Hyperkeratosis induced by sunlight degradation products of the major polybrominated biphenyl in Firemaster.

Sunlight photodegradation of 2,2', 4,4', 5,5' -hexabromobiphenyl, the major component of Firemaster, gave a mixture that produces severe hyperkeratosis of the rabbit ear. This component in its pure state does not cause hyperkeratosis. One or more of the four major photolysis products must be responsible for this activity. A similar photodegradation pattern was observed for 2,2', 3,4,4', 5,5' -heptabromobiphenyl, the second largest component of Firemaster.

Tetrachlorodibenzodioxin: an accidental poisoning episode in horse arenas.

Tetrachlorodibenzodioxin was identified as the apparent cause of an outbreak of poisoning in humans, horses, and other animals. Exposure was related to the spraying of contaminated waste oil on riding arenas for dust control. The contamination resulted from improper disposal of a toxic industrial waste. The pathologic effects and chemical identification of tetrachlorodibenzodioxin are described.

Induction of liver tumors in female Sherman strain rats by polybrominated biphenyls.

Noninbred Sherman strain rats were given the polybrominated biphenyl mixture Firemaster FF-1 (PBB). Rats given a single dose of 1,000 mg PBB/kg or 12 doses of 100 mg PBB/kg body weight in corn oil by gavage had final (when less than or equal to 26 mo old) liver PBB concentrations of 17.1 and 34.8 mg/kg (wet wt), respectively. The respective incidence of hepatocellular carcinomas was 41.4 and 67.8%. No difference in PBB concentrations was found between hepatocellular carcinomas and surrounding liver tissue. In addition, most livers of PBB-dosed rats had adenofibrosis of the liver. Livers of controls were essentially normal. Rats given a single dose of 200 mg PBB/kg as above had a 31.2% incidence of neoplastic nodules, whereas none were seen in the controls. The mean PBB concentrations (when 26 mo old) were 2.68 mg/kg in liver, 244 mg/kg in adipose tissue, and 0.22 mg/kg in blood.

Induction of liver tumor in Sherman strain female rats by polychlorinated biphenyl aroclor 1260.

Sherman strain female rats (200) were fed 100 ppm of polychlorinated biphenyl (Aroclor 1260) for apporximately 21 months, and 200 female rats were kept as controls. The rats were killed when 23 months old. Twenty-six of 184 experimental animals and 1 of 173 controls had hepatocellular carcinomas. None of the controls but 146 of 184 experimental rats had neoplastic nodules in their livers, and areas of hepatocellular alteration were noted in 28 of 173 controls and 182 of 184 experimental animals. Thus the polychlorinated biphenyl Aroclor 1260, when fed in the diet, had a hepatocarcinogenic effect in these rats. The incidence of tumors in other organs did not differ appreciably between the experimental and control groups.

Group B streptococcal meningitis appearing as acute deafness in an adult.

A case of group B streptococcal meningitis developed in a previously healthy adult. The group B streptococcus may be underrecognized as a pathogen in human disease. Survival is good after appropriate therapy, with only six fatalities in 33 cases reported in the literature. However, our patient showed the unusual neurologic complication of bilateral deafness in group B meningitis in adults.

Appropriateness of antibiotic therapy in long-term care facilities.

The objective of this study was to examine the appropriateness of antibiotic therapy in nursing homes. Information was abstracted from infection control reports and patients' charts for a three-month period at two nursing homes in Portland, Oregon. A panel of two board-certified infectious disease specialists and one hospital pharmacist reviewed the information and rated the appropriateness of each prescription using a previously developed scale. Among the 120 infections, treatment was rated as appropriate in 49 percent, as inappropriate in 42 percent, and as unjustified in 9 percent. Cephalosporins received the lowest percent of appropriate ratings (27 percent). The primary reason for an inappropriate rating was that a more effective drug was recommended for empiric therapy of gram-negative bacillary infections. These bacteria are often resistant to oral antibiotics. There were no significant differences in appropriateness by type of organism, infection site, or clinical outcome. Physician education and the development of systems and guidelines for optimal management in this population are appropriate actions for the future.

Characterization of pancreatic-type tissue in the liver of rat induced by polychlorinated biphenyls.

Pancreatic-type tissue induced in the livers of rats treated with polychlorinated biphenyls was characterized by transmission electron microscopy and high-resolution immunocytochemistry. The cells of pancreatic-type tissue were arranged as acini and in small groups. By electron microscopy the pancreatic-type tissue showed features very similar to normal pancreatic acinar tissue, such as well developed rough endoplasmic reticulum (RER), large numbers of mature zymogen granules, and a basally located nucleus. Protein A-gold imunocytochemical technique showed localization of amylase and trypsinogen over the zymogen granules and RER. These findings confirm that this tissue in the liver is morphologically and functionally identical to pancreatic acinar tissue.

Survey of lead exposure around a closed lead smelter.

OBJECTIVE: To test the hypothesis that elevated lead in soil is positively correlated with blood lead (BPb) levels in children in an urban population surrounding a closed lead smelter, a US Environmental Protection Agency Superfund clean-up site was surveyed. METHOD: A total of 827 volunteers including 490 children under 6 years of age participated. A questionnaire was administered. Blood lead was determined as was lead content of samples of house dust, soil, paint, and water of the participants' homes. RESULTS: The arithmetic mean venous BPb in 490 children between 6 and 72 months of age was 6.9 micrograms/dL (0.33 mumol/L) range 0.7 to 40.2 micrograms/dL (0.03 to 1.94 mumol/L). The BPb of 78 (16%) children in this group was > or = 10 micrograms/dL (0.48 mumol/L). Based on multiple regression modeling, lead in house dust accounted for 18% of the variance in BPb. Lead in paint together with the condition of the house were the main contributors to the dust lead variance (26%) with soil lead accounting for an additional 6%. Lead in paint alone accounted for 3% of the BPb variance. Lead in paint together with the condition of the house accounted for 12% of BPb variance, and lead in soil accounted for an additional 3%. Factors other than environmental lead such as education of parents, household income, and behavior were associated with BPb levels. CONCLUSIONS: The mean BPb in children was below the present level of concern of the Centers for Disease Control and Prevention. Children with BPb of > or = 10 micrograms/L (0.48 mumol/L) tended to live in poorly maintained older houses. Based on these findings lead in soil and paint in well-maintained homes contributed little to the lead exposure of children.

Management of children with slightly elevated blood lead levels.

OBJECTIVE: To determine whether counseling of parents reduced blood lead levels in their young children. PARTICIPANTS AND METHODS: A lead exposure study was conducted in the vicinity of a defunct lead smelter. A total of 827 volunteers including 490 children younger than 6 years participated in the study. The mean venous blood lead level in the 490 children was 0.33 mumol/L (6.9 micrograms/dL), with a range of 0.03 to 1.94 mumol/L (0.7 to 40.2 micrograms/dL). A total of 78 (16%) children had blood lead levels > or = 0.48 mumol/L (10 micrograms/dL). However, only 5 (1%) of the children had blood lead levels of > or = 1.21 mumol/L (25 micrograms/dL). The blood lead levels in this community were much lower than levels reported in earlier studies in many areas of the United States, when lead levels in air and in food were higher. Most houses in the study community were built before 1920 and had high lead paint levels. High levels of lead were also found in many house dust and soil samples. Intervention consisted of home visits and counseling of parents of children with blood lead levels of > or = 0.48 mumol/L (10 micrograms/dL). RESULTS: In children with initial blood lead levels of > or = 0.48 mumol/L (10 micrograms/dL) the blood lead test was repeated 4 months later. The arithmetic mean blood lead level 4 months later showed a decrease from 0.72 mumol/L (15 micrograms/dL) to 0.38 mumol/L (7.8 micrograms/dL). An additional blood sample was taken 1 year after the first sample in a subset of 30 children. These children showed a mean blood lead level of 0.43 mumol/L (9 micrograms/dL) at the 1-year follow-up, whereas their mean blood lead level at the 4-month follow-up had been 0.38 mumol/L (8 micrograms/dL). CONCLUSION: Educating parents proved a very effective tool. Further studies are needed in larger populations to evaluate the effectiveness of this approach.

Aflatoxin and Reye's syndrome: a case control study.

Aflatoxin levels were determined in serum and urine of 17 patients with Reye's syndrome and in control subjects. No significant difference in aflatoxin levels was found for the two groups. However, 23% of all persons studied had levels of aflatoxin indicative of recent exposure. Aflatoxin levels were associated with ingestion of cornmeal and corn bread but not peanut-containing products. This prevalence of aflatoxin may be of public health importance.

Laboratory and human studies on polychlorinated biphenyls (PCBs) and related compounds.

Similar qualitative toxic effects have been observed in animals for a class of halogenated aromatic compounds, which include the halogenated biphenyls, naphthalenes, dibenzodioxins, and dibenzofurans. All of these compounds are lipid soluble and persist in the environment and in mammals. The polybrominated biphenyls (PBBs) are the most persistent. They are predominantly stored in fatty tissue; they pass the placenta and are excreted in milk. Some isomers of the halogenated biphenyls are more toxic than others. With some exceptions, the more toxic isomers are retained longer in tissues and are also the carcinogenic components of the mixture. Most of these chemicals seem to be promoters of carcinogenesis in animals rather than initiators. An array of toxic effects in laboratory animals has been ascribed to these compounds and numerous reviews summarizing this information are available. Less information is available on the human health effects of environmental and occupational exposure. Results of recent studies in animals to further elucidate the effects of these chemicals are presented, and results from some human studies conducted in the United States are reviewed.

Toxicity and health effects of selected organotin compounds: a review.

The toxicity of selected tin compounds is reviewed. Over the years, a variety of uses has been found for organic and inorganic tin compounds, as fungicides, as stablizers in plastics, moluscicides, and miticides; they have also been suggested as insect chemosterilants and for other industrial uses. Many of these products are unpalatable when mixed into diets and have been suggested as rodent repellents. Inhaling tin as dust or fumes may cause a benign pneumoconiosis in exposed workers. The organotin compounds can be divided into alkyltin and aryltin compounds. The trimethyl and triethyltin compounds are well absorbed from the gastrointestinal tract and are the most toxic in this group. Triethyltin particularly produces status spongiosus of the white matter of the central nervous system. Most of the other alkyl and aryl tin compounds are poorly absorbed from the gastrointestinal tract, and are less toxic when given orally than when given parentally. Only one compound, tricyclohexyltin hydroxide, is now registered by the Environmental Protection Agency as a miticide. This product produces skin irritation in rabbits. Studies should be conducted to determine whether it causes contact dermatitis in humans.

Acute toxicity of gasoline and some additives.

The acute toxicity of gasoline; its components benzene, toluene, and xylene; and the additives ethanol, methanol, and methyl tertiary butyl ether are reviewed. All of these chemicals are only moderately to mildly toxic at acute doses. Because of their volatility, these compounds are not extensively absorbed dermally unless the exposed skin is occluded. Absorption through the lungs and the gastrointestinal tract is quite efficient. After ingestion, the principal danger for a number of these chemicals, particularly gasoline, is aspiration pneumonia, which occurs mainly in children. It is currently not clear whether aspiration pneumonia would still be a problem if gasoline were diluted with ethanol or methanol. During the normal use of gasoline or mixtures of gasoline and the other solvents as a fuel, exposures would be much lower than the doses that have resulted in poisoning. No acute toxic health effects would occur during the normal course of using automotive fuels.

Persistent liver lesions in rats after a single oral dose of polybrominated biphenyls (firemaster FF-1) and concomitant PBB tissue levels.

In a preliminary study, 12 male and 12 female weanling Sherman strain rats were given a single dose of 1000 mg polybrominated biphenyls (PBBs) FireMaster FF1 Lot 7042 kg/body weight as a 5% solution in corn oil. Three male and three female weanling rats were given corn oil. One day after dosing PBB blood levels ranged from 78 to 162 ppm and 42 days later they ranged from 1.1 to 2.99 ppm. The liver was the only organ with pathological changes. In a long-term recovery study groups of 20 male and female rats, 2 months old, were given 0 or 1000 mg PBBs/kg body weight as a single dose in peanut oil. Five rats per group killed 2, 6, 10, and 14 months after dosing had pronounced liver pathology, including hepatic porphyria in the female rats and neoplastic nodules also mainly in female rats. Chemical analyses of blood, liver, and adipose tissue for PPBs 10 and 14 months after dosing gave the following mean results. Blood levels in females were 2.9 and 2.92 ppm, respectively, and males 0.94 and 1.34 ppm, respectively. Adipose tissue levels in females were 1202 and 783 ppm and in males 713 and 866 ppm, respectively. The liver levels in females were 37 and 22 ppm and in males 60 and 63 ppm, respectively.

Intraocular pressure response to topically administered fluorometholone.

Certain corticosteroids, including fluorometholone, have been reported to have a low propensity for elevating intraocular pressure. Our clinical impression was that the incidence of IOP increase with fluorometholone may be higher than reported. This study was to determine the incidence and degree of IOP response to 0.1% fluorometholone suspension in 43 patients demonstrated to be responsive to 0.1% dexamethasone sodium phosphate solution. Twenty-six patients (60.5%) had IOP increases of 5 mm Hg or more while receiving fluorometholone, and three patients (7%) demonstrated pressure rises greater than 15 mm Hg. Fluorometholone can significantly raise IOP in a significant number of corticosteroid responders.

Betaxolol vs timolol. A six-month double-blind comparison.

Betaxolol hydrochloride (0.5%) and timolol maleate (0.5%) were compared in a six-month randomized, double-blind study involving 29 patients with glaucoma. The two drugs were comparable with regard to efficacy in lowering intraocular pressure. Betaxolol effected an average reduction of 7.6 mm Hg (26%); timolol, 8.4 mm Hg (29%). No patient required adjunctive medications during this study. Ocular side effects were mild and similar for both treatments. Neither drug affected corneal sensitivity, visual acuity, basal tear production, or pupil size. Since betaxolol has been shown to have little effect on the cardiopulmonary system, it should be strongly considered for the treatment of glaucoma.

Porphyrins and hepatotoxicity.

Human porphyrias are rare inborn disorders of porphyrin metabolism. Porphyria cutanea tarda is one such disorder, which may occur spontaneously after the ingestion of drugs and alcohol. This is the "constitutional" type and is associated with a deficiency of uroporphyrinogen decarboxylase in the liver. This constitutional type must be differentiated from the "acquired" type, which occurred in hundreds of people poisoned by hexachlorobenzene in Turkey. Morphological changes observed in the livers of animals and humans vary greatly. Porphyria cutanea tarda may be associated with very little liver pathology or with very pronounced changes, depending on the agent causing the porphyria. Usually, the liver has an increased iron load, and mitochondria contain a crystalline material.

Evaluation of dexamethasone acetate as a topical ophthalmic formulation.

Penetration of an ophthalmic suspension of 0.1% dexamethasone acetate into the rabbit cornea and aqueous humor was unaffected by the status of the corneal epithelium or by the presence or absence of intraocular inflammation. However, the total quantity of this corticosteroid that could be measured in the cornea or aqueous humor was significantly less than that produced by either dexamethason alcohol or dexamethasone sodium phosphate. Despite this, dexamethasone acetate was the most effective of the three dexamethasone derivatives in suppressing inflammation in the cornea, which indicates that following topical administration to the eye it is the most potent of the dexamethasone derivatives studied. This greater therapeutic effect does not seem to be accompanied by a greater propensity to increase intraocular pressure. Comparison of the intraocular pressureincreasing effect in known corticosteroid responders of dexamethasone acetate with that of dexamethasone sodium phosphate, the least effective of the dexamethasone products studied, demonstrated no difference between the two drugs. These data support the conclusion that dexamethasone acetate is superior to the commercially available dexamethasone derivatives for use as a topical ocular anti-inflammatory agent.

Angle-closure glaucoma in nanophthalmos.

Two patients had nanophthalmos with uveal effusion and angle-closure glaucoma. They were treated with a method based on the use of the laser, not only to perform iridotomy but to shrink the iris stroma, which appears to open the anterior chamber angle even without iridotomy. Additionally, we introduced three factors that may be diagnostic of nanophthalmos.