Long-term carcinogenicity study in Syrian golden hamster of particulate emissions from coal- and oil-fired power plants.

Male Syrian golden hamsters were given 15 weekly intratracheal instillations with suspensions of coal fly ash or oil fly ash. Controls were instilled with saline containing gelatine (0.5 g/100 mL) or to check particle effects with suspensions of hematite (Fe2O3). The common weekly dose was 4.5 mg/hamster. In addition, one subgroup of hamsters was treated with oil fly ash at a weekly dose of 3.0 mg/hamster and another with coal fly ash at a weekly dose of 6.0 mg/hamster. Other groups of hamsters were treated with suspensions of benzo[a]pyrene (BaP) or with suspensions on coal fly ash, oil fly ash, or Fe2O3 coated with BaP. The mass median aerodynamic diameters of the coal and oil fly ashes were 4.4 microns and 28 microns, respectively. Hamsters treated with oil fly ash showed a higher frequency of bronchiolar-alveolar hyperplasia than hamsters in the other treatment groups. Squamous dysplasia and squamous metaplasia were most frequent in animals treated with suspensions of BaP or BaP-coated particles. The earliest appearance of a tumor, the highest incidence of tumors, and the highest incidence of malignant tumors were observed in hamsters treated with oil fly ash coated with BaP. Squamous cell carcinoma and adenosquamous carcinoma were the most frequent malignant tumors. No malignant tumors and only few benign tumors were observed in hamsters instilled with suspensions of fly ash not coated with BaP. The present study gives no indication that coal fly ash could create more serious health problems than oil fly ash.

Myoepithelial cells in salivary gland neoplasms.

Archival paraffin sections from normal salivary gland tissue and salivary gland neoplasms were stained by immunoperoxidase technique with a well characterized cytokeratin antibody (PKK1). In normal parotid tissue, myoepithelial cells and peripheral cells of larger ducts were selectively stained. In pleomorphic adenomas, most cells were stained, the staining being somewhat stronger towards the duct lumina. In basal cell adenomas, only cells adjacent to the duct lumina were stained where a differentiation of cells into peripheral and ductal was seen. In adenolymphomas basal cells were stained, and in oncocytomas small elongated cells reacted with the PKK1 antibody. Only a few duct cells in an acinic cell carcinoma were reactive and in mucoepidermoid carcinoma, peripheral epidermoid cells were strongly stained. In adenoid cystic carcinoma, mostly duct cells were stained whereas the peripheral ones remained unstained. Although the intermediate filament protein expression is very stable during tumorigenesis, the staining with the presently used monoclonal antibody in salivary gland neoplasms differed markedly from what could be expected according to current views on the participation of this cell type. This supports our view that cells in tumors should be characterized on the basis of their staining, i.e. state of differentiation and not on their presumed histogenesis.

Dietary effects of barley fibre, wheat bran and rye bran on bile composition and gallstone formation in hamsters.

The effects of brewer's spent grain (BSG), wheat bran and rye bran on bile composition, gallstone formation and serum cholesterol were studied in Syrian golden hamsters. The frequency of gallstone formation in the animals fed diets supplemented with low (10%) and high (20%) concentrations of BSG or wheat bran was significantly lower than that of the animals fed a stone-provoking, fibre-free diet. The ratios of secondary to primary bile acids were lower in the animals fed the diets supplemented with a high dose of BSG, wheat bran and rye bran than in the controls. The ratio of LCA to DCA was reduced only in the animals fed the diet supplemented with rye bran as compared with controls. No significant changes in bile and serum cholesterol levels were observed in the experiment.

The influence of barley fibre on bile composition, gallstone formation, serum cholesterol and intestinal morphology in hamsters.

Frequency of gallstones, concentration of bile acids and cholesterol in bile, concentration of cholesterol in serum, and structure of the small intestinal mucosa were analyzed in male Syrian Golden hamsters fed a stone provoking fibre-free diet with or without supplementation of brewer's spent grain (BSG), a concentrated barley fibre source from the by-product of brewing. A significantly lower frequency of gallstones was found in the animals with 10% BSG dietary supplementation. Addition of 30% BSG after an initial 6-week period with a fibre-free, stone provoking diet seemed to dissolve previously formed gallstones. Total bile acid concentration was higher in bile from animals given a diet supplemented with 10% BSG. In addition, the cholesterol concentration in both serum and bile was lower in the 30% BSG supplemented group. Structurally, a 10% BSG supplementation decreased ileal epithelium height whereas a high supplementation (30%) of BSG induced a decrease in epithelial height both of jejunal and ileal mucosa. The results show that BSG has significant effects on the metabolism of bile acids and cholesterol as well as on the morphology of the small intestinal mucosa.

Reversal by naloxone of hemorrhagic shock in anephric cats.

Hemorrhage, 15 ml/kg induced a rapid fall of blood pressure in intact and anephric cats, but only intact cats demonstrated significant blood pressure recovery following bleeding. Naloxone, 0.1 mg/kg x min, i.v., had a mild promoting effect on blood pressure recovery in the intact cats whereas, in the hemorrhaged anephric cats naloxone re-established an almost complete recovery of blood pressure. These results suggest that endogenous opioid substances play a significant depressor role in hemorrhagic shock, especially in anephric animals.

Advanced gallbladder carcinoma: a case report and review of the literature.

A case with carcinoma of the gallbladder and recurrent metastases to regional lymph nodes is reported. Following primary surgery, secondary resection of node recurrence, and long term combination chemotherapy, the patient is alive and disease free after 9 years. The possibility of a successful cancer suppression, as mirrored by a depressed RES-function test during the treatment with anticancer drugs, is discussed. Only nine other cases with advanced gallbladder cancer and 5 year survival are found in the literature.

Disposition of two tetramethylcyclopropane analogues of valpromide in the brain, liver, plasma and urine of rats.

2,2,3,3-Tetramethylcyclopropane carboxamide (TMCD) and N-methyl TMCD (M-TMCD) are analogues of valpromide (VPD) or amide derivatives of valproic acid (VPA), one of the major antiepileptic drugs (AEDs). In rodent models both TMCD and M-TMCD are more potent as anticonvulsants than VPA. The present study investigates the pharmacokinetics (PK) of TMCD and M-TMCD in rats by monitoring the levels of these two amides in the brain, liver, plasma and urine of rats. The disposition of TMCD and M-TMCD was analyzed in a comparative manner with that of VPD and VPA, previously studied by us. The following similar PK parameters were obtained for TMCD and M-TMCD, respectively: clearance, 5 and 5.6 ml/min/kg; volume of distribution (Vss), 0.72 and 0.96 l/kg; half-life (t1/2), 1.1 and 1. 2 h; and mean residence time (MRT), 2.41 and 2.8 h. The ratio of AUCs of TMCD of liver to plasma and brain to plasma were 1.67 and 1. 13, respectively. The ratios of the AUCs of M-TMCD of liver to plasma and brain to plasma were 1.43 and 0.99, respectively. Thus, both compounds distribute evenly between plasma and brain, but their distribution into the liver is 50% larger than that in the plasma. Therefore, PK analysis of TMCD and M-TMCD brain levels gave major PK parameters similar to those obtained from the plasma data. The fraction metabolized of M-TMCD to TMCD was 32%. The brain was not found to be a metabolic site for the M-TMCD to TMCD biotransformation which occurred primarily in the liver as indicated by the high liver concentrations of TMCD as a metabolite of M-TMCD. Unlike VPD, TMCD and M-TMCD did not undergo amide-acid biotransformation to their corresponding inactive acid, 2,2,3, 3-tetramethylcyclopropane carboxylic acid (TMCA). Both M-TMCD and TMCD distribute better into the brain than VPA, a fact that may contribute to their better anticonvulsant activity.

Effects of methanol vapor on human neurobehavioral measures.

Methanol could become an important motor fuel. The objective of this exploratory study was to provide preliminary information about whether or not acute exposure to methanol at 250 mg/m3 for 75 minutes would have adverse effects on human neurobehavioral functions important in everyday life. This concentration level was selected because it is at the upper limit of the traffic scenario estimates provided by the U.S. Environmental Protection Agency (EPA)2 (86 to 240 mg/m3), but is below the maximum concentrations for eight-hour average exposures currently recommended by the National Institute of Occupational Safety and Health (NIOSH) and the American Conference of Government and Industrial Hygienists (ACGIH) (260 mg/m3). Although traffic scenario exposure estimates suggest that such high levels of exposure last less than 15 minutes, we used a 75-minute exposure to increase the probability of identifying dependent measures that should be studied in more detail in a future confirmatory study. Twelve healthy young men, each serving as his own control, participated in two sham exposures and two methanol exposures under counterbalanced, double-blind control conditions. Because methanol is present in many foods, and because high preexposure levels of methanol or formate might obscure exposure effects, subjects were required to strictly limit their diets for 12 hours before each experimental session. The following endpoints were examined before, during, and after exposure to methanol and sham vapors: blood and urinary methanol; plasma formate; oral temperature; blood pressure; subjective mood, alertness, fatigue, workload, and symptom scales; spectral analysis of the electroencephalogram; visual- and auditory-event-related potentials; contingent negative variation; respiration; cardiac interbeat interval; Symbol Digit substitution task; three-choice reaction time; Stroop color-word test; simple reaction time; visual function; critical flicker fusion frequency; hand steadiness; visual search task; Gamberale reaction time task; visual tracking task; Sternberg memory task; interval production task; and speeded addition task. Two dual tasks were also included in the task batteries. These endpoints were selected from those indicated in the literature to be sensitive to solvents, and from those that are widely used in other neurobehavioral test batteries to identify the effects of environmental pollutants. Because the number of endpoints examined was large and the number of subjects was small, procedures designed to reduce the number of statistical tests performed were used. Mean methanol concentration in the exposure room during methanol exposures was 249 mg/m3 (SD +/- 7 mg/m3). Exposure produced significant increases in blood and urine methanol concentration. As expected, no changes in plasma formate were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

A proposal for the inclusion of optometric vision care in Title XVIII of the Social Security Act.

The need to broaden the Medicare program to include the full scope of optometric vision care is discussed...particularly the need of the elderly for total vision care and how optometry helps to meet this need. This article is particularly timely inasmuch as the Congress is now considering AOA supported legislation (S.2020, H.R.2987, and many identical House bills) to accomplish this objective. Two dozen Senators and nearly 100 Representatives are currently cosponsoring these bills.

Homologous vessel graft as substitute for flexor tendon graft. An experimental study on rabbits.

Homologous vessel grafts were tried as substitutes for flexor tendon grafts. Pieces of different lengths were excised from a flexor tendon and replaced by a homologous abdominal aorta graft which was turned inside out and then anastomised by drawing it over the tendon stumps in a cuff-like manner. The grafts became firm, homogeneous and completely tendon-like with very little adhesion but with a tendency to become extended and thus too long to be functional.

The disposition of valproyl glycinamide and valproyl glycine in rats.

PURPOSE: To investigate the disposition of valproyl glycinamide and valproyl glycine in rats and to compare it with that of valproic acid (VPA) and valpromide which were studied previously. METHODS: The study was carried out by monitoring the brain and liver levels of valproyl glycinamide and valproyl glycine (as a function of time after iv dosing) in addition to the regular pharmacokinetic (PK) monitoring of plasma and urine levels of these compounds. RESULTS: The following PK parameters were obtained for valproyl glycinamide and valproyl glycine, respectively: clearance, 7.1 and 16 ml/ min/kg; volume of distribution (Vss), 0.78 and 0.41 l/kg; half-life, 1.1 and 0.37 h; and mean residence time, 1.8 and 0.4 h. The ratios of AUCs of valproyl glycinamide of liver to plasma and brain to plasma were 0.70 and 0.66, respectively. The ratios of the AUCs of valproyl glycine of liver to plasma and brain to plasma were 0.19 and 0.02, respectively. CONCLUSIONS: Valproyl glycinamide distributes better in the brain than VPA, a fact which may contribute to its better anticonvulsant activity. Valproyl glycine was barely distributed in the brain, a fact which may explain its lack of anticonvulsant activity. In addition to the liver, the brain was found to be a minor metabolic site of the biotransformation of valproyl glycinamide to valproyl glycine.

Comparison of transbronchial fine needle aspiration biopsy, aspiration of bronchial secretion, bronchial washing, brush biopsy and forceps biopsy in the diagnosis of lung cancer.

The accuracy of morphologic diagnosis from transbronchial fine needle aspirates (TBN), bronchial secretions (BS), bronchial washings (BW), brush biopsy (BB) and forceps biopsy (FB) sampled via a flexible fiberoptic bronchoscope, was studied in 60 malignant lung tumours. In visible tumours the best results were obtained with FB (85%) while TBN was positive in 65%. In cases were bronchoscopy only showed secondary signs of tumour, the sensitivity of FB, BB and TBN was higher than that of BW and aspiration of BS. In tumours not visible through the bronchoscope, the diagnostic accuracy of BB, BW and aspiration of BS was higher than that of FB and TBN. In the diagnosis of carcinoma of the lung the diagnostic accuracy of combining FB and one cytologic method (BW) was higher than that of any of the single methods (p less than 0.05) while no appreciable increase was achieved by using additional methods.

Change in bile composition during gallstone formation in gerbils.

Mongolian gerbils form cholesterol gallstones when fed with chow supplemented with cholesterol and cholic acid. The change in bile composition accompanying gallstone formation was found to consist of an increase of the cholesterol fraction at the expense of the bile acid fraction of the total sum of bile acids and lipids. The five animals models for gallstone formation on which reliable information regarding bile composition is now available, were compared. A similar change was found in all five models while the phospholipid fraction showed a tendency to higher values. In all five models the bile acid/phospholipid ratio decreases when gallstones are induced.

Effect of dietary fibre on gallstone formation in hamsters.

This study aimed at investigating the effect of different sources of dietary fibre on gallstone formation in hamsters. The substances studied were pectin, lignin and psyllium hydrocolloid. The two latter compounds protected hamsters against cholesterol gallstone formation. Lignin resulted in a decrease of the deoxycholic acid conentration and in a rise of the cholic/chenodeoxycholic acid ratio. These changes which are similar to those observed with cholestyramine suggest that lignin acts as a bile acid sequestrant. Psyllium hydrocolloid effected a similar shift of the cholic/chenodeoxycholic acid ratio but it also resulted in a rise of the deoxycholic concentration. This latter finding is not compatible with a bile acid sequestering role of this compound. The addition of alcohol to the drinking-water resulted in the formation of stones rich in pigment. Under these conditions the tendency to form such stones was not checked by either of the investigated substances.

Disposition of valpromide, valproic acid, and valnoctamide in the brain, liver, plasma, and urine of rats.

Valpromide (VPD) and valnoctamide (VCD) are amide derivatives of valproic acid (VPA), one of the major antiepileptic drugs (AEDs). In rodent models, both VPD and VCD are more potent as anticonvulsants than VPA. However, in humans, VPD served as a prodrug to VPA, whereas VCD acts as a drug on its own, which is not biotransformed to its corresponding acid--valnoctic acid (VCA). The present study investigates the pharmacokinetics (PKs of VPD and VCD in rats by monitoring the levels of these two amide isomers in the brain, liver, plasma, and urine of rats. The disposition of VPD and VCD was analyzed in a comparative manner with that of VPA. The following PK parameters were obtained for VPD and VCD, respectively: clearance, 6.1 and 3 ml/min/kg; volume of distribution (Vss), 0.63 and 0.58 liter/kg; half-life (t1/2), 42 and 94 min; and mean residence time (MRT), 102 and 196 min. The clearance of VCD in rats was half of that of VPD, and their Vss was similar. Therefore, VCD, t1/2, and MRT were twice as long as those of VPD.PK analysis of VPD and VCD liver and brain levels gave similar major PK parameters to those obtained from the plasma data. VPD underwent hepatic biotransformation to VPA, which persisted in the liver and brain for a longer period than VPD. The fraction metabolized of VPD to VPA was 42%. The brain was not found to be a metabolic site of the VPD-VPA biotransformation. Unlike VPD, VCD did not undergo amid-acid biotransformation to its corresponding acid, but was eliminated by biotransformation to unidentified metabolites. In contrast to VPD and VCD that distributed about evenly between the plasma, liver, and brain, VPA showed different disposition patterns in the plasma, liver, and brain. VCD and VPD distribute better into the brain than VPA, a fact that may contribute to their better anticonvulsant activity.