Physiological and biochemical variables in captive tigers (Panthera tigris) immobilised with dexmedetomidine and ketamine or dexmedetomidine, midazolam and ketamine.

Physiological and biochemical variables in captive tigers (Panthera tigris) immobilised with dexmedetomidine and ketamine or dexmedetomidine, midazolam and ketamine were evaluated. Thirty tigers received either dexmedetomidine (0.025 mg/kg) and ketamine (3 mg/kg) (group DK) or dexmedetomidine (0.0125 mg/kg), midazolam (0.1 mg/kg) and ketamine (3 mg/kg) (group DMK). Heart rate, SPO2 and blood pressure were measured at five-minute intervals. Arterial pH, PO2, PCO2, glucose, K+ and arterial and venous lactate were measured at 15 and 45 minutes after immobilisation. A generalised linear mixed model was used for statistical comparison. There was no difference within or between groups at any time point for any measured variable. Measured PO2 was 73.2±17.5 mm Hg and SPO2 was 88.9±10.8 per cent. Systolic, mean and diastolic blood pressures were 170.5±48.4, 138.9±41.8 and 121.8±37.2 mm Hg, respectively. Venous lactate was higher than arterial lactate within groups at each time point. Seizure-like behaviour was observed in 25 per cent of tigers in group DK but not in group DMK. The addition of midazolam into a protocol for immobilisation of tigers did not result in a difference in any of the measured variables but may have prevented the development of seizure-like behaviour.

Effects of phthalic acid esters on the liver and thyroid.

The effects, over periods from 3 days to 9 months of administration, of diets containing di-2-ethylhexyl phthalate are very similar to those observed in rats administered diets containing hypolipidemic drugs such as clofibrate. Changes occur in a characteristic order commencing with alterations in the distribution of lipid within the liver, quickly followed by proliferation of hepatic peroxisomes and induction of the specialized P-450 isoenzyme(s) catalyzing omega oxidation of fatty acids. There follows a phase of mild liver damage indicated by induction of glucose-6-phosphatase activity and a loss of glycogen, eventually leading to the formation of enlarged lysosomes through autophagy and the accumulation of lipofuscin. Associated changes are found in the kidney and thyroid. The renal changes are limited to the proximal convoluted tubules and are generally similar to changes found in the liver. The effects on the thyroid are more marked. Although the levels of thyroxine in plasma fail to about half normal values, serum triiodothyronine remains close to normal values while the appearance of the thyroid varies, very marked hyperactivity being noted 7 days after commencement of treatment, this is less marked at 14 days, but even after 9 months treatment there is clear cut evidence for hyperactivity with colloid changes which indicate this has persisted for some time. Straight chain analogs of di-2-ethylhexyl phthalate, di-n-hexyl phthalate and di-n-oxtyl phthalate differ entirely in their short-term effects on the liver and kidney but have similar effects on the thyroid. The short-term in vivo hepatic effects of the three phthalate esters can be reproduced in hepatocytes in tissue culture. All three phthalate esters, as well as clofibrate, have early marked effects on the metabolism of fatty acids in isolated hepatocytes. The nature of these changes is such as to increase storage of lipid in the liver. A hypothesis is presented to explain the progress from these initial metabolic effects to the final formation of liver tumors.

Investigations of the genotoxicity and cell proliferative activity of dichlorvos in mouse forestomach.

This study investigated the possible mechanism by which dichlorvos may have caused forestomach tumours in mice in a chronic corn oil gavage cancer bioassay [NTP (1989) Toxicology and carcinogenesis studies of dichlorvos in F344/N rats and B6C3F1 mice (gavage studies). National Toxicology Program Technical Report 342, NIH Publ. No 89-2598]. For this purpose, a method has been developed to assess the genotoxicity of irritant substances on mouse forestomach epithelium. Groups of five B6C3F1 mice were given a single oral dose of dichlorvos, the genotoxic forestomach carcinogen 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) or the irritant, non-genotoxic forestomach carcinogen butylated hydroxyanisole (BHA). After periods of 2-48 h, three parameters were assessed: unscheduled DNA synthesis (UDS) by autoradiography of tissue sections, replicative DNA synthesis (RDS) also by autoradiography of incorporated [3H]thymidine, and histopathological changes, including hyperplasia. MNNG induced UDS but not RDS or hyperplasia in forestomach epithelium, consistent with its genotoxic mode of action. BHA and dichlorvos did not induce UDS, consistent with absence of genotoxic activity in the forestomach after in vivo exposure. In contrast, BHA and dichlorvos induced RDS and subsequent hyperplasia, which is likely to result from irritant damage. These data suggest that the chronic effects of dichlorvos on mouse forestomach epithelium in the oral gavage bioassay were mediated via enforced cell proliferation, rather than by a genotoxic mechanism.

Time and dose study on the response of rats to the hypolipidaemic drug fenofibrate.

Groups of male Wistar albino rats were administered diets containing sufficient fenofibrate to ensure intakes of either 200, 60 or 13 mg/kg/day or sufficient clofibrate to ensure an intake of 400 mg/kg/day. Four rats from each experimental group and 6 control rats were killed, 3, 7, 14 and 28 days, 8, 12 and 20 weeks and 6, 9, 12 and 18 months after commencement of treatment. At all time points livers were subjected to histological, electron microscopic and biochemical examination, the other major abdominal organs were removed for histological examination. A more extensive necropsy was carried out on rats killed after 12 and 18 months. The major alterations were observed in the liver, although there were also morphological changes in the thyroid, pancreas and kidney after prolonged treatment. The hepatic changes followed a distinct time course. Within 24 h of offering diets containing the compounds to the rats there was accumulation of small droplets of lipid, induction of peroxisomal enzymes and of the specific cytochrome P-450 catalysing omega-hydroxylation of fatty acids and an increase in the number of mitotic figures. More slowly developing changes were loss from the centrilobular zone of fat, glycogen and of glucose 6-phosphatase activity. Here maximal changes were observed after 14 days of treatment. A still more slowly developing change was accumulation of enlarged lipid-loaded lysosomes, which was maximal at 26 weeks, accompanied by the development of lipofuscin bodies. Finally, in animals treated for 12 months or more there was evidence for increasing cell turnover as indicated by an increased number of mitotic figures, more dark cells and induction of serum alanine transaminase. The last 2 groups of changes were not observed in rats treated with 13 mg/kg/day of fenofibrate. In general the degree of change in rats treated with 400 mg/kg/day of clofibrate was similar to those found in rats treated with 60 mg/kg/day of fenofibrate.

Lipid accumulation in the livers of chlorpromazine-treated rats does not induce peroxisome proliferation.

Treatment of rats with 25 mg/kg/day of the neuroleptic drug chlorpromazine for periods of 7, 28 or 90 days causes a slow accumulation of lipid in large droplets in centrilobular hepatocytes. There is little or no damage to hepatocytes as assessed by changes in glucose-6-phosphatase activity and by electron microscopy. Furthermore there is no indication of a change in peroxisomal beta-oxidation of fatty acids or in microsomal omega-oxidation of fatty acids. It is, therefore, clear that lipid accumulation in the liver does not automatically induce peroxisomal and microsomal fatty acid oxidising enzymes.

Alterations in the thyroids of rats treated for long periods with di-(2-ethylhexyl) phthalate or with hypolipidaemic agents.

Treatment of rats for periods of 3 months or longer with the hypolipidaemic drugs clofibrate and fenofibrate or with the plasticiser di-(2-ethylhexyl) phthalate causes alterations in the thyroid. The colloid is shrunken and contains calcium-rich inclusions. Electron microscopy shows increases in the number and size of lysosomes, hypertrophy of the Golgi apparatus and dilation of the rough endoplasmic reticulum. These changes are consistent with persistent hyperactivity in the gland.

Effects on male rats of di-(2-ethylhexyl) phthalate and di-n-hexylphthalate administered alone or in combination.

The effects of phthalate esters of branched chain alcohols, typified by di-(2-ethylhexyl)phthalate (DEHP) differ from those of esters of straight chain alcohols typified by di-n-hexyl phthalate (DnHP). The former induce liver enlargement and proliferation of hepatic peroxisomes, while the latter cause no peroxisome proliferation but cause fat accumulation in the liver. Both classes of phthalate esters are hypolipidaemic and cause thyroid changes associated with an increased rate of thyroglobulin turnover. As phthalate esters are used as mixtures, we have examined the effect of mixtures of the compounds. Groups of five male Wistar albino rats were administered either control diet or diets containing either 10000 ppm of DEHP, 10000 ppm of DnHP or 10000 ppm DEHP plus 10000 ppm DnHP for 14 days. Rats receiving diets containing DEHP showed the expected increase in relative liver weight, in "peroxisomal" fatty acid oxidation and in CYP4A1. Serum triglyceride and serum cholesterol were also reduced, and the thyroid showed the histological changes mentioned above. Rats consuming diets containing DnHP showed no increase in relative liver weight and no induction of peroxisomal fatty acid oxidation or CYP4A1. However, there was a marked accumulation of fat in the liver. The fall in serum cholesterol was similar to that in rats treated with DEHP, but the fall of serum triglyceride was more pronounced. Thyroidal changes were again observed. In general, changes in rats treated with a mixture of DEHP and DnHP were very similar to those found with rats treated with DEHP alone. The liver was enlarged, and peroxisomal fatty acid oxidation and CYP4A1 were both induced. The amount of fat in the liver was much less than in rats receiving DnHP alone. Thyroid changes were similar to those in rats receiving the individual compounds. The effect on serum cholesterol seemed additive, but the levels of serum triglyceride were intermediate between the groups receiving the single compounds.

Are inbreeders better colonizers?

In order to test whether inbreeders are better colonizers, the Flora of the British Isles was surveyed for tabulating the distribution of colonizers and noncolonizers in relation to breeding systems and longevity. Several criteria and difficulties associated with such comparative surveys are briefly discussed. No overwhelming evidence for association was found between longevity and colonizing ability although predominant selfing was found to be significantly more common among the colonizers. However, such evidence for associations among various genetic and ecological factors accounting for high colonizing ability must be interpreted with caution when the role of longevity, ploidy, interfamily and interpopulation genetic variation, uncertainties about the habitat classification, etc., are taken into account.

Hepatic nuclear and cytoplasmic effects following intermittent feeding of rats with di(2-ethylhexyl) phthalate.

The effects on rats of intermittent feeding with the peroxisome proliferator and hepatocarcinogen di(2-ethylhexyl) phthalate (DEHP) have been examined. Male Wistar rats were fed for alternate 7-day periods diets containing 20,000 ppm DEHP or the control diet. The rats were examined 3 days after the start or recommencement of administration of the DEHP-containing diet or after 7 days on the control diet. After the commencement or recommencement of feeding with DEHP the expected increases in liver weight and in the number of peroxisomes were found. The increase in liver: body-weight ratio in response to administration of DEHP-containing diets was greater in rats that had been previously exposed to the compound, but re-administration of DEHP had a less marked effect on the increase in peroxisome number. Morphometric analysis showed that administration of DEHP-containing diets resulted in an increase in cell number in the liver and that a fall in the cell number occurred after the rats had been returned to the control diet for 7 days. Analysis of nuclear size gave results consistent with an increase in tetraploid hepatocytes after treatment with DEHP which was reversed when the rats were returned to control diet.

Hepatic and associated response of rats to pregnancy, lactation and simultaneous treatment with butylated hydroxytoluene.

This paper describes changes in the livers of rats fed diets containing butylated hydroxytoluene (BHT) over two generations in two separate studies. BHT did not produce tumours when tested for carcinogenicity in several studies by the conventional way. However, when BHT was given to rats in a two-generation carcinogenicity study, a high incidence of hepatic tumours was found in males but not in female rats of the F1 generation. A sequential study has been carried out to gain an insight into this unexpected finding, paying particular attention to the perinatal period. In the dose-ranging study designed to assess the tolerance of rats to BHT, groups of male and female rats (F0 generation) were fed diets calculated to deliver 0, 500, 750 and 1000 mg/kg body weight/day. Following a loading period of 5 wk the rats were mated. The BHT content of the diet was not adjusted during pregnancy and lactation. Owing to the normal increase in food consumption during lactation, intakes peaked at double the nominal value by 21 days after the birth of pups. At this time the pups (F1) were weaned onto control diet and maintained on it for 4 wk. At birth, the body weights of pups from the BHT-treated dams were comparable to those of the controls but at weaning the body weights of the pups from all three dose levels were less than those of the controls. At the termination of the experiment (4 wk after weaning), the pups from BHT-treated dams still weighed less than those from untreated controls. In the main experiment the F0 generation were fed 0, 25, 100 and 500 mg/kg body weight/day. Their offspring (F1 generation) were weaned on diets containing the same amount of BHT as the respective parents, apart from the group given the highest dose level (500 mg/kg body weight/day). This dose level was reduced to 250 mg/kg body weight/day at weaning in order to conform with previously published findings. The pups from the dams given the highest dose level were maintained on a dietary concentration of 250 mg/kg body weight/day for the entire study. A group of age-matched non-pregnant females was also studied and the results obtained compared with those from pregnant dams. Pups from all groups were examined at day 20 of gestation, at weaning (21 days after birth), and at 4 and 22 wk post-weaning. There were no effects on fertility and no increase in foetal abnormalities at any dose of BHT. Dams receiving BHT at a nominal dose of 500 mg/kg body weight/day showed liver enlargement accompained by induction of pentoxyresorufin O-depentylase and glutathione S-transferase, and proliferation of the endoplasmic reticulum. Pups from these dams were of the same weight at birth as controls but lost weight during the lactation period. This deficit was not recovered by the time the experiment was terminated. Hence, in two independent studies, the only significant finding in rats treated with BHT in utero and during lactation was that the weight gain of pups during lactation was less than expected when dams received at least 500 mg BHT/kg body weight/day. The body weight of pups did not return to normal following a return to a control diet for 4 wk. It is postulated that the retardation in weight gain of the pups could be due to inadequate milk production.

Using a computer to manage the radiation safety and quality control activities in diagnostic radiology.

Software has been developed to aid in the management of a radiation safety quality control program in diagnostic radiology. The core of the system is a data base of radiation safety activities. Software design goals were the prioritization, scheduling, and reporting of these activities. Computerization has helped organize the timely performance of surveys necessary for compliance with regulatory and accreditation agencies. Clear, concise program documentation and reporting are also provided.

Improved calibrations using personal computers.

There are a variety of commercial devices available for the non-invasive verification of x-ray unit calibration. This article describes the use of custom-developed IBM PC compatible software in conjunction with a commercial unit to produce clearer and more meaningful graphical representation of linearity, kilovoltage and timer accuracy. The authors also detail how a personal computer can aid service personnel in the resolution of calibration problems.

Pitfalls of rare earth imaging: conquering the three Ps.

Rare earth technology has become the standard in radiographic imaging, but misapplication and insufficient comprehension of the variables of usage create practical problems. Special problem areas are pediatrics, portable radiography and phototimed exposures. These problems, as well as possible solutions, are addressed in this article.

The influence of film-screen color sensitivity and type of measurement device on kVp measurements.

Three methods for evaluating radiographic kVp were studied: the Wisconsin Test Cassette, the Noninvasive Evaluator of Radiation Outputs (NERO), and the Dynalyzer. The Dynalyzer kVp readings were the highest and were followed by NERO and cassette readings in descending order. By film type, the cassette readings ranged from Kodak OG (green sensitive), TMG (green sensitive), XK (blue sensitive), and XRP (blue sensitive) in descending order. The results show that there is significant variation between the methods.

Chemical substance use among R.T.s in Georgia.

This article describes the results of a survey on the prevalence of chemical substance use by radiologic science professionals. The sample population was a random selection of registered radiographers, nuclear medicine technologists, radiation therapists and diagnostic medical sonographers in Georgia. Prevalence rates of 11 major drug categories among this population are presented and compared with prevalence rates among the general U.S. population, both nationally and regionally. Results showed that the study group had higher use rates than the general population for some drugs, such as analgesics and stimulants, and lower use rates for other drugs, including tobacco, tranquilizers and sedatives. Significant associations regarding drug use also are reported. Implications include the need for increased drug education and increased attention to customized employee assistance programs.

The effects of hyperglycemia and endotoxemia on coagulation parameters in healthy adult horses.

BACKGROUND: Hyperglycemia and endotoxemia have been associated with coagulation abnormalities in horses. Studies in humans suggest greater disturbances in coagulation with hyperglycemia and concurrent endotoxemia. OBJECTIVES: To compare coagulation parameters in horses administered with lipopolysaccharide (LPS) with and without concurrent hyperglycemia. ANIMALS: Twelve healthy adult horses. METHODS: Hyperglycemia (180-240 mg/dL) was maintained for 6 hours in 6 horses (GLU-LPS) using 140 mg/kg IV bolus of dextrose followed by a 20% dextrose constant rate infusion. A similar volume of saline was administered to an additional 6 horses (SAL-LPS). LPS (20 ng/kg) was administered to each horse. Fibrogen concentration, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin antithrombin concentration (TAT), and thromboelastometry were measured at baseline and after 1, 1.5, 2, 2.5, 3, 4, 6, and 22 hours. Repeated measures analysis of variance was used to examine temporal changes. RESULTS: Increases in PT (P = .001) and TAT (P = .027) were observed in the GLU-LPS group. Changes in thromboelastometry parameters including increased clot formation time (In-TEM, P = .006; Ex-TEM, P = .002) and decreased alpha angle (Ex-TEM, P = .04) and maximal clot firmness (Ex-TEM, P = .014) were observed in the SAL-LPS group. Differences between SAL-LPS and GLU-LPS groups were limited to increased maximal clot firmness (Ex-TEM) at 3, 6, and 22 hours (P < .001) in the SAL-LPS group. CONCLUSIONS AND CLINICAL IMPORTANCE: Minor alterations in coagulation parameters identified for each group are most likely not clinically relevant. Observed differences between groups do not suggest that concurrent hyperglycemia and endotoxemia are associated with greater coagulation abnormalities in horses.

Caring for older people: a challenge for nurse administrators.

The findings of this exploratory study emphasize the importance of communication between and among nurse administrators in various settings for patient education, staff development and coordination of services to provide continuity of care for older people. The nurse administrator in all settings is in a key position to seek internal and external funding for creative programs and establishing standards for care. This study has merely tapped the surface; much more research needs to be carried out, especially in nursing homes, to understand the complex health problems of older people.