Infect Immun, 1985 Oct, 50(1), 123 - 9 Sensitivity of Capnocytophaga species to bactericidal properties of human serum; Wilson ME et al.; Capnocytophaga is a newly described genus of gram-negative bacteria which can cause serious oral and extraoral infections in the susceptible host . In the present study, sensitivity of Capnocytophaga spp . to the bactericidal properties of human serum was investigated . Laboratory strains representative of Capnocytophaga sputigena, C . ochracea, and C . gingivalis and seven oral isolates of Capnocytophaga spp . obtained in primary culture were determined to be sensitive to killing by pooled normal serum . In contrast, little or no killing of Capnocytophaga spp . was observed when these organisms were incubated in the presence of hypogammaglobulinemic serum despite evidence for alternative pathway activation . However, hypogammaglobulinemic serum could be reconstituted to bactericidal activity by the addition of the immunoglobulin M fraction of normal serum . Capnocytophaga spp . failed to activate the classical pathway in hypogammaglobulinemic serum, thus ruling out an antibody-independent mechanism of killing . In contrast, good correlation was observed between serum-mediated killing and antibody-dependent classical pathway consumption . These results indicate that complement in the presence of bactericidal antibody may be an important determinant of host resistance to intra- and extraoral infections caused by Capnocytophaga spp. Tijdschr Kindergeneeskd, 1985 Oct, 53(5), 185 - 8 {Neonatal meningitis: is the combination ampicillin-gentamycin obsolete?}; Muytjens HL et al.; The course of E . coli-meningitis in two infants, treated with latamoxef (moxalactam) in combination with ampicillin is described . Because of the disappointing results the potential value of latamoxef for therapy of Gram-negative enteric meningitis of infancy is discussed. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1985 Oct, 260(2), 184 - 96 Membrane proteins of Legionellaceae . II . Serogroup- and species-specific antigens in the outer membrane of Legionella pneumophila; Ehret W et al.; Antigens of the outer membrane of Legionella pneumophila were investigated by means of the immunoblotting-technique using rabbit antisera against three different formaldehyde-inactivated strains, and one heat-inactivated strain of L . pneumophila serogroup 1 . Nitrocellulose blots were prepared from membrane fractions extracted with sodium-N-lauryl-sarcosinate from 14 strains of L . pneumophila (eight strains of serogroup 1, and one strain each of serogroups 2-7) and 12 strains of gram-negative rods of various species . After incubation with 125I-protein A or 125I-anti-rabbit IgG immune complexes were identified . These results were compared with Coomassie-stained and silver-stained SDS gels . There was a diffuse reaction in the homologous system between 20 and 80 kilodalton (kDal) after incubation with 125I-protein A, and an intense reaction between 22 and 29 kDal after incubation with 125I-anti-rabbit IgG . Membrane preparations of the different strains of serogroup 1 exhibited clearly discernible patterns . Immunoblots of formaldehyde-inactivated strains when reacted with antiserum against heat-inactivated immunogen showed a single species-specific antigen of approximately 22.5 kDal which could not be assigned to a major protein . Immunoblots of the same antiserum but with heat-inactivated cell wall preparations gave a second species-specific band of approximately 65 kDal . Antisera against formaldehyde-inactivated bacteria demonstrated more complex characteristic patterns, with protein-associated components occurring at 29, 44, 46, 48, 65 and 80 kDal; in addition, cross-reacting fractions were present at 15.5, 17.5 and 22.5 kDal . The 29 kDal major outer membrane protein was immunogenic in most but not all cases. Arch Intern Med . 1985 Oct;145(10):1908. Escherichia coli bacteremia, meningitis, and hemochromatosis; Christopher GW; A 67-year-old man with Escherichia coli bacteremia and meningitis was found to have hemochromatosis . To my knowledge this is the first documented case of E coli meningitis occurring in the setting of hemochromatosis . The case raises issues regarding the role of chronic liver disease in the pathogenesis of gram-negative sepsis and the impact of iron loading on host immunocompetence and bacterial virulence. J Infect Dis, 1985 Oct, 152(4), 811 - 6 Efficacy of ciprofloxacin in experimental arthritis caused by Escherichia coli--in vitro-in vivo correlations; Bayer AS et al.; Ciprofloxacin, a new carboxyquinolone, has potent in vitro bactericidal activity against the major aerobic, gram-negative bacillary pathogens that cause human pyoarthroses . We investigated the in vivo efficacy of ciprofloxacin in a rabbit model of septic arthritis due to Escherichia coli . Animals received either ciprofloxacin (80 mg/kg per day) or gentamicin (5 mg/kg per day) . Ciprofloxacin was rapidly bactericidal in vivo and was significantly more effective in reducing the numbers of E . coli in synovial tissue than was gentamicin at days 10 and 17 of therapy (P less than .0005 and P less than .05, respectively) . Similarly, ciprofloxacin was significantly more active than was gentamicin in reducing the numbers of E . coli in joint fluid on day 10 of therapy (P less than .0005); however, by day 17 of therapy, the numbers of E . coli in joint fluid were not significantly different in the two therapy groups . Neither regimen was effective in preventing the development of postinfectious inflammatory synovitis . There was no in vivo development of resistance to either antibiotic during therapy . Ciprofloxacin therapy was associated with significantly higher bactericidal titers in serum and joint fluid than were observed with gentamicin therapy (P less than .0005) . Ciprofloxacin warrants further in vivo evaluation in invasive E . coli infections. Eur J Biochem, 1985 Sep 16, 151(3), 613 - 9 Turgor-controlled K+ fluxes and their pathways in Escherichia coli; Meury J et al.; Escherichia coli like most gram-negative bacteria with walls maintains a cytoplasmic osmolarity exceeding that of the medium; the resulting hydrostatic pressure (turgor pressure) pushes the cytoplasmic membrane against the peptidoglycan and creates a tension in the two envelopes . Potassium is the only cation which takes part in the regulation of cellular osmolarity . The adaptation of intracellular K+ concentration to external osmolarity involves K+ turgor-controlled fluxes . When the medium osmolarity is raised an osmodependent influx of K+ can be observed; this is carried out by the K+ transport system TrkA which can also taken up rubidium . A specific and unidirectional pathway allows K+ ions to flow out of the cell when the medium osmolarity is decreased; this pathway reveals two characteristics: it has no affinity for rubidium and it can be blocked by the blockers of eukaryotic K+ channels . Osmodependent fluxes are turned on immediately after the medium osmolarity is disturbed; in contrast, they are turned off gradually as the rate of K+ fluxes approach zero . The rate of K+ influx seems to depend on the level of internal osmolarity and not on the extent of the increase in medium osmolarity . The rate of the efflux is directly proportional to the decrease in medium osmolarity and is independent on the level of internal osmolarity. Eur J Biochem, 1985 Sep 2, 151(2), 209 - 16 Second lytic target of beta-lactam compounds that have a terminal D-amino acid residue; Tsuruoka T et al.; A new biochemical mechanism of lysing bacterial cells by treatment with certain beta-lactam compounds that possess a terminal D-amino acid moiety in their side chain was demonstrated . The two functions of the molecule, the beta-lactam and terminal D-amino acid moiety, are both involved in the activity of lysing gram-negative bacteria, which is characterized by very rapid lysis of the cells in the first few hours after their contact with the compound . This mechanism was proved by studies on one such compound, named MT-141, which contains a terminal D-cysteine moiety with free amino and carboxyl groups in the 7 beta-side chain of the 7 alpha-methoxy-cephalosporin skeleton . This compound bound to the cell-wall peptidoglycan of Escherichia coli through the D-amino group of its terminal D-amino acid moiety and this seemed to cause rapid cell lysis . Both activities, of binding to peptidoglycan and of causing rapid cell lysis, were inhibited by certain D-amino acids, but not by L-amino acids . Mutants were isolated that had simultaneously gained decreased sensitivity to this kind of beta-lactam compound and supersensitivity to globomycin, an inhibitor of formation of lipoproteins which function in linking the peptidoglycan to the outer membrane . These results suggest that binding of the terminal D-amino acid moiety of the beta-lactam compound to peptidoglycan somehow influences formation of the linkage between the outer membrane and the peptidoglycan and consequently enhances the cell lytic activity of the beta-lactam portion of the molecule. J Bacteriol, 1985 Sep, 163(3), 1038 - 46 Waveform analysis and structure of flagella and basal complexes from Bdellovibrio bacteriovorus 109J; Thomashow LS et al.; The structure of sheathed flagella from Bdellovibrio bacteriovorus was investigated . The first three periods of these flagella were characterized by progressively smaller wavelengths and amplitudes in periods more distal to the cell . The damped appearance was due to a single nonrandom transition between two helical structures within each filament . The intersection of the two helices, one of which was a threefold-reduced miniature of the other, occurred at a fixed distance along the filament and resulted in a shift in the flagellar axis . Flagella increased in length as the cells aged and assumed a constant miniature waveform at their distal ends . The core filament was the principal determinant of flagellar morphology . It was composed of 28,000- and 29,500-dalton polypeptides . The 28,000-dalton subunits were located in the cell-proximal segment of the filament, and the 29,500-dalton subunits were located in the more distal region . The heteromorphous appearance of bdellovibrio flagella arose from the sequential assembly of these subunits . The basal complex associated with core filaments was examined because of its potential involvement in sheath formation . Bdellovibrio basal organelles were generally similar to those of other gram-negative species, but appeared to lack a disk analogous to the outer membrane-associated L ring which is a normal component of gram-negative basal complexes. Br J Radiol, 1985 Sep, 58(693), 881 - 4 Anti-lipopolysaccharide toxin therapy for whole body X-irradiation overdose; Gaffin SL et al.; Death in humans from ionising radiation overexposure in the 3-8 Gy (300-800 rad) range is in part due to the toxaemia caused by the entry of gram-negative bacteria and/or their lipopolysaccharide toxin (LPS) into the blood circulation through the walls of partially denuded gut . Anti-LPS hyperimmune equine plasma was evaluated for its ability to lower irradiation-induced lethality . Mice were irradiated with 6.3 Gy (630 rad) and six days later received equine Anti-LPS hyperimmune plasma, control plasma or saline . Mortalities in the three groups were 58%, 92% and 79% (p less than 0.01) respectively . Thus Anti-LPS may prove useful as an adjunct to conventional therapy in treating radiation sickness. Clin Exp Immunol, 1985 Sep, 61(3), 562 - 8 Factors contributing to the development of cerebral malaria . II . Endotoxin; Usawattanakul W et al.; Limulus amoebocyte lysate test (LALT) was used to detect endotoxin-like substances in the plasma of 15 patients with cerebral malaria, 28 patients with uncomplicated falciparum malaria and 30 healthy controls . On admission, 67% of cerebral malaria patients were positive, whereas only 21.4% of uncomplicated malaria patients and none of controls were positive . Among uncomplicated malaria cases, four of eight patients with parasitaemia over 90,000/mm3 were LALT positive whereas only two of 20 patients with parasitaemia of less than 90,000/mm3 were positive . A follow-up study in cerebral malaria patients showed some variation in LALT positivity rate from day to day (85.7% on day 1, 53.3% on day 3 and all negative on discharge from hospital) . LALT positivity bore no relationship to gram negative bacteraemia . Leucocytosis and elevated serum enzymes were more frequently found in LALT-positive patients . Our results suggest that endotoxin (LALT positivity) of the plasma of malaria patients is derived from either the parasites themselves or from the gut . It relates to parasitaemia, leucocytosis and elevated serum enzymes, but not to the clinical syndrome of cerebral malaria. J Gen Microbiol, 1985 Sep, 131 ( Pt 9), 2349 - 57 The outer membrane of Treponema pallidum: biological significance and biochemical properties; Penn CW et al.; Rabbits infected intravenously with Treponema pallidum were not markedly febrile, and the pyrogenicity of treponeme preparations administered intravenously to rabbits was negligible . The antibiotic polymyxin B did not induce any ultrastructural changes on the treponemal surface and was not lethal (immobilizing) for T . pallidum, which was, however, highly susceptible to detergents such as SDS . Extraction of treponemes with Triton X-100 removed the outer membrane (despite the presence of Mg2+) as shown by electron microscopy, and solubilized a limited number of proteins detectable by SDS-PAGE, including a dominant antigen (47 kDal) demonstrated by immunoblotting . None of the proteins were heat-modifiable . Periodic acid-silver staining of polyacrylamide gels for carbohydrate together with protease K digestion did not demonstrate major carbohydrate components in whole treponemes, or in the Triton-soluble fraction . Surface iodination of intact treponemes revealed very little surface exposure of treponemal proteins, although a protein which co-migrated with host albumin was labelled and appeared to be associated with the treponemal surface . Many treponemal proteins were, however, labelled when iodination was done in the presence of Triton . These observations, indicate that the outer membrane of T . pallidum differs significantly from those of many Gram-negative pathogens. J Clin Invest, 1985 Sep, 76(3), 985 - 90 Pretranslational regulation of the synthesis of the third component of complement in human mononuclear phagocytes by the lipid A portion of lipopolysaccharide; Strunk RC et al.; The third component of complement (C3) is a plasma glycoprotein with a variety of biologic functions in the initiation and maintenance of host response to infectious agents . While the hepatocyte is the primary source of plasma C3, mononuclear phagocytes contribute to the regulation of tissue availability of C3 . Lipopolysaccharide (LPS), a constituent of cell walls of gram-negative bacteria, consists of a polysaccharide moiety (core polysaccharide and O antigen) covalently linked to a lipid portion (lipid A) . Using metabolic labeling with {35S}methionine, immunoprecipitation, and SDS-polyacrylamide gel electrophoresis, we examined the effects of LPS on synthesis of C3 by human mononuclear phagocytes as well as synthesis of the second component of complement (C2), factor B, lysozyme, and total protein . LPS increased C3 synthesis 5-30-fold without affecting the kinetics of secretion of C3 or the synthesis of C2, lysozyme, or total protein . Factor B synthesis was consistently increased by LPS . Experiments with lipid A-inactivated LPS (alkaline treated), LPS from a polysaccharide mutant strain, and lipid X (a lipid A precursor) indicated that the lipid A portion is the structural element required for this effect . Northern blot analysis demonstrated at least a fivefold increase in C3 mRNA in LPS-treated monolayers, which suggests that the regulation of the increase in C3 synthesis is pretranslational . C2 mRNA and factor B mRNA were increased approximately twofold . The availability of specific gene products in human mononuclear phagocytes that respond to LPS should permit understanding of the molecular regulation of more complex functions of these cells elicited by LPS in which multiple gene products are coordinately expressed. Clin Nephrol, 1985 Sep, 24(3), 142 - 6 Effect of hemodialysis on ceftazidime pharmacokinetics; Nikolaidis P et al.; Ceftazidime, a new parenteral third generation cephalosporin, is widely used because of its broad aerobic gram-negative bacterial coverage and its apparent low risk of toxicity . To establish the effect of hemodialysis on the elimination kinetics of ceftazidime and to determine the supplementary dose of the drug after each dialysis session, we studied nine anuric patients with end stage chronic renal failure undergoing hemodialysis . After a single 1 g intravenous bolus injection of ceftazidime a two-compartment open model was used to calculate the pharmacokinetic parameters . The mean ceftazidime concentrations in hemodialysis patients were 64.3 micrograms/ml at the start of dialysis and 20.0 micrograms/ml at the end of dialysis session . A 4-h hemodialysis procedure reduced the area under concentration vs time curve from 795.1 mg/l X h to 175.8/l X h and the elimination half life of ceftazidime from 33.6 h to 3.3 h . Dialyzer clearance was 55.6 ml/min and 55% of the administered dose was recovered in the dialysate fluid . Hemodialysis patients should receive a supplemental dose equal to half their usual maintenance dose immediately after each dialysis session. Inflammation, 1985 Sep, 9(3), 297 - 308 Endotoxin tolerance diminishes certain antiinflammatory effects of endotoxin; Rosenbaum JT et al.; Endotoxin (bacterial lipopolysaccharide, LPS) is paradoxically both inflammatory and antiinflammatory . A single intravenous injection of 100 micrograms Escherichia coli LPS markedly inhibits the inflammatory changes associated with cutaneous reversed passive Arthus (RPA) reactions in New Zealand white rabbits . Polymorphonuclear (PMN) leukocytes from LPS-treated rabbits exhibit diminished responsiveness in vitro to complement (C5) -derived peptides . Repeated injections of LPS render animals "tolerant", that is, refractory to the toxic and inflammatory effects of LPS . We examined whether tolerance would enhance the ability of LPS to inhibit inflammation not attributable to LPS . Surprisingly, as compared with rabbits receiving a single dose of LPS, tolerant rabbits demonstrated greater inflammatory changes (i.e., PMN exudation, vascular permeability) associated with RPA reactions . PMNs from LPS-tolerant rabbits responded in vitro to C5-derived peptides significantly more than PMNs from rabbits that received a single dose of LPS . We speculate that some antiinflammatory effects of LPS require the toxic or inflammatory effects of LPS itself . These observations might relate to the limited efficacy of fever therapy and the variable effects of gram-negative sepsis on functions of human PMNs. S Afr Med J, 1985 Aug 31, 68(5), 344 - 5 Aspiration of oral contents in Parkinson's disease . A case report; Cooper RG et al.; A patient with Parkinson's disease developed a non-ketotic hyperosmolar diabetic coma precipitated by chest infection . Initial improvement from treatment with intravenous insulin, ampicillin and fluid therapies was followed by severe deterioration and hypovolaemic shock . Further improvement occurred only when therapy directed against Gram-negative sepsis was added . A barium examination later demonstrated aspiration of oral contents with pulmonary soilage . The differences between the easily recognized early fulminating 'aspiration syndrome' caused by aspiration of gastric contents of low pH and the aspiration of oral contents, which may remain occult for many hours, is highlighted . Life-threatening Gram-negative or anaerobic infection may then occur but remain undiagnosed because the original aspiration of foreign material is unsuspected. Zh Mikrobiol Epidemiol Immunobiol, 1985 Aug, (8), 87 - 91 {Detection of antibodies neutralizing the endotoxins of gram-negative bacteria using the liposomal potentiometric method}; Vlasov GS et al.; For the first time the study of the indicator system consisting of sensitized liposomes with NaF incorporated as a marker and a fluorine-selective electrode has been made and, as a result, the possibility of the potentiometric determination of the immune lysis of liposomes in the presence of complement and specific antibodies has been demonstrated . The dissolution of the lipid components (Re-chemotype glycolipid and lipid A) in the bilayer matrix obviates the necessity for converting lipid antigens into the water-soluble state in the process of serological tests . As compared with other methods, the liposomal potentiometric method for the determination of Re-chemotype glycolipid and lipid A is highly sensitive (20-40 ng/ml), rapid, technically easy to perform, cheap and does not require large volumes of samples . The disadvantages of this analytical system are the instability of liposomes and the diffusion of fluorine ions from the internal aqueous phase of vesicules . For this reason the immunoassay can be made only within 12 hours after the preparation of sensitized liposomes incorporating the marker. Appl Environ Microbiol, 1985 Aug, 50(2), 356 - 63 Microbiology and ration digestibility in the hindgut of the ovine; Lewis SM et al.; Contents of the terminal ilea, ceca-proximal colons, and terminal recta were obtained from nine sheep, three of which were fed 100% orchardgrass hay, three of which were fed 60% cracked corn-40% orchardgrass hay, and three of which were fed 80% cracked corn-20% orchardgrass hay . The digestibility of dry matter in the ceca was greatest when the all-hay diet was fed, whereas the percentage of cellulose digestion in the ceca increased with increasing levels of concentrate . For all diets, the total volatile fatty acid concentrations were higher in the ceca than in the other two sites . The cecal pH levels decreased with increased corn levels in the diet . The total microbiol numbers per gram of ileal and cecal contents increased in response to feeding of concentrate; however, across all diets, the ileal counts were 8% or less of the cecal counts . In contrast, the cellulolytic microbial numbers in the ilea were 50% or more of those in the ceca and were highest with the all-hay diet . Both bacterial and end product concentrations in the ceca were equivalent to those occurring in rumina . A total of 16 cellulolytic cultures were isolated and characterized from ileal and cecal contents of animals fed all three diets . Seven gram-negative-rod-shaped organisms were identified as Butyrivibrio fibrisolvens, whose capacity to digest cellulose exceeded that of several rumen strains . The guanine-plus-cytosine content of the DNA of one strain of B . fibrisolvens was 38.8 mol%, compared with the only previously reported value for this species of 41.2 mol%.(ABSTRACT TRUNCATED AT 250 WORDS) J Clin Microbiol, 1985 Aug, 22(2), 320 - 1 Leptotrichia buccalis bacteremia in neutropenic children; Reig M et al.; Two new cases of Leptotrichia buccalis bacteremia in seriously ill patients were described . The anaerobic, gram-negative microorganism L . buccalis was isolated from blood cultures of two children with severe leukopenia . Anaerobic organisms should be taken into account when a standard protective antibiotic chemotherapy is considered in the immunosuppressed host. J Gen Microbiol, 1985 Aug, 131 ( Pt 8), 2035 - 9 Immunomodulation by myxospores of Myxococcus xanthus; Ruiz C et al.; Glycerol-induced myxospores of Myxococcus xanthus caused non-specific modulation of humoral and cellular immune responses in laboratory animals . The number of cells which formed specific haemolysins in spleens of mice immunized with sheep erythrocytes was increased when 0.5 X 10(8) myxospores were inoculated 2 d after the erythrocytes, and decreased when myxospores were injected 2 d before or at the same time as the erythrocytes . Both the IgG primary response and the secondary response to erythrocytes were decreased in rabbits after pretreatment with 2 X 10(8) myxospores per rabbit . Delayed-type hypersensitivity to sheep erythrocytes was also suppressed in mice after intraperitoneal (i.p.) injection of 0.3 X 10(8) myxospores . One day after i.p . injection of myxospores, neither an inflammatory response nor bone marrow cell depletion was observed in mice . These results support the idea that M . xanthus myxospores possess diverse immunomodulation properties apparently due to factors different from the classical LPS of Gram-negative bacteria. Antimicrob Agents Chemother, 1985 Aug, 28(2), 282 - 8 Comparison of aminoglycoside resistance patterns in Japan, Formosa, and Korea, Chile, and the United States; Shimizu K et al.; The resistance mechanisms of more than 2,000 aminoglycoside-resistant gram-negative aerobic bacteria were estimated by a method that assigned a biochemical mechanism based on susceptibility to selected aminoglycosides . Strains from hospitals in Japan, Formosa, and Korea (the Far East) were compared with strains from Chile and the United States . Of the strains from Chile, 90% had an aminoglycoside resistance pattern indicative of the 3-N-acetyltransferase {AAC(3)-V} enzyme . Of the strains from the Far East, 78% had susceptibility patterns suggesting the presence of AAC(6') enzymes . In contrast, strains from the United States had a wider variety of resistance mechanisms including 2''-O-adenylyltidyltransferase {ANT(2'')}, AAC(3), AAC(6'), and AAC(2') . Reflecting these differences in resistance patterns, the frequencies of resistance to gentamicin, tobramycin, dibekacin, and amikacin in strains from the United States were different from those in strains from the Far East . These differences seem to be correlated with different aminoglycoside usage in the two regions . In the United States, where gentamicin was the most widely used aminoglycoside, 92% of the strains were resistant to gentamicin, 81% were resistant to dibekacin, and 8.8% were resistant to amikacin . In the Far East, dibekacin and kanamycin were widely used in the past and more recently amikacin has been frequently used . Of the strains from this region, 99% were resistant to dibekacin, 85% were resistant to gentamicin, and 35% were resistant to amikacin. J Clin Periodontol, 1985 Aug, 12(7), 507 - 24 Ultrastructure of developing subgingival plaque in beagle dogs; ten Napel JH et al.; The aim of this study was to describe the ultrastructure of developing subgingival plaque . In 6 beagle dogs, healthy gingiva prevailed after a pre-experimental period of intensive plaque control . At the start of the experiment, all oral hygiene measures were withdrawn . Biopsies comprising buccal gingiva and adjacent dental tissues were obtained from premolars and molars on days 0, 4, 7, 21, and 28 and processed for electron microscopy . Sections of day 0 exhibited a junctional epithelium in close contact with the tooth and absence of subgingival aggregations of bacteria on the tooth surface . For each of the subsequent periods studied, some sections did not exhibit subgingival plaque . In the remaining sections with subgingival plaque, almost all bacteria appeared in aggregates attached to the tooth surface . The number of bacteria at the orifice of the gingival sulcus increased with time . Further apically, the micro-organisms formed either a continuous layer of even thickness or, more frequently, discrete microcolonies along the tooth surface . The bacteria comprised practically entirely Gram-negative cocci, rods or spirochetes . The latter were present either mixed with the other types in the discrete microcolonies or constituted the bulk of the continuous layer of plaque . In the apical part of the subgingival plaque, a shift from Gram-negative cocci and rod during the early stages of gingival inflammation, to a predominance of spirochetes in later stages was noted . The study shows that in dogs, starting from a plaque- and gingivitis-free baseline, a predominantly Gram-negative subgingival flora may form within a few days after withdrawal of all oral hygiene measures and that a shift in the bacterial composition of the subgingival plaque takes place during a 4-week period of no oral hygiene. Appl Environ Microbiol, 1985 Aug, 50(2), 441 - 6 Recombinant plasmid conferring proline overproduction and osmotic tolerance; Jakowec MW et al.; A recombinant plasmid carrying the proBA (pro-74) mutant allele which governs osmotic tolerance and proline overproduction was constructed by using the broad-host-range plasmid vector pQSR49 . The physiological, biochemical, and genetic properties of strains carrying the pQSR49 derivatives pMJ101 and pMJ1, mutant and wild type, respectively, were investigated . pMJ101 conferred enhanced osmotolerance compared with strains carrying the wild type, pMJ1 . These results are in contrast to those obtained previously with strains carrying recombinant plasmids based on pBR322 that failed to confer the osmotic tolerance phenotype . gamma-Glutamyl kinase (first step in proline biosynthesis) from strains carrying pMJ101 was 200-fold less sensitive to feedback inhibition than was the wild-type enzyme . As expected, the intracellular proline levels of strains carrying pMJ101 were more than an order of magnitude higher than those of the wild type . An analysis of copy number revealed that the pQSR49 constructs were present in the cell at a level six- to eightfold lower than those of the pBR322 recombinants, which may account for the difference in phenotype . We found that the genetic stability of the pQSR49 derivative in a variety of gram-negative bacteria was dependent on the insert orientation and the presence of foreign DNA on the plasmid . These factors may be significant in future studies aimed at expanding the osmotolerance phenotype to a broad range of gram-negative bacteria. Am J Med, 1985 Jul 15, 79(1A), 28 - 36 Role of amikacin in the management of intra-abdominal sepsis; Dougherty SH; Controversy has developed regarding the antibiotic management of intra-abdominal sepsis because of the recent availability of the third-generation cephalosporins and ureidopenicillins as alternatives to traditional combination therapy (aminoglycosides plus clindamycin) . Most observers now acknowledge the need to provide anti-anaerobic as well as anti-aerobic gram-negative drug coverage . Although most of the newer agents do provide such broad-spectrum coverage, doubt remains regarding their efficacy because of flaws in comparative study design and the observation that resistance to the newer agents, which may even extend to the aminoglycosides, can emerge in individual patients during single courses of antibiotic therapy . Indeed, such resistance is most likely to occur during the treatment of seriously ill, immunodepressed patients who have undergone multiple reoperation for persistent or recurrent intra-abdominal sepsis--the precise group for which the new drugs were most desired as less toxic alternatives to the aminoglycosides . On the basis of such observations, combination therapy with the aminoglycosides, appears to remain the most logical choice . In the setting of nosocomial sepsis and pathogen resistance to other aminoglycosides, amikacin may be especially effective . Recent surveillance data indicate that the use of amikacin under such circumstances not only may provide effective antibiotic therapy, but also may actually reduce the level of microbial resistance to the other aminoglycosides . Past concern regarding the development of resistance to amikacin has probably been excessive and should not deter the use of this agent under appropriate clinical circumstances. Am J Med, 1985 Jul 15, 79(1A), 37 - 42 Three-year experience with amikacin sulfate as an exclusive surgical aminoglycoside in a large acute-care hospital; Lee JT Jr; Aminoglycosides have important roles as perioperative adjunctive antibiotics in the surgical management of peritonitis . In the past, most surgeons have used gentamicin in combination with a drug aimed at intraperitoneal anaerobic pathogens, either clindamycin or metronidazole . Amikacin has been traditionally reserved for culture-proved infections due to gram-negative organisms resistant to gentamicin or other aminoglycosides . At the Minneapolis Veterans Administration Medical Center, a worrisome incidence of gentamicin-resistant hospital isolates led to a decision to make amikacin the exclusive, routine surgical aminoglycoside for all abdominal infections, as well as all hospital-acquired infections in surgical patients involving gram-negative aerobes and requiring parenteral therapy . This report describes the resultant three-year experience with amikacin in surgical patients . Data from four research studies involving these patients suggest that exclusive amikacin use has not led to the emergence of amikacin-resistant organisms or to significant nephrotoxicity . Amikacin use in surgical patients is supported in hospital environments where gentamicin resistance is judged to be a significant clinical risk factor. Lancet, 1985 Jul 13, 2(8446), 59 - 63 Prevention of gram-negative shock and death in surgical patients by antibody to endotoxin core glycolipid; Baumgartner JD et al.; The prophylactic effect of antibody to endotoxin core glycolipid was studied in surgical patients at high risk of gram-negative infection . At randomisation (on admission to intensive care unit), every 5 days thereafter, and at onset of septic shock, patients received plasma taken from donors before (control) or after immunisation with Escherichia coli J5, a mutant with only core determinants in its endotoxin . Gram-negative shock occurred in 15 of 136 controls and 6 of 126 J5 antibody recipients and related deaths in 9 of 136 and 2 of 126, respectively . J5 antibody was most effective in abdominal surgery patients, in whom shock occurred in 13 of 83 controls and 2 of 71 antibody recipients . Although antibody prophylaxis did not lower the infection rate, it prevented the serious consequences of gram-negative infections and thus improved the overall prognosis. J Infect Dis, 1985 Jul, 152(1), 177 - 84 Effects of specific antibodies, hormones, and lipoproteins on bacterial lipopolysaccharides injected into the rat; Munford RS et al.; When gram-negative lipopolysaccharides (LPS) are injected intravenously into experimental animals, approximately one-third of the LPS bind to high-density lipoproteins (HDL) in the plasma and are slowly taken up into tissues by HDL-mediated mechanisms . Molecules of LPS in the plasma that do not bind to HDL are taken up more rapidly by tissues that are rich in phagocytic cells (e.g., liver, spleen) . In these experiments we evaluated the effects of several potential host factors on the binding of LPS to HDL and on the tissue uptake of LPS injected intravenously into rats . Antibodies to LPS inhibited LPS binding to HDL and increased the uptake of the injected LPS (as well as the LPS in preformed LPS-HDL complexes) by the liver and spleen . High levels of circulating HDL decreased the uptake of injected LPS and LPS-HDL complexes by the adrenal gland, presumably by occupying tissue receptors for HDL . Pretreating rats with dexamethasone unexpectedly decreased the uptake of injected LPS-HDL complexes by the adrenal gland and increased uptake of LPS by the gland, a result suggesting that this drug has opposing effects on the uptake of HDL-bound and -unbound LPS by the adrenal gland . The host factors studied appear to influence the fate of injected LPS by acting at different sites: IgG antibody to LPS blocks the binding of LPS to HDL in the plasma, whereas all of the factors studied have effects that modulate the uptake of LPS or LPS-HDL complexes or both by the cells of specific tissues. Arch Intern Med, 1985 Jul, 145(7), 1212 - 6 Improved mortality in gram-negative bacillary bacteremia; McCue JD; From 1979 to 1982, the four years of this study, episodes of gram-negative bacillary bacteremia occurred in a 489-bed community teaching hospital--an increase of 15.9% . Mortality related to bacteremia was 19.4% overall and only 3.2% for the 158 episodes involving nonfatal underlying illnesses, lower figures than those reported in the past . The severity of underlying illnesses in bacteremic patients dominated all other clinical variables that were studied as prognostic factors for the outcome of the episode . The same bacteremia-related mortality was seen in patients who had empirically received (1) multiple-antibiotic regimens in which one or more drugs were active against the pathogenic organism(s), (2) either an appropriate aminoglycoside or beta-lactam antibiotic alone, or (3) both an aminoglycoside antibiotic and a beta-lactam antibiotic active against the pathogenic organism(s). Vestn Khir Im I I Grek, 1985 Jul, 135(7), 35 - 7 {Antibiotic therapy in the surgical treatment of suppurative cholangitis}; Zemskov VS et al.; The pathogenic agents of purulent cholangitis are known to be the conditionally pathogenic mainly gram-negative bacteria of the intestinal group . Kanamycin, monomycin, furazolidon should be used . The antibiotic treatment should be corrected according to data of inoculations of blood taken during the first days of staying in the hospital, then to data of inoculations of bile taken both during operation and at the 3d-4th postoperative days. J Assoc Off Anal Chem, 1985 Jul-Aug, 68(4), 661 - 4 Sensitive enzyme immunoassay of colistin and its application to detect residual colistin in rainbow trout tissue; Kitagawa T et al.; An antibody against colistin (CL), an antibiotic effective for gram-negative bacteria, was produced in rabbits immunized with a colistin-protein conjugate . The conjugate was prepared by a novel and convenient procedure devised to couple an amino group of CL to thiol groups of bovine serum albumin (BSA) introduced by thiol exchange reduction of its disulfide bonds with dithiothreitol, using N-(m-maleimidobenzoyloxy)succinimide (MBS) as a cross-linker . Enzyme labeling of CL with beta-D-galactosidase was performed by utilizing another cross-linker, N-(gamma-maleimidobutyryloxy)succinimide, by means of a convenient labeling method . A double antibody enzyme immunoassay of CL, which could determine as little as 30 ng/mL of CL, was developed using labeled CL and anti-CL antiserum . With this assay, drug levels were easily determined in fish tissue after CL administration . The enzyme immunoassay should provide a useful tool for detection and quantitation of residual drugs in foods and related products. Antibiot Med Biotekhnol, 1985 Jul, 30(7), 495 - 8 {Isoelectric focusing of different classes of beta-lactamases in cell-free extracts of Gram-negative bacteria}; Sazykin AIu; A method of electrofocusing of beta-lactamases in cell-free bacterial extracts was developed . It provided determination of the isoelectric points of beta-lactamases without preliminary preparation of the homogeneous enzyme . Isoelectrofocusing of beta-lactamases of 14 poly-resistant strains of gram-negative bacteria of six species was performed . It was found that the isoelectric points of the beta-lactamase belonging to the same class according to Richmond were different . No species specificity of the beta-lactamases of the gram-negative bacteria was observed. G Batteriol Virol Immunol, 1985 Jul-Dec, 78(7-12), 144 - 54 {Generation of pro-coagulation activity by leukocytes stimulated in vitro with lipoglycans from mycoplasmas}; Monno RA et al.; Lipoglycans represent a special type of lipopoly-saccharide that differs in structure from the well-known gram-negative bacteria lipopolysaccharide . After briefly describing their most important characteristics, the authors take into consideration the in vitro interaction between lipoglycans from Acholeplasma granularum, Acholeplasma oculi, and Acholeplasma axanthum and human leukocytes in terms of production of procoagulant activity . The results obtained show that the examined lipoglycans possess, similarly to lipopolysaccharides, the capacity to induce the production of procoagulant activity, thromboplastin-like, from human mononuclear cells . However, the pathophysiological significance of this endotoxin-like activity remains to be established. Arch Microbiol, 1985 Jun, 142(1), 6 - 11 Nature and linkage type of fatty acids present in lipopolysaccharides of phase I and II Coxiella burnetii; Wollenweber HW et al.; The constituent fatty acids of lipopolysaccharides (LPS) of Coxiella burnetii (phase I and II) were qualitatively and quantitatively analysed by combined gas-liquid chromatography/mass spectrometry . The total fatty acid content (per mg LPS) was determined as 90.0 nmol (2.3 wt%) for LPS of phase I cells (LPS I) and 179.1 nmol (4.8 wt%) for LPS of phase II cells (LPS II) . Of the 24 different acyl residues characterized (12 to 18 carbon atoms), nine were 3-hydroxy fatty acids (normal, iso- and anteiso-branched) which quantitatively predominated . All 3-hydroxylated fatty acids were found to possess the (R)-configuration, to be exclusively amide-linked and to be acylated at their 3-hydroxyl group . Ester-linked nonhydroxylated fatty acids (normal, iso- and anteiso-branched) were present but ester-bound 3-hydroxy- or 3-acyloxyacyl residues were lacking from C . burnetii LPS I and LPS II . As the major acyl group (R)-3-(12-methyl-tetradecanoyloxy)-12-methyl-tetradecanoic acid was identified . Our results show that the complex fatty acid spectrum of C . burnetii differs considerably from that of LPS of other Gram-negative bacteria . They further suggest an enormous heterogeneity of the lipid A component of C . burnetii LPS I and LPS II. Scand J Work Environ Health, 1985 Jun, 11(3 Spec No), 199 - 206 Organic dusts and lung reactions--exposure characteristics and mechanisms for disease; Rylander R; Exposure to organic dusts has been related to pulmonary occupational diseases in a variety of environments . These dusts contain several different agents, but the microbial contamination is always important, particularly regarding molds and Gram-negative bacteria . In the lung, organic dusts cause a series of reactions ranging from irritation with neutrophilic invasion to the initiation of cell mediator release and the development of antibodies . For certain diseases, such as byssinosis, the relation between the cell reactions and the disease is relatively well established; for others, such as allergic alveolitis (hypersensitivity pneumonitis) with fibrosis, more research is needed before the pathogenesis can be established . An understanding of the specific agents causing the disease and the cellular reactions behind its development is essential for its prevention. J Clin Microbiol, 1985 Jun, 21(6), 865 - 8 Detection of endotoxin in the plasma of patients with gram-negative bacterial sepsis by the Limulus amoebocyte lysate assay; Pearson FC et al.; A total of 120 Limulus amoebocyte lysate (LAL) determinations were made on plasma obtained from normal, healthy human blood donors . Results demonstrated a mean endotoxin level in blood of 0.02 to 1.57 pg/ml . The amount of Escherichia coli endotoxin added to human plasma samples can be quantitated by both nephelometry and turbidimetry . Endotoxin-spiked samples were shown to be significantly different from unspiked samples . When plasma samples were collected from 45 patients hospitalized at three centers, a strong association was demonstrated between a positive Limulus amoebocyte lysate assay and a septic condition . Sensitivity, specificity, and false-positive and false-negative rates for the Limulus amoebocyte lysate assay as a diagnostic test for gram-negative bacteremia were estimated. Southeast Asian J Trop Med Public Health, 1985 Jun, 16(2), 291 - 5 Pure red cell aplasia in Thailand: report of twenty four cases; Jootar S et al.; Twenty four cases of pure red cell aplasia were reported . No underlying diseases were found in two cases . Of the 22 cases with secondary form, 10 were from infections, mostly gram negative organisms . Three cases had systemic lupus erythematosus, two had autoimmune hemolytic anemia . The following conditions were found in one each: thymoma, thyroid carcinoma, protein calorie malnutrition, rheumatoid arthritis, non-Hodgkin lymphoma and Sheehan's syndrome . Three patients died, two from uncontrolled infection, the other from uncontrolled SLE and subsequently systemic fungal infection . Only one of the 2 primary cases responded to immunosuppressive drugs . The majority of patients with underlying infections, PRCA resolved after the infections were treated . This is the first reported series of PRCA in Thailand. J Clin Microbiol, 1985 Jun, 21(6), 955 - 8 Evaluation of a lysis direct plating method for pediatric blood cultures; Welch DF et al.; The Isolator 1.5 Microbial tube (E . I . du Pont de Nemours & Co., Inc., Wilmington, Del.) is a commercially available blood culture system for use in pediatrics . The methodology is based on blood lysis followed by direct plating of the sample on culture media to detect bacteria and fungi . Comparative recovery rates of pathogens from blood collected in this and a conventional broth system were similar . The Isolator detected 104 of 120 clinically significant isolates, whereas 106 of 120 isolates were detected by the broth system . The major advantage of the Isolator methodology was early detection of septicemia . Initial detection of gram-negative bacteria occurred an average of 14.2 h earlier by the Isolator system than by the conventional broth method . The Isolator also permitted quantitation of bacteremia and fungemia . Probable contaminants were recovered from 10.0% of the cultures processed by the Isolator, but steps which could be taken to minimize this problem were identified . The Isolator is a useful method for pediatric blood cultures. Am J Physiol, 1985 Jun, 248(6 Pt 1), E732 - 40 Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion; Wolfe RR et al.; The effect of gram-negative sepsis on the kinetics and oxidation of very low-density lipoprotein (VLDL) fatty acids was assessed in conscious dogs in the normal state and 24 h after infusion of live Escherichia coli . VLDL, labeled with {2-3H}glycerol and {1-14C}palmitic acid, was used to trace VLDL kinetics and oxidation, and {1-13C}palmitic acid bound to albumin was infused simultaneously to quantify kinetics and oxidation of free fatty acid (FFA) in plasma . Sepsis caused a fivefold increase in the rate of VLDL production (RaVLDL) . In the control dogs, the direct oxidation of VLDL-fatty acids was not an important contributor to their overall energy metabolism, but in dogs with sepsis, 17% of the total rate of CO2 production could be accounted for by VLDL-fatty acid oxidation . When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis . We conclude that the increase in triglyceride concentration in fasting dogs with gram-negative sepsis is the result of an increase in VLDL production and that the fatty acids in VLDL can serve as an important source of energy in sepsis. J Infect Dis, 1985 Jun, 151(6), 988 - 94 Age-related prevalence of human serum IgG and IgM antibody to the core glycolipid of Escherichia coli strain J5, as measured by ELISA; Law BJ et al.; Administration of antibody to Escherichia coli strain J5 reduces mortality in patients with gram-negative septic shock . Limited evidence suggests that this antibody is present in the serum of healthy individuals and deficient in persons with malignancy; however, the age-related prevalence of serum antibody to strain J5 in normal subjects is unknown . We developed an ELISA method to measure IgG and IgM antibody to purified J5 lipopolysaccharide (LPS) in sera from 33 maternal-newborn cord pairs, 40 neonates, and 253 individuals aged from one day to twenty years . Reciprocal geometric mean titers for serum antibody to strain J5 LPS were as follows: maternal-IgG, 12.3; IgM, 174; one month old or less-IgG, 8.3; IgM, 5.6; one to 24 months old-IgG, 10.5; IgM, 44.7; greater than 24 months old -IgG, 16.2; IgM, 200 . We conclude that human serum antibody to J5 LPS is predominantly IgM and that it is usually present by two years of age . The ELISA method should provide a valuable tool in studying the relation of core glycolipid antibody to immunity and therapy of gram-negative bacterial infections. J Infect Dis, 1985 Jun, 151(6), 1012 - 8 Role of antibiotic class in the rate of liberation of endotoxin during therapy for experimental gram-negative bacterial sepsis; Shenep JL et al.; To evaluate the role of antibiotic class in the rate of liberation of endotoxin during therapy for sepsis caused by gram-negative bacteria, we obtained serial blood samples from rabbits with sepsis caused by Escherichia coli and treated with chloramphenicol, gentamicin, or moxalactam . The concentrations of viable bacteria, free endotoxin, and total endotoxin in each blood sample were measured . In rabbits treated with chloramphenicol, the geometric mean levels of free endotoxin remained proportional to the geometric mean levels of bacteremia, a result indicating the absence of antibiotic-induced endotoxin liberation . In contrast, levels of free endotoxin increased rapidly while levels of bacteremia declined after treatment with gentamicin or moxalactam, a result indicating antibiotic-induced release of endotoxin . Despite similar rates of bacterial killing, mean levels of free endotoxin were as much as 20-fold higher in rabbits treated with moxalactam than in paired rabbits receiving gentamicin (P less than .05) . These results indicate that endotoxin liberation during therapy for sepsis caused by gram-negative bacteria is dependent upon the class of antibiotic administered and is not necessarily correlated with the rate of bacterial killing. Jpn J Antibiot, 1985 Jun, 38(6), 1648 - 53 {Pharmacokinetic study of cefmenoxime concerning its transfer into tissues}; Washida H et al.; Cefmenoxime (1 g) was intravenously administered by one shot to investigate its pharmacokinetic profile with respect to transfer into the kidney, vesical wall and prostatic adenoma . The concentration of cefmenoxime in the kidney reached a peak of 403 micrograms/g at 0.17 hour after administration . The biological half-life was 0.74 hour . In the vesical wall, the level of cefmenoxime reached a peak of 28 micrograms/g at 0.67 hour after administration . The half-life was 2.30 hours . The peak level of cefmenoxime in the prostatic adenoma was 22 micrograms/g at 0.39 hour after administration . The half-life was 2.90 hours . The concentrations of cefmenoxime in these urogenital tissues were higher than its MIC80 and MBC80 against various Gram-negative organisms. Infect Control, 1985 Jun, 6(6), 231 - 2 Bedside resuscitation bags: a source of bacterial contamination; Thompson AC et al.; Resuscitation bags at the bedside of 12 intubated ICU patients with known culture positive sputum were evaluated as possible reservoirs of pathogenic bacteria . As oxygen was constantly flowing into the bags, sampling of gas continuously emitted from the exhalation valve assembly was sampled to detect if a bacteria-laden aerosol was being created . Positive cultures were obtained from 75% of the valves and 25% of the aerosol samples . In those patients with gram-negative bacteria in their sputum, 71% of the valves and 29% of the gas samples were positive for the same organisms . Various methods to control this possible contributing factor to nosocomial infection in the ICU are discussed. J Infect Dis, 1985 Jun, 151(6), 1005 - 11 Failure of monoclonal antibodies to core glycolipid to bind intact smooth strains of Escherichia coli; Gigliotti F et al.; To study the ability of antibody to the core glycolipid (CGL) region of lipopolysaccharide (LPS) to bind intact gram-negative bacterial cells, we produced monoclonal antibodies that bind LPS from the Escherichia coli rough mutant J5 . Four representative monoclonal antibodies that bound four distinct epitopes on the CGL region of LPS were studied . All four antibodies bound both isolated J5 LPS and intact J5 bacterial cells, but none of the antibodies bound to intact cells of E . coli O111:B4 or K1:O7 . Binding of the monoclonal antibodies to isolated LPS from these latter two smooth strains was variable . These results confirm the presence of shared antigenic sites in the CGL region of heterologous LPS molecules but indicate that these sites are not necessarily available on smooth gram-negative bacteria for binding by antibody to CGL. Infection, 1985 May-Jun, 13(3), 120 - 4 Preliminary study on administration of high-titer lipid A antibody serum in sepsis and septic shock patients; Marget W et al.; To determine whether sera containing high titers of lipid A antibody may be applicable at effective doses in treating patients with septicemia, a pharmacokinetic study was performed in seven patients aged 24 to 73 years with gram-negative septicemia and various underlying diseases, one of whom received a placebo, and in one patient without infection . In this study, we attempted to determine the effective dosage, the number of infusions and appropriate administration interval for the prevention and treatment of endotoxin shock . Blood samples from each patient were tested for lipid A antibodies before and at regular intervals after administration using an enzyme-linked immunosorbent assay (ELISA) . Selected, pooled human immunoglobulin preparations containing high titers (expressed as exponents of 10) of IgG (titer = 3-4) and IgM (titer = 2-4) lipid A antibodies were administered first at a dosage of 8 ml/kg body weight . After administration, the mean lipid A antibody titer increased from 0.4 to 2.3 for IgG and from 2 to 2.4 for IgM . The initial increase was followed by a drop in titer within 24 h, which was perhaps due to antibody consumption . Following the second administration (24 h after the first) of only 4 ml/kg body weight, the mean IgG and IgM titers increased to 2.4 and 3.3, respectively, and dropped slower . A notable increase in circulating lipid A antibody titers was achieved, and four of six treated patients recovered from the sepsis . The two patients who died entered the study in a pre-terminal state . These studies encouraged us to initiate a randomized, double-blind controlled study. Infection, 1985 May-Jun, 13(3), 115 - 9 Serum antibodies against common antigens of bacterial lipopolysaccharides in healthy adults and in patients with multiple myeloma; Stoll C et al.; The incidence of infections caused by gram-negative bacteria is increased in patients with multiple myeloma due to secondary humoral immunodeficiency . In order to diagnose patients with increased susceptibility to gram-negative infections, serum antibodies against common determinants of lipopolysaccharides (lipid A and core-polysaccharide) were determined by a rapid enzyme-linked immunosorbent assay (ELISA) . It was possible to define a group of patients at high risk of contracting gram-negative infections using this test . Intravenous IgG preparations used as a substitute were shown to contain antibodies against these common antigens . However, it is suggested that the clinically recognized efficacy of these preparations could be due to their containing anti-LPS antibodies. Antimicrob Agents Chemother, 1985 May, 27(5), 858 - 62 Effect of temocillin and moxalactam on platelet responsiveness and bleeding time in normal volunteers; Nunn B et al.; The effects of temocillin and moxalactam on platelet responsiveness and bleeding time were examined in healthy male volunteers . In the first study, moxalactam (4 g intravenously every 12 h) was given to six subjects; template bleeding times were at least doubled in five subjects 12 to 14 h after 7 doses (P = 0.008) and in all six subjects 12 to 14 h after 13 doses (P = 0.004) . ADP-induced primary aggregation was approximately halved after 7 (P = 0.026) and 13 doses (P = 0.008), and there was a markedly increased tendency toward disaggregation . Collagen-induced aggregation was also halved, but the effect only reached statistical significance after 13 doses (P = 0.008) . There was essentially no effect on primary aggregation in response to the thromboxane receptor agonist U46619 or to platelet activating factor . Temocillin (4 g intravenously every 12 h) was given to eight subjects, three of whom had participated in the moxalactam study 8 weeks earlier . Temocillin had no significant effect on template bleeding time 12 to 14 h after 7 or 13 doses . However, in four subjects, the endpoint may have been less abrupt . There was no significant effect on ADP-induced primary aggregation or responsiveness to collagen . Even after 13 doses of temocillin, secondary aggregation in response to normal concentrations of ADP was demonstrable in the platelet-rich plasma of all eight subjects . Neither antibiotic had any effect on prothrombin times . Thus, with methodology that readily detected the effects of moxalactam on hemostasis, we were unable to demonstrate any unequivocal deleterious effects of temocillin at its maximum recommended dose . Temocillin may therefore be particularly useful for the treatment of many gram-negative infections in patients at increased risk of clinical bleeding. J Bacteriol, 1985 May, 162(2), 693 - 7 Enzymatic release of halogens or methanol from some substituted protocatechuic acids; Kersten PJ et al.; Four strains of gram-negative bacteria capable of growing at the expense of 5-chlorovanillate were isolated from soil, and the metabolism of one strain was studied in particular detail . In the presence of alpha, alpha'-bipyridyl, a suspension of 5-chlorovanillate-grown cells accumulated 5-chloroprotocatechuate from 5-chlorovanillate; in the absence of inhibitor these compounds, and various other 5-substituted protocatechuates and vanillates, were oxidized to completion . Cell suspensions of this strain grown on 5-chlorovanillate or vanillate released chloride quantitatively from 5-chlorovanillate and released methanol from syringate . Extracts of cells grown with 4-hydroxybenzoate, vanillate, or syringate possessed high levels of both protocatechuate 4,5-dioxygenase and 2-pyrone-4,6-dicarboxylate hydrolase; extracts from acetate-grown cells did not . Protocatechuate 4,5-dioxygenase, purified from strains that could grow with 5-chlorovanillate, oxidized 5-halogeno-protocatechuates and 3-O-methylgallate with the formation of 2-pyrone-4,6-dicarboxylate . A crude extract converted 5-chloroprotocatechuate into pyruvate plus oxaloacetate . On the basis of these observations, a meta-fission reaction sequence is proposed for the bacterial degradation of vanillate and protocatechuate substituted at C-5 of the benzene ring with halogen or methoxyl. Jpn J Antibiot, 1985 May, 38(5), 1319 - 30 {Basic and clinical studies of cefminox in obstetrics and gynecology}; Kubota K; The study was done to evaluate the usefulness of cefminox (CMNX, MT-141) injection for the treatment of infections in the field of obstetrics and gynecology . Fundamental and clinical studies were made and following results were obtained . When 1 g of CMNX was administered by intravenous single shot, the maximum concentrations in various tissues of female genital organs were as follows: 34.98 micrograms/g in oviduct at 1 hour 10 minutes after the single shot, and 37.11, 28.01, 26.84, 30.01 and 40.06 micrograms/g in ovary, endometrium, myometrium, cervix uteri and portio, respectively, after 1 hour 20 minutes . In the clinical studies, CMNX was given to 13 cases with female genital organ infections and others . As for the clinical effects, responses were excellent in 1 case, good in 12 cases among 13 cases in total . The efficacy rate was 100% . As for the clinical effects on causative bacteria, the efficacy rates were 100% (3/3) for single infections due to Gram-negative bacteria, 100% (8/8) for mixed infection cases . Side effects were not observed . CMNX showed a satisfactory clinical efficacy and a potent bacteriological effect in treatment of the infection in the field of obstetrics and gynecology, and it has been concluded that CMNX will be a useful addition to the antibiotics for the therapy of these infections. Pediatr Infect Dis, 1985 May-Jun, 4(3), 265 - 9 Use of trimethoprim-sulfamethoxazole to prevent bacterial infections in children with acute lymphoblastic leukemia; Goorin AM et al.; We assessed the efficacy of prophylactic antibiotics in children receiving intensive chemotherapy for acute lymphoblastic leukemia . The patients were randomized to receive either trimethoprim-sulfamethoxazole (TMP-SMX) or placebo in a double-blind trial . Thirty patients were evaluated in each group . Children receiving TMP-SMX had fewer episodes of bacteremia (0 vs . 5) and otitis media (3 vs . 18) . The geometric mean of the neutrophil nadir was 172 in the TMP-SMX group and 287 in controls . However, no increased delay or dose reduction of chemotherapy was observed in the TMP-SMX treated patients . Five patients who received TMP-SMX developed Gram-negative rods resistant to TMP-SMX on surveillance stool cultures . We conclude that TMP-SMX prophylaxis decreased certain bacterial infections in children with acute lymphoblastic leukemia without causing clinically significant toxicity . The emergence of Gram-negative rods resistant to TMP-SMX in treated patients suggests that TMP-SMX prophylaxis should be restricted to patients who are at high risk for developing a bacterial infection or Pneumocystis carinii pneumonia. Infect Immun, 1985 May, 48(2), 464 - 73 Uptake and deacylation of bacterial lipopolysaccharides by macrophages from normal and endotoxin-hyporesponsive mice; Munford RS et al.; Macrophages are thought to play a central role in the responses of animals to gram-negative bacterial lipopolysaccharides (LPS) . Since nothing is known about the metabolism of LPS by these cells, we studied the uptake and deacylation of radiolabeled LPS by thioglycolate-elicited peritoneal macrophages from normal (C3H/HeN) and LPS-hyporesponsive (C3H/HeJ) mice . Macrophages from both kinds of mice took up and deacylated LPS that were added to the culture medium . Opsonization of the LPS with anti-LPS immunoglobulin G antibodies greatly increased LPS uptake; the opsonized LPS also underwent deacylation at rates that were directly related to the amount of cell-associated LPS . An analysis of the fatty acid composition of the cell-associated LPS indicated that the cells have one or more acyloxyacyl hydrolases that remove the non-hydroxylated fatty acids that are normally substituted to the hydroxyl groups of (glucosamine-linked) 3-hydroxytetradecanoate residues in lipid A; we also found evidence for deacylation of 3-hydroxytetradecanoate from the glucosamine backbone . LPS deacylation by macrophages from C3H/HeN and C3H/HeJ mice was qualitatively and quantitatively similar . Nonopsonized LPS are able to stimulate LPS-responsive cells; in these studies we established that animal cells can deacylate nonopsonized LPS, thus raising the possibility that LPS metabolism may play a role in modulating cellular stimulation. J Am Vet Med Assoc, 1985 Apr 15, 186(8), 798 - 801 Prevalence and causes of ram epididymitis in Utah; Bagley CV et al.; Palpation of the testicles and epididymides was used to determine the prevalence of ram epididymitis (RE) in Utah range flocks over a 5-year period . Of 62 range flocks examined, 58 had rams with palpable lesions . A comparison was made of prevalence by right vs left testicle involvement, but no significant difference was found . Culling all rams with palpable lesions from the flock progressively reduced the annual incidence, but did not eliminate RE from any flock . Semen and specimens of reproductive tract tissue were obtained from representative flocks for bacterial culture . Brucella ovis was found commonly in range flocks, but was not isolated from RE-affected rams in virgin, ram-producing flocks . In the ram-producing flocks, a gram-negative, pleomorphic rod-type organism was found . It was concluded that RE should be considered as 2 disease entities, based on the finding of 2 causative organisms and the management systems under which those organisms are found . Brucella ovis was the major cause in persistently infected range flocks, whereas the gram-negative pleomorphic rod-type organism is the apparent cause of RE in virgin, ram-producing flocks. Am J Med, 1985 Apr, 78(4), 687 - 90 Cutaneous infection at dog bite wounds associated with fulminant DF-2 septicemia; Kalb R et al.; Severe DF-2 sepsis with disseminated intravascular coagulopathy developed following dog bites in two patients who had undergone prior splenectomy . Eschariform lesions developed at the site of the animal bite in both patients . DF-2 is an unusual animal-borne slow-growing gram-negative rod that can cause fulminant sepsis in splenectomized patients . Splenectomized patients should be aware of the hazards from a dog bite . The presence of eschariform lesions in such patients should provide a clinical clue to the presence of DF-2 infection. Eur J Cancer Clin Oncol, 1985 Apr, 21(4), 439 - 45 Serum bactericidal activity as a therapeutic guide in severely granulocytopenic patients with gram-negative septicemia; Martino P et al.; The peak and trough levels of bactericidal activity of the serum of 74 severely granulocytopenic patients (less than or equal to 500 polymorphonucleates per microliter) with hematologic malignancies and Gram-negative septicemia were measured using the patient's infectious organism and serum containing the given antibiotics . When the peak titer of bactericidal activity in the serum was greater than 1:8 the septicemia was cured in more than 90% of the cases . However, in order to achieve a satisfactory rate of cure, patients with less than 100 polymorphonucleates/microliter required higher peak levels than patients with 100-500 polymorphonucleates/microliter . Serum bactericidal activity was influenced by the in vitro susceptibility of the offending pathogen and by the presence of in vitro synergism between the given antibiotics . These two variables showed a correlation with the clinical outcome that proved to be increasing with the degree of granulocytopenia . Furthermore, synergistic combination of the antibiotics appeared essential when the in vitro susceptibility shown by the offending pathogen was moderate . These data suggest (i) that determination of the bactericidal activity of the serum may prove to be a useful method to predict the clinical outcome in severely granulocytopenic patients with Gram-negative septicemia; and (ii) under the same conditions, antibiotic combinations that have demonstrable in vitro synergy against the offending pathogen should be given the utmost consideration. Eur J Clin Microbiol, 1985 Apr, 4(2), 108 - 12 Evaluation of pertinent parameters of a new identification system for non-enteric gram-negative rods; von Graevenitz A et al.; The API 20 NE (Rapid NFT) system for identification of non-enteric aerobic gram-negative rods was evaluated using 431 strains of species covered by the analytical profile index and previously identified by conventional methods . In an analysis of several parameters, 343 (80%) of the strains were identified correctly with good to excellent probabilities of positive reactions (80.0-99.9%), 190 (55%) of these within 24 h; 74 (17%) yielded primary identifications with lower probabilities . Only 3% of the strains could not be correctly identified . The system is very satisfactory for routine use, but could be improved by modified pre-testing of the strains and by including more species in the profile index. Nippon Geka Gakkai Zasshi, 1985 Apr, 86(4), 381 - 93 {Hyperdynamic state induced by continuous infusion of E . coli endotoxin in dogs}; Wu TT; It is well established that septic shock is caused by Gram-negative endotoxemia, and is characterized by hyperdynamic state being observed in the early stage of shock . This study is designed to elucidate the hemodynamic and metabolic changes induced by continuous infusion of small amount of endotoxin in the dog, with special reference to the existence of hyperdynamic state . Seven mongrel dogs were continuously infused with 10 micrograms/kg/day of E.coli endotoxin for 4 days under fasted, awake condition . All animals revealed mild hypodynamic state with severe catabolic responses in protein-energy metabolism . In contrast, 11 dogs infused with 36kcal/kg/day of glucose and 10 micrograms/kg/day of endotoxin showed marked increase (+30%) in cardiac index, and decrease in mean arterial pressure as well as total peripheral resistance, indicating the presence of hyperdynamic state . Metabolic studies indicate mild catabolic response . Administration of fat emulsion instead of isocaloric glucose has resulted transient hyperdynamic state, but failed to maintain this condition . In conclusion, it is possible to produce hyperdynamic state similar to that seen in septic shock by continuous administration of small amount of endotoxin in the dog, provided proper amount of glucose is supplied. J Biol Response Mod, 1985 Apr, 4(2), 169 - 84 Biological effects of White-type polysaccharides of gram-negative bacteria; Rothman J et al.; The White-type polysaccharide (WPS), often called Freeman polysaccharide, was obtained by hydrolyzing gram-negative bacteria in 0.2 N acetic acid at 100 degrees C for 2 h . The crude product contained partially degraded O-antigens as well as other components that were active as immune adjuvants, enhancers of macrophage cytotoxicity of tumor target cells, and inducers of osteoclastic bone resorption . The same WPS preparation augmented the tumor cytotoxicity of normal mouse spleen cells and slightly retarded the take of L1210 leukemia in mice . The WPS preparations generated colony-stimulating factor in mice but were not active in lymphoproliferative (mitogenicity) tests . Chemical analyses of the WPS preparations did not detect the presence of components characteristic of the lipid moiety of endotoxins . The WPS samples were also negative in biological assays of endotoxicity such as local Shwartzman and toxicity tests . These findings indicate that gram-negative bacteria contain nonendotoxin components that are potent modifiers of some biological responses. Oral Surg Oral Med Oral Pathol, 1985 Apr, 59(4), 336 - 9 The presentation and complications of odontogenic septic shock . Report of a case; Quinn P et al.; Although most odontogenic infections spread locally to adjacent fascial spaces, usually contiguous with the offending odontogenic pathosis, occasionally such an infection can spread rapidly across the midline and appear on the opposite side of the face and neck . Debilitated chronic alcohol abusers who are nutritionally deficient are more likely to develop serious life-threatening infections, either through serious airway involvement as seen in Ludwig's angina or manifest as a gram-negative septicemia with life-threatening shock and even cardiac arrest, than the usual dental patient with cellulitis . Early recognition through a high index of suspicion and vigorous monitoring will pick up the initial manifestation of toxic shock, as noted in this case report. J Clin Hosp Pharm, 1985 Mar, 10(1), 95 - 100 Microbial contamination of non-sterile pharmaceutical products made in hospitals in the North East Thames Regional Health Authority; Baird RM; Non-sterile pharmaceutical products made in nine hospitals in the North East Thames Regional Health Authority were examined for microbial contamination as part of a quality assurance programme . The incidence of contamination was found to vary between hospitals, but in all cases improvements were seen during the 3-year monitoring period in the microbiological quality of products made in individual hospitals . The most common isolates were aerobic spore bearers--usually less than 10(2) colony forming units/g or ml . Gram-negative isolates were found in at least one product from each hospital . Pseudomonas spp . were isolated from several samples of peppermint water. J Clin Pharmacol, 1985 Mar, 25(2), 67 - 81 Therapeutic initiatives for the avoidance of aminoglycoside toxicity; Whelton A; Aminoglycosides continue to be indispensable in the management of serious and life-threatening aerobic gram-negative infections . On an annual basis in the United States, they are used in the management of four million patients . Despite their clinical utility, they continue to manifest a high profile of toxic side effects such as nephrotoxicity and ototoxicity with the rare occurrence of neuromuscular toxicity . Animal experimental models have been invaluable in elucidating the pathophysiologic mechanisms by which aminoglycosides damage the kidney and the inner ear . However, it is from clinical therapeutic experience and prospective clinical trials that we have been able to solidly define the risk factors that accentuate the development of aminoglycoside-related toxicity . The clinical toxicity of these agents can be kept to a minimum by ensuring the use of an appropriate dose, for periods of time not exceeding nine to ten days, in a well-hydrated, normokalemic patient . Special subpopulation groups such as the elderly, the obese, those with preexisting renal disease, or patients who need the concurrent use of other nephrotoxins, require special care in the monitoring of their aminoglycoside therapy to ensure a safe and effective clinical outcome. J Surg Res, 1985 Mar, 38(3), 298 - 304 Metabolic effects of pretreatment with Escherichia coli J5 antiserum on guinea pig gram-negative bacterial sepsis; Dunn DL et al.; Antiserum raised to a rough mutant Escherichia coli, termed J5 (anti-J5 RS), protected against lethal gram-negative bacterial sepsis in a guinea pig model when animals were pretreated with both antiserum and heparin . This same model was used to examine and compare the effects of pretreatment with anti-J5 RS, normal rabbit serum (NRS), or saline, each +/- heparin on physiologic and metabolic parameters during a septic insult . Results demonstrated that leukopenia and thrombocytopenia occurred to a similar degree in all pretreatment groups; no significant leuko- or thrombostasis was noted on examination of histologic specimens; complement activation was maximal in those animals receiving anti-J5 RS alone without heparin; the most abnormal amino acid profile was present in the NRS + heparin group; and only the anti-J5 RS + heparin group did not develop glomerular lesions indicative of disseminated intravascular coagulation . A complement-mediated cell aggregation-type injury does not appear to occur in this model . It is hypothesized that both excessive complement and coagulation system activation occur after bacterial challenge when antibody directed against the bacteria is present (anti-J5 RS) leading to antigen-antibody complex formation and complement and coagulation cascade activation . Heparin may block either or both these cascade systems allowing enhanced, antibody-mediated opsonization and clearance of blood-borne bacteria, thus preventing end-organ alterations and organ failure during sepsis when combined with anti-J5 RS. Am J Obstet Gynecol, 1985 Mar 1, 151(5), 671 - 4 Endotoxemia in the neonatal lamb; O'Brien WF et al.; Although gram-negative sepsis is a major cause of neonatal morbidity and mortality, our understanding of endotoxemia in the neonate has been hampered by the lack of experimental models . Previous studies have suggested neonatal hyporesponsiveness to endotoxin . We studied unanesthetized neonatal lambs which had been exposed to the environment prior to study . These animals demonstrated the classic early phase changes of endotoxemia including pulmonary hypertension which was dependent upon prostanoid production . This model allows further studies of endotoxemia in the neonate. Med Clin North Am, 1985 Mar, 69(2), 243 - 56 Gram-negative bacillary meningitis; LeFrock JL et al.; The incidence of gram-negative bacillary meningitis has increased significantly in the past two decades . Approximately two thirds of all reported cases have occurred after neurosurgical procedures . With the development of the newer cephalosporins, the overall mortality rate has decreased from 40 to 80 per cent to 10 to 20 per cent. J Periodontol, 1985 Mar, 56(3), 127 - 31 Transmission and colonization of Actinobacillus actinomycetemcomitans in localized juvenile periodontitis patients; Christersson LA et al.; Actinobacillus actinomycetemcomitans is a Gram-negative oral microorganism, which has been implicated in the etiology of localized juvenile periodontitis and in severe medical infections such as bacterial endocarditis . This study evaluated the ability of periodontal probes to transmit A actinomycetemcomitans from juvenile periodontitis lesions to healthy gingival sulci in the same patient . Localized juvenile periodontitis patients exhibiting first molar and incisor alveolar bone loss and with large numbers of A actinomycetemcomitans in deep periodontal pockets were included in this study . A periodontal probe was inserted into periodontal pockets of 6 mm or greater depth . The probe was then placed into a healthy gingival sulcus of 3 mm or less, in the same subject . Fifty-five transfers by probing were made and A actinomycetemcomitans in both the donor and recipient sites was assessed by a selective culture technique . The results indicate that periodontal probes can become contaminated with A actinomycetemcomitans from juvenile periodontitis lesions during routine dental examinations and can transfer this microorganism from infected to previously uninfected sites . However, A actinomycetemcomitans inoculated into the healthy gingival sulci did not permanently colonize these sites since the organisms were eliminated within 3 weeks. Proc Natl Acad Sci U S A, 1985 Mar, 82(6), 1790 - 4 Protection against gram-negative bacteremia and endotoxemia with human monoclonal IgM antibodies; Teng NN et al.; Hybridomas producing human monoclonal IgM antibodies (mAbs) against bacterial lipopolysaccharide (LPS) were generated by fusion of B lymphocytes from sensitized human spleen with heteromyeloma cells . The splenocytes were from patients undergoing splenectomy during staging for Hodgkin disease after vaccination with the J5 mutant of Escherichia coli, which is deficient in O antigenic side chains . This deficiency exposes the core oligosaccharide, common to LPS of all Gram-negative bacteria . The mAbs cross-reacted strongly with endotoxins from a wide range of unrelated species of Gram-negative bacteria . The mAbs also gave strong protection against LPS in the dermal Shwartzman reaction and against lethal Gram-negative bacteremia in mice . These findings indicate that monoclonal IgM against LPS endotoxin can neutralize its toxicity in vivo and might be valuable for treatment of patients with Gram-negative bacteremia . Analysis of one of the hybridoma clones, A6(H4C5), showed that the IgM mAb is directed against the covalently bound lipid A, which represents the most conservative and least variable structural element of LPS. Plasmid, 1985 Mar, 13(2), 149 - 53 Plasmids related to the broad host range vector, pRK290, useful for gene cloning and for monitoring gene expression; Ditta G et al.; Derivatives of plasmid pRK290 that are useful for cloning and for analyzing gene expression in a wide variety of Gram-negative bacteria are described . A smaller broad host range plasmid derived from RK2, with properties similar to that of pRK290, is also described. J Bacteriol, 1985 Mar, 161(3), 955 - 62 Construction of broad-host-range cosmid cloning vectors: identification of genes necessary for growth of Methylobacterium organophilum on methanol; Allen LN et al.; Four new cloning vectors have been constructed from the broad-host-range cloning vector pRK290 . These vectors, pLA2901, pLA2905, pLA2910, and pLA2917, confer resistance to kanamycin and tetracycline . The latter two are cosmid derivatives of pLA2901 . The new vectors can be mobilized into, and are stably maintained in, a variety of gram-negative bacteria . A Sau3A genomic bank of Methylobacterium organophilum strain xx DNA has been constructed in pLA2917, and complementation analysis, with a variety of mutants unable to grow on methanol, revealed at least five separate regions necessary for growth on methanol . Complementation analysis and Tn5 mutagenesis data suggest that at least three genes are responsible for expression of active methanol dehydrogenase. Minerva Med, 1985 Feb 25, 76(7), 261 - 8 {Exogenous infections and environmental flora . Criteria for the characterization of bacteria and parameters influencing their spread}; Pessione E et al.; An assessment was made of environmental micro-organisms isolated in the University of Turin Intensive Surgical Care Unit and Emergency Surgery Department to determine the possible exogenous origin of post-operative infections . The enzymatic characters and antibiotypes were determined for some species, and subsequently compared with similar characters of the "in vivo" isolated flora . A monthly disinfection method based on comparison among three antiseptic agents (chlorexidine, formaldehyde and formotetronium) considerably reduced the flora . The data obtained, while showing that most of the infections observed were endogenous, also provided indications on the way in which the spread of certain Gram-negative germs, often involved in post-operative and post-traumatic infections, could be contained. J Immunol Methods, 1985 Feb 11, 76(2), 299 - 305 Immunoenzymatic analysis by monoclonal antibodies of bacterial lipopolysaccharides after transfer to nitrocellulose; Sidberry H et al.; A rapid, sensitive immunoenzymatic technique for the analysis of lipopolysaccharide (LPS) from gram-negative bacteria using monoclonal antibodies is described . After separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the LPS was either stained with silver or electrophoretically transferred to nitrocellulose . After reaction with anti-LPS monoclonal antibodies, the transferred antigens were visualized by reaction with alkaline-phosphatase-labelled anti-mouse antibodies and a substrate containing naphthol phosphoric acid and Fast Red. Am J Med, 1985 Feb 8, 78(2A), 31 - 3 Aztreonam therapy for gram-negative pneumonia; Greenberg RN et al.; Nineteen patients with community- or hospital-acquired gram-negative pneumonia were treated with aztreonam . Other gram-negative antibiotics were withheld . Thirteen patients (68 percent) had clinical cures and 15 (79 percent) had microbiologic cures with aztreonam . No adverse reactions or drug toxicity occurred in this population. Chemioterapia, 1985 Feb, 4(1), 24 - 7 Mechanisms of resistance to beta-lactam antibiotics; Wiedemann B et al.; The complex mechanism of resistance towards beta-lactam antibiotics in Gram-negative bacteria can be described by a simple equation in which the hydrolytic activity of the enzyme, the affinity to the penicillin binding protein in competition to the affinity to the beta-lactamase, the quantity of the enzyme and the ability of the drug to penetrate the outer membrane are considered . Depending on the characteristics of the drug, the beta-lactamase, and the microorganisms, the hydrolysis of the drug, its binding, or the reduced penetration can be the predominant factors. Appl Environ Microbiol, 1985 Feb, 49(2), 305 - 9 Legionella anisa: a new species of Legionella isolated from potable waters and a cooling tower; Gorman GW et al.; Between March 1980 and June 1981, five strains of Legionella-like organisms were isolated from water . Four were recovered from potable water collected from hospitals in Chicago, Ill., and Los Angeles, Calif., during outbreaks of nosocomial legionellosis . The fifth strain was isolated from water collected from an industrial cooling tower in Jamestown, N.Y . The strains exhibited biochemical reactions typical of Legionella species and were gram-negative motile rods which grew on buffered charcoal-yeast extract agar but not on blood agar, required cysteine, and were catalase positive, urease negative, nitrate negative, hippurate negative, and nonfermentative . All strains were positive for oxidase and beta-lactamase and produced a brown, diffusible pigment . Of the five strains, four exhibited blue-white autofluorescence under long-wavelength UV light . The fatty-acid composition and ubiquinone content of these strains were consistent with those of other Legionella species . Direct fluorescent-antibody examination of the five strains with conjugates to previously described Legionella species demonstrated no cross-reactions except with the conjugates to L . longbeachae serogroup 2 and L . bozemanii serogroup 2 . Four strains gave a 4+ reaction to the L . longbeachae serogroup 2 conjugate and the fifth strain gave a 1+ reaction . Each of the five strains gave a 4+ reaction with the conjugate to L . bozemanii serogroup 2 . DNAs from the five strains were highly related (84 to 99%) and showed 5 to 57% relatedness to other Legionella species . These strains constitute a new species in the genus Legionella, and the name Legionella anisa sp . nov . is proposed . The type strain of L . anisa is WA-316-C3 (ATCC 35292). Am Rev Respir Dis, 1985 Feb, 131(2), 209 - 13 Endotoxin in cotton dust and respiratory function decrement among cotton workers in an experimental cardroom; Rylander R et al.; To study the various reactions of gram-negative bacteria and their endotoxins observed in workers exposed to cotton dust, experiments were undertaken where cotton mill workers carded cottons from different geographic locations, each containing different amounts of bacterial endotoxins . Exposure was determined as the vertical elutriator dust and endotoxin levels . Measurements were made of the forced expiratory volume in one second (FEV1) and the number of blood neutrophils before and after work, and the prevalence of symptoms of byssinosis was recorded . There was a significant correlation between the vertical elutriator endotoxin levels and the group mean changes in FEV1 (p less than 0.01) but no correlation between vertical elutriator dust levels and changes in FEV1 . There was also a dose-response relationship between the endotoxin levels and the presence of symptoms of byssinosis in the exposed workers as well as between endotoxin levels and an increase in blood neutrophils . This observation supports findings from several previous studies and suggests that endotoxin triggers the mechanisms responsible for the decrease in respiratory function in the byssinosis syndrome . Other constituents of cotton dust could also be of importance for this reaction. Mol Gen Mikrobiol Virusol, 1985 Feb, (2), 3 - 14 {Development of a system vector-host in methylotrophic bacteria}; Tsygankov IuD et al.; Cloning of methylotropic and other Gram negative bacteria's genes was performed using vectors derived from IncP4 plasmids . Plasmids, such s RSF1010 are 8.8 kb in length, have a high copy number and broad host range and can be mobilized efficiently by a number of conjugative plasmids . IncP4 plasmids have relatively few restriction enzyme's targets suitable for cloning . In this paper the construction of versatile and special purpose IncP4 vectors available for cloning DNA into broad range of bacterial species are described . The seria of versatile vectors involves the transposon containing plasmid and two-replicon vectors.In genetic construction of special vector for direct cloning of restriction fragments the genetic regulation elements of Tn 1 were used . On the base of IncP4 replicon special vectors for construction of bank genes (cosmids) and the vectors for cloning of regulation sequence were also constructed. Immunobiology, 1985 Feb, 169(1), 1 - 10 Serum anti-lipid A antibodies in multiple myeloma and Waldenström's macroglobulinaemia; Fink PC et al.; Anti-lipid A antibodies were determined in sera from 38 patients with IgG multiple myeloma, 33 patients with IgA multiple myeloma and 38 patients with Waldenstrom's macroglobulinaemia using an enzyme-linked immunosorbent assay (ELISA) . Compared to 34 healthy adults, significantly (p less than 0.025, p less than 0.005, p less than 0.0025) lower serum anti-lipid A antibody levels were measured for the respective patient groups . Low anti-lipid A antibody levels correlated with a higher infection rate with gram-negative bacteria in patients with monoclonal B-cell malignancies . The highest infection rate was seen in patients with simultaneous low anti-lipid A levels and secondary antibody deficiency. Immunopharmacology, 1985 Feb, 9(1), 45 - 52 Synthesis of PAF-acether and blood volume changes in gram-negative sepsis; Inarrea P et al.; Gram-negative sepsis was induced in rats by intraperitoneal injection of Escherichia coli . The development of bacterial peritonitis and septicemia was monitored by counting the number of peritoneal cells and by performing cultures of blood samples . Mortality reached a 50% rate when rats were injected with 2 X 10(8) colony-forming units . Rats injected with the doses of bacteria which induced mortality showed a time- and dose-dependent increase of vascular permeability as judged by the presence of abundant peritoneal exudate and by the depletion of the circulating volume . In order to know whether the generation of PAF-acether could be involved in the development of the permeability changes, the formation of this mediator was measured in the peritoneal cells and spleen of animals at different times and in response to different doses of E . coli . Significant amounts of PAF-acether could be obtained preceding the development of blood volume depletion in response to the injection of doses of E . coli which induced both mortality and the development of permeability . These data suggest that PAF-acether might be one of the inflammatory mediators involved in the pathogenesis of the hemodynamic changes observed in endotoxemia. Antimicrob Agents Chemother, 1985 Feb, 27(2), 217 - 9 Lack of evidence for interaction between tobramycin and shock in their effect on renal function; Ambinder RF et al.; We sought to determine whether there was an interaction between aminoglycoside use and shock in their effect on renal function among seriously ill patients suspected of having gram-negative sepsis . Serial serum creatinine determinations were used to estimate changes in creatinine clearance rates in 179 patients entered onto a prospective randomized trial of tobramycin-nafcillin versus cefotaxime . A 25% decline in estimated creatinine clearance was considered to be clinically important . Univariate chi-square analysis showed that both shock (P less than 0.01) and tobramycin use (P less than 0.001) were independently associated with decline in estimated creatinine clearance . A two-way analysis of variance showed that both shock (F = 10.44, P less than 0.01) and tobramycin use (F = 42.6, P less than 0.001) continued to be significantly associated with renal dysfunction in the presence of each other, but there was no significant interaction between shock and tobramycin in their effect (F = 0.62, P less than 0.43) . A multiple logistic regression with an interaction term representing the occurrence of shock and tobramycin use simultaneously yielded similar results . Our study provided no analytic evidence supporting the existence of an interaction between shock and aminoglycoside use in their effect on renal function. Schweiz Med Wochenschr, 1985 Jan 19, 115(3), 93 - 6 {Aminoglycoside levels in bronchial secretions}; Mombelli G; Aminoglycosides are of limited clinical efficacy in gram-negative bacillary pneumonia, although they are commonly employed to treat this infection . This poor efficacy has been related in part to host factors (abnormalities in the lung, immunocompromise) and in part to pharmacologic factors . In particular, aminoglycoside levels in bronchial secretions are often borderline or inadequate in relation to the minimal inhibitory concentrations for most gram-negative strains . The low aminoglycoside concentrations result from poor penetrance into the respiratory tract or from local inactivation of these drugs, but basically reflect their low therapeutic-to-toxic ratio . The endotracheal injection of aminoglycosides resulted in high bactericidal activity within the bronchial lumen and in increased clinical efficacy, without increasing systemic toxicity . In view of the potential dangers of topical antibiotics, however, endotracheal treatment should be confined to selected patients. Circ Shock, 1985, 17(4), 301 - 11 Effects of toxic and nontoxic endotoxin derivatives on glucose kinetics; Lang CH et al.; Although the polysaccharide portion of bacterial endotoxins (ET) and other components of the bacterial cell wall are known to possess biological activity, the toxic effects produced by ET have been attributed mostly to the lipid-A component . The present study examined the influence of selected gram-negative cell wall components on in vivo carbohydrate homeostasis . Chronically catheterized conscious rats were injected with either ET, lipid A, the White polysaccharide supernatant (WPS-S; polysaccharide-rich and lipid-A-free) or the WPS-precipitate (WPS-P; rich in cell wall components and lipid-A-free) at sublethal doses of 100, 10, and 1 microgram/100 g . The acute hypotensive response to ET and lipid A were similar, while the WPS-P induced a smaller reduction in pressure . Endotoxin, lipid A, or the WPS-P (100 and 10 micrograms) all produced hyperglycemia . Hyperlactacidemia was evident in rats receiving ET, lipid A, and WPS-P; ET-treated animals exhibited the highest lactate concentrations . At the highest doses used, these three fractions increased the rate of glucose appearance . The polysaccharide-rich WPS-supernatant elicited no significant alterations in any of the variables studied . These results indicate that cell wall components of gram-negative bacteria, other than the lipid A of endotoxin, induce changes in carbohydrate metabolism that are similar to those produced by the toxic, lipid-A component of endotoxin. Circ Shock, 1985, 16(2), 195 - 203 Effect of methylprednisolone and of ibuprofen, a nonsteroidal antiinflammatory agent, on bronchoalveolar inflammation following endotoxemia; Rinaldo JE et al.; Septicemia by gram-negative organisms is a common cause of the adult respiratory distress syndrome (ARDS) . The role of neutrophils in causing parenchymal lung damage in ARDS has recently been emphasized . A single intraperitoneal injection of Escherichia coli endotoxin in rats causes acute neutrophil alveolitis similar to that of ARDS . We studied the ability of pretreatment with either ibuprofen (IBU) or methylprednisolone (MP) to ablate directly the alveolar inflammatory response to endotoxin in the rat model . To compare the severity of inflammation, we quantified inflammatory cell recovery by whole lung lavage 24 hours after injection of endotoxin, the time point at which neutrophil alveolitis due to endotoxin is most intense . Pretreatment with a single dose of IBU 3.75 mg/kg prior to endotoxin injections was associated with a significant increase in the total number of inflammatory cells, and in both the percentage and the absolute number of neutrophils recovered from the lung, despite significantly decreasing the plasma level of thromboxane B2, which increased 10-fold after endotoxin . Paradoxically, IBU 30 mg/kg significantly decreased the intensity of neutrophil alveolitis . MP 30 mg/kg had no effect on recovery of inflammatory cells from the lung by bronchoalveolar lavage following endotoxin . Cyclooxygenase inhibitors such as ibuprofen may cause a dose-dependent biphasic effect on lung inflammation following endotoxin: enhancement of inflammation at a low dose and suppression of inflammation at a high dose. Prog Clin Biol Res, 1985, 189, 347 - 67 The importance of intestinal endotoxins in liver disease; Nolan JP et al.; The development and wider use of the Limulus amoebocyte lysate assay (LAL) for the detection of endotoxin, has led to renewed interest in the link between gut-derived endotoxin, liver injury and the extra-hepatic manifestations of clinical liver disease . The concept that endotoxemia may occur and be harmful in clinical states without the concomitant presence of Gram-negative bacteria is a relatively recent one and has been most intensively studied in the context of liver injury . Since the liver stands between the gut and the systemic circulation, it has been postulated that failure to detoxify endotoxins absorbed into the portal circulation after hepatic injury might lead to further liver damage and escape of this toxic material into the general circulation . The present review will update the status of this hypothesis, discuss mechanisms proposed for the damage and present evidence for the association in animal models . Finally, studies both positive and negative, will be cited that have used the LAL to detect endotoxemia and its consequences in human liver disease. Prog Clin Biol Res, 1985, 189, 329 - 45 Plasma Limulus gelation assay in infants and children: correlation with gram negative bacterial infection and evidence for "intestinal endotoxemia"; Cooperstock M et al.; Plasma limulus gelation assays for gram negative bacterial endotoxemia were performed in 103 infants and children with evaluable clinical findings . A strong association between gram negative infection and positive assays was found, provided patients with gastrointestinal disorders were considered separately . Ten of 11 patients (91%) with gram negative bacteremia (p less than .001 compared with controls) and five of 10 (50%) with focal gram negative bacterial infections (p = .002) had a positive assay . Only 1/22 (5%) of those classified as having other forms of infection-like illness with negative cultures, and none of 20 considered to have neither infection nor gastrointestinal disturbances had a positive assay . However, 8/24 (33%) of those with major gastrointestinal disturbances had a positive test (p = .003) . This association supports the possibility that endotoxins produced by indigenous gram negative bacteria in the gut may reach the circulation during states of intestinal disturbance (intestinal endotoxemia) . Individual cases suggest several different possible mechanisms which could account for such an occurrence . Rigorous proof of this concept must await the development of confirmatory methodology. Prog Clin Biol Res, 1985, 189, 169 - 80 Parallel line assays of endotoxins with the LAL chromogenic substrate method; van Noordwijk J; All endotoxins from the gram negative microorganisms studied sofar contain lipid A, which is considered to be responsible for the biological activity . Endotoxins may therefore react in a similar way in quantitative assays . The varying non-lipid A part of different endotoxins may potentiate or reduce the activity of the identical lipid A part without changing the slope of the log-dose vs . response curve of these endotoxins . To test whether 13 endotoxins from different microorganisms react similarly with amoebocyte lysate (LAL) log-dose response curves were made using a chromogenic substrate method . A balanced incomplete block design with 13 blocks and four replications of each endotoxin was applied . A group of eight endotoxins with a common slope was defined with the Student-Newman-Keuls procedure . Two independent potency estimates of these endotoxins were in good agreement. Prog Clin Biol Res, 1985, 189, 117 - 37 Optimalization of a chromogenic assay for endotoxin in blood; Sturk A et al.; Early detection of Gram-negative septicemia or endotoxemia may become feasible with sensitive and reliable endotoxin (LPS) measurements . We recently published an assay for LPS in blood, based upon the LPS dependent activation of Limulus amebocyte lysate (LAL) and the subsequent chromogenic measurement of the activated enzyme(s) . Inhibitors and activated clotting factors potentially interfering in the assay were removed by dilution and heating . In the present study we describe the further improvement of the assay . Optimal conditions include: blood anticoagulated with 30 I.U./ml heparin; dilution of the platelet-rich plasma (PRP) in water; 5 min . heating at 75 degrees C; 15 mM Mg2+, 1.5 mM Ca2+, 125 mM Na+, 50 mM TRIS, pH 8.5 in the LAL activation step; substrate step without extra addition of Ca2+, Mg2+, or Na+, but in the presence of 50 mM TRIS at pH = 9.5 . Under those optimal conditions less than 10 pg LPS per ml blood (PRP) can easily be detected . Prospective clinical trials are presently envisaged to investigate the clinical usefulness of this extremely sensitive LPS assay. Drugs, 1985, 29 Suppl 5, 140 - 5 Biliary concentrations of temocillin; Poston GJ et al.; Temocillin is a new semisynthetic beta-lactam antibiotic with a spectrum of activity against most aerobic Gram-negative bacteria . We investigated the biliary excretion of temocillin after administration of 1g either intravenously or intramuscularly to 15 patients with normal liver and renal function who were undergoing elective cholecystectomy for gallstones . Very high concentrations of temocillin (up to 8 times the corresponding serum concentrations) were found in common bile duct bile and gallbladder bile of functioning gallbladders 1 to 2 hours after administration . However, no temocillin was detected in the bile of non-functioning gallbladders . Concentrations of temocillin were significantly higher in common bile duct bile (p less than 0.01) and gallbladder bile (p less than 0.05) following intravenous administration, and there was also a significant correlation (p less than 0.05) between common bile duct bile and corresponding serum concentrations for both routes of administration . Temocillin 1g readily achieved therapeutic concentrations in bile, and may prove a useful agent in the prophylaxis and management of Gram-negative biliary infections. Drugs, 1985, 29 Suppl 5, 118 - 21 Clinical efficacy, tolerance and pharmacokinetics of temocillin in patients with respiratory tract infections; Legge JS et al.; In this study 13 patients with a history of chronic respiratory disease were treated with temocillin for severe infection of the lower respiratory tract . Eleven patients were clinically improved or cured at the end of treatment and 4 remained free of infection at follow up . However, the 2 remaining patients failed to respond clinically and bacteriologically to temocillin . Blood and sputum pharmacokinetics were studied in patients receiving temocillin at 12-hourly intervals in doses of either 1g by intravenous bolus or 2g by intravenous infusion . On the first day of treatment the mean peak serum concentration was 102 mg/L for the 1g dose and 220 mg/L for the 2g dose, falling to 11 mg/L (1g) and 18.8 mg/L (2g) at 12 hours . Similar results were recorded on the last day of treatment . Temocillin concentrations in the sputum ranged from 1.5 to 2.8 mg/L, with no difference being found in the sputum concentrations of the 2 doses . Temocillin was well tolerated and was found to be an effective treatment for Gram-negative bacterial infections of the lower respiratory tract. Drugs, 1985, 29 Suppl 5, 103 - 5 Temocillin . Summary of safety studies; Cockburn A et al.; Temocillin is a novel injectable beta-lactam antibiotic designed for parenteral use . It is active against the majority of Gram-negative bacteria and is stable to a wide range of beta-lactamases . Disposition and metabolic studies on temocillin in animals and man demonstrate that the drug is well distributed throughout the body tissues and will cross the placenta . The major route of elimination is via the kidney (89%) where the drug is excreted unchanged as parent compound, mainly by the glomerular filtration of unbound temocillin . A full toxicological safety evaluation programme has been completed and includes acute, subacute and chronic toxicology in rat and dog, and reproductive and mutagenicity studies . Temocillin was well tolerated in animals at dosages of up to 1000 mg/kg and appears to be without any potential hazard for man in dosages which are well in excess of the proposed therapeutic dose. Res Exp Med (Berl), 1985, 185(3), 181 - 93 Efficacy of immunoglobulins in gram-negative infections in experimentally induced peritonitis in the rat; Frick S et al.; The effect of adjuvantly administered, newly developed immunoglobulin preparations in combination with an antibiotic is investigated by means of an animal experimental model . The animal model was peritonitis which was induced by a left-open colotomy in the rat . Administration of a combination therapy of immunoglobulins and an antibiotic succeeded in reducing lethality and shock index (according to Staub {15}) significantly by up to 50% as compared to the untreated control group . Using sub-therapeutic dosage of the antibiotic (50% of the human equivalent dose) the synergistic effect of the immunoglobulins could be confirmed clearly . A single summation of the offered immunoglobulin preparations cannot achieve an improvement in the results . In the present examinations additional IgM-enrichment does not result in a further improvement over the usually normal immunoglobulin levels in the preparations. Antibiot Chemother, 1985, 36, 103 - 10 Antibiotic uptake and the cytoplasmic membrane; Bryan LE; Aminoglycoside antibiotics are accumulated through a unique bacterial transport process . Knowledge of the process and how it can alter susceptibility to aminoglycoside antibiotics may be used to investigate mechanisms that might increase the activity of these compounds . It is possible that aminoglycoside activity could be increased by presenting more drug to the cytoplasmic membrane through alteration of the outer membrane of gram-negative bacteria by increasing transporter concentration or driving force in the form of the electrical potential, by decreasing the rate of enzymatic modification so that active drug can be transported, or by changing aminoglycosides to utilize alternative forms of transport and finally to increase ribosomal affinity for these drugs. Circ Shock, 1985, 15(4), 247 - 59 The effect of hyperdynamic sepsis on myocardial performance; McDonough KH et al.; The reviewed studies support the contention that during the high flow or hyperdynamic phase of gram-negative septicemia, cardiac reserve is compromised because of intrinsic myocardial dysfunction . The latter is not referable to coronary hypoperfusion or peripheral pooling or decreased venous return . Although, under resting, nonstressed conditions, indices of myocardial function may appear normal or even elevated, a decreased reserve is evident when additional stress is imposed on the myocardium . Hearts removed from septic rats during the hyperdynamic stage and perfused in vitro (using the isolated perfused working heart preparation) showed a rightward and downward shift in work function curves, indicating a severe depression in cardiac function . Possible mechanisms for the observed dysfunction are discussed . No significant alterations in high energy phosphate production or substrate utilization were observed, indicating that altered myocardial metabolism is not likely to be a significant contributor to the dysfunction . Our results suggest that cardiac dysfunction is partially due to an elevation in the cytosolic calcium concentration which may slow the rate of ventricular relaxation . These studies emphasize that intrinsic cardiac function is depressed early during the course of the septic episode at a time that precedes the onset of circulatory shock. Circ Shock, 1985, 15(4), 227 - 45 Isolated cardiac preparations: models of intrinsic myocardial dysfunction in circulatory shock; Parker JL et al.; Isolated cardiac preparations have been adapted for modeling intrinsic myocardial responses to circulatory shock syndromes independently of immediate influence from depressive or supportive constraints operative in the intact host . Left atrial and left ventricular (LV) papillary muscles and coronary-perfused hearts were removed from guinea pigs during development of Escherichia coli endotoxin shock . Preparations were then subjected to a battery of functional analyses under conditions of constant perfusate pH, pO2, pCO2, electrolyte and substrate concentrations, osmolality, and temperature . Evidence for contractile depression intrinsic to the myocardium itself was a consistent and reproducible finding in all three tissue models . The LV mechanical disadvantage of shock hearts was not correlated with changes in cardiac cycle length (beating frequency), active state duration (contraction-relaxation intervals), or tissue water content; neither was it surmounted by maximally effective increments in coronary flow, {Ca2+}o, or diastolic fiber length . Taken in concert, studies to date suggest that gram-negative endotoxin leads in some way to a reduction of intrinsic contractile reserves of the myocardium, and we have postulated that this change underlies the circulatory shock phase of endotoxicosis . The experimental approach embodied in these models may yield unique cardiodynamic interpretations that will allow the formulation of testable hypotheses about the pathogenesis and prevention of intrinsic cardiac complications of endotoxin and related shock forms. Vet Med Nauki, 1985, 22(1), 36 - 9 {Rapid method for determining the drug resistance of gram-negative bacteria}; Pavlov A et al.; Comparative studies led to the working out of a new diffusion indicative method for the rapid determination of drug sensitivity in Gram-negative bacteria . It is a modification of the diffusion method, consisting in the use of an indicator medium, bromothymol blue in glucose agar, instead of the meat peptone agar or other routinely employed nutritive media . The new method makes it possible to record rapidly the drug sensitivity of bacteria--only for 4-6 hours (compared with 24 hours with the conventional method) . Besides, the new method is readily applicable, precise, distinctive and rapid. Acta Neuropathol (Berl), 1985, 65(3-4), 344 - 6 "Pink spots" in formalin-fixed brains--poor fixation or bacterial byproduct? Hedley-Whyte ET. Circumscribed pink areas 0.3-1.0 cm in diameter seen in deeper parts of otherwise well-fixed brains are usually ascribed to inadequate fixation . Twenty-three patients with pink areas in their fixed brains had evidence of inflammation in at least one organ . Blood vessels in the pink areas contained bacteria . Postmortem cultures identified the organisms in 16 cases . Gram-negative bacteria were the most common . Sharply delineated pink areas in well-fixed brains correlate with postmortem intravascular growth of bacteria. J Reprod Med, 1985 Jan, 30(1), 67 - 8 Capnocytophaga isolated from the endometrium as a cause of neonatal sepsis . A case report; Mercer LJ; Capnocytophaga, a genus of gram-negative, anaerobic organisms, was isolated from the endometrium of a postpartum woman and the blood of the neonate . This unusual organism, usually isolated from the oral cavity, is sensitive to most antibiotics except the aminoglycosides. Arch Surg, 1985 Jan, 120(1), 99 - 103 Serum level monitoring of aminoglycoside antibiotics . Limitations in intensive care unit-related bacterial pneumonia; Flint LM et al.; Serum aminoglycoside assays have been accepted as useful methods of enhancing therapeutic efficacy in the treatment of intensive care unit-acquired pneumonia and in avoiding aminoglycoside nephrotoxicity . We prospectively studied 68 surgical patients with normal renal function and gram-negative bacterial pneumonia who were treated with aminoglycosides . Serum levels indicated subtherapeutic levels in 47 patients and verified optimum levels in 13 patients . Toxic trough levels developed in six patients and, despite immediate dosage adjustment, five patients suffered nephrotoxicity . Six additional patients also had nephrotoxicity . Five of these patients never had toxic peak or trough levels and rising trough levels developed in one patient after serum creatinine levels began to rise . We conclude that routine monitoring of serum levels effectively detects subtherapeutic antibiotic levels . This modality is useful for optimizing dosage schedules, but does not serve to predict or avoid nephrotoxicity in critically ill surgical patients. Drugs Exp Clin Res, 1985, 11(6), 373 - 8 Behaviour of cefmenoxime towards beta-lactamases; Labia R et al.; Using several well-characterized beta-lactamases isolated from Gram-negative bacteria, the interactions of cefmenoxime, a new methoxy-imino-amino-2-thiazol cephalosporin were compared with those of cefotaxime, lamoxactam, cefoperazone and ceftazidime . On-line computerized microacidimetry allowed determination of the affinity of these compounds for the enzymes, which was characterized by Ki values . Microacidimetry showed poor interactions of cefmenoxime with penicillinase TEM-1 (low Vm, poor affinity) whereas it showed a high affinity for the cephalosporinases, as is also the case for cefotaxime or lamoxactam . Both cefmenoxime and cefotaxime showed relative susceptibility in Masuda's double disc technique. Antibiot Med Biotekhnol, 1985 Jan, 30(1), 55 - 61 {Present-day aminoglycosides in the treatment of suppurative-septic diseases}; Lobuseva AN et al.; The therapeutic efficacy, tolerance and pharmacokinetics of sisomicin, gentamicin and a new dosage form of kanamycin sulfate as an ampoule solution for intravenous injection were studied clinically . High therapeutic efficacy of the above three aminoglycosides in the treatment of severe inflammatory infections caused by gram-negative bacteria was shown with the use of the adequate doses . Favourable results of the therapy estimated by the laboratory and clinical data were observed in 81-90 per cent of the patients. Prog Biochem Pharmacol, 1985, 20, 26 - 37 Pulmonary dysfunction caused by diffuse lung inflammation . Roles of metabolites of arachidonic acid; Brigham KL; Gram-negative endotoxemia in chronically instrumented sheep causes diffuse lung inflammation . Pathophysiologic responses of the lung include marked changes in lung mechanics, pulmonary vasoconstriction, increased lung vascular permeability, and capillary endothelial injury . Over the course of the response to endotoxemia, cyclooxygenase and lipoxygenase products of arachidonic acid are released into lung lymph and the time course of the two classes of compounds is different . Thromboxane concentrations in lung lymph increase early,