Search PubMed⌕ Search

Biomedical subjects

P H Berry

Publications and source records attributed to P H Berry.

At least 19 recordsLinked to original sources
PubMed1997

Making a difference.

Explore the source record for details and available documents.

Attitude of Health Personnel↗
PubMed1994

Evaluation of the neurotoxic potential of chemicals in animals.

This review provides a scientific view on how to evaluate effectively the neurotoxic potential of chemicals in order to provide adequate safeguards for human health. Detection of compounds that may cause direct, persistent, adverse effects on the nervous system should be given the most critical attention. Evaluation of the neurotoxic potential of a chemical should include descriptions of functional and morphological effects as well as the determination of the dose response, no-observed-effect level, time course and reversibility of effects. Evaluation of the nervous system in the context of standard toxicity studies that use a variety of species and study durations are appropriate screening tests (Tier 1) for the detection of potential neurotoxicity. Studies specifically designed to assess neurotoxicity (Tier 2) should be performed with chemicals for which there is an indication of neurotoxic potential and where the available data are inadequate for risk assessment. Tier 2 studies should evaluate the function and structure of the nervous system by comprehensive clinical examinations and neuropathological assessment. These studies may be conducted in conjunction with standard toxicity studies so that any potential neurotoxicity can be interpreted in the context of other systemic toxicity. More specific neurotoxicity tests (Tier 3) may be necessary for advanced characterization of discovered neurotoxicants.

Animals↗
PubMed1992

Feeding studies in rats with mineral hydrocarbon food grade white oils.

This investigation compared the effects of feeding rats diets containing food grade white oil processed by either conventional oleum treatment or the more modern method of catalytic hydrogenation. In two separate experiments, male or female Fischer-344 rats were given free access for 90 days to diets containing 0, 10, 100, 500, 5,000, 10,000, or 20,000 ppm of either oleum-treated white oil (OTWO) or hydrotreated white oil (HTWO). There were no mortalities and no adverse clinical signs associated with feeding either white oil. Treatment-related effects evidenced by hematological, clinical chemical, and pathological changes were generally dose-related and more marked in female than in male rats, and the OTWO caused a greater pathological response than the HTWO. Tissue residues of saturated hydrocarbons were up to 5.2 times higher in female rats than in males. Rats fed 5,000 ppm or more of either white oil showed dose-related alterations in several hematological and clinical chemistry variates associated mainly with hepatic damage or functional alteration. At necropsy, mesenteric lymph nodes were enlarged, and increases in weight of liver, kidney, and spleen were significant. Microscopic changes were characterized by multifocal lipogranulomata in mesenteric lymph node and liver. No changes were observed in rats fed OTWO or HTWO for 90 days at dietary concentrations of 10 or 100 ppm, equivalent to a minimum intake of 0.65 and 6.4 mg/kg/day, respectively. Differences in degree of pathological response associated with each oil may have been due to their differences in specification rather than processing method.

Animals↗
PubMed1988

Preclinical evaluation of lovastatin.

Administration of lovastatin to animals at high dosage levels produces a broad spectrum of toxicity. This toxicity is expected based on the critical nature of the target enzyme (HMG CoA reductase) and the magnitude of the dosage levels used. The information reviewed in this paper demonstrates that these adverse findings in animals do not predict significant risk in humans. The reason for this derives from the fact that all the available evidence suggests that the adverse effects observed are produced by an exaggeration of the desired biochemical effect of the drug at high dosage levels. The presence of clear and high no-effect doses for these toxic effects along with the fact that most of the changes observed are clearly mechanism-based (directly attributable to inhibition of mevalonate synthesis) indicate that it is unlikely that similar changes will be observed at the therapeutic dosage levels in humans. This hypothesis is supported by the extensive human safety experience described by Tobert in the following report.

Animals↗
PubMed1988

Brain and optic system pathology in hypocholesterolemic dogs treated with a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

The cholesterol lowering compound lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34 HMG CoA reductase), was given in nine separate experiments to normocholesterolemic dogs at rates up to 180 times the maximum therapeutic dose in man (1 mg/kg/day). Mean serum total cholesterol concentrations were reduced as much as 88% below normal. Clinical evidence of neurotoxicity occurred in up to 37% of animals given 180 mg/kg/day lovastatin for 11 or more days, especially in one laboratory where the dosing regime resulted in higher concentrations of plasma drug levels. Dogs receiving 60 mg/kg/day or less never exhibited neurologic signs. The central nervous system (CNS) of affected dogs exhibited endothelial degeneration and hemorrhagic encephalopathy. Focal extravasation of horseradish peroxidase occurred frequently (6/8) in the retrolaminar optic nerve of asymptomatic or clinically affected dogs given 180 mg/kg/day lovastatin, with endothelial degeneration and discrete optic nerve degenerative lesions interpreted as ischemic. The association between the degree of hypocholesterolemia and occurrence of clinical signs was not exact. Total brain cholesterol was similar in treated and control dogs. Hypocholesterolemic dogs had proportionally lowered serum concentrations of alpha-tocopherol, but oral supplementation of this vitamin did not prevent the neurologic syndrome. Endothelial degeneration in the CNS and optic nerve may have reflected in vitro morphologic effects of HMG CoA reductase inhibitors due to extreme inhibition of nonsterol isoprene synthesis. Retinogeniculate axonal (Wallerian-like) degeneration occurred in greater than or equal to 12% of dogs given 60 mg/kg/day or more lovastatin, with central chromatolysis of occasional retinal ganglion cells. These neuroaxonal changes may have been secondary to vascular effects, but superimposed direct neurotoxic action at the high dosage levels of lovastatin could not be excluded. There was no evidence of drug induced adverse effects in the CNS of dogs given up to 30 mg/kg/day lovastatin for 2 years.

Animals↗
PubMed1986

Community hospital to trauma center.

The Committee on Trauma of the American College of Surgeons published a report in 1976 charging hospitals to provide care for seriously injured patients. Implementing an effective emergency care/trauma system in a not-for-profit community hospital was a task that demanded leadership, substantial time, and commitment. The building process could not have begun without a strong commitment from the hospital's board, administration, medical staff, and nursing service. Initially, the operating rooms, radiology, intensive care units, and emergency departments were renovated or replaced. General surgeons and surgical subspecialists committed to trauma care were recruited. Emergency department (ED) physicians were upgraded and resident rotations in the ED were begun. A ground and helicopter transport system was initiated; dispatch was centered in the ED. Educational programs in prehospital critical care and stabilization for flight nurses and EMT's were developed. The operating rooms began 24-hour service with in-house anesthesia coverage. Radiology provided 24-hour coverage of specialty services. Physicians began in-house coverage of the critical care units. The department of surgery developed a trauma section to encompass all the general surgeons and subspecialty physicians in emergency care. Monthly in-service programs were begun for the intensive care unit (ICU) and ED nurses. In each of the past 3 years, a 2-day trauma update program has been provided to the regional Emergency Medical Services (EMS) and medical community. The dedication and commitment of many people during the past 5 years has resulted in a sound system of emergency/trauma care in a community hospital.

Emergency Medical Services↗
PubMed1986

Effect of diet or reproductive status on the histology of spontaneous pituitary tumors in female Wistar rats.

Hypophyses of four groups of 50 female rats (F0--nulliparous, F0--multiparous, F1--standard diet, and F1--low protein) were examined by light microscopy and immunocytochemistry by the avidin-biotin complex method. In pituitary glands of rats fed a low protein diet, the incidence of neoplasms of the pars distalis, the number of multifocal tumors, and the degree of neoplastic cellular atypia were significantly reduced. Pituitary adenomata in rats fed a low protein diet also caused significantly less brain compression at the time of necropsy than in rats fed a standard diet. All but two neoplastic foci from the 83 tumors stained for prolactin, and 14 of these also stained for growth hormone. No differences were found in the frequency of hemorrhagic or solid patterns of tumor. These findings may reflect a reduction in pituitary tumor initiation, promotion, and/or progression in rats fed a low protein diet.

Adenoma↗
PubMed1983

Computed tomography of the pelvis in patients with multiple injuries.

The extent of osseous pelvic injury in patients suffering multiple organ trauma is difficult to assess. However, accurate information is essential in order to determine an acceptable treatment regimen, either operative (external or internal fixation), or nonoperative (bed rest and early ambulation). Twenty consecutive patients were treated for pelvic fractures from January 1981 through February 1982. All patients had multiple organ injuries, (average = 3.5 organ systems per patient). Each patient had an A-P X-ray projection of the pelvis in the emergency department (E.D.) as a part of the initial evaluation. Three patients (15%) required immediate laparotomy for associated abdominal injuries. Six patients (30%) required prolonged ventilatory support for pulmonary injuries. Computed tomography (CT) of the pelvis was performed on all patients within 4 days of admission. In seven patients, CT examination confirmed the findings of the routine X-rays obtained in the E.D. In 13 patients the CT examination demonstrated significant additional fractures of the pelvis which were not initially demonstrated in the E.D. A consistent pattern of either sacral fracture or injury to the sacroiliac joint which was not appreciated on the initial E.D. X-rays was demonstrated in these 13 patients. Six patients underwent operative intervention, four with Hoffmann frames (external fixation), and two with reduction and internal fixation. CT examination of the pelvis provides a rapid and thorough evaluation which is extremely useful in demonstrating all the fractures of the pelvis on the single examination, thereby allowing the early determination of the best treatment plan for patients with such major injuries.

Accidents, Occupational↗
PubMed1982

Toxicity studies of the toxins isolated from annual ryegrass (Lolium rigidum) infected by Corynebacterium rathayi.

Estimates of the LD50's of 7 glycolipid toxins (corynetoxins) isolated from toxic annual ryegrass varied in the range 0 . 1-1 . 3 mg/kg in 2-week-old rats. The delay in onset of neurological signs in rats and sheep was independent of dose rate and could be the result of inhibition of protein biosynthesis. In sheep, no influence of the route of administration on the delay in onset of neurological signs was demonstrated. The relationship between the partial structures of the two major corynetoxins and their toxicity is discussed.

Animals↗
PubMed1982

Hepatic damage in sheep fed annual ryegrass, Lolium rigidum, parasitised by Anguina agrostis and Corynebacterium rathayi.

Annual ryegrass (Lolium rigidum) parasitised by Anguina agrostis and Corynebacterium rathayi causes neurological signs and brain lesions thought to be associated with a vasoconstrictor effect of the toxic grass. In three separate experiments of six to 112 days duration parasitised ryegrass was fed to 21 adult sheep. The concentrations of many blood constituents were examined, liver biopsies taken, necropsies performed and tissues other than brain examined by light and electron microscopy. The invariable finding was liver damage indicated by increased plasma concentrations of liver specific enzymes and bilirubin. There was diffuse vacuolation of hepatocytes due to gross distension of cisternae of rough endoplasmic reticulum, as well as necrosis of individual hepatocytes, fatty change, biliary hyperplasia and hepatocytic regeneration. The changes were not typical of experimental hepatic ischaemia and may have been due to a cytopathic effect of toxic annual ryegrass.

Animal Feed↗
PubMed1981

Isolation of a group of glycolipid toxins from seedheads of annual ryegrass Lolium rigidum Gaud.) infected by Corynebacterium rathayi.

A group of highly toxic compounds was isolated from galled seedheads of annual ryegrass (Lolium rigidum Gaud.) containing Corynebacterium rathayi. Purified extracts were resolved by reverse-phase high-performance liquid chromatography into eight main fractions which have been partially characterised and shown to be toxic to nursling rats. A mixture of the toxins also produced clinical signs and brain lesions in lambs consistent with annual ryegrass toxicity. The name 'corynetoxin' is tentatively proposed for the series, individual members being designated according to their order of elution from the high performance liquid chromatography column as corynetoxins 1 to 8. The two main fractions are corynetoxins 3 and 4 of which the former has been crystallised. They appear to be of glycolipid character, 3-hydroxyheptadecanoic acid and a C6 amino sugar being identified among the hydrolysis products of corynetoxin 3, and heptadec-2-enoic acid and a C6 amino sugar from corynetoxin 4.

Animals↗