Biomedical subjects

C Cox

Publications and source records attributed to C Cox.

At least 271 records · Page 15Linked to original sources

PubMed1995

Neurodevelopmental test selection, administration, and performance in the main Seychelles child development study.

The Seychelles Child Development Study was designed to provide data on normal neurodevelopment of Seychellois children and to examine the relationship of their neurodevelopmental outcomes to in utero fetal exposure to low concentrations of methylmercury from a maternal diet high in fish. This paper outlines the strategies used to select, modify, and field test evaluation tools used in the main longitudinal prospective study of 740 children (95% of the cohort of 779 initially enrolled in 1989). It also gives population statistics and quality assurance data for the tests administered and the evaluation of the home environments.

Child↗

PubMed1995

Longitudinal neurodevelopmental study of Seychellois children following in utero exposure to methylmercury from maternal fish ingestion: outcomes at 19 and 29 months.

UNLABELLED: Despite the importance of defining developmental consequences for humans of in utero exposure to low levels of methylmercury, it is not yet clear if there are postnatal effects in fish-eating populations. The Seychelles Child Development Study (SCDS), now underway in the Republic of Seychelles, is following children to test the hypothesis that prenatal exposure to low concentrations of MeHg through maternal ingestion of fish is related to child development outcomes. In this study, children were evaluated with the Bayley Scales of Infant Development (BSID) at 19 mos. of age (N = 738). The cohort was evaluated again at 29 mos. (N = 736) with the BSID and the Bayley Infant Behavior Record. Mercury exposure determined by cold vapor atomic absorption analysis of maternal hair segments corresponding to pregnancy revealed a median exposure of 5.9 ppm (Range 0.5 - 26.7 ppm). The association between maternal hair mercury concentrations and neurodevelopmental outcomes at 19 and 29 mo. of age was examined by multiple regression analysis with adjustment for confounding variables. RESULTS: BSID Intertester reliability was ascertained by the Kappa statistic and was high. The mean BSID Mental Scale Indexes at both 19 and 29 mo. were comparable to the mean performance of US children. The mean BSID Psychomotor Scale Indexes at 19 and 29 mo. were 2 SD units above US norms, but consistent with previous findings of motoric precocity in children reared in African countries. No effect of mercury was detected on BSID scores at either age. On the Bayley Infant Behavior Record, activity level in boys, but not girls, decreased with increasing mercury exposure. Only one subjective endpoint was correlated with prenatal exposure to mercury. This study may have implications for environmental health policies concerning mercury in fish or fish consumption during pregnancy. Follow-up data are needed to determine if adverse effects occur at older ages and if such effects are determined to be related to mercury.

Adult↗

PubMed1995

An analysis of autopsy brain tissue from infants prenatally exposed to methymercury.

Brains from 32 neonatal autopsies from the Seychelles were examined histologically and analyzed for mercury levels. Six brain regions were sampled: frontal and occipital cortex, temporal cortex with hippocampus, basal ganglia with thalamus, cerebellum, and pons with medulla. Tissue blocks for histology and mercury analysis were taken from opposing faces to provide for correlation of findings. Similar studies were performed on 12 reference neonatal brains from Rochester, New York. No clear-cut developmental abnormality was found, but some brains exhibited low-grade, non-specific destructive changes. Total mercury levels, most of it in the organic form, were elevated in many of the Seychelles specimens. No correlation was demonstrated between mercury levels and degree or type of histologic change. There was considerable variability in total mercury for each anatomic region among the 32 Seychelles cases, as well as from one region to another in individual brains. All values of total mercury were under 300 ppb. Statistical analysis of mean mercury levels for each region demonstrated higher values in deep subcortical nuclei, brain stem, and cerebellum, phylogenetically older parts of the brain. When total mercury concentration of each region was paired with all other areas in the same brain and the paired values plotted for the entire group of brains, high correlations were obtained for all brain pairs, suggesting a strong concentration-dependent relationship between mercury intake and brain content. Analysis of mercury levels in separately dissected blocks of grey and white matter from 12 specimens revealed no significant differences between grey and white. In comparison with other human developmental studies and with experimental developmental studies in animals, where toxicity has been demonstrated with total mercury brain levels above 1,000 ppb, this study found no evidence of toxicity within a range of mercury levels below 300 ppb. Submicroscopic changes, subcellular alterations, subtle disturbances in the unfolding of brain architectonics -- none of these are excluded with methods used in this report. Further studies of threshold effects of MeHg on fetal brain are essential. That approximately half of the mercury resides in glial elements in white matter reinforces the need to focus attention upon glia as well as neurons during development.

Brain↗

PubMed1995

Monitoring methylmercury during pregnancy: maternal hair predicts fetal brain exposure.

Autopsy brains were obtained from infants dying from a variety of causes within a few days of birth in a population exposed to methylmercury in fish. Infant and maternal blood and hair samples were also obtained. The concentration of total mercury in 6 major brain regions were highly correlated with maternal hair levels. This correlation was confirmed by a sequence of comparisons of maternal hair to maternal blood to infant blood and finally to infant brain. The results lend support to the use of maternal hair in assessing fetal exposure to methylmercury in fish-eating populations.

Brain↗

PubMed1995

Summary of the Seychelles child development study on the relationship of fetal methylmercury exposure to neurodevelopment.

The Seychelles Child Development Study is examining the association between fetal methylmercury exposure from a maternal diet high in fish and subsequent child development. The study is double blind and uses maternal hair mercury as the index of fetal exposure. An initial cross-sectional pilot study of 804 infants aged 1 to 25 months suggested that mercury may affect development. A follow up of 217 pilot children at 66 months of age also suggested that neurodevelopmental effects might be present, but the result was dependent on outcomes in a small number of children. On the basis of initial results in the pilot study a prospective, longitudinal main study with more covariates and expanded endpoints was begun on a new cohort of 779 children. No association with neurodevelopment was seen at 6 1/2, 19, or 29 months of age, but there was an inverse relationship at 29 months in boys only between mercury level and activity as judged by the examiner. Adverse neurodevelopmental effects from fetal mercury exposure in the pilot study are highly dependent on how the data are analyzed and no definite effects have been detected through 29 months of age in the main study. In a related study, 32 brains were obtained at autopsy from Seychellois infants. These were examined histologically and analyzed for mercury. No clear histological abnormalities were found. Mercury levels ranged from a background of about 50 ppb up to 300 ppb, and correlated well between brain regions. For 27 brains maternal hair from delivery was available and hair mercury correlated well with brain mercury.

Child Development↗

PubMed1995

Analysis of data on delayed development from the 1971-72 outbreak of methylmercury poisoning in Iraq: assessment of influential points.

In this paper we report additional results from the analysis of dose-response data on delayed development from the outbreak of methylmercury poisoning in rural Iraq during the winter of 1971-72. The discussion is focused on the importance of four influential points for the estimation of the population threshold for the effects of methylmercury. The point is made that while this study was important for establishing a dose-response relationship in humans, the uncertainty in the parameters of this relationship is large, and further human studies are needed.

Child Development↗

PubMed1994

Classification of red blood cells as normal, sickle, or other abnormal, using a single image analysis feature.

Sickle cell anemia is a disease for which there is currently no effective treatment. One method of evaluating clinical status is the counting of cell types based on morphology. There is a need for a rapid, reproducible method, superior to human inspection, for classification of these cells. Quantitative digital-image analysis is being applied to this need. Blood from 24 patients with sickle cell anemia (SS) and SC disease and ten hematologically normal volunteers (AA) was stressed by bubbling with nitrogen. One hundred fifty cells were analyzed from each sickle specimen, and 100 were analyzed from each nonsickle specimen. Expert observers classified each cell as normal (N), sickle (S), or other abnormal (A). Cells were analyzed with a custom, high-resolution image-analysis instrument. A total of 42 features including metric, optical density-derived, and textural features were extracted. The metric feature Form Factor (4 pi Area/Perimeter2) was selected by recursive partitioning analysis as the sole feature needed for segregating cells into the classes of N, A, and S. The agreement of automated classification (using cutpoints determined by recursive partitioning analysis) with a human expert for specimens from individuals with sickle cell anemia was 89% for N-, 73% for A-, and 92% for S-classified cells. For specimens from AA individuals, the agreement was 92% for N and 76% for A. For specimens from individuals with sickle cell anemia, rates of agreement between two human experts were compared and found to be 86% for N, 84% for A, and 80% for S. For specimens from AA individuals, the agreement was 90% for N and 87% for A.

Adolescent↗

PubMed1994

Textural differences between AA and SS blood specimens as detected by image analysis.

High-resolution image analysis was employed in the analysis of round (discoid) erythrocytes from hematologically normal (AA) individuals, AA individuals with nonspecific anemia, individuals with sickle cell trait (AS), individuals with SC disease (SC), and individuals with sickle cell anemia (SS). The shape feature Form Factor (4 pi Area/Perimeter2) was used to select round cells and to exclude sickle and other abnormal cells. Textural features extracted from round cells of SS and SC patients were found to differ from those derived from cells of normal andanemic AA individuals. Two textural features, Standard Deviation of Run Length Matrix Counts and Rotation Moment of the Cooccurrence Matrix, discriminated between patients mean values from AA samples and those from SS samples. The ability of textural features to separate round cells into classes based on genotype suggests that high resolution image analysis may be an effective tool in the study and monitoring of sickle cell disease.

Adolescent↗

PubMed1994

Adrenal weight and morphology in victims of completed suicide.

Several lines of evidence have implicated hypothalamic-pituitary-adrenal (HPA) axis dysfunction in major depression and suicidal behavior. In the present study, the weight and morphology of postmortem adrenal glands were compared between suicide victims and sudden death, nonpsychiatric controls. The mean adrenal weight of the combined left and right glands was significantly higher in the suicide group; this difference was accounted for specifically by increases in left adrenal weight of suicides compared with the control group. There was a positive correlation between adrenal weight and total cortical thickness in both left and right glands, providing direct evidence that increased adrenal weight in suicide victims is due to cortical hypertrophy. The finding of left-right adrenal weight asymmetry in suicides is consistent with the hypothesis of abnormal lateralized input from higher control centers of the HPA axis.

Adolescent↗

PubMed1994

The influences of age, retinal topography, and gender on retinal degeneration in the Fischer 344 rat.

The Fischer 344 (F344) rat is presently the animal of choice for age-related research. The existence of an age-related retinal degeneration was reported previously in the males of this strain, but a gender comparison has not been performed. In this study, histological and morphometric measurements of the retina related to age, retinal topography, and gender were made on 3- to 24-month-old animals. The thicknesses of the outer nuclear layer (ONL) and the photoreceptor layer (PRL) were measured from sagittal sections at six loci. Retinas of both sexes showed steady decline with age in the thicknesses of the ONL and PRL at all locations. An important finding was the presence, after 12 months of age, of a drastically accelerated rate of peripheral retinal degeneration seen only in male subjects. Females showed a less dramatic rate of peripheral degeneration which did not begin until after 18 months of age. In addition, two other forms of retinal degeneration were found--cystoid degeneration was found earlier and more frequently in the male, while a paving-stone type of degeneration was found in both sexes. These two types of lesions were preferentially, but not exclusively found in the peripheral retina. In conclusion, the F344 rat offers a convenient model to study a pattern of retinal degeneration affected by the combination of gender, regional and age-related factors.

Aging↗

PubMed1994

Measurement of quality of life in patients with lung cancer in multicenter trials of new therapies. Psychometric assessment of the Lung Cancer Symptom Scale.

BACKGROUND: This study continued the development and psychometric testing of the Lung Cancer Symptom Scale (LCSS), a disease- and site-specific instrument primarily measuring the physical and functional dimensions of quality of life for individuals with lung cancer. The instrument contains two scales, one for patients and a counterpart for health professionals as observers. METHODS: Feasibility, reliability, construct validity, and criterion-related validity were evaluated with 207 patients with non-small cell lung cancer (NSCLC) from six cancer centers. Within an interview with an observer, patients completed part of a battery of instruments by self-report and were interviewed for the remaining measures. Observers also completed measures after the interview. RESULTS: Feasibility, reliability, and validity were well supported for this lung cancer population. Feasibility was demonstrated by patient and staff compliance in completion at all six cancer centers. Internal consistency was good, with coefficient alphas of 0.82 for the patient scale and 0.75 for the observer scale. Construct validity was supported by 1. contrasted groups approach: regression lines (with 95% confidence bands) were obtained between the Karnofsky performance scale (KPS) and each of the two LCSS scales; 2. as a refinement, relationship testing: significant correlations between the LCSS and KPS for each item (except hemoptysis for the patient scale); and 3. multitrait-multimethod approach: good reliability (alphas ranging from 0.75 to 0.93), good convergent validity for the two LCSS scales (r = 0.77), and a good discriminant validity pattern from the Brief Symptom Inventory (BSI). Criterion-related validity with relevant gold standard measures (American Thoracic Society Questionnaire [ATS] and McGill Pain questionnaire, KPS, Profiles of Mood States [POMS], and Sickness Impact Profile [SIP]) was supported with significant correlations (0.40-0.67 for the LCSS patient scale; 0.54-0.65 for the LCSS observer scale). CONCLUSIONS: These psychometric properties demonstrate that the LCSS patient and observer scales are feasible, reliable, and valid quality of life measures that are ready for research and clinical use with lung cancer populations.

Adult↗

PubMed1994

Analysis of treatment failure in patients with minimally differentiated acute myeloid leukemia (AML-M0).

Reports of treatment of patients with minimally differentiated acute myeloid leukemia (AML-M0) are limited, heterogeneous, and controversial. We verified the prognosis of this subtype by analyzing the results of 189 consecutive patients with de novo AML. Fifteen cases fitting the criteria of AML-M0 were identified. No clinical features distinguished them from other patients with AML. The median age was 61 years (range 27 to 70), with a leukocyte count ranging from 0.6 to 185 x 10(9)/L. In all cases the leukemic cells expressed CD34 and reacted with at least one of the antibodies to early myeloid antigens, ie, CD13, CD33, or myeloperoxidase. Immunophenotypic analysis also showed positivity for CD7 in seven samples and the multidrug-resistance P-glycoprotein (P-170) in six. Cytogenetic analysis was abnormal in 12 of the 13 patients in whom an adequate number of mitoses could be evaluated. No single abnormality prevailed, the most common findings being trisomy 8 (three cases) and aberrations of chromosome 7 (two cases). Antileukemic treatment differed according to age, but for remission induction, all patients received a combination of cytosine arabinoside and an anthracycline or mitoxantrone. The prognosis of patients with AML-M0 was remarkably poor as compared with the other French-American-British subtypes. Whereas the overall rate of complete remission (CR) was 58% with a median survival of 63 weeks, only 6 of the 15 patients with AML-M0 achieved a CR, and the median survival of this group was 16 weeks (range 3 to 39). The major determinant of treatment failure was unresponsiveness to chemotherapy, as only one patient died of infection during the hypoplastic phase. The CR duration of responders was short, ranging from 3 to 22 weeks, and no second remissions were observed. We conclude that conventional combination chemotherapy yields disappointing results in AML-M0. The reason for this may be the convergence of various unfavorable prognostic factors, such as (1) the high incidence of cytogenetic abnormalities; (2) the lack of differentiation features and the expression of immaturity markers such as CD34 and CD7; and (3) the frequent expression of P-170. Nonconventional therapeutic approaches should be developed to alter the prognosis of this form of leukemia.

Adolescent↗

PubMed1994

Quality of life during clinical trials: conceptual model for the Lung Cancer Symptom Scale (LCSS).

To appreciate the full benefits of treatment for lung cancer, especially in trials that fail to show improvements in survival, data recording the quality of life must be captured and refined to produce meaningful information. A conceptual model for quality of life for lung cancer patients was tested to obtain information about the dimensions of the quality-of-life construct for ongoing development and testing of a subjective measure for clinical trials. Using a longitudinal study design, the stability of predictive factors of the physical and functional dimensions of quality of life were examined using regression analysis. A patient-rated quality-of-life measure, the Lung Cancer Symptom Scale (LCSS), was administered to 144 non-small-cell lung cancer patients at baseline, day 29, and day 71 of a chemotherapy trial. The range of explained variance for all three components of the lung cancer model over three assessment points was as follows: symptomatic distress 41%-53%, activity status 48%-52%, and overall quality of life 35%-53%. The three dimensions fluctuated slightly during intervention, but were relatively stable factors across all three times of evaluation. The LCSS model explained nearly half of the variance for quality of life experienced by lung cancer patients during therapy with a new chemotherapeutic agent. These findings provide support that the physical and functional dimensions are important predictors of quality of life for individuals with lung cancer. Meaningful subjective quality-of-life data can be obtained to evaluate an intervention by using a disease- and site-specific quality-of-life measure for individuals with lung cancer, based on a reproducible conceptual model such as the LCSS, which is suitable for serial measurement for the progressive disease of lung cancer.

Activities of Daily Living↗

PubMed1994

Taxol and taxotere in bladder cancer: in vitro activity and urine stability.

In this study the antimicrotubular agents taxol, taxotere, and vinblastine were compared for their ability to inhibit the clonal growth of human bladder tumor cell lines using a soft-agar clonogenic assay. The stability of taxol and taxotere was evaluated by high-performance liquid chromatography over a range of pH in human urine. Both taxol and taxotere were shown to maximally inhibit the clonal growth of human bladder cell lines within 1 h of drug incubation. The most active agent in the panel of tumor lines was taxotere, with 6 of 12 lines being sensitive to the agent at 0.01 microM and all cell lines being sensitive at 0.1 microM. Taxol was active in 1 of 12 lines at 0.01 microM and in 11 of 12 at 0.1 microM. Only 2 of 12 cell lines were sensitive to vinblastine over the 0.01- to 0.1-microM dose range. Taxol and taxotere were found to be stable in human urine for 4 h over a pH range of 5-7. At least 85% of both drugs were present during this period of drug incubation. Our findings suggest that both taxol and taxotere may be clinically useful agents for systemic and intravesical use in bladder cancer.

Antineoplastic Agents, Phytogenic↗

PubMed1994

Bone marrow cellularity in myeloid stem cell disorders: impact of age correction.

We have reviewed the initial diagnostic bone marrow aspirate and biopsy specimens performed on the same date on 92 patients with acute myeloid leukaemia (AML), 100 patients with myelodysplastic syndrome (MDS), 24 patients with chronic granulocytic leukaemia (CGL), 19 patients with polycythemia vera (PV) and essential thrombocythemia (ET). An excellent assessment of cellularity by aspirate and biopsy was found. The estimation of BM cellularity for each group was utilized with and without age adjustment based on normal marrow biopsies. Without correcting the BM cellularity for age it was observed that the median BM cellularity was > 50% in AML, CGL, PV and ET. In contrast, the median BM cellularity was estimated at 40% for MDS. In the age group 70 years and beyond the median BM cellularity was not changed in CGL, PV and ET, and only slightly decreased (35%) in MDS. However, a trend from hypercellularity to normocellularity was observed in patients with AML in this age group. By utilizing anatomic comparisons with normal age the corrected data disclosed that all patients with CGL, PV and ET, 63% of patients with AML and only 35% of patients with MDS had hypercellular BM according to their age, while only two patients with AML and seven patients with MDS were found to be truly hypocellular by age. The optimal cut-off value for definition of hypocellular AML and hypocellular MDS, and differences between MDS and other myeloid stem cell disorders in terms of BM cellularity have been discussed.

Adolescent↗

PubMed1994

8-12 Hz rhythmic oscillations in human motor cortex during two-dimensional arm movements: evidence for representation of kinematic parameters.

Direct cortical recordings were taken from 12 patients with implanted subdural electrode arrays during performance of a 2-dimensional, multi-joint, visually guided arm movement task. Task-related changes in the amplitude of the motor cortex 8-12 Hz surface local field oscillations were evaluated for the encoding of direction and amplitude of movement in the 6 patients in whom no epileptogenic or ECoG background abnormalities were detected over the motor-sensory cortical areas under the recording electrode array. The topography, time of onset and duration of these responses were evaluated in the context of motor cortex somatotopy, as defined by cortical stimulation delivered through the electrode array. Multi-joint arm movements were accompanied by a decrease in the power of the 8-12 Hz frequency components of the ECoG signal. These power changes were spatially distributed over the upper extremity, motor-sensory representation. Movement amplitude influenced the magnitude, duration, and extent of the spatial distribution of ECoG power changes in the 8-12 Hz band. These effects occurred predominantly over cortical areas corresponding to the upper extremity motor-sensory representations. Direction of movement had a weaker influence on the 8-12 Hz frequency components of the ECoG over the upper extremity motor-sensory representations, but influenced the patterns of 8-12 Hz ECoG response on adjacent cortical regions. These results show that the amplitude of surface electrical oscillations generated over the rolandic cortex are correlated with the kinematics of multi-joint arm movements. These changes in the ECoG signal appear to reflect shifts in the functional state of neuronal ensembles involved in the initiation and execution of motor tasks.

Adult↗

PubMed1994

Feeding premature infants while low umbilical artery catheters are in place: a prospective, randomized trial.

OBJECTIVE: The objective of this prospective, randomized clinical trial was to test the hypothesis that there is no difference in the frequency of feeding problems and necrotizing enterocolitis between a group of premature infants who received early enteral feedings while low umbilical artery catheters (LUACs) were in place, and a late group who were not fed until 24 hours after removal of LUACs. PATIENTS AND METHODS: Twenty-nine premature infants (born at 28.5 +/- 3.0 SD weeks of gestational age) who were in stable condition received early enteral feedings at a median of 2 days while a LUAC was in place; 31 infants (born at 28.6 +/- 2.7 SD weeks of gestational age) received late enteral feedings at a median of 5 days of age, 24 hours after the removal of the LUAC. Feeding complications and interventions and nutritional characteristics were recorded prospectively. RESULTS: There were no differences in the baseline perinatal characteristics of the two groups. The incidence of gastric residua and the incidence of abdominal distention were the same in both groups. The early feeding group had significantly fewer percutaneous central venous catheters, evaluations for sepsis, and episodes of receiving nothing by mouth while a gastric suction tube was in place. Infants in the early group received parenteral alimentation-lipid emulsion infusions for a median of 13 days versus 30 days for the late-fed group (p = 0.0028 by Wilcoxon test). There were two cases of necrotizing enterocolitis in the early group versus four cases in the late group. CONCLUSIONS: Premature infants in stable condition who receive enteral feedings while LUACs are in place do not have an increased incidence of feeding problems compared with infants who do not receive enteral feedings until 24 hours after removal of LUACs.

Catheterization, Peripheral↗

PubMed1994

Prevention of central venous catheter-related coagulase-negative staphylococcal sepsis in neonates.

A randomized, double-blind, controlled trial was conducted to determine whether vancomycin added to parenteral alimentation solution given via a central venous catheter would decrease the incidence of catheter-related coagulase-negative staphylococcal sepsis. Seventy infants with a central venous catheter (CVC) in place were randomly selected to receive total parenteral nutrition--either the standard solution or a solution containing 25 micrograms of vancomycin per milliliter. Catheter-related sepsis was defined as the isolation of the same bacterial species from specimens of both peripheral and CVC blood with the concentration of bacteria at least tenfold greater in the specimen obtained from the CVC. Specimens from the CVCs were cultured on removal of the catheters to determine colonization. The colonization of catheters by coagulase-negative staphylococci was reduced from 40% to 22% (p = 0.03) in the vancomycin group; catheter-related sepsis was reduced from 15% to no cases (p = 0.004). Fewer infants required CVC reinsertion in the vancomycin-treated group (p = 0.02), who also regained birth weight earlier (13.4 vs 17.1 days (p = 0.014)). Adverse effects of vancomycin infusion were not observed. We conclude that vancomycin added to the solution used for total parenteral nutrition effectively reduces catheter-related sepsis in the neonatal intensive care unit and offers other potential benefits such as the need for fewer catheters and earlier weight gain. However, we do not recommend widespread implementation of this technique until there are data regarding the emergence of vancomycin-resistant organisms.

Bacteremia↗