Clin Ther, 2001 Apr, 23(4), 578 - 84 The clinical pharmacokinetics of a new pharmacokinetically enhanced formulation of amoxicillin/clavulanate; Kaye CM et al.; BACKGROUND: A new oral pharmacokinetically enhanced formulation of the broad-spectrum antibiotic amoxicillin/clavulanate has been developed to provide more effective therapy against resistant pathogens than is provided by currently available formulations by maintaining therapeutically useful plasma amoxicillin concentrations for a longer period after dosing . OBJECTIVE: This study explored the pharmacokinetics of the new oral formulation of amoxicillin/clavulanate in healthy male and female subjects . METHODS: A single oral dose of pharmacokinetically enhanced amoxicillin/clavulanate (2000/125 mg; 16:1 ratio) was administered to subjects at the start of a meal . After dosing, blood samples were collected at frequent intervals up to 12 hours, and plasma was assayed for amoxicillin and clavulanate concentrations using validated procedures . The new formulation consisted of 1 layer of immediate-release amoxicillin and clavulanate and another of sustained-release amoxicillin in a proportion such that for an amoxicillin minimum inhibitory concentration (MIC) of 4 microg/mL, the time above the MIC (T >MIC) would be approximately > or = 40% over a 12-hour dosing interval . RESULTS: The study enrolled 24 and 31 healthy male and female subjects, respectively . Their mean age was 35 years (range, 18-58 years) and mean body weight was 69 kg (range, 51-86 kg) . After the expected sharp peak in plasma amoxicillin concentration, there appeared to be a slower decline with the pharmacokinetically enhanced formulation than is usually seen with conventional formulations, and there was evidence of a second amoxicillin absorption phase . The mean T >MIC for an amoxicillin MIC of 4 microg/mL was 49.4% of a 12-hour dosing interval, a value that cannot be achieved with existing approved doses and formulations of amoxicillin/clavulanate . By 12 hours, plasma amoxicillin concentrations were very low (approximately 0.05 microg/mL), suggesting no expectation of notable dose-to-dose accumulation on repeat dosing with a BID regimen . The terminal half-lives of amoxicillin (1.27 hours) and clavulanate (1.03 hours) with the new formulation were similar to those of existing formulations of amoxicillin/clavulanate . No deaths or serious adverse events were reported . CONCLUSIONS: The enhanced pharmacokinetic profile of amoxicillin/clavulanate seen in this study suggests that this formulation is likely to be highly effective for the oral treatment of infections caused by bacteria--including beta-lactamase-producing organisms--and strains with amoxicillin MICs < or = 4 microg/mL. Antimicrob Agents Chemother, 2001 Jun, 45(6), 1937 - 8 Sputum itraconazole concentrations in cystic fibrosis patients; Sermet-Gaudelus I et al.; Itraconazole diffusion in sputum was studied in 11 cystic fibrosis patients with allergic bronchopulmonary aspergillosis . There was a high interindividual variability in sputum itraconazole concentration and sputum/serum drug concentration ratio . Three children had sputum drug concentrations before oral administration that were lower than the itraconazole MIC at which 90% of Aspergillus fumigatus strains were inhibited, although their serum drug concentrations were within the therapeutic range. Antimicrob Agents Chemother, 2001 Jun, 45(6), 1908 - 10 In vitro activities of moxifloxacin and other fluoroquinolones against Mycoplasma pneumoniae; Hamamoto K et al.; A total of 105 isolates of Mycoplasma pneumoniae were evaluated for susceptibility to moxifloxacin, sparfloxacin, levofloxacin, and ciprofloxacin . Moxifloxacin, a newly synthesized compound, showed the greatest activity . The MICs and MBCs at which 50 and 90% of isolates were affected were 0.15 (MIC(50) and MBC(50)) and 0.3 microg/ml (MIC(90) and MBC(90)) respectively . The results indicate that moxifloxacin might be promising an antimycoplasmal agent. Antimicrob Agents Chemother, 2001 Jun, 45(6), 1882 - 5 In vitro activities of terbinafine against Aspergillus species in comparison with those of itraconazole and amphotericin B; Moore CB et al.; Compared with the in vitro activities of itraconazole (geometric mean MIC {GM}, 0.56 microg/ml) and amphotericin B (GM, 0.66 microg/ml), the in vitro activity of terbinafine was inferior against Aspergillus fumigatus (GM, 19.03 microg/ml) (P < 0.05) and superior against A . flavus (GM, 0.10 microg/ml), A . terreus (GM, 0.16 microg/ml), and A . niger (GM, 0.19 microg/ml) . Clinical correlation is required, as trailing endpoints are problematic. Antimicrob Agents Chemother, 2001 Jun, 45(6), 1854 - 9 Correlation between antifungal susceptibilities of Coccidioides immitis in vitro and antifungal treatment with caspofungin in a mouse model; Gonzalez GM et al.; Caspofungin (Merck Pharmaceuticals) was tested in vitro against 25 clinical isolates of Coccidoides immitis . In vitro susceptibility testing was performed in accordance with the National Committee for Clinical Laboratory Standards document M38-P guidelines . Two C . immitis isolates for which the caspofungin MICs were different were selected for determination of the minimum effective concentration (MEC), and these same strains were used for animal studies . Survival and tissue burdens of the spleens, livers, and lungs were used as antifungal response markers . Mice infected with strain 98-449 (48-h MIC, 8 microg/ml; 48-h MEC, 0.125 microg/ml) showed 100% survival to day 50 when treated with caspofungin at > or =1 mg/kg . Mice infected with strain 98-571 (48-h MIC, 64 microg/ml; 48-h MEC, 0.125 microg/ml) displayed > or =80% survival when the treatment was caspofungin at > or =5 mg/kg . Treatment with caspofungin at 0.5, 1, 5, or 10 mg/kg was effective in reducing the tissue fungal burdens of mice infected with either isolate . When tissue fungal burden study results were compared between strains, caspofungin showed no statistically significant difference in efficacy in the organs of the mice treated with both strains . A better in vitro-in vivo correlation was noted when we used the MEC instead of the MIC as the endpoint for antifungal susceptibility testing . Caspofungin may have a role in the treatment of coccidioidomycosis. Antimicrob Agents Chemother, 2001 Jun, 45(6), 1828 - 35 Optimal susceptibility testing conditions for detection of azole resistance in Aspergillus spp.: NCCLS collaborative evaluation . National Committee for Clinical Laboratory Standards; Espinel-Ingroff A et al.; The most important role of susceptibility testing is to identify potentially resistant isolates for the agent being evaluated . Standard testing guidelines recently have been proposed for antifungal susceptibility testing of filamentous fungi (molds) . This collaborative (eight centers) study evaluated further newly proposed guidelines (NCCLS, proposed standard M38-P, 1998) and other testing conditions for antifungal susceptibility testing of Aspergillus spp . to itraconazole and three new triazoles, posaconazole (SCH56592), ravuconazole (BMS-207147), and voriconazole . MICs of itraconazole, posaconazole, ravuconazole, and voriconazole for 15 selected isolates of three species of Aspergillus (A . fumigatus, A . flavus, and A . terreus) with well documented in vitro, clinical, or animal data were determined in each center by using four medium formulations (standard RPMI-1640 {RPMI}, RPMI with 2% dextrose, antibiotic medium 3 {M3}, and M3 with 2% dextrose) and two criteria of MIC determination (complete {MIC-0s} and prominent {MIC-2s} growth inhibition) at 24, 48, and 72 h . The highest reproducibility (92 to 99%) was seen with the standard RPMI and M3 media . Moreover, the distinction between itraconazole-resistant (MICs of >8 microg/ml for clinically resistant strains) and -susceptible (MICs of 0.03 to 1 microg/ml) isolates, as well as between a voriconazole-resistant laboratory mutant and other isolates (voriconazole MICs of 2 to >8 versus 0.12 to 2 microg/ml), was more consistently evident with the standard RPMI medium and when MIC-0s were determined at 48 h . These results provide further refinement of the testing guidelines for susceptibility testing of Aspergillus spp . and warrant consideration for inclusion in the future NCCLS document M38-A. J Clin Oncol, 2001 May 15, 19(10), 2616 - 25 Hürthle cell carcinoma: a critical histopathologic appraisal; Stojadinovic A et al.; PURPOSE: Controversy exists over the ability of morphology to predict the biologic behavior of Hurthle cell carcinoma . The aim of this study was to conduct a critical histopathologic review of Hurthle cell carcinoma and to correlate morphologic parameters with clinical outcome . PATIENTS AND METHODS: Patients with histologically confirmed Hurthle cell carcinoma treated between 1940 and 2000 form the basis of this study . Adenomas were excluded . Tumors of unknown malignant behavior ({UMB} n = 17) had solid growth pattern, incomplete capsular invasion (Ci), or both but no vascular invasion (Vi) . Minimally invasive carcinomas ({MIC} n = 23) had one focus of intra- or extracapsular Vi, one focus of complete Ci, or both . Widely invasive carcinomas ({WIC} n = 33) demonstrated more than one focus of Vi, more than one focus of Ci, or both . The primary end points were relapse-free survival (RFS) and disease-specific survival (DSS) . Rates of recurrence/death were estimated by Kaplan-Meier method . The univariate influence of prognostic factors on end points was analyzed by log-rank test, and multivariate analysis was performed by Cox regression . RESULTS: Median follow-up was 8 years . No patients with UMB or MIC relapsed or died of disease . Of WIC, 73% relapsed and 55% died of disease . Age, size, and extent of resection did not influence outcome . Adverse predictors of RFS and DSS among WIC were extrathyroidal extension, nodal metastasis, positive margin, and solid growth pattern (P <.05) . Both Ci and Vi were associated with worse DSS (P <.05) . On multivariate analysis, extrathyroidal extension and nodal metastases were independent predictors of outcome (P <.05) . CONCLUSION: Patients with Hurthle cell carcinoma have a prognosis that is predicted by well-defined histomorphologic characteristics . Unlike differentiated thyroid cancer, nodal metastases predict a worse outcome in widely invasive Hurthle cell carcinoma, as does extrathyroidal extension. J Investig Med, 2001 May, 49(3), 292 - 6 Use of potassium tellurite for rapid-drug susceptibility testing of Mycobacterium avium complex; Afghani B et al.; BACKGROUND: Mycobacterium avium complex (MAC) is a major cause of infection in immunocompromised patients . MAC possesses an enzyme that reduces potassium tellurite in less than 3 days and results in formation of a black precipitate . The objective of this study was to determine whether reduction of potassium tellurite by mycobacteria can be used as a means of testing the susceptibility of MAC to clarithromycin . METHODS: Minimum inhibitory concentrations (MICs) for 104 clinical isolates of MAC were determined by the tellurite method and compared with those tested by a recommended microdilution method . Microdilution breakpoints were used for interpretation of susceptibility . MIC of less than 8 microg/mL was considered as susceptible, and MIC of greater than or equal to 8 microg/mL was resistant . RESULTS: There was agreement within a 2-fold dilution between MICs for 89% of isolates . Of the 53 isolates that had discrepant MICs by the two methods, 70% had higher MICs by the tellurite method . When the MICs were classified into interpretive categories, there was 100% agreement by the two methods . The MIC tested by the tellurite method was available within 5 days . CONCLUSIONS: These data suggest that use of potassium tellurite is a more rapid, reliable, and inexpensive method of testing the susceptibility of MAC to clarithromycin. Trop Med Int Health, 2001 May, 6(5), 407 - 11 Melarsoprol refractory T . b . gambiense from Omugo, north-western Uganda; Matovu E et al.; Culture adapted T . b . gambiense isolated from Northwest Uganda were exposed to 0.001-0.14 microg/ml melarsoprol or 1.56-100 microg/ml DL-alpha-difluoromethylornithine (DFMO) . Minimum inhibitory concentrations (MICs) of each drug were scored for each isolate after a period of 10 days drug exposure . The results indicate that T . b . gambiense isolates from Northwest Uganda had elevated MIC values for melarsoprol ranging from 0.009 to 0.072 microg/ml as compared with T . b . gambiense isolates from Cote d'Ivoire with MIC values ranging from 0.001 to 0.018 microg/ml or with T . b . rhodesiense from Southeast Uganda with MIC values from 0.001 to 0.009 microg/ml . All MIC values obtained fell below expected peak melarsoprol concentrations in serum of treated patients . However, it may not be possible to maintain constant drug concentrations in serum of patients as was the case in our in vitro experiments . Importantly, the MIC of 0.072 microg/ml exhibited by one of the isolates from Northwest Uganda was above levels attainable in CSF indicating that this isolate would probably not be eliminated from CSF of treated patients . PCR amplification of the gene encoding the P2-like adenosine transporter followed by restriction digestion with Sfa NI enzyme revealed presence of fragments previously observed in a trypanosome clone with laboratory-induced arsenic resistance . From our findings it appears that reduced drug susceptibility may be one factor for the frequent relapses of sleeping sickness after melarsoprol treatment occurring in Northwest Uganda. New Microbiol, 2001 Apr, 24(2), 193 - 6 Sensitivity of Borrelia and Leptospira to Quinupristin-dalfopristin (Synercid) in vitro; Murgia R et al.; In vitro activity of Quinupristin-dalfopristin (Synercid) against seventeen isolates of Borrelia burgdorferi and two representatives of Leptospira spp . was investigated . MICs ranged from 0.03 to 0.125 for B . burgdorferi and 0.125-0.25 microg/ml for Leptospires . Time killing studies carried out with 2 MIC demonstrated U 3 log(10)-unit killing after 72 h, showing a significant activity against spirochetes, though at a lower level than other antibiotics in use in the therapy of Lyme disease and leptospirosis. Planta Med, 2001 Apr, 67(3), 279 - 81 A new antimycobacterial, 3 beta-acetoxy-15 alpha,22-dihydroxyhopane, from the insect pathogenic fungus Aschersonia tubulata; Boonphong S et al.; Bioassay-guided fractionation of the cell extract of the insect pathogenic fungus Aschersonia tubulata BCC 1785 led to the isolation of dustanin (1), 3 beta,15 alpha,22-trihydroxyhopane (3), 5 alpha,8 alpha-epidioxy-24(R)-methylcholesta-6,22-diene-3 beta-ol (6), together with the new 3 beta-acetoxy-15 alpha,22-dihydroxyhopane (4) . Chemical structures of these compounds were elucidated by spectral analyses as well as chemical transformation . Compounds 1 and 4 exhibited antimycobacterial activity with the minimum inhibitory concentration (MIC) of 12.5 micrograms/ml. Clin Infect Dis, 2001 Jun 1, 32(11), 1554 - 61 Epub 2001 May 04. Oropharyngeal candidiasis in patients with human immunodeficiency virus: correlation of clinical outcome with in vitro resistance, serum azole levels, and immunosuppression; Walmsley S et al.; Azole-resistant thrush has emerged as a problem in people who are infected with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), especially those who have low CD4 cell counts who have had a previous relapse of oral candidiasis, and in those who require long-term suppressive antifungal therapy . Because of the development of a standardized methodology for antifungal susceptibility testing and interpretive criteria for resistance testing, studies of the clinical predictive value of in vitro results are possible . In this study, 61% of organisms isolated from patients who were receiving azole therapy and who had clinically resistant thrush had minimal inhibitory concentration values that would classify the isolate as "resistant" or "susceptible dose dependent." In contrast, 86% of isolates from patients with thrush that was clinically responsive to an azole were classified in vitro as "susceptible" or "susceptible dose dependent." No resistant isolates were detected in samples obtained from asymptomatic control patients who were not exposed to azole drugs . Serum levels of azole and CD4 cell counts were also important parameters with regard to prediction of response . We conclude that in vivo and in vitro correlations compare favorably to studies of susceptibility testing in bacteria. Diagn Microbiol Infect Dis, 2001 Mar, 39(3), 177 - 9 In vitro susceptibility of recent clinical isolates of Chlamydia trachomatis to macrolides and tetracyclines; Samra Z et al.; We tested the in vitro activity of clarithromycin, azithromycin, roxithromycin, erythromycin, doxycycline, and tetracycline against 50 clinical isolates of Chlamydia trachomatis . The minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) were determined in a tissue culture system using cycloheximide treated McCoy cells . MIC values for all the isolates were < or =0.015 microg/ml for clarithromycin, < or =0.125 microg/ml for roxithromycin and azithromycin, and < or =0.25 microg/ml for erythromycin and doxycycline . Almost half of the isolates (44%) were inhibited only by a concentration of 0.5 microg/ml of tetracycline . MBC as high as 4 microg/ml was displayed by doxycycline and tetracycline against 8% and 4% of the isolates respectively of the agents recommended by the Center for Disease Control as drugs of choice for the treatment of chlamydial infections, azithromycin exhibited a markedly better in-vitro activity than did erythromycin and doxycycline. J Clin Pathol, 2001 May, 54(5), 408 - 11 Role of screening agar plates for in vitro susceptibility testing of Helicobacter pylori in a routine laboratory setting; Warburton-Timms VJ et al.; BACKGROUND: Resistance of Helicobacter pylori to the more frequently used antibiotics (metronidazole and clarithromycin) reduces eradication rates even with triple treatment . Determining the antibiogram profile of H pylori can take up to 14 days and delays appropriate treatment . AIMS: To determine the role of screening agar plates for more rapid in vitro susceptibility of H pylori to metronidazole, amoxicillin, and clarithromycin . METHODS: Routine gastric biopsy specimens from 507 dyspeptic patients were inoculated on to 10% lysed blood agar plates containing metronidazole (8 microg/ml), clarithromycin (2 microg/ml), or amoxicillin (0.5 microg/ml) . The minimum inhibitory concentration (MIC) of the 90 isolates was determined using the E test . RESULTS: Metronidazole resistance was detected in 28 of 90 isolates by E test and nine of 98 by screening agar . The screening agar detected none of the four clarithromycin resistant isolates detected by the E test . CONCLUSIONS: The screening agar method is not sufficiently sensitive to be used alone. J Antimicrob Chemother, 2001 May, 47(5), 521 - 6 Comparison of Etest and a tablet diffusion test with the NCCLS broth microdilution method for fluconazole and amphotericin B susceptibility testing of Candida isolates; Arendrup M et al.; Three methods were compared for the susceptibility testing of yeast isolates to fluconazole and amphotericin B: two fagar diffusion methods (Etest and a tablet diffusion test) and the National Committee for Clinical Laboratory Standards (NCCLS) broth microdilution method . Given as MIC(50)s (range), fluconazole endpoints were: for the 24 h broth microdilution test, 0.25 mg/L (0.06-32 mg/L); for the Etest, 0.38 mg/L (0.064-24 mg/L); and for the NCCLS broth microdilution test, 2 mg/L (0.06->or=64 mg/L) . With breakpoints of <3 mg/L for susceptible and >16 mg/L for resistant, the Etest and the 24 h microdilution test classified the isolates in agreement with the classification obtained by the NCCLS method . Results obtained by Etest were in closer NCCLS method than those obtained with the tablet test . Amphotericin B endpoints were lower for the 24 h microdilution and Etests than MICs obtained by the NCCLS broth microdilution method . Reproducibility was high for all tests; however, disadvantages of both diffusion tests were microcolonies in the inhibition zone and dependence on stringent standardization of inoculum. Microbios, 2001, 104(409), 149 - 58 A simple classification method for residual antibiotics using E . coli cells transformed by the calcium chloride method and drug resistance plasmid DNA; Lin SY et al.; Using three different plasmid DNA codings for kanamycin (KM), chloramphenicol (CP), and ampicillin- (AMP) and tetracycline- (TC) resistance, four different competent Escherichia coli strains were transformed by the calcium chloride method to produce KM-, CP- and AMP- and TC-resistant strains . Evaluation of minimum inhibitory concentrations (MIC) of 22 antibiotics, showed KM-resistant E . coli to be cross resistant only to fradiomycin (FRM); CP-resistant E . coli, especially HB101 and JM109 strains, exhibited cross-resistance only to thiamphenicol (TP) . On the other hand, AMP- and TC-resistant E . coli showed cross resistance to several penicillins, tetracyclines and erythromycin . E . coli ATCC-27166, the strain most sensitive to all drugs in this experiment, was employed for disc diffusion experiments and from the pattern of appearance of the inhibition zone, eight major antibiotics were divided into three groups depending on their activity against containing each of the three plasmids . Only gentamicin (GM) activity was not affected by any of the drug resistant strains . Assay techniques utilizing three resistant strains may be the technique for screening foods for antibiotic residues in the future. Mol Cell Endocrinol, 2001 Apr 25, 175(1-2), 5 - 13 CCK expression in enteroendocrine cell is regulated by soluble factor(s) from underlying fibroblasts; Ratineau C et al.; Studies on the cross-talk between the intestinal epithelium and the underlying connective tissue have concentrated on enterocytes . In contrast, little is known about the interactions between the mesenchymal compartment and the enteroendocrine cells, scattered among the other cell types of the epithelium . To address this question, a panel of coculture systems between the enteroendocrine STC-1 cell line and three intestinal myofibroblastic cell lines (MIC) was used in order to assess different levels of regulation, namely cell-cell and cell-matrix interactions, and the role of diffusible factors . We demonstrate that the expression of cholecystokinin, a typical intestinal hormone produced by STC-1 cells, is up-regulated in the presence of a fibroblastic environment through a paracrine pathway involving FGF2 . Concomitantly, STC-1 cell morphology and proliferation were also modulated, but through distinct mechanisms according to the origin of fibroblasts . The results reveal definite epithelio-mesenchymal interactions that may be critical for the maintenance of phenotype and function of enteroendocrine cells. Clin Microbiol Infect, 2001 Mar, 7(3), 130 - 7 Isolation and in vitro susceptibility to amphotericin B, itraconazole and posaconazole of voriconazole-resistant laboratory isolates of Aspergillus fumigatus; Manavathu EK et al.; OBJECTIVES: To select voriconazole-resistant mutants of Aspergillus fumigatus in the laboratory from drug-susceptible clinical isolates and examine their in vitro susceptibility to amphotericin B and investigational azoles, and to compare the intramycelial accumulation of voriconazole in the resistant isolates with that in the susceptible parent . METHODS: Voriconazole-resistant Aspergillus fumigatus isolates were selected in the laboratory from three highly susceptible (MIC < or = 0.5 mg/L) clinical isolates by stepwise selection on peptone yeast extract glucose (PYG) agar containing 0.5 mg and 4 mg voriconazole/L . Twenty-three colonies that grew in the presence of 4 mg voriconazole/L on PYG agar (frequency 1.9 x 10(-8)) were tested for their in vitro susceptibility to amphotericin B, itraconazole, voriconazole and posaconazole by a broth macrodilution technique . The accumulation of voriconazole in the mycelia of two representative resistant isolates (VCZ-W42 and VCZ-W45) was determined by a previously described bioassay . RESULTS: The geometric mean MICs (mg/L) of amphotericin B, itraconazole, voriconazole and posaconazole for these isolates were 0.45 +/- 0.19, 0.69 +/- 0.45, 5.24 +/- 3.74 and 0.27 +/- 0.18, respectively . A comparison of the geometric mean MICs of the antifungals obtained for the resistant isolates to those of the susceptible parents showed 1.15-, 2.76-, 16.90- and 1.42-fold increases, respectively, for amphotericin B, itraconazole, voriconazole and posaconazole, suggesting that low-level cross-resistance exists between the azole antifungals . The susceptible parent and the resistant isolates accumulated similar amounts of voriconazole . CONCLUSIONS: These results suggest that spontaneous mutants of Aspergillus fumigatus resistant to voriconazole could emerge among clinical isolates under selection pressure and that the observed reduced in vitro susceptibility to voriconazole may not be due to reduced accumulation of the drug in the mycelia. Mycopathologia, 2001, 149(3), 117 - 21 Electrophoretic karyotyping and antifungal susceptibility patterns of Candida parapsilosis clinical isolates causing deep and superficial fungal infections; Barchiesi F et al.; Forty-six isolates of Candida parapsilosis, each from a single patient, were collected from July 1993 through March 1999 at the University of Ancona Hospitals and Clinics . Twenty-eight strains were isolated from superficial lesioned sites, including skin, nails and other sources while 18 strains were isolated from blood . The isolates were typed by electrophoretic karyotyping (EK) and tested for their susceptibility to fluconazole (FLC), itraconazole (ITC), flucytosine (5-FC), and amphotericin B (AMB) . Our data confirmed that EK is a useful technique for DNA typing of isolates of Candida parapsilosis and showed that the source of isolation is not associated with a given DNA type . Although strains belonging to this species of Candida are susceptible to the most common antifungals, including the triazoles, the degree of ITC susceptibility was dose dependent (MIC ranging from 0.25-0.5 microgram/ml) for 98% of the isolates. Mycopathologia, 2001, 149(3), 109 - 15 Penicillium marneffei: types and drug susceptibility; Imwidthaya P et al.; The PCR fingerprints of 30 Penicillium marneffei isolates from Chiang Rai in Northern Thailand and Bangkok in central Thailand were studied through use of single-nucleotide primers (GACA)4 and the phage M13 core sequence . Discrimination of fingerprint patterns was based on differences in the number of major bands . The P . marneffei isolates were divided into four types, i.e., A, B, C, and D . Type A was found in two isolates from Chiang Rai (6.7%) . Types B and C respectively were found in two (6.7%) and one (3.3%) isolates from Bangkok . The predominate type D (83.3%) was found in isolates obtained from Chiang Rai and Bangkok . The PCR fingerprinting method was found to be useful for the epidemiological study of P . marneffei, a dimorphic opportunistic fungus and an emerging pathogen in the HIV pandemic . In vitro drug susceptibility testing by broth macrodilution to four antifungal agents against the yeast form of P . marneffei was performed . The MIC ranges for amphotericin B, fluconazole, itraconazole, and ketoconazole were 0.125-0.5, 4.0-8.0, < 0.032, and < 0.125 microgram/ml respectively. Scand J Infect Dis, 2001, 33(3), 222 - 6 Pharmacokinetics of ceftazidime in febrile neutropenic patients; Nyhlen A et al.; Eight patients with fever and neutropenia were given 2 g of ceftazidime i.v . as a bolus injection over the course of 3 min . The pharmacokinetic variables for ceftazidime were similar to those found previously in febrile, acutely ill, non-neutropenic patients . The area under the plasma-concentration-time curve was significantly smaller, and the terminal half-life (t1/2lambda(z)) significantly shorter, compared with elderly, healthy subjects (p < 0.005) . Three patients survived long enough to be assayed after normalization of temperature and neutrophil counts . Glomerular filtration rates and clearances tended to be higher and the area under the curve and half-life lower on the day of fever and neutropenia . When considering our data in relation to known MIC values for common pathogens, ceftazidime administered intermittently every 6 h seems an appropriate regimen in patients with febrile neutropenia . Larger studies are needed to confirm this. Antimicrob Agents Chemother, 2001 May, 45(5), 1568 - 71 In vitro activity of clarithromycin against intracellular Helicobacter pylori; Piccolomini R et al.; The in vitro intracellular effect of clarithromycin, amoxicillin, metronidazole, lansoprazole, and rifabutin, tested at concentrations corresponding to one times the MIC, two times the MIC, and four times the MIC, was evaluated against an invasive Helicobacter pylori strain . At four times the MIC, clarithromycin showed an early bactericidal effect within 4 h of incubation and, in determining the complete killing within a 16 h-incubation period, lansoprazole and rifabutin showed comparable activity, yielding bactericidal activities within 4 and 8 h of incubation, respectively . Amoxicillin and metronidazole showed bacteriostatic activity only. Antimicrob Agents Chemother, 2001 May, 45(5), 1500 - 4 Accurate prediction of macrolide resistance in Helicobacter pylori by a PCR line probe assay for detection of mutations in the 23S rRNA gene: multicenter validation study; van Doorn LJ et al.; Helicobacter pylori strains from 299 patients were tested in six laboratories in different countries . Macrolide susceptibility of the strains was determined by agar dilution (17.4%) or the epsilometer test (82.6%) . Mutations in the 23S ribosomal DNA (rDNA) that are associated with macrolide resistance were analyzed by PCR and reverse hybridization (PCR-line probe assay {LiPA}) . This method identifies A2115G, G2141A, A2142G, A2142C, A2142T, A2143G, and A2143C mutations in the 23S rDNA . vacA s-region (s1a, s1b, s1c, and s2) and m-region (m1, m2a, and m2b) genotypes and cagA status were also determined using another PCR-LiPA system . Of the 299 strains investigated by MIC testing, 130 (43.5%) were resistant and 169 (56.5%) were susceptible to clarithromycin . Of the 130 resistant strains, 127 (97.7%) contained 23S rDNA mutations, whereas 167 (98.8%) of the 169 susceptible strains contained wild-type sequences . The predominant mutations were A2143G (45.2%) and A2142G (33.3%) . Twenty-eight (19.8%) strains contained multiple 23S rDNA mutations . Only five resistant strains contained the A2142C mutation (three of these in combination with the A2142G mutation), and the A2115G, G2141A, A2142T, and A2143C mutations were not found . MICs of clarithromycin for the A2142G mutant strains were significantly higher than MICs for the A2143G strains . Although there was no significant association between 23S rDNA mutations and the vacA and cagA status, clarithromycin-susceptible strains more often contained mixed vacA genotypes, indicating the presence of multiple H . pylori strains . In conclusion, our data confirmed the very strong association between 23S rDNA mutations and macrolide resistance and showed that the PCR-LiPA permits accurate and reliable diagnosis of macrolide resistance in H . pylori. Ann Pharmacother, 2001 Apr, 35(4), 409 - 13 Serum concentrations of cefuroxime after continuous infusion in coronary bypass graft patients; Pass SE et al.; OBJECTIVE: To describe the serum concentrations of continuous infusion of cefuroxime for postsurgical prophylaxis of sternal wound infection in patients undergoing coronary artery bypass graft (CABG), and to assess the incidence of sternal wound infection in this population . METHODS: This was a prospective, noncomparative trial involving 54 patients undergoing elective CABG surgery . All patients enrolled in the study received cefuroxime 1.5 g as a single intravenous dose 30 minutes preoperatively, followed by a continuous infusion of 3 g every 24 hours until removal of all central venous catheters . RESULTS: Of the 53 evaluable patients, the mean steady-state cefuroxime serum concentration was 21.6 +/- 14.2 microg/mL (range 6.56-59.5) . No patient developed a sternal wound infection . The mean treatment duration was 2.58 +/- 2.13 days (range 1-13) . The median hospital and intensive care unit lengths of stay were six days and 46 hours, respectively . The average antibiotic cost per day was $32.76 . CONCLUSIONS: These preliminary results of continuous infusion of cefuroxime 3 g/d for prophylaxis of sternal wound infections in CABG patients indicate that serum concentrations are highly variable, but reliably above the minimum inhibitory concentration for the common anticipated pathogens in this setting . Further comparative trials in a larger number of patients are necessary before this mode of administration can be routinely advocated for prophylaxis. Planta Med, 2001 Mar, 67(2), 161 - 3 In vitro anti-Helicobacter pylori activity of irisolidone isolated from the flowers and rhizomes of Pueraria thunbergiana; Bae EA et al.; The inhibitory effect of isoflavones isolated from the flowers and rhizomes of Pueraria thunbergiana (Leguminosae) on the growth of Helicobacter pylori (HP) was investigated . Isoflavone glycosides did not inhibit the growth of HP . However, their aglycones, irisolidone, tectorigenin and genistein, inhibited HP growth . Among them, irisolidone had the most potent inhibitory activity against HP and its MIC was 12.5-25 micrograms/ml . Genistein only weakly inhibited the urease of HP and H+/K(+)-ATPase of rat stomach: its IC50 were 0.43 and 0.89 mg/ml, respectively. J Ethnopharmacol, 2001 May, 75(2-3), 203 - 5 Anti-Helicobacter pylori activity of Aristolochia paucinervis Pomel extracts; Gadhi CA et al.; The anti-Helicobacter pylori effect of the extracts and the fractions obtained from Aristolochia paucinervis rhizome and leaves were studied against a reference strain of H . pylori by using the agar dilution method . Only the methanol extracts and the hexane fractions of either the rhizome or the leaves exhibited an inhibitory activity at a concentration of < or =128 microg/ml . The leaf hexane fraction APLH demonstrated a higher inhibitory activity (MIC: 4 microg/ml) than the rhizome hexane fraction APRH (MIC: 16 microg/ml), the leaf methanol extract APLM (MIC: 32 microg/ml) and the rhizome methanol extract APRM (MIC: 128 microg/ml) . This inhibitory activity was confirmed for the active extracts and fractions against clinical isolates of H . pylori (n = 20) for which MIC50) and MIC90 were determined. Chest, 2001 Apr, 119(4), 1001 - 10 Comparisons of peak diurnal expiratory flow variation, postbronchodilator FEV(1) responses, and methacholine inhalation challenges in the evaluation of suspected asthma; Goldstein MF et al.; STUDY OBJECTIVES: The validity of peak expiratory flow variation (PEFvar) as defined by National Heart, Lung, and Blood Institute (NHLBI) guidelines as a diagnostic tool for suspected asthma or its comparative value to methacholine inhalation challenge (MIC) or postbronchodilator (BD) FEV(1) responses has not been formally assessed . We prospectively analyzed the correlation of 28 different PEFvar indexes (including 4 NHLBI-compatible indexes) with MIC and pre-BD and post-BD FEV(1) responses in suspected asthmatic subjects with normal findings on lung examination, chest radiography, and baseline spirometry . DESIGN: Participants were asked to record peak expiratory flow four times daily for 2 to 3 weeks, followed by an MIC . During a minimum 6-month follow-up period, a clinical diagnosis of asthma was made or ruled out based on testing results and response to antiasthma therapy . SETTING: Medical school-affiliated subspecialty private practice of allergy, asthma, and immunology . PARTICIPANTS: One hundred twenty-one suspected asthmatic patients with normal findings on lung examination, chest radiography, and baseline spirometry . MEASUREMENTS AND RESULTS: Fifty-seven subjects completed both the peak flow diary and the MIC and were accepted for statistical analysis . There were no statistically significant correlations between any peak expiratory flow index and MIC . Among the three diagnostic tools evaluated, MIC had the highest sensitivity (85.71%) . All the PEFvar indexes and post-BD responses had low sensitivity and high false-negative rates . CONCLUSIONS: PEFvar and post-BD FEV(1) responses are poor substitutes for MIC in the assessment of patients with suspected asthma with normal findings on lung examination, chest radiography, and spirometry . Our findings warrant a reconsideration of the NHLBI guidelines recommendation of the utility of PEFvar as a diagnostic tool for asthma in clinical practice. Ther Drug Monit, 2001 Apr, 23(2), 93 - 9 Inhibition of thrombin by iopromide in vitro; Graf LL et al.; Iopromide is a nonionic, iodinated, monomeric, radiographic contrast agent used in various indications, including coronary angiography and visceral and peripheral arteriography . Nonionic contrast media have been postulated to increase thrombogenicity when compared with ionic contrast media . The goal of this study was to characterize the interaction of iopromide with thrombin, specifically to determine the rate, extent, specificity, and reversibility of the thrombin inhibition by iopromide, the integrity of the thrombin-iopromide complex, and the inhibitory potency of iopromide using a validated assay methodology . Iopromide was mixed with purified thrombin or pooled serum from healthy male and female donors . The final concentrations of iopromide in the presence of estimated physiologic concentrations of thrombin (1 nmol/L) were 0-184 mmol/L . After incubation for defined time intervals, the activity of thrombin was determined by adding substrate and measuring the absorbance of the generated chromophores at 405 nm . The possible inhibition of the protease trypsin by iopromide was investigated to evaluate the specificity of thrombin inhibition by iopromide . Iopromide was compared with Thromstop, a known thrombin inhibitor, to assess the relative potency of iopromide . The inhibition of thrombin by iopromide was immediate, rapidly reversible, and proportionate to the iopromide concentrations . The minimum inhibitory concentration of iopromide was 50 mmol/L . At the highest iopromide concentration tested, 184 mmol/L, the mean inhibition of thrombin activity was 44.5% . The mean concentration of iopromide associated with a 50% inhibition was 206 mmol/L . The inhibitory potency of iopromide was 4 x 10(6) times smaller than that of Thromstop . The inhibition of thrombin by iopromide is specific, because trypsin was not inhibited by iopromide . The results indicate that in vitro iopromide at clinically relevant concentrations partially inhibits thrombin activity . However, the in vitro model used does not consider other factors that may be relevant for the overall coagulation response in vivo. Mycoses, 2000, 43 Suppl 2, 45 - 50 {Antifungal susceptibility testing in chronically recurrent vaginal candidosis as basis for effective therapy}; Czaika V et al.; The chronically recidivist vulvo-vaginal candidiasis is one of the most stubborn problematic diagnosis in the dermatology and gynaecology ward . Prognosis and therapy are primarily determined by the causative micro-organism and the interaction of the fungal species with the currently available antifungal agents . Objective of the study was the investigation of vaginal yeast isolates from patients with chronically recidivist vaginal candidiasis against 8 antifungal agents with the aim of optimising the standard therapy with azole antifungal agents and assessment of alternative therapy schemes . 55 clinical isolates (Dermatology, Charite) of 40 patients were tested by microdilution according to DIN 58940-84 . Species differentiation and identification was performed by Fourier-Transform Infrared Spectroscopy (FTIR) . In the result Candida glabrata was the predominant causative agent for the recidivist vaginal candidiasis . MIC-mode values for C . glabrata were: fluconacole 32 micrograms/ml, itraconacole 1 microgram/ml, ketoconacole 1 microgram/ml, amphotericine B, voriconacole 0.03 microgram/ml, amphotericin B 0.5 microgram/ml, terbinafine 128 micrograms/ml, cicloproxolamine 4 micrograms/ml, 5-fluorocytosine 0.03 microgram/ml . Some strains of Patients with suboptimal introductory low doses of fluconacole showed increasing of MIC in course of therapy . Parallel resistance with itraconacole was observed in all these cases . Consecutively isolated strains could be clearly and reliably identified by FTIR . In conclusion of most importance is the initial dose adapatation of the drug used, e.g . for fluconacole 800/d p.o., when C . glabrata is the causative agent . Low dose fluconacole therapy is always unsuccessful in recurrent vaginal candidiasis and induces secondary resistance . Demonstrated high susceptibility of voriconacole, amphotericine B an 5-fluorocytosine particularly for C . glabrata may indicate of an anitmycotic therapy potential unconsidered regarding to dermatological indication up to now. J Med Microbiol, 2001 Apr, 50(4), 375 - 82 Susceptibility to fluconazole of Candida clinical isolates determined by FUN-1 staining with flow cytometry and epifluorescence microscopy; Pina-Vaz C et al.; The susceptibility of clinical Candida isolates to fluconazole was assayed by flow cytometry (FCM) and epifluorescence microscopy (EFM), with FUN-1 staining . In all, 25 clinical isolates of Candida spp . (12 sensitive, 3 dose-dependently sensitive and 10 resistant to fluconazole according to the NCCLS M27-A protocol) were treated with increasing concentrations of fluconazole during 1 or 2 h staining with FUN-1 for 30 min and analysed, respectively, by FCM at 575 nm (FL2) and by EFM . Fluconazole-susceptible strains showed an increased accumulation of FUN-1 in comparison with controls as determined by FCM and a reduced metabolic processing of the probe, confirmed by EFM . Conversely, resistant strains showed decreased FUN-1 staining and were able to process the probe . The fluconazole minimal inhibitory concentrations (MICs) determined by FCM or EFM after FUN-1 staining compared very well with the corresponding values determined by the M27-A protocol, indicating that FUN-1 staining can be used as an alternative to the conventional method . MIC values of resistant strains, with the exception of C . krusei, were lower when treatment with fluconazole followed pre-incubation with 0.1 mM sodium azide, a concentration known to inhibit the activity of efflux pumps . These results show that FUN-1 staining can be used as an alternative and rapid method for the assessment of susceptibility of Candida clinical isolates to fluconazole . Furthermore, the results suggest that resistance of Candida cells to fluconazole, with the exception of C . krusei strains, is likely to be due to the activity of efflux pumps. Diagn Cytopathol, 2001 Apr, 24(4), 233 - 9 Role of immunocytochemistry and DNA flow cytometry in the fine-needle aspiration diagnosis of malignant small round-cell tumors; Brahmi U et al.; In the present study, DNA flow cytometry (FCM) and immunocytochemistry (ICC) with a selected panel of antibodies were performed on 51 cases of malignant tumors which were referred for fine-needle aspiration biopsy (FNAB) to our Department of Cytology for the last 2 yr . Twelve cases were diagnosed as neuroblastoma, 16 as Ewing's sarcoma, 2 as retinoblastoma, 5 as non-Hodgkin's lymphoma (NHL), 5 as rhabdomyosarcoma, 2 as peripheral neuroectodermal tumors (PNETs), and 8 as Wilms' tumor . Eleven of 12 neuroblastomas were diploid by FCM, and 1 was aneuploid, with an S-phase fraction (SPF) of 8.3% . Neuron-specific enolase (NSE) was negative in 3 and positive in 8 cases of neuroblastoma, whereas neuroblastoma marker was positive in 3/11 . Sixteen of 17 Ewing's sarcomas were diploid, and 1 showed tetraploid aneuploidy, with an SPF of 10.06% . Eight of 13 Ewing's sarcomas were positive for Mic-2 gene product (Ewing's marker) . All 5 NHL were positive for leukocyte-common antigen (LCA) . Three of 5 rhabdomyosarcomas were diploid, and 2 cases showed aneuploidy . Rhabdomyosarcoma showed muscle-specific actin positivity in 4 and desmin positivity in 3 cases . All 3 cases of PNET were diploid and positive for the Mic-2 gene product, whereas NSE and vimentin were positive in 2 cases . Both cases of retinoblastoma were diploid . Immunostaining was noncontributory in 1 case, and the other showed positivity for the retinoblastoma gene product, NSE, and chromogranin . Seven of 8 Wilms' tumors were diploid, and 1 showed aneuploid, with an SPF of 11.13% . Seven of 8 Wilms' tumors were positive for cytokeratin (CK), 5 were positive for NSE, 6 were positive for epithelial membrane antigen (EMA), and 5 were positive for vimentin . FNAB diagnosis of malignant round-cell tumors is difficult only by light microscopy . Due to the availability of specific markers for subgrouping tumors, ICC has proved to be more useful these days, while DNA FCM has little diagnostic value, as most of them are diploid . Further ancillary studies, e.g., electron microscopy, image analysis, and other molecular investigations, are required to further categorize these tumors more precisely for better clinical management of these cases . Clin Microbiol Infect, 2001 Jan, 7(1), 11 - 6 In vitro activity of a new echinocandin, LY303366, and comparison with fluconazole, flucytosine and amphotericin B against Candida species; Moore CB et al.; OBJECTIVE: To investigate the in vitro activity of LY303366 (LY) against Candida isolates comprising nine different species and comparison with fluconazole (FLU), flucytosine (5FC) and amphotericin B (AMB) . METHODS: The method used was a microtitre modification of the NCCLS M27-A accepted standard using either RPMI-1640 with 2% glucose (5FC and FLU) or antibiotic medium 3 with 2% glucose (LY and AMB) . The minimum inhibitory concentration (MIC) was the lowest drug concentration that reduced growth by 80% compared with the drug-free control . Minimum fungicidal concentrations (MFCs; 99% kill) were also determined for all isolates for LY and AMB . RESULTS: Overall, 58 of 105 (55.2%) isolates were resistant to FLU (MIC < or = 16 mg/L) . There was no relationship between FLU and LY MICs for C . albicans or non-albicans species . For all isolates, geometric mean (GM) MIC values and ranges (in mg/L) were: LY 0.011 and < or = 0.001-16, FLU 8.72 and < or = 0.125- > 128, 5FC 0.393 and < or = 0.03- > 32, AMB 0.046 and 0.008-0.125 . Differences in susceptibility to LY were seen: C . parapsilosis (n = 12, GM 0.4 and range 0.125-16) and C . guilliermondii (n = 8, GM 0.46 and range 0.25-1) were both found to be significantly less susceptible to LY than all other species (P < or = 0.05) . For all isolates, geometric mean MFC values and ranges (in mg/L) were: LY 0.032 and 0.002-16, AMB 0.143 and 0.03-2 . The MFC value was the same as or only one drug dilution higher than the MIC value for 69.5% and 48.6% of isolates tested for LY and AMB, respectively . Tolerance was described in 13.3% and 5.7% of isolates for LY and AMB, respectively . A reproducibility study performed on 20% of the isolates showed that 90.5%, 100%, 95.2% and 100% of isolates retested were the same or within one well of the original MIC value for LY, FLU, 5FC and AMB, respectively . CONCLUSIONS: LY303366 shows promising antifungal activity in vitro and warrants further in vivo investigation. Int J Antimicrob Agents, 2001 Mar, 17(3), 229 - 31 In vitro activity of four fluoroquinolones against Mycobacterium tuberculosis; Rodriguez JC et al.; The in vitro activity of ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin against strains of Mycobacterium tuberculosis was studied . Moxifloxacin and levofloxacin showed the greatest activity having an MIC(90) of 1 mg/l . The MIC(90) for ofloxacin was 2 mg/l and for ciprofloxacin 4 mg/l . Further studies should be made to determine the role played by these compounds in the treatment of tuberculosis. Int J Antimicrob Agents, 2001 Mar, 17(3), 203 - 8 In vitro activity of mezlocillin, meropenem, aztreonam, vancomycin, teicoplanin, ribostamycin and fusidic acid against Borrelia burgdorferi; Hunfeld KP et al.; The in vitro susceptibility profile of Borrelia burgdorferi is not yet well defined for several antibiotics . Our study explored the in vitro susceptibility of B . burgdorferi to mezlocillin, meropenem, aztreonam, vancomycin, teicoplanin, ribostamycin and fusidic acid . Minimal inhibitory concentrations (MICs) and minimal borreliacidal concentrations (MBCs) were measured using a standardised colorimetric microdilution method and conventional subculture experiments . MIC values were lowest for mezlocillin (MIC(90), < or =0.06 mg/l) and meropenem (MIC(90), 0.33 mg/l) . Vancomycin (MIC(90), 0.83 mg/l) was less effective in vitro . Borreliae proved to be resistant to aztreonam (MIC(90), >32 mg/l), teicoplanin (MIC(90), 6.6 mg/l), ribostamycin (MIC(90), 32 mg/l), and fusidic acid (MIC(90), >4 mg/l) . The mean MBCs resulting in 100% killing of the final inoculum after 72 h of incubation were lowest for mezlocillin (MBC, 0.83 mg/l) . This study gathered further data on the in vitro susceptibility patterns of the B . burgdorferi complex . The excellent in vitro effectiveness of acylamino-penicillin derivatives and their suitability for the therapy of Lyme disease is emphasised. J Biol Chem, 2001 May 18, 276(20), 16911 - 8 Epub 2001 Feb 26. The propeptide of the transforming growth factor-beta superfamily member, macrophage inhibitory cytokine-1 (MIC-1), is a multifunctional domain that can facilitate protein folding and secretion; Fairlie WD et al.; Macrophage inhibitory cytokine-1 (MIC-1) is a divergent member of the transforming growth factor-beta (TGF-beta) superfamily . While it is synthesized in a pre-pro form, it is unique among superfamily members because it does not require its propeptide for correct folding or secretion of the mature peptide . To investigate factors that enable these propeptide independent events to occur, we constructed MIC-1/TGF-beta1 chimeras, both with and without a propeptide . All chimeras without a propeptide secreted less efficiently compared with the corresponding constructs with propeptide . Folding and secretion were most affected after replacement of the predicted major alpha-helix in the mature protein, residues 56-68 . Exchanging the human propeptide in this chimera with either the murine MIC-1 or TGF-beta1 propeptide resulted in secretion of the unprocessed, monomeric chimera, suggesting a specific interaction between the human MIC-1 propeptide and mature peptide . Propeptide deletion mutants enabled identification of a region between residues 56 and 78, which is important for the interaction between the propeptide and the mature peptide . Cotransfection experiments demonstrated that the propeptide must be in cis with the mature peptide for this phenomenon to occur . These results suggest a model for TGF-beta superfamily protein folding. Zhongguo Yao Li Xue Bao, 1999 Nov, 20(11), 1031 - 4 Antimycoplasmal activities of (S)-(-)-9-fluoro-2,3-dihydro-3-methyl-10 -{4-(2-pyridyl)-1-piperazinyl}-7-oxo-7H-pyrido{1,2,3-de}{1,4}benzoxazine -6-carboxylic acid (YH-6) in comparison with other antibiotics in vitro; Ye H et al.; AIM: To determine the susceptibilities of Mycoplasma and Ureaplasma to (S)-(-)-9-fluoro-2,3-dihydro-3-methyl-10 -{4-(2-pyridyl)-1-piperazinyl}-7-oxo-7H-pyrido{1,2,3-de}{1,4}benzoxazine -6-carboxylic acid (YH-6) and to compare it with those referential quinolones, macrolides, and tetracyclines . METHODS: The minimum inhibitory concentration (MIC) were determined by microdilution method in vitro . RESULTS: The MIC of YH-6 for Ureaplasma urealyticum (Uu: 250 micrograms.L-1), Mycoplasma hominis (Mh: 500 micrograms.L-1), M orale (Mo: 125 micrograms.L-1) and M salivarium (Ms: 125 micrograms.L-1) were closely similar to those of macrolides (erythromycin and leucomycin) and were 2-8 folds greater than those of ofloxacin (Ofl) . Uu and Mh easily induced resistance to erythromycin and tetracycline . They did not easily form resistance to quinolone (YH-6, Ofl), josamycin and tylosin . Tetracycline-resistance (Tcr) or erythromycin-resistance (EMr) strains of Uu (or Mh) had cross-resistance to erythromycin or tetracycline . However, they had no cross-resistance to quinolone, josamycin and tylosin . CONCLUSION: YH-6 was a highly active quinolone against Mycoplasma, but could hardly induce resistance to Uu . EMr- or Tcr- strains of Uu (or Mh) had no cross-resistance to YH-6. Med Mycol, 2001 Feb, 39(1), 91 - 5 Synergistic interaction of terbinafine with triazoles or amphotericin B against Aspergillus species; Ryder NS et al.; The in vitro activity of terbinafine alone and in combination with other antifungal agents was tested against isolates of Aspergillus fumigatus, A . flavus and A . niger . Testing was performed in a modified National Committee for Clinical Laboratory Standards (NCCLS) macrodilution broth assay, and interactions were examined using a checkerboard design . Terbinafine was highly active against Aspergillus isolates (minimum inhibitory concentration {MIC} 0.01 to 2 microg ml(-1)) with a primary fungicidal action (minimum fungicidal concentration {MFC} 0.02 to 4 microg ml(-1)) . Amphotericin B was also highly active and cidal as expected (MIC 1 microg ml(-1), MFC 1 to 4 microg ml(-1)) . The triazoles itraconazole and voriconazole were highly active but showed a variable degree of cidal activity against the different strains, voriconazole having the more potent cidal activity . Fluconazole had no significant activity (MIC > 128 microg ml(-1)) . Drug combinations were tested in the A . fumigatus and A . niger strains . Terbinafine and amphotericin showed an additive to synergistic interaction depending on the isolate . Combinations of terbinafine with itraconazole or voriconazole displayed a potent synergistic interaction and fungicidal activity against all isolates . Surprisingly, fluconazole also potentiated the activity of terbinafine in an additive to synergistic fashion, despite its lack of activity alone . The results suggest potential clinical application of terbinafine in aspergillosis, either alone or in combination with amphotericin or triazoles. Med Mycol, 2001 Feb, 39(1), 129 - 33 Effect of sub-MICs of antimycotics on expression of intracellular esterase of Trichophyton rubrum; Fachin AL et al.; The electrophoretic pattern of the intracellular esterase of the dermatophyte Trichophyton rubrum was altered when this fungus was grown in the presence of subinhibitory concentrations of the antimycotics tioconazole or griseofulvin . All strains (original isolate and antimycotic resistant mutants) presented five clearly visible bands when cultivated on medium containing below-minimum inhibitory concentrations (sub-MICs) of tioconazole or griseofulvin, and only two clearly visible bands when cultivated in medium without antimycotics . No extra bands were detected in the electrophoretic patterns of the extracellular esterase of these fungi (mutants or the original isolate) when cultivated with or without tioconazole or griseofulvin (sub-MIC values) . These results suggest that additional forms of esterase are produced inside the cell and may be a nonspecific response to cellular stress, or may participate in cellular detoxification processes in the presence of these antimycotics. Salud Publica Mex, 2001 Jan-Feb, 43(1), 27 - 31 {Prevalence of Moraxella catarrhalis colonization in asymptomatic carriers under 6 years of age}; Leanos-Miranda B et al.; OBJECTIVE: To determine the prevalence of upper respiratory tract colonization by Moraxella catarrhalis in children under six years of age . MATERIAL AND METHODS: A survey was conducted between January and December 1998 in Mexico City, among children aged 2 months to 5 years, selected through cluster sampling . Pharyngeal samples were taken for M . catarrhalis identification . The minimal inhibitory concentration to different antibiotics was obtained and beta-lactamases were determined by the iodometric test . Statistical analysis consisted of frequency distributions, odds ratios, 95% confidence intervals, and Mantel-Haenszel chi 2 . Statistical significance was set at p < 0.05 . RESULTS: After excluding 37 children, the study population was 604 children from Mexico City; M . catarrhalis was present in 130 pharyngeal specimens (22.9%) . Most of the strains were positive for beta-lactamase production (75.4%) . Eighty percent of the strains was resistant to penicillin and 70% to ampicillin and amoxicillin . None were resistant to cefotaxime, imipenem, meropenem and erythromycin . CONCLUSIONS: Prevalence of M . catarrhalis upper respiratory tract colonization is similar to that of other respiratory pathogens . These findings warrant future research on the role of M . catarrhalis as an etiologic agent in acute and chronic respiratory infections in Mexico. Pathol Biol (Paris), 2001 Feb, 49(1), 53 - 6 {In vitro inhibition of Chlamydia trachomatis growth by liposome-encapsulated cyclines}; Sangare L et al.; The antichlamydial activity of tetracycline (Tet) and doxycycline (Dox) encapsulated in cationic (CaL), anionic (AnL) and neutral (NtL) liposomes has been evaluated in vitro by adding serial dilutions of antibiotics (minimum inhibitory concentration, MIC: 0.12-0.007 microgram/ml; MBC: 4 to 0.25 micrograms/ml) to HeLa 229 cell monolayers inoculated with Chlamydia trachomatis L2/434/Bu (10(3) ufi/ml) . Following 72 h incubation at 37 degrees C under a 5% CO2 atmosphere, the chlamydial inclusions were stained by the May-Giemsa method to determine the MICs . After a second and third passage, the MBC1 and MBC2 were determined in antibiotic-free medium . The chlamydial inclusions were then counted to assess the degree of growth inhibition at each antibiotic dilution tested for MBC1 and MBC2 determinations . The MIC, MBC1 and MBC2 of the various antichlamydial agents were as follows: Tet (0.12; 4; 4), AnL-Tet (0.01; 1; 1), NtL-Tet (0.03; 1; 2), Dox (0.06; 1; 2), CaL-Dox (0.03; 0.5; 2), AnL-Dox (0.01; 1; 2), and NtL-Dox (0.03; 0.5; 0.5) . It was found that Tet and Dox liposome-encapsulated antibiotics were more active than their non-encapsulated counterparts, and the inclusion count showed a higher inhibitory activity of the former antibiotics on chlamydial growth . The inhibition of chlamydial growth by AnL-Tet may be of bactericidal nature . In conclusion, liposome-encapsulated drugs could be of value in the treatment of chlamydial infections. Zhonghua Jie He He Hu Xi Za Zhi, 1998 Mar, 21(3), 174 - 7 {Relationship between catalase activity, KatG gene and isoniazid-resistance in M . tuberculosis}; Wang X et al.; OBJECTIVE: To investigate the relationship between catalase activity, KatG gene, gene mutation and INH-resistance in M . tuberculosis . METHOD: Catalase activities in 58 M . tuberculosis isolates were tested, and KatG gene mutations were detected further by PCR-SSCP . RESULT: None of INH-sensitive isolates lacked KatG sequences and all expressed catalase . 8(25%) INH-resistant isolates did not express catalase and 3(10%) lacked KatG gene, most of which were strains of high levels of resistance (MIC > 50 micrograms/ml) . 8 INH-resistant isolates were analyzed further by PCR-SSCP and all were found to have KatG gene mutation . CONCLUSION: These findings indicated that lacking of catalase activity and KatG gene deletion occurred mainly in those highly INH-resistant strains, gene mutation other than complete deletion of KatG gene may be the major mechanism of INH-resistance. Antimicrob Agents Chemother, 2001 Apr, 45(4), 1143 - 50 In vitro activity of a novel antimycobacterial compound, N-octanesulfonylacetamide, and its effects on lipid and mycolic acid synthesis; Parrish NM et al.; beta-Sulfonyl carboxamides have been proposed to serve as transition-state analogues of the beta-ketoacyl synthase reaction involved in fatty acid elongation . We tested the efficacy of N-octanesulfonylacetamide (OSA) as an inhibitor of fatty acid and mycolic acid biosynthesis in mycobacteria . Using the BACTEC radiometric growth system, we observed that OSA inhibits the growth of several species of slow-growing mycobacteria, including Mycobacterium tuberculosis (H37Rv and clinical isolates), the Mycobacterium avium complex (MAC), Mycobacterium bovis BCG, Mycobacterium kansasii, and others . Nearly all species and strains tested, including isoniazid and multidrug resistant isolates of M . tuberculosis, were susceptible to OSA, with MICs ranging from 6.25 to 12.5 microg/ml . Only three clinical isolates of M . tuberculosis (CSU93, OT2724, and 401296), MAC, and Mycobacterium paratuberculosis required an OSA MIC higher than 25.0 microg/ml . Rapid-growing mycobacterial species, such as Mycobacterium smegmatis, Mycobacterium fortuitum, and others, were not susceptible at concentrations of up to 100 microg/ml . A 2-dimensional thin-layer chromatography system showed that OSA treatment resulted in a significant decrease in all species of mycolic acids present in BCG . In contrast, mycolic acids in M . smegmatis were relatively unaffected following exposure to OSA . Other lipids, including polar and nonpolar extractable classes, were unchanged following exposure to OSA in both BCG and M . smegmatis . Transmission electron microscopy of OSA-treated BCG cells revealed a disruption in cell wall synthesis and incomplete septum formation . Our results indicate that OSA inhibits the growth of several species of mycobacteria, including both isoniazid-resistant and multidrug resistant strains of M . tuberculosis . This inhibition may be the result of OSA-mediated effects on mycolic acid synthesis in slow-growing mycobacteria or inhibition via an undescribed mechanism . Our results indicate that OSA may serve as a promising lead compound for future antituberculous drug development. J Assoc Physicians India, 1995 Mar, 43(3), 167 - 9, 172 Efficacy of standard ten millicurie dose of radio-iodine in management of autonomously functioning toxic thyroid nodules; Sharma R et al.; Therapeutic effect of radio-iodine treatment on thyroid patients with autonomously functioning toxic thyroid nodule was evaluated . Fifty one patients were given a standard dose of 10 mci of radioiodine (I-131) and were followed up for 2-3 years . The failure rate (relapse after 10 mci of radioiodine) of this regime was 10% . It was found that the nodules less than or equal to 3 cms . in size were completely cured after a dose of 10 mic . of radio-iodine therapy, over a follow up period of next 6 months . Patients having nodules larger than 3 cms . relapsed after first dose of 10 mci of radio-iodine, but were cured completely after the second dose of 10 mci of radio-iodine therapy . Tri-iodothyronine (T3) and thyroxine (T4) values were both found to be high before giving treatment in all the cases . Only one case developed hypothyroidism after radioiodine therapy. Saudi Med J, 2001 Jan, 22(1), 53 - 7 Antibiotic susceptibilities of Helicobacter pylori; Bindayna KM; OBJECTIVE: The aim of this study was to evaluate the prevalence of resistance among 83 Helicobacter pylori isolates cultured from biopsies taken during routine endoscopies in 1998-1999 . METHODS: Minimum Inhibitory Concentration of amoxicillin, tetracycline, clarithromycin and metronidazole were determined by Epsilometer test . RESULTS: Forty-seven strains (57%) were resistant to metronidazole, and 27 (32.5%) were resistant to clarithromycin . Twenty of the 27 strains resistant to clarithromycin were also resistant to metronidazole . None of the strains were resistant to amoxicillin or tetracycline . CONCLUSION: A high percentage of patients from Bahrain were infected with resistant strains of Helicobacter pylori . Antibiotic resistance monitoring is very important and unified national treatment policies are needed. J Environ Monit, 2000 Oct, 2(5), 462 - 9 Airborne thermal degradation products of polyurethene coatings in car repair shops; Karlsson D et al.; A methodology for workplace air monitoring of aromatic and aliphatic, mono- and polyisocyanates by derivatisation with di-n-butylamine (DBA) is presented . Air sampling was performed using midget impinger flasks containing 10 ml of 0.01 mol l(-1) DBA in toluene and a glass-fibre filter in series after the impinger flask, thereby providing the possibility of collecting and derivatising isocyanates in both the gas and particle phases . Quantification was made by LC-MS, monitoring the molecular ions {MH}+ . Air samples taken with this method in car repair shops showed that many different isocyanates are formed during thermal decomposition of polyurethane (PUR) coatings . In addition to isocyanates such as hexamethylene (HDI), isophorone (IPDI), toluene (TDI) and methylenediphenyl diisocyanate (MDI), monoisocyanates such as methyl (MIC), ethyl (EIC), propyl (PIC), butyl (BIC) and phenyl isocyanate (PhI) were found . In many air samples the aliphatic monoisocyanates dominated . During cutting and welding operations, the highest levels of isocyanates were observed . In a single air sample from a welding operation in a car repair shop, the highest concentrations found were: MIC, 290; EIC, 60; PIC, 20; BIC, 9; PhI, 27; HDI, 105; IPDI, 39; MDI, 4; and 2,4-TDI and 2,6-TDI 140 microg m(-3) . Monitoring the particle size distribution and concentration during grinding, welding and cutting operations showed that ultrafine particles (< 0.1 microm) were formed at high concentrations . Isocyanates with low volatility were mainly found in the particle phase, but isocyanates with a relatively high volatility such as TDI, were found in both the particle and gas phases. Int J Pharm, 2001 Mar 14, 215(1-2), 101 - 11 Gel-forming erodible inserts for ocular controlled delivery of ofloxacin; Di Colo G et al.; A new application of high molecular weight (400 kDa) linear poly(ethylene oxide) (PEO) in gel-forming erodible inserts for ocular controlled delivery of ofloxacin (OFX) has been tested in vitro and in vivo . Inserts of 6 mm diameter, 20 mg weight, medicated with 0.3 mg OFX, were prepared by powder compression . The in vitro drug release from inserts was mainly controlled by insert erosion . The erosion time scale was varied by compounding PEO with Eudragit L100 (EUD) 17% neutralized (EUDNa17) or 71% neutralized (EUDNa71) . The insert erosion rate depended on the strength of interpolymer interactions in the compounds, and on the hydrophilic-hydrophobic balance of compounds . Immediately after application in the lower conjunctival sac of the rabbit eyes, the inserts based on plain PEO, PEO-EUDNa17 or PEO-EUDNa71 formed mucoadhesive gels, well tolerated by the animals; then the gels spread over the corneal surface and eroded . The gel residence time in the precorneal area was in the order PEO-EUDNa71 < PEO < PEO-EUDNa17 . Compared to commercial OFX eyedrops, drug absorption into the aqueous humor was retarded by the PEO-EUDNa71 inserts, and both retarded and prolonged by the PEO-EUDNa17 inserts, while C(max) (maximal concentration in the aqueous) and AUC(eff) (AUC in the aqueous for concentrations > MIC) were barely altered by either insert type . On the other hand, C(max), AUC(eff) and t(eff) (permanence time in the aqueous at concentrations > MIC) were strikingly increased by plain PEO inserts with respect to commercial eyedrops (5.25 +/- 0.56 vs . 1.39 +/- 0.05 microg ml(-1); 693.6 vs . 62.7 microg ml(-1) min; and 290 vs . 148 min, respectively) . Bioavailability increase has been ascribed to PEO mucoadhesion and/or increased tear fluid viscosity. Hum Immunol, 2001 Mar, 62(3), 279 - 85 Sequence analysis of the MHC class I region reveals the basis of the genomic matching technique; Gaudieri S et al.; The genomic matching technique (GMT) improves survival following bone marrow transplantation (BMT) between unrelated donor and recipient pairs correlating with a decrease in incidence and severity of graft-versus-host disease (GvHD) . The principles of this technique are based on the duplication and polymorphic characteristics of the major histocompatibility complex (MHC) . Specifically, the beta block GMT matches for a 300 kb region that contains the human leukocyte antigen (HLA-B and -C) genes as well as other non-HLA genes such as the natural killer cell receptor ligand PERB11 (MIC) . The block contains two large segmental duplications . One results in two PERB11 genes (11.1 and 11.2), the other in two class I genes (HLA-B and -C) . With the complete sequencing of the class I region of the MHC in different haplotypes, we can now show that the beta block GMT profiles reflect amplification of the duplicated PERB11 segments and not the duplicated segments containing HLA-B and -C, and yet provide a signature that characterizes the entire block rather than individual loci. Yao Xue Xue Bao, 1997, 32(1), 15 - 8 {Effect of berberine on intracellular free CA2+ concentration in cultured brain cells}; Wu JF et al.; Intracellular free calcium concentration ({Ca2+}i) was measured with Ca(2+)-sensitive fluorescent indicator, Fura-2/AM, in cultured brain cells using AR-CM-MIC cation measurement system, and the effects of berberine (Ber) on the changes in {Ca2+}i induced by CaCl2, norepinephrine, KCl and H2O2 were studied . The results indicate that the resting {Ca2+}i was 35 +/- 8 nmol.L-1 in Ca(2+)-free Hank's solution . Ber showed no effect on the resting {Ca2+}i when the extracellular Ca2+ were 0.01-10 mmol.L-1 . Ber 1-100 mumol.L-1 dose-dependently inhibited norepinephrine and H2O2 induced {Ca2+}i elevation . Ber at high concentration (10-100 mumol.L-1) inhibited K(+)-induced {Ca2+}i elevation . This suggests that the inhibitory effects of Ber on norepinephrine, K(+)-, and H2O2-induced {Ca2+}i elevation may be one of the mechanisms against cerebral ischemia. Immunity, 2001 Feb, 14(2), 123 - 33 ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor; Cosman D et al.; The human cytomegalovirus glycoprotein, UL16, binds to two members of a novel family of molecules, the ULBPs, and to the MHC class I homolog, MICB . The ULBPs are GPI-linked glycoproteins belonging to the extended MHC class I family but are only distantly related to MICB . The ULBP and MICB molecules are ligands for the activating receptor, NKG2D/DAP10, and this interaction is blocked by a soluble form of UL16 . The ULBPs stimulate cytokine and chemokine production from NK cells, and expression of ULBPs in NK cell-resistant target cells confers susceptibility to NK cell cytotoxicity . Masking of NK cell recognition of ULBP or MIC antigens by UL16 provides a potential mechanism by which human cytomegalovirus-infected cells might evade attack by the immune system. Zhonghua Zhong Liu Za Zhi, 2000 Nov, 22(6), 480 - 2 {Apoptosis and uterine cervical carcinogenesis}; Yao J et al.; OBJECTIVE: To investigate the possible role of apoptosis in the development of uterine cervical carcinoma . METHODS: Formalin-fixed, paraffin-embedded samples from 190 patients {41 patients with severe dysplasia (SD); 37 with carcinoma in situ(CIS); 31 with microinvasive carcinoma (MIC), 40 with fran invasive large cell non-keratinizing epidermoid carcinoma (IC)}, and 41 samples from normal cervical squamous epithelium (NE) were studied . The number of apoptotic cells was assessed in situ by the TDT-mediated dUTP-biotin nick end labeling (TUNEL) method . PCNA, p53 and bcl-2 were demonstrated immunohistochemically . RESULTS: (1) In NE, TUNEL-positive cells were found in the superficial layer and PCNA-positive cells were confined in the lamina profunda, while in cervical neoplasia these cells were irregulasly scattered throughout the cervical lesions . (2) The TUNEL staining index decreased while PCNA increased with progression of the neoplasm, showing a significant negative correlation between apoptosis and proliferation . (3) In patients with SD and CIS who had overexpression of p53 and bcl-2 proteins, the cells positively stained by TUNEL were significantly less in number than in these with negative p53 and bcl-2 expression . No such observation for PCNA expression . CONCLUSION: These results suggest that apoptosis is associated with the early process of cervical carcinogenesis and apoptosis is closely correlated with overexpression of p53 and bcl-2 proteins. J Chemother, 2001 Feb, 13(1), 24 - 33 Comparison of five different methods for detection of SHV extended-spectrum beta-lactamases; Bedenic B et al.; Five different methods for detection of different types of SHV extended-spectrum beta-lactamases (ESBL) were compared: minimum inhibitory concentration (MIC) determination of beta-lactam with and without clavulanic acid, double-disk synergy test (DDST), inhibitor potentiated disk diffusion test (IPDDT), three-dimensional test (TDT) and PCR/Nhe I test . MIC determination of beta-lactam with and without clavulanic acid was the most sensitive method regardless of the type of beta-lactamase . However the specificity of this method was a little above 90% . IPDDT turned out to be a very sensitive method too but it lacks specificity because 26.9% of ceftazidime sensitive strains (putative ESBL negative), gave a positive result . It is important to put all four disks on the plate because ceftazidime and aztreonam were more sensitive indicators for SHV-5 and SHV-12 beta-lactamase producers while cefotaxime and ceftriaxone were more reliable in detecting SHV-2 beta-lactamase producers . The DDST detected all SHV-5 and SHV-12 beta-lactamase producers and 95.2% of SHV-2, so it was less sensitive than MIC determination but was highly specific, since there were no false negative results observed . The sensitivity of DDST can be improved by using all four disks and placing them at the smaller distance from the central disk (2.5 cm) . The TDT was the least sensitive method, particularly for SHV-5 and SHV-12 beta-lactamase producers . The PCR/Nhe I test for detection of ESBL blaSHV genes is a highly sensitive and specific method but it is rather laborious and thus not very practical for use in routine clinical laboratories . Nevertheless it has potential to serve as the gold standard in epidemiological investigations on ESBLs . According to the results of this investigation MIC determination of beta-lactam with and without clavulanic acid, even if only one antibiotic is used and the PCR/Nhe I tests are the most reliable methods for detection of SHV ESBLs. Eur J Med Chem, 2001 Jan, 36(1), 75 - 80 Synthesis and mycological activity of the compounds obtained in the reaction of N(3)-substituted amidrazones with sulphinyl-bis-2,4-dihydroxybenzenethioyl; Modzelewska-Banachiewicz B et al.; 2-Phenyl-5-(2,4-dihydroxybenzene)-1,3,4-thiadiazole (4), 2-(2-pyridyl)-2,4-dihydroxybenzene-1,3,4-thiadiazole (5), N(1)-2,4-dihydroxybenzenecarbothio-N(3)-phenyl-benzamidrazone (6) and N(1)-2,4-dihydroxybenzenecarbothio-N(3)-phenyl-2-picoline-amidrazone (7) were prepared and tested for their antimycotic activity . The chemical structures were confirmed by IR, 1H-NMR, EI-MS and elemental analysis . The minimal inhibitory concentration (MIC) values against dermatophytes, yeasts and moulds were determined for the estimation of potential activity in vitro . The strongest fungistatic activity for compound 5 in relation to dermatophytes was found with MIC 0.48-0.99 microg mL(-1). Can J Vet Res, 2001 Jan, 65(1), 64 - 7 Pharmacokinetics of enrofloxacin after intravenous and intramuscular administration in Angora goats; Elmas M et al.; Pharmacokinetics and bioavailability of enrofloxacin were determined after single intravenous (IV) and intramuscular (IM) administrations of 5 mg/kg body weight (BW) to 5 healthy adult Angora goats . Plasma enrofloxacin concentrations were measured by high performance liquid chromatography . Pharmacokinetics were best described by a 2-compartment open model . The elimination half-life and volume of distribution after IV and IM administrations were similar (t1/2beta, 4.0 to 4.7 h and Vd(ss),1.2 to 1.5 L/kg, respectively) . Enrofloxacin was rapidly (t1/2a, 0.25 h) and almost completely absorbed (F, 90%) after IM administration . Mean plasma concentrations of enrofloxacin at 24 h after IV and IM administration (0.07 and 0.09 microg/mL, respectively) were higher than the minimal inhibitory concentration (MIC) values for most pathogens . In conclusion, once-daily IV and IM administration of enrofloxacin (5 mg/kg BW) in Angora goats may be useful in treatment of infectious diseases caused by sensitive pathogens. Berl Munch Tierarztl Wochenschr, 2001 Jan-Feb, 114(1-2), 57 - 60 {Pharmacokinetics of kanamycin after subcutaneous and intravenous administration in dogs}; Calvo Wieland A et al.; Six beagle dogs were treated with kanamycin subcutaneously or intravenously in a dosage of 5 mg/kg . The plasma kanamycin concentration was measured over 24 hours by high pressure liquid chromatography with UV detection after derivatization and solid phase extraction . After subcutaneous application, kanamycin was absorbed quickly, and maximum plasma levels of 18.9 micrograms/ml in average after ca . 1 hour were measured . With complete systemic availability, the minimal inhibitory concentration of 4 micrograms/ml was maintained for 4 hours . After subcutaneous administration, kanamycin was terminally eliminated with a mean half life period of 2 hours. Nat Immunol, 2001 Mar, 2(3), 255 - 60 Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC induced on virus-infected cells; Groh V et al.; NKG2D is an activating receptor that stimulates innate immune responses by natural killer cells upon engagement by MIC ligands, which are induced by cellular stress . Because NKG2D is also present on most CD8alphabeta T cells, it may modulate antigen-specific T cell responses, depending on whether MIC molecules--distant homologs of major histocompatibility complex (MHC) class I with no function in antigen presentation--are induced on the surface of pathogen-infected cells.We found that infection by cytomegalovirus (CMV) resulted in substantial increases in MIC on cultured fibroblast and endothelial cells and was associated with induced MIC expression in interstitial pneumonia . MIC engagement of NKG2D potently augmented T cell antigen receptor (TCR)-dependent cytolytic and cytokine responses by CMV-specific CD28- CD8alphabeta T cells . This function overcame viral interference with MHC class I antigen presentation . Combined triggering of TCR-CD3 complexes and NKG2D induced interleukin 2 production and T cell proliferation.Thus NKG2D functioned as a costimulatory receptor that can substitute for CD28. Ann Pathol, 2001 Feb, 21(1), 76 - 80 {Congenital fetal neuroblastoma}; Rivasi F et al.; Neuroblastoma are pediatric tumors of neural crest origin, most often localized in adrenal glands and infrequently congenital . We report two fetal cases found at autopsy, performed at 24 and 28 weeks of gestation, respectively . The 24 week old fetus did not show any malformation; systematic histological analysis found neuroblastoma cells in both the adrenal glands and the retroperitoneal fat tissue . The 28 week old fetus was hydropic and exhibited a nodule (3 cm) in the posterior mediastinum, next to the thoracic spinal cord . This tumor responded to a neuroblastoma associated with small metastatic foci in the adrenal glands, the liver and the frontal brain cortex . The placenta was abnormally heavy and showed hemorrhagic and necrotic areas . Microscopically plugged clumps of neuroblastoma cells were found inside fetal vessels . Immunohistochemistry was employed in both cases and the cells showed immunoreactivity for NSE, NB 84, chromogranin, synaptophysin and neurofilaments, while desmin, MIC 2, and protein S-100 were negative . Congenital neuroblastomas are rare and, to our knowledge this is the thirteenth report of congenital neuroblastoma associated with placental metastasis. J Antimicrob Chemother, 2001 Mar, 47(3), 341 - 3 Characterization of high-level fluoroquinolone resistance in Escherichia coli O78:K80 isolated from turkeys; Giraud E et al.; Fluoroquinolone resistance was characterized in Escherichia coli O78:K80 isolated from diseased turkeys . The level of resistance to fluoroquinolones of the isolates appeared closely correlated with substitutions in GyrA and ParC, but not with the production of the AcrAB efflux pump . Among isolates highly resistant to ciprofloxacin (MIC 8 mg/L) and harbouring identical substitutions (two in GyrA and one in ParC), two close but distinguishable ribotypes were identified . This indicated that at least two independent selection events may have occurred. Drugs, 2001, 61(1), 9 - 18 The role of fluoroquinolones in tuberculosis today; Berning SE; Tuberculosis is a growing international health concern; it is the leading infectious cause of death in the world today . The fluoroquinolones are the most recent class of drugs offering hope in the fight against this disease . Ciprofloxacin, ofloxacin, levofloxacin and sparfloxacin are currently the most commonly used agents used against Mycobacterium tuberculosis (TB), with in vitro minimum inhibitory concentrations (MICs) of 0.1 to 4 mcg/ml . Resistance in TB to fluoroquinolones may occur spontaneously or may be acquired, especially when these agents are used inappropriately . Cross-resistance among the fluoroquinolones has been shown in TB . The fluoroquinolones offer a favourable pharmacokinetic profile for the treatment of TB . Most demonstrate excellent oral bioavailability and achieve maximum (peak) serum concentrations well above the MIC . They are also distributed widely, including intracellularly . The fluoroquinolones are cleared renally and/or hepatically, with varying serum half-lives . Fluoroquinolones are most effective when the peak concentration (Cmax) to MIC ratio is maximised . Fluoroquinolones such as ciprofloxacin and ofloxacin have been used in regimens for the prevention of TB, but have been poorly tolerated when used in combination with pyrazinamide . Favourable responses with fluoroquinolones in regimens used in the treatment of clinical TB disease have been seen . They, however, are not to be considered as equal replacements for isoniazid or rifampicin (rifampin) and should be used with at least 2 other antituberculous agents . Therapeutic drug monitoring of fluoroquinolones is beneficial in assuring that maximum Cmax to MIC ratios are being achieved, especially in patients at risk for malabsorption, such as those infected with HIV . Higher, once-daily doses of most fluoroquinolones are becoming more common in treating TB . Fluoroquinolones are generally well tolerated with long term use in treating TB, but rare, serious adverse effects have been reported with general fluoroquinolone use . The most common drug interactions with fluoroquinolones in TB therapy include the malabsorption interactions associated with multivalent cations and cytochrome P450 interactions with ciprofloxacin . An increased risk of central nervous system effects with concomitant cycloserine has been reported and seen clinically . When using fluoroquinolones to treat TB, careful consideration of individual susceptibility patterns, pharmacokinetic and toxicity profiles should be taken . The aid of a TB expert may also be warranted . The exact role of the fluoroquinolones in treating TB remains to be determined. Dig Liver Dis, 2000 Dec, 32(9), 763 - 8 Prevalence of Helicobacter pylori resistance to antibiotics in Northeast Italy: a multicentre study . GISU . Interdisciplinary Group for the Study of Ulcer; Pilotto A et al.; AIMS: To evaluate prevalence of primary Helicobacter pylori antibiotic resistances in Northeast Italy and to identify risk factors associated with this resistance . MATERIALS AND METHODS: A total of 248 patients undergoing upper gastrointestinal endoscopy were enrolled from 19 Endoscopy Units over a 6-month period . From each patient, 4 gastric biopsies were taken for histology and 2 were sent to the Central Referral Microbiological Laboratory for culture and determination of antibiotic activity against Helicobacter pylori by means of E-test . Strains were considered resistant when minimum inhibitory concentration was >8 microg/ml for metronidazole and >1 microg/ml for clarithromycin . No cut-off value was predefined for amoxycillin . RESULTS: Culture of Helicobacter pylori was successfully performed in 167 patients . Primary resistance to metronidazole, clarithromycin or amoxycillin was 14.9%, 1.8% and 0%, respectively Patients infected with Helicobacter pylori strains resistant to antibiotics were more frequently females than males (70.3% vs 41.4%), had a significantly lower coffee intake (66.6% vs 86.6%) and lower body mass index (23.7+/-2.6 vs 25.3+/-3.6) than patients with susceptible Helicobacter pylori strains . Age, smoking, alcohol use, family history of Helicobacter pylori infection, concomitant diseases and treatments, endoscopic diagnoses, Helicobacter pylori density and histological activity of chronic gastritis were not associated with antibiotic resistance . Multivariate analysis confirmed that female gender (odds ratio = 2.74, 95% confidence interval = 1.03-7.27) was the only significant risk factor associated with antibiotic resistance . CONCLUSIONS: In this population, primary Helicobacter pylori resistance to metronidazole was higher than resistance to clarithromycin, and female gender was significantly associated with this resistance . The low prevalence of resistance to metronidazole, clarithromycin and amoxycillin identified in this geographical area suggests that proton pump inhibitor-based triple regimens including these antibiotics may still be used as first line therapies against Helicobacter pylori infection. Eur J Surg, 2001 Jan, 167(1), 46 - 9 Trimethoprim-sulphamethoxazole and metronidazole as prophylaxis in colorectal surgery: a study of bioavailability after an oral single dose; Raab Y et al.; OBJECTIVE: To evaluate oral single dose prophylaxis in colorectal surgery . DESIGN: Prospective study . SETTING: University hospital, Sweden . SUBJECTS: 24 patients (13 women; 11 men; mean age 57 years, range 27-81) listed for elective colorectal operations . INTERVENTION: At 0630 on the day of the operation all patients were given an oral dose of trimethoprim-sulphamethoxazole (TMP 160 mg and SMZ 800 mg) and metronidazole (2 g) . The serum concentrations of TMP and SMZ were analysed in venous samples taken at the start and end of each operation . RESULTS: The earliest operation started at 0830 and the last finished at 1700 . The median (range) serum concentrations of TMP were 1.4 (0.7-2.6) mg/L (start) and 1.3 (1.0-2.8) mg/L (end), and of SMZ 35 (15-65) mg/L (start) and 33 mg (13-70) mg/L (end) . The individual values were above or equal to the minimal inhibitory concentration (TMP 0.8 mg/L; SMZ 15.2 mg/L) for relevant gram-negative species . CONCLUSION: Oral TMP/SMZ in the morning gives satisfactory serum concentrations independently of when the operation is done during the day . The regimen is simple and has the potential for being an effective alternative to intravenous prophylaxis. Bioorg Med Chem Lett, 2001 Feb 12, 11(3), 301 - 3 Antimycobacterial in vitro activity of cobalt(II) isonicotinoylhydrazone complexes . Part 10; Bottari B et al.; Octahedral cobalt(II) complexes of isonicotinoylhydrazones, which were obtained from the primary antituberculous agent isoniazid, have been synthesised and characterised . Their antimycobacterial in vitro activity has been evaluated against Mycobacterium tuberculosis H37Rv: they exhibit MIC values ranging from < 0.1 to 0.39 microg/mL, showing them to be generally more active than previously reported analogous Cu(II) and Ni(II) complexes. J Neural Transm Suppl, 2000, (60), 273 - 6 GDF-15/MIC-1 a novel member of the TGF-beta superfamily; Strelau J et al.; We have cloned, expressed, and raised antibodies against a novel member of the TGF-beta superfamily, growth/differentiation factor-15 (GDF-15) . The predicted protein is identical to macrophage inhibitory cytokine-1 (MIC-1), which was discovered simultaneously . GDF-15 is a more distant member of the TGF-beta superfamily and does not belong to one of the known TGF-beta subfamilies . In the CNS, GDF-15/MIC-1 mRNA is abundantly expressed by the choroid plexus . In addition we have preliminary evidence that GDF-15/MIC-1 is a potent trophic factor for selected classes of neurons in vitro and in vivo . Thus, GDF-15 is a novel neurotrophic factor with prospects for the treatment of disorders of the CNS. Scand J Infect Dis, 2000, 32(6), 669 - 73 Influence of pH and concentration on the postantifungal effect and on the effects of sub-MIC concentrations of 4 antifungal agents on previously treated Candida spp; Garcia MT et al.; This study investigates the impact of different pH values (5.5 and 7.4) on the postantifungal effect (PAFE) and the effect of sub-MIC concentrations (1/4 x MIC) on C . albicans and C . glabrata in the PAFE stage (PAFSE) . The PAFE stage was induced by a 1.5 h pretreatment with different doses (1, 4 and 8 x MIC) of 4 antifungal agents . An increase in the pH and/or an increase in the dose of the antimycotic prolonged the duration of the PAFE induced by amphotericin B or 5-fluorocytosine and the PAFSE induced by all 4 antifungal agents in both species . 5-Fluorocytosine and amphotericin B (except for treatment with 1 x MIC at pH 5.5) induced significant PAFEs (0.5-3.0 h and 1.4-4.8 h, respectively), which were increased (to 0.9-3.2 h and 0.8-3.4 h, respectively) by posterior (PLEASE EXPLAIN WHAT YOU MEAN BY THE WORD "POSTERIOR" HERE) exposure to 1/4 X MIC of the respective antifungal agent . Although ketoconazole and fluconazole were not able to induce significant PAFEs, posterior exposure to 1/4 x MIC of each of these 2 azoles led to significant PAFSEs of up to 2.6 h in both yeast species when the concentrations and pH were high enough. Ophthalmic Surg Lasers, 2001 Jan-Feb, 32(1), 25 - 9 Ocular penetration of cefepime following systemic administration in humans; Ozdamar A et al.; OBJECTIVE: To investigate the penetration of cefepime (a fourth generation cephalosporin) into the aqueous humor after single-dose intravenous administration in humans . PATIENTS AND METHODS: Before receiving cataract surgery, 30 patients received randomly 1 g (group 1, 15 patients) and 2 g (group 2, 15 patients) single intravenous injection of cefepime before surgery . Samples of aqueous humor and serum were obtained at 0.5, 1, 2, 4, and 12 hours after injection . Three patients were sampled each time for 1 g and 2 g of cefepime . Samples were assayed for cefepime concentrations with high performance liquid chromatography (HPLC) . RESULTS: All the patients had detectable cefepime in their aqueous humor and serum measurable by HPLC . A mean peak aqueous humor level was 5.16 +/- 0.88 microg/mL in group 1 and 5.87 +/- 1.64 microg/mL in group 2 at 0.5 hour after injection . The mean level of cefepime in aqueous humor decreased after 0.5-hour measurements in both groups and was measured as 0.82 +/- 0.21 microg/mL in group 1 and 2.04 +/- 0.30 microg/mL in group 2 at 12 hours after injection . CONCLUSION: Aqueous humor levels of cefepime after single IV injection were above the minimum inhibitory concentration (MIC90) for most ocular pathogens, but the duration of exposure to an antibiotic was not sufficient for therapeutic effect. Acta Paediatr Suppl, 2000 Dec, 89(435), 35 - 9 Epidemiology of pneumococcal infections in Swedish children; Eriksson M et al.; OBJECTIVE: This paper provides an overview of pneumococcal infections in Swedish children . METHOD: Data supplied by the Swedish Institute for Infectious Disease Control (SMI) provided information on invasive pneumococcal isolates and on isolates with reduced susceptibility to penicillin . Disease burden was estimated from data collected in northern Stockholm and Malmohus County . Results: Only 3-6% of the total number of invasive pneumococcal isolates came from children 0-15 years of age . Predominant serotypes in descending frequency were 7, 6, 14, and 23 . Strains from all sources with reduced sensitivity to penicillin (MIC > or = 0.5 mg/l) were found in 3% of children and varied between 0.2% and 11%, with the highest value found in Southern Sweden (predominating strains were 9, 19, 15, 6, and 23) . A 10-year review of all cases of meningitis in Northern Stockholm reflected an incidence of 10/100,000 (0-2 years) or 5.8/100,000 (0-5 years), with severe sequelae occurring in 20% of children . This information can be used to predict an annual incidence of 30 cases of meningitis in Sweden . CONCLUSION: The large proportion of serotype 7 among invasive isolates is distressing since this serotype is not represented in the present 7- and 9-valent protein-conjugated vaccines under development . However, the heptavalent vaccine, including serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F would (at a serotype level) provide coverage against 83% of the resistant isolates in Southern Sweden. Analyst, 2000 Nov, 125(11), 1949 - 54 Determination of airborne methyl isocyanate as dibutylamine or 1-(2-methoxyphenyl)piperazine derivatives by liquid and gas chromatography; Henriks-Eckerman ML et al.; The usefulness of a glass fibre filter method to collect airborne methyl isocyanate (MIC) was studied in laboratory experiments and in a workplace during manufacture of mineral wool insulation material . Filter collection was based on derivatisation in situ with 1-(2-methoxyphenyl)piperazine (2MP) . 2MP impinger sampling was also evaluated in the workplace . Impinger sampling with dibutylamine (DBA) was used as an independent method . The samples were analysed by liquid and gas chromatography using various detection techniques: mass spectrometry, ultraviolet and electrochemical detection (LC-MS, LC-UV, LC-EchD and GC-MS) . The sampling efficiency of 2MP filters for MIC varied with the origin of the glass fibre filter . Two Whatman filters (diameter 25 mm) with altogether 21 mumol of 2MP collected 100% of 9.8 micrograms of MIC during 30 min at an airflow rate of 1 l min-1 . The workplace measurements were performed at two concentration levels, 0.003 and 0.09 mg m-3 . The theoretical amounts of derivatisation reagent were 42 mumol (2MP filter), 52 mumol (2MP impinger) and 100 mumol (DBA) . MIC concentrations were 20% lower by the 2MP methods compared with the DBA method (statistically significant difference) . Breakthrough was 6% for the DBA method and 9% for the 2MP impinger method . To trap both MIC and isocyanic acid, which was also present in the workplace samples, a tenfold molar amount of 2MP reagent was used . The precision of sample preparation, expressed as relative standard deviation, was 3.5% (0.17 microgram ml-1, n = 6) . The precision of sampling in the workplace was 15% (0.002 mg m-3, n = 6) . The limit of quantification was 0.0006 mg m-3 for 30 l of air by the 2MP impinger method and 0.03-0.05 mg m-3 by the 2MP filter method . Hence, airborne MIC can be determined using 2MP as derivatisation reagent . Impinger sampling is preferable when low concentration levels are expected. Zhonghua Kou Qiang Yi Xue Za Zhi, 1997 Nov, 32(6), 369 - 71 {Bianticollagen membrane: preparation and analysis of properties}; Li C et al.; This study was undertaken to assess the antiplaque and anticollagenase properties of bianticollagen membrane (BACM) for use in the guided tissue regeneration (GTR) . First, preparing cross-linked collagen membrane (GLCM) from bone collagen by glutaraldehyde and ultraviolet irradiation . Then, the GLCM was coated with tetracycline (TC) delivery device, which is BACM . BACM's properties are as follows: under scan electron microscope (SEM), it is a three dimensional structure with small pores; the modulus of elasticity in low strain regions and swelling ratio are 20.4 g/mm2 and 0.141 respectively; immediate type and delayed type hypersensitivity are negative; BACM with TC 150 micrograms placed into pockets, the average intrasulcular TC concentration measured at the end of the 7-days is 46.76 +/- 5.69 micromol/L, which is 2 times higher than MIC of TC; the period against collagenase (100 u) digestion is over 30 days in vitro; 1 mg GLCM and BACM implanted in mice may maintain about 4 weeks and 7 weeks respectively, and BACM and GLCM placed onto patient's root surface in flap operation and taken at 7th day the bacteria on BACM are significantly less than that on GLCM under SEM . These results indicate that BACM has antiplaque and stronger antidegradation effects than GLCM. Can J Gastroenterol, 2000 Nov, 14(10), 891 - 4 Pathophysiology of antibiotic resistance: clarithromycin; Taylor DE; Resistance of Helicobacter pylori to antibiotics ranges from 3% to 10% and may exceed these levels in some countries . The pathophysiology of clarithromycin resistance is reviewed, including the mode of action by which the antibiotic inhibits protein synthesis and the mechanism of resistance, which involves a mutation at position 2142 or 2143 in the V loop domain of the 23SrRNA genes . Mutations of A2142G confer a higher minimum inhibitory concentration than mutations of A2143G . The former demonstrate cross-resistance to macrolide, lincosamide and streptogramin antibiotics, whereas the latter are susceptible to streptogramin B . In vitro mutagenesis combined with natural transformation were used to create several types of clarithromycin-resistant mutants . H pylori strains with A2142G and A2143G mutations had a higher growth rate than those with A2142C, A2143 or A2142T mutations . Data from this study indicate why clarithromycin-resistant clinical isolates of H pylori are more likely to have A2142G or A2143G mutations and only occassionally A2142C mutations. Int J Antimicrob Agents, 2000 Sep, 16(1), 69 - 71 Comparative in vitro activity of phenothiazines against multidrug-resistant Mycobacterium tuberculosis; Bettencourt MV et al.; The comparative activity of five phenothiazines against multidrug-resistant strains of Mycobacterium tuberculosis (MDRTB) was studied using the Bactec 460 system . The order of antimycobacterial activity of the phenothiazines was: chlorpromazine = thioridazine > promethazine > promazine = desipramine . However, the levels required for an MIC 50 exceeded 1 mg/l and are beyond those that are clinically achievable . As phenothiazines are concentrated by macrophages that phagocytose and have in situ activity against mycobacteria, these agents may be considered for use as adjuvants for the management of freshly diagnosed tuberculosis in patients from populations with a high prevalence of MDRTB. Antimicrob Agents Chemother, 2001 Mar, 45(3), 764 - 7 Activities of linezolid against rapidly growing mycobacteria; Wallace RJ Jr et al.; Linezolid is an oxazolidinone available as an oral drug which has activity against most gram-positive bacteria . However, few species of the genus Mycobacterium have been studied . We tested 249 clinical isolates and 10 reference strains of rapidly growing mycobacteria for susceptibility to linezolid by broth microdilution . Clinical species included the Mycobacterium fortuitum group (n = 74), M . abscessus (n = 98), M . chelonae (n = 50), M . mucogenicum (n = 10), and M . fortuitum third biovariant complex (10) . The modal MIC for M . mucogenicum was 1.0 microg/ml, and the MIC at which 90% of the isolates tested are inhibited (MIC(90)) was 4 microg/ml; the modal MIC for the M . fortuitum group was 4 microg/ml, and the MIC(90) was 16 microg/ml; the modal MIC for the M . fortuitum third biovariant complex was 4 microg/ml, and the MIC(90) was 8 microg/ml; the modal MIC for M . chelonae was 8 microg/ml, and the MIC(90) was 16 microg/ml; and the modal MIC for M . abscessus was 32 microg/ml, and the MIC(90) was 64 microg/ml . Based on peak levels of linezolid in serum of 15 to 20 microg/ml, we propose the following broth MIC breakpoints for these species: susceptible, < or = 8 microg/ml; moderately susceptible, 16 microg/ml; and resistant, > or =32 microg/ml) . These studies demonstrate the excellent potential of linezolid for therapy of rapidly growing mycobacteria. Phytother Res, 2001 Feb, 15(1), 79 - 81 Antidermatophytic properties of extracts from the leaves of Aristolochia paucinervis Pomel; Gadhi CA et al.; Several fractions of a methanol extract from the leaves of Aristolochia paucinervis Pomel (Aristolochiaceae) were screened for their antidermatophytic efficiency against different human pathogenic fungi responsible for tinea and other skin infections . The antifungal study was carried out by the macrodilution agar method and the results showed that, with the exception of the aqueous fraction, all the fractions exhibited antifungal activities against the dermatophytic fungi tested . The hexane fraction was found to be the most effective (MIC range: 64-2048 microg/mL), whereas the butanol fraction was the least active (MIC range: 1024 microg/mL to more than 2048 microg/mL) . The most susceptible fungi were Epidermophyton floccosum and Trichophyton violaceum in contrast to Trichophyton mentagrophytes and Trychophyton rubrum which were less sensitive to the fractions tested . The effects were compared with those of ketoconazole, amphotericin B and griseofulvin, for which MIC ranges were, respectively, 0.12-4 microg/mL, 0.5-4 microg/mL and 0.5-2 microg/mL . Int J Infect Dis, 2000, 4(3), 118 - 22 Lincomycin-induced endotoxin release in Escherichia coli sepsis: evidence for release in vitro and in vivo; Horii T et al.; OBJECTIVE: To evaluate the propensity of lincomycin and clindamycin to induce release of endotoxin, the authors investigated endotoxin release in Escherichia coli isolated from a patient who developed septic shock following lincomycin treatment . METHODS: Endotoxin release from the E . coli isolate exposed to lincomycin, clindamycin, and ceftazidime were determined in vitro and in vivo . RESULTS: In vitro, this E . coli released significantly larger amounts of endotoxin after exposure for 6 hours to lincomycin or clindamycin versus no antibiotic; however, endotoxin release with these antibiotics was significantly less than with ceftazidime . There was no significant difference in in vitro endotoxin release between small (8 mg/L) and large (0.5 minimum inhibitory concentration {MIC}) doses of these antibiotics, and 0.5 MICs of lincomycin and clindamycin were 1024 and 256 mg/L, respectively . These results were supported by scanning electron microscopic observations, which demonstrated that lincomycin, clindamycin, and ceftazidime induced formation of filamentous cells . In addition, plasma endotoxin concentrations after treatment for 4 hours with lincomycin, clindamycin, and ceftazidime (5 mg/kg) were at least 20-fold higher than with no antibiotic in an E . coli sepsis rat model . CONCLUSION: Results of this study suggest that the bacteriostatic antibiotics, lincomycin and clindamycin, induce endotoxin release in the treatment of E . coli infections. Curr Infect Dis Rep, 2001 Feb, 3(1), 29 - 34 Influence of Pharmacokinetic and Pharmacodynamic Principles on Antibiotic Selection; Zhanel GG; When evaluating the efficacy of antibiotics for the treatment of respiratory tract infections, such as community acquired pneumonia and acute exacerbations of chronic bronchitis, assessment of clinical cure may not be the most relevant parameter, as it may not be related to microbiological eradication or to the minimum inhibitory concentration (MIC) of the infecting pathogen . It is more relevant to study the efficacy of the antibiotic in eradicating the bacterial pathogen, because this is frequently related to both the MIC of the pathogen and the antibiotic dosage regimen . Pharmacodynamics correlates the concentration of antibiotic in the blood or at the infection site with its biological effect against the organism (bacteriological eradication) . For beta-lactams, the pharmacodynamic parameter that best correlates with eradication is time (T) above MIC (T > MIC); for aminoglycosides and fluoroquinolones, it is the area under the curve at 24 hours (AUC(24))-to-MIC ratio (AUC(24)/MIC) . Knowledge of pharmacodynamics allows optimum use of antibiotics; in vitro models, animal models, and retrospective and prospective clinical trials have shown that the use of such knowledge optimizes bacteriological eradication and enhances patient outcome . In the future, pharmacodynamic studies will be used not only to assess optimal ways for antibiotics to eradicate resistant pathogens, but also to investigate the ability of antibiotics to prevent the development of resistance on therapy and to eradicate pathogens from colonizing sites. Eur J Dermatol, 2001 Jan-Feb, 11(1), 58 - 62 Recalcitrant trichophytic granuloma associated with NK-cell deficiency in a SLE patient treated with corticosteroid; Akiba H et al.; Although deep trichophytic infection often occurs in immunocompromised patients, the immune deficiency in such patients has not been clarified . A 28-year-old man who suffered from recalcitrant trichophytic granuloma and tinea universalis during treatment for SLE with corticosteroid is described here to define the immunological abnormalities . In addition to routine immunological tests, we evaluated the patient's innate and specific immune functions to dermatophytes, including T cell, natural killer (NK) cell and neutrophil functions and activation of the complement cascade . We measured the minimum inhibitory concentration (MIC) of itraconazole for the isolated fungus and its concentrations in the patient's serum and pus . Trichophyton (T.) rubrum was constantly isolated from the exudates of the patient's skin lesions, although the concentrations of itraconazole in his serum (198 ng/ml) and lesions (210 ng/ml) were sufficient to inhibit the growth of the isolated fungus in vitro . Specific cell-mediated immune responses, determined by T cell stimulation and IFN-gamma production, were evoked following stimulation with trichophytic antigens . The patient's innate immunity, assessed by activation of the complement cascade and neutrophil-mediated phagocytosis, was not impaired . The number of circulating NK cells was markedly decreased (0.2% of the peripheral blood mononuclear cells), and was associated with low NK cell activity against K-562 cells even though lymphopenia had improved . The deficiency of innate immunity mediated by NK cells might be responsible for a part of the persistence of trichophytic granuloma in our case . Dermatophytes usually affect the horny layer of the skin and do not invade the living layers because the host immune system uses various mechanisms to eliminate the fungi . Both specific T cell-mediated immunity and nonspecific immunological mechanisms provide host defense against fungal infections . An adaptive immune response is usually preceded by innate immune responses mediated by neutrophils, NK cells, and circulating proteins such as complement components and anti-microbial peptides . However, in patients with localized or systemic immunological defects, granulomatous cutaneous infection of dermatophytes mostly caused by trichophytic fungi may occur {1} . Trichophytic granuloma includes Majocchi's granuloma {2} and disseminated trichophytic granuloma {3} . Recently, we experienced a patient with trichophytic granuloma and tinea universalis caused by Trichophyton (T.) rubrum infection during treatment with corticosteroid for systemic lupus erythematosus (SLE) . We describe the clinical details of this patient, focusing on his immunological defects which led to the persistence of the fungal infection. Chemotherapy, 2001 Mar-Apr, 47(2), 123 - 7 Experimental in vitro efficacy study on the interaction of epiroprim plus isoniazid against Mycobacterium tuberculosis; Dosso M et al.; Thirty Mycobacterium tuberculosis strains (8: INH(R)/INH(R), 12: INH(R)/RIF(S), 10: INH(S)/RIF(S)) were examined against MICs of epiroprim (EPM) and isoniazid (INH) separately or in association . EPM alone proved to be insufficiently active against the various mycobacterial isolates (MIC > or =256 microg/ml) . The observed average sensitivity to the association of EPM plus INH was, in contrast, considerably increased, as reflected by reduced MICs and lower percentages of resistant strains . MICs ranged between 16 and 32 microg/ml EPM and 2 and 4 microg/ml INH for INH(R) strains . All INH(S) isolates were inhibited by a concentration of 0.125 microg/ml EPM and 0.06 microg/ml INH . The fractional inhibitory concentration indices indicated an additive activity on INH(R)/RIF(R) strains and a synergistic activity on INH(R)/RIF(S) and INH(S)/RIF(S) strains . The synergistic activity of this drug association needs to be confirmed in an animal model . J Nat Prod, 2001 Jan, 64(1), 37 - 41 Antitubercular activity of triterpenoids from Lippia turbinata; Wachter GA et al.; Assay-guided fractionation of the antitubercular MeOH-CH(2)Cl(2) extract obtained from Lippia turbinata led to the isolation of four novel triterpenoids-3beta,25-epoxy-3alpha,21alpha-dihydroxy-22beta-(3-methylbut-2-en-1-oyloxy)olean-12-ene-28-oic acid (1); 3beta,25-epoxy-3alpha,21alpha-dihydroxy-22beta-angeloyloxyolean-12-ene-28-oic acid (2); 3beta,25-epoxy-3alpha,21alpha-dihydroxy-22beta-tigloyloxyolean-12-ene-28-oic acid (3); and 3beta,25-epoxy-3alpha-hydroxy-22beta-(2-methylbutan-1-oyloxy)olean-12-ene-28-oic acid (4)-together with the known triterpenoids lantanilic acid (5), camaric acid (6), lantanolic acid (7), and rehmannic acid (8) . The MIC values of 1-8 for growth inhibition of Mycobacterium tuberculosis were determined in the radiorespirometric BACTEC system. Tissue Antigens, 2001 Jan, 57(1), 55 - 65 Sequence of the swine major histocompatibility complex region containing all non-classical class I genes; Chardon P et al.; A segment of 158,063 nucleotides of the pig major histocompatibility complex (SLA) and corresponding to the junction of the class I and class III regions was sequenced entirely . The centromeric part of the segment contained six class III genes including the three tumor necrosis factor genes, while the telomeric part contained three genes belonging to the class I region . The order and the molecular organization of these genes were exactly conserved in the SLA and HLA complexes, except for the SC1 gene which displayed a shift of the reading frame in swine . The cluster of the three SLA class I-related genes (Ib) and the MIC1 and MIC2 genes were located in the middle of the segment, in the following order from the centromeric side onwards, SLA-6, SLA-7, SLA-8, MIC-1 and MIC-2 . All three SLA Ib genes displayed an overall molecular structure compatible with the expression of membrane-anchored glycoproteins . The SLA-7 and SLA-8 genes bear greater resemblance than to the SLA-6 gene . Six SLA-6 alleles have been previously defined differing each from the other by unique point mutations . One of them, appeared to have arisen through the occurrence of a gene conversion event in which the SLA-7 gene served as template . Only MIC-2 gene might be functional, the second MIC-1 gene being truncated . In all, the 14 genes characterized spans 37% of the total sequence . The remaining 63% nucleotides comprised a number of repeat DNA motives, including LINE fragments, SINEs, microsatellites, and also numerous nucleotide stretches not yet defined in swine. J Vet Pharmacol Ther, 2000 Dec, 23(6), 373 - 8 Administration of ticarcillin in combination with clavulanic acid intravenously and intrauterinely to clinically normal oestrous mares; Van Camp SD et al.; Ticarcillin and clavulanic acid (potassium clavulanate) were administered to normal oestrous mares intravenously (i.v.) at a dose of 50 and 1.67 mg/kg for ticarcillin and clavulanate, respectively . In a crossover design, the same drugs were administered intrauterine (i.u.) at a dose of 12.4 and 0.4 mg/kg for ticarcillin and clavulanate, respectively . The i.u . dose was administered in 100 mL of saline solution . Endometrial tissue biopsies and plasma samples were collected after drug administration for the determination of ticarcillin and clavulanate concentrations by high-pressure liquid chromatography and pharmacokinetic calculations . After i.u . administration both drugs were poorly absorbed into the plasma . The ticarcillin half-life from tissue and plasma was short after i.v . administration . Although concentrations in tissue were higher after i.u . administr