Activity of histone H1.2 in infected burn wounds.

OBJECTIVES: Infections with multidrug-resistant microorganisms (e.g. Pseudomonas aeruginosa and Staphylococcus aureus) cause immense complications in wound care and in the treatment of immunosuppressed patients. Like most antimicrobial peptides, histones are relatively small polycationic proteins located in each eukaryotic nucleus, which naturally supercoil DNA. The aim of this study was to investigate the in vitro and in vivo activity of histone H1.2 in infected burn wounds and its potential toxicity. METHODS: To characterize the antimicrobial properties of histone H1.2 against potential causative organisms of burn wound infections, the in vitro radial diffusion assay and modified NCCLS microbroth dilution MIC assay were carried out. Haemolytic and cytotoxic properties were determined in human red blood cells and primary human keratinocytes. In vivo antimicrobial activity was tested in an infected rat burn model with P. aeruginosa (ATCC 27853). All results were compared with the naturally occurring broad-spectrum antimicrobial peptide protegrin-1 and with antibiotics clinically used against the corresponding bacteria. RESULTS: Human histone H1.2 exerted good antimicrobial activity against all tested microorganisms without significant haemolytic activity. Surprisingly, histone H1.2 showed cytotoxicity with an LD50 of 7.91 mg/L in primary human keratinocytes. The in vivo burn model data revealed a significant three-fold higher reduction in bacterial counts within 4 h compared with carrier control. CONCLUSIONS: These findings indicate that histone H1.2 is a potential candidate for use as a local and, because of its low haemolytic activity, systemic antimicrobial agent. However, further investigations are needed to specify the cytotoxicity and the dose-response relationship for histone H1.2.

Integrating primary medical care with addiction treatment: a randomized controlled trial.

CONTEXT: The prevalence of medical disorders is high among substance abuse patients, yet medical services are seldom provided in coordination with substance abuse treatment. OBJECTIVE: To examine differences in treatment outcomes and costs between integrated and independent models of medical and substance abuse care as well as the effect of integrated care in a subgroup of patients with substance abuse-related medical conditions (SAMCs). DESIGN: Randomized controlled trial conducted between April 1997 and December 1998. SETTING AND PATIENTS: Adult men and women (n = 592) who were admitted to a large health maintenance organization chemical dependency program in Sacramento, Calif. INTERVENTIONS: Patients were randomly assigned to receive treatment through an integrated model, in which primary health care was included within the addiction treatment program (n = 285), or an independent treatment-as-usual model, in which primary care and substance abuse treatment were provided separately (n = 307). Both programs were group based and lasted 8 weeks, with 10 months of aftercare available. MAIN OUTCOME MEASURES: Abstinence outcomes, treatment utilization, and costs 6 months after randomization. RESULTS: Both groups showed improvement on all drug and alcohol measures. Overall, there were no differences in total abstinence rates between the integrated care and independent care groups (68% vs 63%, P =.18). For patients without SAMCs, there were also no differences in abstinence rates (integrated care, 66% vs independent care, 73%; P =.23) and there was a slight but nonsignificant trend of higher costs for the integrated care group ($367.96 vs $324.09, P =.19). However, patients with SAMCs (n = 341) were more likely to be abstinent in the integrated care group than the independent care group (69% vs 55%, P =.006; odds ratio [OR], 1.90; 95% confidence interval [CI], 1.22-2.97). This was true for both those with medical (OR, 3.38; 95% CI, 1.68-6.80) and psychiatric (OR, 2.10; 95% CI, 1.04-4.25) SAMCs. Patients with SAMCs had a slight but nonsignificant trend of higher costs in the integrated care group ($470.81 vs $427.95, P =.14). The incremental cost-effectiveness ratio per additional abstinent patient with an SAMC in the integrated care group was $1581. CONCLUSIONS: Individuals with SAMCs benefit from integrated medical and substance abuse treatment, and such an approach can be cost-effective. These findings are relevant given the high prevalence and cost of medical conditions among substance abuse patients, new developments in medications for addiction, and recent legislation on parity of substance abuse with other medical benefits.

Improving alcoholism treatment across the spectrum of services.

This article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The chair was Michael E. Hilton. The presentations were (1) The effects of brief advice and motivational enhancement on alcohol use and related variables in primary care, by Stephen A. Maisto, Joseph Conigliaro, Melissa McNiel, Kevin Kraemer, Mary E. Kelley, and Rosemarie Conigliaro; (2) Enhanced linkage of alcohol dependent persons to primary medical care: A randomized controlled trial of a multidisciplinary health evaluation in a detoxification unit, by Jeffrey H. Samet, Mary Jo Larson, Jacqueline Savetsky, Michael Winter, Lisa M. Sullivan, and Richard Saitz; (3) Cost-effectiveness of day hospital versus traditional alcohol and drug outpatient treatment in a health maintenance organization: Randomized and self-selected samples, by Constance Weisner, Jennifer Mertens, Sujaya Parthasarathy, Charles Moore, Enid Hunkeler, Teh-Wei Hu, and Joe Selby; and (4) Case monitoring for alcoholics: One year clinical and health cost effects, by Robert L. Stout, William Zywiak, Amy Rubin, William Zwick, Mary Jo Larson, and Don Shepard.

[Effect of variations in middle ear pressure on ruptures of the round window membrane of the inner ear of the guinea pig (Cavia porcellus)]. / Untersuchungen zum Einfluss von Mittelohrdruckschwankungen bei Rupturen der runden Fenstermembran auf das Innenohr des Meerschweinchens (Cavia porcellus).

The electrical activity of the inner ear before and after rupture of the round window membrane was monitored in guinea pigs under different pressure conditions with the aid of electrocochleography. Following studies were conducted weekly over a period of 4 weeks. Findings showed that overpressure below the pressure needed to open the Eustachian tube caused strong temporary functional disturbance of the cochlea, especially at high frequencies. Irreversible changes that were pressure-dependent were observed and occurred mainly at high frequencies. Application of low pressure to the round window membrane caused a functional loss comparable to changes after overpressure. Animals with a predamaged cochlea reacted to overpressure that was below opening pressure of the tube and to corresponding low pressure with a longer lasting functional loss than did animals with an undamaged cochlea.

The reaction of the guinea pig cochlea to perforations of the round window membrane with and without perilymph aspiration.

The influence of simple opening of the round window (RW) membrane and the effect of aspiration of perilymph on the electrophysiological characteristics of the cochlea was tested in guinea pigs by measurement of the compound action potentials. We found that perforations of the RW membrane failed to lead to either short-term or long-term damage in cochlear function. There was only a slight spontaneous escape of perilymph but without measurable functional loss. Additional aspiration of perilymph led to entry of air into the basal turn and to an immediate loss of function of the cochlea. This regressed within 4 weeks in the middle- and low-frequency ranges. Measurable long-term damage persisted only in the high-frequency ranges. We attribute contradictory results of other authors to methodological errors which we avoided by a specific selection of healthy animals and the development of standardized operation, recording and measurement procedures.

Isolation and pharmacological characterization of vernolepin.

Vernolepin, a sesquiterpene lactone, was isolated from the dried fruit of Vernonia amygdalina Del. The different steps used during the extraction were: continuous extraction with chloroform, partition of the chloroform-extract between pertroleum ether and 10% aqueous methanol, column chromatography of the methanol extract, isolation of the active fractions by pharmacological and chemical characterization. Vernolepine was obtained as colorless prisms and identified by melting point, uv, ir, 1H nmr, optical rotation, and mass spectrometry. The total content of the dried fruit was 0.09% vernolepin. The first pharmacological characterization of vernolepin revealed: (1) a competitive antagonism against histamine in guinea pig ileum (pA2 = 5.61; 15 min incubation); (2) a biphasic enhancement/inhibition of coaxial stimulation of guinea pig ileum; (3) an antiaggregating and disaggregating activity against rabbit platelet aggregation induced by arachidonic acid (1 X 10(-4) g/ml; 3.3 X 10(-4)M) or ADP (4 X 10(-6) g/ml; 1 X 10(-5)M) without inhibition of cyclo-oxygenase or lipoxygenase. All these reactions were time dependent and occurred at concentrations of 5 X 10(-6) to 1 X 10(-5) g/ml vernolepin (1.8 to 3.5 X 10(-5)M).