relatives of all individuals in the Utah Population Database known to have died in Utah. RESULTS: All sites showed an excess of cancers of the same site among relatives, with thyroid and colon cancers and lymphocytic leukemia showing the highest familial risks. When the analyses were restricted to cases with early ages at diagnosis, increased familial components for most cancer sites became evident. A significant difference in familial relative risk (FRR) between male (FRR = 4.04; 95% confidence interval [CI] = 3.13-5.07) and female (FRR = 2.24; 95% CI = 1.54-3.08) probands was found for colon cancer. Highly significant familial associations (one-sided; P < .001) were found among breast, colon, and prostate cancers and between breast and thyroid cancers. Statistically significant (one-sided, P < .01) associations were also found between tobacco-associated sites (lung, larynx, lip, and cervix). CONCLUSIONS: This study represents a unique comprehensive population-based study of familial cancer. The familial associations reported here will be useful in generating hypotheses about specific genetic and environmental factors that can be tested in genetic linkage and case-control studies.

Aged↗
PubMed1996

The relationship between capsid protein (VP2) sequence and pathogenicity of Aleutian mink disease parvovirus (ADV): a possible role for raccoons in the transmission of ADV infections.

Aleutian mink disease parvovirus (ADV) DNA was identified by PCR in samples from mink and raccoons on commercial ranches during an outbreak of Aleutian disease (AD). Comparison of DNA sequences of the hypervariable portion of VP2, the major capsid protein of ADV, indicated that both mink and raccoons were infected by a new isolate of ADV, designated ADV-TR. Because the capsid proteins of other parvoviruses play a prominent role in the determination of viral pathogenicity and host range, we decided to examine the relationship between the capsid protein sequences and pathogenicity of ADV. Comparison of the ADV-TR hypervariable region sequence with sequences of other isolates of ADV revealed that ADV-TR was 94 to 100% related to the nonpathogenic type 1 ADV-G at both the DNA and amino acid levels but less than 90% related to other pathogenic ADVs like the type 2 ADV-Utah, the type 3 ADV-ZK8, or ADV-Pullman. This finding indicated that a virus with a type 1 hypervariable region could be pathogenic. To perform a more comprehensive analysis, the complete VP2 sequence of ADV-TR was obtained and compared with that of the 647-amino-acid VP2 of ADV-G and the corresponding VP2 sequences of the pathogenic ADV-Utah, ADV-Pullman, and ADV-ZK8. Although the hypervariable region amino acid sequence of ADV-TR was identical to that of ADV-G, there were 12 amino acid differences between ADV-G and ADV-TR. Each of these differences was at a position where other pathogenic isolates also differed from ADV-G. Thus, although ADV-TR had the hypervariable sequence of the nonpathogenic type 1 ADV-G, the remainder of the VP2 sequence resembled sequences of other pathogenic ADVs. Under experimental conditions, ADV-TR and ADV-Utah were highly pathogenic and induced typical AD in trios of both Aleutian and non-Aleutian mink, whereas ADV-Pullman was pathogenic only for Aleutian mink and ADV-G was noninfectious. Trios of raccoons experimentally inoculated with ADV-TR and ADV-Utah all became infected with ADV, but only a single ADV-Pullman-inoculated raccoon showed evidence of infection. Furthermore, none of the ADV isolates induced pathological findings of AD in raccoons. Finally, when a preparation of ADV-TR prepared from infected raccoon lymph nodes was inoculated into mink and raccoons, typical AD was induced in Aleutian and non-Aleutian mink, but raccoons failed to show serological or pathological evidence of infection. These results indicated that raccoons can become infected with ADV and may have a role in the transmission of virus to mink but that raccoon-to-raccoon transmission of ADV is unlikely.

Aleutian Mink Disease↗
PubMed1997

An instrument to evaluate the process of psychiatric care in ambulatory settings.

As part of an evaluation of the Utah Prepaid Mental Health Plan, the Process of Care Review Form was developed to assess the quality of the process of psychiatric care provided by Utah's community mental health centers (CMHCs) to clients with schizophrenia. This article briefly reviews issues in the measurement of quality of care and describes the development and implementation of the form. The 67-item form was designed for use by a trained abstracter to gather data from CMHC medical records in six areas: general management of the patient, medication management, medical management, social support, psychiatric hospitalization, and psychiatric assessment. A 59-item version of the form that omits the section on psychiatric assessment has been used in three waves of data collection to document data spanning five years (1990-1994) in the evaluation of the process of psychiatric care in the Utah plan. It is currently being used longitudinally to examine differences between Utah CMHCs receiving capitated payments and those paid on a fee-for-service basis by Medicaid.

Ambulatory Care↗
PubMedDate not supplied

Improving health care systems performance: a human factors approach.

Under contract from the Centers for Medicare & Medicaid Services (CMS), Medicare Quality Improvement Organizations (QIOs) promote improvement in health care system performance. With the QIO contract cycle that began in the fall of 1999, CMS adopted a broad national improvement agenda emphasizing 24 quality measures from 6 clinical topic areas. The Utah QIO developed a human factors and organizational safety management-based intervention strategy for the inpatient clinical topic areas, borrowing approaches and principles previously applied in hospital-based medication systems safety improvement efforts. Evaluation used measures and methods established by CMS to assess the adequacy of QIO performance nationwide. Comparison of statewide inpatient quality indicator performance rates in 1998 and 2000 showed absolute improvement on 15 of the 16 measures used. The average reduction in the failure rate for these clinical topic areas in Utah was 27.3%; this was the highest rate of improvement for any state in the nation. Utah's overall ranking on the combined inpatient clinical topic areas went from 16th at baseline to first at follow-up. The evaluation demonstrates exceptional levels of performance improvement in Utah hospitals when compared with national trends. It is, however, neither possible to uniquely isolate the effects of the QIO intervention from larger trends operating statewide, nor can the contributions of the various facets of the QIO intervention be disaggregated. The application of human factors and organizational safety management principles represents a promising strategy for accelerating the pace of improvement in health care.

Aged↗
PubMed2005

Population-based analysis of prognostic factors and survival in familial melanoma.

PURPOSE: Familial melanoma patients are reported to present with thinner melanomas, to be younger at the time of diagnosis, and to have a greater likelihood of developing multiple primary tumors. We sought to determine whether melanomas that occur in a familial setting demonstrate different prognostic and survival statistics relative to sporadic melanoma. PATIENTS AND METHODS: This population-based study used the Utah Cancer Registry and Utah Population Database to objectively evaluate prognostic and survival statistics of the familial melanoma population. From 1973 to 1999, there were 7,785 cases of invasive melanoma identified through the Utah Cancer Registry. These were linked to the Utah Population Database, resulting in 2,659 subjects with family-history information from which a familiality score could be calculated. Cases scored in the top ninth percentile were assigned as high familial risk, and the remaining 91% were considered low familial risk. RESULTS: Multivariate logistic-regression analysis found no association between sex, Breslow depth, Clark level, or survival and the familial status. Age at first diagnosis of invasive melanoma was slightly lower in the high-familial-risk group (57 v 60 years; P = .03). High-familial-risk subjects had more melanomas diagnosed at age 30 or younger (12% v 6%; P < .001). A significant difference in the overall number of individuals with two or more primary malignant melanomas was not detected among the groups (P = .2). CONCLUSION: These data suggest that melanomas occurring in the context of an underlying inherited susceptibility do not have a significantly different biologic behavior.

Adult↗
PubMed2000

Injuries sustained by students in shop class.

OBJECTIVE: Injuries in the school environment are a serious public health problem. Injuries occurring within the school shop class are a part of this problem that has received little to no attention. The purpose of our study was to describe the epidemiology of shop class injuries in Utah public schools for the years 1992-1996. METHODS: Utah statewide grades 7 through 12 school injury data for 1992-1996 were used. The data were generated from a standardized Student Injury Report form completed by school personnel immediately after the occurrence of an injury on school premises that: 1) caused loss of at least one half of a day of school; and/or 2) warranted medical attention and treatment. Shop injuries were defined as injuries that occurred in industrial art classes, vocational educational classes, or automotive classes. To determine the medical outcome and hospital charges associated with shop class injuries, we linked the Student Injury Report database to Utah statewide emergency department (ED) records (available for 1996 only), and to Utah statewide hospital inpatient discharge records (1992-1996). RESULTS: During 1992-1996, 14 133 students in grades 7 through 12 were injured at school, of which 1008 (7.1%) were injured during a shop class. The majority (88. 4%) of shop injuries involved equipment use. Equipment was misused in 37.9% and malfunctioned in 3.5% of the incidents. The leading injuries reported for shop equipment were lacerations (70.9%), burns (6.0%), and abrasions (4.6%), whereas the leading for nonequipment injuries were lacerations (45.4%), fractures (9.2%), and pain/tenderness (6.7%). In 1996, 167 students were injured in a shop class and 45 (26.9%) visited an ED as a result of the shop injury. Equipment was a factor in 88.9% of the shop injuries admitted to the ED. Table saws (15.0%), other saws (15.0%), and band saws (12.5%) were involved in nearly one half of the equipment injuries. Equipment was misused in 44.7% and malfunctioned in 10.5% of the incidents resulting in an ED visit. The majority (64.4%) of students sustained an open wound injury. The total ED charges were $16 571. For 1992-1996, 1008 students were injured in a shop class, 7 (.7%) required inpatient hospital care. Six of the students were injured using a table saw and 1 sustained injuries attributable to automotive cleaning fluid. Equipment was used improperly in 4 of the table saw injuries. Six of the students sustained hand injuries, with 3 suffering a traumatic amputation of a finger or thumb. The total inpatient charges were $26 747. CONCLUSION: School shop injuries have a great impact on students, their families, and schools because of the loss of productivity for the student and the financial impact. Many of the injuries are preventable. These findings stress the need for school administrators, teachers, and students to develop and improve safety policies and practices in school shop classes. In addition, the findings may provide useful information to pediatricians and enable them to better inform patients of risks in school shop classes.

Adolescent↗
PubMed2005

Adverse events and preventable adverse events in children.

CONTEXT: Patient safety has been recognized as an important problem in health care. However, knowledge about adverse events and preventable adverse events in children is relatively limited. OBJECTIVE: To describe the incidence and types of adverse events and preventable adverse events in children. DESIGN: Analysis of pediatric hospitalizations in the Colorado and Utah Medical Practice Study, which involved a retrospective, 2-level (nurse and physician) medical record review of a population-based, representative sample of all pediatric hospital discharges. MAIN MEASURES: Adverse events were defined as an injury caused by medical management rather than disease processes that resulted in either prolonged hospitalization or disability at discharge. A preventable adverse event was defined as an avoidable adverse event based on currently available knowledge and accepted practices. PATIENTS: 3719 discharged hospital patients, 0-20 years old, and 7528 nonelderly (21-65 years old) discharged adult patients in Colorado and Utah. SETTING: All hospitals in Colorado and Utah. RESULTS: Adverse events occurred in 1% of pediatric hospitalizations in Colorado and Utah; 0.6% were preventable. Preventable adverse events rates were 0.53% in neonates and infants (0-0.99 years), 0.22% in children 1-12 years of age, and 0.95% in adolescents 13-20 years of age, compared with a rate of 1.50% in nonelderly adults. Of preventable adverse event types, birth related (32.2%) and diagnostic related (30.4%) events were the most common and were significantly more common than surgically related preventable adverse events (3.5%). CONCLUSIONS: These data suggest that approximately 70,000 children hospitalized in the United States experience an adverse event each year; 60% of these events may be preventable. The epidemiology of adverse events and preventable adverse events in children is different than in adults. To reduce the adverse events that occur in hospitalized children, research should focus on adolescent hospitalized patients, birth-related medical care, and diagnostics in pediatric medicine.

Adolescent↗
PubMedDate not supplied

Perioperative mechanical circulatory support for transplantation.

Mechanical circulatory assistance has become a necessary supplement to more conventional means of hemodynamic support as a shortage of donor organs and associated increase in waiting time have contributed to an increased incidence of hemodynamic deterioration in potential transplant recipients. This review summarizes the experience with circulatory support before and after transplantation of the Utah Transplantation Affiliated Hospitals (UTAH) Cardiac Transplant Program and draws conclusions on the efficacy of one program's use of mechanical circulatory support. Between March 1985 and October 1990, 401 patients were accepted for first-time heart transplantation by the UTAH program. One hundred and eighty patients (46%) were supported before transplantation with conventional hemodynamic therapies, 72 patients (18%) with oral enoximone, 96 patients (25%) with intravenous inotropes, and 34 patients (9%) with an intraaortic balloon; nine patients (2%) required centrifugal blood pump circulatory support. Not included in these statistics are 10 patients awaiting transplantation as of October 10, 1990. Thirty-eight candidates (10%) died awaiting transplantation, 329 (84%) received transplantation, and 24 (6%) were removed from the transplantation list for other reasons. Ten patients (3%) required mechanical circulatory support after transplantation with 38% of this group surviving 1 year after after transplantation. No single factor, including either hemodynamic support before transplantation or donor heart ischemic time, was found to be predictive of the need for mechanical circulatory support after transplantation. One-year survival rates after transplantation of patients requiring mechanical circulatory support before transplantation (86%) were not significantly different than for all transplant patients (88%). The experience of the UTAH Cardiac Transplant Program shows that with the judicious use of mechanical circulatory support transplant patients with advanced forms of hemodynamic support can have as equal a probability of survival as patients who undergo elective transplantation.

Adult↗
PubMed1992

Prevention of familial cardiovascular disease by screening for family history and lipids in youths.

We analyzed medical family history information from 51,053 families of high school students in Utah and Texas and cholesterol measurements from 853 youths and 1618 adults in Utah families with cardiovascular disease (CVD) to assess the utility of different approaches to risk-factor evaluation for youths. The major question addressed was in which youths should blood cholesterol be tested? Applying National Cholesterol Education Program recommendations suggested that 36% in Utah and 38% in Texas be tested. Heterozygous familial hypercholesterolemia (hFH) is the best documented and most serious cholesterol disorder readily diagnosed in youths. In Utah families ascertained for CVD in adults, blood cholesterol levels among youths were significantly bimodal with hFH present in 84% of youths in the upper cholesterol mode. Blood cholesterol levels in adults from the same families were less bimodal with hFH present in 38% of adults in the upper mode. More overlap existed between high and normal modes in adults than in youths. Data from this study suggest that family histories and cholesterol concentrations obtained from high school students may meet the needs of cholesterol screening, education, and follow-up in a controlled and cost-effective setting.

Adolescent↗
PubMed2001

Usefulness of cardiovascular family history data for population-based preventive medicine and medical research (the Health Family Tree Study and the NHLBI Family Heart Study).

Detailed medical family history data have been proposed to be effective in identifying high-risk families for targeted intervention. With use of a validated and standardized quantitative family risk score (FRS), the degree of familial aggregation of coronary heart disease (CHD), stroke, hypertension, and diabetes was obtained from 122,155 Utah families and 6,578 Texas families in the large, population-based Health Family Tree Study, and 1,442 families in the NHLBI Family Heart Study in Massachusetts, Minnesota, North Carolina, and Utah. Utah families with a positive family history of CHD (FRS > or =0.5) represented only 14% of the general population but accounted for 72% of persons with early CHD (men before age 55 years, women before age 65 years) and 48% of CHD at all ages. For strokes, 11% of families with FRS > or =0.5 accounted for 86% of early strokes (<75 years) and 68% of all strokes. Analyses of >5,000 families sampled each year in Utah for 14 years demonstrated a gradual decrease in the frequency of a strong positive family history of CHD (-26%/decade) and stroke (-15%/decade) that paralleled a decrease in incidence rates (r = 0.86, p <0.001 for CHD; r = 0.66, p <0.01 for stroke). Because of the collaboration of schools, health departments, and medical schools, the Health Family Tree Study proved to be a highly cost-efficient method for identifying 17,064 CHD-prone families and 13,106 stroke-prone families (at a cost of about $27 per high-risk family) in whom well-established preventive measures can be encouraged. We conclude that most early cardiovascular events in a population occur in families with a positive family history of cardiovascular disease. Family history collection is a validated and relatively inexpensive tool for family-based preventive medicine and medical research.

Adult↗
PubMed2005

A multifaceted intervention to improve antimicrobial prescribing for upper respiratory tract infections in a small rural community.

BACKGROUND: Antibiotic prescribing for upper respiratory tract infections (URTIs) is widespread, is often inappropriate, and may contribute to antibiotic resistance among community-acquired pathogens, such as Streptococcus pneumoniae. METHODS: A multifaceted intervention involving health care professionals and patients was introduced to a small rural Utah community and included the repetitive use of printed diagnostic and treatment algorithms by professionals. Data on the quantity and class of antibiotic prescribing, which were collected from multiple sources, were measured for the intervention period (from January through June) in 2001 and compared with data for the baseline period during the same months in 2000. RESULTS: Medicaid claims data revealed that the percentage of patients in the community who received antibiotics for URTIs during the intervention period was 15.6% less than that for the baseline period, whereas the percentage in the rest of rural Utah was relatively stable, with a 1.5% decrease (P=.006). The greatest impact of the intervention was on prescribing for acute bronchitis (decreases of 56.1% and 1.7% in the community and rural Utah, respectively; P=.024) and on prescribing of macrolides (decreases of 13.4% and 0.2% in the community and rural Utah, respectively; P<.001). Community pharmacy data likewise revealed a 17.5% decrease in the rate of antibiotic prescribing during the intervention period (P<.001), with the largest decrease observed for macrolide prescribing (50.9%; P<.001). Chart review data, in contrast, revealed no significant decrease in the percentage of patients with URTI who were prescribed an antibiotic (3.8%; P=.49), although there was a significant decrease of 11.2% in macrolide use (P=.045). CONCLUSIONS: A multifaceted intervention involving the repetitive use of printed algorithms resulted in modest improvements in antibiotic prescribing for outpatient URTIs, although one data source did not corroborate this. However, macrolide prescribing decreased sharply, irrespective of the source of data.

Adolescent↗
PubMed1984

Aleutian disease virus, a parvovirus, is proteolytically degraded during in vivo infection in mink.

The polypeptides of the highly virulent mink-passaged Utah I and the nonvirulent cell culture-adapted ADV-G strain of Aleutian disease virus (ADV) were compared. When CRFK cells infected with either Utah I or ADV-G were analyzed by immunoprecipitation, both viruses induced proteins with molecular weights characteristic of the ADV-G 85,000 ( 85k )- and 75k-dalton structural proteins (p85 and p75) as well as the 71k -dalton nonvirion protein p71 . However, when Utah I, Pullman ADV, and DK ADV (a Danish isolate of ADV) were purified from infected mink, only polypeptides with molecular weights between 27k and 30k could be identified. In addition, trypsin treatment of ADV-G degraded p85 and p75 to smaller antigenic proteins with molecular weights of 24k and 27k, similar to those found for the virulent in vivo viruses. The effect of proteolytic treatment of ADV was then studied in detail. Purification of Utah I ADV from mink organs in the presence of protease inhibitor did not prevent the appearance of the low-molecular-weight proteins and ADV-G proteins were not degraded upon purification from a homogenate of normal mink organs, suggesting that artifactual proteolysis was not occurring. When a serum pool from terminally diseased mink was analyzed by radioimmunoassay for antibody reactivity against trypsinized and nontrypsinized ADV-G, five times higher reactivity was found for the trypsinized ADV-G than for the nontrypsinized ADV-G, an effect which could not be elicited by chymotrypsin or V8 protease treatment, implying that in vivo-produced ADV was being modulated in vivo by trypsin or a trypsin-like enzyme. Trypsinization was shown not to cause a change in ADV virion density, but to decrease the in vitro infectivity of ADV-G for CRFK cells. These studies suggested that during infection of mink ADV proteins are degraded to highly antigenic smaller polypeptides.

Aleutian Mink Disease↗
PubMed1993

Characterization of chimeric full-length molecular clones of Aleutian mink disease parvovirus (ADV): identification of a determinant governing replication of ADV in cell culture.

The ADV-G strain of Aleutian mink disease parvovirus (ADV) is nonpathogenic for mink but replicates permissively in cell culture, whereas the ADV-Utah 1 strain is highly pathogenic for mink but replicates poorly in cell culture. In order to relate these phenotypic differences to primary genomic features, we constructed a series of chimeric plasmids between a full-length replication-competent molecular clone of ADV-G and subgenomic clones of ADV-Utah 1 representing map units (MU) 15 to 88. After transfection of the plasmids into cell culture and serial passage of cell lysates, we determined that substitution of several segments of the ADV-Utah 1 genome (MU 15 to 54 and 65 to 73) within an infectious ADV-G plasmid did not impair the ability of these constructs to yield infectious virus in vitro. Like ADV-G, the viruses derived from these replication-competent clones caused neither detectable viremia 10 days after inoculation nor any evidence of Aleutian disease in adult mink. On the other hand, other chimeric plasmids were incapable of yielding infectious virus and were therefore replication defective in vitro. The MU 54 to 65 EcoRI-EcoRV fragment of ADV-Utah 1 was the minimal segment capable of rendering ADV-G replication defective. Substitution of the ADV-G EcoRI-EcoRV fragment into a replication-defective clone restored replication competence, indicating that this 0.53-kb portion of the genome, wholly located within shared coding sequences for the capsid proteins VP1 and VP2, contained a determinant that governs replication in cell culture. When cultures of cells were studied 5 days after transfection with replication-defective clones, rescue of dimeric replicative form DNA and single-stranded progeny DNA could not be demonstrated. This defect could not be complemented by cotransfection with a replication-competent construction.

Aleutian Mink Disease Virus↗
PubMed1993

Aleutian mink disease parvovirus infection of mink peritoneal macrophages and human macrophage cell lines.

Aleutian mink disease parvovirus (ADV) mRNAs are found in macrophages in lymph nodes and peritoneal exudate cells from ADV-infected mink. Therefore, we developed an in vitro infection system for ADV by using primary cultures of mink macrophages or macrophage cell lines. In peritoneal macrophage cultures from adult mink, virulent ADV-Utah I strain showed nuclear expression of viral antigens with fluorescein isothiocyanate-labeled ADV-infected mink serum, but delineation of specific viral proteins could not be confirmed by immunoblot analysis. Amplification of ADV DNA and production of replicative-form DNA were observed in mink macrophages by Southern blot analysis; however, virus could not be serially propagated. The human macrophage cell line U937 exhibited clear nuclear expression of viral antigens after infection with ADV-Utah I but not with tissue culture-adapted ADV-G. In U937 cells, ADV-Utah I produced mRNA, replicative-form DNA, virion DNA, and structural and nonstructural proteins; however, virus could not be serially passaged nor could [3H]thymidine-labeled virions be observed by density gradient analysis. These findings indicated that ADV-Utah I infection in U937 cells was not fully permissive and that there is another restricted step between gene amplification and/or viral protein expression and production of infectious virions. Treatment with the macrophage activator phorbol 12-myristate 13-acetate after adsorption of virus reduced the frequency of ADV-positive U937 cells but clearly increased that of human macrophage line THP-1 cells. These results suggested that ADV replication may depend on conditions influenced by the differentiation state of macrophages. U937 cells may be useful as an in vitro model system for the analysis of the immune disorder caused by ADV infection of macrophages.

Aleutian Mink Disease Virus↗
PubMed1997

Expression of Aleutian mink disease parvovirus capsid proteins in defined segments: localization of immunoreactive sites and neutralizing epitopes to specific regions.

The capsid proteins of the ADV-G isolate of Aleutian mink disease parvovirus (ADV) were expressed in 10 nonoverlapping segments as fusions with maltose-binding protein in pMAL-C2 (pVP1, pVP2a through pVP2i). The constructs were designed to capture the VP1 unique sequence and the portions analogous to the four variable surface loops of canine parvovirus (CPV) in individual fragments (pVP2b, pVP2d, pVP2e, and pVP2g, respectively). The panel of fusion proteins was immunoblotted with sera from mink infected with ADV. Seropositive mink infected with either ADV-TR, ADV-Utah, or ADV-Pullman reacted preferentially against certain segments, regardless of mink genotype or virus inoculum. The most consistently immunoreactive regions were pVP2g, pVP2e, and pVP2f, the segments that encompassed the analogs of CPV surface loops 3 and 4. The VP1 unique region was also consistently immunoreactive. These findings indicated that infected mink recognize linear epitopes that localized to certain regions of the capsid protein sequence. The segment containing the hypervariable region (pVP2d), corresponding to CPV loop 2, was also expressed from ADV-Utah. An anti-ADV-G monoclonal antibody and a rabbit anti-ADV-G capsid antibody reacted exclusively with the ADV-G pVP2d segment but not with the corresponding segment from ADV-Utah. Mink infected with ADV-TR or ADV-Utah also preferentially reacted with the pVP2d sequence characteristic of that virus. These results suggested that the loop 2 region may contain a type-specific linear epitope and that the epitope may also be specifically recognized by infected mink. Heterologous antisera were prepared against the VP1 unique region and the four segments capturing the variable surface loops of CPV. The antisera against the proteins containing loop 3 or loop 4, as well as the anticapsid antibody, neutralized ADV-G infectivity in vitro and bound to capsids in immune electron microscopy. These results suggested that regions of the ADV capsid proteins corresponding to surface loops 3 and 4 of CPV contain linear epitopes that are located on the external surface of the ADV capsid. Furthermore, these linear epitopes contain neutralizing determinants. Computer comparisons with the CPV crystal structure suggest that these sequences may be adjacent to the threefold axis of symmetry of the viral particle.

Aleutian Mink Disease Virus↗
PubMed1999

Replication of Aleutian mink disease parvovirus in vivo is influenced by residues in the VP2 protein.

Aleutian mink disease parvovirus (ADV) is the etiological agent of Aleutian disease of mink. Several ADV isolates have been identified which vary in the severity of the disease they elicit. The isolate ADV-Utah replicates to high levels in mink, causing severe Aleutian disease that results in death within 6 to 8 weeks, but does not replicate in Crandell feline kidney (CrFK) cells. In contrast, ADV-G replicates in CrFK cells but does not replicate in mink. The ability of the virus to replicate in vivo is determined by virally encoded determinants contained within a defined region of the VP2 gene (M. E. Bloom, J. M. Fox, B. D. Berry, K. L. Oie, and J. B. Wolfinbarger. Virology 251:288-296, 1998). Within this region, ADV-G and ADV-Utah differ at only five amino acid residues. To determine which of these five amino acid residues comprise the in vivo replication determinant, site-directed mutagenesis was performed to individually convert the amino acid residues of ADV-G to those of ADV-Utah. A virus in which the ADV-G VP2 residue at 534, histidine (H), was converted to an aspartic acid (D) of ADV-Utah replicated in CrFK cells as efficiently as ADV-G. H534D also replicated in mink, causing transient viremia at 30 days postinfection and a strong antibody response. Animals infected with this virus developed diffuse hepatocellular microvesicular steatosis, an abnormal accumulation of intracellular fat, but did not develop classical Aleutian disease. Thus, the substitution of an aspartic acid at residue 534 for a histidine allowed replication of ADV-G in mink, but the ability to replicate was not sufficient to cause classical Aleutian disease.

Aleutian Mink Disease↗
PubMed2004

Diagnostic controversies in adult attention deficit hyperactivity disorder.

OBJECTIVE: While it is increasingly recognized that attention deficit hyperactivity disorder (ADHD) persists into adulthood, there is no consensus on diagnostic criteria for adult ADHD. In this article the authors describe and contrast competing approaches for diagnosis of adult ADHD used in clinical and research practice. METHOD: The authors review the Wender Utah criteria, DSM criteria, and laboratory assessment strategies for adult ADHD. Advantages and disadvantages of each approach are described, and recommendations are made as a basis for clinical assessment and future research. RESULTS: Both the Wender Utah criteria and DSM-based approaches identify significantly impaired ADHD adults with neurocognitive, biological, and treatment response patterns similar to pediatric ADHD patients. The Wender Utah criteria established the need for retrospective childhood diagnosis and recognize developmental differences in adult symptom expression. The Wender Utah criteria fail to identify patients with predominantly inattentive symptoms, exclude some patients with significant comorbid psychopathology, and diverge significantly from the DSM conception of ADHD. The DSM criteria have never been validated in adults, do not include developmentally appropriate symptoms and thresholds for adults, and fail to identify some significantly impaired adults who are likely to benefit from treatment. There are insufficient scientific data to justify use of laboratory assessment measures, including neuropsychological tests and brain imaging, in diagnosing adult ADHD. CONCLUSIONS: Adult ADHD remains a clinical diagnosis. Clinicians should be flexible in application of the current ADHD criteria to adults. Additional research is required to validate adult diagnostic criteria.

Adult↗
PubMed2003

A genealogical assessment of heritable predisposition to aneurysms.

OBJECT: This study was conducted to investigate the familial and genetic contribution to intracranial, abdominal aortic, and all other types of aneurysms, and to define familial relationships among patients who present with the different aneurysm types. METHODS: The authors used a unique Utah resource to perform population-based analysis of the familial nature of aneurysms. The Utah Population Data Base is a genealogy of the Utah population dating back eight generations, which is combined with death certificate data for the state of Utah dating back to 1904. Taking into account the genetic relationships among all aneurysm cases derived from this resource, the authors used a previously published method to estimate the familiality of different aneurysm types. Using internal, birth-cohort-specific rates of disease calculated from the database, they estimated relative risks by comparing observed to expected rates of aneurysm incidence in defined sets of relatives of probands. CONCLUSIONS: Each of the three aneurysm types investigated showed significant evidence for a genetic component. Relatives of patients with intracranial aneurysms do not appear to be at increased risk for abdominal or other lesions, but relatives of patients with abdominal aortic aneurysms appear to be at increased risk for other types of these lesions.

Aged↗