Towards a carbon independent and CO2-free electrochemical membrane process for NH3 synthesis.

Ammonia is exclusively synthesized by the Haber-Bosch process starting from precious carbon resources such as coal or CH4. With H2O, H2 is produced and with N2, NH3 can be synthesized at high pressures and temperatures. Regrettably, the carbon is not incorporated into NH3 but emitted as CO2. Valuable carbon sources are consumed which could be used otherwise when carbon sources become scarce. We suggest an alternative process concept using an electrochemical membrane reactor (ecMR). A complete synthesis process with N2 production and downstream product separation is presented and evaluated in a multi-scale model to quantify its energy consumption. A new micro-scale ecMR model integrates mass, species, heat and energy balances with electrochemical conversions allowing further integration into a macro-scale process flow sheet. For the anodic oxidation reaction H2O was chosen as a ubiquitous H2 source. Nitrogen was obtained by air separation which combines with protons from H2O to give NH3 using a hypothetical catalyst recently suggested from DFT calculations. The energy demand of the whole electrochemical process is up to 20% lower than the Haber-Bosch process using coal as a H2 source. In the case of natural gas, the ecMR process is not competitive under today's energy and resource conditions. In future however, the electrochemical NH3 synthesis might be the technology-of-choice when coal is easily accessible over natural gas or limited carbon sources have to be used otherwise but for the synthesis of the carbon free product NH3.

Single-cell analysis of the nervous system at small and large scales with instant partitions.

Single-cell RNA sequencing is a new frontier across all biology, particularly in neuroscience. While powerful for answering numerous neuroscience questions, limitations in sample input size, and initial capital outlay can exclude some researchers from its application. Here, we tested a recently introduced method for scRNAseq across diverse scales and neuroscience experiments. We benchmarked against a major current scRNAseq technology and found that PIPseq performed similarly, in line with earlier benchmarking data. Across dozens of samples, PIPseq recovered many brain cell types at small and large scales (1,000-100,000 cells/sample) and was able to detect differentially expressed genes in an inflammation paradigm. Similarly, PIPseq could detect expected and new differentially expressed genes in a brain single cell suspension from a knockout mouse model; it could also detect rare, virally-la-belled cells following lentiviral targeting and gene knockdown. Finally, we used PIPseq to investigate gene expression in a nontraditional model species, the little skate (Leucoraja erinacea). In total, PIPSeq was able to detect single-cell gene expression changes across models and species, with an added benefit of large scale capture and sequencing of each sample.

Cyclin E is the only cyclin-dependent kinase 2-associated cyclin that predicts metastasis and survival in early stage non-small cell lung cancer.

Progression through G1-S transition and S phase of the cell cycle is mediated by cyclin-dependent kinase 2 (cdk2), which interacts with several cyclins. Two of these, cyclin E and cyclin A2 (also known as cyclin A), are overexpressed in many cancers. Cyclin E2 and cyclin A1 are recently discovered cdk2-interacting cyclins that are found in malignant tumor cell lines and in acute myeloid leukemia, respectively. Expression and prognostic role of these cyclins in solid tumors is unknown. Here, we have analyzed expression and prognostic relevance of the cdk2-associated cyclins in non-small cell lung cancer (NSCLC). Fresh-frozen biopsies (n = 70) from completely resected tumors with stage I to IIIA NSCLC were studied. Gene expression was analyzed by quantitative real-time reverse transcription-PCR. Expression levels of cyclin E (P = 0.04) and cyclin A2 (P = 0.004) were significantly higher in the tumor samples than in normal controls. Cyclin A1, cyclin A2, and cyclin E2 expression levels did not have prognostic relevance for survival. The mean survival time associated with low and high levels of cyclin E was 69.4 and 47.2 months, respectively, which was statistically significant (P = 0.03). Differences in survival were particularly pronounced in stages I and II. Cyclin E was also closely associated with the development of distant metastasis (P = 0.01). Finally, we confirmed by immunohistochemistry analyses that cyclin E mRNA expression was closely associated with cyclin E protein expression. In conclusion, cyclin E is a strong independent prognostic indicator in patients with early-stage NSCLC, whereas cyclin E2, cyclin A1, and cyclin A2 do not have a prognostic role in NSCLC.

Expression of the p14ARF tumor suppressor predicts survival in acute myeloid leukemia.

Cell cycle aberrations are associated with therapy outcome in many types of cancer. We analyzed mRNA expression levels of 18 cell cycle-related genes in bone marrow samples from 78 acute myeloid leukemia (AML) patients and six controls using high-throughput quantitative RT-PCR. Samples of AML patients contained significantly increased mRNA expression levels of the mdm2 and c-myc oncogenes. Also, the average expression levels of p14ARF and p16INK4A were higher in patient samples compared to controls. Leukemic blasts and control bone marrow samples did not differ significantly in the expression levels of proliferation-associated genes such as cyclin A2 and pcna. When single genes were analyzed for prognostic significance in Kaplan-Meier and Cox regression analyses, a low p14ARF level emerged as a strong and independent predictor for poor survival (P=0.04 and 0.029). Subsequently, p14ARF mRNA levels were analyzed in a second, independent patient population (n=57). Again, low p14ARF levels were associated with a worse outcome. Finally, immunohistochemistry analysis of AML tissue arrays confirmed the widespread expression of c-myc and p14ARF in AML on the protein level. Taken together, the expression of the p53 regulators mdm2 and p14ARF are altered in AML, and low p14ARF levels indicate a poor prognosis.

Therapy of focal viral encephalitis in children with aciclovir and recombinant beta-interferon - results of a placebo-controlled multicenter study.

Focal viral encephalitis in childhood is a rare but life-threatening disease. Animal experiments and case reports suggest a positive effect of an additional therapy with interferon-beta on the course of the disease. Therefore, we initiated a prospective, double-blind placebo-controlled study to investigate the benefit of a combination therapy of Aciclovir (ACV) and recombinant interferon-beta (rIFN-beta) in juvenile focal viral encephalitis. - Initial inclusion criterium was suspicion of focal viral encephalitis. Diagnosis was proven by demonstration of characteristic focal lesions in cerebral imaging or virological evidence of HSV in cerebrospinal fluid. Patients were treated with ACV plus rIFN-beta or ACV plus placebo. Neurological outcome was determined 21 days and 3 months after onset of the disease. - Initially 59 patients were enrolled in the study. Encephalitis was proven in 14 patients (7 ACV + rIFN-beta, 7 ACV + placebo). The study groups were balanced in terms of important prognostic criteria. 10 patients (5 ACV + rIFN-beta, 5 ACV + placebo) were cured or had slight defects, 4 patients (2 ACV + rIFN-beta, 2 ACV + placebo) showed moderate to severe defects. There was no significant difference in favour of the additive therapy with rIFN-beta.

Determination of the antimicrobial activity of 29 clinically important compounds tested against fastidious HACEK group organisms.

HACEK group organisms are very fastidious organisms (Haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominus, Eikenella corrodens, Kingella spp.) that can produce serious invasive infections such as endocarditis. Problems with susceptibility testing methods and their rarity of isolation limit available information of therapeutic choices, particularly among newer antimicrobial agents. Forty-two HACEK strains were tested by the Etest (AB BIODISK, Solna, Sweden) method against 29 antimicrobial agents. Nearly all compounds exhibited activity with best potency observed among the tested beta-lactamase inhibitor combinations, "third- or fourth-generation" cephems, meropenem, fluoroquinolones, and rifampin. Numerous therapeutic options appear possible for initial parenteral treatment followed by oral "step-down" or switch therapy. Each case of HACEK infection therapy should be guided by accurate susceptibility tests, for which the Etest seems preferred for these fastidious species.

Bacterial pathogens isolated from patients with skin and soft tissue infections: frequency of occurrence and antimicrobial susceptibility patterns from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 1997). SENTRY Study Group (North America).

As part of the SENTRY Antimicrobial Surveillance Program, 1562 bacterial isolates were recovered from hospitalized patients with skin and soft tissue infections (SSTIs) in 30 United States (U.S.) and 8 Canadian medical centers between October and December, 1997. The overall rank order of recovery of the six most common pathogens was Staphylococcus aureus (42.6%) > Pseudomonas aeruginosa (11.3%) > Enterococcus spp. (8.1%) > Escherichia coli (7.2%) > Enterobacter spp. (5.2%) > beta-hemolytic streptocci (5.1%). With one exception, essentially the same order was observed in both the U.S. and Canada. The single exception was the Enterococcus group, which were the third most common isolate in the U.S. (9.6%), but the seventh most common isolate in Canada (3.7). Of note, 24.0% of S. aureus isolates were oxacillin resistant; vancomycin was uniformly active. Vancomycin resistance among Enterococcus spp. (16.5%) was observed only in the U.S. Several antimicrobial agents remained broadly active for SSTI isolates of P. aeruginosa, including meropenem, amikacin, tobramycin, and piperacillin with or without tazobactam. Imipenem resistance (MICs, > or = 8 micrograms/mL) was observed in 11.9% of isolates of P. aeruginosa and ceftazidime, and cefepime had equivalent activity (85.2% and 85.8% susceptible, respectively). Numerous beta-lactams, aminoglycosides and fluoroquinolones were broadly active against E. coli SSTI isolates (i.e. < 5% resistance). Extended-spectrum beta-lactamase production was uncommon both with E. coli and Klebsiella spp. in both nations. Cefepime, imipenem, and meropenem; the aminoglycosides; and fluoroquinolones were conspicuously more active against Enterobacter spp. than other agents tested. High-level, stably derepressed Amp C beta-lactamase production was commonly observed in this group (26.8%), but cefepime generally retained activity against these ceftazidime-resistant organisms. The results of this study serve to define the most common bacterial causes of SSTIs in North America, elucidate patterns of antimicrobial resistance and can be used as a basis for making initial empiric antimicrobial management decisions in hospitalized patients with such infections.

Respiratory tract pathogens isolated from patients hospitalized with suspected pneumonia: frequency of occurrence and antimicrobial susceptibility patterns from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 1997).

Thirty-seven sentinel hospitals (29 in the United States [US]; eight in Canada) collected bacterial isolates from hospitalized patients with a diagnosis of pneumonia. The antimicrobial susceptibility patterns of these pathogens were determined to more than 60 agents (40 reported) using the reference broth microdilution method described by the National Committee for Clinical Laboratory Standards. The five most frequently recorded species among the 2757 isolates collected during the study were (no. tested/%): Staphylococcus aureus (632/22.9%), Pseudomonas aeruginosa (498/18. 1%), Haemophilus influenzae (284/10.3%), Klebsiella spp. (240/8.7%), and Streptococcus pneumoniae (213/7.7%). There was a significant difference in the susceptibility to antimicrobials between the US and Canada for S. aureus to oxacillin (50.1% versus 93.8% susceptible, respectively), gentamicin (78.7% versus 97.8%), and fluoroquinolones (49.5 to 53.0% versus 89.8 to 94.9%). Amikacin (92. 8% susceptible) was the most active antimicrobial agent against P. aeruginosa, and meropenem was the most potent beta-lactam. Against H. influenzae, most drugs retained a high level of activity, whilst against the S. pneumoniae, only the newer fluoroquinolones (gatifloxacin, levofloxacin, sparfloxacin) remained highly effective in vitro. Only two antimicrobial agents (imipenem and meropenem) were >99% active against the Klebsiella spp. and Enterobacter spp. isolated in this survey (possess extended spectrum beta-lactamases or hyperproduction of Amp C cephalosporins); cefepime (95.6-100.0% susceptible) was significantly more active than other cephalosporins tested. Clonal, epidemic outbreaks of multiply resistant strains were very rare in monitored hospitals. In conclusion, important differences exist between the US and Canada in the susceptibility patterns of some respiratory tract pathogens to commonly used antimicrobial agents with Canadian strains generally being more susceptible to currently available antimicrobial agents.

Antibacterial activity of 41 antimicrobials tested against over 2773 bacterial isolates from hospitalized patients with pneumonia: I--results from the SENTRY Antimicrobial Surveillance Program (North America, 1998).

Pneumonia is the second most frequent cause of nosocomial infection, and hospitalization frequently is needed for community-acquired pneumonia. Knowledge of causative pathogens through periodic surveillance, and their prevailing antimicrobial susceptibility patterns becomes paramount in choosing appropriate empiric therapy. The SENTRY Antimicrobial Surveillance Program, tracks pathogen distribution worldwide since 1997 and documents emerging resistance to a wide range of antimicrobial agents. During the respiratory disease season in 1998, each of 30 medical centers (25 in the United States [US], and five in Canada [CAN]) contributed 100 consecutive isolates obtained from hospitalized patients with suspected pneumonia. The 2773 organisms, processed by the monitor consisted of a total of 35 species, with Staphylococcus aureus comprising 25.6% of all isolates and five other species (Pseudomonas aeruginosa 18.7%, Haemophilus influenzae 9.4%, Streptococcus pneumoniae 7.8%, Klebsiella spp. 7.0%, and Enterobacter spp. 6.7%) making up almost 50% of the total. In the US, pneumococci (8.5%) were more prevalent than in CAN (4.1%; p = 0.001). The US isolates of S. pneumoniae were variably susceptible to penicillin (76.8%), with non-susceptible strains demonstrating greater levels of cross resistance to macrolides (31.8%), cefepime (9.0%) and cefotaxime (6.8%), but remaining susceptible to gatifloxacin and quinupristin/dalfopristin. H. influenzae and Moraxella catarrhalis were generally ampicillin-resistant, 40.4-44.4% and 93.7-95.7%, respectively. P. aeruginosa remained very susceptible to amikacin (91.3-93.8%) > tobramycin > meropenem > piperacillin/tazobactam > gentamicin > piperacillin > cefepime (80.0-81.8%). Extended spectrum beta-lactamase phenotypes among the Klebsiella spp. were isolated from five medical centers in the US and were 4.8-6.0% overall; a rate similar to the previous year. Among the US isolates of Enterobacter spp., only 77.6% and 79.6% were susceptible to ceftazidime and cefotaxime, respectively, but >90% were inhibited by cefepime, imipenem, meropenem, aminoglycosides, and fluoroquinolones. Isolates from CAN were generally more susceptible, except for Pseudomonas isolates, where resistance to aminoglycosides, fluoroquinolones and imipenem was greater. The SENTRY Program results outline important national differences in the frequencies of pathogen occurrence, but more importantly, identify unstable patterns of resistance to available antimicrobial drugs, and serves as a reference for results of other local, national or international investigations.

Characteristics of pathogens causing urinary tract infections in hospitals in North America: results from the SENTRY Antimicrobial Surveillance Program, 1997.

Urinary tract infection (UTI) is common and involves pathogens with changing susceptibility patterns. The SENTRY Antimicrobial Surveillance Program evaluates international pathogen incidence patterns to detect and manage the emergence of resistant strains. We describe the antimicrobial resistance patterns among 1617 pathogens recovered from UTIs during the third-quarter of 1997 in North America (United States and Canada), as part of this worldwide program. The isolates were tested against more than 50 antimicrobial agents (20 reported) by reference broth microdilution methods, and selected isolates were characterized by pulsed-field gel electrophoresis (PFGE) and automated ribotyping. The five most frequently isolated species were Escherichia coli (48.6%), Enterococcus spp. (13.7%), Klebsiella spp. (12.0%), Pseudomonas aeruginosa (6.2%), and Enterobacter spp. or Proteus mirabilis (3.8% each). For each nation, imipenem and cefepime produced the widest spectrum of coverage among the beta-lactams and amikacin was best among the aminoglycosides. For Gram-negative species, high resistance among beta-lactam antimicrobial agents was noted especially for various penicillins against E. coli (37.9% to 42.8%) and for the cephalosporins tested against enterococci (99.4% and 100%). Approximately 7.0% of enterococci in the USA were vancomycin-resistant (88% with Van A). P. aeruginosa provided the most consistent levels of resistance, but the following agents were most active against these organisms: amikacin (96.6 to 97.4% susceptible), tobramycin (89.5 to 100.0%), piperacillin/tazobactam (89.5 to 100.0%), piperacillin (89.5 to 96.6%), imipenem (89.7 to 92.1%), cefepime (77.6 to 89.7%), and ceftazidime (82.9 to 86.2%). E. coli (2.2 to 2.7%), K. pneumoniae (6.2 to 6.4%), and a single Enterobacter cloacae strain produced extended-spectrum beta-lactamases; and five other Enterobacter spp. were likely to have expressed chromosomally mediated (Amp C) Stably derepressed cephalosporinases with associated resistance to ceftazidime (16.7 to 21.2% resistance). These data demonstrated that several UTI isolates in SENTRY hospitals have high levels of resistance to various classes of antimicrobial agents with little evidence of clonal dissemination.

Serious streptococcal infections produced by isolates resistant to streptogramins (quinupristin/dalfopristin): case reports from the SENTRY antimicrobial surveillance program.

The emergence and sustained prevalence of Gram-positive organisms resistant to antimicrobials has been of interest for over a decade. Quinupristin/dalfopristin (formerly RP 59500 or Synercid) is a new injectable streptogramin combination that has been reported to have activity against Gram-positive organisms, even those with documented MLS(B) resistance. However, the two case reports presented here illustrate three well-documented Streptococcus spp. strains (S. mitis, S. pneumoniae) to be resistant to quinupristin/dalfopristin (MICs at 3, 8, and 12 microg/ml) following referral as routine isolates in the SENTRY Antimicrobial Surveillance Program. The S. pneumoniae pleural fluid isolate was cross-resistant to erythromycin. Both bacteremic S. mitis strains were resistant to macrolides (erythromycin, azithromycin, clarithromycin), lincosamides (clindamycin), and fluoroquinolones. Patient histories indicated no prior use of MLS class antimicrobials for the S. mitis case, but the patient having the S. pneumoniae isolate did receive prior treatment of erythromycin and clindamycin. All isolates had modestly increased penicillin MICs of 0.12 microg/ml. The mode of resistance to quinupristin/dalfopristin was not evident (sat A-negative by PCR); and these cases illustrate the existence of streptogramin-resistant isolates before the introduction of this antimicrobial class into human clinical practice.

Antimicrobial susceptibility patterns for pathogens isolated from patients in Latin American medical centers with a diagnosis of pneumonia: analysis of results from the SENTRY Antimicrobial Surveillance Program (1997). SENTRY Latin America Study Group.

Pneumonia is the most common fatal hospital-acquired infection, with attributable mortality rates ranging from 30 to 60%. Rapid initiation of optimal antimicrobial therapy is essential for obtaining treatment success. In this report the antimicrobial susceptibility of 556 strains from the lower respiratory tract were collected by the SENTRY Antimicrobial Surveillance Program (1997). These strains were isolated from hospitalized patients with pneumonia in 10 Latin American centers (6 countries) as part of this 68-center worldwide program. The isolates were susceptibility tested against more than 70 drugs (35 reported) by the reference broth microdilution method. Klebsiella pneumoniae and Escherichia coli phenotypically consistent with extended spectrum beta-lactamase (ESBL) production were characterized further by ribotyping and pulsed-field gel electrophoresis. The five most frequently isolated species were (n/%): Pseudomonas aeruginosa (149/26.8%), Staphylococcus aureus (127/22.8%), Acinetobacter spp. (66/11.9%), Klebsiella spp. (56/10.1%), and Enterobacter spp. (40/7.2%). P. aeruginosa demonstrated high rates of resistance to a majority of the antimicrobial drugs tested. Carbapenems, amikacin, and piperacillin/tazobactam demonstrated the highest susceptibility rates (73.8-77.2%) against P. aeruginosa, however the lowest resistance rate was observed for cefepime (6.7%). Acinetobacter spp. also showed very high rates of resistance and the most active compounds were imipenem and meropenem (89.0% susceptibility) followed by the tetracyclines. Cephalosporin susceptibilities among Klebsiella spp. were low: cefoxitin, 73.0%; ceftazidime, 69.4%; and ceftriaxone, 65.9%. Approximately 37% and 28% of K. pneumoniae and E. coli isolates, respectively, were considered ESBL producers based on NCCLS criteria. Ceftriaxone was active against only 52.5% of Enterobacter spp. isolates, whereas cefepime was active against 90.0% of isolates (MIC50, < or = 0.12 microgram/mL). Oxacillin resistance was detected in nearly 50% of S. aureus isolates. The most active drugs against S. aureus were vancomycin, teicoplanin, and quinupristin/dalfopristin (MIC90, 1 microgram/mL). In summary, our study of pneumonias in Latin American medical centers demonstrated a greatly increased prevalence of Acinetobacter spp. and higher resistance rates among Gram-negative bacilli when compared with similar controlled studies from North America.

Gatifloxacin (AM-1155, CG 5501) susceptibility testing interpretive criteria and quality control guidelines for dilution and disk (5-microgram) diffusion methods. The Quality Control Study Group.

Gatifloxacin (formerly AM-1155 and CG5501), a new 8-methoxy fluoroquinolone, has an expanded spectrum of activity against Gram-positive cocci and some anaerobic bacteria. This compound was tested against 600 recent clinical strains of rapidly growing aerobic species to establish susceptibility testing interpretive criteria for the reference broth microdilution and standardized disk (5-microgram) diffusion methods of the National Committee for Clinical Laboratory Standards (NCCLS). These strains included 285 Enterobacteriaceae (17 species), 165 staphylococci, 49 enterococci, and 101 nonfermentative Gram-negative bacilli. Based on achievable serum levels with projected gatifloxacin dosing regimens, MIC break points of < or = 2 micrograms/mL (> or = 18 mm) for susceptibility and > or = 8 micrograms/mL (< or = 14 mm) for resistance were selected. The absolute agreement between tests was 94.3% with no very major false-resistant errors. The quality control ranges (MIC and zone diameters) for the NCCLS recommended strains were determined in a nine-laboratory NCCLS protocol as follows: Escherichia coli ATCC 25922 = 0.008-0.03 microgram/mL and 31-37 mm; Enterococcus faecalis ATCC 29212 = 0.12-1 microgram/mL; Pseudomonas aeruginosa ATCC 27853 = 0.5-2 micrograms/ml and 21-27 mm; Staphylococcus aureus ATCC 25923 = 27-33 mm and S. aureus ATCC 29213 = 0.03-0.12 microgram/mL. Gatifloxacin appears to be a promising new fluoroquinolone with acceptable susceptibility testing methods for routine clinical laboratory use.

Survey of blood stream infections attributable to gram-positive cocci: frequency of occurrence and antimicrobial susceptibility of isolates collected in 1997 in the United States, Canada, and Latin America from the SENTRY Antimicrobial Surveillance Program. SENTRY Participants Group.

The SENTRY Antimicrobial Surveillance Program was established in January, 1997 to monitor the predominant pathogens and antimicrobial resistance patterns of nosocomial and community-acquired infections via a network of sentinel hospitals in the United States (30 sites), Canada (eight sites), Latin America (10 sites), and Europe (24 sites). During the first 12-month study period (January to December, 1997), a total of 9519 blood stream infections (BSI) were reported by SENTRY participants in the U.S. (6150), Canada (1727), and Latin America (1642). The Gram-positive cocci, Staphylococcus aureus, coagulase-negative staphylococci (CoNS), enterococci, and streptococci accounted for 53.9% (5131 infections) of all BSI (56.5% U.S., 55.7% Canada, and 42.9% Latin America). The staphylococci, Enterococcus spp., S. pneumoniae, beta-hemolytic streptococci, and viridans group streptococci accounted for 6 of the top 11 BSI pathogens in the U.S. and Canada, whereas only S. aureus (1st), CoNS (3rd), and Enterococcus spp. (9th) were among the top 11 pathogens in Latin American hospitals. The results of this survey affirm the importance of Gram-positive cocci as causes of BSI in both North America and Latin America and demonstrate that important antimicrobial resistance exists among isolates of staphylococci, streptococci, and enterococci from all three geographic regions. This includes oxacillin-resistance among S. aureus (26.9% U.S., 29.2% Latin America, and 4.0% Canada) and CoNS (71.5% U.S., 68.4% Latin America, and 65.6% Canada), penicillin resistance among viridans group streptococci (48.5% U.S., 45.1% Canada, and 33.3% Latin America) and pneumococci (36.1% U.S., 27.5% Canada, and 65.6% Latin America), high-level resistance (HLR) to aminoglycosides among enterococci (27.2 to 70.1% U.S., 33.3 to 75.7% Canada and 16.7 to 51.5% Latin America), and macrolide resistance among beta-hemolytic streptococci (12.4 to 14.2% U.S., 10.5 to 12.3% Canada, and 0.0 to 4.0% Latin America), viridans group streptococci (32.4 to 39.7% U.S., 22.5-35.2% Canada, and 20.0% Latin America), and pneumococci (10.0 to 10.6% U.S., 9.8-10.8% Canada, and 9.4-18.7% Latin America). BSI isolates of Gram-positive cocci from the U.S. and Latin America were considerably more resistant than those from Canada. New agents with Gram-positive activity will be essential for optimal treatment of BSI attributable to Gram-positive cocci in both North and Latin America.

Evaluation of quinupristin/dalfopristin (Synercid) and RPR 106972 stability in susceptibility testing media.

In response to conflicting reports on the chemical stability of quinupristin/dalfopristin, a study was designed to assess the in vitro longevity and effects of media and storage conditions on this streptogramin combination. Broth microdilution trays containing parenteral (quinupristin/dalfopristin) and oral (RPR 106972) streptogramin combinations as well as pristinomycin components (P-I and P-II) were preincubated at 35 degrees C for 12-72 h before inoculation with control strains (Streptococcus pneumoniae ATCC 49619, Haemophilus influenzae ATCC 49247, Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 29213) and five clinical isolates with various drug resistance phenotypes. Overall, the mean quinupristin/dalfopristin activity loss was 24%/12 h, 41%/18 h, 43%/24 h, 69%/48 h and 79%/72 h with no detected loss of potency when measured by E. faecalis until 18 h. RPR 106972 mean activity loss was 6%/12 h, 19%/18 h, 19%/24 h, 56%/48 h and 71%/72 h with no loss of potency as measured by S. aureus until 48 h. Overall, P-I components had greater stability as compared with P-II for both drug combinations. Bioassays showed similar trends in decreased activity. Bioassay differences among media types were only significant (> 3 mm; greater loss of potency) for haemophilus test media for both P-II components at 72 h. The presence of an organism in the medium had no effect on stability assay results. The effect of storage temperature (4, 25 degrees C) on quinupristin/dalfopristin and RPR 106972 stability was also detrimental to drug potency indicating the requirement for rigid quality assurance for streptogramin diagnostic reagents when determining activity by reference or standardized susceptibility tests.

Trends in antimicrobial susceptibility of bacterial pathogens isolated from patients with bloodstream infections in the USA, Canada and Latin America. SENTRY Participants Group.

From January through June of 1998, 4579 bloodstream infections (BSI) due to bacterial pathogens were reported from SENTRY hospitals in Canada, the USA and Latin America. Staphylococcus aureus, Escherichia coli, and coagulase-negative staphylococcus (CoNS) were the most common pathogens, together accounting for 55.2% of all BSI during this time period. Compared with the 5794 BSI reported from SENTRY from January through June of 1997, no major change was seen in the frequencies of occurrence of the most common bacterial causes of BSI. Between 1997 and 1998, the major change in antimicrobial resistance was an increase in oxacillin-resistance in both S. aureus and CoNS in all regions. These data demonstrate widespread antimicrobial resistance in Canada, Latin America and the USA, with a notable increase in oxacillin-resistance among staphylococci. Ongoing surveillance remains essential, and will enhance efforts to limit the scope of this worldwide problem.

The Guilt Inventory.

The Guilt Inventory contains subscales measuring trait guilt, state guilt, and moral standards. Previous research has suggested the reliability of these scales and the validity of their interpretations. The items, coding, and scoring procedure for the Guilt Inventory are presented here as well as additional evidence regarding the reliability and measurement characteristics of its subscales.

[The effect of health care reform in Germany on the pharmacist's role in pharmacotherapy]. / Vliv zdravotní reformy v SRN na roli lékárníka ve farmakoterapii.

The present paper describes the pharmacist's role in Germany during the health-service reform and shows his prospects within pharmacological therapy and his role in contemporary modern society. However, emphasis is placed on the out-patient provision of drugs. The development of the recent years clearly indicates the effects of the health-service reform on all concerned in German health services. For this reason the present paper has been extended to include the description of the current social and health guidelines for health services. Moreover, it also describes the individual stages of the health-service reform in Germany between 1989 and 1997. The theoretical part was supported by patient's opinion polls. With examples of 500 interviewees from Bavaria and Baden-Württemberg, patient habits were surveyed regarding drug consumption, compliance, self-treatment, and drug information as well as the patient's expectations of the pharmacist. Depending on the growth of scientific knowledge in health services and on the need for medical care, the pharmacist's role has to undergo continuous changes, worldwide. Due to the analysis and scrutiny of the transformation of German health services--for Germany has a state health insurance in traditional solidarity--the present paper gives a prediction concerning further development, and, above all, the necessary changes in the pharmacist's work in the framework of health services to be carried out. Generally it is possible to say that the obtained knowledge has general validity which other countries can make use of while considering their local conditions.