More exercise, less central fat distribution in women.
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Absorptiometry, Photon↗
Biomedical subjects
C Cox
Publications and source records attributed to C Cox.
Clear lessons to be learned.
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Clinical Competence↗
Synthesis of 2-thiothiazolidine-4-carboxylic acid and its chromatography in rat and human urine.
2-Thiothiazolidine-4-carboxylic acid (TTCA), the urinary biological monitoring marker for carbon disulfide in humans was synthesized by reacting carbon disulfide with L-cystine. Validation of TTCA purity required elemental as well as mass spectral and chromatographic analyses. Two reversed-phase high-performance liquid chromatographic columns in series were necessary to resolve picomole amounts of TTCA from rat and human urine background peaks on detection at 272 nm even after prior diethyl ether extraction from acidified urines in the presence of saturated sodium chloride. The isolation procedure for TTCA from urine had a recovery of 94.0 +/- 8.1% in the linear 1.1-330 microM concentration range (0.0165-4.95 nmol injected mass) with a coefficient of variation of 8.6%. The detection limit was about 100 nM (1.5 pmol injected mass).
Animals↗
Water escape performance of adult RCS dystrophic and congenic rats: a functional and histomorphometric study.
The dystrophic Royal College of Surgeons (RCS) rat undergoes photoreceptor degeneration due to a hereditary defect in the retinal pigment epithelium. The congenic rat remains unaffected. Although the retinal degeneration is well characterized, few functional studies of this strain are available. We wished to compare the visual function of congenic and dystrophic RCS rats using a water escape paradigm that tested their ability to find a submersed, randomly placed platform using a light source as a clue. Three different behavioral experiments were sequentially performed on all animals: Experiment 1--The Light and Platform test measured the time to swim from the center of the pool to a platform located under a light clue. Each animal was given 10 trials. Experiment 2--The No Light with Platform test was performed as above except no light clue was used. Experiment 3--The Light and No Platform test was performed with a light clue but without a platform. The animal was allowed to swim for 2 min. All trials were videotaped. After the final experiment, the animals were sacrificed and a histomorphometric analysis of their retinas were performed. Expt. 1--The time to find the platform using light as a clue was greater for the dystrophic than for the congenic rats. Expt. 2--In the absence of light clue, there was no significant difference in performance between the congenic and dystrophic animals. Expt. 3--In the absence of a platform, a significantly greater amount of time was spent in the area indicated by the light clue by the congenic animals as compared to the dystrophic. Morphometric analysis revealed a mean number of 133 photoreceptor nuclear profiles/90 microns of retina for congenic rats as compared to 0.14 for dystrophic rats. This simplified version of the Morris water maze permits quantitative evaluation of visually-guided behavior in an important model of retinal degeneration.
Animals↗
Understanding leadership: challenges, changes and opportunities.
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Delivery of Health Care↗
Biological profile of 23 cases of minimally differentiated acute myeloid leukemia (AML-M0) and its clinical implications.
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Acute Disease↗
Cognitive performance and regional brain volume in human immunodeficiency virus type 1 infection.
BACKGROUND: Brain atrophy has been reported to occur in advancing human immunodeficiency virus (HIV) infection, particularly in patients with HIV-related dementia. Atrophy of the caudate region, as assessed by magnetic resonance imaging measures, has been reported to correlate with cognitive impairment in patients with HIV infection; however, differences in the severity of HIV-induced immunosuppression may have contributed to these findings. OBJECTIVE: To determine the relationship between regional brain volumes and cognitive performance in individuals with HIV infection. PATIENTS AND METHODS: We evaluated 11 patients with advanced HIV disease by using neuropsychologic tests and quantitative magnetic resonance imaging volume analysis. SETTING: University hospital, involving patients from a clinical trial. RESULTS: Caudate volume, expressed as a ratio of total intracranial volume, correlated with performance on the Trails A and Grooved Pegboard tests, but not with other tests of memory, motor speed, or mood (adjusted for age and education). Hippocampal volume did not correlate with any of the neuropsychologic tests. CONCLUSIONS: Caudate volume in patients with advanced HIV disease is associated with poor performance on neuropsychologic tests of complex motor and sequencing skills. Hippocampal volume does not appear to be related to impairment on neuropsychologic tests. These findings are independent of the degree of immunosuppression and the overall extent of brain atrophy; however, these results must be interpreted with some caution, given the limited sample size.
Adult↗
Immunisation of common marmosets with vaccinia virus expressing Epstein-Barr virus (EBV) gp340 and challenge with EBV.
Epstein-Barr virus (EBV) is the cause of infectious mononucleosis and is associated with a variety of life-threatening diseases in humans. Therefore the development of an effective vaccine is an important objective. Many of the initial studies of vaccine efficacy analyse the ability of vaccine preparations to prevent the induction of lymphomas in cottontop tamarins by the B95-8 strain of EBV. We used a vaccinia virus recombinant expressing gp340, vMA1, tested previously in the cotton-top tamarin, to evaluate a common marmoset model in which the challenge virus, M81, resembles more closely the wild-type strains of EBV in the general population than does the standard B95-8 strain. We characterised the M81 strain of EBV with respect to the sequence of its gp340/220 gene and in regard to the presence of a region deleted in B95-8. Replication of the challenge virus in the group vaccinated with vMA1 was decreased when compared to control groups.
Amino Acid Sequence↗
Liquid assisted ventilation: an alternative ventilatory strategy for acute meconium aspiration injury.
Evidence of surfactant inactivation by meconium has led to the use of exogenous surfactant therapy in the management of meconium aspiration syndrome (MAS). Liquid assisted ventilation has been shown to improve the cardiopulmonary function in lungs with high surface tension. We compared exogenous surfactant therapy with liquid assisted ventilation in the management of experimental acute meconium aspiration injury. Thirty-two newborn lambs were ventilated at peak inspiratory pressures of 13-16 cm H2O, positive end expiratory pressure of 3-4 cm H2O, fractional inspired oxygen concentration (FiO2) of 1.0, and a respiratory frequency range between 30 and 35 breaths/min. Baseline arterial blood gases, pulmonary function, and arterial blood pressure measurements were taken. All lambs were given 2-3 ml/kg of an unfiltered 25% meconium solution. Lambs were then randomized into either gas-ventilated meconium control, or one of three treatment groups: 1) surfactant; 2) partial liquid ventilation (PLV); or 3) total liquid ventilation (TLV) for 4 hours after meconium injury. All treated groups demonstrated a significant increase in arterial oxygenation (P < 0.05); surfactant and PLV-treated lambs demonstrated significantly decreased arterial PCO2 (P < 0.05). Compliance in all groups increased compared with injury values; compliance of the TLV group increased more than in all other treatment groups (P < 0.05). In addition, lung histology of the TLV group demonstrated clear, intact alveolar epithelium and homogeneously expanded alveoli, while no such improvement was evident in the other groups. These data suggest roles for both exogenous surfactant therapy and liquid assisted ventilation techniques in the management of MAS.
Animals↗
Exposure to combined static and 60 Hz magnetic fields: failure to replicate a reported behavioral effect.
Two experiments failed to confirm the Thomas, Schrot, and Liboff report that low-intensity magnetic fields disrupted the operant behavior of rats. In their experiment, food-deprived rats were trained to press a lever to obtain food pellets under a multiple fixed-ratio (FR) 30, differential reinforcement of low rate 18-24 s (DRL 18-24) schedule. After baseline training, the rats were exposed to a 30 min treatment in a different chamber prior to behavioral testing. When the treatment consisted of a horizontal 60 Hz magnetic field at 5 x 10(-5) Telsa aligned along the north-south axis combined with a static field that reduced the background to 2.61 x 10(-5) Telsa, the rate of lever pressing in the DRL component of the multiple schedule increased reliably during the immediately following test session. Changes in responding were not observed when the rats were exposed to either the static field or the 60 Hz field independently nor during sham exposures to the fields. In the present experiments, only the combined fields, i.e., those reported to be effective, were studied in rats using the same general behavioral and exposure protocol used by Thomas et al [1986a]. In experiment 1, the 2.61 x 10(-5) Telsa was achieved by reducing the vertical component of the static field. In experiment 2, both the horizontal and the vertical components were altered to match those used by Thomas et al. In both experiments additional magnetic field conditions were also studied to ensure that threshold values were exceeded and, in experiment 2, to address concerns about the role of harmonic frequencies of the 60 Hz field. The baseline performances approximated those of Thomas et al. Performances were compared between exposure, sham-exposure and control sessions. None of the exposure conditions altered any of the behavioral measures. The reasons for failing to replicate the results of Thomas et al. remain unknown.
Animals↗
Brazilian Baccharis toxins: livestock poisoning and the isolation of macrocyclic trichothecene glucosides.
Samples of the toxic Brazilian plant, Baccharis coridifolia, which is responsible for numerous cases of livestock poisoning in southern Brazil and Argentina, were collected during the growing season, and the toxicities in calves of the plant materials were correlated with the levels of macrocyclic trichothecenes present. Female plants in flower were considerably more toxic than male plants or plants not in flower. Plants not in flower were of intermediate toxicity. The female plants in flower typically contained 5-10 times the levels of toxins as were found in the male plants. In addition, six new glucosides of the macrocyclic trichothecenes were isolated and characterized. The most prominent glucosides, those of roridins A and E, were found in high levels in the female plants.
Acetylation↗
Metallothionein induction and pulmonary responses to inhaled cadmium chloride in rats and mice.
Inhaled CdCl2 is a pulmonary carcinogen in rats but not in mice. We hypothesized that pulmonary metallothionein (MT) induction may be different in both species and thereby may lead to different levels of protection from Cd-induced lung injury. Fisher-344 rats and B6C3F1 mice were exposed for 4 weeks to CdCl2 aerosols of 0, 30, 50, and 150 micrograms/m3 air or 0, 10, 30, and 100 micrograms/m3 air, respectively. Animals from each exposure group were terminated at 1, 30 and 133 days after the end of exposure. The lungs were lavaged for cell and biochemical analyses. Cadmium and MT in lavagate and lung tissue were measured. The retention half-time of pulmonary Cd was greater in mice (290 vs 90 days, p < 0.05). Cd exposure provoked an inflammatory response which was dose-dependent in both species, and while it was only short-lived in rats, it persisted throughout the observation period in mice at the high exposure concentrations. Mice were found to have a greater baseline level of MT (18.04 +/- 6.96 vs 11.7 +/- 1.98 micrograms MT/g control lung, p < 0.05). Mice showed greater inducibility of MT for a given CdCl2 exposure concentration; however, both species had a similar relationship between retained pulmonary Cd and MT induction though mice maintained increased MT levels for a longer period of time. The greater pulmonary baseline MT together with the longer presence of Cd-induced pulmonary MT may result in greater protection from Cd carcinogenicity in spite of the greater pulmonary Cd-induced inflammation in mice.
Animals↗
Perinatal methanol exposure in the rat. I. Blood methanol concentration and neural cell adhesion molecules.
Although the acute toxicity of methanol is well documented, few studies have addressed the consequences of perinatal exposures to the low concentrations that are expected to arise from its proposed use as a component of automobile fuel. This report describes the general research design of a series of studies, the effects of methanol exposures on blood concentrations in dams and neonates, and indices of brain development. Four cohorts of Long-Evans pregnant rats, each cohort consisting of an exposure (n = 12) and a control (n = 12) group, were exposed whole-body to 4500 ppm methanol vapor or air for 6 hr daily beginning on Gestation Day 6. Both dams and pups were then exposed through Postnatal Day 21 (PND 21). Blood methanol concentrations determined by gas chromatography from samples obtained immediately following a 6-hr exposure reached approximately 500-800 micrograms/ml in the dams during gestation and lactation. Average concentrations for pups attained levels about twice those of the dams. Selected offspring from Cohort 4 were exposed for one additional 6-hr session at ages that extended out to PND 52. Regression analyses showed that the blood methanol concentrations of the pups declined until about PND 48, at which time their levels approximated those of their dams. Such pharmacokinetic differences might increase the risks posed to developing organisms. Light-microscopic analysis showed no significant abnormalities in the brains of the methanol-treated animals. However, assays of neural cell adhesion molecules (NCAMs) in brains of pups sacrificed on PND 4 showed staining for both the 140 and the 180 kDa isoforms to be less intense in the cerebellum of exposed animals. NCAM differences were not apparent in animals sacrificed 15 months after their final exposure.
Animals↗
Age-related decline in central cholinergic function demonstrated with scopolamine.
Scopolamine hydrobromide was administered intravenously to 23 normal subjects (40-89 years) in doses of 0.1 mg, 0.25 mg, and 0.5 mg, in a double-blind. Placebo-controlled, random-order fashion. The effects of scopolamine, as compared to placebo, were assessed using a comprehensive cognitive test battery, as well as behavioral and physiological measures. Scopolamine produced the expected dose-dependent impairments in most of the cognitive functions assessed. Behavioral and physiological measures were also affected, but only minimally. More importantly, there was a significant overall correlation between age and scopolamine-impaired performances on psychomotor speed, short-term recall, visual tracking speed, visuo-motor coordination, and sequencing ability. There was, however, some inter-individual variability in this phenomenon. The results provide further evidence that cholinergically mediated cognitive functions show an increased sensitivity to scopolamine with age, albeit with heterogeneity that bears further investigation.
Adult↗
Thresholds for ultrasonically induced lung hemorrhage in neonatal swine.
The threshold for generation of lung hemorrhage in adult mice by pulsed ultrasound has been shown to be approximately 1 MPa at the surface of the lung (10-microseconds pulse and a carrier frequency of 2 MHz). This investigation used neonatal swine to determine if the findings for mice can be generalized to other species. After exploratory observations, the inverse sampling method was used in a primary study (22 animals, 88 exposure sites) to determine the threshold for lung hemorrhage in neonatal swine. The primary study was followed by a separate confirmation study (13 animals, 48 exposure sites), testing the conclusions of the first study and comparing damage at subthreshold levels with sham-exposed animals. A separate investigation explored the histological nature of tissue damage at suprathreshold levels. A 2.3-MHz focused transducer (10 microseconds at 100-Hz pulse-repetition frequency) was incremented vertically for a distance of 2 cm over the chest of the subject for a total exposure period of 16 min. Animals were euthanized and lungs were scored by visual inspection for numbers and areas of gross hemorrhages. The threshold level for hemorrhage was approximately 1.5 MPa peak positive pressure in water at the surface of the animal or, at the surface of the lung, 1.1 MPa peak positive pressure, 1 MPa fundamental pressure, 0.9 MPa maximum negative pressure, 25 W cm-2 pulse average intensity or a mechanical index of 0.6. These values are essentially the same as those reported for adult mice.
Animals↗
Exposure-time dependence of the threshold for ultrasonically induced murine lung hemorrhage.
Although the extent of suprathreshold damage to murine lung that results from exposure to pulsed ultrasound increases with time, the threshold level for lung hemorrhage is relatively insensitive to total exposure time. Adult mice were exposed for 20 s and 3 min to 2.3-MHz ultrasound (10-microseconds pulses, 100-Hz pulse repetition frequency) at peak positive pressures ranging up to 3 MPa. Threshold pressures for the two exposure times, 1.6 MPa and 1.4 MPa, respectively, are the same within the statistical significance of the measurements.
Animals↗
Hemolysis of albunex-supplemented, 40% hematocrit human erythrocytes in vitro by 1-MHz pulsed ultrasound: acoustic pressure and pulse length dependence.
The tested hypothesis was that ultrasound-induced hemolysis in blood supplemented with a microbubble contrast agent varies with ultrasound intensity and pulse duration. Human erythrocytes in autologous plasma containing 3.6% v:v Albunex microspheres were exposed to 1.07-MHz ultrasound pulses of 5 to 1000 mus at SPTP intensities of 0 to 1100 W/cm2. The dependence of hemolysis on the mechanical index (MI) value of the exposures was also examined. Ultrasound-induced hemolysis: (1) was evident at all pulse/intensity combinations; (2) increased generally with increasing pulse duration at constant intensity; and (3) increased with increasing MI at constant pulse duration. For pulses of 10 to 30 mus, ultrasound-induced hemolysis remained low (< or = 2%) at MI values < approximately 2 and increased sharply with further increase in MI; for 5-mus pulses, this abrupt increase in hemolysis was associated with a larger MI (approximately 3).
Adult↗
Effect of very delayed repair of congenital diaphragmatic hernia on survival and extracorporeal life support use.
BACKGROUND: Since November 1992, operative repair in neonates with congenital diaphragmatic hernia (CDH) at this institution was delayed until respiratory insufficiency had resolved. METHODS: A retrospective analysis was performed (n = 33) comparing delayed repair with our previously reported institutional experience with immediate repair from January 1988 to October 1992 (n = 66). Infants with severe genetic defects or moribund conditions or who were premature were not considered candidates for repair or extracorporeal life support (ECLS), but they were included in the survival analysis. Survival was defined as hospital discharge. Data were compared with an independent t test or Pearson chi-squared test. RESULTS: Mean age at repair was 8.9 +/- 4.5 days (range, 3 to 20 days). Eleven infants in the study group were placed on ECLS (33% versus 68% in the comparison group; p = 0.001). Six of these infants survived (55% versus 58% in the comparison group; p = 0.846). Of these survivors, one patient was repaired while on ECLS, and the remainder underwent repair after decannulation from ECLS. All 20 of the remaining candidates for repair survived without need for ECLS. Overall survival was 79% versus 56% in the comparison group (p = 0.027). CONCLUSIONS: Our current data suggest that very delayed repair of newborns with CDHs is associated with an increase in the overall survival and a decrease in the use of ECLS when compared with previous experience at this institution.
Extracorporeal Membrane Oxygenation↗