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Biomedical subjects

P M Phillips

Publications and source records attributed to P M Phillips.

17 recordsLinked to original sources
PubMed2005

Neurobehavioral effects of chronic dietary and repeated high-level spike exposure to chlorpyrifos in rats.

This study aimed to model long-term subtoxic human exposure to an organophosphorus pesticide, chlorpyrifos, and to examine the influence of that exposure on the response to intermittent high-dose acute challenges. Adult Long-Evans male rats were maintained at 350 g body weight by limited access to a chlorpyrifos-containing diet to produce an intake of 0, 1, or 5 mg/kg/day chlorpyrifos. During the year-long exposure, half of the rats in each dose group received bi-monthly challenges (spikes) of chlorpyrifos, and the other half received vehicle. Rats were periodically tested using a neurological battery of evaluations and motor activity to evaluate the magnitude of the acute response (spike days) as well as recovery and ongoing chronic effects (non-spike days). Effects of the spikes differed as a function of dietary level for several endpoints (e.g., tremor, lacrimation), and in general, the high-dose feed groups showed greater effects of the spike doses. Animals receiving the spikes also showed some neurobehavioral differences among treatment groups (e.g., hypothermia, sensory and neuromotor differences) in the intervening months. During the eleventh month, rats were tested in a Morris water maze. There were some cognitive deficits observed, demonstrated by slightly longer latency during spatial training, and decreased preference for the correct quadrant on probe trials. A consistent finding in the water maze was one of altered swim patterning, or search strategy. The high-dose feed groups showed more tendency to swim in the outer annulus or to swim very close to the walls of the tank (thigmotaxic behavior). Overall, dietary exposure to chlorpyrifos produced long-lasting neurobehavioral changes and also altered the response to acute challenges.

Animals↗
PubMed2004

Neurotoxicity produced by dibromoacetic acid in drinking water of rats.

An evaluation of potential adverse human health effects of disinfection byproducts requires study of both cancer and noncancer endpoints; however, no studies have evaluated the neurotoxic potential of a common haloacetic acid, dibromoacetic acid (DBA). This study characterized the neurotoxicity of DBA during 6-month exposure in the drinking water of rats. Adolescent male and female Fischer 344 rats were administered DBA at 0, 0.2, 0.6, and 1.5 g/l. On a mg/kg/day basis, the consumed dosages decreased greatly over the exposure period, with average intakes of 0, 20, 72, and 161 mg/kg/day. Weight gain was depressed in the high-concentration group, and concentration-related diarrhea and hair loss were observed early in exposure. Testing with a functional observational battery and motor activity took place before dosing and at 1, 2, 4, and 6 months. DBA produced concentration-related neuromuscular toxicity (mid and high concentrations) characterized by limb weakness, mild gait abnormalities, and hypotonia, as well as sensorimotor depression (all concentrations), with decreased responses to a tail-pinch and click. Other signs of toxicity at the highest concentration included decreased activity and chest clasping. Neurotoxicity was evident as early as one month, but did not progress with continued exposure. The major neuropathological finding was degeneration of spinal cord nerve fibers (mid and high concentrations). Cellular vacuolization in spinal cord gray matter (mostly) and in white matter (occasionally) tracts was also observed. No treatment-related changes were seen in brain, eyes, peripheral nerves, or peripheral ganglia. The lowest-observable effect level for neurobehavioral changes was 20 mg/kg/day (produced by 0.2 g/l, lowest concentration tested), whereas this dosage was a no-effect level for neuropathological changes. These studies suggest that neurotoxicity should be considered in the overall hazard evaluation of haloacetic acids.

Acetates↗
PubMed2002

Constraints on cosmological parameters from the analysis of the cosmic lens all sky survey radio-selected gravitational lens statistics.

We derive constraints on cosmological parameters and the properties of the lensing galaxies from gravitational lens statistics based on the final Cosmic Lens All Sky Survey data. For a flat universe with a classical cosmological constant, we find that the present matter fraction of the critical density is Omega(m)=0.31(+0.27)(-0.14) (68%)+0.12-0.10 (syst). For a flat universe with a constant equation of state for dark energy w=p(x)(pressure)/rho(x)(energy density), we find w<-0.55(+0.18)(-0.11) (68%).

Journal Article↗
PubMed1998

Carbon disulfide neurotoxicity in rats: VII. Behavioral evaluations using a functional observational battery.

The neurobehavioral consequences of inhalational exposure to carbon disulfide (CS2) were evaluated as part of a joint project between the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency. Behavioral changes in rats were measured using a functional observational battery (FOB), which is a series of observations and manipulations designed to assess the neuronal integrity of autonomic, motor, sensory, and integrative functions. Young adult male and female Fischer-344 rats were exposed to one of four CS2 concentrations (0, 50, 500, or 800 ppm, six hours/day, five days/week) and tested at the end of one of several exposure durations (two, four, eight, or 13 weeks). All rats were also tested before exposure began to obtain baseline values. Neuromuscular deficits which were more pronounced in the hindlimbs, e.g., decreased strength and gait alterations, were detected in rats of both sexes. These changes were closely related to CS2 concentration and exposure duration, with mild gait changes evident after only two weeks of exposure. Other effects, mostly observed at 13 weeks, included decreased responsiveness to a visual stimulus and mild tremors. Reactivity in response to handling was generally increased, and excitability in the open field was decreased, in rats tested after the shorter exposures (two and four weeks). Thus, the exposure-concentration and -duration characteristics of the neuromotor syndrome produced by CS2 were detected and defined using the FOB. These studies provide a more complete evaluation of rats under these CS2 exposure conditions, which can then be used to compare with other mechanistic-related endpoints from this collaborative study.

Administration, Inhalation↗
PubMed1997

Relationship of diabetic microvascular complications to outcome in panretinal photocoagulation treatment of proliferative diabetic retinopathy.

Argon laser panretinal photocoagulation for proliferative diabetic retinopathy was shown in the Diabetic Retinopathy Study and Early Treatment Diabetic Retinopathy Study to reduce the incidence of blindness by 50% with relatively small amounts of treatment. However, some diabetics require much more extensive photocoagulation for control of proliferative disease. We attempted to determine risk factors for poor response to treatment with panretinal photocoagulation (PRP) by studying outcome in relation to the argon laser burn count and the presence of diabetic vascular complications. Sixty-six consecutively treated eyes undergoing PRP were studied, of which 57% showed resolution of new vessels 6 weeks after treatment. This was significantly related to the total amount of laser treatment given (mean no. in regressed eyes 5800 burns, non-regressed 3510 burns; p < 0.05). Renal disease and age (< 50 years) were identified as risk factors for non-regression (p < 0.05); hypertension, neuropathy, duration of disease and insulin dependence had no significant effect on outcome. We conclude that regression of proliferative disease is significantly related to the cumulative total number of laser burns applied and that successful laser photocoagulation in patients with diabetic renal disease requires considerably more treatment than that suggested by earlier studies.

Age Factors↗
PubMed1995

An apparent excess of operative site infections: analyses to evaluate false-positive diagnoses.

OBJECTIVE: To investigate an apparent excess of operative site infections (OSI) reported according to doctor's diagnosis (presumptive OSI) by applying objective criteria for classification (documented OSI). To examine potential consequences of habitual overdiagnosis of OSI. DESIGN: A case-control design was used to examine the clinical course of 18 case patients (12 presumptive OSI, six documented OSI) and 18 matched controls. Comparisons also were made between presumptive and documented OSI patients. SETTING: A nonteaching community hospital. PATIENTS: Thirty-six patients having laminectomies done by the same surgeon. INTERVENTION: Implementation of objective criteria for diagnosis of confirmed OSI and reclassification of presumptive OSI patients. RESULTS: Postoperatively, the frequency of specific adverse events within the operative site (including postoperative hematoma or bleeding; wound necrosis, dehiscence, or sinus tract; and dural tear) was 83% for documented OSI patients, contrasted with 16.7% for presumptive OSI patients (P < .01) and controls (P = .007). Median days of inpatient stay were 27 for documented OSI, contrasted with 9.5 for presumptive OSI (P = .01) and 7 for controls (P < .001). CONCLUSION: Documented OSI patients were found to have significantly more adverse findings and longer lengths of stay than presumptive OSI patients or controls. The similarity of findings for presumptive OSI patients and controls suggests that the apparent excess frequency of OSI was caused by incorrect diagnosis. Whereas doctor's diagnosis may be useful as an initial screen for OSI, use of objective criteria for confirming OSI may avert the consequences of overdiagnosis including excessive length of stay and unnecessary therapy, which lead to elevated healthcare costs and threaten a physician's practice.

Aged↗
PubMed1992

Does too much urology damage your eyesight? Study of macular function.

A study comparing the macular function of both eyes of 130 urological surgeons was carried out to investigate whether the increased light exposure to the endoscoping eye caused any deterioration of macular function. The non-endoscoping eye was used as a control. A sophisticated computer test of colour contrast sensitivity was used. The computer assesses the degree of brightness at which the subject is just able to detect a coloured grating, and for each eye this is expressed as a threshold for the red/green axis and the blue/yellow (tritan) axis. The subjects also completed a questionnaire about their working patterns and their general and ophthalmic history and had a brief examination of the fundus. The results do not suggest that urologists are suffering any significant macular damage as a result of their work with endoscopes.

Color Perception↗
PubMed1992

Blue light emission from urological equipment. Can it damage the eyes?

Blue light present in the visible spectrum at the lower wavelengths can cause damage to the retinas of monkeys and rats. In the present study the light sources and instrumentation available to the urologist were evaluated to see whether they posed a hazard. The light emitting directly from the sources, cables and telescopes was tested and these levels were found to be dangerous to the eye when compared with the safety limit recommended by the American Conference of Governmental Industrial Hygienists (ACGIH). When the light at the eyepiece of the telescopes which had been reflected off a surface was measured, the blue light levels did not appear to be harmful when compared with the ACGIH safety limit. The use of filters is discussed and the transmission of 2 types of filters shown. While the level of blue light emission from the eyepiece remains within the ACGIH level, there are no data on long-term exposure. The addition of a blue light filter may be beneficial until such time as videoendoscopy becomes the norm. The light from light sources should be protected by a shutter and more care taken with the emission from cables and telescopes.

Equipment Safety↗
PubMed1991

Rat strain and stock comparisons using a functional observational battery: baseline values and effects of amitraz.

A functional observational battery (FOB) was utilized to assess the effects of 3-day exposure to the formamidine pesticide amitraz in outbred Sprague-Dawley-derived and inbred Fischer-344-derived (F344) rats (both from Charles River Laboratories) and in outbred Long-Evans rats obtained from two commercial suppliers (Charles River Breeding Laboratories and Blue Spruce Farms). Significant strain and stock differences were obtained in baseline values for one-third of the FOB measures. In most cases, F344 rats were different from the others. Characteristic signs of amitraz exposure consisting of increased excitability, hyper-reactivity, and physiological and autonomic changes were evident in all treated rats. These effects increased with repeated dosing, and many were still present 6 days after dosing. On individual measures, there were differences between the strains and stocks in terms of sensitivity and time course of amitraz effects. In general, Blue Spruce Long-Evans rats displayed more effects of amitraz and F344 rats recovered more quickly than others. Although Sprague-Dawley rats showed the least effect overall, they displayed the largest increases in the sensorimotor responses to stimuli. These data indicate that although some behavioral and physiological parameters showed strain and supplier differences, in both baseline values and the effects of amitraz, conclusions concerning its neurotoxic potential in a screening context would be similar.

Animals↗
PubMed1989

Sporadic bacteremia complicating central venous catheter use in a community hospital: a model to predict frequency and aid in decision-making for initiation of investigation.

Sporadic bacteremia complicating single-lumen central venous catheter (CVC) use was prospectively recorded in a community hospital in 1981 and 1982. Sixty-four of 1258 (5.1%) patients had definite bacteremia. A nested case-control study was then undertaken to identify predictive risk factors. Fifteen statistically significant factors found in the 1981 cohort were tested in the 1982 cohort, and four remained significant for both years. Univariate and multiple logistic regression analysis on both years' findings, separately and together, identified two independently associated factors: diagnosed respiratory colonization/infection (p less than 0.0001) and serum albumin level (p less than 0.001). Based on these factors, an equation was developed to express the probability of bacteremia. Solving this equation provides an infection control practitioner with an expected rate of bacteremia that complicates CVC use and provides an aid for decision-making for investigation in the absence of clusters.

Catheterization, Central Venous↗
PubMed1986

Mitotic activity in cells of the wool follicle bulb.

Mitotic activity in the cells of the germinative region of wool follicle bulbs was quantified by using small (0.1-0.5 ml) intradermal doses of colchicine and selective staining of the metaphase-blocked nuclei using either crystal violet, iodine and eosin or haematoxylin and eosin. The number of metaphase nuclei present 3 h after colchicine administration increased with colchicine dose from 0 to 1 microgram and thereafter remained relatively constant up to 200 micrograms colchicine. The accumulation of metaphase nuclei was linear for up to 6 h after intradermal colchicine. The metaphase-blocking effect of intradermal colchicine was confined to a radius of less than 5 cm from the injection site, allowing a number of estimates of mitotic rates to be made over a small area of skin. Such estimates revealed little variation in mitotic activity over the midside region of the sheep, although there were substantial differences in follicle activity at different sites over the body. The technique is simple, allows serial or concurrent estimates of mitotic activity to be made in the same animal, and eliminates problems associated with intravenous colchicine administration. It was used to derive the relationship between follicle activity and fibre production after nutritional changes, and to define the time course of mitotic events after administration of the antimitotic defleecing agent cyclophosphamide.

Animal Nutritional Physiological Phenomena↗
PubMedDate not supplied

Potential developmental toxicity of anatoxin-a, a cyanobacterial toxin.

Some 2000 species of cyanobacteria (blue-green algae) occur globally in aquatic habitats. They are able to survive under a wide range of environmental conditions and some produce potent toxins. Toxin production is correlated with periods of rapid growth (blooms) and 25%-70% of blooms may be toxic. Anatoxin-a is an alkaloid neurotoxin that acts as a potent neuro-muscular blocking agent at the nicotinic receptor. Acute toxicity, following consumption of contaminated water, is characterized by rapid onset of paralysis, tremors, convulsions and death. Human exposures may occur from recreational water activities and dietary supplements, but are primarily through drinking water. The current studies were conducted to examine the effect of in utero exposure on postnatal viability, growth and neurodevelopment, to evaluate the potential of in vitro embryotoxicity, and to explore the synergistic relationship between anatoxin-a and the algal toxin microcystin-LR by the oral route. The results of preliminary studies on amphibian toxicity are also reported. Time-pregnant mice received 125 or 200 microg kg(-1) anatoxin-a by intraperitoneal injection on gestation days (GD) 8-12 or 13-17. Pup viability and weight were monitored over a 6-day period. Maternal toxicity (decreased motor activity) was observed at 200 microg kg(-1) in both treatment periods. There were no significant treatment-related effects on pup viability or weight on postnatal day (PND) 1 or 6. The GD 13-17 pups were evaluated on PND 6, 12 and 20 for standard markers of neurodevelopmental maturation (righting reflex, negative geotaxis and hanging grip time). No significant postnatal neurotoxicity was observed. In vitro developmental toxicity was evaluated in GD 8 mouse embryos exposed to 0.1-25 microm anatoxin-a for 26-28 h. Perturbations in mouse yolk sac vasculature were noted from the 1.0 microm concentration in the absence of significant embryonic dysmorphology. Potential algal toxin synergism was tested in mice receiving either 0, 500 or 1,000 microg kg(-1) microcystin-LR by gavage and approximately 50 min later receiving either 0, 500, 1,000 or 2,500 microg kg(-1) anatoxin-a by the same route. No deaths occurred at any dose and no definitive signs of intoxication were observed. Stages 17 and 25 toad embryos (Bufo arenarum) were exposed to 0.03-30.0 mg l(-1) of anatoxin-a for 10 days. Adverse effects included a dose-dependent transient narcosis, edema and loss of equilibrium. Most notable was the occurrence of 100% mortality at the high dose in both groups 6-13 days post-exposure. The observed delay between initial exposure and death is highly unusual for anatoxin-a.

Animals↗
PubMedDate not supplied

Behavioral evaluation of the neurotoxicity produced by dichloroacetic acid in rats.

Dichloroacetic acid (DCA) is commonly found in drinking water as a by-product of chlorination disinfection. It is a known neurotoxicant in rats, dogs, and humans. We have characterized DCA neurotoxicity in rats using a neurobehavioral screening battery under varying exposure durations (acute, subchronic, and chronic) and routes of administration (oral gavage and drinking water). Studies were conducted in both weanling and adult rats, and comparisons were made between Long-Evans and Fischer-344 rats. DCA produced neuromuscular toxicity comprised of limb weakness and deficits in gait and righting reflex; altered gait and decreased hindlimb grip strength were the earliest indicators of toxicity. Other effects included mild tremors, ocular abnormalities, and a unique chest-clasping response (seen in Fischer-344 rats only). Neurotoxicity was permanent (i.e., through 2 years) following a 6-month exposure to high dose levels, whereas the effects of intermediate dose levels with exposures of 3 months or less were slowly reversible. The severity, specificity, and recovery of neurological changes were route, duration, and strain dependent. Fischer-344 rats were more sensitive than Long-Evans rats, and weanling rats may be somewhat more sensitive than adults. Oral gavage produced significantly less toxicity compared to the same intake level received in drinking water. Neurotoxicity was progressive with continued exposure, and was observed at exposure levels as low as 16 mg/kg/day (lowest dose level tested) when administered via drinking water in subchronic studies. The data from these studies characterize the neurotoxicity produced by DCA, and show it to be more pronounced, persistent, and occurring at lower exposures than has been previously reported. Further research should take into account these marked route, age, and strain differences.

Administration, Oral↗