Changes in the activity of metabolic and non-metabolic liver enzymes in rats following co-administration of gossypol with phenobarbital.
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Animals↗
Biomedical subjects
C Cox
Publications and source records attributed to C Cox.
A prospective evaluation of cognitive decline in early Huntington's disease: functional and radiographic correlates.
We examined prospectively the relationship between progressive disability in Huntington's disease (HD) and concomitant alterations in neuropsychological functioning and brain imaging indices in a cohort of 60 patients who were enrolled and followed for 30 to 42 months in a controlled clinical trial. Standardized measures of functional capacity and neuropsychological performance were collected, and CT was performed, at regular intervals every 6 to 12 months. Psychomotor skills showed the most significant and consistent decline among the cognitive functions assessed. Memory disturbances were already present at the time of enrollment, but memory did not deteriorate until patients reached advanced stages. Other cognitive operations, such as visual construction and semantic knowledge, manifested small and variable changes over time. CT indices of striatal atrophy correlated only with changes in psychomotor function, while the CT index of frontal atrophy weakly predicted memory and semantic knowledge scores at 42 months. These results confirmed earlier cross-sectional findings and extended our knowledge of the evolution of cognitive dysfunction in HD.
Adult↗
A functional analysis of the age-related degeneration in the Fischer 344 rat.
We have previously described how the expression of photoreceptor cell degeneration in the Fischer 344 rat is affected by age, retinal topography, and gender. Degeneration in the central and equatorial regions progresses linearly with age throughout the life span of the animal, while the periphery of the male is subject to sudden and dramatic losses of cells in the superior hemisphere after 12 months and in the inferior hemisphere after 18 months of age. The purpose of the present study was to determine how this degeneration affected retinal function and visual ability in the male Fischer 344 from 3 to 24 months of age. Functional testing included the electroretinogram (ERG, measuring both a-wave and b-wave amplitudes and implicit times) and the behavioral method of startle reflex modification (RM, which measures the degree to which a light flash inhibits the response to an immediately subsequent loud noise). All of the functional measures showed a decline with age, but varied in their time course. ERG amplitudes showed a linear decline in amplitude over the entire age range. In contrast, the implicit times of the ERG waves and the degree to which the light flash inhibited the startle reaction both showed a slight maturation in function (faster implicit times and greater inhibition) from 8 or 12 months of age. After 18 months of age, the implicit time showed a significant increase and the startle response showed a significant decrease. This study shows how visual function correlates with the histopathological changes seen in age-related retinal degeneration.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
CD7 expression in acute myeloid leukemia.
The clinical significance of the expression of CD7 antigen on the blasts of 207 consecutive patients with de novo acute myeloid leukemia (AML) was evaluated. For this purpose, fifty-three CD7+ patients (23 females and 30 males; mean age 52 years) were analyzed and classified into the following subtypes according to French-American-British (FAB) classification: 7 M0, 13 M1, 9 M2, 1 M3, 9 M4, 14 M5. Immunophenotypic studies were carried out by flow cytometry and blast cells were selected on the basis of forward light scatter gating and pan-myeloid marker, either CD13 or CD33. All the CD7+ patients were negative for surface CD3 and T-cell-receptor (TCR) molecules. We found no correlation between CD7 expression and sex, age, hepatosplenomegaly and/or central nervous system involvement. The immaturity of CD7+ leukemic cells was supported by the high expression of CD34 (P = 0.001). CD7 positivity was significantly associated with a white blood cell count (WBC) greater than 100 x 10(9)/L (P = 0.003). P-Glycoprotein (P-170) expression was also evaluated in 135 patients by a flow-cytometric assay: there was a close relationship between CD7 and P-170 positivity (P < 0.001). For remission induction, all patients received therapeutic regimens routinely used for AML. The complete remission (CR) rate was significantly lower in CD7+ cases (32% vs 74%, P = 0.001). The overall survival and disease free survival rate of CD7+ AML was lower than those of CD7- patients (P < 0.001 and = 0.002, respectively). CD7+ AML with coexpression of CD14 had a particularly unfavourable response and prognosis in comparison with CD7+ patients without CD14.(ABSTRACT TRUNCATED AT 250 WORDS)
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Is there a con in your contract?
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Contract Services↗
The use of recombinant human dornase alfa in CF.
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Child↗
Effects of coconut oil, butter, and safflower oil on lipids and lipoproteins in persons with moderately elevated cholesterol levels.
The physiological effects of coconut oil, butter, and safflower oil on lipids and lipoproteins have been compared in moderately hypercholesterolemic individuals. Twenty eight participants (13 men, 15 women) followed three 6-week experimental diets of similar macronutrient distribution with the different test fats providing 50% total dietary fat. Total cholesterol and low density lipoprotein cholesterol were significantly higher (P < 0.001) on the diet containing butter [6.8 +/- 0.9, 4.5 +/- 0.8 mmol/l] (mean +/- SD), respectively than on the coconut oil diet (6.4 +/- 0.8; 4.2 +/- 0.7 mmol/l) when levels were significantly higher (P < 0.01) than on the safflower diet (6.1 +/- 0.8; 3.9 +/- 0.7 mmol/l). Findings with regard to the other measures of lipids and lipoproteins were less consistent. Apolipoprotein A-I was significantly higher on coconut oil (157 +/- 17 mg/dl) and on butter (141 +/- 23 mg/dl) than on safflower oil (132 +/- 22 mg/dl). Apolipoprotein B was also higher on butter (86 +/- 20 mg/dl) and coconut oil (91 +/- 32 mg/dl) than on safflower oil (77 +/- 19 mg/dl). However gender differences were apparent. In the group as a whole, high density lipoprotein did not differ significantly on the three diets whereas levels in women on the butter and coconut oil diet were significantly higher than on the safflower oil diet. Triacylglycerol was higher on the butter diet than on the safflower and coconut oil diets but the difference only reached statistical significance in women. Cholesteryl ester transfer activity was significantly higher on butter than safflower oil in the group as a whole and in women.(ABSTRACT TRUNCATED AT 250 WORDS)
Butter↗
Comparing the experiences of black and white caregivers of dementia patients.
Caregivers' capacities to cope with dementia patients are severely challenged as demands for care and impairment levels concomitantly increase. Consequently, the experience can be extremely stressful because it affects many areas of the caregiver's life. Using a conceptual stress development model that treats informal supports and competency as potential mediators, the outcomes of caregiving were examined in samples of black and white caregivers. A perceived lack of informal supports and a sense of incompetency exacerbated stress among the black caregivers but had no effects among the white caregivers. White caregivers were predominantly affected by the impairment of the patient. Cultural differences in caregiver expectations that influence needs are proposed as an explanation for these findings. To be most effective in reducing caregiver stress, social workers must be sensitive to the diversity of values and expectations that can affect the experiences of these individuals.
Black or African American↗
Asymptotic confidence bands for generalized nonlinear regression models.
Asymptotic confidence bands for generalized nonlinear regression models are developed. These are based on a combination of the S method of Scheffe, together with the delta method which is used to approximate the mean function by a linear combination of the parameters. The approach can be used in any situation where large sample theory can be applied to yield asymptotically normal estimates of the parameters, together with a consistent estimate of the large sample covariance matrix. Alternative formulations for various special cases allow the use of restricted range bands. A number of examples are given, including a pharmacokinetic model, a logit model with a background response rate, and a parametric survival model.
Administration, Inhalation↗
Stability of bladder function two years following simultaneous pancreas-kidney transplantation.
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Adult↗
School-age follow-up of a single-dose prophylactic surfactant cohort.
This study reports the school-age developmental and health status of a preventilatory surfactant cohort. The sample consisted of 39 surviving subjects (21 experimental and 18 controls) born at 25 to 29 weeks gestation who were studied at 6 and 12 months and 5 to 7 years of age. At 6- and 12-month follow-ups, the cohort was functioning close to the population normative mean. Although cognitive and motor assessments at school age also showed no group differences, 8 of 19 (42%) in the surfactant group and 9 of 17 (53%) in the normal saline group attained a McCarthy General Cognitive Index score of < or = 84 (abnormal range). On the Connors' Parental Questionnaire, both groups scored high on the Learning Disability Subscale. The surviving cohort at 5 to 7 years had no identified long-term sequelae due to surfactant therapy, yet both groups were at risk for neurodevelopmental and educational morbidity.
Birth Weight↗
Hypocellular acute myeloid leukemia: the Rochester (New York) experience.
Fourteen patients with hypocellular acute leukemia (HAL) were reviewed. The median age was 72 years, with an equal male-to-female ratio. Severe granulocytopenia with marrow hypocellularity and increased marrow blasts and absence of physical findings were common features. The median peripheral blood blast count was 2%. All except 3 cases of erythroleukemia had marrow blast count that exceeded 30% of all nucleated marrow cells. All cases were classifiable with the FAB criteria. FAB classification revealed a preponderance of the M1 category followed by M2 and M6 types. The majority of blasts were type I and the median myeloperoxidase positivity was 14%. Immunophenotyping of bone marrow cells by flow cytometry in 9 cases showed expression of myeloid antigens (CD13, CD33); 6 cases also expressed CD34 antigen. Significant dysplasia involving erythroid and megakaryocytic lineages was seen in most of the cases. Trilineage dysplasia was observed in 5 cases. Median survival of the entire group was 10.5 months. Eleven patients underwent induction therapy consisting of daunorubicin and cytosine arabinoside +/- 6 thioguanine; 8 patients achieved complete remission (72.6%). Remission duration was 14.5 months. Three patients (27.4%) died secondary to infections during induction therapy. Higher frequencies of trilineage dysplasia and FAB M6 type together with low percentage of peripheral blasts and presence of antecedent hematologic disorders suggest that some of these cases might represent the hypocellular form of acute myeloid leukemia with trilineage dysplasia.
Adult↗
The Seychelles study of fetal methylmercury exposure and child development: introduction.
Studies of outbreaks of methylmercury poisoning in Japan and Iraq from consumption of methylmercury (MeHg)-contaminated fish or bread proved that brain was the target organ, the toxic effects were dose-related, and the fetal brain was especially susceptible. Previous population studies suggested that a 5% risk of minimal fetal effect may be associated with a maternal hair mercury concentration during pregnancy of 10-20 ppm (mu g/g), a level that can be readily achieved by frequent consumers of fish. However, these studies had limitations, and as a result no definite conclusion concerning the lowest effect level could be reached and the question of a possible hazard to public health remained unanswered. There was a clear need for a more definitive study that would be prospective, involve a large enough cohort for risk analysis and adhere to accepted epidemiological principles. An appropriate site for such a study is the Republic of Seychelles, a location that afforded successful collaboration between the Seychelles Ministry of Health and faculty of the University of Rochester. A pilot study of 804 infant-mother pairs was followed by a main study of 779 mother-infant pairs. In the pilot study children were examined once between 5 and 109 weeks of age; in the main study they are being evaluated longitudinally starting at 6 1/2 months of age. This paper introduces both the pilot and main studies, describes their design, and summarizes the findings through 6 1/2 months of age. When the Seychelles study is completed, the analyses will provide a database for those nations that choose to regulate their citizens' fish consumption and/or provide dietary education.
Child↗
The Seychelles child development study on neurodevelopmental outcomes in children following in utero exposure to methylmercury from a maternal fish diet: background and demographics.
Studies in Japan showed that fetal exposure to methylmercury during pregnancy can lead to severe neurodevelopmental changes in the infant while the mother suffers no or minimal effects. Fish contains methylmercury and there is concern that adverse neurodevelopmental effects may occur secondary to low-dose methylmercury exposure in utero from maternal fish consumption. The Seychelles Child Development Study has been examining the relationship between prenatal exposure to methylmercury during pregnancy in a population with high fish consumption and the neurodevelopmental outcome. Over 80% of Seychellois women eat fish daily, and the median fish meals per week during pregnancy is 12. Following a pilot study of 804 mother-infant pairs, a longitudinal main study of another 779 mother-infant pairs was initiated. The main study design includes collection of educational and socioeconomic information about the family and periodic standardized neurodevelopmental tests at specific ages from 6 1/2 months to 66 months of age. In this paper, we describe the background to the studies and give demographic characteristics of both the pilot and main study cohorts.
Age Distribution↗
The biological monitoring of mercury in the Seychelles study.
The concentration of total mercury in maternal hair during pregnancy was used as a measure of fetal exposure to methylmercury in a study of a fish-eating population in the Seychelles islands. A segment of scalp hair approximately 10 centimeters in length, that grew during pregnancy, was selected for measurement. Total and inorganic mercury were measured by cold vapor atomic absorption (CVAA) using the Magos reagents (Magos, 1971). For comparative purposes, total mercury was measured by X-ray Fluorescent Spectrometry (XRF) and methylmercury by gas chromatography/atomic fluorescence detection (GC/AFD) in a subset of hair samples. A limited number of fish samples were also analyzed. Extensive interlaboratory testing was conducted to ensure accuracy of the mercury measurements. Concentrations of organic mercury calculated as the difference between total and inorganic mercury as measured by CVAA agreed with those of methylmercury measured on the same samples of hair by GC/AFD. Methylmercury measured by GC/AFD and organic mercury measured by CVAA accounted for over 80% of the total mercury in hair and over 90% of the total mercury in fish muscle. To test the accuracy of recapitulation by hair sampling, hair samples were collected from mothers at the time of delivery and 6 months later. The segment corresponding to the pregnancy term was selected for measurement assuming a hair growth rate of 1.1 cm/month. Results from both samples were in close agreement. As part of both a pilot investigation followed by the main study, maternal hair samples were collected each year from 1986 to 1989 for a total of 1604 samples. The median and mean values for each year's collection fell in the range of 5.9 to 8.2 ppm and exhibited no statistically significant trend with time. The highest recorded concentration was 36 ppm. In hair samples from 654 mothers, the mean concentration of total mercury was compared with the mean concentrations in segments corresponding to each trimester, approximately 3.3 centimeters in length. A high degree of correlation was found between mean levels in each trimester versus the entire pregnancy segment.
Child Development↗
A pilot neurodevelopmental study of Seychellois children following in utero exposure to methylmercury from a maternal fish diet.
It is not known if fetal neurodevelopmental damage occurs in humans at the low-level methylmercury exposure achieved by eating fish. To address this question, a cohort of 804 children in the Republic of Seychelles was identified who had fetal methylmercury exposure from a maternal diet high in oceanic fish. Mercury was determined by measuring the maternal total hair mercury during pregnancy, a standard index of methylmercury exposure. The median fetal mercury exposure was 6.6 ppm. Children were evaluated once between 5 to 109 weeks of age. Testing included the revised Denver Developmental Screening Test (DDST-R) and a neurological examination. The association between maternal hair mercury levels and developmental outcome was evaluated by multiple logistic regression analysis. Covariates for the child included gender, birth weight, one and five-minute Apgar score, age at testing, and medical problems, and, for the mother, age, tobacco and alcohol consumption during pregnancy, and medical problems. An association between fetal mercury exposure and development was found when DDST-R scores of questionable and abnormal were combined, a procedure used by previous investigators. These results should be viewed with caution since the association disappeared when DDST-R scores of questionable were treated in the standard manner as passes.
Animals↗
Neurodevelopmental outcomes of Seychellois children sixty-six months after in utero exposure to methylmercury from a maternal fish diet: pilot study.
The Seychelles Child Development Study (SCDS) is testing the hypothesis that prenatal exposure to low concentrations of methylmercury from a maternal diet high in fish is related to the child's developmental outcome. In this report, 217 children from a pilot cohort were reevaluated at 66 months of age. The evaluation included the McCarthy Scales of Children's Abilities, the Preschool Language Scale, and age-appropriate sub-tests from the Woodcock-Johnson Tests of Achievement. Maternal hair total mercury, measured by cold vapor atomic absorption in a maternal hair segment corresponding to pregnancy, revealed a median exposure of 7.1 ppm. The association between maternal hair mercury levels and neurodevelopmental outcomes at 66 months of age was examined by multiple linear regression analysis with adjustment for important confounding variables. The results indicated that mercury exposure was negatively associated with four endpoints (the McCarthy General Cognitive Index and Perceptual Performance subscale and The Preschool Language Scale Total Language and Auditory Comprehension subscale). After normalizing the data by removal of a small number of outliers or highly influential scores, the mercury effects were no longer significant except for auditory comprehension. These results should be viewed as preliminary and interpreted with caution, since the SCDS main study 66-month evaluations, which are better controlled with more detailed endpoints are being analyzed. This study highlights the difficulties in interpreting epidemiologic studies of this type and the degree to which overall results in multivariate analyses can be influenced by a very small number of cases.
Animals↗
Main neurodevelopmental study of Seychellois children following in utero exposure to methylmercury from a maternal fish diet: outcome at six months.
Methylmercury (MeHg) is a human neurotoxin to which the developing fetal brain is especially sensitive. The lowest dose of MeHg that impairs neurodevelopment in the human fetus is not known. The Seychelles Child Development Study (SCDS) is testing the hypothesis that fetal MeHg exposure from a maternal diet high in oceanic fish is related to child neurodevelopmental outcomes. Fish is the major protein source in the Republic of Seychelles, where a cohort of 779 mother-infant pairs was enrolled in a prospective longitudinal study. Maternal total hair mercury values during pregnancy were determined by cold vapor atomic absorption and ranged from 0.5 ppm to 26.7 ppm with a median of 5.9 ppm. When the children were 6 1/2 months of age, an examiner blinded to the maternal mercury value performed a neurological examination, the Fagan test of visual recognition memory, and the Denver Developmental Screening Test-Revised (DDST-R). On the DDST-R 2% scored other than normal while 3.4% had an overall neurological score other than normal. The Fagan test of visual recognition memory showed a median score of 60.5%, and the Rose attention measure from that test showed a median score of 37.9. The association between fetal mercury exposure and neurodevelopmental endpoints was examined by multiple regression analyses. After adjusting for covariates, no association between the maternal hair mercury level during pregnancy and an adverse neurodevelopmental outcome of the child was identified at 6 1/2 months of age.
Adult↗