Analyst, 1998 Jul, 123(7), 1507 - 12 Determination of complex mixtures of airborne isocyanates and amines . Part 5 . Determination of low molecular weight aliphatic isocyanates as dibutylamine derivatives; Karlsson D et al.; A method is presented for the determination of low molecular weight aliphatic isocyanates, methyl isocyanate (MIC), ethyl isocyanate (EIC), propyl isocyanate (PIC) and butyl isocyanate (BIC), as their dibutylamine (DBA) derivatives . The method is based on sampling in midget impinger flasks containing 10 ml of 0.01 mol l-1 DBA in toluene (as in Parts 1-4 in this series) . The samples are analysed using liquid chromatography-electrospray mass spectrometry (LC-ESP-MS) or gas chromatography-mass spectrometry using chemical ionisation with ammonia, monitoring positive ions (GC-PCI) . Quantification was effected by monitoring the molecular ions MH+ . Aliquots of 10 ml of toluene solutions containing 0.01 mol l-1 DBA were spiked with 0.03-0.85 microgram of MIC-, EIC-, PIC- and BIC-DBA . The correlation coefficients for LC-ESP-MS were in the range 0.9952-0.9999 (n = 14) . The repeatability (RSD) was in the range 0.37-1.2% (0.12-0.34 microgram ml-1, n = 10) . The instrumental detection limit for MIC was about 15 micrograms l-1, which corresponds to about 0.5 microgram m-3 in a 15 l air sample . The correlation coefficients for GC-PCI were in the range 0.9913-0.9990 . The repeatability (RSD) was in the range 1.1-4.9% (0.12-0.34 microgram ml-1, n = 10) . The instrumental detection limit for MIC was about 0.2 microgram l-1, which corresponds to about 0.05 microgram m-3 in a 15 l air sample . Using electron ionisation, the instrumental detection limit for MIC was about 10 micrograms l-1 . No derivatisation reaction losses were seen when the derivatization reaction between PIC and DBA took place in the presence of morpholine, propylamine, ethanol, phenol and water . When mineral wool with a phenol-formaldehyde-urea resin was thermally degraded, 0.1% m/m of MIC was released . In air samples taken on top of a new electric oven insulated with mineral wool, MIC was found in the range 0.1-3 mg m-3 . No MIC in air was found from a pre-heated oven. Clin Infect Dis, 1998 Nov, 27(5), 1117 - 27, quiz 1128-9 Antibiotic pharmacodynamics in cerebrospinal fluid; Lutsar I et al.; The CSF half-lives of lipophilic agents, such as quinolones, are similar to those in serum and peak concentrations in CSF are achieved relatively quickly . In contrast, the pharmacokinetics of hydrophilic agents (beta-lactams and vancomycin) in CSF often differ from those in serum . In particular, the half-lives of these agents in CSF tend to be extended, and the time to achieve peak concentrations in CSF is delayed . Hydrophilic antibiotics, such as beta-lactams, penetrate poorly through the BBB, but CSF penetration is significantly increased in the presence of inflammation . In contrast, lipophilic antibiotics, such as quinolones, enter the CSF more efficiently and their penetration is not inflammation dependent . The pharmacodynamic properties of antibiotics in CSF are generally similar to those in other body sites; beta-lactam agents and vancomycin are time-dependent, whereas the quinolones and aminoglycosides are concentration-dependent . However, a notable difference from infections in other sites is that quinolones have a short PAE in CSF and need to continually exceed the MBC for maximal effectiveness . Thus, in CSF, quinolones demonstrate features of both concentration-dependency and time-dependency, evidence that the AUC/MBC is an important predictor of effectiveness . With the exception of quinolones, many antibiotics appear to have prolonged sub-MIC effects and longer half-lives in CSF than in serum, suggesting that dosing intervals longer than those used traditionally would be effective in meningitis . However, this requires clinical verification. Pol Merkuriusz Lek, 1998 May, 4(23), 281 - 3 {Otitis media in children}; Dzierzanowska D; Actual antibiotic therapy i children with otitis media is discussed . Empiric antibiotic therapy is suggested according to real serum concentration and MIC of bacteria. Presse Med, 1998 Oct 17, 27(31), 1580 - 1 {Can aminopenicillin be prescribed as monotherapy in case of community-acquired pneumonia?}; Leophonte P; In France the current consensus for the treatment of community-acquired pneumonia is based on the French Society for Infectious Diseases 1991 guidelines . In healthy adults without signs of severe disease, oral amoxicillin is recommended at the dose of 3 g per day for 8 to 10 days . This empirical choice is warranted by the prevalence of pneumococcal infections, found as causal agents in half to two-thirds of the bacteriologically proven cases . The 3 g dose is recommended due to the increasing risk of penicillin-resistant S . pneumoniae with MIC > 1 microgram/ml and exceptionally > 2 micrograms/ml . Clinical experience has shown that with a threshold at 2 micrograms/ml, 3 g of amoxicillin is a safe and sure choice . The duration is undoubtedly too long for most patients, but is a prudent measure due to the lack of clinical signs distinguishing between patent infection and its prolongation by inflammatory processes . Indiscriminate prescription of amoxicillin alone is however unacceptable as aminopenicillin is not effective against all microbial agents responsible for community-acquired pneumonia . The risk of selecting resistant strains is very real . Use of a large spectrum antibiotic could be indicated as first line treatment in patients with risk factors (underlying chronic disease, institutionalization, exposure to Gram negatives or S . aureus) . For such patients, combination with a beta-lactamase inhibitor (coamoxiclav) or a cephalosporin with a MIC similar to that for penicillin G (cefpodoxime proxetil, cefuroxime axetil) could be recommended . In case of severe disease, Legionella pneumophila must be taken into consideration, implicating adjuction of a macrolide . Wide spectrum fluoroquinolones such as the soon to be available trovafloxacin offer a safe alternative, covering the main microorganisms responsible for community acquired pneumonia . Widespread use would however increase the risk of microbial resistance . In the current epidemiological situation in France, prescription of an aminopenicillin alone for alveolar community-acquired pneumonia in healthy adults remains the gold standard for first line therapy. J Antimicrob Chemother, 1998 Oct, 42(4), 535 - 8 Emergence of clinical Escherichia coli isolates with decreased susceptibility to ceftazidime and synergic effect with co-amoxiclav due to SHV-1 hyperproduction; Miro E et al.; Between 1994 and 1996 we detected 28 out of 7054 (0.4%) clinical isolates of Escherichia coli with abnormal or reduced inhibition diameters to co-amoxiclav and ceftazidime in a disc diffusion test . The increased MIC of ceftazidime (1-32 mg/L) and the effect of synergy between this antibiotic and co-amoxiclav according to the disc diffusion test suggest the presence of an extended-spectrum beta-lactamase . However, enzymatic characterization and the nucleotide sequence confirm the hyperproduction of the SHV-1 enzyme. J Antimicrob Chemother, 1998 Oct, 42(4), 531 - 3 Comparison of the in-vitro activity of voriconazole (UK-109,496), itraconazole and amphotericin B against clinical isolates of Aspergillus fumigatus; Cuenca-Estrella M et al.; Voriconazole was compared with amphotericin B and itraconazole by a modification of the NCCLS microdilution reference method for yeasts against 62 clinical isolates of Aspergillus fumigatus . MICs of voriconazole were slightly lower than those of amphotericin B and itraconazole . The MIC of voriconazole at which 90% of isolates were inhibited was 1 mg/L and the MIC range was 0.25-2 mg/L . Voriconazole is a new antifungal agent with potential for use in the treatment of A . fumigatus infections. J Antimicrob Chemother, 1998 Oct, 42(4), 497 - 502 In-vitro testing of susceptibility to amphotericin B is a reliable predictor of clinical outcome in invasive aspergillosis; Lass-Florl C et al.; Invasive aspergillosis is a life-threatening fungal infection which, in neutropenic patients, is associated with an extremely high mortality rate despite optimal treatment . In order to investigate microbiological risk factors for treatment failures in more detail, Aspergillus spp . obtained from 29 patients with haematological diseases after myelo-ablative chemotherapy and bone marrow transplantation were analysed for their susceptibility to amphotericin B in vitro and this was compared with clinical outcome to see if there was a correlation . Aspergillus flavus was present in 12 (41 %) of the 29 patients, Aspergillus terreus in nine (31%) and Aspergillus fumigatus in eight (28%) . The susceptibility of these isolates to amphotericin B varied between and within the three species . A . terreus was the only organism against which the MIC was consistently high, A . fumigatus and A . flavus showing variation between isolates in the degree of resistance to amphotericin B . The degree of in-vitro resistance was the only parameter correlating with clinical outcome in a univariate analysis and the only prognostic value in a multivariate analysis considering known risk factors . Irrespective of the species, all six patients with isolates against which the MIC was <2 mg/L survived, whereas most (22/23) of those with isolates resistant to > or = 2 mg/L died . Infections among the six survivors were caused by amphotericin B-susceptible A . fumigatus and A . flavus, but not A . terreus . We conclude that the outcome of aspergillus infection depends on the in-vitro susceptibility of the isolates to amphotericin B . Survival was poor in patients with isolates resistant to amphotericin B and good in those with amphotericin B-susceptible specimens . A . terreus was always associated with high resistance to amphotericin B and with poor survival. Zhongguo Yao Li Xue Bao, 1996 Jul, 17(4), 357 - 60 Intracellular Ca2+ during fertilization and artificial activation in mouse oocytes; Deng MQ et al.; AIM: To study the mechanism of oocyte activation in mammals . METHODS: Mouse oocytes arrested at metaphase of the second meiotic division were loaded with Fura 2-AM and then activated with ethanol, calcimycin, electric pulse or fertilization . Intracellular free Ca2+ during activation were measured by Spex AR-CM-MIC cation system . Cortical granule exocytosis after activation was detected under electron microscopy . RESULTS: Sperm penetration initiated a long lasting Ca2+ oscillation in Ca2+ containing IVF medium in mouse ova . The Ca2+ oscillation lasted for over 3-4 h until the ova developed to pronuclear stage . The Ca2+ oscillated faster as extracellular Ca2+ concentration was increased from normal 1.7 mmol.L-1 to 5.0 mmol.L-1 and ceased to oscillate when extracellular Ca2+ was removed . The ova resumed Ca2+ oscillation after transferred back to IVF (Ca2+ 1.7 mmol.L-1) . The ova which exhibited Ca2+ oscillation all extruded second polar body and formed pronuclei . Suppression the Ca2+ oscillation by intracellular injection of egtazic acid (2-10 pL, 200 mumol.L-1) blocked the activation of oocytes . Heparin (100 mumol.L-1) injection failed to prevent the Ca2+ oscillation . In artificial activation, ethanol, calcimycin, and a single electric pulse usually induced a monotonic Ca2+ rise and resulted in the activation only in older oocytes (> 18 h after CG injection) . Activation of freshly ovulated oocytes required multiple intracellular Ca2+ increases induced by repetitive electric pulses . Artificial activation elicited the similar cortical granule exocytosis in oocytes as occurring at fertilization . Suppression of the intracellular Ca2+ elevation by introduction of egtazic acid into the oocytes blocked the activation process . CONCLUSIONS: The increase of intracellular free Ca2+ is the primary signal responsible for the initiation of oocyte activation but there are distinct differences between fertilization and artificial activation both in Ca2+ change patterns and Ca2+ sources . Young oocytes require oscillatory Ca2+ signals for activation. J Bacteriol, 1998 Nov, 180(22), 5809 - 14 Purification, gene cloning, targeted knockout, overexpression, and biochemical characterization of the major pyrazinamidase from Mycobacterium smegmatis; Boshoff HI et al.; The pyrazinamidase from Mycobacterium smegmatis was purified to homogeneity to yield a product of approximately 50 kDa . The deduced amino-terminal amino acid sequence of this polypeptide was used to design an oligonucleotide probe for screening a DNA library of M . smegmatis . An open reading frame, designated pzaA, which encodes a polypeptide of 49.3 kDa containing motifs conserved in several amidases was identified . Targeted knockout of the pzaA gene by homologous recombination yielded a mutant, pzaA::aph, with a more-than-threefold-reduced level of pyrazinamidase activity, suggesting that this gene encodes the major pyrazinamidase of M . smegmatis . Recombinant forms of the M . smegmatis PzaA and the Mycobacterium tuberculosis pyrazinamidase/nicotinamidase (PncA) were produced in Escherichia coli and were partially purified and compared in terms of their kinetics of nicotinamidase and pyrazinamidase activity . The comparable Km values obtained from this study suggested that the unique specificity of pyrazinamide (PZA) for M . tuberculosis was not based on an unusually high PZA-specific activity of the PncA protein . Overexpression of pzaA conferred PZA susceptibility on M . smegmatis by reducing the MIC of this drug to 150 micrograms/ml. Zentralbl Bakteriol, 1995 Oct, 282(4), 394 - 401 Comparison of the E test and a proportion dilution method for susceptibility testing of Mycobacterium tuberculosis; Fabry W et al.; Minimal inhibitory concentrations (MICs) of amikacin, streptomycin, fusidic acid, rifampicin, clarithromycin, ciprofloxacin, ofloxacin, and fleroxacin were determined by the E test for 20 strains of Mycobacterium tuberculosis . The resulting discrimination in resistant or sensitive strains was compared with the results of an extended proportion dilution method . There were no more than three strains per antibiotic with different ratings with the exception of ciprofloxacin and ofloxacin . In these discrepant cases, the breakpoint concentrations had a position at the top of the test strip, which may be unfavourable for MIC reading . The MICs of streptomycin (1-2 mg/l) and rifampicin (2-4 mg/l) for the control strain M . tuberculosis H37Rv (ATCC 27,294) were close to the reference values according to the German standard DIN 58,943 . It is concluded that the E test is suitable for susceptibility testing of slowly growing M . tuberculosis isolates. Onderstepoort J Vet Res, 1998 Dec, 65(4), 317 - 20 Correlation between ability of Ornithobacterium rhinotracheale to agglutinate red blood cells and susceptibility to fosfomycin; Fitzgerald SL et al.; Twenty five freeze-dried isolates of Ornithobacterium rhinotracheale were used for the determination of minimum inhibitory concentrations (MIC) against the antibiotic fosfomycin (Fosbac, produced by Bedson SA, consisting of a 25% mixture of fosfomycin) . The same isolates were tested for their ability to haemagglutinate chicken red blood cells . Ten of the 25 isolates were found to be susceptible to fosfomycin (MIC values below 128 ug/ml) . All of these isolates were able to agglutinate red blood cells . This is the first report on the ability of O . rhinotracheale to agglutinate red blood cells . The remaining 15 isolates were resistant to fosfomycin (MIC values above 128 ug/ml) . Only five of these isolates were found to have the ability to agglutinate red blood cells . There appears to be a correlation between the ability of O . rhinotracheale isolates to agglutinate red blood cells and their susceptibility to fosfomycin . The ability of certain isolates of O . rhinotracheale to agglutinate red blood cells, raises the questions of differences in virulence between the isolates which can agglutinate red blood cells and those which cannot and the use of this ability to agglutinate red blood cells as an alternative method for serotyping O . rhinotracheale. Appl Environ Microbiol, 1998 Nov, 64(11), 4482 - 4 Antifungal metabolites (monorden, monocillin IV, and cerebrosides) from Humicola fuscoatra traaen NRRL 22980, a mycoparasite of Aspergillus flavus sclerotia; Wicklow DT et al.; The mycoparasite Humicola fuscoatra NRRL 22980 was isolated from a sclerotium of Aspergillus flavus that had been buried in a cornfield near Tifton, Ga . When grown on autoclaved rice, this fungus produced the antifungal metabolites monorden, monocillin IV, and a new monorden analog . Each metabolite produced a clear zone of inhibition surrounding paper assay disks on agar plates seeded with conidia of A . flavus . Monorden was twice as inhibitory to A . flavus mycelium extension (MIC > 28 microg/ml) as monocillin IV (MIC > 56 microg/ml) . Cerebrosides C and D, metabolites known to potentiate the activity of cell wall-active antibiotics, were separated from the ethyl acetate extract but were not inhibitory to A . flavus when tested as pure compounds . This is the first report of natural products from H . fuscoatra. Antimicrob Agents Chemother, 1998 Nov, 42(11), 2898 - 905 Antifungal efficacy, safety, and single-dose pharmacokinetics of LY303366, a novel echinocandin B, in experimental pulmonary aspergillosis in persistently neutropenic rabbits; Petraitis V et al.; LY303366 is a novel semisynthetic derivative of echinocandin B and a potent inhibitor of fungal (1,3)-beta-D-glucan synthase . The antifungal efficacy and safety of LY303366 were investigated in treatment and prophylaxis of primary pulmonary aspergillosis due to Aspergillus fumigatus in persistently neutropenic rabbits . Treatment study groups were either not treated (controls) or treated with amphotericin B (AmB) at 1 mg/kg of body weight per day or with LY303366 at 1, 5, 10, and 20 mg/kg/day . In rabbits treated with LY303366, there was a significant improvement in survival and a reduction in organism-mediated pulmonary injury measured by the number of infarcts, total lung weight, and ultrafast computerized tomography scan pulmonary lesion score . Rabbits receiving prophylactic LY303366 also demonstrated significant improvement in survival and reduction in organism-mediated pulmonary injury . AmB and LY303366 had comparable therapeutic efficacies by all parameters with the exception of reduction in tissue burden of A . fumigatus, where AmB was superior to LY303366 . LY303366 demonstrated a dose-dependent effect on hyphal injury with progressive truncation, swelling, and vacuolization . LY303366 administered in single doses of 1, 5, 10, and 20 mg/kg demonstrated dose-proportional increases in the maximum concentration of drug in plasma and the area under the concentration-time curve from 0 to 72 h with no changes in plasma drug clearance . The 1-mg/kg dosage maintained plasma drug levels above the MIC for 18 h, and dosages of >/=5 mg/kg maintained plasma drug levels above the MIC for the entire 24-h dosing interval . There was no significant elevation of the concentrations of hepatic transaminases or creatinine in serum in LY303366-treated rabbits . In summary, LY303366 improved survival and decreased pulmonary injury with no apparent toxicity in the treatment and prevention of invasive pulmonary aspergillosis in persistently neutropenic rabbits. Nippon Rinsho, 1998 Oct, 56(10), 2699 - 705 {Emergence of hetero-VRSA strains in Japanese hospitals and its countermeasure}; Inaba Y et al.; Vancomycin-resistant MRSA (VRSA with MIC > or = 8 mg/L) has been described, recently . Although the incidence of VRSA has been low in Japanese MRSA strains, hetero-VRSA (heterogeneously resistant VRSA with MIC levels of 2-4 mg/L) is found in considerable abundance in Japanese hospitals, that may explain fairly frequent therapeutic failure in the vancomycin treatment of MRSA infection . Hetero-VRSA may also serve as precursor for VRSA in some clinical settings where it is exposed to high concentrations (8 mg/L or above) of vancomycin. Eur J Pharm Sci, 1998 Apr, 6(2), 141 - 4 Antimycobacterial activity of lichen metabolites in vitro; Ingolfsdottir K et al.; Several compounds, whose structures represent the most common chemical classes of lichen metabolites, were screened for in vitro activity against Mycobacterium aurum, a non-pathogenic organism with a similar sensitivity profile to M . tuberculosis . Of the compounds tested, usnic acid from Cladonia arbuscula exhibited the highest activity with an MIC value of 32 microg/ml . Atranorin and lobaric acid, both isolated from Stereocaulon alpinum, salazinic acid from Parmelia saxatilis and protolichesterinic acid from Cetraria islandica all showed MIC values >/=125 microg/ml. Hautarzt, 1998 Sep, 49(9), 705 - 8 {Limits of brief treatment of onychomycoses}; Seebacher C; New antifungals for oral therapy have improved the chances of healing onychomycoses . Nevertheless, in daily practice the failure rate is 20-30% both with itraconazole and terbinafine . In our investigations for the fungicidal effects of terbinafine, we could show that the same strain of Trichophyton rubrum or T . mentagrophytes in the rest period needs 1000 times higher concentration of terbinafine (2.0 to 0.002 microgram/ml) for complete fungal killing as in the growth phase . Thus resting fungi in the nail are not harmed, and if the concentration of terbinafine is lower than the MIC for the fungi, they can cause a relapse . Itraconazole is a fungistatic agent . Its concentration in the nail plate must be higher than the MIC for the causative fungi for a long time-10 to 12 months . The usual short-term treatment of onychomycosis over 3 months can be insufficient in individual cases such as patients with disorders, e.g . circulatory disorders or slowed nail growth. Scand J Infect Dis, 1998, 30(3), 253 - 6 Pneumonia caused by penicillin-non-susceptible and penicillin-susceptible pneumococci in adults: a case-control study; Einarsson S et al.; The objective of this study was to investigate the observation that patients with pneumonia due to penicillin-non-susceptible pneumococci (PNSP) in many instances present with milder disease than patients with pneumonia caused by penicillin-susceptible pneumococci (PSP) and to compare the cost of treatment . The clinical data, APACHE II score and laboratory features of hospitalized adults with pneumonia caused by PNSP or PSP were compared, along with antibiotic and hospital costs . Each patient with PNSP pneumonia (n = 36) was matched to a control with PSP pneumonia of the same age and gender . There was no difference in smoking history, but PNSP pneumonia patients had received prior antibiotics more frequently (p < 0.007) . The mean APACHE II score was not different, but when broken down into acute vs . chronic scores those with PSP pneumonia had a significantly higher acute score (p = 0.005) . Bacteraemia was present in 9 of 31 (29%) patients with PSP compared to 2 of 25 (8%) with the PNSP pneumonia (p = 0.09) . The majority of isolates in the PNSP group were of serotype 6B (minimum inhibitory concentration range 0.125-2.0 mg/l), whereas serotypes 7, 9, 14, 18 and 19 were noted among the 9 PSP isolates . Compared with the control group, patients with the PNSP strains had a significantly longer hospital stay, 26.8 vs . 11.5 days (p = 0.001) and higher average antibiotic cost, $736 vs . $213 (p < 0.0001) . In conclusion, pneumonia in adults caused by PNSP is associated with a milder clinical presentation than infection caused by PSP, suggesting either that resistance carries a price or that the serotypes of PNSP are less virulent . Pneumonia due to PNSP resulted in increased cost because of prolonged hospitalization and the use of more expensive antibiotics. J Antimicrob Chemother, 1998 Sep, 42(3), 389 - 92 In-vitro activities of amphotericin B, itraconazole and voriconazole against 150 clinical and environmental Aspergillus fumigatus isolates; Verweij PE et al.; The in-vitro activity of amphotericin B, itraconazole and voriconazole against 130 clinical and 20 environmental Aspergillus fumigatus isolates was tested with an agar dilution method using RPMI 1640 medium . Itraconazole-susceptible (AF71) and -resistant (AF90) isolates were included in each test and all isolates were tested in duplicate . Geometric mean MIC values (ranges) at 48 h and 72 h were, respectively, amphotericin B, 0.91 (0.25-2) and 1.50 (1-4) mg/L; itraconazole, 0.25 (0.06-1) and 0.48 (0.125-8) mg/L; and voriconazole, 0.56 (0.25-8) and 0.78 (0.25-8) mg/L . The reproducibility of the results was high for all drugs . In-vitro resistance of A . fumigatus to the tested antifungal agents was uncommon and the MICs of itraconazole were half those of voriconazole (P < 0.01). J Antimicrob Chemother, 1998 Sep, 42(3), 309 - 14 Study of the combination of ranitidine bismuth citrate and metronidazole against metronidazole-resistant Helicobacter pylori clinical isolates; Lopez-Brea M et al.; The in-vitro activity of a combination of ranitidine bismuth citrate (RBC) and metronidazole against metronidazole-resistant Helicobacter pylori strains (MIC > or = 8 mg/L) was evaluated by agar dilution chequerboard and killing curve methods . Twenty-five metronidazole-resistant strains were used in the chequerboard method, using Mueller-Hinton agar plus 7% lysed horse blood, an inoculum of 10(6) cfu/spot and incubation in a 10% CO2 atmosphere at 37 degrees C for 3-5 days . Synergy was defined as a fractional inhibitory concentration (FIC) index of < or = 0.5, partial synergy as 0.5 < FIC < or = 1, indifference as 1 < FIC < or = 4 and antagonism as FIC > 4 . For nine strains, killing curves were constructed for metronidazole and RBC individually and in combination at 1 x MIC . The number of viable colonies was counted at time 0 and after 2, 4, 6, 8 and 24 h; the combination was defined as synergic if it produced a decrease of > or = 2 log10 cfu/mL compared with the most active single agent . Metronidazole MICs ranged from 8 to 128 mg/L and RBC MICs from 0.125 to 4 mg/L . The minimum FIC ranged from 0.28 to 1 and the maximum FIC from 1 to 1.25 . When RBC and metronidazole were combined, all the metronidazole-resistant H . pylori strains revealed partial (68%) or total (32%) synergy . Five out of the nine strains also exhibited synergy at 4, 6 or 8 h incubation when tested by the killing curve method although three other strains exhibited no synergy . In the last strain, a 2log10 decrease in the initial number was observed with RBC alone or combined with metronidazole. Infect Immun, 1998 Nov, 66(11), 5099 - 106 Novel selection for isoniazid (INH) resistance genes supports a role for NAD+-binding proteins in mycobacterial INH resistance; Chen P et al.; The genetic basis of isoniazid (INH) resistance remains unknown for a significant proportion of clinical isolates . To identify genes which might confer resistance by detoxifying or sequestering INH, we transformed the Escherichia coli oxyR mutant, which is relatively sensitive to INH, with a Mycobacterium tuberculosis plasmid library and selected for INH-resistant clones . Three genes were identified and called ceo for their ability to complement the Escherichia coli oxyR mutant . ceoA was the previously identified M . tuberculosis glf gene, which encodes a 399-amino-acid NAD+- and flavin adenine dinucleotide-requiring enzyme responsible for catalyzing the conversion of UDP-galactopyranose to UDP-galactofuranose . The proteins encoded by the ceoBC pair were homologous with one another and with the N terminus of the potassium uptake regulatory protein TrkA . Each of the three Ceo proteins contains a motif common to NAD+ binding pockets . Overexpression of the M . tuberculosis glf gene by placing it under the control of the hsp60 promoter on a multicopy plasmid in Mycobacterium bovis BCG produced a strain for which the INH MIC was increased 50% compared to that for the control strains, while similar overexpression of the ceoBC pair had no effect on INH susceptibility in BCG . Mycobacterial extracts containing the overexpressed Glf protein did not bind radiolabeled INH directly, suggesting a more complex mechanism than the binding of unmodified INH . Our results support the hypothesis that upregulated mycobacterial proteins such as Glf may contribute to INH resistance in M . tuberculosis by binding a modified form of INH or by sequestering a factor such as NAD+ required for INH activity. Med Mycol, 1998 Aug, 36(4), 243 - 6 In vitro evaluation of terbinafine and itraconazole against dematiaceous fungi; McGinnis MR et al.; Two hundred and three isolates representing 15 species of filamentous ascomycetes were evaluated against terbinafine and itraconazole using a modification of the NCCLS M27-A standard reference method for yeasts . The MIC ranges and geometric means were similar, although terbinafine tended to have the lowest values . The loculoIascomycete clade tested had consistently low MIC geometric mean values for its members, ranging from 0.03 to 0.17 microg ml-1 for terbinafine and 0.03-0.37 microg ml-1 for itraconazole. Med Mycol, 1998 Aug, 36(4), 239 - 42 In vitro activity of voriconazole against selected fungi; McGinnis MR et al.; Fifty-nine isolates consisting of 14 genera and 33 species of ascomycetes, basidiomycetes, and zygomycetes were tested against amphotericin B, fluconazole, itraconazole and voriconazole using an in vitro modified macrobroth dilution procedure based upon the NCCLS M27-A standard method for yeasts . The triazoles voriconazole and itraconazole had similar MIC values, except for Acremonium alabamensis, A . strictum, Fusarium oxysporum, F . solani and Wangiella dermatitidis, which had substantially lower voriconazole MIC values . Voriconazole MIC values were lower than those for itraconazole for the 17 species of Trichosporon tested . Fluconazole had high MIC values, often greater than 128 microg ml-1. Proc Natl Acad Sci U S A, 1998 Oct 13, 95(21), 12510 - 5 Diversification, expression, and gamma delta T cell recognition of evolutionarily distant members of the MIC family of major histocompatibility complex class I-related molecules; Steinle A et al.; Distant relatives of major histocompatibility complex (MHC) class I molecules, human MICA and MICB, function as stress-induced antigens that are broadly recognized by intestinal epithelial gamma delta T cells . They may thus play a central role in the immune surveillance of damaged, infected, or otherwise stressed intestinal epithelial cells . However, the generality of this system in evolution and the mode of recognition of MICA and MICB are undefined . Analysis of cDNA sequences from various primate species defined translation products that are homologous to MICA and MICB . All of the MIC polypeptides have common characteristics, although they are extraordinarily diverse . The most notable alterations are several deletions and frequent amino acid substitutions in the putative alpha-helical regions of the alpha1 alpha2 domains . However, the primate MIC molecules were expressed on the surfaces of normal and transfected cells . Moreover, despite their sharing of relatively few identical amino acids in potentially accessible regions of their alpha1 alpha2 domains, they were recognized by diverse human intestinal epithelial gamma delta T cells that are restricted by MICA and MICB . Thus, MIC molecules represent a family of MHC proteins that are structurally diverse yet appear to be functionally conserved . The promiscuous mode of gamma delta T cell recognition of these antigens may be explained by their sharing of a single conserved interaction site. Res Vet Sci, 1998 Jul-Aug, 65(1), 77 - 81 Pharmacokinetics of amoxicillin/clavulanic acid combination after intravenous and intramuscular administration to pigeons; Escudero E et al.; The pharmacokinetics of amoxicillin/clavulanic acid (4:1) combination were studied after intravenous and intramuscular administration of single doses (25 mg kg(-1) bodyweight) to 50 pigeons . The plasma concentrations-time data were analysed by compartmental pharmacokinetics and non-compartmental methods . The disposition curves for both drugs after intravenous administration were best described by a two-compartment open model . The apparent volumes of distribution of amoxicillin and clavulanic acid were 1.77 litres kg(-1) and 1.30 litres kg(-1) respectively . The body clearances of amoxicillin and clavulanic acid were not significantly different . The elimination half-lives of amoxicillin after intravenous and intramuscular administration were 1.22 (0.09) hour and 1.52 (0.09) hour respectively, and those of clavulanic acid were 1.15 (0.08) hour and 1.49 (0.08) hour . After intramuscular administration both drugs had a significantly longer half-life (P<0.05) than that after the intravenous treatment . The bioavailability after the intramuscular injection was high and similar for both drugs (75.98 per cent for amoxicillin and 74.61 per cent for clavulanic acid) . The mean peak plasma concentration of clavulanic acid (0.29 hour) was reached earlier than amoxicillin (0.38 hour) and peak concentrations were proportional to the dose of both products administered (5.81 mg litre(-1) of amoxicillin and 1.89 mg litre(-1) of clavulanic acid) . From a single administration it is proposed that an intramuscular dosage regimen of 105 mg kg(-1) of the combination (84 mg kg(-1) of amoxicillin and 21 mg kg(-1) of clavulanic acid) every 12 hours will achieve minimum concentrations > or =0.5 mg litre(-1) (minimum inhibitory concentration of most susceptible pathogens). Res Microbiol, 1997 Dec, 148(9), 785 - 93 The relationship between microbial metabolic activity and biocorrosion of carbon steel; Dzierzewicz Z et al.; The effect of metabolic activity (expressed by generation time, rate of H2S production and the activity of hydrogenase and adenosine phosphosulphate (APS)-reductase enzymes) of the 8 wild strains of Desulfovibrio desulfuricans and of their resistance to metal ions (Hg2+, Cu2+, Mn2+, Zn2+, Ni2+, Cr3+) on the rate of corrosion of carbon steel was studied . The medium containing lactate as the carbon source and sulphate as the electron acceptor was used for bacterial metabolic activity examination and in corrosive assays . Bacterial growth inhibition by metal ions was investigated in the sulphate-free medium . The rate of H2S production was approximately directly proportional to the specific activities of the investigated enzymes . These activities were inversely proportional to the generation time . The rate of microbiologically induced corrosion (MIC) of carbon steel was directly proportional to bacterial resistance to metal ions (correlation coefficient r = 0.95) . The correlation between the MIC rate and the activity of enzymes tested, although weaker, was also observed (r = 0.41 for APS-reductase; r = 0.69 for hydrogenase; critical value rc = 0.30, p = 0.05, n = 40). Res Microbiol, 1997 Nov, 148(8), 673 - 81 Postantibiotic effect of amikacin, rifampin, sparfloxacin, clofazimine and clarithromycin against Mycobacterium avium; Horgen L et al.; Antimycobacterial drugs acting efficiently against Mycobacterium avium complex have in common low MICs and MBC/MIC ratios . The recently reported clinical efficacy of some of the newer drugs is also clearly linked to their pharmacokinetic properties such as higher serum level and/or intracellular concentrations and half-life . In the present investigation, comparative postantibiotic effects (PAEs) of amikacin, rifampin, sparfloxacin, clofazimine and clarithromycin were investigated . Bacteria were exposed to MIC, MIC x 4 and MIC x 8 concentrations of each drug for 2 h, the drug was removed by centrifugation and cells were thoroughly washed and resuspended in drug-free medium . Growth was compared to control organisms which underwent a similar treatment (but without drugs) and PAEs were assessed using the equation "T-C", where T equals the time required for colony counts to increase by 1 log10 in test samples after antibiotic exposure and C equals the time for 1 log10 growth in control . Our results underlined two distinct patterns concerning PAE: pattern I included drugs for which PAE (in hours) was dose-dependent and varied (for MIC, MIC x 4 and MIC x 8 concentrations) for amikacin (10.3 +/- 1.7, 14.7 +/- 1.9 and 17.7 +/- 4.1), rifampin (28.0 +/- 7.6, 62.0 +/- 18.5 and 71.0 +/- 3.2) and clarithromycin (2.6 +/- 1.0, 15.0 +/- 4.0 and 22.0 +/- 4.0), whereas pattern II included drugs with a stable PAE, relatively independent of the drug concentrations: sparfloxacin (11.0 +/- 2.5, 12.3 +/- 6.4 and 13.0 +/- 2.1) and clofazimine (26.0 +/- 2.8, 28.8 +/- 2.5 and 27.3 +/- 1.3) . These results may be useful for guidance in scheduling of drug administration in M . avium-infected AIDS patients overburdened with too many drugs given for various opportunistic infections. Diagn Microbiol Infect Dis, 1998 Aug, 31(4), 543 - 7 Multisite reproducibility of MIC results by the Sensititre YeastOne colorimetric antifungal susceptibility panel; Pfaller MA et al.; Reproducibility of MIC results between laboratories, a major performance criterion used for evaluation of any susceptibility test method, was determined at three test sites using the Sensititre YeastOne Antifungal Panel, which incorporates Alamar Blue as a colorimetric indicator . MICs of five antifungals were determined using a set of 10 isolates of Candida species . Each isolate was tested a total of nine times against each antifungal agent in each of the three laboratories . A total of 1350 MICs were evaluated . MICs were read visually after incubation at 35 degrees C for 24 and 48 h . Overall, 99 to 100% of MIC values were encompassed by a range defined by the modal MIC +/- 1 dilution for each antifungal agent tested at both 24 h and 48 h . Replicate testing of the quality control isolates recommended by the National Committee for Clinical Laboratory Standards demonstrated excellent agreement between results obtained with the Sensititre YeastOne panel and the MIC reference range for each antifungal agent . These studies demonstrated that the Sensititre YeastOne Antifungal Panel may be used to generate MIC values for at least five different antifungal agents with a high degree of intra- and interlaboratory reproducibility. Nutrition, 1998 Sep, 14(9), 672 - 7 Automated, eight-cage indirect calorimetry in rats; Luketich JD et al.; We have constructed an automated, eight-cage indirect calorimeter (AIC) for the measurement of energy expenditure in rats . We compared the measurements of resting energy expenditure (REE) in rats during a 30-h fast obtained with the AIC with those obtained with a manual indirect calorimetry (MIC) system . There was both a high degree of correlation between the two techniques during the initial 18 h of the fast (r = 0.90, P < 0.05) and strong intertechnique agreement . REE (AIC) decreased during the final 12 h of the 30-h fast (79.6 +/- 2.7-72.0 +/- 4.4 kcal.kg-0.75.d-1 {mean +/- SD, P < 0.01}) . REE (MIC) did not show a significant decrease during this part of the fast (79.7 +/- 2.6 - 75.2 +/- 4.7 kcal.kg-0.75.d-1 {P = NS}) . During the final 12 h of the fast agreement between the two systems gradually dissipated and correlation was poor (r = 0.375, P < 0.05) . The frequency of animal handling necessitated by MIC may have resulted in a stress-induced increase in metabolic work that would mask the animals' adaptive response to starvation . This investigation demonstrates the advantages of the AIC and calls into question the accuracy of manual methods under long-term starvation conditions. Antimicrob Agents Chemother, 1998 Oct, 42(10), 2749 - 51 Explaining the bias in the 23S rRNA gene mutations associated with clarithromycin resistance in clinical isolates of Helicobacter pylori; Debets-Ossenkopp YJ et al.; A single point mutation in the 23S rRNA gene of Helicobacter pylori is known to confer resistance to clarithromycin . Most prevalent among clarithromycin-resistant clinical H . pylori isolates are the mutations from A-2142 to G and A-2143 to G in the 23S rRNA gene . The bias in the 23S rRNA gene mutations conferring clarithromycin resistance may result from the higher MIC, stability of resistance, and growth rate found for the strains with the above-mentioned mutations. Antimicrob Agents Chemother, 1998 Oct, 42(10), 2726 - 30 In vitro activity of the echinocandin antifungal agent LY303,366 in comparison with itraconazole and amphotericin B against Aspergillus spp; Oakley KL et al.; LY303,366 (LY) is a novel derivative of the echinocandin class of antifungal agents . The in vitro activities of LY, itraconazole (ITZ), and amphotericin B (AMB) were assessed against 60 Aspergillus isolates, including 35 isolates of A . fumigatus, eight isolates of A . terreus, eight isolates of A . flavus, eight isolates of A . niger and one isolate of A . nidulans . Four A . fumigatus isolates were resistant to ITZ . Susceptibility testing for all drugs was performed with a broth microdilution procedure . LY was tested in two media: antibiotic medium 3 (AM3) and Casitone with 2% glucose (CAS) with an inoculum of 2 x 10(3) spores/ml . ITZ and AMB were tested in RPMI 1640 with 2% glucose with an inoculum of 1 x 10(6) spores/ml . All tests were incubated at 37 degrees C for 48 h . A novel end point was used to determine a minimal effective concentration (MEC) for LY, i . e., almost complete inhibition of growth save a few tiny spherical colonies attached to the microplate . MICs were measured for ITZ and AMB with a no-growth end point . Ranges and geometric mean (GM) MECs were from 0.0018 to >0.5 and 0.0039 mg/liter and from 0.0018 to >0.5 and 0.008 mg/liter for LY in AM3 and LY in CAS, respectively . Differences between species were apparent, with A . flavus being significantly less susceptible to LY than any other species tested with both media (P </= 0.05) . Ranges and GM MICs were from 0.125 to >16 and 0.7 mg/liter for ITZ and from 0.25 to 16 and 1.78 mg/liter for AMB . Minimal fungicidal concentrations (MFCs) were also determined for all drugs . GM MFCs were 0.018, 0.09, 19.76, and 12.64 mg/liter for LY in AM3, LY in CAS, ITZ, and AMB, respectively . LY in AM3 and LY in CAS were fungicidal for 86.7 and 68% of isolates, respectively (98% killing) . In comparison, ITZ and AMB were fungicidal for 35 and 70% of isolates, respectively (99.99% killing) . A reproducibility study was performed on 20% of the isolates . For 12 isolates retested, the MEC or MIC was the same or was within 1 dilution of the original value for 11, 11, 10, and 9 isolates for LY in AM3, LY in CAS, ITZ, and AMB, respectively . In conclusion, LY seems to be a promising antifungal agent with excellent in vitro activity against Aspergillus spp. Antimicrob Agents Chemother, 1998 Oct, 42(10), 2474 - 81 Sequencing of gyrase and topoisomerase IV quinolone-resistance-determining regions of Chlamydia trachomatis and characterization of quinolone-resistant mutants obtained In vitro; Dessus-Babus S et al.; The L2 reference strain of Chlamydia trachomatis was exposed to subinhibitory concentrations of ofloxacin (0.5 microg/ml) and sparfloxacin (0.015 microg/ml) to select fluoroquinolone-resistant mutants . In this study, two resistant strains were isolated after four rounds of selection . The C . trachomatis mutants presented with high-level resistance to various fluoroquinolones, particularly to sparfloxacin, for which a 1,000-fold increase in the MICs for the mutant strains compared to the MIC for the susceptible strain was found . The MICs of unrelated antibiotics (doxycycline and erythromycin) for the mutant strains were identical to those for the reference strain . The gyrase (gyrA, gyrB) and topoisomerase IV (parC, parE) genes of the susceptible and resistant strains of C . trachomatis were partially sequenced . A point mutation was found in the gyrA quinolone-resistance-determining region (QRDR) of both resistant strains, leading to a Ser83-->Ile substitution (Escherichia coli numbering) in the corresponding protein . The gyrB, parC, and parE QRDRs of the resistant strains were identical to those of the reference strain . These results suggest that in C . trachomatis, DNA gyrase is the primary target of ofloxacin and sparfloxacin. Bull Cancer, 1998 Apr, 85(4), 319 - 27 {Microinvasive carcinoma uterine cervix . Which approach in 1998?}; Lecuru F et al.; Numerous definitions of microinvasive carcinoma (MIC) have been proposed . The SGO takes into account the depth of stromal invasion and presence of capillary like space involvement (LVI) . The Figo uses the lesion width and describes different substages according to the depth of stromal invasion . Two major prognostic factors can be identified in the literature: the depth of invasion and the presence of LVI . The lesion volume is probably more accurate than the depth of stromal invasion but cannot be measured in routine . Taking into account that a classification must be a guide for the evaluation of prognosis and treatment, the SGO definition seems more reliable . Pelvic lymph node metastasis rate and recurrence increase with these two factors . MIC with stromal invasion under 3 mm and without LVI have a little risk of parametrial and nodal involvement: with a high rate of survival . Conversely, MIC with invasion over 3.1 mm depth or LVI have a greater risk of spread beyond the cervix (1% versus 7.7%) and many authors now consider them as true invasive cancers . For lesion invading the stroma within 3 mm, the treatment can be limited to a standard hysterectomy with good results . Some authors have proposed more conservative therapy as conization . This procedure is interesting for young women willing to preserve their anatomy, fertility and sexual function . In selected cases, short term results are similar to those of hysterectomy but there is a lack of controlled studies with long term follow-up . Lesions over 3.1 mm with LVI should be treated as true invasive cancers . Intermediate cases should have a conservative therapy associated with a laparoscopic lymphadenectomy. Electroencephalogr Clin Neurophysiol, 1998 Aug, 109(4), 290 - 6 Reproducibility of electromyographic recordings of submaximal concentric and eccentric muscle contractions in humans; Finucane SD et al.; OBJECTIVES: to determine the intratester and intertester reliability of measures of electromyographic activity (EMG) of submaximal concentric and eccentric contractions and to compare the reliability of normalized and non-normalized measures of EMG . There were 10 subjects, of 22-33 years old . METHODS: Subjects performed submaximal concentric and eccentric contractions at 60 degrees/s, and maximal isometric contractions (MIC) of their knee extensors . The target power of the submaximal contractions was 90%+/-10% of the subject's maximal concentric power . EMG was recorded via bipolar surface electrodes from 3 of the quadriceps femoris muscles . The rmsEMG for submaximal contractions that were within the target power range were determined . The rmsEMG for the submaximal contractions were normalized to the rmsEMG of the maximal isometric contractions . Intraclass correlation coefficients (ICC version 1.1) were calculated to determine intratester and intertester reliability . RESULTS: For non-normalized rmsEMG, ICC values for intratester reliability ranged from 0.62 to 0.91 for concentric and from 0.84 to 0.97 for eccentric contractions . ICC values for intertester reliability ranged from 0.66 to 0.96 for concentric and 0.78 to 0.90 for eccentric contractions . CONCLUSIONS: Non-normalized rmsEMG of submaximal concentric and eccentric isokinetic contractions were found to be reliable . Normalization did not lead to consistently improved reliability. Mycopathologia, 1998, 141(2), 73 - 7 In vitro activity of a new triazole antifungal agent, Sch 56592, against clinical isolates of filamentous fungi; Marco F et al.; Sch 56592 is a new triazole derivative that possesses potent, broad-spectrum antifungal activity . We evaluated the in vitro activity of Sch 56592 compared with that of itraconazole, amphotericin B and 5-fluorocytosine against 51 clinical isolates of filamentous fungi, including Aspergillus flavus (10), A . fumigatus (12), Fusarium spp . (13), Rhizopus spp . (6), Pseudallescheria boydii (5), and one isolate each of Acremonium spp., A . niger, A . terreus, Paecilomyces spp., and Trichoderma spp . In vitro susceptibility testing was performed using the microdilution broth method outlined in the NCCLS 27-A document . Sch 56592 was highly active against A . flavus (MIC90, 0.25 micrograms/ml), A . fumigatus (MIC90, 0.12 micrograms/ml), P . boydii (MIC50, 1 microgram/ml) and Rhizopus spp (MIC50, 1 microgram/ml) . By comparison with itraconazole, Sch 56592 was four-to eight-fold more active against isolates of Aspergillus and both compounds showed equipotent in vitro activity against P . boydii and Rhizopus spp . Sch 56592 was four- to 16-fold more active than amphotericin B against Aspergillus spp . and P . boydii and both antifungal drugs displayed similar activity against Rhizopus spp . Overall, Sch 56592 showed good in vitro activity against all isolates tested (MIC, < or = 2 micrograms/ml) except isolates of Fusarium (MIC range, (1-->4 micrograms/ml) . On the basis of these data Sch 56592 has promising activity against Aspergillus spp . and other species of filamentous fungi that are likely to be encountered clinically . Additional in vitro and in vivo studies are warranted. Med Microbiol Immunol (Berl), 1998 Jun, 187(1), 11 - 6 Balance of proinflammatory and antiinflammatory cytokines in mice immunized with Escherichia coli and correlation with mortality after lethal challenge; Raponi G et al.; The balance of proinflammatory and antiinflammatory cytokines, their correlation with endotoxin levels and mortality rate after lethal challenge of Escherichia coli was investigated in mice immunized weekly for 8 weeks with formalin-killed E . coli either untreated or treated with 0.5x minimal inhibitory concentration of aztreonam . Control mice treated in parallel with saline, died within 24 h after challenge with 100x lethal dose (LD50) of viable E . coli O6:K- . Mice immunized with antibiotic-treated bacteria showed a significantly higher survival than mice immunized with untreated E . coli . Cytokines were not detected in the sera of control mice during the entire period of immunization . At 90 min after immunization, mice immunized with antibiotic-treated E . coli showed tumor necrosis factor-alpha (TNF-alpha) levels significantly lower and interleukin (IL)-6 levels significantly higher (P < 0.05) than mice immunized with untreated E . coli, while comparable levels of interferon-gamma (IFN-gamma were measured in both groups . TNF-alpha and IL-10 levels measured 90 min after lethal challenge correlated with the mortality rate observed in each group (r = 0.96 for TNF-alpha and 0.94 for IL-10) . IL-6 levels correlated with survival (r = 0.95), while IFN-gamma serum levels did not differ in the two immunized groups, but were significantly higher than those measured in the control mice . IL-4 was detected only after challenge of mice immunized with antibiotic-treated bacteria . Comparable levels of circulating endotoxin were measured after lethal challenge in both control and immunized mice . These data showed that in the presence of a protective immune response the survival of immunized mice was correlated with an early alteration of cytokine expression pattern including enhanced secretion of IL-4, IL-6 and IFN-gamma, and reduced secretion of TNF-alpha and IL-10. Phytochemistry, 1998 Sep, 49(2), 559 - 64 Antimycobacterial evaluation of germacranolides; Fischer NH et al.; The minimum inhibitory concentrations (MIC) against Mycobacterium tuberculosis and M . avium of parthenolide, costunolide, 1 (10)-epoxycostunolide and other germacranolide-type sesquiterpene lactones and derivatives were determined by use of a radiorespirometric bioassay . Structure-activity relationship studies with natural and semisynthetic sesquiterpene lactones suggested that the alpha-methylene-gamma-lactone moiety is an essential, but not sufficient, structural requirement for significant in vitro activity against M . tuberculosis and M . avium. Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1994 Feb, 27(1), 38 - 45 A study on the in vitro susceptibility of Trichomonas vaginalis to metronidazole; Lin PR et al.; The susceptibility of 32 clinical isolates of Trichomonas vaginalis to metronidazole has been studied under aerobic and anaerobic conditions . Of 32 patients with vaginal trichomoniasis, 27 (84%) were cured by a standard metronidazole treatment regimen (200 mg thrice daily for seven days) . The geometric means of minimum inhibitory concentration (MIC) under aerobic and anaerobic conditions for these isolates were 2.0 and 0.4 micrograms/ml, respectively; the geometric means of minimum lethal concentration (MLC) under aerobic and anaerobic conditions were 7.4 and 2.0 micrograms/ml, respectively . However, for those five patients with treatment failure, the geometric means of MIC for these isolates under aerobic and anaerobic conditions were 6.8 and 1.1 micrograms/ml, respectively; the geometric means of MLC under aerobic and anaerobic conditions were 18 and 5.5 micrograms/ml, respectively . Trichomonads reisolated from patients after treatment failure had similar susceptibility to metronidazole as before treatment . However, all five women were cured by a second course of metronidazole treatment . Although primary treatment failure was common when isolates of T . vaginalis had aerobic MLC values of > 18 micrograms/ml or anaerobic MLC values > 5.5 micrograms/ml, two cases with isolates having high MLC values (aerobic: 20 micrograms/ml, anaerobic: 5 micrograms/ml) responded well to the standard treatment . It was evident that no metronidazole-resistant trichomonads were found in this study. Biol Pharm Bull, 1998 Aug, 21(8), 853 - 7 Enhanced rectal absorption of amphotericin B lyophilized with glycyrrhizinate in rabbits; Tanaka M et al.; The influence of bases and additives in the formulation for rectal absorption of amphotericin B (AMB) lyophilized with dipotassium glycyrrhizinate (GLYK) was investigated using rabbits in relation to an in vitro release test . The release of AMB from the fatty base of Witepsol or a medium chain triglyceride (MCT) was markedly faster than that from the hydrophilic base of macrogol . The addition of polyoxyethylene (2) lauryl ether (POE(2)LE) into the fatty bases led to a marked increase in the release rate, whereas POE(9)LE or sodium lauryl sulfate resulted in a significantly lower release rate . Animals received rectally each of seven AMB formulations of Witepsol H-15, macrogol, MCT with surfactants and aqueous solution . The absorption of the AMB lyophilized mixture with GLYK at a 1:9 molar ratio from a MCT base was significantly superior to that from macrogol . The addition of POE(2)LE into the MCT base resulted in a marked increase in bioavailability, showing the highest bioavailability of 4.9% . High serum levels of over 100 ng/ml of serum were maintained for 24 h following administration . The lowest bioavailability was 0.32% for the macrogol suppository . There was a good correlation between the release rate of AMB from the formulations and bioavailability . These results suggest that an AMB rectal formulation may provide a promising therapeutic alternative to infusion, taking into account the serum level of AMB exceeding the minimal inhibitory concentration of the infecting organism. J Periodontol, 1998 Aug, 69(8), 879 - 83 Calprotectin and lactoferrin levels in the gingival crevicular fluid of children; Miyasaki KT et al.; The purpose of this study was to determine the levels of calprotectin and lactoferrin, 2 microbiostatic proteins, in the gingival crevicular fluid (GCF) of normal children . The children represented a population, primarily underprivileged, seeking care at a regional dental health care center . GCF was collected from Ramfjord teeth (or their deciduous equivalent) . GCF volume was quantified by conductance . Calprotectin and lactoferrin levels were quantified by sandwich ELISA, and found to have a mean value of 70.8+/-94.2 microg/mL and 68.2+/-108.7 microg/mL, respectively . The levels of calprotectin and lactoferrin varied directly with one another and inversely with the amount of fluid obtained in a 20-second sampling period . The mean levels were at or above the minimum inhibitory concentration determined in vitro. Semin Oncol, 1998 Aug, 25(4 Suppl 9), 27 - 34 The activity of gemcitabine plus cisplatin in randomized trials in untreated patients with advanced non-small cell lung cancer; Rosell R et al.; Three separate phase III randomized studies were conducted to compare the efficacy of a gemcitabine plus cisplatin combination (GC) with other chemotherapy regimens in the treatment of European and North American patients with inoperable (stage IIIB or IV) non-small cell lung cancer (NSCLC) . The Spanish Lung Cancer Group (SLCG) compared the GC regimen with an etoposide plus cisplatin combination (EP), the Hoosier Oncology Group (HOG) compared it with single-agent cisplatin, and the Italian Lung Cancer Project (ILCP) compared it with a mitomycin plus ifosfamide plus cisplatin combination (MIC) . The three studies each had a different primary objective (response rate, survival, or quality of life, respectively) . From July 1995 to February 1997, 751 patients were enrolled into the three studies . In the SLCG study, 69 were entered in the GC arm and 64 in the EP arm; in the HOG study, 155 were entered in the GC arm and 154 in the cisplatin-alone arm; and in the ILCP study, 154 were entered in the GC arm and 152 in the MIC arm . In the SLCG study, gemcitabine 1,250 mg/m2 was given by 30-minute infusion on days 1 and 8 of each 21-day cycle . In the HOG and ILCP studies, gemcitabine 1,000 mg/m2 was given on days 1, 8, and 15 of each 28-day cycle . Cisplatin 100 mg/m2 was given on day 1 in the SLCG and HOG studies and on day 2 in the ILCP study . In the EP arm, etoposide 100 mg/m2 was given on days 1, 2, and 3 of each 21-day cycle . In the MIC arm, mitomycin 6 mg/m2 and ifosfamide 3 g/m2 were given on day 1 of each 28-day cycle . In the SLCG study, 28 patients (40.6%) in the GC arm and 14 patients (21.2%) in the EP arm achieved an objective response (P = .01) . In the HOG study, 48 patients (31%) in the GC arm and 14 patients (9.1%) in the cisplatin-alone arm attained on objective response (P < .001) . In the ILCP study, 61 patients (40%) in the GC arm and 42 patients (28%) in the MIC arm achieved an objective response (P = .03) . Progression-free time was significantly longer for the GC arm (6.8 months) than for the cisplatin-alone arm (4.2 months) (P < .001) . The median survival time was remarkably identical for the GC arms in the three studies (8.7 months), whereas it was 7.2 months for the EP arm, 7.6 months for the cisplatin-alone arm, and 9.5 months for the MIC arm . The main toxicities were myelosuppression and vomiting . The assessment of quality of life in the ILCP study is ongoing . Both 21- and 28-day cycles of GC were effective in the treatment of NSCLC, and this combination can be considered as a current "standard" therapy for advanced NSCLC patients. Indian J Pathol Microbiol, 1995 Oct, 38(4), 369 - 74 Disk diffusion susceptibility testing of dermatophytes with imidazoles; Venugopal PV et al.; In vitro susceptibility testing of 43 isolates of dermatophytes was carried out against imidazoles-ketoconazole, miconazole and econazole and griseofulvin by agar dilution and disk diffusion methods . Econazole was the most effective drug inhibiting all the isolates at a concentration of 0.1 microgram ml-1 . The MIC 50s and MIC 90s for ketoconazole and miconazole were 1 and 2.5 mg ml-1 whereas the values for griseofulvin were 1 and 5 micrograms ml-1 . Good correlation was seen between the MIC and sizes of zones of inhibition around the disks . Regression analysis was used to measure the degree of correlation between the MIC values and matched averaged zones of inhibition and the correlation coefficients for econazole, ketoconazole, miconazole and griseofulvin were -0.5554, -0.5886, -0.8558 and -0.8268 (p < 0.001) respectively. Indian J Pathol Microbiol, 1995 Oct, 38(4), 345 - 8 In vitro susceptibility of filamentous fungi to itraconazole; Venugopal PV et al.; The in vitro activity of itraconazole was investigated against 25 clinical isolates of filamentous fungi by agar dilution method . The isolated included Aspergillus sp., hyalohypomycetes, dematiaceous fungi and zygomycetes . Intraconazole was more active, inhibiting 50% (MIC 50) and 90% (MIC 90) of the Aspergillus sp., at a concentration of 0.5 and 2.5 ug ml-1 (MIC range 0.1 and 5 micrograms ml-1) Ketoconazole (MIC range 0.5-10 ug ml-1) required 1 and 5 ug ml-1 for inhibiting 50% and 90% of the isolates . For the hyalophypomycetes and dematiaceous fungi, the MIC 50s for itraconazole were 1 and 0.5 ug ml-1 and Ketoconazole required 2.5 ug ml-1 for both the groups . For the zygomycetes, the MIC range and MIC 50s for Ketoconazole were 1-100 and 10 ug ml-1 whereas the values for itraconazole were 5- > 100 and > 100 micrograms ml-1. J Oral Pathol Med, 1998 Aug, 27(7), 325 - 32 Adhesion of oral C . albicans to human buccal epithelial cells following limited exposure to antifungal agents; Ellepola AN et al.; The major aetiologic agent of oral candidosis is C . albicans, and adhesion to oral mucosal surfaces is considered a vital prerequisite for successful colonisation and subsequent infection by this agent . Although many antimycotics are available for the treatment of oral candidosis, the diluent effect of saliva and the cleansing action of the oral musculature often tend to reduce the availability of the agents below that of the effective therapeutic concentration . Therefore, the yeasts undergo only a limited exposure to the antifungals during therapy . Hence, the main aim of the present study was to determine the in vitro adhesion of ten isolates of oral C . albicans to buccal epithelial cells (BEC) following a short exposure to sublethal concentrations of four antifungal agents . The yeasts were exposed to sublethal concentrations of nystatin (x6 MIC), 5-fluorocytosine (x8 MIC), ketoconazole (x4 MIC) and fluconazole (x4 MIC) for a period of 1 h . Following subsequent removal of the drug, the adhesion of these isolates to BEC was assessed by a previously described adhesion assay . The mean percentage reductions of candidal adhesion to BEC following exposure to sublethal concentrations of nystatin, 5-fluorocytosine, ketoconazole and fluconazole were 72.88%, 16.52%, 40.16% and 24.36%, respectively . Ultrastructural studies revealed that short exposure to nystatin and the azoles (but not 5-fluorocytosine) resulted in aberrant cellular features . These findings indicate that subtherapeutic levels of antifungals may modulate candidal colonisation of the oral mucosa and thereby suppress the invasive potential of the pathogen. J Control Release, 1998 Jul 31, 54(2), 167 - 75 In vitro and in vivo release of ciprofloxacin from PLGA 50:50 implants; Ramchandani M et al.; Poly(lactides-co-glycolides) {PLGA} are widely investigated biodegradable polymers and are extensively used in several biomaterials applications as well as drug delivery systems . These polymers degrade by bulk hydrolysis of ester bonds and break down into their constituent monomers, lactic and glycolic acids which are excreted from the body . The purpose of this investigation was to develop and characterize a biodegradable, implantable delivery system containing ciprofloxacin hydrochloride (HCl) for the localized treatment of osteomyelitis and to study the extent of drug penetration from the site of implantation into the bone . Osteomyelitis is an inflammatory bone disease caused by pyogenic bacteria and involves the medullary cavity, cortex and periosteum . The advantages of localized biodegradable therapy include high, local antibiotic concentration at the site of infection, as well as, obviation of the need for removal of the implant after treatment . PLGA 50:50 implants were compressed from microcapsules prepared by nonsolvent-induced phase-separation using two solvent-nonsolvent systems, viz., methylene chloride-hexane (non-polar) and acetone-phosphate buffer (polar) . In vitro dissolution studies were performed to study the effect of manufacturing procedure, drug loading and pH on the release of ciprofloxacin HCl . The extent of penetration of the drug from the site of implantation was studied using a rabbit model . The results of in vitro studies illustrated that drug release from implants made by the nonpolar method was more rapid as compared to implants made by the polar method . The release of ciprofloxacin HCl . The extent of the penetration of the drug from the site of implantation was studied using a rabbit model . The results of in vitro studies illustrated that drug release from implants made by the nonpolar method was more rapid as compared to implants made by the polar method . The release of ciprofloxacin HCl from the implants was biphasic at < or = 20% w/w drug loading, and monophasic at drug loading levels > or = 35% w/w . In vivo studies indicated that PLGA 50:50 implants were almost completely resorbed within five to six weeks . Sustained drug levels, greater than the minimum inhibitory concentration (MIC) of ciprofloxacin, up to 70 mm from the site of implantation, were detected for a period of six weeks. Mod Pathol, 1998 Aug, 11(8), 769 - 73 CD99, keratin, and vimentin staining of sex cord-stromal tumors, normal ovary, and testis; Gordon MD et al.; CD99, a marker for MIC-2, reacts with normal Sertoli cells and granulosa cells . We investigated CD99 expression in the development of normal ovary and testis as well as in 25 sex cord-stromal tumors (SCSTs), 7 epithelial neoplasms, and 6 germ cell tumors . Normal Sertoli cells and mature granulosa cells showed 3+ staining with CD99 . Pregranulosa cells of primordial follicles were negative . All of the eight Sertoli-Leydig cell tumors were positive with antibody to CD99, with the well-differentiated tumors showing the greatest degree of staining intensity . Reactivity of 2+ to 3+ with CD99 was observed in all of the 11 granulosa cell tumors and in yolk sac components of the germ cell tumors investigated . All of the poorly differentiated carcinomas were negative with CD99 . We concluded that CD99 might be a useful marker for SCSTs and that its degree of reactivity correlates with the degree of differentiation in Sertoli-Leydig cell tumors . Additionally, CD99 might aid in distinguishing granulosa cell tumors of the ovary from poorly differentiated carcinomas. Mod Pathol, 1998 Aug, 11(8), 747 - 53 Small round-cell type of malignant peripheral nerve sheath tumor; Abe S et al.; Five cases of primitive, small, round-cell tumor that are a type of hitherto unclassified neurogenic sarcoma are described . The tumors were located deep within the soft tissue of the trunks and limbs without association with major nerves . The histologic features consisted mainly of uniform, small, round, tumor cells with scanty cytoplasm . Foci of uniform, short, spindle-shaped tumor cells arranged in whorl-like patterns were observed in some areas . Although the immunoreactivity for the neural markers, Leu-7 and MIC-2, was not marked, cell processes and fragmentous basal laminae, which are ultrastructural neural features, were found in both spindle-shaped and round tumor cells . In four cases, EWS chimeric transcripts were analyzed by reverse-transcription polymerase chain reaction . EWS chimeric mRNA (EWS-FLI-1, EWS-ERG, EWS-E1AF, EWS-ETV1, EWS-FEV) was not detected in any cases . The tumors were not consistent with peripheral primitive neuroectodermal tumor . We propose them as a small round-cell type of MPNST that might differentiate toward the immature neural cells. J Pathol, 1998 May, 185(1), 25 - 31 Rapid and prognostically valid quantification of immunohistochemical reactions by immunohistometry of the most positive tumour focus . A prospective follow-up study on breast cancer using antibodies against MIB-1, PCNA, ER, and PR; Biesterfeld S et al.; The prognostic significance of immunohistochemical markers for cell proliferation {MIB-1, proliferating cell nuclear antigen (PCNA)} and hormone receptor analysis {oestrogen receptor (ER), progesterone receptor (PR)} was tested by means of immunohistometry in a series of 103 breast cancer patients in comparison with the lymph node status N, the tumour size T, histomorphological grading, and the biochemical ER and PR status . Immunohistochemical reactions were performed on 2 microns sections from paraffin-embedded tissue, using an indirect peroxidase method . The proportion of immunostained tumour cell nuclei was determined using a TV-image analysis system . Measurements were performed using a 20 x objective on 40 viewing fields (1.94 mm2, MIB-1 and PCNA) or 20 viewing fields (0.97 mm2, ER and PR) . The mean immunopositivity of all viewing fields and the value of the most immunopositive viewing field (MIB-1max, PCNAmax, PRmax, ERmax) were calculated . The mean values and the maximal values were highly correlated (r = 0.903, P < 0.001) . After 1:2:1 quantilization, 84.2 per cent of the 412 single measurements revealed mean and maximal values in the same category (P < 0.0001) . For each of the four immunohistochemical markers, the prognostic significance of the maximal values was higher than that of the mean values . The highest prognostic significance was found for MIC-1max (P = 0.0002), followed by PRmax (P = 0.0046), ERmax (P = 0.0154), and PCNAmax (P = 0.0161) . From the results of a Cox model, a 'prognostic index (PI)' was developed, ranging from -1 to 8: PI = 2 x N + T + MIB-1max-PRmax . The four groups of patients with PI values of < 2, 2-3, 4-5, and > 5 revealed significantly different 7.5-year survival probabilities (P < 0.0001) . The simplicity of the PI makes it a clinically useful, routinely applicable, and understandable parameter in the surgical pathology of breast carcinoma. Mycoses, 1998 May-Jun, 41(5-6), 203 - 11 Cross-sectional study of oral Candida carriage in a human immunodeficiency virus (HIV)-seropositive population: predisposing factors, epidemiology and antifungal susceptibility; Schoofs AG et al.; The Candida species isolated from oral rinses of 130 human immunodeficiency virus (HIV) infected patients were compared with those of 130 healthy non-matched volunteers . The oral rinses were plated on CHROMagar Candida medium (CAC) and on CAC supplemented with 10 micrograms (CF10) and 100 micrograms (CF100) of fluconazole per ml . The prevalence of non-albicans Candida spp . in oral rinses of HIV-infected patients and their correlation with the clinical and epidemiological characteristics of the patients were studied . Susceptibility of the Candida spp . isolated was determined by a microbroth dilution method based on the NCCLS reference procedure . Results of susceptibility tests of the yeast isolates were compared with their growth at the time of isolation on CAC supplemented with fluconazole . Thirty-five (30.7%) strains of non-albicans Candida spp . were isolated from the HIV-positive population, vs . seven (15.9%) from the immunocompetent population . Growth on CF10 correlated in 96% of the cases with fluconazole minimum inhibitory concentration (MIC) > 8 micrograms ml-1 . Smoking and use of azoles were significantly associated with oral carriage of non-albicans Candida spp . (P < 0.05) . The prevalence of non-albicans Candida spp . in HIV-positive persons in oral rinse samples is twice as high as in the HIV-negative population . Smoking and treatment with azoles are risk factors for the oral carriage of non-albicans Candida spp . The isolation of yeasts on CAC plates supplemented with fluconazole allows combination of presumptive yeast identification and fluconazole susceptibility testing. Eur J Clin Microbiol Infect Dis, 1998 Apr, 17(4), 278 - 81 Mycobacterium celatum infection in two HIV-infected patients treated prophylactically with rifabutin; Gholizadeh Y et al.; Mycobacterium celatum is a recently described slow-growing species . It was identified on the basis of genomic sequencing that differentiates three types . The present report describes two cases of Mycobacterium celatum type 1 infection in patients with AIDS . Both patients had CD4+ lymphocyte counts of < 10/mm3, were receiving rifabutin prophylaxis, and had attended the same treatment units . The minimum inhibitory concentration of rifabutin for both strains was 8 mg/l, which may account for the failure of prophylaxis . As all type 1 strains have the same pulsed-field gel electrophoresis pattern, nosocomial transmission or acquisition from a common source could not be ruled out. Arzneimittelforschung, 1998 Jul, 48(7), 758 - 63 Synthesis and structure-activity relationships of 3-hydrazono-1H-2-indolinones with antituberculosis activity; Karah N et al.; A series of 3-{S-(4-substituted phenacyl)-4-substituted-isothiosemicarbazono}-1H-2-indolinones+ ++ 2a-h and 3-{(3,4-disubstituted-4-thiazolin-2-ylidene)hydrazono}-1H-2- indolinones 3a-f were synthesized . These new hydrazonoindolinone derivatives and 3-(4-substituted-thiosemicarbazono)-1H/1-acetyl-2-indolinones++ + 1a-g 3-{(2-substituted-4-thiazolidinon-2-ylidene)hydrazono}-1H-2- indolinones 4a-o, 3-{(2-substituted-4-carboxy/carbetoxy-5-methyl-4-thiazolin-2 -ylidene) hydrazono}-1H-2-indolinones 5a-e and 3-substituted-hydrazono-1H-2-indolinones 6a-o which had been previously reported were evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv . These compounds exhibited varying degrees of inhibition in the in vitro primary screening that was conducted at 12 micrograms/ml against M . tuberculosis H37Rv in BACTEC 12B medium using the BACTEC 460 radiometric system . 2a, 2c, 2f-h, 3c and 3f demonstrating activity in the primary screen were re-tested at lower concentrations against M . tuberculosis H37Rv to determine the actual minimum inhibitory concentration (MIC) in CABTEC 460 . The structure-activity relationships of the derivatives were investigated. J Clin Microbiol, 1998 Sep, 36(9), 2609 - 12 Clinical evaluation of the ASTY colorimetric microdilution panel for antifungal susceptibility testing; Pfaller MA et al.; A method using a commercially prepared colorimetric microdilution panel (ASTY; Kyokuto Pharmaceutical Industrial Co., Ltd.) was compared in four different laboratories with the National Committee for Clinical Laboratory Standards (NCCLS) reference microdilution method by testing 802 clinical isolates of Candida spp . (C . albicans, C . glabrata, C . tropicalis, C . parapsilosis, C . krusei, C . lusitaniae, C . guilliermondii, C . lipolytica, C . rugosa, and C . zeylanoides) against amphotericin B, 5-fluorocytosine (5FC), fluconazole, and itraconazole . Reference MIC endpoints were established after 48 h of incubation, and ASTY endpoints were established after 24 and 48 h of incubation . ASTY endpoints were determined to be the time at which the color of the first well changed from red (indicating growth) to purple (indicating growth inhibition) or blue (indicating no growth) . Excellent agreement (within 2 dilutions) between the reference and colorimetric MICs was observed . Overall agreement was 93% at 24 h and 96% at 48 h . Agreement ranged from 90% with itraconazole and 5FC to 96% with amphotericin B at 24 h and from 92% with itraconazole to 99% with amphotericin B and 5FC at 48 h . The ASTY colorimetric microdilution panel method appears to be comparable to the NCCLS reference method for testing the susceptibilities of Candida spp . to a variety of antifungal agents. Clin Oncol (R Coll Radiol), 1998, 10(3), 165 - 9 A phase II trial of four courses of preoperative chemotherapy in squamous or anaplastic carcinoma of the oesophagus; Steyn RS et al.; We have reported the results of a previous Phase II trial of two courses of neoadjuvant mitomycin (6 mg/m2), ifosfamide (3 g/m2) and cisplatin (50 mg/m2) (MIC) in squamous or anaplastic carcinoma of the oesophagus . In this current study, we have investigated whether there was any clinical benefit in extending the preoperative treatment to four courses for patients who responded after two courses . Response was assessed by barium swallow, which was compared with previous barium swallows performed prior to any treatment and after the second course of MIC . Of an initial 43 patients, 27 (63%) were assessed as responders after two courses of MIC . Twenty of these 27 patients were entered into the study with a view to receiving two further courses of MIC prior to surgery . Seventeen completed four courses . Five patients were complete responders after two courses and remained complete responders after four courses . Twelve patients were partial responders after two courses; six of these became complete responders after four courses, five remained partial responders, and one showed progression . Haematological toxicity and alopecia were increased after extending the number of courses beyond two . On pathological assessment, three patients with a complete response after four courses, and one with a complete response after three courses, had microscopic clearance of tumour . Extension beyond two courses of neoadjuvant MIC gives an improvement in response, as judged by barium assessment, but increases toxicity, cost of treatment and delay before surgery . Although the numbers are small, the results suggest that a worthwhile improvement in the radiological response of squamous or anaplastic oesophageal tumours may be gained by proceeding beyond two courses of MIC . A randomized trial, with larger numbers of patients, is needed to show whether there is any improvement in radiological and pathological response rates and in survival to be gained by the extension of treatment beyond two courses. Pathol Int, 1998 Jun, 48(6), 475 - 80 Ganglion cells in Ewing's sarcoma following chemotherapy: a case report; Maeda G et al.; A case of Ewing's sarcoma of the bone, arising in the right radius of a 12-year-old girl, which showed unique histologic features after pre-operative treatment, is reported . The light microscopic features of a biopsy sample were those of a small round cell tumor showing positive immunoreaction with antibodies against the product of the MIC 2 gene (O13), neuron-specific enolase, neurofilament, and synaptophysin, but no morphological differentiation . The patient received combined intensive multi-drug chemotherapy and radiation before surgery . Examination of the surgical specimen showed that the tumor was less cellular than that in the biopsy specimen, and was composed mainly of loosely textured large cells mimicking ganglion cells, occasionally forming Homer-Wright rosettes . An immunohistochemical study revealed that neural differentiation was enhanced . Immunoreactivity for Leu-7 also became positive . Although the patient underwent postoperative chemotherapy, she died of multiple lung and bone metastases 30 months after the diagnosis . Autopsy showed that metastatic foci were made up of densely packed small round cells like those seen in the biopsy samples, but associated with prominent Homer-Wright rosettes . To the authors' knowledge, this is the first report of a tumor being replaced almost entirely by ganglion cells after pre-operative chemotherapy and radiotherapy. Aliment Pharmacol Ther, 1998 Jul, 12(7), 635 - 9 Amoxycillin resistance is one reason for failure of amoxycillin-omeprazole treatment of Helicobacter pylori infection; Dore MP et al.; BACKGROUND: The efficacy of omeprazole and amoxycillin dual therapy to treat Helicobacter pylori infection has been inconsistent, suggesting the presence of host or bacterial factors influencing treatment success . The aim of this study was to assess the role of pre-treatment amoxycillin resistance in the efficacy of omeprazole and amoxycillin dual therapy . METHODS: We studied 43 consecutive dyspeptic patients with H . pylori infection . Pre-treatment H . pylori infection was established by the combination of positive rapid urease test, culture and histology . Amoxycillin susceptibility testing was performed by an Epsilometer test (E-test) method and amoxycillin resistance was defined as minimum inhibitory concentration greater than 8 microg/mL . Patients received 20 mg omeprazole twice daily for 28 days and amoxycillin 1000 mg twice daily for 2 weeks . Adverse effects were documented using a questionnaire . H . pylori status was reassessed 6-8 weeks after the end of treatment by rapid urease testing and histological examination of gastric biopsies . RESULTS: Forty-two dyspeptic patients completed the study, and one patient dropped out . H . pylori infection was cured in 2 3 of 42 patients (55%) . The cure rate was higher in patients harbouring amoxycillin-sensitive organisms than in those with resistant strains: 66% (19/29) vs . 31% (4/13), respectively (P = 0.049) . No significant differences in cure rates were evident in relation to age, sex, smoking habits or compliance . CONCLUSIONS: The effectiveness of amoxycillin-omeprazole dual therapy was greatly reduced in the presence of pre-treatment amoxycillin-resistant H . pylori . The success rate in patients with amoxycillin-sensitive H . pylori was only 66%, suggesting the presence of additional factors affecting the efficacy of this therapy. J Antimicrob Chemother, 1998 Jul, 42(1), 91 - 4 In-vitro activity of voriconazole against Aspergillus spp . and comparison with itraconazole and amphotericin B; Oakley KL et al.; The in-vitro activity of the triazole antifungal agent voriconazole was compared with itraconazole and amphotericin B against 60 aspergillus isolates . Susceptibility tests were performed using two methods: a macrodilution and a microdulution method . For macrodilution methodology, geometric mean (GM) MIC values and ranges were 0.4 and 0.125-4 mg/L for voriconazole, 0.24 and 0.06-->16 mg/L for itraconazole, and 1.04 and 0.5-4 mg/L for amphotericin B . For the microdilution method, GM MICs and ranges were 0.66 and 0.125-2 mg/L for voriconazole, 0.27 and 0.06-->16 mg/L for itraconazole, and 1.62 and 0.25-32 mg/L for amphotericin B . In conclusion, voriconazole is active against Aspergillus spp . in vitro, and at similar concentrations to itraconazole. J Formos Med Assoc, 1998 Jul, 97(7), 453 - 7 beta-Lactam resistance and beta-lactamase isoforms of Moraxella catarrhalis isolates in Taiwan; Fung CP et al.; Moraxella catarrhalis is an important pathogen in both upper and lower respiratory tract infections . More than 90% of isolates worldwide produce beta-lactamase . The beta-lactamases produced by M . catarrhalis can be differentiated by isoelectric focusing (IEF) into BRO-1 and BRO-2 patterns . In this study, we investigated the prevalence of various beta-lactamase isoforms in clinical isolates of M . catarrhalis in Taiwan, as well as the relationships of these isoforms with antibiotic resistance . A total of 271 clinical isolates of M . catarrhalis were collected from 12 large medical laboratories in Taiwan from 1 August 1993 to 31 July 1995 . The overall prevalence of beta-lactamase production was 98.2% (266 of 271 isolates) . Analytical IEF revealed BRO-1 was the most common beta-lactamase pattern among the isolates (238 isolates, 88%); BRO-2 was the only other pattern found, with 32 (12%) isolates . The geometric mean minimum inhibitory concentration of ampicillin for BRO-1 producers was 63-fold higher than that for beta-lactamase-negative isolates, and 6.5-fold higher than that for BRO-2 producers . beta-Lactam antibiotics, such as amoxicillin + clavulanate and the cephalosporins, tested were very active against this species, regardless of whether the isolate produced beta-lactamase or not . In conclusion, beta-lactamase is common among clinical isolates of M . catarrhalis in Taiwan, with BRO-1 being the most common isoform . However, because most isolates tested were still sensitive to amoxicillin + clavulanate and cephalosporins, these agents appear to be reliable alternatives to first-line therapy when M . catarrhalis is contributing to a clinical infection. Tissue Antigens, 1998 Jun, 51(6), 649 - 52 Sequencing-based typing reveals six novel MHC class I chain-related gene B (MICB) alleles; Visser CJ et al.; The MHC class I chain-related gene A (MICA) is highly polymorphic . In this paper we demonstrate polymorphism in the other expressing member of the MIC family of genes: MICB . Using a sequencing-based typing approach on cDNA, analysis of exons 2 through 6 revealed eight polymorphic sites resulting in six unique MICB sequences . Although MICB has high nucleotide homology with MICA, its polymorphism is restricted and at different sites compared to those in MICA. Arch Pharm (Weinheim), 1998 May, 331(5), 193 - 7 Substituted xanthones as antimycobacterial agents, Part 2: Antimycobacterial activity; Pickert M et al.; A series of substituted xanthones was tested for their activity against four mycobacterial strains (Mycobacterium tuberculosis, M . avium, M . lufu, M . smegmatis) by determination of the minimum inhibitory concentrations (MIC values) . For the most active compounds, supplementary characterisation was performed by bacterial growth kinetics, which allows a more precise interpretation of their antimycobacterial effects . From the test set, 1-methyl-2,4,7-trinitroxanthone (8a) showed the highest antimycobacterial activity with a MIC value of 3 micrograms/mL against M . tuberculosis, which is comparable to the effect of well known drugs used in the treatment of tuberculosis . For all other compounds, the MIC values could not be determined, due to the comparatively low activity and to the poor solubility of the compounds, respectively . The semiquantitative evaluation of activity against the different strains of mycobacteria resulted in a classification into three activity classes, which will be used as dependent parameter in QSAR investigations, to be published in Part 3 of this series. Int Clin Psychopharmacol, 1998 May, 13(3), 129 - 31 Effect of trifluoperazine, a potential drug for tuberculosis with psychotic disorders, on the growth of clinical isolates of drug resistant Mycobacterium tuberculosis; Gadre DV et al.; The effect of the antipsychotic drug trifluoperazine (TFP) on the in-vitro growth of 50 clinical isolates of Mycobacterium tuberculosis was tested . Of these isolates, 29 were susceptible to all five of the antitubercular drugs isoniazid, rifampicin, streptomycin, ethambutol and pyrazinamide, and 21 were resistant to one or more of the five drugs . The minimum inhibitory concentration (MIC) of TFP was 4 microg/ml for 40% of both the susceptible (12/29) and resistant (8/21) isolates and 8 microg/ml for 55% (16/29) and 48% (10/21) of the susceptible and resistant isolates respectively . Further analysis of the data for resistant isolates indicated that the MIC of TFP was 4 microg/ml and 16 microg/ml respectively for 50% (4/8) and 75% (6/8) of the isolates resistant to one drug only from isoniazid, streptomycin or pyrazinamide . Of the nine isolates resistant to two drugs, isoniazid and streptomycin, the MIC was 4 microg/ml for 33% (3/9) and 16 microg/ml for 80% (7/9) . The MIC of TFP for two isolates resistant to the three drugs isoniazid, rifampicin and streptomycin was 8 microg/ml for one and 32 microg/ml for the other . Of two isolates resistant to all five drugs, it is of interest to note that the MIC of TFP was only 4 microg/ml for one but 32 microg/ml for the other . Because the above MICs are for TFP as a single drug, it would be desirable to study the antitubercular activity of the serum of tuberculosis patients with psychotic problems receiving regular antitubercular therapy supplemented with TFP at its recommended and tolerated dose. Am J Med, 1998 Jul, 105(1), 7 - 11 A randomized trial of continuous or intermittent therapy with fluconazole for oropharyngeal candidiasis in HIV-infected patients: clinical outcomes and development of fluconazole resistance; Revankar SG et al.; PURPOSE: The effects of continuous or intermittent therapy with fluconazole on the recurrence of and the development of fluconazole resistance are not known . PATIENTS AND METHODS: We studied human immunodeficiency virus (HIV)-positive patients with CD4 cell count <350 x 10(6)/L and oropharyngeal candidiasis in a prospective, randomized study . After initial treatment, 20 patients (16 of whom completed 3 months of follow-up) received continuous fluconazole at 200 mg/day, and 48 patients (28 of whom completed follow-up) received intermittent therapy at the time of symptomatic relapses . Oral samples were obtained weekly during episodes of infection and quarterly as surveillance cultures . Development of resistance was defined as a fourfold rise in minimum inhibitory concentration (MIC) to at least 16 microg/mL from the initial culture in the same species, the emergence of new, resistant (MIC > or =16 microg/mL) species, or a significant increase in the proportion of resistant isolates . RESULTS: During a mean follow-up of 11 months, median annual relapse rates were lower in patients on continuous therapy (0 episodes/year) than in patients on intermittent therapy (4.1 episodes/year; P <0.001) . Sterile cultures were seen in 6 of 16 (38%) patients on continuous therapy compared with 3 of 28 (11%) on intermittent therapy (P = 0.04) . Microbiological resistance developed in 9 of 16 (56%) patients on continuous treatment, compared with 13 of 28 (46%) on intermittent treatment (P = 0.75) . However, despite isolates with increased MICs, 42 of 44 patients responded to fluconazole in doses up to 800 mg/day . CONCLUSIONS: In patients with frequent recurrences, continuous suppressive therapy significantly reduced relapses and colonization . Resistance occurred with both continuous and intermittent therapy; however, therapeutic responses were excellent. Antimicrob Agents Chemother, 1998 Aug, 42(8), 2070 - 3 In vitro susceptibility of Mycobacterium ulcerans to clarithromycin; Portaels F et al.; Buruli ulcer (BU), caused by Mycobacterium ulcerans, was recently recognized by the World Health Organization as an important emerging disease . While antimycobacterial therapy is often effective for the earliest nodular or ulcerative lesions, medical management of BU lesions in patients presenting for treatment is usually disappointing, leaving wide surgical excision the only alternative . Advanced ulcerated lesions of BU rarely respond to antimycobacterial agents; however, perioperative administration of such drugs may prevent relapses or disseminated infections . Clarithromycin possesses strong activity in vitro and in vivo against most nontuberculous mycobacteria . In this study we determined the antimycobacterial activity of this drug in vitro against 46 strains of M . ulcerans isolated from 11 countries . The MIC of clarithromycin was determined at pH 6.6 (on 7H11 agar) and at pH 7.4 (on Mueller-Hinton agar) . The MICs ranged from 0.125 to 2 microg/ml at pH 6.6 and from <0.125 to 0.5 microg/ml at pH 7.4 . For the majority of the strains, geographic origin did not play a significant role . Thirty-eight strains (83%) were inhibited by 0.5 microg/ml at pH 7.4 . These MICs are below peak therapeutic concentrations of clarithromycin obtainable in blood . These results suggest that clarithromycin is a promising drug both for the treatment of early lesions of M . ulcerans and for the prevention of hematogenous dissemination of the etiologic agent during and after surgery . Studies should be initiated to evaluate the effects of clarithromycin in combination with ethambutol and rifampin on M . ulcerans both in vitro and in experimentally infected mice . Multidrug regimens containing clarithromycin may also help control the secondary bacterial infections sometimes seen in BU patients, most importantly osteomyelitis. Antimicrob Agents Chemother, 1998 Aug, 42(8), 2066 - 9 In vitro and in vivo activities of moxifloxacin and clinafloxacin against Mycobacterium tuberculosis; Ji B et al.; On 10% oleic acid-albumin-dextrose-catalase-enriched 7H11 agar medium, the MIC at which 90% of the isolates are inhibited for 20 strains of Mycobacterium tuberculosis was 0.5 microg of sparfloxacin (SPFX) or moxifloxacin (MXFX) per ml and 1.0 microg of clinafloxacin (CNFX) per ml, indicating that the in vitro activities of SPFX and MXFX were virtually identical and were slightly greater than that of CNFX . However, the in vivo activities of these drugs in a murine tuberculosis model differed considerably . Female Swiss mice were infected intravenously with 6.2 x 10(6) CFU of the H37Rv strain and treated for 4 weeks, beginning the next day after infection, with isoniazid (INH) serving as the positive control . By the criteria of 30-day survival rate, spleen weight, gross lung lesion, and mean number of CFU in the spleen, treatment with CNFX at up to 100 mg/kg of body weight six times weekly displayed no measurable effect against M . tuberculosis, whereas both SPFX and MXFX were effective; administration six times weekly of either of the latter two drugs demonstrated dosage-dependent bactericidal effects, as measured by enumeration of CFU in the spleens, and MXFX appeared more bactericidal than the same dosage of SPFX . Of the three fluoroquinolones, only MXFX at 100 mg/kg six times weekly appeared as bactericidal as INH at 25 mg/kg six times weekly . Thus, MXFX may be an important component of the newer combined regimens for treatment of tuberculosis. Antimicrob Agents Chemother, 1998 Aug, 42(8), 2002 - 5 Activities of three quinolones, alone and in combination with extended-spectrum cephalosporins or gentamicin, against Stenotrophomonas maltophilia; Visalli MA et al.; The present study examined the activities of trovafloxacin, levofloxacin, and ciprofloxacin, alone and in combination with cefoperazone, ceftazidime, cefpirome, and gentamicin, against 100 strains of Stenotrophomonas maltophilia by the MIC determination method and by synergy testing of the combinations by the time-kill and checkerboard titration methods for 20 strains . The respective MICs at which 50% and 90% of isolates were inhibited for the drugs used alone were as follows: trovafloxacin, 0.5 and 2.0 microg/ml; levofloxacin, 2.0 and 4.0 microg/ml; ciprofloxacin, 4.0 and 16.0 microg/ml; cefoperazone, >128.0 and >128.0 microg/ml; ceftazidime, 32.0 and >128.0 microg/ml; cefpirome, >128.0 and >128.0 microg/ml; and gentamicin, 128.0 and >128.0 microg/ml . Synergistic fractional inhibitory concentration indices (</=0.5) were found for >/=50% of strains for trovafloxacin-cefoperazone, trovafloxacin-ceftazidime, levofloxacin-cefoperazone, levofloxacin-ceftazidime, ciprofloxacin-cefoperazone, and ciprofloxacin-ceftazidime, with other combinations affecting fewer strains . For 20 strains tested by the checkerboard titration and time-kill methods, synergy (>/=100-fold drop in count compared to the count achieved with the more active compound) was more pronounced after 12 h due to regrowth after 24 h . At 12 h, trovafloxacin at 0.004 to 0.5 microg/ml showed synergy with cefoperazone for 90% of strains, with ceftazidime for 95% of strains with cefpirome for 95% of strains, and with gentamicin for 65% of strains . Levofloxacin at 0.03 to 0.5 microg/ml and ciprofloxacin at 0.5 to 2.0 microg/ml showed synergy with cefoperazone for 80% of strains, with ceftazidime for 90 and 85% of strains, respectively, with cefpirome for 85 and 75% of strains, respectively, and with gentamicin for 65 and 75% of strains, respectively . Time-kill assays were more discriminatory than checkerboard titration assays in demonstrating synergy for all combinations. J Antimicrob Chemother, 1998 Jun, 41(6), 615 - 9 In-vitro isolation and antifungal susceptibility of amphotericin B-resistant mutants of Aspergillus fumigatus; Manavathu EK et al.; Aspergillus fumigatus mutants resistant to amphotericin B were selected in the laboratory following UV irradiation . A total of 18 colonies (frequency 1.8 x 10(-7)) that grew in the presence of amphotericin B (8 mg/L and 16 mg/L) on peptone yeast extract glucose agar were tested for their susceptibility to amphotericin B, nystatin, azoles, and the echinocandin L-743872 . Ten of the 18 isolates showed an eight-fold rise in amphotericin B MIC (4 mg/L) compared with the susceptible parent whereas the remaining isolates showed a 16 to 32-fold rise in amphotericin B MIC (8-16 mg/L) . Subculturing of three representatives from each of the groups that had MIC values of 4 mg/L and 8-16 mg/L for six cycles revealed that the resistance trait was stably expressed . All amphotericin B-resistant isolates showed a significant level of cross-resistance to nystatin but not to azoles and L-743872 . Kill-curve studies with amphotericin B revealed that the killing of the resistant isolates was significantly less than that of the susceptible parent strain . These results show that amphotericin B-resistant mutants of A . fumigatus can be isolated in the laboratory following a single-step UV-induced mutagenesis and suggest that similar mechanisms could operate in nature for the emergence of resistance in clinical isolates. J Ethnopharmacol, 1998 May, 61(1), 81 - 3 Effect of the extract of Annona muricata and Petunia nyctaginiflora on Herpes simplex virus; Padma P et al.; Annona muricata (Annonaceae) and Petunia nyctaginiflora (Solanaceae) were screened for their activity against Herpes simplex virus-1 (HSV-1) and clinical isolate (obtained from the human keratitis lesion) . We have looked at the ability of extract(s) to inhibit the cytopathic effect of HSV-1 on vero cells as indicative of anti-HSV-1 potential . The minimum inhibitory concentration of ethanolic extract of A . muricata and aqueous extract of P . nyctaginiflora was found to be 1 mg/ml. J Ethnopharmacol, 1998 May, 61(1), 57 - 65 Antiamoebic and phytochemical screening of some Congolese medicinal plants; Tona L et al.; Results from the in vitro antiamoebic activity of some Congolese plant extracts used as antidiarrhoeic in traditional medicine indicated that of 45 plant extracts tested, 35 (77.78%) exhibited an antiamoebic activity and 10 (22.22%) were inactive . The highest activity (MIC < 100 microg/ml) was obtained with extracts from root bark of Paropsia brazzeana, Cryptolepis sanguinolenta, Alchornea cordifolia, Hensia pulchella, Maprounea africana, Rauwolfia obscura and Voacanga africana, leaves and stem bark of Psidium guajava, stem bark of Dialum englerianum, Harungana madagascariensis and Mangifera indica, mature seeds of Carica papaya, and leaves of Morinda morindoides and Tithonia diversifolia . Metronidazole used as reference product showed a more pronounced activity than that of all plant extracts tested. Pediatr Infect Dis J, 1998 Jul, 17(7), 631 - 8 Management of acute otitis media caused by resistant pneumococci in infants; Roger G et al.; OBJECTIVES: To assess the clinical outcome and risk of failure after oral vs . intravenous treatment in otitis media caused by penicillin-resistant pneumococci . To determine the possible correlations between pneumococcal minimal inhibitory concentration (MIC) to penicillin and clinical outcome . DESIGN: Retrospective study of 156 cases collected between 1993 and 1995 . Mean follow-up: 5 months . Setting . Two tertiary academic medical centers in Paris, France . PATIENTS AND METHODS: Pneumococcus was isolated from 191 of 570 ear samples obtained from children with otitis media and shown to be penicillin-resistant in 156 . Medical history, antibiotic therapy during the previous 3 months and day-care center attendance were reviewed . For the current episode microbiologic characteristics of the isolated strains, type of treatment, therapy efficacy and clinical outcome were analyzed . Patients were predominantly young (76.3% were <1 year old) and bacteriologic samples were taken mainly because of previous treatment failure . RESULTS: Among 156 children with pneumococcal penicillin-resistant otitis media, 72.2% attended day-care centers, 71.8% had been previously treated with aminopenicillin and 52.5% with cephalosporins . Failure of previous empirical oral therapy was noted in 84% (one-third of these had been receiving amoxicillin-clavulanate) . Patients treated intravenously had had a more protracted otitis but no greater number of previous episodes of acute otitis media than those receiving oral therapy . Acute mastoiditis occurred in 4 infants resulting in mastoidectomy . Oral treatment (mainly with high dose amoxicillin,120 to 150 mg/kg/day) and intravenous therapy (cephalosporin or glycopeptide) had been used in 59 and 41%, respectively . Mean duration of therapy was 10.7 days . Three failures (1.9%) and 10 recurrences (6.4%, average 28 days) occurred . No statistical difference was found between intravenous and oral therapy with respect to risk of recurrence . A high penicillin MIC value was correlated with previous antibiotic treatment but not with clinical outcome . CONCLUSIONS: Oral therapy appears to be as effective as intravenous therapy for the treatment of penicillin-resistant pneumococcal otitis media . Intravenous treatment should not necessarily be dictated by the penicillin susceptibility value but should be considered in cases of failure to thrive, persistent otitis or other complications. J Vet Intern Med, 1998 Jul-Aug, 12(4), 259 - 66 Infectious bovine keratoconjunctivitis: a review; Brown MH et al.; The economic impact of infectious bovine keratoconjunctivitis (IBK) warrants continued investigation of the mechanisms by which Moraxella bovis survives on and colonizes the corneal surface . Virulent strains of M bovis produce hemolysin and exhibit different plasmid profiles than nonvirulent strains . Interactions among host, environment, vector, season, and concurrent infection influence the prevalence of IBK . Mycoplasma sp . or infectious bovine rhinotracheitis virus may enhance or hasten the disease process . The manifestations of IBK may range from mild conjunctivitis to severe ulceration, corneal perforation, and blindness . Treatment of IBK is dictated by economic considerations, intended animal use, and feasibility of administration . Antibiotic therapy is aimed at achieving drug concentrations in tears to meet or exceed the minimum inhibitory concentration for prolonged periods . At present, IBK is not a preventable disease . Affected animals must be separated from the herd and vector control vigorously instituted . Carrier animals must be identified and removed from the herd . Vaccination trials have been unsuccessful because of pili antigen cross-reactivity, variable strains, and uncontrolled environmental factors . Recent investigations have determined that M bovis may utilize host iron sources via iron-repressible outer membrane proteins and siderophores for growth . Elucidation of normal defense mechanisms of the bovine eye may lead to new strategies to enhance the immune response against M bovis. J Control Release, 1998 Mar 2, 52(1-2), 215 - 20 Optimized release of dexamethasone and gentamicin from a soluble ocular insert for the treatment of external ophthalmic infections; Baeyens V et al.; In the case of external ophthalmic infections, repeated instillations of antibiotics are required to reach therapeutic level, above the minimal inhibitory concentration (MIC) . An additional administration of a corticosteroid is often needed, in order to limit the precorneal damages caused by the infection . However, repeated administration of a corticosteroid can increase intraocular pressure and thus lead to glaucoma . To overcome the disadvantages of separated and repeated instillations of two products and to avoid the side effects of dexamethasone, a soluble insert containing gentamicin sulfate and dexamethasone phosphate was developed . The new system ensures the concomitant release of the two drugs during the first 10 h of treatment, followed by an adequate concentration of gentamicin sulfate, above the MIC of 4.0 microgram ml-1, during 50 h, due to a combination of gentamicin sulfate with cellulose acetate phthalate, which reduces the solubility of gentamicin. CLAO J, 1998 Jul, 24(3), 166 - 8 Collagen shield delivery of tobramycin to the human eye; Taravella M et al.; PURPOSE: The purpose of this study was to determine the ocular penetration of tobramycin into the anterior chamber of the human eye when delivered by a pre-soaked collagen shield . METHODS: We conducted a prospective, randomized study of 32 patients undergoing cataract surgery . The subjects were divided into two groups . The first group received three preoperative drops of commercially available combination tobramycin-dexamethasone drops at 15 minute intervals . In the second group, a collagen shield soaked in the same medication was applied to the eye prior to surgery . At the beginning of surgery, the aqueous humor was extracted for analysis . RESULTS: The samples from 11 patients could not be analyzed due to an insufficient aqueous sample . Of the remaining 21 patients, the mean aqueous concentration was 0.026 microgram/mL (range: 0.0-0.09) in the drops group and 0.024 microgram/mL (range: 0.04-0.8 microgram/mL) in the shield group . This difference was not statistically significant . The aqueous concentration in both groups did not approach the minimum inhibitory concentration (4 micrograms/mL) for common ocular pathogens . No adverse effects related to the use of collagen shields occurred . CONCLUSIONS: Perioperative use of a pre-soaked collagen shield utilizing a commercially available preparation of tobramycin-dexamethasone combination drops appears safe . However, the use of this system to prevent endophthalmitis is not warranted based on the concentrations obtained from the aqueous humor. Eye, 1998, 12 ( Pt 2), 266 - 72 The use of corticosteroids for choroidal neovascularisation in young patients; Flaxel CJ et al.; PURPOSE: To investigate the role of systemic corticosteroids in the treatment of sight-threatening choroidal neovascularisation (CNV) in patients with punctate inner choroidopathy (PIC) and multifocal inner choroiditis (MIC) . METHODS: Twelve eyes of 10 patients with evidence of PIC or MIC with recent visual symptoms were identified . All eyes had CNV within the foveal avascular zone on fundus fluorescein angiography (FFA) . Systemic oral prednisolone at an initial dose of 1 mg/kg (60-80 mg) was given for 3-5 days and the dose was subsequently tapered . Changes in best corrected visual acuity and leakage on FFA were recorded during follow-up . Systemic side-effects of the corticosteroids were monitored . RESULTS: In 10 of 12 eyes vision improved or stabilised . Leakage on FFA resolved in 9 eyes and was reduced in 3 . Four patients required more than one course of oral corticosteroids . One patient was maintained on low-dose oral corticosteroids for recurrent CNV activity . No systemic complications from the treatment were observed . CONCLUSION: A course of oral corticosteroids in healthy young patients with subfoveal CNV in PIC or MIC may reduce subretinal vascular leakage and stabilise vision when no other proven treatment option is available. Ann Trop Med Parasitol, 1998 Jun, 92(4), 449 - 58 Why is it that antimalarial drug treatments do not always work? White NJ. The objective of antimalarial drug treatment in severe malaria is to save the patient's life . In uncomplicated malaria it is to reduce the parasite biomass to zero, or down to a level where host defences can deal with the remainder . Treatment regimens with rapidly eliminated drugs must generally cover four asexual life-cycles (i.e . > 6 days for Plasmodium falciparum and P . vivax) to eradicate all the parasites in the blood . For slowly eliminated drugs, blood concentrations must exceed the parasites' minimum inhibitory concentration (and preferably the minimum parasiticidal concentration) until all parasites have been eradicated . Resistance means that there is a right shift in the concentration-effect relationship . This may be large and abrupt, as with the point mutations that confer pyrimethamine, sulphonamide or atovaquone resistance, or slow and gradual, as with the processes that determine resistance to chloroquine, quinine or mefloquine . Although treatment failure in malaria usually results from poor compliance, inadequate dosing, pharmacokinetic factors or resistance, some infections will recrudesce when none of these factors operates . How parasites persist despite apparently adequate antimalarial treatment remains unresolved. J Nat Prod, 1998 Jul, 61(7), 965 - 8 A new antitubercular mulinane diterpenoid from Azorella madreporica Clos; Wachter GA et al.; Bioactivity-guided fractionation of the petroleum ether extract of Azorella madreporica Clos has led to the isolation of the novel, antitubercular mulinane diterpenoid 1 . The structure has been elucidated on the basis of its 1D and 2D NMR spectra and by comparison with mulinolic acid 2 and a dehydration product 3 obtained from 1 . The MIC of 1 for growth inhibition of the H37Rv strain of Mycobacterium tuberculosis was determined as 20 microg/mL . LC-MS and NMR have suggested the presence of this new compound in four other species of Azorella. Hindustan Antibiot Bull, 1996 Feb-Nov, 38(1-4), 32 - 6 Antifungal activity (invitro) of certain polyene macrolide antibiotics against various plant pathogens; Bhat JM et al.; Certain polyene macrolides were developed from different actinomycetes at Research and Development of Hindustan Antibiotics Limited . These antibiotics were screened for the antifungal activity against various plant pathogens . IC50 and MIC of each of the antibiotic against the plant pathogens was found out and is being reported. Clin Infect Dis, 1998 Jul, 27(1), 10 - 22 The pharmacodynamics of beta-lactams; Turnidge JD; Considerable information on the pharmacodynamics of beta-lactams has accumulated in the past 20 years . In vitro, beta-lactams demonstrate time-dependent killing and variable postantibiotic effects . Animal models have shown that the time for which drug levels exceed the minimum inhibitory concentration (MIC) correlates best with bacterial eradication, and this is now being borne out in human studies . In investigations on osteomyelitis and endocarditis, trough serum inhibitory titers have generally correlated better with cure than have peak titers, and studies that have analyzed outcomes in relation to the MIC for the infecting pathogen have shown decreasing clinical efficacy with increasing MICs . One prospective study has shown that time above MIC correlated better with time to pathogen eradication than did area under the curve . In some continuous-infusion studies, significantly better outcomes were achieved with continuous infusion against susceptible bacteria or for patients with persistent, profound neutropenia . With use of time above MIC as the predictor of efficacy, it is possible to reexamine current dosing schedules critically. Mycoses, 1998 Mar-Apr, 41(3-4), 153 - 62 Efficacy of oral fluconazole in tinea pedis of the hyperkeratotic type . Stratum corneum levels; Tanuma H et al.; In this study, in addition to studying the efficacy and safety of the once-daily administration of 100-mg capsules of fluconazole over an 8-week administration period with six patients with hyperkeratotic-type tinea pedis, we also measured the serum and horny layer concentrations of fluconazole to study the mobility into