Clin Infect Dis, 2004 Feb 15, 38(4), 476 - 82 Epub 2004 Jan 26. Acceptable rates of treatment failure in osteomyelitis involving the diabetic foot: a survey of infectious diseases consultants; Perencevich EN et al.; Shortening the duration of antibiotic therapy is an attractive strategy for delaying the emergence of antimicrobial resistance . The paucity of data about optimal treatment durations hinders adoption of this approach . This study used contingent valuation analysis to identify failure rates for treatment of diabetic foot osteomyelitis acceptable to infectious diseases consultants (IDCs) . The Infectious Diseases Society of America's Emerging Infections Network (EIN) provided members with the case scenario and 1 of 10 failure rates; members were asked, assuming delivery of standard therapy, if they would accept or reject the given failure rate . The relationship between specific failure rates and the willingness of IDCs to accept them was analyzed . The median acceptable failure rate for EIN members was 18.1%; 75% of IDCs found a failure rate of 7.8% to be acceptable, and 25% found a rate of 28.4% to be acceptable . The methodology used in this study may prove useful in delineating acceptable treatment failure thresholds, an initial step in shortening durations of antimicrobial therapy. J Immunol, 2004 Feb 15, 172(4), 2177 - 85 A novel role for an insect apolipoprotein (apolipophorin III) in beta-1,3-glucan pattern recognition and cellular encapsulation reactions; Whitten MM et al.; Lipoproteins and molecules for pattern recognition are centrally important in the innate immune response of both vertebrates and invertebrates . Mammalian apolipoproteins such as apolipoprotein E (apoE) are involved in LPS detoxification, phagocytosis, and possibly pattern recognition . The multifunctional insect protein, apolipophorin III (apoLp-III), is homologous to apoE . In this study we describe novel roles for apoLp-III in pattern recognition and multicellular encapsulation reactions in the innate immune response, which may be of direct relevance to mammalian systems . It is known that apoLp-III stimulates antimicrobial peptide production in insect blood, enhances phagocytosis by insect blood cells (hemocytes), and binds and detoxifies LPS and lipoteichoic acid . In the present study we show that apoLp-III from the greater wax moth, Galleria mellonella, also binds to fungal conidia and beta-1,3-glucan and therefore may act as a pattern recognition molecule for multiple microbial and parasitic invaders . This protein also stimulates increases in cellular encapsulation of nonself particles by the blood cells and exerts shorter term, time-dependent, modulatory effects on cell attachment and spreading . All these responses are dose dependent, occur within physiological levels, and, with the notable exception of beta-glucan binding, are only observed with the lipid-associated form of apoLp-III . Preliminary studies also established a beneficial role for apoLp-III in the in vivo response to an entomopathogenic fungus . These data suggest a wide range of immune functions for a multiple specificity pattern recognition molecule and may provide a useful model for identifying further potential roles for homologous proteins in mammalian immunology, particularly in terms of fungal infections, pneumoconiosis, and granulomatous reactions. Bioinformatics, 2004 Apr 12, 20(6), 970 - 3 Epub 2004 Feb 05. Sequence analysis and membrane partitioning energies of alpha-helical antimicrobial peptides; Han X et al.; Sequences of 221 alpha-helical antimicrobial peptides (alphaAMPs) were compared and 63-166 of them were selected and analyzed using Perl programs . The results showed that aliphatic amino acids Gly, Leu, Ala, Ile and two positively charged amino acids Lys and Arg were composed of more than 63% of the first 20 residues of alphaAMPs . The weighed mean membrane partitioning energies at positions from 1 to 25 of alphaAMPs were calculated . Profile of the partitioning energies suggests oblique membrane insertion and an amphipathic alpha-helical structure of the N-terminus of alphaAMP (residues from 1 to 13), a bend structure at positions 13 and 14, and a less structured C-terminus that parallels the surface of the membrane . These structural features are in good agreement with the experimentally determined membrane structure of hemagglutinin fusion peptide from influenza virus . We hypothesize that this (N-terminal oblique alpha-helix)-central bend-(C-terminus) could be a common structural motif of membrane-disruptive peptides. Ann Otol Rhinol Laryngol, 2004 Jan, 113(1), 76 - 81 Tolerability of N-chlorotaurine in the guinea pig middle ear: a pilot study using an improved application system; Neher A et al.; The tissue tolerance of N-chlorotaurine (NCT), a mild endogenous antimicrobial oxidant, has been investigated by application to the guinea pig middle ear . The animals were implanted with a novel cannula system that allows chronic external drug delivery to the round window niche . In the first part of the study, 3 animals each received 100 microL of 0.1% NCT (5.5 mmol/L) and 1% NCT, respectively, in aqueous solution twice daily for 8 days . In the second part, NCT was dissolved in phosphate-buffered saline solution to 300 milliosmolar (isotonic), and 27 microL was injected in 3 additional animals twice daily for 7 days . The guinea pigs injected with 100 microL of NCT developed immediate dizziness and nystagmus and did not thrive . Other reactions included mucosal thickening in the middle ear, rupture of the tympanic membrane, and blood and gelatinous material in the cochlea accompanied by hair cell loss and a 10- to 90-dB elevation of the hearing threshold as determined by auditory brain stem responses . The effects seemed to be dose-dependent, but the rate of variability was high across animals . In contrast, the guinea pigs treated with 27 microL of isotonic NCT showed no signs of discomfort, no or only moderate thickening of the middle ear mucosa, no shift of the hearing threshold, and no hair cell loss . Positive control animals injected with 10% neomycin sulfate developed extensive hair cell loss . Provided that the membranes of the inner ear are intact and that low single-dose volumes are used to avoid increased middle ear pressure, isotonic NCT seems to be well tolerated in the tympanic cavity . The new drug delivery system proved to be advantageous for ototoxicity studies. Mem Inst Oswaldo Cruz, 2003 Oct, 98(7), 967 - 74 Epub 2004 Jan 07. Screening of Brazilian basidiomycetes for antimicrobial activity; Rosa LH et al.; A total of 103 isolates of basidiomycetes, representing 84 species from different Brazilian ecosystems, were evaluated for their antifungal and antibacterial activity in a panel of pathogenic and non-pathogenic microorganisms . Tissue plugs of the fruiting bodies were cultivated in liquid media and the whole culture extracted with ethyl acetate . Crude extracts from Agaricus cf . nigrecentulus, Agrocybe perfecta, Climacodon pulcherrimus, Gloeoporus thelephoroides, Hexagonia hydnoides, Irpex lacteus, Leucoagaricus cf . cinereus, Marasmius cf . bellus, Marasmius sp., Nothopanus hygrophanus, Oudemansiella canarii, Pycnoporus sanguineus, Phellinus sp., and Tyromyces duracinus presented significant activity against one or more of the target microorganisms . Eight isolates were active only against bacteria while three inhibited exclusively the growth of fungi . Two extracts presented wide antimicrobial spectrum and were active against both fungi and bacteria . Differences in the bioactivity of extracts obtained from isolates from the same species were observed. Mem Inst Oswaldo Cruz, 2003 Oct, 98(7), 963 - 5 Epub 2004 Jan 07. Antimicrobial activity of Hyptis ovalifolia towards dermatophytes; Souza LK et al.; The essential oil and the aqueous, hexane and methanolic fractions from Hyptis ovalifolia leaves were evaluated for their antifungal activity in vitro against 60 strains of dermatophytes: 10 strains of Microsporum canis, 10 of M . gypseum, 20 of Trichophyton rubrum and 20 of T . mentagrophytes . The extracts inhibited growth of the dermatophytes tested at different concentrations . The most biologically active was the essential oil from the leaves which inhibited 57 isolates (95%) at a concentration of 500 g/ml. Euro Surveill, 2004 Jan 01, 9(1), 1 - 3 The European Community strategy against antimicrobial resistance; Bronzwaer S et al.; In 2001 the European Commission presented a 'Community strategy against Antimicrobial Resistance' . In previous years, the problem was addressed through an increasing number of isolated measures, but in this strategy the Commission outlined a comprehensive European Community approach across all sectors . The strategy consists of fifteen actions in four key areas: surveillance, prevention, research and product development, and international cooperation . An important part of this strategy is the 'Council Recommendation on the prudent use of antimicrobial agents in human medicine' . The Recommendation provides a detailed set of public health actions to contain antimicrobial resistance . This paper presents the eleven points of action of the strategy that are directly related to human medicine, and discusses related European Community activities . Under the new public health programme as well as under the research programme of the European Union, antimicrobial resistance is a key priority. J Med Chem, 2004 Feb 12, 47(4), 973 - 7 Formation of water-soluble pincer silver(I)-carbene complexes: a novel antimicrobial agent; Melaiye A et al.; Silver(I)-2,6-bis(ethanolimidazolemethyl)pyridine hydroxide (4a) and silver(I)-2,6-bis(propanolimidazolemethyl)pyridine hydroxide (4b) are water-soluble silver(I)-carbene complexes that were synthesized in high yield by reacting silver(I) oxide with N-substituted pincer ligands 3 (a = 2,6-bis(ethanolimidazoliummethyl)pyridine diiodide, b = 2,6-bis(propanolimidazoliummethylpyridine)pyridine dibromide) . The X-ray crystal structure of 4a is a one-dimensional linear polymer, whereas the mass spectroscopy confirms a monomer in the gas phase . A change in the anion of 4a from a hydroxide to a hexafluorophosphate formed a silver(I)-carbene complex 4c that is dimeric in structure and insoluble in water . The bactericidal activities of the water-soluble silver(I)-carbene complexes were found to be improved over that of silver nitrate. Inflammation, 2003 Dec, 27(6), 341 - 9 Syntheses of prostaglandin E2 and E-cadherin and gene expression of beta-defensin-2 by human gingival epithelial cells in response to Actinobacillus actinomycetemcomitans; Noguchi T et al.; The interaction between epithelial cells and microorganisms is the most important step in bacterial infections . Actinobacillus actinomycetemcomitans was suggested to play a significant role in the initiation of periodontitis because of its bacteriological characteristics . Prostaglandins (PG) mediate the inflammatory response . Human beta-defensin-2 (hBD-2) is an antimicrobial peptide and contributes to innate immunity . E-cadherin is responsible for an epithelial intercellular junction . In this study, we investigated the syntheses of PGE2 and E-cadherin and the expression of hBD-2 in human gingival epithelial cells (HGEC) following exposure to A . actinomycetemcomitans . The levels of PGE2 and cyclooxygenase-2, which are responsible for an increase in PGE2, were increased depending on bacteria exposure time . hBD-2 mRNA was induced by A . actinomycetemcomitans, while HGEC exposed to A . actinomycetemcomitans showed a decrease in E-cadherin levels . Etodolac, a selective cyclooxygenase-2 inhibitor reinforced the increase in hBD-2 mRNA levels by A . actinomycetemcomitans . Furthermore, the etodolac suppressed the decrease in E-cadherin levels . Thus, endogenous PGE2 is involved in the hBD-2 and E-cadherin responses of HGEC to A . actinomycetemcomitans . These findings suggest that the inflammatory and antimicrobial response of gingival epithelial cells to A . actinomycetemcomitans is involved in the initiation of periodontal inflammation . A . actinomycetemcomitans may destroy the mechanical epithelial barrier by destroying E-cadherin. Best Pract Res Clin Anaesthesiol, 2004 Mar, 18(1), 37 - 52 Acute toxic renal failure; Evenepoel P; Acute renal failure (ARF) is a common problem in intensive care medicine . Even modest degrees of ARF not requiring dialysis treatment increase the risk of death approximately fivefold . Despite the widespread appreciation of the role of nephrotoxic drugs in their contribution to ARF, these drugs continue to have an ongoing aetiological role . Potentially nephrotoxic drugs include non-steroidal anti-inflammatory drugs, radiocontrast agents, antimicrobial and anaesthetic agents . Endogenous compounds such as myoglobin and haemoglobin may furthermore cause toxic nephropathy . Tubular injury initiated by toxins often results from a combination of acute renal vasoconstriction and direct cellular toxicity due to intracellular accumulation of the toxin, or, alternatively, may be mediated immunologically in case of interstitial nephritis . Patients with reduced renal functional reserve, cardiovascular co-morbidity, diabetes mellitus, and advanced age are at increased risk . Awareness of the range of toxins on the one hand and simple measures such as adequate pre-hydration of the patient and drug monitoring on the other hand may be sufficient to avoid drug-induced ARF or minimize its clinical severity in susceptible patients. Bull World Health Organ, 2003, 81(11), 806 - 14 Epub 2004 Jan 20. Training pharmacy workers in recognition, management, and prevention of STDs: district-randomized controlled trial; Garcia P et al.; OBJECTIVES: To determine the effectiveness of an intervention for pharmacy workers in improving their recognition and management of sexually transmitted disease (STD) syndromes . METHODS: We randomly selected 14 districts (total population nearly 4 million) from the 24 districts of low socioeconomic status in Lima, Peru . We randomly assigned paired districts to receive training and support for management and prevention of STDs or a control intervention about management of diarrhoea . The STD intervention included interactive luncheon seminars on recognition and management of four STD syndromes (urethral discharge, vaginal discharge, genital ulcers, and pelvic inflammatory disease) and STD/HIV prevention counselling; monthly pharmacy visits by "prevention salespersons" who distributed materials that included "STD/HIV prevention packets" containing information, condoms, and cards given to patients for referral of their sex partners; and workshops for physicians on managing patients with STD syndromes referred from pharmacies . Standardized simulated patients visited pharmacies in intervention and control districts at one, three, and six months after training to assess outcomes . FINDINGS: Standardized simulated patients reported significantly better recognition and management (appropriate antimicrobial regimens provided for discharge syndromes and referral to specially trained physicians for genital ulcers or pelvic inflammatory disease) by pharmacy workers of all four STD syndromes . They also reported significantly more frequent recommendations for use of condoms and treatment of partners at pharmacies in intervention districts than in control districts (by "intention-to-train" analyses, P<0.05 for 47/48 primary outcome comparisons) . CONCLUSION: Training was feasible and effectively improved pharmacy workers' practices. Eur J Pharm Sci, 2004 Feb, 21(2-3), 115 - 8 Studies of antimicrobial activity of N-alkyl and N-acyl 2-(4-thiazolyl)-1H-benzimidazoles; Pawar NS et al.; Various N-alkyl and N-acyl derivatives of 2-(4-thiazolyl)-1H-benzimidazole, an anthelmintic and systemic fungicide, were synthesized by polymer-supported reactions and screened for their antifungal and antibacterial potency to establish structure-activity relationships. J Dermatol Sci, 2004 Feb, 34(1), 25 - 33 Roxithromycin decreases ultraviolet B irradiation-induced reactive oxygen intermediates production and apoptosis of keratinocytes; Takahashi H et al.; BACKGROUND: In addition to their antimicrobial action, roxithromycin (RXM), a new 14-membrane macrolide antibiotics, have immunomodulatory, anti-inflammatory and anti-oxidative activity . Ultraviolet B (UVB) irradiation induces reactive oxygen intermediates and apoptosis of keratinocytes . OBJECTIVE: To examine the anti-apoptotic and anti-oxidative effect of RXM on UVB-irradiated keratinocytes . METHODS: UVB-induced apoptosis was determined by cell death assay using crystal violet staining, and DNA fragmentation assay . Superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and calatase activities were measured in UVB-irradiated SV40-trasnformed human keratinocytes (SVHK cells) . Detection of superoxide was performed histologically using hydroethidine and colorimetric quantitative assay using ferrous irons . H(2)O(2) was measured by colorimetrical assay . RESULTS: RXM suppressed UVB-induced apoptosis of SVHK cells . UVB-irradiated SVHK cells showed decreased SOD, GPx, GR, and catalase activities . RXM pretreatment suppressed the decrease in these enzyme activities with the maximal effect detected at 10microM of RXM . The effect was associated with suppression of UVB-induced superoxide and H(2)O(2) production . CONCLUSION: The present study demonstrated that RXM has anti-apoptotic and anti-oxidative effects against UVB-irradiated keratinocytes. Biochim Biophys Acta, 2004 Jan 28, 1660(1-2), 131 - 7 Stabilisation of mixed peptide/lipid complexes in selective antifungal hexapeptides; Lopez-Garcia B et al.; The design of antimicrobial peptides could have benefited from structural studies of known peptides having specific activity against target microbes, but not toward other microorganisms . We have previously reported the identification of a series of peptides (PAF-series) active against certain postharvest fungal phytopathogens, and devoid of toxicity towards E . coli and S . cerevisiae {Lopez-Garcia et al . Appl . Environ . Microbiol . 68 (2002) 2453} . The peptides inhibited the conidia germination and hyphal growth . Here, we present a comparative structural characterisation of selected PAF peptides obtained by single-amino-acid replacement, which differ in biological activity . The peptides were characterised in solution using fluorescence and circular dichroism (CD) spectroscopies . Membrane and membrane mimetic-peptide interactions and the lipid-bound structures were studied using fluorescence with the aid of extrinsic fluorescent probes that allowed the identification of mixed peptide/lipid complexes . A direct correlation was found between the capability of complex formation and antifungal activity . These studies provide a putative structural basis for the mechanism of action of selective antifungal peptides. Enferm Infecc Microbiol Clin, 2004 Jan, 22(1), 46 - 54 {Basis, types and application of DNA arrays in clinical microbiology}; Domenech-Sanchez A et al.; The DNA microarrays or microchips are sets of DNA probes bound to a solid support in a prefixed and regular disposition . The target nucleic acid that can be detected is either DNA or RNA, which is previously labeled with a fluorochrome or a radioactive compound . The main advantage with respect to other molecular biological tools, such as polymerase chain reaction, is that thousands of genes can be detected in a single procedure . The application of the DNA arrays in the field of clinical microbiology is so far scarce . Among the specific applications we can point out: 1 . Investigation of bacterial pathogenesis; 2 . Analysis of bacterial evolution and molecular epidemiology; 3 . Study of the mechanisms of action and resistance to antimicrobial agents and 4 . Microbiological diagnostic of the infectious diseases . This methodology is still in an embryonic phase with respect to its application in clinical microbiology . However, it presents a series of advantages that make it very attractive and in the future it may become a valuable tool for the diagnosis of infectious diseases. Enferm Infecc Microbiol Clin, 2004 Feb, 22(2), 113 - 20 {Multilocus sequence typing: the molecular marker of the Internet era}; Vazquez JA et al.; Global or longer term epidemiology track the spread of clonal lineages, associated with hipervirulence or resistance or multi-resistance to antimicrobial agents . Therefore, the application of a molecular typing system for this purpose should produce data easily shared by different and geographically distant laboratories, as well as distinguish those clonal lineages even with low levels of variability accumulated in the genome.A marker based on the DNA sequence will produce objective results easily organized in data bases accessible by Internet . The application of a similar strategy that was used in the analysis of isoenzymes, by sequencing variable fragments of selected housekeeping genes, will allow obtaining a general view of the distribution of the clonal lineages and tracking their spread. Dermatol Ther, 2004, 17(1), 50 - 4 Hidradenitis suppurativa: a review; Wiseman MC; Hidradenitis suppurativa is a recurrent disease involving apocrine-bearing skin with a predilection for intertriginous areas, including genital skin . It has a highly variable clinical course . Mild cases may present as recurrent isolated nodules, while severe instances of the disease with chronic inflammation may lead to scarring, functional impairment, and rarely, squamous cell carcinoma . While genetic factors, patient characteristics, hormones and infection play a role in disease expression, a comprehensive understanding of the pathogenesis remains to be elicited . Additionally, effective treatment is largely unknown . While the mainstay of therapy had been surgery, and topical or systemic antimicrobial agents, other therapeutic modalities such as retinoids, hormonal therapy and immunosuppresive medications may also hold some promise. Bioorg Med Chem, 2004 Feb 15, 12(4), 763 - 70 Synthesis and biological activity of isopentenyl diphosphate analogues; Scholte AA et al.; A series of analogues of isopentenyl diphosphate (IPP) having a dicarboxylate moiety in place of the diphosphate were synthesized and investigated as inhibitors of undecaprenyl diphosphate (UPP) synthase and protein farnesyltransferase (PFTase) . PFTase is involved in control of cell proliferation and is known to be inhibited by certain maleic acid derivatives bearing long alkyl substituents (> or =12 carbons, e.g., chaetomellic acid) . UPP synthase is a potential target for antimicrobial agents and utilizes isopentenyl diphosphate (IPP) as a substrate . A number of dicarboxylate-containing IPP analogues were prepared in 2-5 steps from commercially available starting materials with good overall yield (20-78%) . These syntheses involved the conjugate addition of an organocuprate to dimethyl acetylenedicarboxylate (DMAD) followed by basic ester hydrolysis . The E-pentenylbutanedioic acid 32 showed inhibition of UPP synthase with an IC(50) of 135 microM . Compound 30 displays competitive inhibition of PFTase with a K(i) of 287 microM. Clin Microbiol Infect, 2004 Apr, 10 Suppl 2, 1 - 5 Introduction: standards of antibacterial performance; Finch RG; The development and clinical use of antimicrobial agents continue to evolve in line with new science, understanding and needs . While antimicrobial resistance remains an important determinant for drug development and therapeutic choice, pharmacokinetic and pharmacodynamic parameters are having an ever-increasing importance in defining performance targets for new and established agents . Recently licensed new therapies are largely directed at serious hospital-associated Gram-positive infections, whereas in the community, therapeutic choice remains dependent on well-established agents from limited classes of antimicrobials . In order to maximise the benefits from such agents, it is appropriate that dosage regimens and antibacterial choices be reviewed in the light of new knowledge, particularly in the area of pharmacokinetics and pharmacodynamics . Antimicrobial resistance continues to evolve, notably within respiratory pathogens, therefore steps must be taken to maintain optimum therapeutic outcomes and also limit the development and spread of resistant strains . Whilst changes in patient and physician attitudes and behaviour towards better quality prescribing are important, new agents must also be developed to provide adequate coverage for resistant pathogens . Development times for novel agents and classes of antimicrobials are long, with uncertain safety profiles and chances of success . Thus, the development of new formulations of existing agents, designed to overcome current resistance patterns, constitutes a potentially important additional strategy towards appropriate prescribing. J Clin Invest, 2004 Feb, 113(3), 401 - 13 TNF-alpha is a critical negative regulator of type 1 immune activation during intracellular bacterial infection; Zganiacz A et al.; TNF-alpha has long been regarded as a proimmune cytokine involved in antimicrobial type 1 immunity . However, the precise role of TNF-alpha in antimicrobial type 1 immunity remains poorly understood . We found that TNF-alpha-deficient (TNF(-/-)) mice quickly succumbed to respiratory failure following lung infection with replication-competent mycobacteria, because of apoptosis and necrosis of granuloma and lung structure . Tissue destruction was a result of an uncontrolled type 1 immune syndrome characterized by expansion of activated CD4 and CD8 T cells, increased frequency of antigen-specific T cells, and overproduction of IFN-gamma and IL-12 . Depletion of CD4 and CD8 T cells decreased IFN-gamma levels, prevented granuloma and tissue necrosis, and prolonged the survival of TNF(-/-) hosts . Early reconstitution of TNF-alpha by gene transfer reduced the frequency of antigen-specific T cells and improved survival . TNF-alpha controlled type 1 immune activation at least in part by suppressing T cell proliferation, and this suppression involved both TNF receptor p55 and TNF receptor p75 . Heightened type 1 immune activation also occurred in TNF(-/-) mice treated with dead mycobacteria, live replication-deficient mycobacteria, or mycobacterial cell wall components . Our study thus identifies TNF-alpha as a type 1 immunoregulatory cytokine whose primary role, different from those of other type 1 cytokines, is to keep an otherwise detrimental type 1 immune response in check. Bone Marrow Transplant, 2004 Apr, 33(7), 735 - 9 Antimicrobial prophylaxis in hematopoietic stem cell transplant recipients: heterogeneity of current clinical practice; Trifilio S et al.; Antimicrobial agents are commonly used after hematopoietic stem cell transplant (HSCT) to prevent bacterial, viral and fungal infections . A pharmacy practice survey was undertaken to evaluate prevailing practices . The 31 centers evaluated transplanted over 3400 patients in 2001 . Over half used bacterial prophylaxis; all with fluoroquinolones . A significantly higher proportion (90-100%) used fungal and viral prophylaxis . Most centers used fluconazole for fungal prophylaxis, but the dose used varied from 400 mg (the recommended dose) to 100 mg . Itraconazole and amphotericin preparations were used by some centers for allograft recipients because of their activity against aspergillosis . Most centers used brief viral prophylaxis for autograft recipients aimed at preventing HSV reactivation . Viral prophylaxis for allograft recipients was usually much more prolonged, reflecting concern over cytomegalovirus infections . Overall, there was significant deviation from recommended guidelines in many of the practices . Our survey suggests that substantial variation exists among transplant centers in their approach to antimicrobial prophylaxis after HSCT . This probably stems from the lack of definitive studies and strong recommendations in several areas, availability of newer agents that have not been adequately studied in the HSCT setting, and a desire to improve outcome before definitive studies are available for newer agents, a process that could take several years. Int J Food Microbiol, 2004 Feb 1, 90(3), 303 - 8 Prevalence of Arcobacter species in retail meats and antimicrobial susceptibility of the isolates in Japan; Kabeya H et al.; A survey was conducted to examine the prevalence of Arcobacter species among meat samples and to investigate the antimicrobial susceptibility of the isolates in Japan . In 1998 and 1999, samples of beef (n=90), pork (n=100) and chicken meat (n=100) were purchased from seven retail shops . Arcobacter species were isolated from 2.2%, 7.0% and 23.0% of beef, pork and chicken meat samples, respectively . The rate of isolations in chicken meats was shown to be significantly higher than those of beef and pork . Species-specific polymerase chain reaction (PCR) demonstrated that the most dominant Arcobacter species was Arcobacter butzleri among the isolates examined . Multiple contaminations with different Arcobacter species were observed in 5% of the chicken samples . Almost all the strains tested showed resistance to vancomycin (100%) and methicillin (97.5%) . Strains resistant to cephalothin, sulfamethoxazole-trimethoprim, nalidixic acid and chloramphenicol were detected at the rate of 81.1%, 67.2%, 53.5% and 24.6%, respectively . All Arcobacter strains examined were susceptible to ampicillin, tetracycline, streptomycin and kanamycin. J Neurobiol, 2004 Feb 15, 58(3), 355 - 68 Inducible transcript expressed by reactive epithelial cells at sites of olfactory sensory neuron proliferation; Stoss TD et al.; The continuous replacement of cells in the spiny lobster olfactory organ depends on proliferation of new cells at a specific site, the proximal proliferation zone (PPZ) . Using representational difference analysis of cDNA, we identified transcripts enriched in the PPZ compared to the mature zone (MZ) of the organ . The 12 clones identified included four novel sequences, three exoskeletal proteins, a serine protease, two protease inhibitors, a putative growth factor, and a sequence named PET-15 that has similarity to antimicrobial proteins of the crustin type . PET-15 mRNA was only detected in epithelial cells . It was abundant in all epithelial cells of the PPZ, but was only detected in the MZ at sites of damage to the olfactory organ . PET-15 mRNA was increased by types of damage that are known to induce proliferation of new olfactory sensory neurons in the olfactory organ . It increased in the PPZ after partial ablation of the olfactory organ and in the MZ after shaving of aesthetasc sensilla . These ipsilateral effects were mirrored by smaller increases in the undamaged contralateral olfactory organ . These contralateral effects are most parsimoniously explained by the action of a diffusible signal . Because epithelial cells are the source of proliferating progenitors in the olfactory organ, the same diffusible signal may stimulate increases in both cellular proliferation and PET-15 mRNA . The uniformity of expression of PET-15 in the PPZ epithelium suggests that the epithelial cells that give rise to new olfactory sensory neurons are a subset of cells that express PET-15 . Curr Opin Pulm Med, 2004 Jan, 10(1), 7 - 14 Macrolide and occult infection in asthma; Cazzola M et al.; PURPOSE OF REVIEW: A small percentage of asthma exacerbations are linked with infection by an atypical bacterium, such as Chlamydia pneumoniae or Mycoplasma pneumoniae . These bacteria also have been proposed to cause occult chronic lower airway inflammation and to initiate nonatopic asthma in adults . Consequently, the logical procedure would be to eliminate these pathogens as soon and as thoroughly as possible using antibiotics . Nonetheless, antibiotics are not recommended even for the treatment of acute asthma exacerbations except as needed for comorbid conditions . These discrepancies highlight the need to define the role, if any, of antimicrobials that are active against atypical pathogens, mainly macrolides, but also tetracyclines and fluoroquinolones, in the treatment of asthma . RECENT FINDINGS: Macrolides are antibiotics with both antimicrobial and antiinflammatory activities . Some studies have documented that these agents could be useful in the treatment of occult infection in asthma because of their antimicrobial activity against atypical pathogens . They could also lead to reduction of the airways inflammation by decreasing the transcription of mRNA for a variety of cytokines and inhibiting interleukin-8 release by eosinophils, and therefore improvement of symptoms and pulmonary function . These effects are not caused by bronchodilation, elevation of serum theophylline level, or steroid-sparing mechanism . SUMMARY: The available clinical evidence seems to support use of macrolides in the treatment of asthma because of their antimicrobial activity . However, studies that may confirm this hypothesis are scarce and with limited scientific value because of their open, uncontrolled design. J Antimicrob Chemother, 2004 Mar, 53(3), 506 - 11 Epub 2004 Jan 28. Effect of norepinephrine on cefpirome tissue concentrations in healthy subjects; Steiner IM et al.; OBJECTIVES: To test whether norepinephrine (NOR) affects tissue microcirculation and impairs plasma-to-tissue equilibration of antimicrobial agents . MATERIALS AND METHODS: Eight healthy male volunteers were enrolled to an analyst-blinded, randomized, two-period two-sequence crossover study . A single intravenous dose of 2 g of cefpirome was administered simultaneously with starting a continuous infusion of NOR (0.16 microg/kg per min) or placebo (PL) over 180 min . The microdialysis technique was used for the assessment of unbound cefpirome concentrations in skeletal muscle tissue and subcutaneous adipose tissue . Free plasma concentrations were related to corresponding tissue concentrations . Haemodynamics were determined by the measurement of mean arterial blood pressure (MAP), heart rate and forearm blood flow (FBF) . RESULTS: Area under the concentration-time-curve (AUC) values of cefpirome for interstitium and plasma were not significantly different between the PL and NOR groups (P > 0.47) . Tissue penetration of cefpirome as described by the ratios of the AUCs from 0 to 180 min for tissue to the AUC values for plasma were 0.81 +/- 0.34 for the PL group and 0.80 +/- 0.26 for the NOR group (P > 0.05) . Baseline values of MAP, heart rate and FBF were not significantly different between study days . MAP increased significantly following NOR administration from 73.3 +/- 3.5 mmHg at baseline to 94.0 +/- 5.2 mmHg during infusion (P = 0.017) . NOR exerted no significant effects on FBF . CONCLUSIONS: We have shown that intravenous administration of NOR does not exert a significant effect on peripheral blood flow and tissue penetration of cefpirome in healthy men . This might be attributed to systemic regulatory mechanisms, which probably fully compensate for major changes in blood flow in peripheral tissues. J Antimicrob Chemother, 2004 Mar, 53(3), 418 - 31 Epub 2004 Jan 28. An assessment of the risks associated with the use of antibiotic resistance genes in genetically modified plants: report of the Working Party of the British Society for Antimicrobial Chemotherapy; Bennett PM et al.; Development of genetically modified (GM) plants is contentious, in part because bacterial antibiotic resistance (AR) genes are used in their construction and often become part of the plant genome . This arouses concern that cultivation of GM plants might provide a reservoir of AR genes that could power the evolution of new drug-resistant bacteria . We have considered bacterial DNA transfer systems (conjugation, transduction and transformation) and mechanisms of recombination (homologous recombination, transposition, site-specific recombination and DNA repair) that together might productively transfer AR genes from GM plants to bacterial cells, but are unable to identify a credible scenario whereby new drug-resistant bacteria would be created . However, we cannot entirely rule out the possibility of rare transfer events that involve novel mechanisms . Hence, we also considered if occasional transfers of AR genes (bla(TEM), aph(3'), aadA) from GM plants into bacteria would pose a threat to public health . These AR genes are common in many bacteria and each is found on mobile genetic elements that have moved extensively between DNA molecules and bacterial cells . This gene mobility has already severely compromised clinical use of antibiotics to which resistance is conferred . Accordingly, the argument that occasional transfer of these particular resistance genes from GM plants to bacteria would pose an unacceptable risk to human or animal health has little substance . We conclude that the risk of transfer of AR genes from GM plants to bacteria is remote, and that the hazard arising from any such gene transfer is, at worst, slight. Harefuah, 2004 Jan, 143(1), 28 - 32, 85 {Simple method to detect factors influencing drug expenditures}; Lustig A; BACKGROUND: Analysis of drug expenditures as part of an assessment of various forms of management interventions is rarely reported . Several strategies have been used to decrease injudicious drug use: restricted availability of specific drugs under formulary instructions, educational programs for prescribing practices and streamlining to discontinue or limit therapy . Each intervention has limited effectiveness . OBJECTIVE: To detect factors influencing drug expenditures by a simple and accessible method . METHOD: Data analysis on drug utilization and expenditures was performed according to the "Pareto" technique and changes were calculated . Changes in expenditure due to inflation were also calculated; the cost value of each drug in 2000 was multiplied by its quantity used in years 2000 and 2001 . Comparison of expenditures using this method of calculation enabled us to find the inflation rate of the drugs used in the hospital . RESULTS: Five important factors were found to have an impact on the pharmacy budget and calculations: drug inflation rate (-1%), new drugs introduced through the Pharmaceuticals & Therapeutic Committee (1.9%), extended usage of drugs due to new approved clinical indications (0.7%), opening of new services or widening of special old services (3.4%) and usage of commonly high volume prescribed drugs in various wards of the hospital (-8.9%) . Quantities and costs for the 80 most expensive pharmaceuticals showed factors responsible for the drug expenditure when compared with the leading drug classes, as well as with leading drugs . Antimicrobials (27.5%), high volume IV infusions (11.0%), small volume infusions (8.5%), and anticoagulants (6.7%) were the most prominent drug classes that contributed to the high cost of the drug budget . Small volume infusions of Sodium Chloride 0.9% (7.8%), Piperacillin and tazobactam injections (5.6%) . Ofloxacin & Ciprofloxacin drugs (4.7%), and Enoxaparin injections (4.6%) were the highest costing drugs . CONCLUSION: This simple method based on comparison of costs, utilization and judicious drug use, can provide accurate information that can be useful in planning and implementing a reasonable drug budget. J Gen Appl Microbiol, 2003 Dec, 49(6), 315 - 20 Analysis of genetic relationships and antimicrobial susceptibility of Escherichia coli isolated from Clethrionomys glareolus; Swiecicka I et al.; Eleven strains of Escherichia coli were isolated from 54 bank voles living in the LomZa Landscape Park of the Narew River Valley, indicating that E . coli is not common in the alimentary tract of these mammals . On the basis of pulsed-field gel electrophoresis and computer-assisted analysis, the isolates were grouped into six genotypes at similarities of 39% . Chromosome length of E . coli under study differed by as much as 900 kb, ranging 2.7-3.6 Mb . All strains were susceptible to amikacin and ciprofloxacin, whereas, for tetracycline, streptomycin, ampicillin, and cefonicid, different results were noted . No differences were detected among the plasmid complements of eight strains (73%), for which plasmid profiles revealed the presence of two plasmidic bands . One, three and four plasmids were observed in a plasmid pattern of single isolates . The observation from the study indicated the high genetic polymorphism among the isolates recovered from the animals of one species living in the same environment. J Ind Microbiol Biotechnol, 2004 Jan, 31(1), 16 - 22 Epub 2004 Jan 28. Selective antimicrobial action of chitosan against spoilage yeasts in mixed culture fermentations; Gomez-Rivas L et al.; The effect of chitosan on Saccharomyces cerevisiae (the yeast that carries out alcohol fermentation), Brettanomyces bruxellensis and Brettanomyces intermedius (contaminants of alcohol fermentations), was investigated . The effect of chitosan was tested on each yeast, as well as on mixed cultivations of S . cerevisiae + B . bruxellensis and S . cerevisiae + B . intermedius . Chitosan enhanced the lag period of both strains of Brettanomyces (80 h for B . bruxellensis and 170 h for B . intermedius with 6 and 2 g/l chitosan, respectively) . The growth rate of S . cerevisiae was inversely proportional to the chitosan concentration; the former was 50% when 6 g/l polysaccharide was used . Moreover, in mixed cultivations of S . cerevisiae and Brettanomyces strains, it was found that both B . bruxellensis and B . intermedius failed to grow while growth of S . cerevisiae was not affected (using 3 and 6 g/l chitosan, respectively) . An interesting collateral result was that the presence of chitosan accelerated the consumption of glucose in the mixed cultivations (60 h instead of 120 h). Mymensingh Med J, 2004 Jan, 13(1), 63 - 6 Antimicrobial use in paediatric wards of teaching hospitals in Bangladesh; Akter FU et al.; To ascertain the pattern of antimicrobial use and to assess its appropriateness a 4-month prospective study was conducted from January through April 1998 in paediatric wards of five selected medical college hospitals in Bangladesh . The hospitals were selected by simple random technique . Every patient in the paediatric wards of the selected hospitals who was being treated with antimicrobials during the data collection period was considered for the study . The treatment charts of 2171 admitted paediatric patients were reviewed . Pneumonia and diarrhoea were the two most common infectious diseases among them . The most commonly used antimicrobials were ampicillin, gentamicin, amoxicillin, cloxacillin and ceftriaxone . The majority of the admitted paediatric patients (56.1%) included in this study received two or more antimicrobials in combination for their treatment . The percentages of appropriate antimicrobial treatment of pneumonia, and diarrhoea were 57.1% and 67.8% respectively across the hospitals . The evident of high percentages of inappropriate antimicrobial treatment for the most common infectious diseases suggested the need for intervention to improve antimicrobial use in hospitals. J Clin Pathol, 2004 Feb, 57(2), 205 - 7 Infection of the CNS by Scedosporium apiospermum after near drowning . Report of a fatal case and analysis of its confounding factors; Kowacs PA et al.; This report describes a fatal case of central nervous system pseudallescheriasis . A 32 year old white man presented with headache and meningismus 15 days after nearly drowning in a swine sewage reservoir . Computerised tomography and magnetic resonance imaging of the head revealed multiple brain granulomata, which vanished when steroid and broad spectrum antimicrobial and antifungal agents, in addition to dexamethasone, were started . Cerebrospinal fluid analysis disclosed a neutrophilic meningitis . Treatment with antibiotics and amphotericin B, together with fluconazole and later itraconazole, was ineffective . Miconazole was added through an Ommaya reservoir, but was insufficient to halt the infection . Pseudallescheria boydii was finally isolated and identified in cerebrospinal fluid cultures, a few days before death, three and a half months after the symptoms began . Diagnosis was delayed because of a reduction in the lesions after partial treatment, which prevented a stereotactic biopsy . Physicians should be aware of this condition, and provide prompt stereotactic biopsy . Confirmed cases should perhaps be treated with voriconazole, probably the most effective, currently available treatment for this agent. J Clin Pharmacol, 2004 Feb, 44(2), 188 - 92 Characterization of the penetration of garenoxacin into the breast milk of lactating women; Amsden GW et al.; The primary objective of this study was to characterize the extent of excretion of garenoxacin, a novel des-F(6)-quinolone antimicrobial, into the breast milk of lactating women . A secondary objective was to determine the time after dose administration that garenoxacin was no longer detected in breast milk so as to define when a mother may resume breastfeeding if it was interrupted for garenoxacin administration . Six healthy, lactating women (age {mean +/- SD}: 32 +/- 6 years; weight: 68.3 +/- 19.8 kg; body mass index: 26 +/- 5 kg/m(2)) who had completed weaning their infants were administered a single 600-mg oral dose of garenoxacin . Plasma samples were collected predose and repeatedly up to 72 hours postdose . Breast milk was collected predose and for 6- to 12-hour intervals repeatedly up to 120 hours postdose . Breast milk/plasma concentration ratios for garenoxacin ranged from 0.35 to 0.44 up to 24 hours postdose, and the mean peak breast milk concentration was 3.0 microg/mL (0- to 6-h collection interval) . Overall, garenoxacin exposure in breast milk was minimal, with a mean of 0.07% of the administered dose recovered within 120 hours . Indeed, garenoxacin was undetectable in the breast milk of a majority of subjects within 84 hours of dosing . As such, an infant nursing from a mother who had received a single 600-mg oral dose of garenoxacin could theoretically be exposed to 0.42 mg of garenoxacin (0.105 mg/kg/day for a 4-kg infant over the period of 5 days of nursing) . If extrapolated to a 14-day course of garenoxacin 600 mg once daily, total exposure would be approximately 5.88 mg . These findings indicate that, like other quinolone antimicrobials, garenoxacin is secreted in breast milk. Regul Toxicol Pharmacol, 2004 Feb, 39(1), 12 - 24 Safety determination for the use of bovine milk-derived lactoferrin as a component of an antimicrobial beef carcass spray; Taylor S et al.; Bovine milk-derived lactoferrin (BMDL), an iron-binding glycoprotein, is known to be an effective natural antimicrobial . It is used as a spray, applied electrostatically, to raw beef carcasses to detach bacteria adhering to the surface in order to reduce microbial contamination . The use of BMDL as a component (at not more than 2% by weight) of an antimicrobial spray was determined Generally Recognized As Safe (GRAS) (GRN 67) for three proposed uses (i.e., beef carcasses, subprimals, and finished cuts), provided that the ingredient statement of food products that contain milk-derived lactoferrin identifies the source of the protein . The use of BMDL spray on only beef carcasses (not subprimals or finished cuts) at a level not to exceed 0.20 ml of formulation per kg of beef was determined safe without the requirement of labeling of food products so treated . The two key components of the assessment are: (1) a determination that exogenous lactoferrin exposure (resulting from its application to beef carcasses) is in the range of existing background exposures of lactoferrin as a result of lactoferrin found naturally in beef, and (2) a determination that this potentially small incremental increase in lactoferrin is safe (i.e., there is no reasonable expectation that BMDL will become an allergen under the conditions of its intended use). J Appl Toxicol, 2004 Jan-Feb, 24(1), 1 - 4 Significance of the detection of esters of p-hydroxybenzoic acid (parabens) in human breast tumours; Harvey PW et al.; This issue of Journal of Applied Toxicology publishes the paper Concentrations of Parabens in Human Breast Tumours by Darbre et al . (2004), which reports that esters of p-hydroxybenzoic acid (parabens) can be detected in samples of tissue from human breast tumours . Breast tumour samples were supplied from 20 patients, in collaboration with the Edinburgh Breast Unit Research Group, and analysed by high-pressure liquid chromatography and tandem mass spectrometry . The parabens are used as antimicrobial preservatives in underarm deodorants and antiperspirants and in a wide range of other consumer products . The parabens also have inherent oestrogenic and other hormone related activity (increased progesterone receptor gene expression) . As oestrogen is a major aetiological factor in the growth and development of the majority of human breast cancers, it has been previously suggested by Darbre that parabens and other chemicals in underarm cosmetics may contribute to the rising incidence of breast cancer . The significance of the finding of parabens in tumour samples is discussed here in terms of 1) . Darbre et al's study design, 2) . what can be inferred from this type of data (and what can not, such as the cause of these tumours), 3) . the toxicology of these compounds and 4) . the limitations of the existing toxicology database and the need to consider data that is appropriate to human exposures . Magn Reson Chem, 2004 Feb, 42(2), 155 - 61 Peptide-related alterations of membrane-associated water: deuterium solid-state NMR investigations of phosphatidylcholine membranes at different hydration levels; Mendonca Moraes C et al.; Deuterated water associated with oriented POPC bilayers was investigated before and after the addition of 2 mol% peptide . Membranes in the presences of antimicrobial-(LAH4), pore-forming- (the segments M2 of influenza A and S4 of the domain I of rat brain sodium channels) or lysine-containing model peptides (LAK1 and LAK3) were investigated by (2)H and proton-decoupled (31)P solid-state NMR . The NMR spectra were recorded as a function of hydration in the range between 15 and 93% relative humidity and of sample composition . In the presence of peptides an increased association of water is observed . A quantitative analysis suggests that the peptide-induced changes in the lipid bilayer packing have a significant effect on membrane-water association . The quadrupolar splittings of (2)H(2)O at a given degree of hydration indicate that the changes of the water deuterium order parameter are specific for the peptide sequence and the lipid composition . J Biol Chem, 2004 Apr 9, 279(15), 14853 - 9 Epub 2004 Jan 26. Primary structure and in vitro antibacterial properties of the Drosophila melanogaster attacin C Pro-domain; Rabel D et al.; In Drosophila melanogaster, seven distinct families of antimicrobial peptides with different structures and specificities are synthesized by the fat body and released into the hemolymph during the immune response . Using microscale high performance liquid chromatography, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and Edman degradation, we have isolated and characterized from immune-challenged Drosophila two novel induced molecules, under the control of the Imd pathway, that correspond to post-translationally modified antimicrobial peptides or peptide fragments . The first molecule is a doubly glycosylated form of drosocin, an O-glycosylated peptide that kills Gram-negative organisms . The second molecule represents a truncated form of the pro-domain of the Drosophila attacin C carrying two post-translational modifications and has significant structural similarities to proline-rich antibacterial peptides including drosocin . We have synthesized this peptide and found that it is active against Gram-negative bacteria . Furthermore, this activity is potentiated when the peptide is used in combination with the Drosophila antimicrobial peptide cecropin A . The synergistic action observed between these two molecules suggests that the truncated post-translationally modified pro-domain of attacin C by itself may play an important role in the antimicrobial defense of Drosophila. Eur J Drug Metab Pharmacokinet, 2003 Oct-Dec, 28(4), 253 - 8 In vivo interaction between ciprofloxacin hydrochloride and the pulp of unripe plantain (Musa paradisiaca); Sv N et al.; The absorption of quinolone antibiotics is seriously impaired by polyvalent cations due to the formation of unabsorbable complexes . M . paradisiaca Linn . (Musaceae), an important staple food in most parts of the world, has been demonstrated to contain many polyvalent cations . The aim of the work was to study the influence of concurrent administration of M . paradisiaca and ciprofloxacin HCI on the pharmacokinetic profiles of ciprofloxacin . The study was carried out in two phases in five healthy male rabbits . Phase one involved oral administration of ciprofloxacin (40 mg/kg) to rabbits, withdrawing blood from the marginal ear vein at 1, 2, 4, and 24 h intervals and checking the serum ciprofloxacin concentration . After a one-week drug "wash-out" period, the second phase started with concurrent oral administration of M . paradisiaca (800 mg/kg) and ciprofloxacin (40 mg/kg) . Blood was again withdrawn and analyzed for serum ciprofloxacin content . Antimicrobial activity of the serum was also assessed and expressed as reciprocal serum inhibitory titer . Co-administration of both agents resulted in significant (P<0.05) decrease in serum concentration of ciprofloxacin at all the time interval except at the 24th hour . The following pharmacokinetic parameters were also decreased: area under the curve (81.53%), peak serum concentration (94.37%), elimination rate constant (42.35%); while increase in half-life (81.08%) and clearance rate (69.64%) were noted . Antimicrobial study showed that the antimicrobial potency against E . coli was also decreased by such concurrent administration . The pharmacokinetic parameters and antimicrobial activities of ciprofloxacin were significantly decreased when it was given concurrently with pulp of unripe plantain . Complex formation between the drug and the polyvalent cations present in plantain, leading to decrease in absorption and hence bioavailability, may be responsible for the observed antagonistic interactions. Rev Med Chil, 2003 Nov, 131(11), 1313 - 20 {Antimicrobial resistance of Helicobacter pylori: clinical and molecular aspects}; Vallejos C et al.; Helicobacter pylori is a relevant pathogen for gastroduodenal diseases in human beings . Although its eradication often improves gastroduodenal diseases, H pylori is acquiring an elevated rate of resistance to various antimicrobials, such as metronidazole, clarithromycin, tetracycline and amoxicillin . Multi-drug resistance is a major problem to select the appropriate treatment of infectious diseases . To improve our understanding on the complexity of the problem, in this article we review the resistance mechanisms and give an update on H pylori antimicrobial resistance. Pediatr Infect Dis J, 2004 Jan, 23(1), 82 - 4 Legionella pneumonia: infection during immunosuppressive therapy for idiopathic pulmonary hemosiderosis; Watson AM et al.; We report a case of Legionella pneumonia in a 10-year-old girl with idiopathic pulmonary hemosiderosis who was chronically immunosuppressed and had exposure to a hot tub . Prompt diagnosis with bronchoalveolar lavage and subsequent antimicrobial therapy resulted in full recovery . Legionellosis should be included in the differential diagnosis of the immunosuppressed child with respiratory illness . High risk patients should avoid exposure to hot tubs. Pediatr Infect Dis J, 2004 Jan, 23(1), 61 - 7 Predicting bacteremia in children with fever and chemotherapy-induced neutropenia; Ammann RA et al.; BACKGROUND: Fever and neutropenia are common clinical problems in pediatric oncology and frequently necessitate emergency hospitalization and immediate empiric broad spectrum antimicrobial therapy . Estimating the risk of bacteremia in fever and neutropenia is a challenge . The purpose of this study was to develop an algorithm predicting the risk of bacteremia and Gram-negative bacteremia in children and adolescents with fever and neutropenia, based on information accessible at presentation . METHODS: We collected information available within 2 h of presentation of children with fever and neutropenia and, on outcome, from all pediatric cancer patients presenting with fever and neutropenia from 1993 through 2001 in a retrospective single center cohort study . After univariate analyses a multivariate decision tree was constructed, and its performance was evaluated by cross-validation . RESULTS: Bacteremia was detected in 87 (24%) and Gram-negative bacteremia in 30 (8%) of 364 episodes of fever and neutropenia . At the predetermined sensitivity level, > or =95%, decision tree models reached cross-validated specificities of 37 and 43%, with negative predictive values of 96 and 99%, for bacteremia and Gram-negative bacteremia, respectively . Absence of a clinically or radiologically evident source of infection and previous episodes of fever and neutropenia were defined as two newly described factors associated with bacteremia . CONCLUSIONS: Based on this retrospective analysis, it appears that bacteremia can be predicted with clinically useful specificity at a high level of sensitivity, using clinical information available at presentation in pediatric cancer patients with fever and neutropenia. Antimicrob Agents Chemother, 2004 Feb, 48(2), 673 - 6 Antimicrobial activity and bacterial-membrane interaction of ovine-derived cathelicidins; Anderson RC et al.; Three ovine-derived cathelicidins, SMAP29, OaBac5mini, and OaBac7.5mini, were compared with respect to their antibacterial activities and interactions with membranes . SMAP29 was confirmed to be alpha-helical, broad spectrum, and able to disrupt both the outer and the cytoplasmic membranes at relatively low concentrations . In contrast, the two proline- and arginine-rich OaBac peptides had more-modest antibacterial activities, reduced levels of lipopolysaccharide binding, and a lesser ability to depolarize the cytoplasmic membrane, consistent with a cytoplasmic target. Antimicrob Agents Chemother, 2004 Feb, 48(2), 641 - 3 Safety and efficacy of antimicrobial peptides against naturally acquired leishmaniasis; Alberola J et al.; Leishmaniases, which are important causes of morbidity and mortality in humans and dogs, are extremely difficult to treat . Antimicrobial peptides are rarely used as alternative treatments for naturally acquired parasitic diseases . Here we report that the acylated synthetic antimicrobial peptide Oct-CA(1-7)M(2-9) is safe and effective for treating naturally acquired canine leishmaniasis. Antimicrob Agents Chemother, 2004 Feb, 48(2), 602 - 4 In vitro activities of new antimicrobials against Nocardia brasiliensis; Vera-Cabrera L et al.; The in vitro sensitivities of 30 strains of Nocardia brasiliensis to DA-7867, gatifloxacin, moxifloxacin, and BMS-284756 (garenoxacin) were determined using the broth microdilution method . All N . brasiliensis strains were sensitive to these antimicrobials . The most active drug in vitro was DA-7867, with a MIC at which 90% of the isolates tested were inhibited of 0.03 micro g/ml and a MIC at which 50% of the isolates tested were inhibited of 0.06 micro g/ml. Xenobiotica, 2004 Jan, 34(1), 61 - 71 Oxidative one-carbon cleavage of the octyl side chain of olanexidine, a novel antimicrobial agent, in dog liver microsomes; Umehara K et al.; 1 . The oxidative one-carbon cleavage reaction in the octyl side chain of olanexidine {1-(3,4-dichlorobenzyl)-5-octylbiguanide}, a new potent biguanide antiseptic, was characterized in dog liver microsomes . 2 . Olanexidine was initially biotransformed to a monohydroxylated metabolite, 8-{5-(3,4-dichlorobenzyl)-1-biguanidino}-2-octanol (DM-215), and DM-215 was subsequently oxidized to the diol derivative, 8-{5-(3,4-dichlorobenzyl)-1-biguanidino}-1,2-octandiol (DM-220) . DM-220 was further biotransformed to 2-hydroxy aldehyde derivative, 2-hydroxy carboxylic acid derivative, and an oxidative C-1-C-2 bond cleavage metabolite, 7-{5-(3,4-dichlorobenzyl)-1-biguanidino} heptanoic acid {DM-223 (C7), a seven-carbon chain derivative}, after incubation with dog liver microsomes . 3 . DM-223 formation required NADPH as a cofactor and was inhibited by quinidine and quinine, relatively selective inhibitors of CYP2D subfamilies in dogs . 4 . The results suggest that the one-carbon fragment of the octyl side chain of olanexidine could be removed by the oxidative C-C bond cleavage with the possible involvement of cytochrome P450 systems such as CYP2D subfamily . This oxidative C-C bond cleavage reaction by cytochrome P450s could play an important role in the removal of one-carbon fragment of other drugs or endogenous compounds containing aliphatic chains. J Dairy Sci, 2003 Dec, 86(12), 3927 - 32 In vitro antimicrobial susceptibility of Escherichia coli isolates from clinical bovine mastitis in Finland and Israel; Lehtolainen T et al.; Minimal inhibition concentration (MIC) values of 100 Finnish and 100 Israeli Escherichia coli isolated from clinical bovine mastitis were determined for ampicillin, cephalexin, ceftazidime, dihydrostreptomycin, gentamicin, tetracycline, trimethoprim-sulfadiazine, and ciprofloxacin by an agar dilution method . The in vitro antimicrobial susceptibility of the E . coli isolates was high; only 27% showed resistance to one or more tested antimicrobial agents . Fifteen percent of the Israeli isolates and 14% of the Finnish isolates were resistant to tetracycline, 3 and 16% to cephalexin, 10 and 7% to ampicillin, 13 and 9% to dihydrostreptomycin, and 4 and 2% to trimethoprim-sulfadiazine . No gentamicin-, ceftazidime-, or ciprofloxacin-resistant isolates were detected . Eleven percent of all the isolates were resistant to two or more antimicrobial agents . Tetracycline was most often associated with multiresistant patterns . Most of the multiresistant isolates had very high MIC values, whereas most of those that were resistant to only one tested antibiotic had MIC values close to the susceptibility breakpoint . Antimicrobial resistance appeared to pose no problem in E . coli isolated from mastitic milk of both countries . This is probably due to the controlled use of antimicrobial agents in the treatment of dairy herds . Some differences were present in the resistance patterns, which may reflect the different use of antimicrobial agents in these two countries. Vet Clin North Am Equine Pract, 2003 Dec, 19(3), 645 - 63, vi Antimicrobial therapy for gastrointestinal diseases; Papich MG; Antibiotics will always be needed in horses for many types of infections, but the adverse consequences also must be considered . For the conditions described in this article, there is justification for antibiotic therapy . The intestinal problems that antibiotics can induce are among the risks from their administration to horses . Disruption of the endogenous bacterial population, colitis, and diarrhea are the most common complications from antibiotic therapy. Clin Exp Rheumatol, 2003 Nov-Dec, 21(6), 763 - 6 ANCA against the bactericidal/permeability increasing protein (BPI-ANCA) can compromise the antibiotic function of BPI in a Wegener's granulomatosis patient; Schultz H et al.; A 54-year old Wegener's granulomatosis patient with PR3-ANCA at diagnosis 2 years ago was admitted with a pulmonary relapse and new subglottic stenosis preceded by pulmonary infections . The patient presented with bactericidal/permeability increasing protein (BPI)-ANCA in ELISA whereas at the same time PR3-ANCA had disappeared . Bronchoalveolar lavage revealed pulmonary infection with Gram-negative bacteria . After antibiotic treatment, immunosuppression was started with cyclophosphamide and infliximab due to refractory disease . Remission was induced and BPI-ANCA disappeared . A bacterial growth inhibition assay with BPI and the patient's IgG purified during the actual pulmonary relapse showed inhibition of the antimicrobial activity of BPI in vitro, in contrast to IgG from sera taken 2 years before and after remission was induced . The patient's BPI-ANCA recognised the bioactive N-terminal portion of BPI . Thus a possible mechanism is demonstrated for how BPI-ANCA may contribute to a pro-inflammatory setting during the development of a pulmonary relapse in the absence of PR3-ANCA by impeding bacterial clearance. Intensive Care Med, 2004 Mar, 30(3), 381 - 7 Epub 2004 Jan 23. Short-term outcome of critically ill patients with severe acute respiratory syndrome; Gomersall CD et al.; OBJECTIVE: To document the outcome and determine prognostic factors for patients with severe acute respiratory syndrome who require admission to an intensive care unit . DESIGN: Observational cohort study involving retrospective analysis of demographic, clinical, laboratory and radiological data . SETTING: Adult intensive care unit in a tertiary referral university hospital involved in a major outbreak of severe acute respiratory syndrome (SARS) . PATIENTS: The first 54 patients admitted with SARS to an intensive care unit (ICU) . All were treated with corticosteroids, ribavirin, broad spectrum antimicrobials and supportive therapy . INTERVENTIONS: None . MEASUREMENTS AND RESULTS: All patients were admitted for respiratory failure . The median APACHE II score was 11 (interquartile range 8-13) . At 28 days 34 patients (63%; 95% CI 49.6-74.6) were alive and not mechanically ventilated . Six patients were alive but ventilated (11.3%; 95% confidence interval 5.3-22.6) and 14 had died (25.9%; CI 16.1-38.9) . Seven of 27 ventilated patients developed evidence of barotrauma (25.9%; 95% CI 13.2-44.7) . Median maximal multiple-organ dysfunction score was 5 (interquartile range 3.3-9) . Median maximal respiratory dysfunction score was 3 (interquartile range 3-4) . Increased age, severity of illness, lymphocyte count, decreased steroid dose, positive fluid balance, chronic disease or immunosuppression and nosocomial sepsis were associated with poor outcome on univariate analysis . Poor outcome was defined as death or need for mechanical ventilation at 28 days after ICU admission . CONCLUSIONS: Mortality amongst critically ill patients with SARS is high . It causes predominantly severe respiratory failure, with little other organ failure, and a high incidence of barotrauma amongst those requiring mechanical ventilation. Proc Natl Acad Sci U S A, 2004 Feb 3, 101(5), 1315 - 20 Epub 2004 Jan 22. Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis; Kurt-Jones EA et al.; Human neonates infected with herpes simplex virus 1 (HSV-1) develop one of three distinct patterns of infection: (i) infection limited to the skin, eye or mouth; (ii) infection of the CNS; or (iii) disseminated infection . The disseminated form usually involves the liver, adrenal gland, and lung, and resembles the clinical picture of bacterial sepsis . This spectrum of symptoms in HSV-1-infected neonates suggests that inflammatory cytokines play a significant role in the pathogenesis of the disease . Recent studies suggest that the Toll-like receptors (TLRs) may play an important role in the induction of inflammatory cytokines in response to viruses . TLRs are mammalian homologues of Toll, a Drosophila protein that is essential for host defense against infection . Engagement of TLRs by bacterial, viral, or fungal components leads to the production and release of cytokines and other antimicrobial products . Here, we demonstrate that TLR2 mediates the inflammatory cytokine response to HSV-1 by using both transfected cell lines and knockout mice . Studies of infected mice revealed that HSV-1 induced a blunted cytokine response in TLR2(-/-) mice . Brain levels of monocyte chemoattractant protein 1 chemokine were significantly lower in TLR2(-/-) mice than in either wild-type or TLR4(-/-) mice . TLR2(-/-) mice had reduced mortality compared with wild-type mice . The differences between TLR2(-/-) mice and both wild-type and TLR4(-/-) mice in the induction of monocyte chemoattractant protein 1, brain inflammation, or mortality could not be accounted for on the basis of virus levels . Thus, these studies suggest the TLR2-mediated cytokine response to HSV-1 is detrimental to the host. J Biol Chem, 2004 Apr 9, 279(15), 14784 - 91 Epub 2004 Jan 22. Systematic peptide engineering and structural characterization to search for the shortest antimicrobial peptide analogue of gaegurin 5; Won HS et al.; As part of an effort to develop new, low molecular mass peptide antibiotics, we searched for the shortest bioactive analogue of gaegurin 5 (GGN5), a 24-residue antimicrobial peptide . Thirty-one kinds of GGN5 analogues were synthesized, and their biological activities were analyzed against diverse microorganisms and human erythrocytes . The structural properties of the peptides in various solutions were characterized by spectroscopic methods . The N-terminal 13 residues of GGN5 were identified as the minimal requirement for biological activity . The helical stability, the amphipathic property, and the hydrophobic N terminus were characterized as the important structural factors driving the activity . To develop shorter antibiotic peptides, amino acid substitutions in an inactive 11-residue analogue were examined . Single tryptophanyl substitutions at certain positions yielded some active 11-residue analogues . The most effective site for the substitution was the hydrophobic-hydrophilic interface in the amphipathic helical structure . At this position, tryptophan was the most useful amino acid conferring favorable activity to the peptide . The introduced tryptophan played an important anchoring role for the membrane interaction of the peptides . Finally, two 11-residue analogues of GGN5, which exhibited strong bactericidal activity with little hemolytic activity, were obtained as property-optimized candidates for new peptide antibiotic development . Altogether, the present approach not only characterized some important factors for the antimicrobial activity but also provided useful information about peptide engineering to search for potent lead molecules for new peptide antibiotic development. Clin Exp Immunol, 2004 Feb, 135(2), 303 - 9 Paneth cell granule depletion in the human small intestine under infective and nutritional stress; Kelly P et al.; Paneth cells are important contributors to the intestinal antimicrobial barrier through synthesis and release of antimicrobial peptides and proteins . Animal studies indicate that Paneth cell numbers, location and granule morphology are altered by infection and zinc status . We examined human tissue to determine whether Paneth cell numbers, distribution or granule morphology are altered in infective, inflammatory and nutritional disorders . Archival sections from infective disorders (giardiasis, cryptosporidiosis, HIV, helminth infection) were compared with active inflammatory conditions (coeliac, Crohn's and graft-versus-host diseases) and histologically normal tissues . A subset of tissues was studied by electron microscopy and TUNEL staining for apoptosis . Human defensin-5 (HD5) peptide and mRNA was analysed by immunohistochemistry, in situ hybridization and quantitative reverse transcription polymerase chain reaction . Sections from a tropical population cohort study were then analysed to determine the relationship of granule depletion to infection, nutritional status and plasma zinc concentration . In HIV-related cryptosporidiosis, but not other disorders, Paneth cells were reduced in number and markedly depleted of granules . Paneth cell granule depletion was associated with reduced HD5 immunoreactivity, but this was not due to apoptosis and there was no reduction in mRNA transcripts . In the tropical population studied, depletion of granules was associated with reduced body mass index, reduced plasma zinc levels and HIV infection . Paneth cell granules in human small intestine may be depleted in response to infective and nutritional stress . We postulate that this is one mechanism through which zinc status influences host susceptibility to intestinal infection. J Nat Prod, 2004 Jan, 67(1), 88 - 90 Syncarpamide, a new antiplasmodial (+)-norepinephrine derivative from Zanthoxylum syncarpum; Ross SA et al.; A new (+)-norepinephrine derivative, syncarpamide (1), along with a known coumarin, (+)-S-marmesin (2), and one known alkaloid, decarine (3), have been isolated from the stem of Zanthoxylum syncarpum . The structure of compound 1 was elucidated on the basis of 1D and 2D NMR, MS, IR, optical rotation, and CD analyses . Its absolute stereochemistry was elucidated by synthesis of its enantiomer and subsequent comparison of CD data . Characterizations of compounds 2 and 3 were based on spectral analysis and comparison with reported data . Compounds 1 and 3 showed antiplasmodial activity, with IC(50) values of 2.04 and 1.44 microM against Plasmodium falciparum D(6) clone and 3.06 and 0.88 microM against P . falciparum W(2) clone, respectively . Compound 3 showed cytotoxicity at 56.42 microM, whereas compound 1 was not cytotoxic at 10.42 microM . Compound 1 was tested for hypotensive activity, but no activity was observed . Compound 2 showed no antiplasmodial or antimicrobial activities. Rev Med Interne, 2004 Jan, 25(1), 54 - 64 {Helicobacter pylori infection and antimicrobial agents resistance}; de Korwin JD; PURPOSE: Seven days triple therapies combining a proton pump inhibitor (PPI) and 2 antimicrobial agents (clarithromycin {C}, amoxicillin {A}, metronidazole {M}), are recommended for the treatment of Helicobacter pylori infection . The eradication failures have increased these last years, particularly in France (about 30%) . They are essentially related to the development of antimicrobial agents resistance, mainly concerning macrolides and nitro-imidazoles . CURRENT KNOWLEDGE AND KEY POINTS: Primary resistance to clarithromycin is variable, but reaching now about 10% throughout the world and about 20% in France . It reduces the eradication success rate at 25% . The secondary resistance is very high, contra-indicating the use of clarithromycin in second line regimens . Primary resistance to amoxicillin has recently appeared, but remains very low until now, less than 2%, as the tetracyclin (T) resistance . Primary resistance to metronidazole is 3 times higher than macrolides resistance, but its determination is less accurate . Metronidazole resistance reduces eradication rate of about 25%, leading to the use of metronidazole in second line therapy, in increasing the triple therapy duration at 14 days (PPI-A-M), or in combination with quadruple therapy (Bismuth-PPI-T-M) . Other rescue-treatments are efficacious, based on ranitidine bismuth citrate combined regimens or on rifabutine (R) based regimens (PPI-A-R) . FUTURE PROSPECTS AND PROJECTS: The recent knowledge of the mutations mainly responsible for H . pylori resistance to antimicrobial agents now allows the development of detection methods based on the study of bacterial DNA . These methods have been validated for clarithromycin and should favour in the near future the determination of resistance by the use of biopsy culture or directly on the gastric biopsy. J Am Vet Med Assoc, 2004 Jan 15, 224(2), 275 - 9 Outcome and subsequent fertility of sheep and goats undergoing cesarean section because of dystocia: 110 cases (1981-2001); Brounts SH et al.; OBJECTIVE: To determine the outcome and subsequent fertility of sheep and goats undergoing a cesarean section because of dystocia . DESIGN: Retrospective study . ANIMALS: 85 sheep and 25 goats . PROCEDURE: Medical records were reviewed, and information was obtained on signalment, history, physical examination findings, anesthesia protocol, surgical technique, number of lambs or kids delivered, pre- and postoperative treatments, duration of hospitalization, and postoperative complications . Follow-up information was obtained through telephone conversations with owners . RESULTS: The proportion of sheep admitted to the veterinary teaching hospital during the study period that underwent a cesarean section (4.4%) was significantly higher than the proportion of goats that did (2.2%) . Pygmy goats were overrepresented, compared with the hospital population . The most common reason for cesarean section was inadequate dilatation of the cervix . The most common surgical approach was via the left paralumbar fossa . Two hundred one lambs and kids were delivered, of which 116 were dead at delivery or died shortly afterward . Forty-two of the 65 dams with 1 or more dead fetuses had been in stage-2 labor for > 6 hours, and fetal death was significantly associated with a prolonged duration of dystocia . The most common complication following surgery was retained placenta (n = 49) . Use of antimicrobials was associated with a lower rate of complications . All 16 dams that were rebred became pregnant and had no problems with dystocia . CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that cesarean section is an effective method of resolving dystocia in sheep and goats and does not adversely affect subsequent fertility. J Am Vet Med Assoc, 2004 Jan 15, 224(2), 250 - 3, 224 Thermal cautery of the cornea for treatment of spontaneous chronic corneal epithelial defects in dogs and horses; Bentley E et al.; A thermal cautery technique was used to treat spontaneous chronic corneal epithelial defects (SCCEDs) in 9 eyes of 8 dogs and 2 eyes of 2 horses . Animals were sedated, and a topical anesthetic was applied . A handheld thermal cautery unit was then used to make multiple, small (< or = 1 mm in diameter), superficial burns throughout the affected area . The cautery unit was applied just until the slightest degree of contraction of the collagen fibrils was observed . After the stromal bed of the defect was treated, a rim of epithelium that extended approximately 1 mm around the denuded stroma was also subjected to thermal cautery . Following surgery, a contact lens was placed in dogs but not in horses, and the eye was treated with broad-spectrum antimicrobial ophthalmic solutions . Defects in all 11 eyes healed with minimal scarring; mean time to healing in dogs was 2.1 weeks (range, 2 to 3 weeks) . The defect healed in 1 week in 1 horse and in 2 weeks in the other . Many therapeutic options are available for the treatment of SCCEDs . Procedures such as epithelial debridement and anterior stromal puncture have been shown to have a high rate of success . In cases for which these less invasive procedures fail, our results suggest that thermal cautery may be a reasonable alternative to previously described treatments for SCCEDs in dogs and horses prior to more invasive procedures such as superficial keratectomy. J Immunol, 2004 Feb 1, 172(3), 1763 - 7 Selective killing of vaccinia virus by LL-37: implications for eczema vaccinatum; Howell MD et al.; Possible bioterrorism with smallpox has led to the resumption of smallpox (vaccinia virus) immunization . One complication, eczema vaccinatum, occurs primarily in patients with atopic dermatitis (AD) . Skin lesions of patients with AD, but not psoriasis, is deficient in the cathelicidin antimicrobial peptide (LL-37) and human beta-defensin-2 (HBD-2) . We hypothesized that this defect may explain the susceptibility of patients with AD to eczema vaccinatum . The Wyeth vaccine strain of vaccinia virus was incubated with varying concentrations of human (LL-37) and murine (CRAMP) cathelicidins, human alpha-defensin (HBD-1, HBD-2), and a control peptide . Outcomes included quantification of viral PFU, vaccinia viral gene expression by quantitative real-time RT-PCR, and changes in virion structure by transmission electron microscopy . CRAMP knockout mice and control animals were inoculated by skin pricks with 2 x 10(5) PFU of vaccinia and examined daily for pox development . Physiologic amounts of human and murine cathelicidins (10-50 micro M), but not human defensins, which had antibacterial activity, resulted in the in vitro reduction of vaccinia viral plaque formation (p < 0.0001), vaccinia mRNA expression (p < 0.001), and alteration of vaccinia virion structure . In vivo vaccinia pox formation occurred in four of six CRAMP knockout animals and in only one of 15 control mice (p < 0.01) . These data support a role for cathelicidins in the inhibition of orthopox virus (vaccinia) replication both in vitro and in vivo . Susceptibility of patients with AD to eczema vaccinatum may be due to a deficiency of cathelicidin. Curr Opin Immunol, 2004 Feb, 16(1), 4 - 9 Immunity in Caenorhabditis elegans; Millet AC et al.; Until very recently it was not known whether the invertebrate Caenorhabditis elegans was capable of mounting a specific immune response to protect itself from pathogens . It has only just become clear that this simple nematode in fact possesses a complex innate immune system, involving multiple signalling pathways and an armoury of antimicrobial proteins and peptides . Genetic and microarray approaches are now revealing the molecular cross-talk that exists between the different signalling cascades. Biochem Biophys Res Commun, 2004 Feb 6, 314(2), 615 - 21 Effects of L- or D-Pro incorporation into hydrophobic or hydrophilic helix face of amphipathic alpha-helical model peptide on structure and cell selectivity; Song YM et al.; A synthetic amphipathic alpha-helical model peptide, KLW, displays non-cell selective cytotoxicity . To investigate the effects of L- or D-Pro kink incorporation into hydrophobic or hydrophilic helix face of KLW on structure, cell selectivity, and membrane-binding affinity, we designed a series of four peptides, in which Leu(9) and Lys(11) in the hydrophobic and hydrophilic helix face of KLW, respectively, are substituted with L- or D-Pro . A L- or D-Pro substitution (KLW-L9P or KLW-L9p) of Leu(9) at the hydrophobic helix face of KLW induced a more significant reduction in hemolytic activity with improved antibacterial activity than that (KLW-K11P or KLW-K11p) of Lys(11) in the hydrophilic helix face . In addition, D-Pro-containing peptides (KLW-L9p and KLW-K11p) displayed less hemolytic activity than L-Pro-containing peptides (KLW-L9P and KLW-K11P) . Tryptophan fluorescence studies revealed that bacterial cell selectivity of KLW-L9P, KLW-L9p, and KLW-K11p is closely related to selective interactions with negatively charged phospholipids . CD analysis revealed that L- or D-Pro incorporation into KLW reduces the alpha-helicity of the peptide and D-Pro incorporation induces more significant disruption in alpha-helical structure than L-Pro incorporation . Our results collectively suggest that D-Pro incorporation into the hydrophobic helix face of non-cell selective amphipathic alpha-helical peptides may be useful for the design of novel antimicrobial peptides possessing high bacterial cell selectivity without hemolytic activity. J Endotoxin Res, 2003, 9(6), 385 - 9 An overview of clinical studies in healthy subjects and patients with severe sepsis with IC14, a CD14-specific chimeric monoclonal antibody; Axtelle T et al.; An overview and discussion of clinical studies with IC14, a chimeric monoclonal antibody directed against human CD14 is presented . These studies include phase 1 trials in: (i) healthy subjects; (ii) healthy subjects challenged with lipopolysaccharide (LPS); and (iii) patients with severe sepsis . The results from clinical studies of IC14 demonstrate this chimeric monoclonal antibody diminishes the systemic inflammatory response directed against LPS and may have potential as a treatment to prevent organ dysfunction in patients with severe sepsis . Furthermore, IC14 treatment was generally well-tolerated in both healthy subjects and severe sepsis patients and did not increase the incidence of secondary infections . Analysis of pharmacology data indicate that higher doses of IC14 are required to saturate membrane-bound CD14 receptors effectively in patients with severe sepsis than in healthy subjects . Finally, the results of non-clinical studies indicate that IC14 should only be administered with concurrent antimicrobial therapy in patients with infection. Vector Borne Zoonotic Dis, 2003 Winter, 3(4), 175 - 86 Cationic antimicrobial peptide killing of African trypanosomes and Sodalis glossinidius, a bacterial symbiont of the insect vector of sleeping sickness; Haines LR et al.; Nine biochemically distinct cationic antimicrobial peptides were tested in vitro for their effects on bloodstream forms and procyclic (insect) forms of African trypanosomes, the protozoan parasites that cause African sleeping sickness in humans and trypanosomiasis in domestic animals . At low concentrations, one peptide completely inhibited growth of bloodstream forms, one inhibited procyclic forms, and five inhibited both trypanosome life cycle stages . The peptides were also tested on Sodalis glossinidius, a bacterial symbiont of tsetse flies . S . glossinidius was highly resistant to seven of the nine peptides, including both that specifically inhibited either bloodstream or procyclic forms and three of the five that inhibited both trypanosome life cycle stages . The results indicate that several of these peptides may be ideal candidates for therapy of trypanosome infected mammals or for transgenic expression in S . glossinidius as a strategy for inhibiting trypanosome survival, development, and maturation in tsetse and interference with transmission of African sleeping sickness. Biochem J, 2004 May 1, 379(Pt 3), 665 - 72 Interactions of histatin 5 and histatin 5-derived peptides with liposome membranes: surface effects, translocation and permeabilization; Den Hertog AL et al.; A number of cationic antimicrobial peptides, among which are histatin 5 and the derived peptides dhvar4 and dhvar5, enter their target cells and interact with internal organelles . There still are questions about the mechanisms by which antimicrobial peptides translocate across the membrane . We used a liposome model to study membrane binding, translocation and membrane-perturbing capacities of histatin 5, dhvar4 and dhvar5 . Despite the differences in amphipathic characters of these peptides, they bound equally well to liposomes, whereas their membrane activities differed remarkably: dhvar4 translocated at the fastest rate, followed by dhvar5, whereas the histatin 5 translocation rate was much lower . The same pattern was seen for the extent of calcein release: highest with dhvar4, less with dhvar5 and almost none with histatin 5 . The translocation and disruptive actions of dhvar5 did not seem to be coupled, because translocation occurred on a much longer timescale than calcein release, which ended within a few minutes . We conclude that peptide translocation can occur through peptide-phospholipid interactions, and that this is a possible mechanism by which antimicrobial peptides enter cells . However, the translocation rate was much lower in this model membrane system than that seen in yeast cells . Thus it is likely that, at least for some peptides, additional features promoting the translocation across biological membranes are involved as well. BioDrugs, 2004, 18(1), 9 - 22 Proinflammatory cytokines in the treatment of bacterial and fungal infections; Netea MG et al.; Mortality due to severe bacterial infections has not been markedly effected by the introduction of new antimicrobial drugs over the last 30-40 years . This has emphasized the need for development of new therapeutic strategies to combat sepsis . The outcome of an infection depends on two factors: the growth of the microorganisms (including the effect of antibacterial drugs), and the host's defensive response to the invading organism . It is known that injection of bacterial products into experimental animals leads to enhanced nonspecific resistance to a variety of microorganisms . The discovery of the specific mediators responsible for modulation of host defense has created new possibilities for the development of alternative treatment strategies . Molecules such as interleukins, interferons, tumor necrosis factors and hematopoietic growth factors have become available in recombinant form, and their therapeutic potential in various infectious diseases has been tested in various experimental models of infections . Initial data in various patient groups indicate that adjunctive therapy with recombinant proinflammatory cytokines may have beneficial effects in the treatment of bacterial and fungal infections. Int J Infect Dis, 2004 Mar, 8(2), 103 - 10 Osteomyelitis due to Aspergillus spp . in patients with chronic granulomatous disease: comparison of Aspergillus nidulans and Aspergillus fumigatus; Dotis J et al.; OBJECTIVE: Chronic granulomatous disease (CGD) is a rare inherited disorder of NADPH oxidase in which phagocytes fail to generate reactive antimicrobial oxidants . Invasive fungal infections are an important cause of morbidity and mortality in CGD patients, with Aspergillus spp . being the most frequent fungal pathogens . We reviewed the reported cases of osteomyelitis in CGD patients due to Aspergillus nidulans and compared them with those due to Aspergillus fumigatus . METHODS: Twenty-four cases of osteomyelitis due to Aspergillus spp . in 22 male CGD patients were found in MEDLINE . RESULTS: Fourteen cases (58%) were due to Aspergillus nidulans and ten cases to Aspergillus fumigatus . No other aspergilli were reported as causes of osteomyelitis . Osteomyelitis due to Aspergillus nidulans was associated with pulmonary infection and involved 'small bones' more frequently than Aspergillus fumigatus osteomyelitis (p=0.032) . Half of the CGD patients with Aspergillus nidulans osteomyelitis died compared with none of those with Aspergillus fumigatus osteomyelitis (p=0.019) . In both Aspergillus nidulans and Aspergillus fumigatus cases, cure was achieved by prompt antifungal treatment combined with surgery and immunotherapy . CONCLUSION: Aspergillus nidulans causes osteomyelitis in CGD patients relatively frequently compared with Aspergillus fumigatus and may be accompanied by higher mortality . This contrasts with the low frequency with which Aspergillus nidulans causes osteomyelitis in patients with other types of immunodeficiency. Trends Cell Biol, 1995 Mar, 5(3), 114 - 9 Defensins in granules of phagocytic and non-phagocytic cells; Selsted ME et al.; Antimicrobial proteins stored in lysosome-like granules of neutrophils and macrophages probably play an important role in killing phagocytosed microbes after delivery to the phagolysosome . Among the granules' antimicrobial armamentarium are defensins, peptides that kill a broad spectrum of microorganisms in vitro . Antimicrobial defensins were recently also isolated from non-phagocytic granulocytes of the mouse small intestinal epithelium, from where they are secreted into the lumen to function extracellularly . Clarification of the antimicrobial mechanisms of defensins in intracellular and extracellular environments will provide a key to understanding peptide-mediated host defence. Mol Cell, 2004 Jan 16, 13(1), 1 - 2 Learning the codes of fly immunity; Bettencourt R et al.; Insect antimicrobial response serves as an excellent model for studying human innate immunity . In this issue of Molecular Cell, Senger and colleagues demonstrate that a large number of immunity genes in Drosophila fat bodies can be regulated by a simple code, REL-GATA. Skin Res Technol, 2004 Feb, 10(1), 1 - 9 Cleansing, dehydrating, barrier-damaging and irritating hyperaemising effect of four detergent brands: comparative studies using standardised washing models; Gloor M et al.; BACKGROUND AND PROBLEM: It is well known that the damaging effect of surfactants on the stratum corneum varies according to the surfactant used . The present investigations aim to compare four standard commercial cleansing solutions (Esemptan Cleansing Lotion, Stephalen Shower Gel, Manipur Antimicrobial Cleansing Solution and Tork Mevon 55 Liquid Soap) with respect to their cleansing and skin barrier-damaging effects . MATERIAL AND METHODS: The cleansing effect of the solutions was determined in relation to their concentrations in a first experimental series involving 15 subjects using a standardised test method . The product concentrations with the most divergent cleansing effects were tested for their dehydrating (corneometry), epidermal barrier-damaging (TEWL) and irritating effects (laser Doppler) in a standardised washing test . In a second experimental series, the concentration used for the cleansing solutions was based on the quantity of cleansing solution obtained from dispenser actuations (six actuations/L) . These concentrations were used to test the cleansing and damaging effect on the stratum corneum using the same methods as in the first experimental series . RESULTS: There were no significant differences in the first experimental series . In the second experimental series, Stephalen Shower Gel showed disadvantages in terms of a small cleansing effect, but without evidence of a smaller stratum corneum-damaging effect, and Tork Mevon 55 Liquid Soap showed advantages in terms of a smaller stratum corneum-damaging effect, but without evidence of a smaller cleansing effect . CONCLUSIONS: These studies showed that the relationship between the cleansing and the damaging effect on the stratum corneum can be properly assessed only by testing different concentrations . Furthermore, this experimental approach allowed to differentiate the four tested cleansing solutions. HIV Med, 2004 Jan, 5(1), 50 - 4 Oral candidiasis and seborrheic dermatitis in HIV-infected patients on highly active antiretroviral therapy; Dunic I et al.; BACKGROUND: Mucocutaneous manifestations such as oral candidiasis (OC) and seborrheic dermatitis (SD) are very common HIV-related opportunistic events and are usually initial markers of immunodeficiency . AIM: The purpose of this study was to evaluate the efficacy of highly active antiretroviral therapy (HAART) in the regression of HIV-associated OC and SD . METHODS: In a prospective study, 120 HIV-infected patients with OC and SD were divided into two groups: HAART-treated patients (group 1, n=76) and non-HAART-treated patients (group 2, n=44) . Non-HAART-treated patients were given antimicrobial therapy . Study subjects were matched for sex, age, risk, and stage of HIV infection . The results were analysed by chi2 test and the Kaplan-Meier method . RESULTS: At baseline, OC was evident in 59 (77.7%) of the HAART-treated patients and in 34 (77.3%) of the non-HAART-treated patients, while SD was present in 19 (25.0%) of the HAART-treated patients and in 17 (38.6%) of the non-HAART-treated patients . After a median follow-up period of 22 months, regression of OC and SD occurred in 49 (83.1%) and 16 (84.2%) of the HAART-treated patients, respectively . In the control group, regression of OC and SD occurred in only five (14.7%) and seven (41.2%) patients, respectively, during the same period . CONCLUSIONS: HAART showed greater efficacy than standard antimicrobial therapy for the treatment of OC and SD in HIV-infected patients. J Cosmet Sci, 2003 Nov-Dec, 54(6), 537 - 50 Improving the aqueous solubility of triclosan by solubilization, complexation, and in situ salt formation; Grove C et al.; Triclosan, an antimicrobial, although widely incorporated into many skin care products, toothpastes, and liquid soaps, presents formulation difficulties because it is practically insoluble in water . The objective of this study was to improve the aqueous solubility of triclosan through solubilization, complexation, and salt formation . The solubility of triclosan in distilled water and in phosphate buffers (pH 7.4) was determined at 30 degrees C . The order of solubilizing performance of the solubilizers was: N-methylglucamine> or =L-arginine>sodium lauryl sulfate>beta-cyclodextrin> or =hydroxypropyl-beta-cyclodextrin>ethanolamine>sodium benzoate>sodium methyl 4-hydroxybenzoate>triethanolamine> or =diethanolamine . These solubilizers increased the solubility of triclosan from 80- to 6000-fold . Micellar solubilization and the formation of either salts or complexes are postulated as possible mechanisms for the increase in the solubility of triclosan by the surfactant sodium lauryl sulphate, the cyclic sugar derivatives beta-cyclodextrin and 2-hydropropyl-beta-cyclodextrin, the amino acid L-arginine, and the amino sugar alcohol N-methylglucamine . Furthermore, although the bacteriostatic efficacy of triclosan was significantly increased when solubilized with N-methylglucamine, L-arginine, and ethanolamine, increased solubilization did not increase the effectiveness of triclosan for all solubilizers tested. ORL J Otorhinolaryngol Relat Spec, 2003 Sep-Oct, 65(5), 245 - 9 Lactoferrin inhibits growth of malignant tumors of the head and neck; Wolf JS et al.; Lactoferrin, a naturally occurring glycoprotein found in breast milk, has previously been shown to have antimicrobial properties and recently has been demonstrated to inhibit malignant tumor growth, presumably through immunomodulation . We hypothesized that intratumoral injection of human and murine recombinant lactoferrin would decrease the growth of malignant tumors in vivo . Using an orthotopic murine model for both squamous cell carcinoma and fibrosarcoma of the floor of the mouth, we administered lactoferrin directly into the tumors using variable dosing strategies . Additionally, we performed in vitro experiments to assess whether the effects of lactoferrin are due to direct cytotoxicity . Our results revealed growth inhibition of 50% (p=0.03)and 54% (p=0.01) as compared with controls for both human and murine tumor cells in immunodeficient and immunocompetent mice, respectively . There was a more dramatic effect in immunocompetent models which may identify immunomodulation as an important mechanism of action for lactoferrin . Support for immunomodulation as a possible mechanism was the lack of any difference between controls and the experimental groups in vitro . Lactoferrin proved effective in reducing malignant tumor growth in a murine model . These properties offer hope for its use as a primary or adjuvant chemotherapeutic agent . Further investigation focused on mechanism and delivery is needed . Biosci Biotechnol Biochem, 2003 Dec, 67(12), 2584 - 90 Synthetic racemate and enantiomers of cytosporone E, a metabolite of an endophytic fungus, show indistinguishably weak antimicrobial activity; Ohzeki T et al.; The racemate and the enantiomers of cytosporone E {3-heptyl-4,5,6-trihydroxyphthalide (1)}, a metabolite of the endophytic fungus, CR200 (Cytospora sp.), were synthesized . The key steps were (i) Sharpless asymmetric dihydroxylation of an alkene (8) and (ii) HPLC separation of the enantiomers of tert-butyldimethylsilyl ether (12) on a chiral stationary phase . The racemate and enantiomers of cytosporone E showed only weak antimicrobial activity with no difference among them. Pol J Pharmacol, 2003 Nov-Dec, 55(6), 1111 - 7 Synthesis of some new 2,5-disubstituted 1,3,4-thiadiazoles containing isomeric pyridyl as potent antimicrobial agents; Zamani K et al.; Several new 2,5-disubstituted derivatives of 1,3,4-thiadiazoles containing isomeric pyridyl were obtained from cyclization of corresponding thiosemicarbazides under acidic conditions . The newly synthesized compounds were characterized using different methods of spectroscopy such as IR, 1H-NMR, 13C-NMR, MS and elemental analysis . The minimal inhibitory concentration (MIC) results of screening of some of the synthesized compounds were also reported . Most of the synthesized compounds have been found to be active against both Gram-positive and Gram-negative bacteria at less than 3.6 mg/ml . The compound (10b) is most active against all seventeen used gram-positive and gram-negative bacteria. J Antimicrob Chemother, 2004 Feb, 53(2), 258 - 65 Epub 2004 Jan 16. Comparisons of the in vitro susceptibility testing results for garenoxacin using six different national methods: report from the garenoxacin international bridging study; Jones RN et al.; BACKGROUND: Laboratories worldwide carry out MIC/disc diffusion (DD) tests using various national methods, often published by local organizations . Potentially different results may complicate drug development or registration between the US methods and those used in the European Union (EU) . This study uses a new des-F(6)quinolone, garenoxacin, to compare in vitro results among the most utilized antimicrobial susceptibility testing methods . METHODS: Investigators in France, Germany, Spain, Sweden and the UK tested two bacterial collections designated, challenge (CC; n = 330) containing quinolone-resistant strains and national (NC; n = 540) that were recent clinical isolates (2000-2001) . Results were compared with values derived from the National Committee for Clinical Laboratory Standards (NCCLS) methods, carried out by the US coordinating site . Discords (greater than four-fold) between MIC method results were repeated . Results were analysed for variation from the NCCLS results (+/-1-2 dilutions or greater than 3-6 mm) and by regression statistics . Ciprofloxacin was used as the control quinolone agent . RESULTS: CC and NC testing compliance averaged 98.4% and 86.4% among participating centres, respectively, and correlation (r) of the national method to the NCCLS MIC was: France (0.98), Germany (0.95), Spain (0.98), Sweden (0.96) and UK (0.95) . CC produced MIC results that were identical to the NCCLS (Spain) to 0.6 x log(2) greater (Germany), but the percentage of strains +/-2 dilutions versus NCCLS MIC results was 98% (Germany)-100% (Sweden, UK) . Similar patterns were observed for the NC (r = 0.93-0.98), and all nations had >99% of results within +/-2 dilutions (+/-6 mm for disc tests) of NCCLS values . MIC results from four national methods were slightly elevated compared to the NCCLS result (average 0.2 x log(2)) . Control ciprofloxacin MIC and DD test results showed similar patterns . CONCLUSIONS: Inter-method garenoxacin susceptibility test results indicate that MIC and zone diameter endpoints derived from five EU methods compare favourably to the NCCLS method results, and generally were identical or a fraction of a log(2) dilution step higher . In contrast, zone diameters for garenoxacin and ciprofloxacin were routinely larger for the EU methods . This unique inter-method 'bridging' experiment allows regulatory agencies to better correlate in vitro testing results derived from procedures that use different national methodologies. J Antimicrob Chemother, 2004 Feb, 53(2), 174 - 9 Epub 2004 Jan 16. Dicloxacillin and erythromycin at high concentrations increase ICAM-1 expression by endothelial cells: a possible factor in the pathogenesis of infusion phlebitis; Lanbeck P et al.; OBJECTIVES: Antimicrobial agents are important risk factors for infusion phlebitis, but the risk varies between different antibiotics . Erythromycin and dicloxacillin are known to induce phlebitis frequently, as well as to exert toxic effects on cultured endothelial cells . The pathogenesis of infusion phlebitis is unclear, but chemical toxicity is thought to lead to inflammation and subsequent thrombosis . In the present study, endothelial cells were exposed to antibiotics at the range of concentrations used for intravenous administration, followed by analysis of pro-inflammatory and pro-coagulant surface molecules . METHODS: Primary human umbilical vein endothelial cells (HUVEC) and the endothelial hybrid cell line EaHy926 were exposed to dicloxacillin, erythromycin, benzylpenicillin and cefuroxime (all at 6250 mg/L) for 60 min, followed by washing . After 5 or 24 h additional incubation, cells were analysed for E-selectin (CD62E), tissue factor (TF) or intercellular adhesion molecule 1 (ICAM-1, CD54) density by flow cytometry . RESULTS: Despite constitutive expression of ICAM-1 (34%) in HUVEC, 6250 mg/L of dicloxacillin or erythromycin significantly increased the number of cells with ICAM-1 expression by 37% and 30%, respectively . In contrast, cefuroxime and benzylpenicillin did not up-regulate ICAM-1 above background levels . A similar pattern was seen with the endothelial cell line EaHy926 . The E-selectin and TF density were not affected by the antibiotics examined . CONCLUSIONS: The results of this study support the theory that endothelial cells that are affected by high concentrations of antibiotics may initiate an inflammatory response through expression of ICAM-1 . This is a novel finding in the pathogenesis of infusion phlebitis. J Antimicrob Chemother, 2004 Feb, 53(2), 230 - 9 Epub 2004 Jan 16. In vitro activity and mode of action of diastereomeric antimicrobial peptides against bacterial clinical isolates; Pag U et al.; OBJECTIVES: Increasing resistance of pathogenic bacteria to antibiotics is a severe problem in health care and has intensified the search for novel drugs . Cationic antibacterial peptides are the most abundant antibiotics in nature and have been frequently proposed as new anti-infective agents . Here, a group of diastereomeric (containing d- and l-amino acids) peptides is studied regarding their potency against multiply resistant clinical isolates and their modes of action against Gram-positive cocci . METHODS: MIC determinations and chequerboard titrations followed established procedures . Mode of action studies included killing kinetics and a series of experiments designed to characterize the impact of the diastereomeric peptides on bacterial membranes . RESULTS: The tested diastereomers displayed high antimicrobial and broad spectrum activity with amphipathic-2D being the most active peptide . Synergic activities were observed with individual strains . Mode of action studies clearly demonstrated that the cytoplasmic membrane is a primary target for the peptides and that membrane disruption constitutes a significant bactericidal activity for the major fraction of a bacterial population . However, depending on the indicator strain, the results also suggest that additional molecular events contribute to the overall activity. J Inorg Biochem, 2004 Feb, 98(2), 245 - 53 Preferences of kanamycin A towards copper(II) . Effect of the resulting complexes on immunological mediators production by human leukocytes; Szczepanik W et al.; The widespread presence of pathogenic bacteria is a cause of permanent demand for investigating the properties of antimicrobial agents . The chemical basis of several toxic effects induced by antibiotics still remains unclear . Aminoglycosides, highly ototoxic and nephrotoxic drugs, are capable of copper(II) ions chelating . In this study we established the affinity of kanamycin A towards copper(II), in contrast with other metal ions: iron(III), nickel(II), cobalt(II) and zinc(II) by means of potentiometry . Circular dichroism spectroscopy was applied to monitor the competition of copper(II) partition between kanamycin A and human serum albumin . We show, that the drug is able to digest Cu(II) ions from HSA to some extent and comparing the stability constants for metal and antibiotic with those, obtained for the N-terminal Asp-Ala-His-Lys (DAHK) sequence, which constitutes a copper(II) binding domain within albumin, we demonstrate that the Cu(II)-kanamycin A complex formation is possible also in blood plasma . Bioassays and immunoassay were used to find out the possibility of Cu(II)-kanamycin A complexes to induce cytokines: tumor necrosis factor (TNF), interferon (IFN) and interleukin-10 (IL-10) in human peripheral blood leukocytes . The effect on the cytokines release was dose and time dependent and the interdependence between IL-10 and TNF stimulation was found . We report that Cu(II)-aminoglycoside systems can act as moderate inducers of TNF-alpha, IFN-alpha/beta and IL-10 released from human leukocytes . We have also found that these complexes are non-toxic for human A549 cells. J Inorg Biochem, 2004 Feb, 98(2), 231 - 7 X-ray, spectral and biological (antimicrobial and superoxide dismutase) studies of oxalato bridged CuII-NiII and CuII-ZnII complexes with pentamethyldiethylenetriamine as capping ligand; Patel RN et al.; X-band electron spin resonance (ESR) and electronic spectra of oxalatobridged heterodinuclear Cu-Ni and Cu-Zn complexes, viz., {(PMDT)Cu-Ox-Ni(PMDT)}(BPh(4))(2).2CH(3)CN and {(PMDT)Cu-Ox-Zn(PMDT)}(BPh(4))(2).2CH(3)CN, where PMDT=pentamethyldiethylenetriamine, Ox=oxalate ion have been described . Complex {(PMDT)Cu-Ox-Ni(PMDT)}(BPh(4))(2).2CH(3)CN has been structurally characterized . This complex crystallizes in the monoclinic space group, C(2) (No . 5) with the unit parameters a=20.445(4) A, b=14.884(3) A, c=23.174(5) A, alpha=90 degrees, beta=102.693(4) degrees, gamma=90 degrees, V=6880(2) A(3) and Z=4 . The structure refined to R=0.0354 and R(w)=0.0853 for 21,109 reflections with I>2 sigma(I) using 765 parameters, shows the presence of a MN(3)O(2) chromophore in a distorted trigonal-bipyramidal (TBP) heterometallic complex with oxalate dianion . Taking with an equatorial Cu-O=2.137(8) A and an axial Cu-O=1.961(6) A coordination site at Cu(II) ion and equatorial Ni-O=2.178(7) A and axial Ni-O=1.994 (9) A coordination site at Ni(II) ion . The Cu-Ni distance is 5.3532(9) A and Cu-C(2)O(4)-Ni unit is planar . The {(PMDT)Cu-Ox-Ni(PMDT)}(2+) shows the ESR spectrum of the antiferromagnetic spin exchange with each dinuclear delocalization of the unpaired electron over the unit and spin-doublet ground state which demonstrates the Cu-Ox-Ni core . Antimicrobial and superoxide dismutase (SOD) activities of these complexes have also been measured. Zhonghua Er Ke Za Zhi, 2003 Nov, 41(11), 849 - 51 {Histopathological changes of duodenal salami ulcer in children}; Tang HF et al.; OBJECTIVE: Duodenal salami ulcer is a common disease found on routine endoscopic examination in children . The purpose of the study was to explore the characteristics and the clinicopathological features of duodenal salami ulcer in children and to deepen the understanding of duodenal salami ulcer . METHODS: The endoscopic results of 117 cases with the duodenal salami ulcer were analyzed . The specimens of gastric antrum and duodenal bulb were subjected to HE and Giemsa staining and were examined for any alteration in histopathology and infection with Helicobacter pylori (Hp) . The duodenal mucosa was stained with AB (pH 2.5)/PAS in order to diagnose the duodenal metaplasia . RESULTS: The major endoscopic finding was a kind of hoarfrost, which was dotty or flaky, covered on the hyperemic and edematous mucosa . The detection rate of this c