In vitro microbial inhibition and cellular response to novel biodegradable composite wound dressings with controlled release of antibiotics.

About 70% of all people with severe burns die from related infections, despite advances in treatment regimens and the best efforts of nurses and doctors. Although silver-eluting wound dressings are available for addressing this problem, there is growing evidence of the deleterious effects of such dressings in delaying the healing process owing to cellular toxicity. A new concept of antibiotic-eluting composite wound dressings is described here. These dressings are based on a polyglyconate mesh coated with a porous poly-(dl-lactic-co-glycolic acid) matrix loaded with antibiotic drugs. The effect of antibiotic release on bacterial inhibition was studied, and cell cytotoxicity was examined. The dressings resulted in a 99.99% decrease in the viable counts of Pseudomonas aeruginosa and Staphylococcus albus at very high initial inoculations of 107-108 CFU ml⁻¹ after only 1 day, while such a decrease in Staphylococcus aureus was obtained within 3 days. Bacterial inhibition zones around the dressing material were found to persist for 2 weeks, indicating a long-lasting antimicrobial effect. Despite severe toxicity to bacteria, the dressing material was found to have no toxic effect on cultured fibroblasts, indicating that the new antibiotic-eluting wound dressings represent an effective option for selective treatment of bacterial infections.

Neural activity changes to emotional stimuli in healthy individuals under chronic use of clomipramine.

Previous functional magnetic resonance imaging (fMRI) studies examined neural activity responses to emotive stimuli in healthy individuals after acute/subacute administration of antidepressants. We now report the effects of repeated use of the antidepressant clomipramine on fMRI data acquired during presentation of emotion-provoking and neutral stimuli on healthy volunteers. A total of 12 volunteers were evaluated with fMRI after receiving low doses of clomipramine for 4 weeks and again after 4 weeks of washout. Fear-, happiness-, anger-provoking and neutral pictures from the International Affective Picture System (IAPS) were used. Data analysis was performed with statistical parametric mapping (P < 0.05). Paired t-test comparisons for each condition between medicated and unmedicated states showed, to negative valence paradigms, decrease in brain activity in the amygdala when participants were medicated. We also demonstrated, across both positive and negative valence paradigms, consistent decreases in brain activity in the medicated state in the anterior cingulate gyrus and insula. This is the first report of modulatory effects of repeated antidepressant use on the central representation of somatic states in response to emotions of both negative and positive valences in healthy individuals. Also, our results corroborate findings of antidepressant-induced temporolimbic activity changes to emotion-provoking stimuli obtained in studies of subjects treated acutely with such agents.

Restless legs syndrome (RLS) in anemic patients with congestive heart failure and chronic renal failure: lack of effect of anemia treatment.

OBJECTIVE: To assess the prevalence of Restless Legs Syndrome (RLS) in anemic patients with Congestive Heart Failure (CHF) and Chronic Renal Failure (CRF) and to evaluate the effect of anemia treatment on RLS. METHODS: 38 anemic CHF-CRF patients were treated with subcutaneous Erythropoietin (EPO) and intravenous (IV) iron over 1 year. They were questioned initially and at 3 months post treatment about symptoms of RLS according to standard criteria. They were also contacted by telephone about RLS symptoms 12 months after onset of anemia treatment. RESULTS: RLS was found in 15 (39.5%) of the 38 patients. In 10 (66.7%) patients it was present at least 6 days a week. The prevalence of the RLS initially was not related to Hb, to serum iron or % Transferrin Saturation. Diabetes and lower serum ferritin were more common in the RLS group (p<0.05). After 3 months of treatment, Hb increased from 10.4+/-0.8 to 12.3+/-1.2 g/dl, but RLS symptoms did not change. By 12 months the prevalence and frequency of RLS complaints was similar to what it had been initially. CONCLUSION: RLS is common and often undiagnosed and untreated in anemic CHF-CRF patients. Unfortunately, successful treatment of anemia with EPO and IV iron did not improve this condition.

Structured drug-eluting bioresorbable films: microstructure and release profile.

Bioresorbable drug-eluting films can be used in many biomedical applications. Examples for such applications include biodegradable medical support devices which combine mechanical support with drug release and antibiotic-eluting film coatings for prevention of bacterial infections associated with orthopedic implants or during gingival healing. In the current study, bioresorbable drug-loaded polymer films are prepared by solution processing. Two film structures are studied: A polymer film with large drug crystals located on its surface (A-type) and a polymer film with small drug particles and crystals distributed within the bulk (B-type). The basic mode of drug dispersion/location in the film (A or B-type) is found to be determined mainly by the process of film formation and depends mainly on the solvent evaporation rate, whereas the drug's hydrophilicity has a minor effect on this structuring process. Most release profiles from A-type films exhibit a burst effect of approximately 30% and a second release stage that occurs at an approximately constant rate and is determined mainly by the polymer weight loss rate. An extremely high burst release is exhibited only by a very hydrophilic drug. The matrix (monolithic) nature of the B-type film enables release profiles that are determined mainly by the host polymer's degradation profile, with a very low burst effect in most of the studied systems. In addition to the drug location/ dispersion in the film, the host polymer and drug type also strongly affect the drug's release profile from the film. It has been demonstrated that appropriate selection of the process parameters and film components (polymer and drug) can yield film structures with desirable drug release behaviors. This can lead to the engineering of new bioresorbable drug-eluting film-based implants for various applications.

Molecular and cellular characterization of mesenchymal progenitors for skeletal biomedical devices.

Mesenchymal cells are successfully used to create cell-loaded devices in tissue engineering. Molecular properties of the cells and interaction with polymer scaffolds regulate the development of desired tissues. The present study compared the molecular markers in mesenchymal pleuripotent C3H10T1/2 and osteogenic MBA-15 cells. The cells express transcription factors (TF) of chondro-ostegenic pathway (cbfa-1 and c-fos) and MyoD - TF of muscle differentiation pathway, but not myogenin. Analyzed cells expressed receptors for glucocorticoids, growth hormone, prolactin, and PTH, which indicates their potential responsiveness to systemic signals. Analysis of mRNA encoding for receptors of TGFbeta, TNF, and various interleukins revealed differential expression of IL-2r and TGFbeta-1r receptors, which were expressed by MBA-15 but not by C3H10T1/2 cells. Expression of functional genes indicates differences in the stages of cell differentiation: ALK was present in MBA-15 only, while both cell types expressed collagen-I. Furthermore, we evaluated the expression of adhesion proteins that mediate cell-polymer interactions by flow cytometry analysis. Cell adhesion molecules (CAMs) analyzed were integrinalpha-M (CD11b), selectin-E (CD62E), and PECAM-1 (CD31), which have shown differential expression on cells cultured on plastic, poly(L-lactic acid) (PLLA) or poly(DL-lactide-glycolide acid) (PDLGA) polymer films. Detailed molecular characterization of mesenchymal cells will enable optimization of culture conditions for successful creation of implantable cell-loaded constructs.

Congenital hepatic arteriovenous malformation: an unusual cause of neonatal persistent pulmonary hypertension.

Congenital hepatic arteriovenous malformations are rare anomalies, which typically present in infancy with congestive heart failure, anemia, and hepatomegaly. Morbidity and mortality is high if the condition is not recognized and treated promptly. Hepatic arteriovenous malformation associated with persistent pulmonary hypertension of the newborn has been reported in two cases in the literature. We report a neonate who was referred for management of persistent pulmonary hypertension and was subsequently diagnosed with a large hepatic arteriovenous malformation. He underwent coil embolization following which pulmonary hypertension resolved.

Two-dimensional echocardiographic valve measurements in healthy children: gender-specific differences.

The goal of this study was to create nomograms of echocardiographic two-dimensional valve dimensions based on a large group of children without heart disease. Children aged 0-18 years underwent standard echocardiographic evaluation. Referring diagnoses were chest pain, heart murmur, or syncope. Only patients with a structurally normal heart and normal systolic and diastolic function were included. All four valves were measured at their maximal dimensions. A total of 748 children (314 girls and 434 boys) met the inclusion criteria. Mean values and standard deviations were calculated, and z value nomograms based on body surface area were developed. Surprisingly, the boys had larger valve dimensions at all ages. These valve dimension differences were statistically significant for three of four valves even after adjustment for the differences in body sizes. The difference may be due to higher circulating blood volume in boys compared to that in girls. Because the differences are subtle, they reach statistical significance only when evaluated in a large group of subjects. Presented normal value data will be helpful in following cardiology patients and evaluating intervention strategy in patients with valve hypoplasia.

Adhesion molecule expression by osteogenic cells cultured on various biodegradable scaffolds.

Design of tissue-engineered cell-loaded device involves cells seeding onto scaffolds in vitro, allowing them to settle and grow before in vivo transplantation. Interaction between scaffold and cells is important in the development of desired tissues. The present study aimed to investigate the effect of cell-polymer interactions on cell morphology and expression of surface markers of osteogenic MBA-15 cells cultured on various bioresorbable polymers. In this study, we used various polymers: poly(L-lactic acid) (PLLA), poly(DL-lactic acid) (PDLLA), poly(L-lactic-glycolic acid) (PLGA), and poly(DL-lactide-glycolide acid) PDLGA1 and PDLGA2. Expression of integrinalpha-M (CD11b), selectin-E (CD62E), and PECAM-1 (CD31), important in cell-cell and cell-matrix interactions, were quantified by flow-cytometry analysis. Cells grown on PDLGA1 films demonstrated fivefold increase in CD62E expression and two-folds increase in CD11b expression. None of the polymers affected the levels of CD31. Identified differential effect of polymers on the expression of cell-adhesion molecules by osteoprogenitors in vitro might help to choose optimal parameters for successful engraftment of cell-loaded constructs.

Dexamethasone loaded bioresorbable films used in medical support devices: structure, degradation, crystallinity and drug release.

Bioresorbable polymer films containing dexamethasone (DM) were prepared using a solution processing technique. Investigation of the films focused on cumulative DM release as affected by film morphology (drug location/dispersion in the film) and degradation processes. Two film structures were studied: A-type, a polymer film with large drug crystals located on the film's surface, and B-type, a polymer film with small drug particles and crystals distributed within the bulk. The effect of the polymer's degree of crystallinity on the drug release profile was also studied. Prototypical applications of these films are biodegradable medical support devices which combine mechanical support with drug release. In most of our studied systems the drug release profile from the film is determined mainly by both drug location/dispersion in the film and the polymer's weight loss rate. All release profiles from A-type films exhibited a burst effect of approximately 30%, accompanied by a second release phase at a constant rate, whereas the release profiles from B-type films were determined mainly by the degradation profile of the host polymer, and did not exhibit any burst effect. A high degree of crystallinity is important for the current application, since good mechanical properties are required. This contributes to slower drug release rates, mainly at relatively low weight losses, whereas at high weight losses, where a porous structure is created, the crystallinity almost does not affect the rate of drug release. The shape of the porous structure that develops with degradation also affects the drug release profile from the B-type films.

Dobutamine stress echocardiography in the evaluation of young patients with Kawasaki disease.

There has been no consistent approach to the follow-up of Kawasaki disease patients for remote coronary perfusion abnormalities. Dobutamine stress echocardiography (DSE) has become a standard method for evaluation of perfusion abnormalities in adults with coronary artery disease. In addition, DSE has been used with success in some pediatric patients. The purposes of this study were to evaluate safety and accuracy of DSE in the follow-up of patients with Kawasaki disease, to evaluate whether DSE adds any additional value to the resting echocardiogram, and to determine the association of DSE results with American Heart Association (AHA) risk level categories. DSE was performed 1 month to 13 years after acute Kawasaki disease in 47 patients (range, 3.8-22.6 years; 33 males and 16 females). Patients were stratified according to AHA risk level categories (I-V). Ischemia was defined as a new or worsening regional wall motion abnormality or >1 mm ST segment depression on the electrocardiogram during DSE. In 45/47 patients, DSE was completed successfully (i.e., achievement of target heart rate or development of ischemia). No patients in risk levels lower than V (i.e., patients without coronary artery stenoses) had positive DSE, whereas 2/4 (50%) in the risk level V category had positive DSE, both of whom had coronary occlusion >50% confirmed by angiography. Of the 2 AHA risk level V patients with negative DSE, 1 had extensive collateralization and the other had coronary obstruction <50%. DSE is a safe and feasible method for the evaluation of children with Kawasaki disease. DSE provides a confirmatory benefit and may be a useful screening alternative to cardiac catheterization during follow-up. Patients in AHA risk levels I-IV are unlikely to have dobutamine-induced coronary perfusion abnormalities. Patients in the risk level V category may or may not have positive DSE depending on the degree of both coronary obstruction and collateralization.

In vitro study of drug-loaded bioresorbable films and support structures.

Bioresorbable films can serve simultaneously as anatomic support structures and as drug delivery platforms. In the present study, bioresorbable poly(L-lactic acid) (PLLA) films containing dexamethasone were prepared by solution processing methods. Their in vitro studies focused on the mechanical properties with respect to morphology and degradation and erosion processes. Novel expandable support devices (stents) developed from these films were studied. Such a stent would support conduits, such as the neonatal trachea to treat tracheal malacia, until the airway matures, and would then be totally resorbed, obviating the need for a removal operation. The PLLA films showed good initial mechanical properties. They can accommodate drug incorporation on the film surface and also in the bulk. Water incubation of the films results in a decrease in their tensile mechanical properties, due to chain scission and morphological changes. These changes can vary from degradation and small changes in morphological features to erosion, leading to a microporous structure, depending on the polymer. The cumulative release of dexamethasone from the films is linear. The rate of release is determined by the film's structure (drug location/dispersion). The stents demonstrated good mechanical properties. The initial radial compression strength of the stent is determined mainly by the polymer structure. Drug incorporation has a minor effect on the initial stent strength. Exposure to radial compression stress results in elastic reversible deformation or a sudden brittle fracture, depending on the polymer. A 20-week in vitro study of the stents showed that they are applicable for supporting body conduits, such as the trachea.

Gender differences in gambling progression.

The authors compared 39 women and 38 men entering an outpatient treatment program for pathological gambling. They were diagnosed according to DSM-IV and selected by SOGS, followed by a semi-structured interview for demography and progression of the gambling behavior prior to treatment. Women were more often single (59% vs. 26%; p = .005) and started gambling significantly later than men (34.2 vs. 20.4 years; p < .001). The progression of the disorder was more than 2 times faster in women than in men. There was no difference in the age of seeking treatment (44.7 vs. 42.3 years). Findings from this study resemble gender differences in other addictions--in particular the faster progression among women--challenge pharmacodynamic hypotheses for this phenomenon, and suggest gender into account when devising treatment strategies for pathological gambling.

Structured drug-loaded bioresorbable films for support structures.

Bioresorbable films can serve simultaneously as anatomic support structures and as drug delivery platforms. In the present study, bioresorbable PLLA films containing dexamethasone were developed through solution processing. The effect of processing parameters on the film morphology and the resulting mechanical properties was studied. A model describing the structuring of these films is suggested. Generally, the solvent evaporation rate determines the kinetics of drug and polymer crystallization and thus, both the mode of drug dispersion in the polymer and the resulting mechanical properties. Two types of structured films were studied: (1) a polymer film with drug located on its surface, obtained due to drug skin formation accompanied by a later polymer core formation; and (2) a polymer film with small drug particles and crystals distributed within the bulk, obtained by parallel solidification of the two components. A prototypical application of these films is an expandable biodegradable support structure (stent). which we have developed. This stent demonstrated good initial mechanical properties. The film structure has only a minor effect on the stent radial compression strength, but more significantly affects the tensile mechanical properties.

Induction of proinflammatory and chemokine genes by lipopolysaccharide and paclitaxel (Taxol) in murine and human breast cancer cell lines.

In murine macrophages, the anti-tumor agent, paclitaxel, induces expression of a wide variety of inflammatory and anti-inflammatory genes, and causes cytokine secretion via signaling pathways that overlap with those engaged by lipopolysaccharide (LPS), the endotoxic component of Gram-negative bacteria. Using semi-quantitative RT-PCR for detection of gene expression, coupled with ELISA for the detection of secreted gene products, we analyzed the responsiveness of an extensive panel of cytokine and non-cytokine genes to induction by paclitaxel and LPS in the murine DA-3 breast cancer line. A subset of the genes examined (e.g., G-CSF, MIP-2, iNOS, and IL-1 beta, and GM-CSF) was upregulated >3-20-fold by both LPS and paclitaxel in the DA-3 cell line, while IP-10 mRNA was induced by paclitaxel, but not by LPS. In the human MDA-MB-231 breast cancer cell line, LPS also increased mRNA levels for both GM-CSF and IP-10 significantly, while, paclitaxel increased IP-10 mRNA levels with delayed kinetics and failed to induce GM-CSF mRNA. Co-cultures of murine breast cancer cells and macrophages, stimulated with IFN-gamma plus either paclitaxel or LPS, resulted in augmented release of nitric oxide. As both GM-CSF and IP-10 have been implicated in tumor rejection in vivo through either indirect actions on the host immune system or by inhibiting tumor angiogenesis, our data strengthen the hypothesis that tumor cell-derived inflammatory mediators may, in part, underlie the anti-tumor efficacy of paclitaxel in breast cancer.

Drug-dependent women: demographic and clinical characteristics in a Brazilian sample.

This study compared baseline demographics, clinical characteristics and patterns of substance use of 99 substance misusing women seeking treatment in a Brazilian hospital who had been diagnosed with drug dependence (alcohol dependence, if present, was not the most important) against 162 women diagnosed with alcohol dependence. Most of the drug-dependent women in this study were dependent on cocaine (73.7%). It was found that drug-dependent women, at entry, were younger, with a higher educational level, single or lived alone, and had a job outside home more often than alcoholics; they also had less alcohol-use related problems in the family and more relatives with problems with other drugs. They sought treatment mainly by self-initiative and reported more past suicide attempts than their alcoholic counterparts. In addition, they began drug use at the same age but increased drug use, as well as seeking treatment, significantly earlier. Alcoholics had more psychiatric comorbidity. The findings point out heterogeneity among chemically-dependent Brazilian women.

CD11b/CD18 acts in concert with CD14 and Toll-like receptor (TLR) 4 to elicit full lipopolysaccharide and taxol-inducible gene expression.

Overproduction of inflammatory mediators by macrophages in response to Gram-negative LPS has been implicated in septic shock. Recent reports indicate that three membrane-associated proteins, CD14, CD11b/CD18, and Toll-like receptor (TLR) 4, may serve as LPS recognition and/or signaling receptors in murine macrophages. Therefore, the relative contribution of these proteins in the induction of cyclooxygenase 2 (COX-2), IL-12 p35, IL-12 p40, TNF-alpha, IFN-inducible protein (IP)-10, and IFN consensus sequence binding protein (ICSBP) genes in response to LPS or the LPS-mimetic, Taxol, was examined using macrophages derived from mice deficient for these membrane-associated proteins. The panel of genes selected reflects diverse macrophage effector functions that contribute to the pathogenesis of septic shock. Induction of the entire panel of genes in response to low concentrations of LPS or Taxol requires the participation of both CD14 and TLR4, whereas high concentrations of LPS or Taxol elicit the expression of a subset of LPS-inducible genes in the absence of CD14. In contrast, for optimal induction of COX-2, IL-12 p35, and IL-12 p40 genes by low concentrations of LPS or by all concentrations of Taxol, CD11b/CD18 was also required. Mitigated induction of COX-2, IL-12 p35, and IL-12 p40 gene expression by CD11b/CD18-deficient macrophages correlated with a marked inhibition of NF-kappa B nuclear translocation and mitogen-activated protein kinase (MAPK) activation in response to Taxol and of NF-kappa B nuclear translocation in response to LPS. These findings suggest that for expression of a full repertoire of LPS-/Taxol-inducible genes, CD14, TLR4, and CD11b/CD18 must be coordinately engaged to deliver optimal signaling to the macrophage.

Transabdominal pelvic sonography in the preoperative evaluation of patients with congenital adrenal hyperplasia.

PURPOSE: We assessed the clinical value of transabdominal pelvic sonography in the preoperative evaluation of patients with congenital adrenal hyperplasia (CAH) who required feminizing genitoplasty. METHODS: From 1987 to 1998, 31 patients with female pseudohermaphroditism due to CAH underwent feminizing genitoplasty. The median age of the patients was 9 months (range, 1-18 years). Radiologic evaluation performed before surgical reconstruction included retrograde genitography in the first 10 patients and sonographic examination in all 31 patients. Imaging was used to evaluate the anatomic positions and the length of the vagina, whether the junction of the vagina and the urogenital sinus occurred distal or proximal to the pelvic floor, and the presence of internal genitalia. RESULTS: Abdominal sonography identified internal female genitalia in all 31 patients, identified the anatomic shape and position of the vagina in 30 patients (97%), and confirmed the site of communication between the vagina and the urogenital sinus relative to the pelvic floor in 28 patients (90%). Sonographic findings were confirmed by intraoperative panendoscopy. Genitography was less useful than sonography, identifying the site of communication between the vagina and urogenital sinus in only 6 (60%) of 10 patients. CONCLUSIONS: In patients with CAH undergoing vaginal reconstruction, sonography provides adequate information about the anatomy of the vagina and urogenital sinus for surgical decision-making.

Laser prostatectomy. Long-term follow-up of 303 patients.

OBJECTIVE: This retrospective study was undertaken to evaluate results and complications in 303 patients with symptomatic bladder outlet obstruction due to benign prostatic hyperplasia (BPH) who underwent laser prostatectomy focusing on the long-term follow-up, 57 patients had a follow-up of more than 3 years. MATERIALS AND METHODS: A total of 303 patients were treated with the neodymium:YAG laser system for 1993 to 1997, of whom 57 patients were followed up for at least 3 years. All of the patients have been evaluated after 3 months, 6 months and 2 years. 57 patients were evaluated after 3 years. Pre- and postoperative American Urological Association (AUA) symptom score, uroflowmetry (UF), and immediate and long-term complications were assessed. RESULTS: The mean AUA symptom scores of 303 patients decreased over the 24 months follow-up from 16.9 to 7.6. In 57 patients after 36 months the mean AUA symptom score was 7.1. The mean maximal UF increased over the 24 months from 9 to 14.1 cm3/s in 303 patients. In 57 patients at 3 years the mean UF was 13. 9 cm3/s. The overall complications of 303 patients included two perforations of the bladder wall and two perforations of the prostatic capsule. Six (1.9%) patients had postoperative febrile UTI and 28 (9.2%) patients had acute urinary retention after catheter removal. Early bleeding occurred in 3 (0.9%) patients, late bleeding in 8 (2.4%), 4 (1.2%) had urethral stricture, and 1 had stricture of the bladder neck. The overall reoperation rate for symptomatic residual tissue was 1.9% (6 patients). CONCLUSION: Neodymium:YAG laser ablation of prostate represents an efficacious surgical intervention for symptomatic bladder outlet obstruction due to BPH with minimal associated morbidity.

[Tension-free vaginal tape--a new surgical treatment of female urinary stress incontinence].

Female urinary stress incontinence diminishes the quality of life of about 5% of women. It is usually dealt with by surgery to correct the relaxed pelvic floor, the cause of the incontinence. Tension-free vaginal tape is used in a newly described procedure. It consists of the vaginal introduction of a prolene needle-guided mid-urethral sling. The procedure is easy to perform under local anesthesia, recovery is rapid, and results are similar to those of other effective operations. We report 44 patients who underwent this type of surgery. There were no significant complications. The early results were good and although the follow-up has been short, we believe that experience with this operation will play an important role in the treatment of urinary stress incontinence.

Induction of adrenomedullin mRNA and protein by lipopolysaccharide and paclitaxel (Taxol) in murine macrophages.

Lipopolysaccharide (LPS), a potent inflammatory stimulus derived from the outer membrane of gram-negative bacteria, has been implicated in septic shock. Plasma levels of adrenomedullin (AM), a potent vasorelaxant, are increased in septic shock and possibly contribute to the characteristic hypotension. As macrophages play a central role in the host response to LPS, we studied AM production by LPS-stimulated macrophages. When peritoneal exudate macrophages from C3H/OuJ mice were treated with protein-free LPS (100 ng/ml) or the LPS mimetic paclitaxel (Taxol; 35 microM), an approximately 10-fold increase in steady-state AM mRNA levels was observed, which peaked between 2 and 4 h. A three- to fourfold maximum increase in the levels of immunoreactive AM protein was detected after 6 to 8 h of stimulation. While LPS-hyporesponsive C3H/HeJ macrophages failed to respond to protein-free LPS with an increase in steady-state AM mRNA levels, increased levels were observed after stimulation of these cells with a protein-rich (butanol-extracted) LPS preparation. In addition, increased AM mRNA was observed following treatment of either C3H/OuJ or C3H/HeJ macrophages with soluble Toxoplasma gondii tachyzoite antigen or the synthetic flavone analog 5, 6-dimethylxanthenone-4-acetic acid. Gamma interferon also stimulated C3H/OuJ macrophages to express increased AM mRNA levels yet was inhibitory in the presence of LPS or paclitaxel. In vivo, mice challenged intraperitoneally with 25 microg of LPS exhibited increased AM mRNA levels in the lungs, liver, and spleen; the greatest increase (>50-fold) was observed in the liver and lungs. Thus, AM is produced, by murine macrophages, and furthermore, LPS induces AM mRNA in vivo in a number of tissues. These data support a possible role for AM in the pathophysiology of sepsis and septic shock.