FAT GRAFT MYRINGOPLASTY—A PROSPECTIVE TRIAL

Fat graft myringoplasty—a prospective trial A prospective trial to determine the success rate of the fat graft myringoplasty technique is reported. A success rate of 76% overall was attained at review 1 year postoperatively with increased success for smaller perforations of the tympanic membrane.     

Association between Adverse Maternal and Embryo-Fetal Effects in Norfloxacin-Treated and Food-Deprived Rabbits

Association between Adverse Maternal and Embryo-Fetal Effectsin Norfloxacin-Treated and Food-Deprived Rabbits. CLARK, R.L.,ROBERTSON, R.T., PETER, C.P., BLAND, J.A., NOLAN, T.E., OPPENHEIMER,L., AND BOKELMAN, D.L. (1986) Fundam. Appl Toxicol 7, 272–286.Norfloxacin is a new antibiotic which caused embryo-fetal toxicityin association with materno-toxicity when given orally to rabbitsat 100 mg/kg/day. The intestinal flora of rabbits is unusuallysensitive to many antibiotics and it was suspected that thematernotoxicity and embryo-fetal toxicity caused by oral norfloxacinwere secondary to an effect on the intestinal flora. To testthis idea, a teratologic study was conducted in which rabbitswere dosed on Days 6 to 18 of gestation with norfloxacin givenorally at 100 mg/kg/day or subcutaneously at 20 mg/kg/day. Theoral treatment caused decreased food consumption (to less than15 g/day in some animals), body weight loss, an increased resorptionrate, and decreased fetal weight. Among the females in the orallydosed group, there was a significant correlation (p0.005) betweenthe effects on maternal body weight and the resorption rate.The subcutaneous treatment caused little intestinal exposure(biliary excretion=only 2-4% of dose) and no maternotoxicityor embryo-fetal toxicity, even though blood levels of drug wereat least as high as those in the oral group. Since the maternotoxicityand embryo-fetal toxicity were specific to the oral route andnot correlated with the level of systemic exposure, the maternotoxicitymay have been secondary to an effect on the intestinal floraand the embryo-fetal toxicity may have been secondary to thematernotoxicity. The decreased food consumption observed inthe oral group may have contributed to the embryo-fetal toxicitysince, in a separate study, it was found that lowering the amountof food provided to rabbits on Days 6 to 18 of gestation from150 g/day to 50 or 15 g/day also caused adverse maternal andfetal effects including, at 15 g/day, fetal malformations.     

Mucous Cell Metaplasia in the Airways of Rats Exposed to Machining Fluids

Occupational exposure to microbial-contaminated machining fluidsis associated with a variety of adverse pulmonary effects includingchronic bronchitis and increased sputum production. We havepreviously demonstrated in F344 rats that inhaled endotoxincan increase the amount of stored intraepithelial mucosubstances(Vs) in the respiratory tract. The purpose of the present studywas to examine the effect of endotoxin-contaminated machiningfluid aerosols on mucous production. Rats were exposed to aerosolsof pyrogen-free water, 1 or 10 mg/m³ used machining fluid, or10 mg/m³ unused machining fluid for 3 hr/day for 3 days. Twenty-fourhours after the final exposure, right lung lobes were lavagedand the nasal cavity and left lung were fixed in formalin. Theamount of Alcian blue/periodic acid-Schiff-stained mucosubstanceswas determined by morphometry. Exposure to 10 mg/m³ used machiningfluid (equivalent to 0.8 µg/m³ endotoxin) produced a significantincrease in Vs in the epithelial lining of both the nasal septumand intrapulmonary airways. These changes in Vs were accompaniedby a significant increase in total cells and neutrophils inthe lavage fluid. No changes in stored mucosubstances or lavageparameters were found in animals exposed to 1 mg/m³ used machiningfluid aerosols. A significant increase in Vs was observed inthe nasal septum but not in the intrapulmonary airways of animalsexposed to 10 mg/m³ unused machining fluids (no measurable endotoxin).These results suggest that in addition to endotoxin, nonendotoxincomponents of machining fluids may contribute to the increasein sputum and chronic bronchitis reported for workers exposedto machining fluid aerosols.     

Comparative Toxicology of Temelastine: A Novel H1 Antagonist in Dog, Rat, and Monkey

Comparative Toxicology of Temelastine: A Novel H, Antagonistin Dog, Rat, and Monkey. POOLE, A., BETTON, G. R., SALMON, G.,SUTTON, T., AND ATTERWILL, C. K. (1990). Fundam. Appl. Toxwol.14, 71–83. The toxicity of temelastine 2-[4-(5-bromo-3-methylpyrid-2-yl)butyl-amino]-5-[(6-methylpyTid-3-yl)methyl]-4-pyrimidone a potent, selective, competitive hista-mineHrreceptor antagonist was examined in dogs and rats. The majortoxicologjcal response seen in the dog was marked, but intermittentand reversible, increases in the plasma activity of a numberof liver-associated enzymes, viz alanine aminotransferase (ALT),glutamate dehydro-genase (GLDH), and alkaline phosphatase (ALP).The increases first seen in two male dogs treated for 30 consecutivedays at a dose of 300 mg/kg became apparent at lower doses,i.e., 100 and 33.3 mg/kg/day, in 6- and 12-month studies. Althoughthe increases were suggestive of hepatotoxicity, the only histologicalchanges were increases in hepatocellular lipofuscin pigmentand foci of macrophages seen in dogs treated at 300 mg/kg for12 months. Rats treated for up to 12 months at doses as highas 300 mg/kg/day showed no treatment-related increases in plasmaenzymes although increases in liver weights and hepatocellularlipofuscin pigment together with centrilobular hypertrophy wereseen in the 300 mg/kg/day treatment group. To investigate differencesin hepatic responsiveness between species dogs, rats, and monkeyswere exposed to high concentrations of temelastine by continuous24-hr intravenous infusion. The results of the study showedthe dog to be most sensitive to the hepatic effects of temelastine.The major toxicological effect of temelastine in the rat wasa histopathological lesion of the thyroid gland characterizedby agglomeration and depletion of colloid, follicular epithelialhypertrophy and reduced follicular size. The no-effect dosefor this lesion was between 10 and 33.3 mg/kg/day. These histopathologicalchanges, characteristic of a "TSH-driven" thyroid gland, werenot seen in the thyroid glands of dogs.