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The acute, subacute and chronic toxicity of (8r)-3alpha-hydroxy-8-isopropyl-1alphaH,5alphaH-tropaniumbromide (ipratropiumbromide, Sch 1000, Atrovent) was studied on mice, rats, dogs and monkeys following oral, s.c., i.v. administration and inhalation. With toxic doses all typical symptoms of atropine or atropine derivatives were present, like mydriasis, dryness of the mucosa and meteorism with coprostasis. It was not possible to determine the LC50 of the substance due to its low toxicity.

The in-situ sweat test is prone to errors from various sources. This paper examines errors due to evaporation, absorption of water into the skin, and pressure of the electrode on the skin. Only evaporation caused serious errors. The accuracy and precision when measuring small chloride/sweat samples on the skin are not significantly worse than when measuring bulk solutions.

The acute and sub-acute inhalation toxicity of methacholine to cynomolgus monkeys was assessed by exposure of animals to an aerosol of a 2% solution of the material in sterile saline. The acute response was characterized by a decrease in tidal volume, increase in respiratory rate, a fall in dynamic compliance and an increased pulmonary resistance. Onset of the acute response was rapid, reached a peak after 2-3 min of exposure and recovery appeared to be complete after 30 min following termination of an exposure. The sub-acute inhalation toxicity of methacholine was assessed by single daily aerosol exposure of primates to graded doses of the compound for 7 days. Pre- and post-exposure measurements of haematology and blood biochemistry, urinalysis, blood gas analysis and ECG showed no changes which could be attributed to exposure to methacholine. Nor were treatment-related histopathological changes observed in exposed animals. Distinct changes were seen in the mechanical characteristics of the lungs of exposed animals. Pulmonary resistances, measured on the day following final exposure, were increased in all animals exposed to the methacholine aerosol. During 9 weeks following the last of the daily exposures, increased pulmonary resistance values persisted in the animals retained for this period, although there was some indication of a gradual return to pre-exposure resistance values.

We reviewed 144 consecutive patients with flail chest and/or pulmonary contusion between 1979 and 1984. The purpose was to analyze the factors adversely affecting morbidity and mortality. There were 97 males and 47 females, with an average age of 40 years +/- 18 S.D. (range, 2-83). Seventy-five per cent of the injuries were caused by motor vehicle accidents, with the remainder due to falls (17%), cardiopulmonary resuscitation (4%), altercations (2%), or falling objects (2%). The Injury Severity Score (ISS) averaged 32 +/- 14 S.D. in all survivors versus 60 +/- 14 S.D. in those who died. Eighty-three patients (58%) required mechanical ventilation. Thirty-six patients died (25%). Isolated pulmonary contusion or flail chest had a mortality of 16% each. However, the mortality more than doubled when there was a combined pulmonary contusion and flail chest (42%). More than half of all deaths were directly attributed to central nervous system injuries with another third due to massive hemorrhage. Factors that were associated with a higher morbidity and mortality included severe associated thoracic injuries, a high ISS, the presence of shock, falls from heights, and the combination of pulmonary contusion and flail chest.

Redirecting the posterior tibial tendon has improved the function of symptomatic flat feet. A modification that appears to improve the final result by increasing the support and fixation of the tendon is reported.

Hexachlorocyclopentadiene (Hex or C-56) is a highly reactive intermediate used in the production of some insecticides, flame retardants, and resins. The present study was conducted to evaluate the inhalation toxicity of high-purity Hex (97.7%) in rats and monkeys to provide information on the potential hazards of accidental exposure of workers to Hex vapors. Acute, range-finding (14-d), and subchronic (90-d) inhalation studies were conducted with Sprague-Dawley rats and subchronic (90-d) inhalation studies were conducted with cynomolgus monkeys. Both acute and range-finding studies with rats showed a steep dose-response curve, and male rats were more sensitive than females. In the range-finding study with rats the threshold of toxicity for Hex was 0.11-0.5 ppm. Histopathologic examination on rats in the 0.5 ppm group revealed lesions in the olfactory and bronchiolar epithelium and inflammatory exudate in the lumens of the respiratory tract; these changes were consistent with observed impaired respiratory function, confirming the lung as the main target organ. Recovery and regression of lung lesions in rats were noted 2-3 wk after termination of exposure. In the 90-d study, inhalation of Hex vapors at concentrations up to 0.2 ppm for 6 h/d, 5 d/wk, produced no detectable physical or clinical effect and no remarkable gross or histological alterations in rats or monkeys.

The acute toxicity of inhaled eugenol was assessed by exposure of three groups of five male and five female rats to a submicron aerosol of eugenol for 4 h followed by a 14-day observation period. A fourth group, also of five male and five female rats and exposed to air only under similar conditions, served as a control group for comparison. The three concentrations of eugenol to which the different groups were exposed were 2.58, 1.37 and 0.77 mg/l. The mass median aerodynamic diameters and geometric standard deviations of the aerosols were, respectively, 0.82 micron (sigma g 2.26), 0.88 micron (sigma g 2.05) and 0.9 micron (sigma g 1.87). Clinical signs observed during exposure consisted principally of moderately increased salivation and restlessness (indicative of irritation) and abnormal breathing patterns. The signs were graded, being less marked in animals exposed to the lower concentrations of eugenol. All three groups, exposed to high, medium and low levels of eugenol, lost weight overnight following exposure. Associated with the weight loss were marked reductions in food and water intake. The responses appeared to be largely independent of the concentration of eugenol inhaled, although there was some evidence of a graded effect on water intake. There was rapid recovery, with food and water consumption data comparable with control values throughout most of the remainder of the 14-day observation period. Also, by the end of the observation period, group mean body weights were comparable. Upon sacrifice and macroscopic examination of the animals, abnormalities were detected in the lungs only of a few animals: 3/10 control, 2/10 eugenol 2.58 mg/l, and 2/10 eugenol 0.77 mg/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Technical chlordane (1,2,4,5,6,7,8,8-octachloro-3a,4,7,7-tetrahydro-4,7-methanoinda ne) is used extensively for control of certain wood-boring insects. The present study was conducted to evaluate the inhalation toxicity of technical chlordane in rats and monkeys. Range-finding (28-d) and subchronic (90-d) inhalation studies with Wistar rats, and subchronic (90-d) inhalation studies with cynomolgus monkeys were conducted. In the range-finding study in rats, the threshold of toxicity for technical chlordane was approximately 5.8 micrograms/l. Among the observations made during the course of the 90-d study, in which technical chlordane was administered by inhalation to rats and monkeys at concentrations close to 0.1, 1.0, and 10 micrograms/l, the most significant were associated with alterations in the liver and were confined to rats only. However, in the rat, the effects on the liver were largely reversible during 90 d following cessation of administration of technical chlordane. The no-effect level of chlordane inhalation in rats appears to be between 0.1 and 1.0 microgram/l, while in monkeys the no-effect level is in excess of 10 micrograms/l. This study demonstrated that the monkey, a species closely related to humans, can tolerate relatively high chlordane concentrations without any adverse effects.

The corrosion of the pure metals aluminium, cobalt, copper, chromium, molybdenum, nickel, and titanium and of a cobalt-chromium molybdenum casting alloy has been studied in buffered saline with and without the presence of the proteins serum albumin and fibrinogen. The corrosion of aluminium and titanium was unaffected by the protein. The corrosion rates of chromium and nickel showed a slight increase, while cobalt and copper dissolved to a very much greater extent in the presence of protein. However, with molybdenum the corrosion was inhibited by protein.

Filling solution leakage, reproducibility, stability, interferences and temperature effects have been studied in relation to the use of the Orion 96-17-01 combination chloride ion-selective electrode in sweat testing for cystic fibrosis. While stability and reproducibility is good, certain antiseptic systems and especially Hibitaine (chlorhexidine gluconate) interfere with the electrode and therefore need to be absent during sweat testing. Temperature conditions during calibration and sweat testing need to be controlled in view of the extent of response variations for even modest temperature differences between sensor-skin interface and electrode stem.

Phorbol myristate acelate (PMA), a potent tumor promoter, has a variety of effects on cells of the immune system resulting in altered patterns of cell proliferation and differentiation. Although PMA is mitogenic or co-mitogenic for human lymphocytes and murine T-cells, it inhibits proliferation of murine B-cells stimulated by LPS or anti-Ig. PMA, however, does not inhibit the ability of LPS or anti-Ig to activate B-cells, as evidenced by increased Ia antigen expression and RNA synthesis. In the present studies it was shown that inhibition of DNA synthesis by PMA coincided with qualitative and quantitative changes in phosphorylated proteins. In particular, PMA treatment resulted in a unique profile of phosphoproteins independent of LPS or anti-Ig treatment. Inhibition of DNA synthesis occurred over a wide range of PMA concentrations. At concentrations up to 10(-9) M, inhibition of proliferation correlated with decreased phosphatidylinositol turnover and decreased intracellular Ca2+ levels, suggesting that PMA affects the phosphoinositide signal transduction pathway. However, at PMA concentrations less than 10(-10) M, inhibition of anti-Ig- and LPS-mediated proliferation occurred without inhibition of the phosphoinositide transduction signal. At these concentrations, PMA-induced inhibition of DNA synthesis was highly sensitive to recombinant IL-2. These data suggest that the antiproliferative effects of PMA on B-cells stimulated by LPS or anti-Ig may be mediated by two mechanisms. At high concentrations, PMA causes a feedback regulation of the phosphoinositide-dependent messenger system, while at lower concentrations, PMA alters the response to specific growth factors. Since PMA induces unique phosphoproteins and both of these events can be regulated by protein phosphorylation, it is possible that these unique phosphoproteins are responsible for the antiproliferative effects of PMA.