Is Taurolidine a candidate for treatment of rheumatoid arthritis?

OBJECTIVE: To study the therapeutic potential of taurolidine (TRD), a derivative of taurine with known anti-inflammatory and anti-proliferative properties, in various experimental models of synovitis. METHODS: In vitro: fibroblast-like synoviocytes (RA FLS) isolated from the synovial tissue of patients with rheumatoid arthritis (RA) were cultured in the presence of either TRD or polyvinylpyrrolidine (PVP), the pharmaceutical stabilizer of TRD, which was used as a control. Proliferation of RA FLS and cytokine (IL-6 and IL-8) release were measured. In vivo: (A). The effect of systemic TRD treatment on the development of collagen-induced arthritis (CIA) in female DBA1/J mice was investigated. Mice were treated either with intraperitoneal injections of 1 ml of 2% Taurolin Boehringer Ingelheim (TRD +PVP) or with PVP as placebo. The incidence of arthritis, myeloperoxidase (MPO) activity in periarticular tissue, as well as serum concentration of IgG specific to collagen II (IgG alphaCII) were determined. (B). The effect of intra-articular TRD treatment was studied in rabbits with antigen-induced monoarthritis (AIA). After the induction of AIA of right knees rabbits were treated either with intra-articular injections of 0.5 ml of 2% Taurolin or 0.5ml PVP ( placebo). The animals were examined for clinical signs of arthritis and diameter of joints was measured. After termination of the experiment, the arthritic knees were examined and histopathology of the joints was assessed. In addition, serum amyloid A (SAA) concentration was measured. RESULTS: n vitro: TRD exerted cytotoxic effect on RA FLS when applied at concentrations >100 microM. TRD at non-cytotoxic concentrations, inhibited PDGF-triggered RA FLS proliferation, reduced IL-1beta - stimulated production of IL-6 and slightly decreased intracellular content of IL-8. In vivo: (A). Intraperitoneal treatment with Taurolin significantly reduced the incidence (30%) of CIA when compared to the control mice (79%). However, Taurolin failed to control the development of CIA in mice with high serum level of IgG alphaCII (>1000 U).(B). Intra-articular application of 2% Taurolin resulted in amelioration of AIA in all treated rabbits (reduced diameter of arthritic joints and smaller rise of SAA level as compared to the control animals). Histopathologic evaluation revealed pannus formation in both groups and extensive necrotic lesions of synovial tissue treated with TRD, suggesting synoviorthesis-like effect. CONCLUSION: Results from AIA and from in vitro RA FLS studies suggest that intra-articular administration of TRD could be used as a "pharmacological scalpel" to remove the inflamed synovium. Our data confirmed anti-inflammatory and anti-proliferative properties of TRD in all experimental models encouraging further studies which should evaluate its therapeutic potential in RA.

Differential inflammatory mediator response in vitro from murine macrophages to lactobacilli and pathogenic intestinal bacteria.

Chronic active colitis (including inflammatory bowel disease - IBD) is maintained by a variety of pro-inflammatory mediators. Certain intestinal bacterial strains may induce colitis, whereas some strains (e.g. Lactobacillus spp.) show a protective effect in colitis owing to their anti-inflammatory activity. In this study, we have examined the production of selected inflammatory cytokines, reactive oxygen species (ROS), nitric oxide (NO) and the expression of haeme oxygenase-1 (HO-1) by murine peritoneal macrophages stimulated in vitro by the intestinal bacterial strains, isolated from mice with colitis. Lactobacillus strains (Lactobacillus reuteri, L. johnsonii, L. animalis/murinus) and two potentially pathogenic bacteria (Escherichia coli and Enterococcus faecalis) induced the production of substantial amounts of cytokines with a strain specific profile. Despite some interstrain differences, all lactobacilli induced production of anti-inflammatory cytokines (IL-10(high), IL-6(low), IL-12p70(low)). Conversely, E. faecalis and E. coli induced the production of proinflammatory cytokines (TNF-alpha, IL-12p70), the cytokines essential for chronic IBD. Macrophages released comparably substantial amounts of ROS in response to all Lactobacillus strains tested, while E. coli and E. faecalis ability to induce generation of ROS was negligible. In contrast to ROS, the production of NO/NO(2) (-) by macrophages activated with all bacterial strains tested was similar. Moreover, for the first time, it has been shown that intestinal bacteria differed in their ability to induce expression of HO-1, a stress-inducible enzyme with antioxidant and anti-inflammatory properties. The beneficial immunoregulatory properties of candidate probiotic bacteria for the treatment of IBD are discussed.

Dynamics of cervical langerhans cell counts in the course of HPV-positive CIN treatment with the use of human recombinant interferon gamma.

OBJECTIVES: Langerhans cells play a pivotal role as professional antigens presenting cells in cervical epithelium, thus changes in their density or/and function may profoundly influence the proper activation of the afferent arm of immune response in cases of HPV-related intraepithelial lesions. AIM OF THE STUDY: Assessment of intraepithelial Langerhans cell count changes in CIN I/CIN II after human recombinant interferon gamma (IFNgamma) application and correlation with clinical outcome. MATERIAL & METHODS: The present study is a part of prospective trial on IFNgamma application in the treatment of CIN I/CINII associated with high-risk HPV infection. Seventeen subjects underwent uniform IFNgamma treatment (four intracervical injections in a two-day interval for a total dose of 6,000,000 IU). Langerhans cells were stained within cervical punch biopsy specimens with the use of polyclonal anti-S-100 antibody according to the three-step indirect peroxidase protocol, and their mean count calculated for the following groups: before IFNgamma treatment launching, immediately after completion of the treatment, and after two months of follow-up. RESULTS: The analysis revealed a rapid and significant increase in Lagerhans' cell count immediately after treatment completion (21.17/mm2 and 25.94/mm2, respectively, at p = 0.019) which further increased in the group of complete response (in 9 subjects; 32.22/mm2). After transient elevation of the Langerhans' cell count it returned to a level even lower than initially in the non-responder group (4 subjects; 20.25/mm2). CONCLUSION: Our data strongly support the observation from static studies suggesting that regression of HPV-related cervical lesions is associated with increased density of epithelial Langerhans cells.

Administration of enoxaparin by continuous infusion in a naturalistic setting: analysis of renal function and safety.

STUDY OBJECTIVE: To describe the clinical use and safety of continuous infusion (CI) enoxaparin in a naturalistic setting and to evaluate the influence of renal function on enoxaparin elimination. DESIGN: Retrospective medical record review. SETTING: 1000-bed tertiary care teaching centre. PATIENTS: Hospitalized patients that received enoxaparin by CI during a 2-year period. INTERVENTIONS: None. MEASUREMENTS: Specific details of dosage and monitoring were collected. Adverse drug reactions (ADR) were recorded. Creatinine clearance (CrCl) was calculated using Cockroft and Gault and Brater equations. A population pharmacokinetic analysis was performed using the non-linear mixed effect model (NONMEM). For patients located in the intensive care unit (ICU) and ward, POSTHOC pharmacokinetic parameter estimates were evaluated using the Wilcoxon rank-sum. Pearson correlation coefficient was calculated to determine the association between renal function and anti-Xa clearance. MAIN RESULTS: Sixty-seven patients received enoxaparin by CI of which 61.2% were in the ward and 38.8% in the ICU. The average initial rate and duration of infusion were 5.2 mg/h and 5.6 days, respectively. The number of anti-Xa concentration measurements averaged five per patient. Nine patients experienced an ADR. The most frequent ADR was gastrointestinal bleeding (n = 4). Among the 67 patients, 48 had available anti-Xa concentrations and were included in the NONMEM model. The anti-Xa CL and volume of distribution for ICU and ward patients averaged 0.64 +/- 0.34 L/h, 10.6 +/- 1.55 L and 1.01 +/- 0.39 L/h, 9.08 +/- 1.17 L, respectively. CrCl was not a significant covariate when included in the NONMEM model, and the association between CrCl and anti-Xa clearance was not significant (R2 = 0.0005; P = 0.8916). CONCLUSIONS: This study is the first to report the use and safety of prolonged CI enoxaparin. Pharmacokinetic parameters of enoxaparin differ in ICU vs. ward patients. Overall, we found the safety of CI to be comparable to subcutaneous administration. Also, we found no effect of renal function on enoxaparin elimination.

Is there a role of taurine bromamine in inflammation? Interactive effects with nitrite and hydrogen peroxide.

OBJECTIVE AND DESIGN: The myeloperoxidase system of neutrophils generates chlorinating and brominating oxidants in vivo. The major haloamines of the system are taurine chloramine (TauCl) and taurine bromamine (TauBr). It has been demonstrated in vitro that TauCl exerts both antiinflammatory and anti-bacterial properties. Much less is known about TauBr. The present study was conducted to compare bactericidal and immunoregulatory capacity of TauBr with that of the major chlorinating oxidants: HOCl and TauCl. Moreover, the effect of nitrites and H(2)O(2) on TauBr activity was investigated. MATERIALS: TauBr was prepared by reaction of HOBr with taurine. The reaction was monitored by UV absorption spectra. METHODS: Bactericidal activity of TauBr, TauCl and HOCl was tested by incubation of E. coli with the compounds and determined by the pour-plate method. To test the anti-inflammatory activity the compounds were incubated with LPS and IFN-gamma stimulated murine peritoneal macrophages. The production of following mediators was measured: nitrites by Griess reaction; TNF-alpha, IL-6, IL-10, IL-12p40 using capture ELISA. In some experiments the compounds were incubated with either nitrites or H(2)O(2). RESULTS: In our experimental set-up TauBr and HOCl exerted strong bactericidal effects on E. coli (MBC = 110 microM and 8 microM, respectively), while TauCl (< 1000 microM) did not kill test bacteria. However, both, TauBr and TauCl, at noncytotoxic concentrations (< 300 microM) inhibited the cytokine and nitric oxide production by macrophages. H(2)O(2) completely abolished the biological activities of TauBr but not those of TauCl. Nitrites did not affect any activity of TauBr or TauCl while they diminished the HOCl(-) mediated bacterial killing. CONCLUSION: TauBr, despite very low concentration of Br(-) in body fluids, may support TauCl and HOCl in the regulation of inflammatory response and in killing of bacteria by neutrophils. However, TauBr activity in vivo will depend on the presence of H(2)O(2) and possible other mediators of inflammation which can compete with target molecules for TauBr.

Effect of taurine chloramine, the product of activated neutrophils, on the development of collagen-induced arthritis in DBA 1/J mice.

Taurine chloramine (TauCl), a product of neutrophil myeloperoxidase - halide system, formed by a reaction of taurine with HOCl, is known as an anti-microbial and anti-inflammatory long-lived oxidant. We previously reported that TauCl inhibits in vitro the production of proinflammatory cytokines (IL-6, IL-8) by RA synoviocytes. Therefore we performed this study to investigate the effect of TauCl treatment on the development of collagen-induced arthritis (CIA) in DBA1/J mice. Early administration of TauCl (after primary immunization) resulted in the delay of the onset of CIA, but had no effect on severity of arthritis. TauCl, given daily for 21 days after booster immunization, did not reduce the symptoms of arthritis in those mice, which already developed CIA, but significantly diminished incidence of the disease (55% vs. 90% of placebo mice). The mechanism of this effect is unknown. This is the first in vivo study suggesting that TauCl may be used for immune intervention in chronic inflammatory diseases.

Distinctive molecular profiles of high-grade and low-grade gliomas based on oligonucleotide microarray analysis.

Astrocytomas are heterogeneous intracranial glial neoplasms ranging from the highly aggressive malignant glioblastoma multiforme (GBM) to the indolent, low-grade pilocytic astrocytoma. We have investigated whether DNA microarrays can identify gene expression differences between high-grade and low-grade glial tumors. We compared the transcriptional profile of 45 astrocytic tumors including 21 GBMs and 19 pilocytic astrocytomas using oligonucleotide-based microarrays. Of the approximately 6800 genes that were analyzed, a set of 360 genes provided a molecular signature that distinguished between GBMs and pilocytic astrocytomas. Many transcripts that were increased in GBM were not previously associated with gliomas and were found to encode proteins with properties that suggest their involvement in cell proliferation or cell migration. Microarray-based data for a subset of genes was validated using real-time quantitative reverse transcription-PCR. Immunohistochemical analysis also localized the protein products of specific genes of interest to the neoplastic cells of high-grade astrocytomas. Our study has identified a large number of novel genes with distinct expression patterns in high-grade and low-grade gliomas.

Implementation and pharmacoeconomic analysis of a clinical staff pharmacist practice model.

The implementation and pharmacoeconomic analysis of a clinical staff pharmacist (CSP) practice model are described. Staff pharmacists at a large, tertiary care, academic medical center were selected and trained to perform clinical pharmacy services under the direction of clinical pharmacy specialist mentors. Clinical interventions by these CSP practitioners were evaluated in terms of direct cost savings (the difference in actual acquisition costs between therapies) and cost avoidance (the dollar value of adverse drug events [ADEs] avoided). The CSPs performed a total of 4959 interventions during a 12-month period. The interventions provided direct cost savings of $92,076 and an estimated cost avoidance of $488,436. Comparing cost savings and cost avoidance with the expenses of providing these services indicated a net economic benefit of $392,660. A new model of pharmacy practice that integrates staff pharmacists into existing clinical practice has the potential to minimize the risks, decrease the costs, and improve the outcomes associated with drug therapy.

Visual compatibility of amiodarone hydrochloride injection with various intravenous drugs.

The Notes section welcomes the following types of contributions: (1) practical innovations or solutions to everyday practice problems, (2) substantial updates or elaborations on work previously published by the same authors, (3) important confirmations of research findings previously published by others, and (4) short research reports, including practice surveys, of modest scope or interest. Notes should be submitted with AJHP's manuscript checklist. The text should be concise, and the number of references, tables, and figures should be limited.

The gene for the axonal cell adhesion molecule TAX-1 is amplified and aberrantly expressed in malignant gliomas.

The human TAX-1 gene encodes a Mr 135,000 glycoprotein that is transiently expressed on the surface of a subset of neurons during development and is involved in neurite outgrowth. The TAX-1 gene has been mapped to a region on chromosome 1 that has been implicated in microcephaly and the Van der Woude syndrome. Using restriction landmark genome scanning to search for amplified genes in gliomas, we found TAX-1 to be amplified in 2 high-grade gliomas among a group of 26 gliomas investigated. Real-time reverse transcription-quantitative PCR analysis detected high levels of TAX-1 mRNA in glial tumors, even in the absence of TAX-1 gene amplification. Immunohistochemical analysis revealed abundant levels of TAX-1 in neoplastic glial cells of glioblastoma multiforme tumors. Because glial tumors are highly invasive and in view of the role of TAX-1 in neurite outgrowth, we investigated the potential role of TAX-1 in glioma cell migration. Using an in vitro assay, we found that the migration of glioma tumor cells is profoundly reduced in the presence of either an anti-TAX-1 antibody or a TAX-1 antisense oligonucleotide. Our findings suggest that TAX-1 plays a role in glial tumorigenesis and may provide a potential target for therapeutic intervention.

Interrater reliability of 2 sedation scales in a medical intensive care unit: a preliminary report.

BACKGROUND: Critical care nurses must assess the effectiveness of sedatives and analgesic agents in order to titrate doses. OBJECTIVES: To measure the interrater reliability of 2 sedation scales used to assess patients in medical intensive care units. METHODS: The interrater reliabilities of the Motor Activity Assessment Scale and the Luer sedation scale were compared prospectively in 31 patients receiving mechanical ventilation in an 18-bed medical intensive care unit of a tertiary care institution. Three registered nurses, 1 clinical pharmacist, and 1 physician simultaneously and independently followed a standardized procedure to rate each patient by using the 2 scales. Scales were randomly ordered to counteract ordering effect. Analysis of variance with post hoc Duncan multiple range tests was used to detect bias; a correlation coefficient matrix was used to examine degree of association among raters; and the intraclass correlation coefficient was measured to control for multiple raters. RESULTS: No significant bias was detected with either scale. The Motor Activity Assessment Scale had less variation (Pearson r = 0.75-0.92) than did the Luer scale (Pearson r = 0.37-0.94) and had a stronger intraclass correlation coefficient (0.81 vs 0.79). CONCLUSIONS: The Motor Activity Assessment Scale showed the highest consistency among raters.

Influence of clinicians' values and perceptions on use of clinical practice guidelines for sedation and neuromuscular blockade in patients receiving mechanical ventilation.

BACKGROUND: Although popular, clinical practice guidelines are not universally accepted by healthcare professionals. OBJECTIVES: To compare nurses' and physicians' actual and perceived rates of adherence to practice guidelines used in sedation of patients receiving mechanical ventilation and to describe nurses' and physicians' perceptions of guideline use. METHODS: Pairs of fellows and nurses caring for 60 eligible patients were asked separately about their rationale for medicating patients, effectiveness of medication, and their perceived adherence to the guidelines. Actual adherence was determined independently by review of medical records. An additional 18 nurses and 11 physicians were interviewed about perceptions of guideline use. RESULTS: Use of mechanical ventilation was the most common reason given by physicians (53%) and nurses (48%) for medicating patients, although reasons for administering medication to a given patient differed in up to 30% of cases. Physicians and nurses disagreed on the effectiveness of medication in 42% (P = .01) of cases. Physicians reported following guidelines in 69% of cases, but their actual adherence rate was only 20%. Clinicians sometimes had difficulty distinguishing among anxiety, pain, and delirium. Clinicians justified variations from guidelines by citing the value of individualized patient care. Nurses and physicians sometimes had different goals in the use of sedation. CONCLUSIONS: Physicians may think they are following sedation guidelines when they are not, and they may prescribe incorrect medications if the cause of agitation is misdiagnosed. Differences between physicians and nurses in values and perceptions may hamper implementation of clinical practice guidelines.

A pilot study of penicillin skin testing in patients with a history of penicillin allergy admitted to a medical ICU.

BACKGROUND: Penicillin skin testing is an accurate method to determine whether a person with a history of penicillin allergy is at risk of having an immediate reaction to penicillin. A patient with a negative reaction to a skin test may be able to use a penicillin compound safely, which could reduce the use of broad-spectrum antibiotics in this patient population. METHODS: We prospectively studied all patients with histories of penicillin allergy who were admitted to a medical ICU during a 3-month period and who received antibiotics. Skin testing was performed with benzylpenicilloyl polylysine and penicillin G. We determined the incidence of true allergy, the percentage of patients in whom antibiotic coverage was modified, and the safety of the test. RESULTS: Two hundred fifty-seven patients were admitted to the medical ICU of The Cleveland Clinic Foundation during the study period. Twenty-four patients (9%), labeled as penicillin allergic and receiving antibiotics, were enrolled. Three patients (13%, 3 of 21) gave histories of type I reaction to penicillin and were not skin tested. Twenty patients (95%, 20 of 21) had negative skin test reactions to penicillin and positive skin test reactions to histamine control. One patient (4%, 1 of 21) with negative skin test reactions to both penicillin and histamine control had a test dose challenge with piperacillin that was well tolerated. There were no adverse events. Antibiotic coverage was changed in 10 patients (48%) as a result of skin testing. CONCLUSION: Most patients with histories of allergy to penicillin have negative reactions to skin tests and may receive penicillin safely. Penicillin skin testing can be utilized as a safe and effective strategy to reduce the use of broad-spectrum antibiotics.

Differential effects of pentoxifylline, a non-specific phosphodiesterase inhibitor, on the production of IL-10, IL-12 p40 and p35 subunits by murine peritoneal macrophages.

Pentoxifylline (PTX), a methylxanthine derivative, has been reported to be an effective drug in inhibiting TNF-alpha responses during septic shock. The inhibition of TNF-alpha production seems to be correlated with increased intracellular cAMP levels. PTX also affects the production of other cytokines such as IL-1, IL-6, IL-10, IL-12, and IFN-gamma. However, inhibition, as well as enhancement of cytokine production, has been observed in vitro, depending on the PTX concentration and cell type used.IL-12 is a heterodimeric cytokine that plays an important role in the development of Th1-mediated inflammatory responses. IL-12 along with TNF-alpha and other proinflammatory cytokines has shown to be responsible for the pathological reaction, which may lead to septic shock. For biological activity, the expression of both subunits of IL-12, p35 and p40, is required. Moreover, the p40 chain of IL-12 specifically inhibits the effects of the IL-12 heterodimer. In this study, we investigated the effects of PTX on the production of both proinflammatory (TNF-alpha, IL-6, IL-12) and anti-inflammatory (IL-10) cytokines by murine macrophages (Mφ). We have found that PTX, at concentrations below 100 microg/ml, selectively inhibited the production of TNF-alpha. Forskolin, a cAMP-elevating agent, similarly affected the production of the cytokines tested. However, at higher concentrations, PTX inhibited the production of TNF-alpha, IL-10, and IL-12 p35, but surprisingly, PTX enhanced the production of IL-12 p40. Concentrations of IL-10 were negatively correlated with the concentrations of IL-12 p40 subunit. These results further confirm the relevance of the use of PTX in clinical trials of immunological disorders characterised by inappropriate Th1 type immune responses.

Hypertensive urgency induced by an interaction of mirtazapine and clonidine.

Mirtazapine is a new antidepressant with a tetracyclic chemical structure that is not related to selective serotonin reuptake inhibitors, tricyclic antidepressants, or monoamine oxidase inhibitors. The antidepressant effect results from stimulation of the noradrenergic system through antagonism at central (alpha2-inhibitory receptors. Clonidine exerts its antihypertensive effect by stimulating these receptors to cause a reduction in endogenous release of norepinephrine. Therefore, the two agents have mechanisms of action that potentially oppose one another. We report a case of hypertensive urgency that ensued after a patient stabilized on clonidine began taking mirtazapine.

Whole-genome methylation scan in ICF syndrome: hypomethylation of non-satellite DNA repeats D4Z4 and NBL2.

The ICF (immunodeficiency, centromeric instability and facial abnormalities) syndrome is a rare recessive disease characterized by immunodeficiency, extraordinary instability of certain heterochromatin regions and mutations in the gene encoding DNA methyltransferase 3B. In this syndrome, chromosomes 1 and 16 are demethylated in their centromere-adjacent (juxtacentromeric) heterochromatin, the same regions that are highly unstable in mitogen-treated ICF lymphocytes and B cell lines. We investigated the methylation abnormalities in CpG islands of B cell lines from four ICF patients and their unaffected parents. Genomic DNA digested with a CpG methylation-sensitive restriction enzyme was subjected to two-dimensional gel electrophoresis. Most of the restriction fragments were identical in the digests from the patients and controls, indicating that the methylation abnormality in ICF is restricted to a small portion of the genome. However, ICF DNA digests prominently displayed multicopy fragments absent in controls. We cloned and sequenced several of the affected DNA fragments and found that the non-satellite repeats D4Z4 and NBL2 were strongly hypomethylated in all four patients, as compared with their unaffected parents. The high degree of methylation of D4Z4 that we observed in normal cells may be related to the postulated role of this DNA repeat in position effect variegation in facio- scapulohumeral muscular dystrophy and might also pertain to abnormal gene expression in ICF. In addition, our finding of consistent hypomethylation and overexpression of NBL2 repeats in ICF samples suggests derangement of methylation-regulated expression of this sequence in the ICF syndrome.

Introduction of sedative, analgesic, and neuromuscular blocking agent guidelines in a medical intensive care unit: physician and nurse adherence.

OBJECTIVE: To determine physician and nurse adherence with sedative, analgesic, and neuromuscular blocking agent guidelines in the management of mechanically ventilated patients in a medical intensive care unit. DESIGN: Prospective cohort study. SUBJECTS: One hundred consecutively admitted patients to a medical intensive care unit who required mechanical ventilatory support. A sample of 29 nurses, residents, and attending physicians were interviewed regarding their attitudes and perceptions of the guidelines. MEASUREMENT: Data were collected from concurrent medical records and included the following: demographic characteristics; clinical variables; physician prescriptions of sedative, analgesic, and/or neuromuscular blocking agents; nurse administration of these medications; documentation of monitoring; and assessment of patient hemodynamic status and behaviors. A semistructured interview was elicited from both nurses and physicians about their rationale for the use or nonuse of the guidelines. RESULTS: Patients ranged in age from 24 to 87 yrs, mean 60.7 (+15.3) yrs. Admission Acute Physiology and Chronic Health Evaluation III scores ranged from 36 to 192, mean 93.8 ( 30.5) and median 88. Length of mechanical ventilatory support ranged from 1 to 112 days, mean 14.8 ( 20.0) days, and median 8 days; medical intensive care unit length of stay ranged from 1 to 46 days, with a mean of 9.8 ( 8.1) days and a median of 8 days. Of the 100 patients, 47% died, 28% returned home, and 25% were discharged to a nursing facility. Eighty-five patients were administered one or more sedative, analgesic, and/or neuromuscular blocking agent, range 1-9 drugs, mean 2.5 (+1.5) drugs. Physicians prescribed 14 different medications; the most commonly administered drug was lorazepam (n = 71), followed by morphine (n = 39). Physicians and nurses had partial or total adherence to the guidelines in 58% of patients. The initial choice of the drug followed the guidelines in 60% of patients; the overall guideline was followed in 23% of patients. The most common rationales for nonadherence to the guidelines stated by both physicians and nurses were patient-specific factors, resident guideline learning curve, and physician medication preferences. CONCLUSION: Most patients required treatment for agitated behaviors. The majority of treatment regimens partially or totally adhered to the guidelines. Factors such as patient-specific disease states, resident guideline learning curve, and physician preferences of medications may have decreased adherence. Improving adherence to the guidelines is essential to assess their effectiveness in improving clinical outcomes.

Regulation of murine dendritic cell functions in vitro by taurine chloramine, a major product of the neutrophil myeloperoxidase-halide system.

Taurine chloramine (TauCl) is a major chloramine generated in activated neutrophils as a result of the reaction of highly toxic hypochlorous acid and taurine, the most abundant free amino acid in cytosol. In this study we have tested the influence of TauCl on the properties of murine dendritic cells (DC), the major cell population involved in the initiation of an adaptive immune response against pathogenic organisms. N418+, MHC II+, B7-2+ dendritic cells, generated from the mouse bone marrow cells cultured in the presence of granulocyte-macrophage colony-stimulating factor, were stimulated by interferon-gamma and lipopolysaccharide to produce nitric oxide, reactive oxygen species, interleukin-6 (IL-6), tumour necrosis factor-alpha, and IL-12, in the presence of different doses of TauCl. TauCl differently inhibited the generation of these inflammatory mediators in a dose-dependent manner. Furthermore, TauCl selectively modulated the ability of DC to induce the release IL-2 and IL-10 from T cells. These results suggest that neutrophil-derived mediators, such as TauCl, at a site of inflammation, may affect the functions of sentinel DC and macrophages, and play a role in maintaining the balance between the inflammatory response and the induction of an antigen-specific immune response.

Use of factor IX complex in warfarin-related intracranial hemorrhage.

OBJECTIVE: Anticoagulation-treated patients presenting with intracranial hemorrhage, including subdural hematoma, epidural hematoma, subarachnoid hemorrhage, and intracerebral hemorrhage, require urgent correction of their coagulopathy to prevent worsening hemorrhage and to facilitate surgical intervention when necessary. In this study, we compared the use of fresh frozen plasma (FFP) with that of Factor IX complex concentrate (FIXCC) to achieve rapid correction of warfarin anticoagulation. METHODS: Patients admitted to a tertiary care center with computed tomography-proven intracranial hemorrhage and a prothrombin time of more than 17 seconds were considered for inclusion in the study protocol. Complete data sets were obtained for eight patients randomized to treatment with FFP and five patients randomized to treatment with FFP supplemented with FIXCC. The prothrombin time and International Normalized Ratio were measured every 2 hours for 14 hours. Correction of anticoagulation was defined as an International Normalized Ratio of < or =1.3. RESULTS: A difference in repeated International Normalized Ratio measurements during the first 6 hours of correction was observed between the FIXCC and FFP groups (P < 0.03). The rate of correction was greater (P < 0.01) and the time to correction was shorter (P < 0.01) for the FIXCC-treated group. No difference in neurological outcomes was detected between groups, but a higher complication rate was observed for the FFP-treated group. CONCLUSION: The use of FIXCC accelerated correction of warfarin-related anticoagulation in the presence of intracranial hemorrhage.

Aseptic meningitis caused by Teflon implantation for microvascular decompression. Case report.

The authors present the case of a 47-year-old man who, after undergoing microvascular decompression for trigeminal neuralgia, experienced symptomatic pain relief but developed prolonged aseptic meningitis. This case is unusual in that the patient remained dependent on steroid medications for nearly 5 months following the initial surgery and the aseptic meningitis did not resolve until after surgical removal of the Teflon used to pad the trigeminal nerve. The pathophysiological characteristics of the body's reaction to implanted Teflon are discussed along with the rationale for removing this substance in cases of prolonged intractable aseptic meningitis.