Cognitive decline in the middle-aged after surgery and anaesthesia: results from the Wisconsin Registry for Alzheimer's Prevention cohort.

Surgery and anaesthesia might affect cognition in middle-aged people without existing cognitive dysfunction. We measured memory and executive function in 964 participants, mean age 54 years, and again four years later, by when 312 participants had had surgery and 652 participants had not. Surgery between tests was associated with a decline in immediate memory by one point (out of a maximum of 30), p = 0.013: memory became abnormal in 77 out of 670 participants with initially normal memory, 21 out of 114 (18%) of whom had had surgery compared with 56 out of 556 (10%) of those who had not, p = 0.02. The number of operations was associated with a reduction in immediate memory on retesting, beta coefficient (SE) 0.08 (0.03), p = 0.012. Working memory decline was also associated with longer cumulative operations, beta coefficient (SE) -0.01 (0.00), p = 0.028. A reduction in cognitive speed and flexibility was associated with worse ASA physical status, beta coefficient (SE) 0.55 (0.22) and 0.37 (0.17) for ASA 1 and 2 vs. 3, p = 0.035. However, a decline in working memory was associated with better ASA physical status, beta coefficient (SE) -0.48 (0.21) for ASA 1 vs. 3, p = 0.01.

Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults.

OBJECTIVE: To evaluate the longitudinal influence of family history (FH) of Alzheimer disease (AD) and apolipoprotein E ε4 allele (APOE4) on brain atrophy and cognitive decline over 4 years among asymptomatic middle-aged individuals. METHODS: Participants were cognitively healthy adults with (FH+) (n = 60) and without (FH-) (n = 48) a FH of AD (mean age at baseline 54 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention. They underwent APOE genotyping, cognitive testing, and an MRI scan at baseline and 4 years later. A covariate-adjusted voxel-based analysis interrogated gray matter (GM) modulated probability maps at the 4-year follow-up visit as a function of FH and APOE4. We also examined the influence of parent of origin on GM atrophy. Parallel analyses investigated the effects of FH and APOE4 on cognitive decline. RESULTS: Neither FH nor APOE4 had an effect on regional GM or cognition at baseline. Longitudinally, a FH × APOE4 interaction was found in the right posterior hippocampus, which was driven by a significant difference between the FH+ and FH- subjects who were APOE4-. In addition, a significant FH main effect was observed in the left posterior hippocampus. No significant APOE4 main effects were detected. Persons with a maternal history of AD were just as likely as those with a paternal history of AD to experience posterior hippocampal atrophy. There was no longitudinal decline in cognition within the cohort. CONCLUSION: Over a 4-year interval, asymptomatic middle-aged adults with FH of AD exhibit significant atrophy in the posterior hippocampi in the absence of measurable cognitive changes. This result provides further evidence that detectable disease-related neuroanatomic changes do occur early in the AD pathologic cascade.

Hormone effects on fMRI and cognitive measures of encoding: importance of hormone preparation.

We compared fMRI and cognitive data from nine hormone therapy (HT)-naive women with data from women exposed to either opposed conjugated equine estrogens (CEE) (n = 10) or opposed estradiol (n = 4). Exposure to either form of HT was associated with healthier fMRI response; however, CEE-exposed women exhibited poorer memory performance than either HT-naive or estradiol-exposed subjects. These preliminary findings emphasize the need to characterize differential neural effects of various HTs.

Wisconsin cystic fibrosis chest radiograph scoring system: validation and standardization for application to longitudinal studies.

This study was designed to achieve a final modeling, validation, and standardization plan for the Wisconsin cystic fibrosis (CF) chest radiographic scoring system. Sixty chest radiographs were selected to reflect a range of severity of lung pathology in children with CF. Seven experienced volunteer raters (three radiologists and four pediatric pulmonologists) from five institutions were recruited to evaluate and score the films. Analysis of scores revealed that the subcomponents of the Wisconsin system showed considerable variation from rater to rater, but reliability assessment indicated satisfactory Cronbach's alpha coefficients (0.83-0.90) among the seven raters. It was found that an additive method of total score computation is significantly more reliable (P < 0.05) than either the original multiplicative model or the traditional Brasfield scoring system. Comparison of radiologists and pulmonologists revealed a marked, systematic difference in scoring with the former group being more conservative in interpretation of abnormalities than the pulmonologists, and some of the raters showing very limited sensitivity. Quantitative chest radiology applied to children with cystic fibrosis studied long-term in longitudinal research projects requires the careful use of sensitive scoring methods and careful selection and training of multiple raters. This is particularly important since pulmonologists and radiologists can differ systematically in interpreting/scoring abnormalities.

Health risk taking and human immunodeficiency virus risk in collegiate female athletes.

Risky health behaviors of female intercollegiate varsity athletes and their nonathlete peers were compared. Five hundred seventy-one female university students (109 athletes and 462 nonathlete peers) at two midwestern universities completed a self-administered, anonymous questionnaire during team meetings or class sessions. Each athlete was matched with two nonathlete controls of similar age, ethnicity, and class year to test for dichotomous outcome variables. A human immunodeficiency virus (HIV) risk scale was developed to identify factors associated with increased HIV risk for all of the female participants. Measures of alcohol and other drug use were associated with HIV risk. The athletes were found to engage in significantly fewer risk-taking behaviors than the nonathletes and to be at less risk for HIV. High levels of risk behaviors generally indicated the need for increased efforts to change risky behaviors in all college women.

Newborn screening for cystic fibrosis in Wisconsin: comparison of biochemical and molecular methods.

OBJECTIVES: To evaluate neonatal screening for cystic fibrosis (CF), including study of the screening procedures and characteristics of false-positive infants, over the past 10 years in Wisconsin. An important objective evolving from the original design has been to compare use of a single-tier immunoreactive trypsinogen (IRT) screening method with that of a two-tier method using IRT and analyses of samples for the most common cystic fibrosis transmembrane regulator (CFTR) (DeltaF508) mutation. We also examined the benefit of including up to 10 additional CFTR mutations in the screening protocol. METHODS: From 1985 to 1994, using either the IRT or IRT/DNA protocol, 220 862 and 104 308 neonates, respectively, were screened for CF. For the IRT protocol, neonates with an IRT >/=180 ng/mL were considered positive, and the standard sweat chloride test was administered to determine CF status. For the IRT/DNA protocol, samples from the original dried-blood specimen on the Guthrie card of neonates with an IRT >/=110 ng/mL were tested for the presence of the DeltaF508 CFTR allele, and if the DNA test revealed one or two DeltaF508 alleles, a sweat test was obtained. RESULTS: Both screening procedures had very high specificity. The sensitivity tended to be higher with the IRT/DNA protocol, but the differences were not statistically significant. The positive predictive value of the IRT/DNA screening protocol was 15.2% compared with 6.4% if the same samples had been screened by the IRT method. Assessment of the false-positive IRT/DNA population revealed that the two-tier method eliminates the disproportionate number of infants with low Apgar scores and also the high prevalence of African-Americans identified previously in our study of newborns with high IRT levels. We found that 55% of DNA-positive CF infants were homozygous for DeltaF508 and 40% had one DeltaF508 allele. Adding analyses for 10 more CFTR mutations has only a small effect on the sensitivity but is likely to add significantly to the cost of screening. CONCLUSIONS: Advantages of the IRT/DNA protocol over IRT analysis include improved positive predictive value, reduction of false-positive infants, and more rapid diagnosis with elimination of recall specimens.

Nutritional benefits of neonatal screening for cystic fibrosis. Wisconsin Cystic Fibrosis Neonatal Screening Study Group.

BACKGROUND: Many patients with cystic fibrosis are malnourished at the time of diagnosis. Whether newborn screening and early treatment may prevent the development of a nutritional deficiency is not known. METHODS: We compared the nutritional status of patients with cystic fibrosis identified by neonatal screening or by standard diagnostic methods. A total of 650,341 newborn infants were screened by measuring immunoreactive trypsinogen on dried blood spots (from April 1985 through June 1991) or by combining the trypsinogen test with DNA analysis (from July 1991 through June 1994). Of 325,171 infants assigned to an early-diagnosis group, cystic fibrosis was diagnosed in 74 infants, including 5 with negative screening tests. Excluding infants with meconium ileus, we evaluated nutritional status for up to 10 years by anthropometric and biochemical methods in 56 of the infants who received an early diagnosis and in 40 of the infants in whom the diagnosis was made by standard methods (the control group). Pancreatic insufficiency was managed with nutritional interventions that included high-calorie diets, pancreatic-enzyme therapy, and fat-soluble vitamin supplements. RESULTS: The diagnosis of cystic fibrosis was confirmed by a positive sweat test at a younger age in the early-diagnosis group than in the control group (mean age, 12 vs. 72 weeks). At the time of diagnosis, the early-diagnosis group had significantly higher height and weight percentiles and a higher head-circumference percentile (52nd, vs. 32nd in the control group; P=0.003). The early-diagnosis group also had significantly higher anthropometric indexes during the follow-up period, especially the children with pancreatic insufficiency and those who were homozygous for the deltaF508 mutation. CONCLUSIONS: Neonatal screening provides the opportunity to prevent malnutrition in infants with cystic fibrosis.

Substance use and other health risk behaviors in collegiate athletes.

OBJECTIVES: To (a) determine the prevalence of alcohol and other drug use, and health risk behaviors among a general university population; and (b) compare health risk-taking behaviors between genders, and varsity athletes and their non-athlete peers. DESIGN: Descriptive survey of multiple health risk behaviors, including physical, mental health, alcohol and other drug, and sexual risk taking. SETTING: Two large midwestern universities. PARTICIPANTS: A convenience sample of 86% of 1,210 eligible students (271 athletes and 775 nonathlete peers) completed a self-administered, anonymous questionnaire during team meetings or class sessions. INTERVENTION: None. MAIN OUTCOME MEASURES: Differences between gender and athlete status were assessed using Cochran-Mantel-Haenszel statistics for the following variables, determined by questionnaire responses: physical risk, mental health, alcohol and other drug use, and sexual behaviors. RESULTS: Common risk behaviors in the entire collegiate sample included riding in a car with a driver who was under the influence of alcohol, driving and swimming under the influence of alcohol, binge drinking, and low rate of condom use for all types of sexual intercourse. Risk-taking behaviors varied by gender, with men showing more risk behaviors than women, except for suicide and sexual behaviors. Male athletes had a higher prevalence of risk behaviors than their male nonathlete counterparts, in contrast to female athletes, who had fewer risk behaviors than their female nonathlete counterparts. CONCLUSION: In contrast to previous studies, results of the present study show, when results are stratified by gender, that not all athletes engage more frequently than nonathletes in high risk behaviors. Results suggest that educational and early intervention strategies to decrease risk may need to be tailored according to gender and athletic status.

Effect of linoleic acid intake on growth of infants with cystic fibrosis.

Essential fatty acid deficiency as a result of inadequate linoleic acid impairs growth in healthy infants and is common in infants with malabsorption due to cystic fibrosis (CF). We investigated the effect of dietary linoleic acid intake on the growth of infants with CF. In this study, predigested formula preparations A and B, with linoleic acid contents of 12% and 7% of energy, respectively, were fed before and after 1989 to infants enrolled in the evaluation and treatment protocol of the Wisconsin CF Neonatal Screening Project. Outcome was assessed from height-for-age (HAZ) and weight-for-age (WAZ) Z scores on follow-up exams during the first year. Baseline characteristics did not differ significantly between groups A (n = 43) and B (n = 33). At diagnosis, 53% of the enrolled infants (n = 76) showed low plasma linoleic acid concentrations and 22% had a high ratio of triene to tetraene. After correcting for the effect of potentially confounding variables, we found that HAZ (by .27, P < 0.05) and WAZ (by 0.26, P = 0.081) were higher in group A than in group B. This occurred despite a significantly higher energy intake in group B. This difference was most pronounced between 6 and 9 mo of age. Our results suggest that a high linoleic acid content in formula benefits infants with CF because it optimizes nutrition, growth, and feeding efficiency.

Sweat chloride concentrations in infants homozygous or heterozygous for F508 cystic fibrosis.

OBJECTIVE: To determine whether an adequate volume of sweat could be obtained routinely from infants younger than 6 weeks old and to evaluate sweat chloride levels in infants with known genotype statuses, including heterozygote carriers for cystic fibrosis (CF). METHODOLOGY: Infants were evaluated using pilocarpine iontophoresis and measurement of sweat volume and chloride concentration. The majority of these infants were referred because of newborn screening test results positive for CF based on immunoreactive trypsinogen analysis. DNA analyses for the 3-base pair deletion at codon 508 of the CF transmembrane regulator gene (F508 mutation) were performed whenever possible, and patients with CF were categorized by genotype. RESULTS: Sweat tests were performed successfully (>/-50 mg of sweat) in 99.3% of the infants tested, and there was no difference in the proportion of unsuccessful tests in infants younger than or older than 6 weeks of age. The normal mean +/- SD sweat chloride was 10.6 +/- 5.2 mEq/L (95% confidence interval, 9.9-11.3). Patients with CF who are F508 homozygotes or F508 compound heterozygotes or who have two other non-F508 mutant alleles were shown to have similar sweat chloride levels, with mean values of 99.9, 98.8, and 96.6 mEq/L, respectively. The group of infants who were found to be CF (F508) heterozygote carriers, when compared with the healthy group, had mildly but significantly increased sweat chloride concentrations, with a mean +/- SD of 14.9 +/- 8.4 mEq/L (95% confidence interval, 13.4-16.4). CONCLUSIONS: Quantitative pilocarpine iontophoresis can be used successfully in infants younger than 6 weeks of age who are undergoing routine diagnostic evaluations to follow up newborn screening test results that are positive for CF. The upper limit of normal sweat chloride in infants should be revised to 40 mEq/L (mean + 3 SD of the CF heterozygote carrier group). CF heterozygote carrier infants with one F508 mutant allele show phenotypic manifestations of CF, including subclinical elevations of sweat chloride.

Bronchoalveolar oxyradical inflammatory elements herald bronchopulmonary dysplasia.

OBJECTIVES: To quantify oxyradical inflammatory markers in serial endotracheal tube aspirates obtained from premature neonates at risk for developing bronchopulmonary dysplasia, and to correlate these parameters with clinical manifestations of the disease. DESIGN: Prospective cohort study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: Twenty-eight intubated, premature infants, with 15 infants displaying simple respiratory distress syndrome and 13 infants eventually developing bronchopulmonary dysplasia. INTERVENTIONS: Endotracheal tube aspirates were collected and clinical severity scores were calculated longitudinally from an inception cohort during the first week of life. Diagnosis of bronchopulmonary dysplasia by standard criteria was recorded at 30 days of life. Various biochemical analyses related to pulmonary oxyradical stress were determined on endotracheal tube aspirates and were normalized according to the magnitude of serum/aspirate urea ratios. The demographic, illness severity, and biochemical characteristics of infants with simple respiratory distress syndrome and those characteristics of infants developing bronchopulmonary dysplasia were evaluated by masked comparison. MEASUREMENTS AND MAIN RESULTS: Populations of respiratory distress syndrome and bronchopulmonary dysplasia infants could be differentiated during the first week of life by means of the following parameters: gestational age; birth weight; Score of Neonatal Acute Physiology; Neonatal Therapeutic Intervention Scoring System; epithelial lining fluid leukocytes; elastase; myeloperoxidase; xanthine oxidase and catalase enzyme activities; and total sulfhydryls. CONCLUSIONS: Infants with simple respiratory distress syndrome could be segregated from those infants who developed bronchopulmonary dysplasia by the magnitude of the epithelial lining fluid oxyradical inflammation markers. While infants developing bronchopulmonary dysplasia typically exhibited increased concentrations of these markers during the first week of life, those infants with simple respiratory distress syndrome displayed low, uniform, or decreasing values of these markers over this interval. Infants developing bronchopulmonary dysplasia demonstrate an early pulmonary inflammatory response, and one key aspect of this response involves various oxyradical-generating systems.

Validation of risk factors in predicting recoarctation after initially successful balloon angioplasty for native aortic coarctation.

Despite gratifying immediate results, significant recoarctation at follow-up has been observed after balloon angioplasty of native aortic coarctation. Risk factors for such recurrences have been identified in one of our previous studies. In this study we examined the value of these risk factors in the prediction of recoarctation after balloon angioplasty. During a 6-year period ending in September 1993, 37 infants and children aged 2 days to 15 years underwent balloon angioplasty of native coarctation with resultant reduction in coarctation gradient from 45 +/- 17 (mean +/- SD) to 12 +/- 9 mm Hg (p < 0.001). On the basis of results of 4- to 48-month follow-up catheterization in 30 children, recoarctation developed in 8 (27%) children. The data from these patients were scrutinized to identify subjects that exhibited the previously determined risk factors, namely age < 12 months, size of aortic isthmus less than two thirds the size of the ascending aorta, coarcted aortic segment < 3.5 mm before angioplasty, and coarcted segment < 6.0 mm after angioplasty. Then, thirty variables (Table I) were examined by logistic regression to identify factors responsible for recoarctation; the data from both study groups were combined for this analysis. The prevalence of recoarctation in each subgroup with a given number of risk factors is similar (p < 0.1) to that observed in the initial study identifying the risk factors. In addition, logistic regression identified age (p = 0.014), size of isthmus (p = 0.006), preangioplasty coarcted segment (p = 0.01), and postangioplasty coarcted segment (p = 0.006) as risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

A model alcohol and other drug use curriculum for pediatric residents.

While alcohol and other drug (AOD) use is a major health risk for adolescents in the United States, there is a paucity of AOD training for pediatric residents. In 1991-92, the University of Wisconsin Medical School developed an experiential, community-based AOD curriculum for pediatrics residents. The curriculum included resident participation in a community-based AOD adolescent assessment and intervention program, interactive didactic sessions, role-playing practice, and interviewing skills sessions. The residents who participated in the curriculum (n = 25) were compared with a control group (n = 19). Evaluation included pre- and post-curriculum written tests, objective structured clinical examinations, and residents' ratings of the curriculum components. The residents who participated showed significant gains in AOD knowledge, utilization of screening techniques, and clinical management skills as compared with the controls. The residents gave positive ratings to all curriculum components. This well-received curriculum can serve as a national model both for AOD education in pediatrics and for curriculum development in other areas of adolescent health-risk-taking.

Oral supplementation with a high-fat, high-energy product improves nutritional status and alters serum lipids in patients with cystic fibrosis.

OBJECTIVE: To assess the tolerance and acceptability of a nutrition supplement in patients with cystic fibrosis (CF), to monitor changes in dietary intake, and to evaluate nutritional status. DESIGN: Subjects were their own controls for this 3-month, prospective, open study. Acceptability and tolerance questionnaires and 3-day food records were completed at baseline and monthly intervals. Compliance and nutritional status were also assessed. SETTING: This study was conducted at the University of Wisconsin Hospital and Clinics Cystic Fibrosis Center, Madison. SUBJECTS: Patients with CF older than 4 years of age were recruited during clinic or hospital visits if they met specific weight or growth criteria (n = 19). INTERVENTION: Subjects were asked to consume the supplement at a maximum of 30% their estimated daily energy requirements. MAIN OUTCOME MEASURES: Responses to acceptability ratings of and tolerance questions about the supplement were obtained along with anthropometric data and biochemical measurements of serum albumin, plasma retinol, alpha-tocopherol, and fatty acid levels. STATISTICAL ANALYSES PERFORMED: Data were analyzed using Minitab and Statistical Analysis Software. Paired and unpaired t tests and nonparametric sign tests were used, as well as regression and Pearson correlations. A significance level of .05 was used for all tests. RESULTS: All subjects tolerated the supplement, although 12 reported mild symptoms of fullness, nausea, and/or bloating, which were resolved when intake was distributed throughout the day. Mean compliance was 69% of recommended intake. Weight gain in children was strongly correlated with compliance (r = .98). Linoleic acid intake increased significantly (P = .0003) as did plasma linoleic acid in the phospholipid fraction (P = .03). CONCLUSION: The supplement studied would be a beneficial addition to the supplementation choices available to patients with CF.

Echocardiographic predictors of success of catheter closure of atrial septal defect with the buttoned device.

Transcatheter occlusion of ostium secundum atrial septal defects (ASD) with the buttoned device has been shown to be feasible, effective, and safe. The final decision to implant the device is largely based on the balloon sizing of the ASD during cardiac catheterization. Only subjective criteria of ASD size and the septal rims on echocardiography have been used before catheterization, balloon sizing, and transcatheter occlusion. The purpose of this study was to determine whether objective echo criteria could be developed to predict successful occlusion of the ASD. During a 46-month period ending August 1992, 29 children with secundum ASD were evaluated for transcatheter occlusion. The device was successfully implanted in 15 (group A); in the remaining 14 children, this procedure could not be performed (group B). Preocclusion echos were analyzed by independent investigators who had no knowledge of outcome of the procedure. Echo parameters studied included size of ASD, length of atrial septum (LAS), and size of the superior and inferior rims in precordial and subcostal views and maximum jet width by color flow mapping. From these measurements several ratios were derived, and the data were compared. A smaller (p < 0.05) ASD was present in the group of patients with successful implantation of the device; LAS was similar (p > 0.1) in both groups. A lower (p < 0.05) ratio of ASD to LAS and a higher (p < 0.05) ratio of the superior and inferior septal rims to ASD were associated with the group of patients with successful implantation of the device.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical versus balloon therapy for aortic coarctation in infants < or = 3 months old.

OBJECTIVES: This study compared the efficacy and safety of balloon angioplasty with surgical correction of native aortic coarctation in infants < or = 3 months old. BACKGROUND: There is a controversy with regard to the role of balloon angioplasty in the treatment of aortic coarctation, especially in young infants. METHODS: Data from 29 infants < or = 3 months old undergoing therapy for aortic coarctation during the decade ending 1992 were analyzed. Fourteen infants underwent surgery, and 15 had balloon angioplasty. The sole criterion for allotment to the balloon group was the availability of an interventional cardiologist at the time of presentation of the infant. RESULTS: The surgical and balloon groups were comparable (p > 0.1) with regard to age (27 +/- 35 [mean +/- SD] vs. 29 +/- 27 days), weight (3.5 +/- 0.9 vs. 3.8 +/- 1.0 kg) and prevalence (7 of 14 vs. 8 of 15) and type of associated defects. Operative (1 of 14 vs. 1 of 15) and late (3 of 13 vs. 3 of 14) mortality, immediate gradient relief (36 +/- 25 to 10 +/- 9 mm Hg vs. 41 +/- 14 to 6 +/- 6 mm Hg) and follow-up gradient (27 +/- 27 vs. 24 +/- 19 mm Hg) were similar (p > 0.1). Infants with a gradient > 20 mm Hg at follow-up (6 of 13 vs. 7 of 14) and need for reintervention (6 of 13 vs. 7 of 14) were also similar (p > 0.1) in both groups. Duration of hospital stay during the first intervention was higher (p < 0.05) in the surgical (32 +/- 37 days) than the balloon (7 +/- 6 days) group. Similarly, duration of endotracheal intubation and mechanical ventilation was longer (p < 0.05) in the surgical (12 +/- 16 days) than the balloon (2 +/- 3 days) group. Complications after surgical intervention (0.86 events/patient) were higher (p < 0.01) than those seen after balloon angioplasty (0.27 events/patient). However, the lack of significant differences observed for mortality rates and residual gradients may be due to low statistical power to detect differences (16% to 49%), implying that this may be due to either actual lack of statistical difference or small sample size. CONCLUSIONS: The data indicate that the degree of relief from aortic coarctation and the frequency with which reintervention is needed are similar in both groups. However, the morbidity and complication rates are lower with balloon than with surgical therapy. These data suggest that balloon angioplasty may be an acceptable alternative to surgical correction in the treatment of symptomatic aortic coarctation in infants < or = 3 months old.