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C Cox

Publications and source records attributed to C Cox.

At least 145 records · Page 8Linked to original sources

Physiologic, biochemical, and histologic correlates associated with tidal liquid ventilation.

Tidal liquid ventilation (TLV) with perfluorochemical fluid (PFC) has been successfully used experimentally for up to 4 h. However, no studies of prolonged TLV have been reported. We hypothesized that full-term newborn lambs can safely and effectively be liquid-ventilated for up to 24 h. To test this hypothesis, 17 lambs were liquid-ventilated; 7 for 4 h, 5 for 12 h, and 5 for 24 h. Arterial blood samples were obtained for PFC uptake, lipid analysis, and blood gas measurements. Tissues were obtained for histologic and biochemical analysis. Arterial blood gas and mean arterial blood pressure were as follows (mean +/- SEM): pH 7.48 +/- 0.04; PaCO2 30.6 +/- 2.8; PaO2 424 +/- 17; mean arterial pressure 76 +/- 16 mm Hg. PFC blood levels increased rapidly to a mean of 5.2 +/- 3.9 microg/mL. PFC tissue levels increased significantly (p < 0.01) from 260 +/- 45 microg/g at 4 h to 400 +/- 140 microg/g at 12 h. There was no further increase in PFC tissue levels by 24 h (456 +/- 181 microg/g). There was a significant difference in PFC concentration as a function of tissue (p < 0.01). Furthermore, there was a significant correlation (r = 0.88; p < 0.01) between the amount of PFC and lipid in blood and tissue. Microscopic examination of the lungs demonstrated no evidence of barotrauma. These data demonstrate that prolonged TLV can be safe and efficacious for up to 24 h in full-term newborn lambs.

Animals↗

Semiparametric modeling of age at achieving developmental milestones after prenatal exposure to methylmercury in the Seychelles child development study.

Controversy exists concerning the fetal risk associated with exposure to low-dose methylmercury from maternal fish consumption. Previous studies of the effects of acute prenatal mercury exposure identified delays in achieving developmental milestones among exposed children. This led to public health concern that prenatal low-dose exposure from fish consumption could adversely affect the fetus. We evaluated the effects of prenatal methylmercury exposure (through maternal fish consumption) on the age that children walked and first said words in the main study cohort of the Seychelles Child Development Study. We used semiparametric generalized additive models to identify nonlinearities in the relationships between prenatal exposure and developmental outcomes, after adjusting for covariates, and to evaluate their importance. Very slight delays (<1 day) in walking were seen as mercury levels increased from 0 to 7 ppm, but this effect did not persist at the higher exposure levels represented by the cohort, making it difficult to conclude that a cause and effect relationship existed at the exposure levels seen in this cohort. There was no evidence for any association between prenatal exposure and age at talking.

Child Development↗

School-age follow-up of prophylactic versus rescue surfactant trial: pulmonary, neurodevelopmental, and educational outcomes.

BACKGROUND: Exogenous surfactant replacement has improved survival and reduced pulmonary complications of prematurity. Improved early outcomes for infants of <30 weeks' gestation treated with a strategy of prophylactic versus rescue surfactant, if needed, were demonstrated in a multicenter, randomized trial conducted between 1985 and 1988. We reevaluated a subset of survivors from this trial to determine the pulmonary and neurodevelopmental outcomes at school age. METHODS: At 4.5 to 8 years of age, all survivors from one of the three centers were located, and 96% were evaluated. The original randomization included stratification by center and followed an intention-to-treat methodology in assessing the efficacy of prophylactic versus rescue treatment with surfactant. The follow-up test battery included a health-assessment questionnaire, spirometry, 88% saturation test, neurologic examination, and the McCarthy Scales of Children's Abilities (MSCA) and the Conners' Parent Rating Scale-48. Educational achievement was determined by school class placement and teachers' reports of achievement. RESULTS: Of the 192 children originally enrolled, 154 survived. Evaluations were performed on 148 of these infants. An abnormal pulmonary history was found in 45 (30%) of the children: 16 (22%) in the prophylactic group and 29 (39%) in the rescue group. Formal pulmonary function was evaluated in 81 children; 29 (78%) in the prophylactic group and 33 (75%) in the rescue group were considered abnormal. No significant differences were found between the two groups on either cognitive or motor subscales of the MSCA, the Conners' Parent Rating Scale-48, the neurologic examination, the education services received in school, or the teacher ratings of below-average academic performance. Intelligence scores measured on the MSCA were low-normal for both groups. Some level of educational assistance was being provided to 72 (49%) of the cohort studied, and both groups had below average educational performance and increased needs for educational assistance. CONCLUSIONS: Prophylactic surfactant administration to infants of <30 weeks' gestation was associated with fewer long-term clinical pulmonary complications than assignment to rescue administration. Formal pulmonary testing at school age did not reveal significant differences between treatment groups in those infants who could be tested. There also were no group differences found on neurologic, cognitive, behavioral, or educational assessments at school age.

Child↗

Comparison of two strategies for surfactant prophylaxis in very premature infants: a multicenter randomized trial.

INTRODUCTION: Previous trials of surfactant therapy in premature infants have demonstrated a survival advantage associated with prophylactic therapy as an immediate bolus, compared with the rescue treatment of established respiratory distress syndrome. The optimal strategy for prophylactic therapy, however, remains controversial. When administered as an endotracheal bolus immediately after delivery, surfactant mixes with the absorbing fetal lung fluid and may reach the alveoli before the onset of lung injury. This approach, however, causes a brief delay in the initiation of standard neonatal resuscitation, including positive pressure ventilation, and is associated with a risk for surfactant delivery into the right main stem bronchus or esophagus. As an alternative approach, surfactant prophylaxis may be administered in small aliquots soon after resuscitation and confirmation of endotracheal tube position. Although this strategy has substantial logistical advantages in clinical practice, its efficacy has not been established. OBJECTIVE: The purpose of this study was to determine whether the established benefits of the immediate bolus strategy for surfactant prophylaxis could still be achieved using a postventilatory aliquot strategy after initial standard resuscitation and stabilization. DESIGN: Multicenter randomized clinical trial with patients randomized before delivery to immediate bolus or postventilatory aliquot therapy. PARTICIPANTS: Inborn premature infants delivered to mothers at an estimated gestational age of 24[0/7] to 28[6/7] weeks. INTERVENTIONS: Those infants who were randomized to the immediate bolus strategy were intubated as rapidly as possible after birth, and a 3-mL intratracheal bolus of calf lung surfactant extract (Infasurf) was administered before the initiation of positive pressure ventilation. Those infants who were randomized to the postventilatory aliquot strategy received standard resuscitation measures with intubation by 5 minutes of age, if not required earlier. At 10 minutes after birth, 3 mL of surfactant was administered in 4 divided aliquots of 0.75 mL each. Patients in both groups were eligible to receive up to three additional doses of surfactant as rescue therapy in the neonatal intensive care unit, if needed. OUTCOME MEASURES: The primary outcome variable was survival to discharge to home. Secondary variables included neonatal complications and requirement for oxygen therapy at 36 weeks' postmenstrual age. RESULTS: Among three centers, 651 infants were enrolled and randomized before delivery. Survival to discharge to home was similar for the two strategies for surfactant therapy as prophylaxis: 76% for the immediate bolus group and 80% for the postventilatory aliquot group. In a secondary analysis, the rate of supplemental oxygen administration at 36 weeks' postmenstrual age was 18% for the immediate bolus group and 13% for the postventilatory aliquot group. CONCLUSIONS: Survival to discharge to home was similar with immediate bolus and postventilatory aliquot strategies for surfactant prophylaxis. Because of its logistical advantages in the delivery room and its beneficial effects on prolonged oxygen requirements, we recommend the postventilatory aliquot strategy for surfactant prophylaxis of premature infants delivered before 29 weeks' gestation.

Drug Administration Schedule↗

Cerebrovascular risk factors and later-life major depression. Testing a small-vessel brain disease model.

The topic of vascular depression has received increasing prominence as a putative etiology of depression in later life. The authors examined one aspect of this model by comparing the burden of systemic cerebrovascular risk factors (CVRFs) in 130 psychiatric inpatients with major depression and 64 normal control (NC) subjects, all age > or = 50 years. Depressed subjects did not differ statistically from NCs on cumulative CVRF scores. Diabetes mellitus and atrial fibrillation were both associated with depression, but only atrial fibrillation retained an independent association after medical disability was statistically controlled. Among the depressed subjects, CVRF scores were not significantly associated with overall symptom severity, psychiatric disability, age at onset of depression, melancholic subtype, or psychotic depression. These data did not support the notion that a linear model of small-vessel disease might apply to the great majority of older inpatients with major depression.

Aged↗

Changes in visually guided behavior of Royal College of Surgeons rats as a function of age: a histologic, morphometric, and functional study.

PURPOSE: To compare the changes in visually guided performance as a function of age between Royal College of Surgeons (RCS) dystrophic and congenic rats and to correlate photoreceptor cell number with visually guided performance in age-matched populations of RCS dystrophic rats. METHODS: The visually guided performances of RCS dystrophic (n=6) and congenic (n=7) rats were studied from 0.75 to 12 months of age using a water escape paradigm that tested their ability to find a submersed, randomly placed platform that used a light source as a clue. The time to find the platform (latency) was recorded. In age-matched dystrophic RCS rats, histopathologic changes were described and the number of photoreceptor cell nuclear profiles per midsagittal retinal section was counted. Changes with age in visually guided behavior and photoreceptor cell populations of RCS dystrophic rats then were compared. RESULTS: The latency of RCS dystrophic rats increased significantly beyond that of congenic rats after 6 months of age. Photoreceptor cell number in dystrophic rats precipitously decreased through 6 months of age, stabilized at 9 months, and decreased further at 12 months. Two unexpected results were seen in the dystrophic animals: At 6 months of age, as few as 22+/-3 photoreceptor cell nuclei per midsagittal section provided similar latencies as at 2 months when there were as many as 400. Although the number of photoreceptor cells remained stable from 6 to 9 months of age, functional vision significantly deteriorated. CONCLUSIONS: Two important phenomena were observed. First, the RCS rats performed very well in the water escape test even while their photoreceptor cell population was being decimated. Second, once a low threshold was reached, a dramatic deterioration of visually guided behavior occurred without a further reduction in photoreceptor cell numbers.

Aging↗

Age differences in behaviors leading to completed suicide.

The authors described retrospectively the premorbid self destructive behaviors of suicide victims to determine whether these behaviors differ with age. One hundred forty one suicide victims, age 21-92 years, were studied by psychological autopsy. Older age was significantly associated with more determined and planful self-destructive acts, less violent methods, and fewer warnings of suicidal intent. Age differences in the behaviors leading to suicide indicate that intervention in the midst of a suicidal crisis may be less effective in elderly persons than in younger people. Primary prevention should be the focus of efforts to decrease suicide rates in late life.

Adult↗

Short-term administration of selegiline for mild-to-moderate dementia of the Alzheimer's type.

As a follow-up to an earlier study showing short-term benefit in inpatients with more severe dementia, the authors studied the short-term cognitive, functional, and behavioral effects of selegiline in outpatients with mild-to-moderate dementia of the Alzheimer type (DAT) by means of a double-blind, randomized, crossover study of placebo vs. selegiline. Fifty outpatients with mild-to-moderate DAT and no behavioral disturbances were given selegiline in two 8-week treatment periods separated by a 4-week washout. Outcome was assessed with standardized measures of dementia severity, daily functioning, behavior, and cognition. There was no drug-placebo difference in any outcome measure. Selegiline did not show short-term benefit in this study, contrary to the earlier study, perhaps because the patients were studied less intensively and/or lacked behavioral problems that could show response, although the medication was well tolerated.

Aged↗

A more flexible regression-to-the-mean model with possible stratification.

We consider a regression-to-the-mean model that includes both additive and multiplicative treatment effects. We allow either or both of these treatment effects to be stratified by ranges of the first measurement. We focus on the situation where there is a very large sample on the first measurement and a relatively small subsample for the second measurement is selected, which often occurs in screening trials. We propose some asymptotically efficient estimators for the parameters of the model that are very simple to compute. We begin with a discussion of the full model, and more on tests and estimation for reduced models follows. An example from a large screening trial is discussed.

Biometry↗

Suicide in widowed persons. A psychological autopsy comparison of recently and remotely bereaved older subjects.

Using the psychological autopsy method, the authors sought to determine whether widowed people who commit suicide more than 4 years after their spouse's death (n = 21) can be clinically distinguished from those who commit suicide after a shorter period of widowhood (n = 14). The latter had a higher rate of psychiatric treatment (P = 0.018), early loss/separation (P = 0.03), and a nonsignificantly higher rate of lifetime substance abuse (P = 0.07). Spousal bereavement increases the likelihood of physician visits, so the recently widowed represent a population for whom interventions may be readily implemented. Clinicians should monitor suicide risk in their recently widowed patients, especially those with psychiatric, substance abuse, and/or early loss/separation histories.

Aged↗

Prenatal and lactational exposure to methylmercury affects select parameters of mouse cerebellar development.

Animal studies of the neuropathological effects of prenatal methylmercury (MeHg) seldom use regimens that represent environmental exposures. While acute administration of high doses of MeHg to developing rodents can model some of the outcomes MeHg produces in the human cerebellum, their long-term relevance to cerebellar development is unknown. The present study was undertaken to determine the effect of chronic dietary exposure to MeHg. Pregnant mice were exposed throughout gestation to 0.0 or 4.0 ppm methylmercury in their drinking water. Postpartum exposure of pups and lactating dams continued to postnatal day (PND) 30. On PND7, 14, 21, and 30, several morphometric indices of cerebellar cortex development, as well as blood and brain levels of total Hg, were measured in pairs of male and female littermates. No signs of overt toxicity were observed in the dams or offspring. Blood and brain levels of total Hg were highest in the exposed PND7 offspring and fell throughout the sampling period despite continued exposure. In a region of molecular layer in the anterodorsal lobe, MeHg exposure reduced the density of migrating cells in PND7 offspring. Molecular layer widths were reduced in PND30 offspring. In a region of the inferior lobe of PND7 offspring, MeHg exposure reduced external granular layer widths and decreased the density of migrating cells in the molecular layer. However, MeHg did not affect cerebellar cortex development in the central lobe, suggesting a regional sensitivity to chronic, low-level MeHg exposure during development.

Analysis of Variance↗

Variability of DNA analysis by image cytometry. Bladder Tumor Marker Network.

Two laboratories equipped with CAS 200 (Becton Dickinson Image Cytometry Systems, San Jose, CA) instruments participated in this study of variability of DNA analysis of bladder tumor specimens. Formalin fixed paraffin embedded specimens were disaggregated and centrifuged onto microscope slides from ten bladder tumor specimens and two specimens of normal urothelium. Sources of variability considered were Specimen, Slide, Run, Laboratory, and Error. Slides were systematically scanned and 200 cells measured followed by the operator selecting 100 nuclei with abnormal morphology. DNA index (DI) and hyperdiploid fraction (HDF) were calculated from the DNA frequency distributions. For systematic sampling, 92% of the variability was due to Specimen indicating that differences in HDF values between specimens reflect biological differences. With selective sampling, only 67% of the variability in HDF is due to Specimen differences. Other factors, Laboratory, Error, and Laboratory x Specimen interaction each accounted for approximately 10% of the variability. Similarly variability of DI with selective sampling was also higher, and less specimen dependent than systematic sampling. It is important that sampling schemes and selection criteria be carefully documented in order to control variability. Enriched (or selective) sampling for abnormal cells has the potential to increase sensitivity but specimen classification based on these measurements must depend on determination of the frequency of such cells in the total population.

Analysis of Variance↗

Right on your side.

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Employee Grievances↗

Equal at last.

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Female↗

International scoring system for evaluating prognosis in myelodysplastic syndromes.

Despite multiple disparate prognostic risk analysis systems for evaluating clinical outcome for patients with myelodysplastic syndrome (MDS), imprecision persists with such analyses. To attempt to improve on these systems, an International MDS Risk Analysis Workshop combined cytogenetic, morphological, and clinical data from seven large previously reported risk-based studies that had generated prognostic systems. A global analysis was performed on these patients, and critical prognostic variables were re-evaluated to generate a consensus prognostic system, particularly using a more refined bone marrow (BM) cytogenetic classification. Univariate analysis indicated that the major variables having an impact on disease outcome for evolution to acute myeloid leukemia were cytogenetic abnormalities, percentage of BM myeloblasts, and number of cytopenias; for survival, in addition to the above, variables also included age and gender. Cytogenetic subgroups of outcome were as follows: "good" outcomes were normal, -Y alone, del(5q) alone, del(20q) alone; "poor" outcomes were complex (ie, > or = 3 abnormalities) or chromosome 7 anomalies; and "intermediate" outcomes were other abnormalities. Multivariate analysis combined these cytogenetic subgroups with percentage of BM blasts and number of cytopenias to generate a prognostic model. Weighting these variables by their statistical power separated patients into distinctive subgroups of risk for 25% of patients to undergo evolution to acute myeloid leukemia, with: low (31% of patients), 9.4 years; intermediate-1 (INT-1; 39%), 3.3 years; INT-2 (22%), 1.1 years; and high (8%), 0.2 year. These features also separated patients into similar distinctive risk groups for median survival: low, 5.7 years; INT-1, 3.5 years; INT-2, 1.2 years; and high, 0.4 year. Stratification for age further improved analysis of survival. Compared with prior risk-based classifications, this International Prognostic Scoring System provides an improved method for evaluating prognosis in MDS. This classification system should prove useful for more precise design and analysis of therapeutic trials in this disease.

Acute Disease↗

Screening for depression in elderly primary care patients. A comparison of the Center for Epidemiologic Studies-Depression Scale and the Geriatric Depression Scale.

BACKGROUND: Later-life depressive disorders are a major public health problem in primary care settings. A validated screening instrument might aid in the recognition of depression. However, available findings from younger patients may not generalize to older persons, and existing studies of screening instruments in older patient samples have suffered substantial methodological limitations. METHODS: One hundred thirty patients 60 years or older attending 3 primary care internists' practices participated in the study. Two screening scales were used: the Center for Epidemiologic Studies-Depression Scale (CES-D) and the Geriatric Depression Scale (GDS). The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders. Third Edition, Revised, was used to establish "gold standard" diagnoses including major and minor depressive disorders. Receiver operating curve analysis was used to determine each scale's operating characteristics. RESULTS: Both the CES-D and the GDS had excellent properties in screening for major depression. The optimum cutoff point for the CES-D was 21, yielding a sensitivity of 92% and a specificity of 87%. The optimum cutoff point for the GDS was 10, yielding a sensitivity of 100% and a specificity of 84%. A shorter version of the GDS had a sensitivity of 92% and a specificity of 81% using a cutoff point of 5. All scales lost accuracy when used to detect minor depression or the presence of any depressive diagnosis. CONCLUSIONS: The CES-D and the GDS have excellent properties for use as screening instruments for major depression in older primary care patients. Because the GDS's yes or no format may ease administration, primary care clinicians should consider its routine use in their practices.

Aged↗