Lower cognitive performance of older football players possessing apolipoprotein E epsilon4.
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Aging↗
Biomedical subjects
C Cox
Publications and source records attributed to C Cox.
Violence, alcohol, and completed suicide: a case-control study.
OBJECTIVE: Violent behavior may represent a risk factor for suicide. The authors tested the hypothesis that violent behavior in the last year of life is associated with completed suicide, even after controlling for alcohol use disorders. METHOD: The authors analyzed data from the 1993 National Mortality Followback Survey, a nationally representative survey conducted by telephone interview with decedents' next of kin. Data on 753 victims of suicide were compared with data on 2,115 accident victims. Decedents ranged in age from 20 to 64. Dichotomous measures of violent behavior in the past year and history of alcohol misuse were derived by using the four-item CAGE questionnaire. Multiple logistic regression was used to evaluate the interactions of violent behavior with alcohol misuse, gender, and age, respectively, in predicting suicide versus accidental death. Education and race were included as covariates. RESULTS: Violent behavior in the last year of life was a significant predictor of suicide; the relationship was especially strong in individuals with no history of alcohol misuse, those who were younger, and women. CONCLUSIONS: Violent behavior distinguished suicide victims from accident victims, and this finding is not attributable to alcohol use disorders alone. Given that violent behavior increases the risk of suicide, violence prevention initiatives may serve to decrease the risk of suicide as well.
Accidents↗
Depression and self-reported functional status in older primary care patients.
OBJECTIVE: The authors' goal was to examine whether depression is associated with overreporting of functional disability. METHOD: The subjects were 304 patients 60 years old or older who were recruited from primary care settings. Measures included examiner ratings of depression diagnosis and medical burden and self-reported and examiner-rated functional assessments. Multiple regression techniques were used to determine the independent association of depression with self-reported function after examiner-rated function was added to the analysis as a covariate. RESULTS: Depression diagnosis was associated with poorer self-reported role functioning, whether the patient attributed the disability to physical or emotional causes. Depression was not independently associated with poorer self-reported physical functioning. CONCLUSIONS: Clinicians and researchers should recognize that depression can confound the self-reporting and attribution of functional disability.
Activities of Daily Living↗
Encephalopathy associated with respiratory syncytial virus bronchiolitis.
Respiratory syncytial virus is an extremely common cause of childhood respiratory infections resulting in significant morbidity and mortality. Although apnea is a well-known complication in young infants with respiratory syncytial virus bronchiolitis, the encephalopathy associated with this infection is not well recognized. Our study reveals an incidence of encephalopathy of 1.8% in a total of 487 patients with respiratory syncytial virus bronchiolitis studied over a period of almost 4 years. Seizures were the presenting complication. Based on our study of a cohort of children with respiratory syncytial virus bronchiolitis, we believe that neurologic complications, although relatively uncommon, represent a significant component of this common childhood illness. Furthermore, respiratory syncytial virus has been shown to release several mediators that could directly or indirectly be neurotoxic and induce an encephalopathy associated with the respiratory illness.
Bronchiolitis, Viral↗
Personality correlates of hopelessness in depressed inpatients 50 years of age and older.
In this study we examined the relationship between scores on the Beck Hopelessness Scale and the personality traits that constitute the Five-Factor Model in a sample of 77 depressed inpatients, 50 years of age and older. Multiple regression analyses showed that Hopelessness is related to low Extraversion domain scores, and to specific facets of both Extraversion (low positive emotions) and Neuroticism (low self-consciousness, high impulsiveness). Efforts to tie Hopelessness with the motivational, affective, and interpersonal constructs subsumed under Extraversion are warranted.
Affective Symptoms↗
Altered operant responding for motor reinforcement and the determination of benchmark doses following perinatal exposure to low-level 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Pregnant Holtzman rats were exposed to a single oral dose of 0, 20, 60, or 180 ng/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the 18th day of gestation. Their adult female offspring were trained to respond on a lever for brief opportunities to run in specially designed running wheels. Once they had begun responding on a fixed-ratio 1 (FR1) schedule of reinforcement, the fixed-ratio requirement for lever pressing was increased at five-session intervals to values of FR2, FR5, FR10, FR20, and FR30. We examined vaginal cytology after each behavior session to track estrous cyclicity. Under each of the FR values, perinatal TCDD exposure produced a significant dose-related reduction in the number of earned opportunities to run, the lever response rate, and the total number of revolutions in the wheel. Estrous cyclicity was not affected. Because of the consistent dose-response relationship at all FR values, we used the behavioral data to calculate benchmark doses based on displacements from modeled zero-dose performance of 1% (ED(01)) and 10% (ED(10)), as determined by a quadratic fit to the dose-response function. The mean ED(10) benchmark dose for earned run opportunities was 10.13 ng/kg with a 95% lower bound of 5.77 ng/kg. The corresponding ED(01) was 0.98 ng/kg with a 95% lower bound of 0.83 ng/kg. The mean ED(10) for total wheel revolutions was calculated as 7.32 ng/kg with a 95% lower bound of 5.41 ng/kg. The corresponding ED(01) was 0.71 ng/kg with a 95% lower bound of 0.60. These values should be viewed from the perspective of current human body burdens, whose average value, based on TCDD toxic equivalents, has been calculated as 13 ng/kg.
Administration, Oral↗
Improving adolescent preventive care in community health centers.
OBJECTIVE: To evaluate implementation of the Guidelines for Adolescent Preventive Services (GAPS) in Community and Migrant Health Centers (CMHCs). DESIGN: Before and after comparison of health center policy, clinician and adolescent self-report, and chart reviews in 5 CMHCs. PARTICIPANTS: Eighty-one preintervention and 80 one-year postintervention providers and 318 preintervention and 331 postintervention 14- to 19- year-old adolescent patients being seen for well visits at 5 CMHCs. INTERVENTION: Health center staff were trained to implement GAPS and were provided resource materials, patient questionnaires, and clinician manuals. MAIN OUTCOME MEASURES: Delivery of and receipt of preventive services and perceived access to care. RESULTS: CMHC systems changes were related to stronger leadership commitment to adolescent care. Providers reported high levels of preventive services delivery before and after guideline implementation. After guideline implementation, adolescents reported increases in having discussed prevention content with providers in 19 of 31 content areas, including increased discussion of physical or sexual abuse (10% before to 22% after), sexual orientation (13% to 27%), fighting (6% to 21%), peer relations (37% to 52%), suicide (7% to 22%), eating disorders (11% to 28%), weapons (5% to 22%), depression (16% to 34%), smokeless tobacco (10% to 29%), and immunizations (19% to 48%). Adolescents were also more likely to report knowing where to get reproductive or mental health services and were more likely to have received health education materials. Implementation also increased documentation of recommended screening and counseling in 51 of 79 specific content areas assessed in chart reviews. CONCLUSION: Implementing GAPS increased the receipt of preventive services at these health centers. Adolescents received more comprehensive screening and counseling, more health education materials, and had greater access to care after implementation. GAPS implementation may help improve the quality of care for adolescents.
Adolescent↗
Depression, medical illness, and interleukin-1beta in older cardiac patients.
OBJECTIVE: A model has been proposed in which atherosclerosis contributes to depression in later life by the effects of cytokines on central monoamine systems. We collected pilot data to test the hypothesis that interleukin-1beta (IL-1beta) is associated with depression in a cardiac patient group. METHOD: Thirty-seven subjects completed research evaluations that included depression diagnosis (Structured Clinical Interview for DSM-III-R), depressive symptom severity (Hamilton Rating Scale for Depression), medical illness burden (Cumulative Illness Rating Scale), and serum IL-1beta level measured by enzyme linked immunosorbent assay. RESULTS: Serum IL-1beta level was not significantly associated with depressive symptom severity or depression diagnosis, whether or not controlled for medical illness burden, age, and gender. IL-1beta level was significantly correlated with medical illness burden. CONCLUSIONS: We did not confirm our study hypothesis. The correlation of IL-1beta level with medical illness burden likely reflects its release as part of the "sickness response" in a wide variety of disease states. Further research using a larger sample size and a non-cardiac comparison group is warranted.
Aged↗
Placebo-controlled study of divalproex sodium for agitation in dementia.
The authors assessed the efficacy, tolerability, and safety of divalproex sodium for the treatment of agitation associated with dementia in a 6-week, randomized study of 56 nursing home patients with agitation and dementia treated with either placebo or individualized doses of divalproex sodium. Participants were blinded to treatment except for a physician-monitor and a pharmacist. When several covariates were taken into account, the drug/placebo difference in Brief Psychiatric Rating Scale Agitation scores became statistically significant (P=0.05). Sixty-eight percent of patients on divalproex were rated as showing reduced agitation on the Clinical Global Impression scale, vs. 52% on placebo (P=0.06 in the adjusted analysis). Side effects occurred in 68% of the divalproex group vs. 33% of the placebo group (P=0.03) and were generally rated as mild. This placebo-controlled study, despite some limitations, suggests possible short-term efficacy, tolerability, and safety of divalproex for agitation in dementia and supports further placebo-controlled studies.
Aged↗
Attitudes and beliefs about exercise among elderly African Americans in an urban community.
Older African Americans are less likely to exercise compared with their white counterparts. Few studies have examined the facilitating factors and barriers to exercise among older African Americans living in urban communities. This study represented the first phase of a program to develop an exercise intervention in an urban community. Qualitative research was conducted to identify culturally determined attitudes that could be useful in designing an effective exercise program. Five focus groups involving 38 persons from a variety of settings were facilitated by trained professionals. Transcripts were analyzed to identify themes and contrasts among group participants. Contrary to the expectations of the investigative team, focus-group participants: (1) uniformly preferred group exercises compared with exercising at home, (2) rejected walking as a feasible option because of safety concerns, and (3) expressed limited interest in using weights or Eastern exercises such as Tai Chi. Concepts and goals of exercise differed according to the physical capabilities of the participants. The analysis of these focus-group discussions provided valuable insights with regard to the development of our community-based exercise-intervention protocol. These findings may be important in designing effective exercise programs for older African Americans in urban settings.
Black or African American↗
Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia.
We used flow cytometry to quantify minimal residual disease (MRD) in 56 patients with acute myeloid leukemia (AML) expressing a leukemia-associated phenotype. Thirty-four patients aged 18 to 60 years were entered into the AML-10 protocol (induction, consolidation, and autologous stem-cell transplantation [ASCT]), whereas 22 patients older than 60 years received the AML-13 protocol (induction, consolidation, and consolidation II). After induction, the level of MRD that was best associated with treatment outcome was 4.5 x 10(-4) residual leukemic cells. However, the outcome in patients with at least 4.5 x 10(-4) cells (n = 26) was not significantly different from that in patients with fewer leukemic cells (n = 30); there were 15 (58%) relapses in the first group and 12 (40%) relapses in the second. After consolidation, the most predictive MRD cutoff value was 3.5 x 10(-4) cells: 22 patients had an MRD level of 3.5 x 10(-4) cells or higher and 17 (77%) of these patients had relapse, compared with 5 of 29 patients (17%) with lower MRD levels (P <.001). An MRD level of 3.5 x 10(-4) cells or higher after consolidation was significantly correlated with poor or intermediate-risk cytogenetic findings, a multidrug resistance 1 (MDR1) phenotype, short duration of overall survival, and short duration of relapse-free survival (P =.014,.031,.00022, and.00014, respectively). In multivariate analysis, this MRD status was significantly associated with a high frequency of relapse (P <.001) and a short duration of overall (P =.025) and relapse-free survival (P =.007). ASCT did not alter the prognostic effect of high MRD levels after consolidation: the relapse rate after transplantation was 70%. Thus, we found that an MRD level of 3.5 x 10(-4) cells or higher at the end of consolidation strongly predicts relapse and is significantly associated with an MDR1 phenotype and intermediate or unfavorable cytogenetic findings. (Blood. 2000;96:3948-3952)
Actuarial Analysis↗
Synthesis of the functionalized tricyclic core of lactonamycin by oxidative dearomatization.
[reaction: see text] We report in this Letter a synthesis of the densely oxygenated CDEF ring system (27) corresponding to that found in the recently discovered antibiotic lactonamycin. The key steps in the synthesis consist of an intramolecular Wessely oxidative lactonization of acid 18, followed by a hydroxyl-directed epoxidation of enol ether 21.
Anti-Bacterial Agents↗
Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy.
BACKGROUND: The childhood-onset cerebral form of X-linked adrenoleukodystrophy, a demyelinating disorder of the central nervous system, leads to a vegetative state and death within 3-5 years once clinical symptoms are detectable. The hypothesis to be tested was whether bone-marrow transplantation can over an extended period of time halt the inexorable progressive demyelination and neurological deterioration. METHODS: 12 patients with childhood onset of cerebral X-linked adrenoleukodystrophy have been followed for 5-10 years after bone-marrow transplantation. Magnetic resonance imaging (MRI), neurological, neuropsychological, electrophysiological, and plasma very-long-chain fatty acid (VLCFA) measurements were used to evaluate the effect of this treatment. FINDINGS: MRI showed complete reversal of abnormalities in two patients and improvement in one. One patient showed no change from baseline to last follow-up. All eight patients who showed an initial period of continued demyelination stabilised and remained unchanged thereafter. Motor function remained normal or improved after bone-marrow transplantation in ten patients. Verbal intelligence remained within the normal range for 11 patients. Performance (non-verbal) abilities were improved or were stable in seven patients. Decline in performance abilities followed by stability occurred in five patients. Plasma VLCFA concentrations decreased by 55% and remained slightly above the upper limits of normal. INTERPRETATION: 5-10-year follow-up of 12 patients with childhood-onset cerebral X-linked adrenoleukodystrophy shows the long-term beneficial effect of bone marrow transplantation when the procedure is done at an early stage of the disease.
Adrenoleukodystrophy↗
Incidental discovery of pelvic cholelithiasis on diagnostic laparoscopy.
Laparoscopic cholecystectomy, although a safe technique for removal of the gallbladder, is associated with surgery-related complications. We report a complication caused by this procedure in a young woman, in whom a diagnostic laparoscopy led to the incidental finding of retained gallstones in the pelvis. A 30-year-old woman underwent diagnostic laparoscopy for exclusion of an ectopic pregnancy. She had undergone laparoscopic cholecystectomy 3 years before presentation. Diagnostic laparoscopy ruled out ectopic pregnancy, but yellow nodules were noted in her pelvis. Removal of these nodules was not attempted because of their close proximity to the ureter. A biopsy of these lesions confirmed amorphous material suggestive of gall stones. The finding was documented in the case notes and explained to the patient after the procedure.
Adult↗
Breast cancer screening in childhood cancer survivors.
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Adult↗
Twenty-seven years studying the human neurotoxicity of methylmercury exposure.
Research at the University of Rochester (U of R) has been focused on mercury for nearly half a century. Initially studies focused on dosimetry, especially the accuracy of measuring exposure, and experimental work with animal models. Clinical studies in human populations started when the U of R mercury group was asked to assist with dosimetry in the Iraq epidemic of 1971-1972. Initial clinical studies described the effects of methylmercury (MeHg) poisoning on adults and children. A dose-response curve for prenatal exposure was determined and it suggested that relatively low exposures might be harmful to the fetus. Since most human exposure to MeHg is dietary from fish consumption, these theoretical dangers had far-reaching implications. After Iraq, the Rochester team pursued exposure from fish consumption in both adults and children. Populations with high fish consumption were identified in Samoa and Peru for studying adults and in Peru and the Seychelles islands for studying children. The possible health threat to the fetus from maternal fish consumption quickly became the focus of research efforts. This paper reviews the Rochester experience in studying human exposure to MeHg from fish consumption.
Adult↗
Association between methylmercury exposure from fish consumption and child development at five and a half years of age in the Seychelles Child Development Study: an evaluation of nonlinear relationships.
Studies to date of the developmental effects of pre- and postnatal methylmercury exposure from fish consumption in the Seychelles Islands, using linear regression models for analysis, have not shown adverse effects on neurodevelopmental test scores. In this study we evaluated whether nonlinear effects of methylmercury exposure were present, using scores on six tests administered to cohort children in the Seychelles Child Development Study at 66 months of age. Prenatal exposure was determined by measuring mercury in a segment of maternal scalp hair representing growth during pregnancy. Postnatal exposure was measured in a segment of the child's hair taken at 66-months of age. Generalized additive models (GAMs), which make no assumptions about the functional form of the relationship between exposure and test score, were used in the analysis. GAMs similar to the original linear regression models were used to reanalyze the six primary developmental endpoints from the 66-month test battery. Small nonlinearities were identified in the relationships between prenatal exposure and the Preschool Language Scale (PLS) Total score and Child Behavior Check List (CBCL) and between postnatal exposure and the McCarthy General Cognitive Index (GCI) test scores. The effects are best described graphically but can be summarized by computing the change in the predicted test score from 0 to either 10 or 15 ppm and then above this point. For the PLS the trend involved a decline of 0.8 points between 0 and 10 ppm followed by an increase (representing improvement) of 1.3 points above 10 ppm. For the CBCL there was an increase of 1 point from 0 to 15 ppm, and then a decline (improvement) of 4 points above 15 ppm. The GCI increased by 1.8 points through 10 ppm and then declined 3.2 points (representing worse performance) above 10 ppm. These results are not entirely consistent. Two of the trends involve what appear to be beneficial effects of prenatal exposure. The one possibly adverse trend involves postnatal exposure. In every case the trend changes direction, so that an effect in one direction is followed by an effect in the opposite direction. Because of the descriptive nature of GAMs it is difficult to provide a precise level of statistical significance for the estimated trends. Certainly above 10 ppm there is less data and trends above this level are estimated less precisely. Overall there was no clear evidence for consistent (across the entire range of exposure levels) adverse effects of exposure on the six developmental outcomes. Further nonlinear modeling of these data may be appropriate, but there is also the risk of fitting complex models without a clear biological rationale.
Animals↗
Neurodevelopmental outcomes of Seychellois children from the pilot cohort at 108 months following prenatal exposure to methylmercury from a maternal fish diet.
The Seychelles Child Development Study has been unable to confirm any relationship between maternal exposure to MeHg during pregnancy and adverse developmental outcomes. In this report, 87 children from a pilot cohort were evaluated at 9 years of age. Each child was given a battery testing specific cognitive, visual motor, and motor skills using standardized psychometric and neuro-psychological tests. The results indicated no adverse association between maternal MeHg exposure and any developmental outcome measure. For three endpoints (Boston Naming Test and two tests of visual motor coordination), enhanced performance in males was associated with increasing prenatal MeHg exposure. A secondary analysis including both prenatal MeHg and postnatal MeHg exposure was done even though we lacked postnatal hair for about 35% of the cohort. The results of the secondary analysis mirrored the outcomes of the primary analysis regarding prenatal exposure but were less robust. The results of this study are consistent with earlier findings from the 66-month evaluations of the SCDS Main cohort. Since MeHg is neurotoxic, this effect is likely due to other factors associated with consumption of fish.
Adult↗