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Numerous attempts to move nursing handoff to the bedside failed within our organization. Upon retrospect, previous attempts lacked standardization, coordination, and clear expectations. With emphasis on implementing patient- and family-centered care to increase patient experience scores, we developed a standardized staff training methodology using didactic and simulation to address staff barriers to adoption, a standardized implementation process, and a process to hardwire the practice.

The food additive butylated hydroxytoluene (BHT) is capable of damaging centrilobular or periportal cells in the liver according to the dose and duration of treatment. The effect of two hepatotoxicity potentiating agents on the site specificity of acute cell damage was investigated in Sprague-Dawley rats. A 500 mg/kg oral dose of BHT did not cause overt hepatic necrosis or alter the cytochrome P450 concentration, but increased ethoxycoumarin-O-deethylation, implying an alteration in the ratio of P450 isoenzymes. Pretreatment with either phenobarbitone (3 X 80 mg/kg, ip) or the glutathione depleting agent buthionine sulfoximine (900 mg/kg, ip) produced liver necrosis in approximately 50% of animals: mainly in centrilobular areas, but with some necrosis in midzonal or periportal areas. Phenobarbitone and BHT did not significantly change the cytochrome P450 concentration, but did alter the ratio of P450 isoenzymes. In phenobarbitone-pretreated rats centrilobular hepatocyte damage was clearly localized in cells with high immunocytochemical staining for the cytochrome P450IIB subfamily. Buthionine sulfoximine and BHT reduced the cytochrome P450 concentration without reducing ethoxycoumarin-O-deethylase activity, implying a different alteration in the ratio of P450 isoenzymes. These results indicate that phenobarbitone-inducible enzymes are capable of activating high doses of BHT to reactive oxidizing intermediates, which in the absence of adequate glutathione can cause cell death. Enzymes of the P450IIB subfamily are implicated in this mechanism.

Cocaine (60 mg/kg i.p.) caused centrilobular necrosis in the livers of 55% of DBA/2Ha mice. Pretreatment with phenobarbital (PB, 3 x 80 mg/kg i.p.) increased the incidence of necrosis to 70% and shifted this damage to the midzonal region. Pretreatment with butylated hydroxytoluene (BHT, 0.1% in diet) increased the severity of the centrilobular damage and increased the incidence to 90%. Combined treatment with both PB and BHT shifted the site of necrosis to the periportal region of the liver, and induced necrosis in all animals. Microsomal malondialdehyde (MDA) did not reflect the extent of the damage and/or correlate with the site of damage. These results argue against a causal role for lipid peroxidation in the mechanism of cocaine hepatotoxicity, and demonstrate that prior exposure to enzyme-inducing agents can increase sensitivity and dramatically alter the site of cell damage.

The membrane-bound beta-lactamase from Bacillus cereus, strain 569/H/9, has been purified to apparent homogeneity. Nonionic detergent (0.5% Triton X-100) is required to keep the enzyme (traditionally called gamma-penicillinase and now called beta-lactamase III) in solution. Antibodies to beta-lactamase III have been prepared, and the membrane-bound enzyme is immunochemically distinct from the extracellular enzymes. beta-Lactamase III has a molecular weight of 31 500, in contrast to the extracellular enzymes beta-lactamase I and beta-lactamase II which have molecular weights of 30 000 and 22 000, respectively. The isoelectric point of beta-lactamase III is pH 6.8, whereas beta-lactamase I and beta-lactamase II have isoelectric points about 8.6 and 8.3. The amino acid composition of beta-lactamase III differs from those of beta-lactamase I and beta-lactamase II; however, the difference index between the compositions of beta-lactamase I and beta-lactamase III (52%) suggests relatedness. beta-Lactamase III is inactivated by 6 beta-bromopenicillanic acid and by the sulfone of 6 alpha-chloropenicillanic acid, and cephalosporins are poorer substrates than penicillins. beta-Lactamase III may be a membrane-bound class A beta-lactamase.

Morphological changes in bile duct lining cells precede morphological changes in hepatocytes in rats treated with 300 mg/kg body wt of alpha-naphthylisothiocyanate (ANIT). Four hours after dosing, electron microscopy showed dilation of bile ducts, loss of microvilli from bile duct epithelial cells, and an apparent opening of the tight junctions between some bile duct epithelial cells. These changes were more pronounced after 6 hr and there was in some bile duct lining cells detachment of the nuclear membrane and vacuolation of the endoplasmic reticulum. Light microscopy 6 hr after treatment with ANIT showed some portal edema and loss of gamma-glutamyl transpeptidase activity from the bile duct lining cells. By 8 hr after treatment many ducts showed clear-cut damage, with bile plugs forming and cells exfoliating into the ducts. Twenty-four hours after treatment the majority of bile ducts were destroyed but by 48 hr there was some evidence of regeneration. No tissue changes were seen at the light microscopy level in the liver parenchymal cells 4, 6, or 8 hr after treatment. At the ultrastructural level some alterations in the tight junctions between hepatocytes were seen 6 hr after treatment. No other changes were observed before this time point. By 24 hr after treatment there was focal necrosis in the parenchyma. Assay of gamma-glutamyl transpeptidase and albumin in bile gave results consistent with the histochemical evidence for the loss of activity from bile duct lining cells and for weakening of the tight junctions between hepatocytes.