Acta Paediatr Scand, 1983 Jul, 72(4), 521 - 4 Deficiency of neutrophil phagocytosis in premature infants: effect of vitamin E supplementation; Chirico G et al.; In 20 healthy premature infants, 10 of whom were administered a total dose of 120 mg/kg vitamin E intramuscularly during the first 13 days after birth, polymorphonuclear leukocyte (PMN) bactericidal activity, frequency and index of phagocytosis, NBT reduction, random movement, chemotaxis and metabolic activity were evaluated within the first 48 hours and again at 5, 14 and 30 days of age . PMN function was also assessed in 30 adult controls . In the treated and untreated infants no differences were found in PMN function before treatment with vitamin E; however phagocytosis, bactericidal activity and chemotaxis were significantly lower than in the adult controls . At 5 days of age, in the untreated infants both index and frequency of phagocytosis remained low but in the treated groups increased significantly . At 14 and 30 days phagocytosis was normal in both treated and untreated infants . No differences were found in the bactericidal activity, NBT reduction, random movement, chemotaxis or metabolic activity of the treated and untreated infants at the ages studied . This preliminary report suggests that vitamin E may be used in premature newborns for accelerating normalization of phagocytic function in the neonatal period. Lepr India, 1983 Jul, 55(3), 576 - 83 How much non-infectious are the "non-infectious" lepromatous leprosy patients? Prabhakar MC, Appa Rao AV, Krishna DR, Ramanakar TV. Nose forms an important site at which the M . leprae in lepromatous leprosy (LL) patients lodge and multiply . Nose forms an important reservoir for M . leprae, from where they may be transmitted to healthy contacts . Inspite of realizing the above fact, nose does not normally receive due importance during the chemotherapy of leprosy . LL patients, after regular treatment with dapsone or rifampin for about 20 wks and 3 wks respectively are normally considered non-infectious . From the present investigation it is clear that local treatment of the ones with a bactericidal agent should perhaps be necessary during chemotherapy of LL patients to make them non-infectious and to control the transmission of the disease. Lepr India, 1983 Jul, 55(3), 455 - 64 Effect of lysozyme on Mycobacterium leprae; Dhople AM; Because large amounts of lysozyme are present in phagocytes, it was selected, as one of the bactericidal substances, to study the in vitro effects on M . leprae . The results obtained led the author to conclude that M . leprae is not susceptible to lysozyme as many other atypical as well as attenuated pathogenic mycobacteria . This resistance of M . leprae to lysozyme was seen up to a level of 100-500 micrograms per ml, while levels of 1000 micrograms and more had very significant effect; the ATP content of such treated M . leprae declined to 30% of the original levels in 5 days of incubation at 37 degrees C, with optimum pH of 6.0, and these M . leprae after such exposure to lysozyme failed to multiply in the foot pads of mice . The interpretation of these results, though not definitive, have been discussed. Infection, 1983 Jul-Aug, 11(4), 235 - 8 Interaction of bacterial pili and leukocytes; Silverblatt FJ et al.; Since Duguid and Guilles first described the ability of piliated bacteria to bind to leukocytes, much has been learned about the nature of this interaction . Mannose-sensitive (MS) pili bind to specific mannose-containing receptors on the leukocyte surface . While MS pili are responsible for attachment, the relative hydrophobicity of the bacterial surface determines whether the organism is internalized . Both binding and ingestion trigger the leukocyte to respond with degranulation and enhanced oxidative activity . The response to piliated bacteria, however, is delayed as compared to bacteria opsonized with serum, which may account for the reduced bactericidal activity associated with pili-mediated phagocytosis . A number of factors appear to influence the significance of pili-mediated phagocytosis in vivo . These include natural selective pressures in the host tissue, the ability of the organism to undergo pili phase transition and the presence of serum or other host opsonic factors . Antipili antibody does not enhance leukocyte killing of MS + Escherichia coli, but does stimulate leukocyte metabolic activity . Antipili antibody may, therefore, have an adverse effect on the infectious process by promoting the extracellular release of inflammatory material from the granulocyte. J Bacteriol, 1983 Jul, 155(1), 15 - 21 Temperature-sensitive autolysis-defective mutants of Escherichia coli; Harkness RE et al.; Two independently isolated temperature-sensitive autolysis-defective mutants of Escherichia coli LD5 (thi lysA dapD) were characterized . The mutants were isolated by screening the survivors of a three-step enrichment process involving sequential treatments with bactericidal concentrations of D-cycloserine, benzyl-penicillin, and D-cycloserine at 42 degrees C . Cultures of the mutants underwent autolysis during beta-lactam treatment, D-cycloserine treatment, or diaminopimelic acid deprivation at 30 degrees C . The same treatments at 42 degrees C inhibited growth but did not induce lysis of the mutants . The minimum inhibitory concentrations of selected beta-lactam antibiotics and D-cycloserine were identical for the parent and mutant strains at both 30 and 42 degrees C . Both mutants failed to form colonies at 42 degrees C, and both gave rise to spontaneous temperature-resistant revertants . The revertants exhibited the normal lytic response when treated with D-cycloserine and beta-lactams or when deprived of diaminopimelic acid at 42 degrees C . The basis for the autolysis-defective phenotype of these mutants could not be determined . However, a nonspecific in vitro assay for peptidoglycan hydrolase activity in cell-free extracts indicated that both mutants were deficient in a peptidoglycan hydrolase . Both mutations were localized to the 56- to 61-min region of the E . coli chromosome by F' complementation. J Thorac Cardiovasc Surg, 1983 Jun, 85(6), 933 - 5 Vancomycin prophylaxis in cardiac operations: determination of an optimal dosage regimen; Farber BF et al.; Vancomycin is thought to be an acceptable alternative prophylactic antibiotic to the cephalosporins in penicillin allergic patients undergoing cardiopulmonary bypass . We studied the pharmacokinetics of vancomycin in 10 patients undergoing cardiopulmonary bypass . Our results suggest that the commonly used 500 mg dose (7 mg/kg) of vancomycin given preoperatively may provide serum concentrations during cardiopulmonary bypass which are not bactericidal for many S . epidermidis strains . Thus we believe that a higher initial dose, at least 15 mg/kg, should be given. Zentralbl Bakteriol Mikrobiol Hyg {B}, 1983 Jun, 177(5), 406 - 11 The bactericidal mats in the pediatric intensive care unit; Dragas AZ et al.; An evaluation of dry adhesive bactericidal mats S-Entry was conducted in pediatric intensive care unit (ICU) . From April to June 1981 192 floor and 48 shoe samples were taken in three parallels in the periods with the mats used and in the periods without the mats for bacteriological control . The statistical analysis of the number of CFU showed no significant difference between the two periods . Under the conditions of work in the ICU the bactericidal mats cannot play an expected role . The bacterial flora of the floor and shoe soles had no influence on the degree of hospital infections in the ICU. J Clin Lab Immunol, 1983 May, 11(1), 27 - 32 Blood groups and susceptibility to gonococcal infection . II . The relationship of lipopolysaccharide type to gonococcal sensitivity to the bactericidal activity of normal human serum; Winstanley FP et al.; This study examines the bactericidal activity of normal human sera from individuals of blood groups A and B for gonococcal strains with simple and complex lipopolysaccharides (defined by pyocin-sensitivity) isolated from localised and disseminated infection . The bactericidal activity did not depend on A or B isohaemagglutinins . Resistance to normal human serum exhibited by strains from localised infections appeared to be due to lack of part of the lipopolysaccharide antigen, whereas resistance of strains from disseminated infection appeared to depend on a separate mechanism yet to be defined. Am Rev Respir Dis, 1983 May, 127(5), 650 - 4 Successful treatment of melioidosis caused by a multiresistant strain in an immunocompromised host with third generation cephalosporins; So SY et al.; A 32-yr-old woman with active systemic lupus erythematosus receiving prednisone and azathioprine developed lung abscesses of the right lower lobe caused by Pseudomonas pseudomallei, which was resistant concomitantly to chloramphenicol, co-trimoxazole, and tetracycline, but highly sensitive to a new cephalosporin, ceftazidime . Melioidosis was treated successfully with lobectomy and parenteral ceftazidime, which was given for 2 months without major side effects . Ceftazidime, being bactericidal, may be more promising for the eradication of P . pseudomallei, especially in immunocompromised hosts . This was also the first reported case of melioidosis in Hong Kong, where the disease might be endemic, as 4 more cases were found later. J Immunol, 1983 May, 130(5), 2316 - 23 Exposure of human neutrophils to chemotactic factors potentiates activation of the respiratory burst enzyme; Bender JG et al.; NADPH oxidase activity in particulate fractions from human neutrophils stimulated with phorbol myristate acetate (PMA) or opsonized zymosan was enhanced by prior exposure of the neutrophils to chemotactic factors . Enhanced activity was seen measuring both NADPH-dependent chemiluminescence and superoxide anion production . Enhancement was observed to be both time and dose dependent with several chemotactic stimuli, including casein, N-formyl-methionyl-leucyl-phenylalanine (f-MLP), and C5a . F-MLP and C5a showed similar patterns, with peak enhancement occurring within 2 to 15 min of preincubation and lasting up to 1 hr . In contrast, enhancement of PMA-stimulated oxidase activity by casein was more gradual and sustained, lasting up to 2 hr . Fractions from cells treated only with chemotactic factors and not stimulated with PMA showed no oxidase activity . Kinetic studies of this enhanced activity show that chemotactic factors induce increases in Vmax values but do not significantly alter Km values for the oxidase . Further experiments using agents that modulate degranulation suggest that enzyme release is not involved in this enhancement . These data suggest that pretreatment with chemotactic factors results in an increase in the amount of activated oxidase in membrane fractions obtained from PMA-stimulated neutrophils . This alteration of NADPH oxidase activity provides a subcellular basis for the enhanced bactericidal activity and increased oxidative metabolism seen in neutrophils treated with chemotactic factors. Toxicol Lett, 1983 May, 16(3-4), 167 - 74 Studies on the possible mutagenicity of beta-adrenergic blocker drugs; Okine LK et al.; The mutagenic potential of nine beta-adrenergic blocking agents was investigated in the Ames and micronucleus tests . None of the drugs studied showed any mutagenic response in the Ames test, either in the presence or in the absence of an activation system . At the highest concentration oxprenolol and propranolol exhibited a bactericidal effect . In the micronucleus test the same drugs showed a weak, but statistically non-significant response, but only at the highest doses . It is concluded that there is no overt mutagenic or carcinogenic potential associated with beta-adrenergic blocking drug activity. Acta Pathol Microbiol Immunol Scand {C}, 1983 Apr, 91(2), 117 - 21 Chemotaxis of resident, elicited and immunologically activated murine peritoneal macrophages; Staer AF et al.; The in vitro chemotactic response of peritoneal macrophages fourteen days after immunization with BCG was greater than that of macrophages from control mice . Peritoneal macrophages from mice treated with other agents which enhance bactericidal activity, and macrophages induced with proteose-peptone were less responsive to chemotactic stimuli than resident macrophages . The addition of PPD or PHA lymphokines to the peritoneal cells from BCG injected mice depressed the chemotactic response, but increased unstimulated migration . PPD had no effect on the migration of resident macrophages, but PHA lymphokines depressed the chemotactic activity of these cells. Exp Mol Pathol, 1983 Apr, 38(2), 193 - 207 Lung macrophage defense responses during suramin-induced lysosomal dysfunction; Warr GA et al.; Lysosomes form an integral part of the degradative mechanisms of the phagocytic cells . Mice were injected with suramin, a lysosomotrophic drug, to investigate the effects of lysosomal pathology on the cell biology and in situ bactericidal activity of the pulmonary macrophage . Treatment with suramin resulted in marked alterations in the cell biology of the macrophage: (i) increased vacuolization and protein content, (ii) suppressed intracellular phagosome-lysosome fusion, (iii) decreased activity of the lysosomal enzymes beta-glucuronidase and N-acetyl-glucosaminidase, and (iv) enhanced exocytosis of acid phosphatase during phagocytosis . Addition of suramin, in vitro, to cell lysates resulted in a reduction in the catalytic activities of acid phosphatase, beta-glucuronidase, and N-acetyl-glucosaminidase; thereby suggesting that selective interaction, in vivo, between suramin and lysosomes containing beta-glucuronidase and N-acetyl-glucosaminidase may have occurred . Plasma membrane 5'-nucleotide phosphodiesterase activity was increased in macrophages recovered from suramin-treated animals . Although the "resting-state" reduction of nitroblue tetrazolium (NBT) was lower in these macrophages, cells stimulated by a phagocytic challenge demonstrated normal increases in NBT reduction . Phagocytosis, in vitro, and pulmonary bactericidal activity were not altered . These data demonstrate that suramin altered numerous aspects of the phagocyte's lysosomal system . Despite these changes in the cell biology of the pulmonary macrophage, the cell's defense functions were not reduced. Surg Gynecol Obstet, 1983 Apr, 156(4), 489 - 92 Impaired in vitro bactericidal power of polymorphonuclear leukocytes in patients with protein calorie malnutrition; Belghiti J et al.; Bactericidal power of polymorphonuclear leukocytes was determined in eight patients with protein calorie malnutrition before and after nutritional therapy . Oxygen consumption associated with the uptake of zymosan particle by polymorphonuclear leukocytes, which is an exact reflection of the bactericidal power of leukocytes, was significantly decreased in untreated patients in the presence of both autologous and AB serum when compared with two control groups of eight normal patients . After nutritional therapy, oxygen consumption was found to be in the normal range in the presence of both autologous and AB serum . It is concluded that, in patients with protein calorie malnutrition, polymorphonuclear leukocytes have an intrinsic dysfunction, and this dysfunction is corrected after nutritional repletion. Am Rev Respir Dis, 1983 Apr, 127(4), 460 - 4 Cell-mediated cytotoxic responses in lungs of cotton rats infected with respiratory syncytial virus; Sun CS et al.; Pneumonia induced in cotton rats (Sigmodon hispidus) after inoculation of respiratory syncytial virus (RSV) was accompanied by the appearance of leukocytes in infected lungs . The number of these leukocytes increased until Day 5 after inoculation when sixfold more leukocytes were recovered from infected lungs using transpleural lavage than were recovered from lungs of uninfected control animals . Although macrophages and lymphocytes constituted approximately 65 and 25%, respectively, of the cells observed in lavage suspensions from both infected and uninfected lungs, only leukocytes in suspensions from infected animals appeared to be activated, as judged by cellular morphologic examination, cytochemical staining, and bactericidal activity . Leukocytes from lungs and adjacent lymph nodes of infected cotton rats, but not similar cells from uninfected animals, caused significant chromium release when they were added to primary cotton rat embryo and Hep-2 tissue culture cells infected with RSV in cytotoxicity assays . Cytotoxic activity peaked 5 days after inoculation, was neither virus-specific nor H-2 restricted, and was associated with both adherent and nonadherent fractions of lung cells . There was a close temporal relationship between the appearance of cytotoxic activity in the lung and termination of virus replication in this organ, suggesting a role for cytotoxic effector cells in recovery from respiratory syncytial virus infection of cotton rats. Can J Microbiol, 1983 Mar, 29(3), 331 - 7 Natural immunity to murine gonococcal bacteremia: roles of complement, leucocytes, and sex; Streeter PR et al.; The roles of the serum bactericidal system, inflammatory cells, and sex in resisting gonococcal infection were studied in a murine model of gonococcal bacteremia . The role of serum killing in defense was investigated with complement component 5 deficient (C5-deficient) (B1O.D2/OSN) and normal (B1O.D2/NSN) mice . No significant differences were found between LD50's with either murine serum-sensitive or serum-resistant gonococci in those two mouse strains . However, in vitro experiments revealed a heat-stable factor in mouse serum which killed gonococci . Thus it appeared that the C5-deficient mouse is not a good model for the study of the role of C-mediated killing in resistance to gonococcal infection . Mice with Chediak-Higashi disease were used to study the role of phagocytes and natural killer cells . The difference in LD50's between affected mice (C57B1/6J beige J) and controls (C57B1/6J) was significant . The CBA/N mice, which have a B-cell maturation defect, were no more resistant to infection than control mice, which was taken as further evidence that B cells were less important than other leucocytes in innate immunity to gonococcal infection . Finally, male mice were significantly more resistant than female mice to gonococcal bacteremia . Thus, in this study the two most important determinants of resistance to gonococcal infection were inflammatory cells and sex. J Antibiot (Tokyo), 1983 Mar, 36(3), 289 - 95 Studies on a new antibiotic M-92 produced by Micromonospora . IV . Bactericidal action of the component VA-2; Tani K et al.; The action of VA-2, the most active component of antibiotic M-92, against S . aureus is bactericidal but not bacteriolytic . The bactericidal action is markedly affected by incubation temperature, whether bacterial cells are prolific or resting . The bactericidal kinetics of VA-2 is biphasic, since addition of VA-2 caused rapid and straight decrease in viability curve and reached a plateau after several minutes . The bactericidal activity of VA-2 is blocked by 2,4-dinitrophenol . Alike to many membrane-active bacteriocins, VA-2 seems to exert its action through two stages. Infect Immun, 1983 Mar, 39(3), 1136 - 41 Influence of growth temperature of Escherichia coli on K1 capsular antigen production and resistance to opsonization; Bortolussi R et al.; When Escherichia coli strains that produce K1 capsular polysaccharide antigen at 37 degrees C were grown at 22 degrees C, K1 antigen was not detected in the supernatant or washed-cell fraction of broth cultures . Significant amounts of K1 polysaccharide were detected only when the organism was grown at temperatures of 30 degrees C or higher . Rabbits immunized with an E . coli K1 strain (serotype O18ac:K1:H7) grown at 37 degrees C produced agglutinating antibody to somatic antigen and precipitating and agglutinating antibody to capsular K1 antigen; those immunized with this strain grown at 22 degrees C produced antibody to somatic antigen, but not to K1 antigen . Antibody to somatic antigen was markedly reduced by adsorption with the organism grown at 22 degrees C, while antibody to capsular antigen was not . E . coli K1 strains grown at 37 degrees C (K1 present) resisted phagocytosis and killing if they were opsonized solely by the alternative complement pathway (ACP) using magnesium ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid-chelated serum . When these strains were grown at 22 degrees C (K1 absent), they were opsonized efficiently by the ACP (28 versus 94% killing, respectively; P less than 0.001) . In addition, a non-K1 mutant of an E . coli K1 strain was opsonized efficiently by the ACP although its encapsulated K1 parent was not . Sensitivity of E . coli strains to the bactericidal activity of serum was observed in strains with and without K1 capsular antigen . These studies demonstrated that production of K1 polysaccharide antigen was regulated by environmental temperature and that K1 capsule plays an essential role in rendering the organism resistant to opsonization by the ACP. Acta Trop, 1983 Mar, 40(1), 29 - 38 The effect of parasitization by Leishmania mexicana mexicana on macrophage function in vitro; Bray RS et al.; Macrophages infected with amastigotes of Leishmania mexicana mexicana as compared to normal macrophages show decreased migration both randomly and through a 5 microns pore in response to a known chemotaxin, an increased ability to pinocytose and an increased bactericidal ability . Unless very heavily parasitized their ability to phagocytose is unaltered . Parasitized macrophages are unaltered in their ability to secrete extracellularly lysosomal enzymes, prostaglandins and lysozyme in response to known stimuli, or to kill target cells in an antibody dependent cell mediated cytotoxicity assay. Environ Res, 1983 Feb, 30(1), 129 - 41 Rabbit lung after inhalation of soluble nickel . I . Effects on alveolar macrophages; Wiernik A et al.; Alveolar macrophages from eight rabbits, exposed for about 1 month (5 days/week, 6 hr/day) to an aerosol of nickel chloride, 0.3 mg/m3 (as Ni), were studied . The number of macrophages in the lavage fluid and the variance of the cell diameter increased . The macrophages contained laminated structures and most cells had an active cell surface . A few macrophages had a large number of laminated structures and a smooth cell surface . The capacity of the macrophages to reduce nitroblue tetrazolium (NBT) tended to be increased at rest and was significantly increased after stimulation with Escherichia coli . The bactericidal capacity of the macrophages was decreased . The effects were similar to those earlier described after exposure of rabbits for 1 month to about 1 mg/m3 of metallic nickel dust . After exposure both to metallic and soluble nickel the effects are probably caused by an increased amount of surfactant produced by the type II cells in response to nickel ions. Cryobiology, 1983 Feb, 20(1), 7 - 16 Neutrophil migration in canines: in vivo comparison of granulocyte function following 24-hour storage at 6 or 20 degrees C of leukocyte concentrates or of granulocytes purified by counterflow centrifugation--elutriation; Jemionek JF et al.; The use of granulocyte-rich concentrates from leukaphresis purified by counterflow centrifugation--elutriation to obtain pure granulocytes for transfusion studies in cyclophosphamide-induced neutropenic animal models is reported . Our data for granulocyte-rich leukapheresis concentrates indicate that room temperature (20 degrees C) appears to be preferred to 6 degrees C for short-term granulocyte storage . The data also indicate that although the granulocytes isolated by counterflow centrifugation--elutration may retain in vitro functions of chemotaxis, phagocytosis, and bactericidal activity, the in vivo function of migration into skin chambers for isolated granulocytes is seriously impaired after storage for 18 to 24 hr at both 6 and 20 degrees C . This loss of in vivo function of stored granulocytes occurs in isolated granulocytes obtained by both counterflow centrifugation--elutriation and dextran sedimentation, and it is not observed in the leukocyte concentrates held at 20 degrees C . The results of these studies are four-fold . First, freshly isolated granulocytes display no apparent loss of either in vivo or in vitro function . Second, granulocytes isolated by counterflow centrifugation--elutriation or dextran sedimentation and stored at 6 or 20 degrees C are severely impaired in terms of their in vivo chemotactic function but display no loss of in vitro efficacy . Third, 20 degrees C storage of granulocyte-rich leukapheresis concentrates for 18 to 24 hr is superior to 6 degrees C storage . Fourth, in vitro analysis may be limited in its ability to indicate in vivo function as a measure of success in granulocyte preservation studies. Ann Rheum Dis, 1983 Feb, 42(1), 45 - 51 Neutrophil functions and clinical performance after total fasting in patients with rheumatoid arthritis; Uden AM et al.; The effects of fasting for 7 days were investigated in 13 patients with rheumatoid arthritis (RA) in comparison with a control regimen in a cross-over trial . The effects of fasting on clinical performance and blood neutrophil functions were studied . During fasting, with a mean weight loss of 5.1 kg, clinical inflammation in the joints and the erythrocyte sedimentation rate (ESR) decreased . During the control period the joints either remained unchanged or deteriorated, and no change was observed in the body weight or the ESR . The locomotion of neutrophils under agarose, induced by a reference serum, decreased during the fasting period (p less than 0.001), but no change in their locomotion was induced by an Escherichia coli bacterial factor . During the control period, however, the locomotion induced by either stimulant was significantly decreased . Generation of migration-stimulating factors from the patients' plasma declined 3 days after the end of fasting (p less than 0.001) . The adherence of the neutrophils to nylon fibres was unchanged during both periods . The bactericidal capacity improved during fasting, both in comparison with the initial value (p less than 0.005) and with the values from the control period (p less than 0.001) . An association was found between improvement in inflammatory activity of the joints and enhancement of neutrophil bactericidal capacity . Fasting appears to improve the clinical status of patients with RA . This could partly be due to the observed changes in the functions of the neutrophils, since the latter contribute to the inflammatory joint reactions. Agents Actions, 1983 Feb, 13(1), 59 - 62 Impairment of leukocyte myeloperoxidase bactericidal mechanisms with ketamine (Ketalar); Pekoe GM et al.; The ability of general anesthetics to depress immune function may lead to increased risk of infection in surgical patients . Recently, halothane, an inhalational anesthetic, was shown to inhibit neutrophil bactericidal mechanisms, the center of which is the reaction of myeloperoxidase with H2O2 and Cl . This study demonstrates the ability of ketamine, an injectable anesthetic, to interfere with the cytotoxic neutrophil myeloperoxidase-H2O2-Cl- reaction, as tested using a luminol-enhanced chemiluminescence assay . Ketamine, due to its phenolic structure, may scavenge the cytotoxic free radical intermediates of this reaction, as shown previously for non-steroidal anti-inflammatory drugs . This paper, then, identifies a potential mechanism whereby ketamine anesthesia could suppress neutrophil defense mechanisms, thus rendering the surgical patient more susceptible to infection. Zh Mikrobiol Epidemiol Immunobiol, 1983 Feb, (2), 62 - 6 {Structural and functional analysis of the effect of cationic surfactants on Escherichia cells and spheroplasts}; Cherniavskaia MA et al.; The character of the growth of Escherichia culture after treatment with alkyl dimethylbenzyl ammonium chloride (a cation surface-active substance) has been studied . The action of the preparation at bacteriostatic concentrations is reversible and manifested only by the increased duration of the lag phase . The complete restoration of the processes ensuring the growth and mitosis of the cells usually occurs . The preparation causes disturbances in the permeability barrier of the cell membranes, appearing immediately on contact with cation surface-active substances . This compound affects the cytoplasmic membranes of Escherichia cells at extremely low concentrations (0.0001-0.0002%); as a result, the leakage of low-molecular substances from the cells occurs . These disturbances in permeability are not accompanied by the disappearance of nucleic acids from the cells . The preparation used at bactericidal and subbactericidal concentrations denatures high-molecular cell components to a variable degree . The study of the ultrastructure of cells and spheroblasts shows that alkyl dimethyl-benzyl ammonium chloride destroys the structure of the outer and cytoplasmic membranes, as well as the ribosomal apparatus of Escherichia cells. Transfusion, 1983 Jan-Feb, 23(1), 25 - 9 Effect of microaggregate blood filtration on granulocyte concentrates in vitro; Snyder EL et al.; To determine the effect of transfusing granulocyte concentrates through microaggregate blood filters, granulocytes prepared with a cell processor were passed through screen and depth microaggregate filters . Pre- and postfiltration evaluations were made of total granulocyte count, levels of muramidase, granulocyte viability, motility, phagocytosis, bactericidal activity, and hydrogen peroxide-forming capacity . Compared to prefiltration levels, a significant (p less than 0.05) decrease in postfiltration granulocyte counts was seen for all the depth filters studied but not for the standard 170 microns (control) or the 40 microns screen filter . For the various tests of granulocyte function evaluated prefiltration, no significant postfiltration differences (p greater than 0.05) were seen for any of the filters studied . Screen microaggregate filters retained only 1 to 3 percent of granulocytes contained in the concentrates, and thus appear satisfactory for use in clinical transfusions . The large percentage of neutrophils retained by the depth filters (20-62%), however, precludes their use for transfusion of granulocyte concentrates. Antibiotiki, 1983 Jan, 28(1), 44 - 8 {Phagocyte functional activity and bactericidal systems after exposure to rifampicin, lincomycin and methicillin}; Ratnikov VI et al.; To show possible mechanisms of the inhibitory effect of rifampicin, lincomycin and methicillin on the functional activity of the phagocytes, their effect on the intracellular bactericidal systems and the state of the regulatory function of the macrophages in the immunogenesis were studied . Correlation between the decrease in the values of the phagocytosis completeness and the changes in the activity of the myeloperoxidase bactericidal system and the alkaline phosphatase in the neutrophilic granulocytes was shown . The decrease in the number of the antibody producers at the maximum level of the immune response to administration of sheep red cells as the test antigen due to rifampicin or lincomycin was not accompanied by impairment of the immune regulatory function of the macrophages. Ann Biol Clin (Paris), 1983, 41(6), 397 - 401 {Aspects of the interrelationship between the infected host and the pathogenic agent}; Clumeck N; The severity of an infection is related to the disequilibrium in the complex relationship between the infected host and the pathogenic agent . The bacterial factors include the size of the inoculum, the pathogenicity and particular virulence of certain strains which, because of their antigenic structures (capsular antigen, lipopolysaccharide, exotoxins), may escape the bactericidal defence mechanisms of the serum, phagocytosis and intracellular bacterial destruction . The principal host factor, which also determines the prognosis of the infection, is the subject's immune status which can be affected in its non-specific elements (complement system) and in its specific elements (humoral and cellular immunity) . Thus, in the normal host, only extremely virulent bacteria are capable of causing severe infections, while in the immunodepressed patient, even non-pathogenic organisms which are usually commensual are capable of being invasive. Digestion, 1983, 27(2), 93 - 9 Excretion of azlocillin and mezlocillin by the normal pancreas and in acute pancreatitis in dogs and rats; Demol P et al.; Dogs and rats were studied to evaluate the excretion of two new acyl-ureidopenicillins, azlocillin and mezlocillin, in the pancreatic fluid . After intravenous administration of 55 mg X kg-1 of either drug, an extremely low concentration (less than 3.0 micrograms X ml-1) of both antibiotics was measured in pancreatic juice of conscious dogs . In rats, both azlocillin and mezlocillin were excreted by the pancreas in bactericidal concentrations (greater than 10 micrograms X ml-1) during the first 15 min following their injection . In anesthetized dogs and rats in which acute pancreatitis was induced by injection of sodium taurocholate into the main pancreatic duct, the tissue concentration of mezlocillin (55 mg X kg-1 i.v.) was significantly higher than in the pancreatic tissue of control animals . In both instances, bactericidal concentrations of mezlocillin were measured in the pancreatic tissue . During the first 30 min following its injection, the concentration of mezlocillin was about five times higher in inflammed pancreatic tissue than in the normal pancreas (dogs: 44 +/- 14 vs . 5 +/- 3 micrograms X g-1 tissue; rats: 67 +/- 10 vs . 13 +/- 2 micrograms X g-1) . These data indicate that (1) azlocillin and mezlocillin are excreted in bactericidal concentrations by the normal pancreas only in rats but not in dogs, and (2) in both species, bactericidal concentrations of mezlocillin can be observed in the normal pancreatic tissue and in acute pancreatitis; its concentration being significantly higher in acute pancreatitis than in controls. Acta Obstet Gynecol Scand, 1983, 62(3), 275 - 7 Vaginal cleansing at vacuum aspiration abortion does not reduce the risk of postoperative infection; Lundh C et al.; Does a thorough vaginal cleansing with bactericidal solutions prior to induced first-trimester vacuum aspiration abortion reduce the frequency of postabortal pelvic inflammatory disease (PID)? To answer this question we compared the frequency of PID in 372 women where a thorough preoperative vaginal cleansing with a bactericidal solution was undertaken at abortion with that in 350 women where the upper part of the vagina was swabbed with a pad moistened with a 0.9% saline solution . A postoperative PID was recorded in 25 (6.7%) of the former women and in 23 (6.6%) of the latter women. Acta Chir Scand, 1983, 149(4), 437 - 9 Pyogenic liver abscess . A case report with a short review of current concepts of diagnosis and management; Sorensen MR et al.; A case of a large pyogenic liver abscess in a 16-year-old boy with appendicitis is presented . The clinical picture, bacteriology and treatment of the disease are discussed on the basis of 397 cases reported in the literature . It is concluded that ultrasound scanning of the liver is essential for early diagnosis and that the treatment of choice is percutaneous needle aspiration in combination with bactericidal antibiotics. Pharmacology, 1983, 27(1), 29 - 39 Effect of cancer chemotherapeutic agents on the chemiluminescence of human granulocytes; Matamoros MC et al.; 21 unilateral breast cancer patients taking different combinations of chemotherapeutic agents (cyclophosphamide, methotrexate, 6-fluorouracil, vincristine, and prednisone) were studied to determine how chemotherapy affected their granulocytes . It is widely believed that in cancer patients chemotherapeutic agents increase susceptibility to infection . Therefore, luminol-enhanced chemiluminescence was used to evaluate leukocyte function since the chemiluminescence response has been correlated to bacterial killing . the chemiluminescence response in cancer patients (6-week treatment) was significantly reduced (approximately 50%; p less than 0.01) compared to nontreated volunteers . Preliminary studies using 3H-formyl-methionyl-leucyl-phenyl alanine binding showed similar decreases . We postulate that chemotherapy for 6 weeks may affect granulocyte precursor cells in bone marrow, thereby weakening peripheral granulocytes and reducing both their bactericidal capacity and 3H-formyl-methionyl-leucyl-phenyl alanine receptors. Scand J Rheumatol Suppl, 1983, 51, 36 - 41 The effect of auranofin on polymorphonuclear granulocytes; Hafstrom I; The effects of auranofin on the function of neutrophil polymorphonuclear granulocytes (PMN) have been studied in vitro and in vivo . Preincubation of human PMN with auranofin (1-4 micrograms/ml) increased their adherence to nylon fibres and f-met-leu-phe-(fMLP) induced aggregation . PMN migration, phagocytosis, bactericidal capacity and phagocytosis-associated enzyme release were all significantly inhibited by auranofin in a dose-dependent way . Enzyme release stimulated by f-MLP, chemoluminescence and the release of superoxide anions all showed a biphasic response to preincubation with auranofin . They showed an increase at low concentrations and inhibition at high concentrations . In studies of 3H-fMLP binding auranofin did not affect receptor numbers but increased binding affinity . Auranofin at higher concentrations decreased phorbolmyristate acetate and fMLP induced changes in surface charge and membrane potential . In vivo, auranofin administered to rats, did not prevent either the neutropenia induced by zymosan-activated serum or the corresponding rise in plasma lactoferrin levels . PMNs from six rheumatoid arthritis patients treated with auranofin (6 mg/day) for 23 weeks showed changes in bactericidal activity, chemotaxis and chemiluminescence independent of the clinical response . Enzyme release, however, was reduced in PMNs from clinical responders and showed no change in non-responders. Ann N Y Acad Sci, 1983, 419, 1 - 11 Tuftsin, a natural activator of phagocyte cells: an overview; Najjar VA; The recognition that a small oligopeptide was responsible for the full stimulation effect of specific cytophilic gamma-globulin on blood neutrophils arose from a study of the kinetics of phagocytosis . These were unusual in that the stimulation was short lived and that preincubation of the phagocyte with the gamma-globulin rendered the latter inactive . The oligopeptide was isolated, its structure determined (Thr-Lys-Pro-Arg) and synthesized . The discovery of human mutants with tuftsin deficiency exhibiting signs and symptoms of frequent severe infection further emphasized the specific biological function of the tetrapeptide . The mutant peptide was isolated, sequenced (Thr-Glu-Pro-Arg), and synthesized . Further studies showed that tuftsin requires two enzymes for its liberation from the parent carrier gamma-globulin . One enzyme is in the spleen that cleaves distal to the arginine end, and the other, on the outer side of the plasma membrane, cleaves proximal to the threonine residue . The tetrapeptide tuftsin stimulates all functions of phagocytic cells: phagocytosis, pinocytosis, motility, immunogenic activity including processing of the antigen and augmentation of the number of antibody-forming cells, bactericidal activity, and, above all, tumoricidal activity . The latter has been shown by several laboratories. Infection, 1983, 11 Suppl 2, S93 - 6 The bactericidal activity in serum and its prognostic clinical value; Klastersky J; The determination of the bactericidal activity in serum also gives valuable information on the bacteria, the host and the antibiotics . Clinical studies have proven its value, especially in predicting the outcome of septicemia and other infections . Thus, the bactericidal activity in serum is a useful tool for monitoring therapy . It can also be used as an investigational means for comparing the respective efficacy of antibiotics administered alone or in combination. Ann Rech Vet, 1983, 14(3), 281 - 6 Experimental mastitis with Escherichia coli: sequential response of leukocytes and opsonic activity in milk of immunised and unimmunised cows; Rainard P; Two immunised and three unimmunised cows were challenged in a single mammary gland with 10(4) colony forming units of the vaccinal Escherichia coli strain . Immunisation comprised subcutaneous injection of killed bacteria with adjuvant at drying-off, and one intramammary infusion (without adjuvant) five weeks later . Somatic-cell counts and bacterial counts were monitored throughout the experiment . Bactericidal and opsonic properties of milk were assessed before inoculation and at 6, 12, and 24 h post-inoculation . Before challenge, cell-free milk of immunised cows enabled blood PMN leukocytes to kill the E . coli vaccine strain (B117) whereas in cell-free milk of unimmunised cows growth resulted . Nevertheless, in vivo E . coli B117 were able to grow in milk of all of the cows until they triggered an inflammatory reaction . Influx of cells started between 8 and 10 h post-inoculation in all of the cows but was more intense in immunised cows during the first six hours of inflammation . In vitro tests showed that whole mastitic milk acquired high bactericidal activity at the onset of inflammation . Although one immunised cow displayed clinical signs, milk yields of unimmunised animals were depressed to a higher extent . These results suggest that immunisation was able to enhance recruitment of phagocytic cells and to establish pre-inflammatory opsonic activity in milk. Ann Rech Vet, 1983, 14(3), 271 - 9 Sequential changes in serum albumin, immunoglobulin (IgG1, IgG2, IgM) and lactoferrin concentrations in milk following infusion of Escherichia coli into the udder of immunised and unimmunised cows; Rainard P et al.; Two immunised and three unimmunised cows were infected in a single mammary gland with 10(4) CFU of the vaccine Escherichia coli strain . Immunisation comprised systemic (subcutaneous) injection of killed bacteria at drying-off and one intramammary infusion five weeks later . Immunoglobulin (Ig) G1, IgG2, lgM, serum albumin (BSA) and lactoferrin concentrations were monitored by sampling the inoculated glands at 2 h-intervals during the first 16 h post-inoculation, then at each milking for four days . Whether immunised or not, mammary glands started to react at 10 h post-inoculation . During the early acute phase, IgG1 and IgG2 permeated from blood into milk at a rate similar to BSA . Later on, IgM (and at a lower degree IgG1) concentrations were higher than expected on the basis of passive transfer . Marked protein exudation was seen in all of the cows but one . Nevertheless, this cow (immunised) showed an intense cellular reaction like the other animals . Lactoferrin concentrations rose from 24-32 h post-inoculation and remained elevated to the end of the observed period in inoculated quarters in unimmunised cows . By contrast, in immunised cows lactoferrin concentrations remained low . Heat-labile bactericidal activity against a serum-sensitive E . coli strain appeared concomitantly with rise in BSA concentration . Heat-resistant bactericidal activity of cell-free milk was detected one or two days later in three of the cows . Bacteriological cure of quarters occurred without therapy in all cases. Schweiz Med Wochenschr Suppl, 1983, 14, 64 - 9 The role of the new penicillins and cephalosporins in the management of infection in granulocytopenic patients; Klastersky J; Overall, the use of the new cephalosporins has not so far been a major breakthrough in the empire therapy of febrile episodes and infections in granulocytopenic patients . In the only controlled large study available so far (EORTC), the cefotaxime-containing regimen was definitely not the best among the combinations tested . It remains to be seen whether other cephalosporins such as cefoperazone or ceftazidime would perform better in the future; especially with ceftazidime alone or in combination with aminoglycosides, the early results appear to be very promising . Whether single drug therapy with one of these new cephalosporins, which usually results in a high serum bactericidal activity, will eventually prove to be as good as combination therapy will await evaluation of more patients over extended periods of time, with a special attention to the possible emergence of resistant pathogens. Arzneimittelforschung, 1983, 33(9), 1232 - 5 {Comparison of the activity of cefaclor with amoxicillin, erythromycin and doxycycline in an in vitro model}; Wiedemann B; Bactericidal antibiotics like cefaclor and amoxicillin do have a better and prolonged effect on the reduction of the viable cellcount than bacteriostatic ones like erythromycin and doxycyclin, as has been demonstrated in the in vitro model . The influence of the production of beta-lactamases on the kill-kinetics could be studied in this model . While amoxillin became ineffective by the production of beta-lactamases of E . coli and S . aureus the activity of cefaclor was generally maintained . Only a marginal destruction of the drug by the enzymes was observed. Arkh Patol, 1983, 45(5), 3 - 13 {Structuro-functional characteristics of neutrophilic leukocytes and their role in the development of inflammatory and immune processes}; Paukov VS et al.; Neutrophilic polymorphonuclear leukocytes (NPNL) are an important part of the protection system of higher animals against infection and related with specific immune response taking part in immediate and delayed type hypersensitivity reactions and affecting some parameters of mononuclear phagocytes and lymphocytes . Among bactericidal mechanisms of NPNL, neutral proteases and nonenzymatic cation proteins are particularly important . NPNL have fine autoregulation mechanisms among which of special importance is the synthesis of biologically active substances: leukotrienes, including a slow acting anaphylaxis substance, prostaglandins, and prostacyclins . These metabolites of arachidonic acid affect chemotropism of NPNL, phagocytosis activity, and secretion processes . The real activity of NPNL bactericidal mechanisms is determined by the following factors: (1) the state of genetically programmed structural-functional parameters common to NPNL, (2) the state of autoregulation mechanisms of NPNL function, (3) the stage of the infectious process, (4) NPNL--macrophage-lymphocyte system interaction, (5) regulatory effect of the neurohumoral and endocrine systems, (6) serum factors of nonspecific resistance, (7) characteristics of the causative agent of infection. Chemotherapy, 1983, 29(1), 24 - 7 Oxolinic acid--trimethoprim combination: effects on DNA synthesis and on viability of Escherichia coli; Genedani S et al.; The synergistic bactericidal effect of the oxolinic acid-trimethoprim combination has been confirmed on an exponentially growing strain of Escherichia coli, and is paralleled by a synergistic inhibition of 14C-uracil incorporation into the bacterial DNA . These data provide experimental support for the postulate that the synergistic effect of quinolone-trimethoprim combinations, observed both in vitro and in vivo, is due to a complementary blockade of bacterial DNA synthesis. Antimicrob Agents Chemother, 1983 Jan, 23(1), 108 - 12 Effect of methylprednisolone on entry of ampicillin and gentamicin into cerebrospinal fluid in experimental pneumococcal and Escherichia coli meningitis; Scheld WM et al.; The influence of methylprednisolone on the passage of ampicillin and gentamicin into and activity within cerebrospinal fluid was examined in two models of experimental meningitis . Steroid pretreatment reduced the concentrations of these drugs in purulent cerebrospinal fluid of rabbits with experimental pneumococcal and Escherichia coli meningitis (P less than 0.05) . However, the resultant mean concentrations of these antibiotics in cerebrospinal fluid still exceeded the minimal bactericidal concentrations of the infecting organisms . The rate of bactericidal effect in vivo was unaffected by steroid therapy in each model . Methylprednisolone did not have deleterious effects on the course of treated experimental meningitis under these short-term (24-h) experiments. Zentralbl Mikrobiol, 1983, 138(8), 605 - 16 {Behavior of benzo(a)pyrene in the soil and passage from soil to crops}; Fritz W; The behaviour of Benzo{a}pyren (BaP) in the soil and its passage from the soil into the crops has been investigated by means of model tests . In situ fluorescence spectroscopy enables a detection of 0.01 micrograms/BaP/kg with recoveries ranged from 75 to 99.6% and an average variation coefficient of 15% . A decomposition of BaP in test soils within 18 months from 30 mg/kg to 1.5 mg/kg could be attributed to decomposition by soil bacteria . After addition of bactericidal substances to the soil there was no decomposition for several years . In soils with concentrations below 1000 micrograms BaP/kg no passage of BaP into the crops can be detected . Contrary to the opinion of several authors that BaP does not pass from the soil into the crops, model tests conducted for a few years show that a relevant passage into crops such as carrots and radish, as well as into lettuce, spinach and parsley, is possible . The passage into potatoes, tomatoes, peas, and beans is less significant . The degree of contamination of crops is in a certain relation to the degree of the contamination of the soils, but this has only been found with a BaP content of more than 1000 micrograms/kg . Sandy soils which significantly exceed the BaP content of about 1000 micrograms/kg, as they may occur in industrial areas, above all near emittents, are not suitable for the cultivation of some vegetables, such as lettuce and carrots, for human nutrition. Rev Fr Mal Respir, 1983, 11(4), 455 - 66 {Bronchoalveolar lavage in pneumoconiosis of coal miners . Cytologic aspects}; Voisin C et al.; The cytological characteristics of broncho-alveolar fluid were studied in 94 coal workers and six subjects exposed to varied risks of silicosis . In coal worker's pneumoconiosis with the usual micronodular or nodular type, there was a significant increase in the cellularity of the peripheral airways compared to non-exposed controls, making allowances for smoking habits . There were no striking changes in the white cell count nor any correlation with the possible elevation in the serum angiotensin I-enzyme conversion level . On the other hand a striking elevation of the alveolar lymphocyte count was noted in three cases with rapidly developing silicosis . Where there was the co-existence of another disorder (connective tissue disorders, sarcoid, extrinsic allergic alveolitis, radiation lung or diffuse interstitial fibrosis) the anomalies noted were those occurring during the progress of the associated disease . At the time of collection the alveolar macrophages in the dust exposed subjects showed a similar vitality to these observed in control subjects . After 24 hours of observation " in vitro ", the vitality of the cells and their phagocytic and bactericidal activity was markedly diminished. Am J Clin Pathol, 1983 Jan, 79(1), 45 - 51 Leukemic cells as probes for sequential functional differentiation of the human granulocyte; Glasser L; The purpose of this study was to sequence the functional properties of the neutrophil during maturation, using leukemic cells as experimental probes . Twenty-nine cases of acute leukemia, derived from granulocytic precursors, were studied . The functional tests that were evaluated included phagocytosis, bactericidal activity, random locomotion, and chemotaxis . These functional properties were correlated with Fc receptors and the stimulated nitroblue tetrazolium dye reduction test . The results indicated that the various functions of the neutrophil are acquired sequentially rather than concurrently . It is postulated that the sequence of functional differentiation is: phagocytosis leads to microbial killing leads to random locomotion leads to chemotaxis. Acta Microbiol Pol, 1983, 32(1), 53 - 64 Production of H2O2 by bovine blood and milk polymorphonuclear leucocytes; Korhonen HJ et al.; The ability of bovine polymorphonuclear leucocytes (PMN) to release H2O2 was investigated . Resting PMN suspended in buffer released only small amounts of H2O2 which was appreciably increased during phagocytosis of heat killed coliforms . However, in the presence of bovine serum (BS), foetal calf serum (FCS) and milk whey (MW) no increase of H2O2 could be detected unless sodium azide (NaN2) was added . It appears that the enzyme content of these fluids (catalase and lactoperoxidase) consumed the released H2O2 and NaN2, which inactivates these enzymes, abolished this interference . Live organisms required BS or MW both for phagocytosis and for H2O2 production . Bovine IgG2 and, to a lesser extent, IgG1 but not SIgA or IgM stimulated the release of H2O2 independently of phagocytosis; this indicates the presence of receptors specific for IgG2 and IgG1 on the cell surface . Ingestion of casein micelles triggered the greatest burst of H2O2 production by cells suspended in buffer . In general, PMN isolated from blood were more active than cells isolated from milk . Since the extracellular release of H2O2 reflects the intracellular level of H2O2, the lower metabolic activity of milk PMN may contribute to the lesser intracellular bactericidal activity of milk leucocytes . The possibility that the release of H2O2 may activate extracellularly the lactoperoxidase system, known to be bactericidal in milk, is discussed. Appl Environ Microbiol, 1983 Jan, 45(1), 48 - 57 Bacteriostatic and bactericidal modes of action of bis(tributyltin)oxide on Legionella pneumophila; Soracco RJ et al.; The modes of action of bis(tributyltin)oxide (TBTO) doses between 1 X 10(4) and 6 X 10(7) molecules per cell on a single environmental isolate of Legionella pneumophila were studied by monitoring the following parameters: (i) growth, (ii) cell viability, (iii) 14C-amino acid incorporation, (iv) 14CO2 production from 14C-amino acids, (v) {3H}uridine incorporation, (vi) {3H}thymidine incorporation, (vii) oxygen consumption, (viii) cellular ATP levels, and (ix) adenylate energy charge . The amount of TBTO associated with the cells in these laboratory cultures was also compared with that remaining in the suspending medium . Most of the TBTO (68 to 88%) was found to be associated with the cells . This result explained why the cellular responses which were measured did not correlate with the TBTO concentration, but rather with the dose of TBTO to which the cells were exposed . At the lower TBTO doses tested (10(4) to 10(7) molecules per cell) a log-normal relationship was observed between the reduction in growth rate and the TBTO concentration . At intermediate TBTO doses (ca . 10(7) molecules per cell) growth stasis occurred, with nearly 100% of the cells in these cultures remaining viable for at least 5 h after treatment . The cellular function which seemed to be primarily affected at these levels of TBTO was the energy conversion mechanism, since the decline in the rates of CO2 production, oxygen consumption, and macromolecular synthesis was preceded by an immediate (within 1 min) drop in the intracellular levels of ATP and the adenylate energy charge . At the higher TBTO doses greater than 10(7) molecules per cell) an initial, precipitous, drop in the number of viable cells was observed, which was followed by a further exponential reduction of viable cells in the treated culture . This dramatic increase in bactericidal activity with a slight increase in the TBTO dose indicated that the modes of bacteriostatic and bactericidal action of TBTO were different. J Biol Chem, 1982 Dec 10, 257(23), 14055 - 7 The role of phospholipase A2 lysines in phospholipolysis of Escherichia coli killed by a membrane-active neutrophil protein; Forst S et al.; Purified rabbit bactericidal/permeability-increasing protein at bactericidal concentrations is a membrane-perturbing agent that triggers hydrolysis of envelope phospholipids of a phospholipase A-less Escherichia coli (S17) mutant by a highly basic (pI greater than 10) phospholipase A2, purified from Agkistrodon halys blomhoffii snake venom . Most other purified phospholipases A2 do not degrade the phospholipids of E . coli killed by the bactericidal protein . To study the role of enzyme charge in bactericidal protein-dependent phospholipid hydrolysis, lysines of the Agkistrodon phospholipase A2 were modified, either by carbamylation (decreases net charge), or by reductive methylation (no delta charge) . Incorporation of {14C}cyanate or {14C}formaldehyde and amino acid analysis served to monitor modification . Modification appears to be limited to epsilon-NH2 groups . Incorporation of up to 5 mol of cyanate or formaldehyde/mol of enzyme did not affect catalytic activity . In contrast, incorporation of, on average, 1 mol of either reagent/mol of protein reduced by 80% the activity of the enzyme toward E . coli S17 killed by the bactericidal protein . Since this loss is similar with carbamylation and reductive methylation, the role of the epsilon-NH2 group in the bactericidal protein-dependent hydrolysis seems independent of charge . Thus, the lysines in this phospholipase A2 are not essential for catalysis and substrate binding, but are essential for the action of this enzyme on E . coli killed by the bactericidal protein. Arch Microbiol, 1982 Dec 3, 133(4), 278 - 82 Ultrastructural analysis of the effects of erythromycin on the morphology and developmental cycle of Chlamydia trachomatis HAR-13; Clark RB et al.; The effect of erythromycin (10 micrograms/ml) on the morphology and developmental cycle of Chlamydia trachomatis HAR-13 was examined by electron microscopy . When the antibiotic was added later than 24 h post infection, the HAR-13 morphology or developmental cycle was not altered . Addition at 18 or 24 h post infection inhibited glycogen production, blocked the transformation of the reticulate body to elementary body, and produced ghost bodies and reticulate bodies twice the diameter of untreated reticulate bodies . When erythromycin was added within 12 h post infection, the conversion of the elementary body to reticulate body was inhibited . Erythromycin (10 micrograms/ml) was bactericidal to strain HAR-13 throughout the developmental cycle. Antimicrob Agents Chemother, 1982 Dec, 22(6), 990 - 4 Pharmacokinetics of cefuroxime in infants and children with bacterial meningitis; del Rio Mde L et al.; A total of 38 patients with bacterial meningitis received either 50 or 75 mg of cefuroxime per kg of body weight given as a 15-min intravenous infusion during the first to third days of therapy . The mean peak plasma concentrations of cefuroxime after doses of 50 and 75 mg/kg were 105 and 152 micrograms/ml, respectively . In five patients, pharmacokinetic values were determined after multiple doses of 50 mg of cefuroxime per kg every 6 h . The mean peak plasma concentrations were 120 micrograms/ml after the first dose and 130 micrograms/ml after the last dose . The concentrations at 6 h were 3.25 and 11.0 micrograms/ml after the first and last doses, respectively . The elimination half-life was approximately 1.5 h, and the apparent volume of distribution was 650 ml/kg . The plasma clearance rate was 195 to 198 ml/min per 1.73 m2 . Penetration into the cerebrospinal fluid, expressed as the ratio of the cerebrospinal fluid to serum areas under the curve times 100, was 6.4% in patients given 50 mg of cefuroxime per kg and 10% in those who received 75 mg/kg . The cerebrospinal bactericidal activity in 27 patients was less than or equal to 1:8; only 2 patients had bactericidal activity of less than or equal to 1:2. J Gen Microbiol, 1982 Dec, 128 (pt 12), 3083 - 91 Properties of Escherichia coli grown in vivo using a chamber implant system; Finn TM et al.; Strains of Escherichia coli were examined for their ability to grow in diffusion chambers implanted into the peritoneal cavities of mice and rabbits . In rabbit chambers E . coli K12 strains grew poorly, whereas isogenic strains harbouring ColV plasmids and wild-type isolates from extra-intestinal infections grew well . The difference was much less marked with strains grown in mouse chambers . Differences in sensitivity to the bactericidal action of human or rabbit serum were found in some cases between organisms of the same strain grown in vivo or in vitro . Host immunoglobulins were bound to the surface of all in vivo bacteria . Comparison of the polypeptide composition of bacterial cell envelope preparations on SDS-PAGE gels revealed differences between in vivo and in vitro grown E . coli growing in vivo may possess properties significantly different from the same organisms growing on laboratory medium. Pathol Biol (Paris), 1982 Dec, 30(10), 840 - 2 {Bactericidal activity of antibiotics as a function of pharmacokinetic constants . II . Effect of pharmacokinetic parameters (C max and Ke) on the bactericidal activity of gentamicin}; Drugeon HB et al.; The authors studied the influence of certain pharmacokinetic parameters on the bactericidal activity of gentamicin using an experimental model simulating the variations of antibiotic concentration . These parameters are the maximal concentration (C max) and the elimination constant (Ke) . The bactericidal activity of gentamicin was studied on the strain of E . coli ATCC 25922 . The result is that an influence of C max on the bactericidal activity is more important than that of Ke from these experiments . Considering only bacteriological parameters, the rapid intravenous injection will be superior to slow perfusion . However, the pharmacological parameters must be considered and modify also these conclusions. Pathol Biol (Paris), 1982 Dec, 30(10), 837 - 9 {Bactericidal activity of antibiotics as a function of pharmacokinetic constants . I . Experimental dynamic model simulating variations in the concentrations of antibiotics}; Drugeon HB et al.; In order to study the bactericidal effect of antibiotics in a system approaching actual therapy, a dynamic model which simulates concentration variations was developed . This was done using a dialysis intermediary . Three aminoglycosides (amikacin, gentamicin, tobramycin) were taken in a system resembling the serum rates of the normal individual . The apparatus is fairly accurate, the variation coefficients being of the order of 10 to 14% . This model enables the simulation of numerous therapeutic situations . It is however limited to only dialysable antibiotics. Antimicrob Agents Chemother, 1982 Dec, 22(6), 961 - 8 Iron requirement in the bactericidal mechanism of streptonigrin; Yeowell HN et al.; Mutants of Escherichia coli K-12 that are unable to make use of the enterochelin transport system were used to confirm that streptonigrin requires iron for its bactericidal action . Correlation of viability studies and 55Fe3+ uptake experiments showed that killing by streptonigrin increased with an increase in 55Fe3+ uptake by the cells . Streptonigrin did not kill iron-starved mutants that were unable to import iron . The level of iron uptake by these mutants was manipulated by agents such as (i) the enterochelin biosynthetic precursors 2,3-dihydroxybenzoic acid (2 x 10(-5) M) and shikimic acid (2 x 10(-4) M), (ii) citrate (10(-2) M), which promotes iron uptake by an independent pathway, and (iii) the chelating agents desferrioxamine (2 x 10(-4) M) and orthophenanthroline (10(-4) M) . Addition of the precursors shikimate and dihydroxybenzoate to strain AB2847 (aroB) and dihydroxybenzoate to strain AN193 (entA), allowing these strains to make enterochelin, resulted in an increase in Fe3+ uptake and a corresponding sharp increase in killing by streptonigrin . Addition of enterochelin itself (10(-6) M) caused an even more pronounced effect . Studies on the effect of citrate in strain AN102 (fep) showed that this mutant was not killed by streptonigrin (4 x 10(-5) M), even in the presence of citrate; however, overnight growth in citrate induced Fe3+ uptake by means of the ferric citrate transport system and resulted in killing by streptonigrin . These studies showed a clear correlation between the change in levels of intracellular iron and the bactericidal effectiveness of streptonigrin. Am J Vet Res, 1982 Nov, 43(11), 1912 - 6 Isolation of equine neutrophils and analysis of functional characteristics by chemiluminescence and bacterial assays; Jacobsen K et al.; Equine neutrophils (PMN) were isolated to greater than 99% purity by isopyknic sedimentation on coated colloidal silica particles . A cell recovery of 84.7 +/- 4.0%, with a viability of greater than 99%, was observed with this method . The isolated PMN were compared with mixed population of equine peripheral leukocytes with respect to functional integrity by chemiluminescence and bactericidal assays . There was no significant difference (P less than 0.01) observed in either assay between the isolated equine PMN and the mixed-cell populations . The methods used in both the isolation as well as the functional characterization of the equine PMN, were rapid and highly reproducible and should readily find use in clinical and research laboratories . It is now feasible to rapidly assess equine PMN integrity in those cases which warrant this type of study . This is the first direct comparison of the chemiluminescence assay with the microbicidal assay, using equine PMN. J Ethnopharmacol, 1982 Nov, 6(3), 361 - 4 Geaster mammosum: a bactericidal fungus used in Himalayan folklore; Joshi GC et al.; The discovery is described of the high bactericidal and healing properties of basidiospores of a "star fungus" identified as Geaster mammosum Chev . (family: Geastraceae) growing saprophytically in pine forests . It is used in folk medicine for burns by the inhabitants of Kumaon . This drug was clinically tried on 25 patients with karnasrava (otorrhoea), 8 with karnasula (earache), 7 with vrana (wounds) and 2 with nabhipaka (umbilical sepsis) showing an improvement/cure in almost all cases . The drug offers potential for development as a therapeutic agent. Arch Ophthalmol, 1982 Nov, 100(11), 1817 - 9 Intraocular penetration of amikacin . Iris binding and bioavailability; Eiferman RA et al.; The penetration of amikacin sulfate into the anterior chamber of the human eye was determined by radioimmunoassay . Bactericidal concentrations of amikacin were not achieved by topical or intravenous administration . Subconjunctival injection did not produce consistent bactericidal concentration of amikacin in aqueous humor . Poor corneal penetration and subsequent tight binding to iris pigment are responsible for these observations . Tissue or pigment binding is adsorptive, nonspecific, and readily reversible . Amikacin released after being bound retains its bactericidal potency. Blood, 1982 Nov, 60(5), 1151 - 8 Monocyte function in patients with chronic granulomatous disease of childhood; Donowitz GR et al.; Adults with chronic granulomatous disease of childhood (CGD) have been described who remain relatively free of infection despite markedly abnormal neutrophil function . Monocyte function in four adults with this mild or atypical CGD syndrome was examined and compared to that of normal controls and to that of two patients with the more severe or classic CGD syndrome . Monocytes from patients with atypical CGD killed 75.7% +/- 2.6% (mean +/- SEM) of ingested organisms at 30 min, while monocytes from the patients with classic CGD killed only 50.3% +/- 4.2% of bacteria (p less than 0.001) . The difference in bactericidal activity between atypical CGD monocytes and normal monocytes was relatively small (75.7% +/- 2.6% versus 88.1% +/- 3.7%, respectively) but was statistically significant (p = 0.007) . Monocytes from both atypical and classic CGD patients showed markedly impaired oxidative metabolism . Differences in monocyte bactericidal activity may explain why atypical CGD patients have fewer infections than classic CGD patients . The presence of nonoxidative bactericidal mechanisms in atypical CGD monocytes is suggested by the demonstration of bactericidal activity despite severe oxidative metabolic defects. Am J Med, 1982 Nov, 73(5), 652 - 7 Folic acid deficiency and neutrophil dysfunction; Youinou PY et al.; Polymorphonuclear leukocyte functions were studied in 92 patients with protein-calorie malnutrition . Serum folic acid levels were higher than 3 ng/ml in 38 patients and 3 ng/ml or less in 54 patients . Significant differences were found between these two groups of patients with regard to phagocytosis (81.5 +/- 1.9 versus 69.2 +/- 2.0 percent, p less than 0.001) and bactericidal ability (90.6 +/- 1.1 versus 84.5 +/- 2.3 percent, p less than 0.05) . Correction of folic acid deficiency in 22 patients was associated with recovery of normal phagocytosis (p less than 0.001) but not bactericidal function . Adding folic acid to the serum of eight patients also restored normal phagocytic function (p less than 0.001) . A correlation was found in vivo and in vitro between changes over time in folic acid levels and in phagocytosis. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1982 Nov, 253(2), 164 - 74 {The effect of plasmids of various incompatibility groups on the serum sensitivity of Escherichia coli K 12}; Falkenhagen U et al.; Using the method of Henkel and Taylor (11, 18) 60 Escherichia coli K 12 J 53 strains carrying R-plasmids of 15 incompatibility groups (FI, FIme, FII, FIV, FV, FVI, I alpha, I gamma, I omega, I5, B, C, K, M, S) have been tested with respect to their serum sensitivity in pooled human serum . We found for 41 plasmid carrying strains a grade of resistance to serum bactericidal activity of 0, for 19 strains a grade of 1, 2 or 3 according to the method of Henkel . Applying the method the method of Taylor the results of the bactericidal tests of the same 60 strains could all graded in category 1 . The results obtained show that there was not any change of sensitivity to serum bactericidal activity after the uptake of a plasmid . 29 strains carrying different plasmids of the same 15 incompatibility groups were selected for studies in a low concentration system of serum . Survivors' curves in 1, 2, 3, 5, 10 and 20% of serum after different times of incubation (10, 20, 30, 60, 90, 120 and 180 min) were established . In relation to the control strain E . coli K 12 J 53 R- a difference in the percentage of survivors of 18 strains carrying plasmids of 10 incompatibility groups (FI, FIme, FIV, FVI, I alpha, I omega, I5, C, K, and M) could be demonstrated . However, this could only be observed in concentrations of serum from 1 to 5% and most clearly after an incubation time of 10 min . The results were graded into 3 categories in dependence of the difference of the percentage of survivors to the control strain . The plasmid pIE 307 and pIE 403 (Inc FI and C) showed the strongest activity in increasing the serum resistance . We found the method used to be suitable for the estimation of small alterations of serum sensitivity . The results obtained in E . coli K 12 made us control their influence in other E . coli strains carrying a complete O-antigen. Antimicrob Agents Chemother, 1982 Nov, 22(5), 735 - 42 Mechanism of action of dnacin B1, a new benzoquinoid antibiotic with antitumor properties; Tanida S et al.; Dnacin B1 preferentially inhibited the incorporation of {3H}thymidine into acid-insoluble fractions in Escherichia coli . At a sublethal concentration, dnacin B1 caused filamentous growth in E . coli and induced prophage lambda . The antibiotic also showed potent bactericidal activity against repair-deficient E . coli strains, such as recA, recB, and polA strains, In in vitro studies, dnacin Ba raised the melting temperatures of various double-stranded DNAs . In addition, the antibiotic showed DNA-cleaving activity against PM2 DNA in the presence of reducing agents, and the activity was suppressed by scavengers for oxygen free radicals and an iron-specific chelator, desferrioxamine E . The stimulation of the generation of superoxide radical by dnacin B1 was confirmed by measuring the reduction of neotetrazolium . Therefore, it can be presumed that the primary cellular target of dnacin B1 is DNA in susceptible cells, and the autooxidation of DNA-bound dnacin B1 causes the generation of oxygen-free radicals that result in the damage of DNA and the inhibition of its synthesis. Am J Med, 1982 Nov, 73(5), 756 - 64 Mycobacterium fortuitum infection: evidence of bactericidal defect due to hyperactive antigen-specific suppressor cells . Correction in vitro and in vivo by cholinergic agonist and indomethacin; Gardner JD et al.; Immunologic studies in a patient with long-standing Mycobacterium fortuitum infection revealed normal numbers of T cells, T inducers, T suppressors, B cells, and monocytes, significant in vitro proliferative response to M . fortuitum antigen, and poor bactericidal activity against M . fortuitum but not against Escherhicia coli . M . fortuitum antigen-activated suppressor cells contributed to the bactericidal defect . The activity of these suppressor cells could be eliminated by the in vitro treatment of blood mononuclear cells with a combination of a cholinergic agonist and indomethacin, but not with either alone . Administration of the two drugs to the patient resulted in reversal of the bactericidal defect and dramatic clinical improvement . Systemic atypical (nontuberculous) mycobacterial infection may activate specific suppressor cells that could compromise the host's phagocytic cell function . Modulation of those suppressor cells by a combination of a cholinergic agonist and prostaglandin synthetase inhibitor could reverse this abnormality and may be beneficial to the patient. Acta Pathol Microbiol Immunol Scand {C}, 1982 Oct, 90(5), 265 - 70 Antibody response and opsonization afer pneumococcal vaccination in splenectomized children and healthy persons; Johansen KS et al.; A significant rise in antibody against pneumococcal types 3, 6A and 25 after pneumococcal vaccination could be demonstrated in 26 of 30 individuals (87%) using an enzyme-linked immunosorbent assay . Similar geometric mean antibody fold increases were found in splenectomized children, non-splenectomized children and healthy adults for types 6A and 25 . Splenectomized children exhibited a somewhat lower, but not statistically significant, geometric mean antibody fold increase against type 3 (p = 0.10), as compared to non-splenectomized children . For the whole group a negative correlation could be demonstrated between prevaccination antibody concentration and antibody fold increase after vaccination . After vaccination an enhanced serum opsonic activity against type 3 was found by granulocyte glucose-l-14C oxidation for the whole group of 30 patients (p less than 0.05) but nine individual patients (30%) failed to exhibit an increase . No differences between the three patient groups were demonstrable . Changes in serum opsonic activity could not be detected by a pneumococcal bactericidal assay. Clin Orthop, 1982 Oct, (170), 62 - 75 Reimplantation in infection: a 12-year experience; Salvati EA et al.; Three groups of patients underwent reimplantation for infected hip prostheses during the period from 1968 to 1979 . The first group (N = 19) was diagnosed mainly by hip aspiration and treated with antibiotics selected by disc sensitivity and one-stage reimplantation in 14 hips . The second group (N = 26) was diagnosed by strict hip infection criteria and treated with a similar antibiotic regimen . Reimplantation was performed in one stage in 13 patients and in two stages in the remaining 13 . The third group (N = 16) was diagnosed by the same criteria but treated with standardized bactericidal antibiotics evaluated by the tube dilution method . There were five one-stage reimplantations, ten two-stage, and one radical debridement without removal of components . The follow-up period ranged from two to 12 years . The present guidelines for reimplantation include subacute hip sepsis caused by susceptible bacteria, according to tube dilution methods in immunocompetent patients with adequate soft tissue and bone stock to allow a satisfactory biomechanical reconstruction . Patients should be aware of the risk of recurrence of infection, persistent pain, limited durability, and further surgical treatment. Agents Actions, 1982 Oct, 12(4), 489 - 98 Effect of in vivo administration of gold sodium thiomalate on rat macrophage function; Turkall RM et al.; It has been shown that gold accumulates in macrophages . In vitro studies have also shown that long-term anti-inflammatory and immuno-regulatory effects on these cells may be responsible for the effectiveness of gold in the treatment of rheumatoid arthritis . However, the relevance of this information to the in vivo circumstance is largely untested . In this study, the effect of gold sodium thiomalate (AuTM) on rat alveolar macrophage (AM) lysosomal enzymes, bacterial killing, and metabolic activities associated with phagocytosis were assessed after in vivo administration . The activities of beta-glucuronidase, acid phosphatase, and lysozyme were inhibited 1 day following a single AuTM injection (50 mg/kg, subcutaneous) . However, lysozyme returned to normal, while the activities of beta-glucuronidase and acid phosphatase were elevated from 4 to 12 days thereafter . When AuTM was administered weekly for 8 weeks, the activities of acid phosphatase and beta-glucuronidase were elevated throughout, while lysozyme was largely unaffected . The increased lysosomal enzyme activities were not due to contamination of polymorphonuclear leukocytes . These long-term effects of AuTm on enzyme activity were in marked contrast to its in vitro effect which inhibited the activities of beta-glucuronidase and acid phosphatase . No effect of AuTM administration on the release of beta-glucuronidase upon phagocytosis of opsonized zymosan was observed . At 1 day following a single AuTM injection or 3 days after a second weekly injection, in vivo bactericidal activity of AM toward S . aureus was diminished . This bacterial killing defect was not due to decrease phagocytosis; the in vivo binding and ingestion of bacteria were normal . The defect correlated with imparied metabolic activities associated with phagocytosis, namely a significant decrease in the reduction of nitroblue tetrazolium and the stimulation of the hexose monophosphate shunt . This may be an attractive anti-inflammatory effect in light of the destructive potential of the reactive oxygen species produced by macrophages in an arthritic circumstance. J Bacteriol, 1982 Oct, 152(1), 81 - 8 Potentiation by L-cysteine of the bactericidal effect of hydrogen peroxide in Escherichia coli; Berglin EH et al.; Under anaerobic conditions an exponentially growing culture of Escherichia coli K-12 was exposed to hydrogen peroxide in the presence of various compounds . Hydrogen peroxide (0.1 mM) together with 0.1 mM L-cysteine or L-cystine killed the organisms more rapidly than 10 mM hydrogen peroxide alone . The exposure of E . coli to hydrogen peroxide in the presence of L-cysteine inhibited some of the catalase . This inhibition, however, could not fully explain the 100-fold increase in hydrogen peroxide sensitivity of the organism in the presence of L-cysteine . Of other compounds tested only some thiols potentiated the bactericidal effect of hydrogen peroxide . These thiols were effective, however, only at concentrations significantly higher than 0.1 mM . The effect of L-cysteine and L-cystine could be annihilated by the metal ion chelating agent 2,2'-bipyridyl . DNA breakage in E . coli K-12 was demonstrated under conditions where the organisms were killed by hydrogen peroxide. Antimicrob Agents Chemother, 1982 Oct, 22(4), 622 - 7 Pharmacokinetics and cerebrospinal fluid bactericidal activity of ceftriaxone in the treatment of pediatric patients with bacterial meningitis; Del Rio M et al.; Single-dose pharmacokinetics of ceftriaxone were determined in 19 patients with proven bacterial meningitis . The dosage was 50 mg of ceftriaxone per kg . The plasma concentration time curve declined in a biexponential manner . The mean peak plasma concentration was 207 micrograms/ml, and the elimination half-life was 4 h . In 12 patients, multiple-dose pharmacokinetics were determined after a loading dose of 75 mg of ceftriaxone per kg, followed by 50-mg/kg doses every 8 h in 5 patients or every 12 h in 7 patients . The mean peak plasma concentration was 230 micrograms/ml after the first dose and 263 micrograms/ml after the last dose . Of 12 patients, 5 had trough values that were larger after multiple doses than after a single dose . Mean penetration of ceftriaxone into cerebrospinal fluid was 3.1% . The median cerebrospinal fluid bactericidal titer against the patients pathogens was greater than 1:1,024 and less than 1:2,048 . The drug was well tolerated without adverse effects. Vopr Med Khim, 1982 Sep-Oct, 28(5), 119 - 22 {Effect of vitamin A on immunological status of patients with chronic pneumonia}; Pletsitnyi KD et al.; Effect of vitamin A on some patterns of specific and unspecific immunity was studied in patients with chronic pneumonia . The vitamin was administered into the patients during 7 days at a daily dose of 500,000 IU . Administration of vitamin A was found to stimulate several immunological patterns: content of T- and B lymphocytes in peripheral circulation as well as IgG and IgM blood serum were increased . After the vitamin A treatment the cellular immunity was also stimulated, involving the activation of lymphocyte blast transformation with PHA and the increase in exhibition of skin reaction towards PHA . In response to vitamin A administration activation was observed of unspecific bactericidal, and complement activities in blood serum as well as of the myeloperoxidase activity in leukocytes of peripheral circulation . Administration of vitamin A into the control patients within a week at a daily dose of 10,000 IU did not alter the immunological patterns studied. Antimicrob Agents Chemother, 1982 Sep, 22(3), 461 - 9 Penetration of cefazolin into normal and osteomyelitic canine cortical bone; Daly RC et al.; The ability of cefazolin to cross the capillary membrane and its concentrations in the interstitial fluid spaces were studied in normal and osteomyelitic canine bone . The maximum extraction after a single capillary passage and the net extraction after 3 min, determined with triple-tracer indicator-dilution techniques, demonstrated that cefazolin readily traversed the capillaries of normal and osteomyelitic bone . These studies suggest that the altered pathophysiology of osteomyelitic tissue and the complex diffusional characteristics of cefazolin enhanced the ability of this agent to cross the endothelial cells lining the capillaries of osteomyelitic bone . Volume of distribution studies demonstrated that cefazolin was distributed in the plasma and interstitial fluid spaces of normal cortical bone . Although these spaces were increased 330 and 941% in osteomyelitic tissue, the distribution of cefazolin increased proportionally . There was a direct correlation between the calculated concentrations of cefazolin in the interstitial fluid spaces of normal and osteomyelitic cortical bone and the simultaneous serum levels in animals in which a steady-state equilibrium had been achieved . These studies suggest that a physiological barrier or concentration gradient for cefazolin does not exist in normal or osteomyelitic bone . Cefazolin can cross the capillary membranes of bone and achieve bactericidal concentrations in the interstitial fluid space of normal and osteomyelitic tissue. Blut, 1982 Sep, 45(3), 157 - 66 Effects of hyperoxia on phagocytosis; Rister M; The development of bacterial infections is a common complication during treatment with high concentrations of oxygen . To study the effect of hyperoxia on phagocytes, the adherence, chemotaxis, ingestion rates, degranulation as well as the bactericidal activity were measured in alveolar macrophages (AMs) and polymorphonuclear leukocytes (PMNs) obtained from guinea pigs exposed to 85% oxygen . The animal exposure to a Fi O2 of 85% impaired the adherence to nylon-wool, the chemotactic activity and the phagocytic rate of paraffinoil-droplets of AMs and PMNs . In AMs the secretion of beta-glucuronidase upon stimulation with opsonized zymosan was also diminished . In addition, the bacterial activity of AMs and PMNs demonstrated a reduction of 50% . These phagocytic defects may be caused by cytoskeleton alteration, induced by the increase of oxygen derived metabolites, representing an additional sepsis promoting factor during hyperoxia. J Infect Dis, 1982 Sep, 146(3), 381 - 7 Resistance and susceptibility of mice to bacterial infection . IV . Genetic and cellular basis of resistance to chronic infection with Brucella abortus; Ho M et al.; The number of Brucella abortus strain 19 organisms in the spleens of CBA/H mice peaked two weeks after intravenous injection of 5 X 10(6) organisms . With the onset of specific cell-mediated immunity, 90% of the bacteria were killed, but approximately 10(6) bacteria persisted up to seven weeks after infection . In contrast, in BALB/c, C57BL/10, and B10Br mice, bacterial numbers peaked at two weeks but decreased steadily with the onset of bactericidal activity . In all strains, clearance of bacteria from the liver was relatively efficient . The course of infection in (CBA/H X BALB/c) F1 mice was similar to that in CBA/H mice, indicating that the mechanism(s) leading to slower recovery from infection was dominant . The H-2 haplotype of the mice did not influence the rate of recovery from infection . The use of backcross mice showed that multiple genes were involved . In bone marrow-chimeric mice, resistance was determined by the genome of the bone marrow donor, not that of the host. J Reticuloendothel Soc, 1982 Sep, 32(3), 179 - 87 Decreased phagocytic and bactericidal activity of the hepatic reticuloendothelial system during chronic ethanol treatment and its restoration by levamisole; Galante D et al.; The effect of chronic ethanol feeding (3 weeks) on the phagocytic and the bactericidal activity of hepatic RES versus viable Escherichia coli was studied using the isolated rat liver perfused with a serum-containing medium . Controls or ethanol-fed animals were used as liver or serum donors . The bactericidal activity of serum from ethanol-fed rats was similar to controls and accounted for the disappearance of nearly one-tenth of the bacterial inoculum from the system . When control livers were perfused with a medium containing serum from ethanol-fed animals, phagocytosis was comparable to controls while intracellular killing was greatly reduced . When livers were isolated from ethanol-fed rats, phagocytosis was significantly depressed and no killing occurred, irrespective of the source of serum . Levamisole was able to restore the macrophage activity depressed by ethanol . Our data indicate that the direct effect of ethanol on hepatic macrophages plays a major role in reducing the bactericidal activity of hepatic RES, although alterations of serum factors may contribute to an ineffective preparation of bacteria for intracellular killing. Infect Immun, 1982 Sep, 37(3), 956 - 60 K antigen and serum sensitivity of rough Escherichia coli; Opal S et al.; We prepared bacterial hybrids which express both K1 and K27 antigens and examined the relative contributions of these capsules to serum resistance . Escherichia coli Hfr strain F639 (rough, K27+, serum sensitive) was conjugated with E . coli recipient strain E412 (rough, K1+, His- Trp- Strr, serum resistant) . Transconjugants which inherited both the his and trp linked genes for K27 antigen synthesis were analyzed . These hybrids retained and expressed the K1 antigen since the K1 locus is nonallelic with K27 gene loci . Hybrid strains which express both K1 and K27 antigens exhibit serum resistance, but not at the level of the K1+ parental strain . An isogenic K1 derivative of a hybrid which expressed only K27 antigen was serum sensitive (greater than 99% kill, 60 min) . These findings indicate that the presence of the K1 capsular antigen can protect some rough strains of E . coli from serum bactericidal activity, whereas K27 and perhaps other K antigens fail to provide such a protective effect. Rev Infect Dis, 1982 Sep-Oct, 4 Suppl, S396 - 400 Penetration of cefotaxime and moxalactam into cerebrospinal fluid of rabbits with experimentally induced Escherichia coli meningitis; Nolan CM et al.; Penetration of the new beta-lactam antibiotics cefotaxime and moxalactam into cerebrospinal fluid (CSF) was studied in rabbits with experimentally produced Escherichia coli meningitis . Cefotaxime reached peak concentrations (mean +/- SEM) of 31.9 +/- 5.4 micrograms/ml in serum and 2.8 +/- 0.3 micrograms/ml in CSF after an infusion of 50 mg/kg per hr for 8 hr . Moxalactam, after an infusion of 12.5 mg/kg per hr iv, produced peaks of 31.0 +/- 13.1 micrograms/ml in serum and 9.7 +/- 1.2 micrograms/ml in CSF . Both drugs reduced the initial concentration of E . coli in the CSF by greater than 1,000-fold . An infusion of 100 mg/kg per hr of cephalothin produced a peak concentration of 76.5 +/- 15.2 micrograms/ml in serum but resulted in a concentration of only 0.17 +/- 0.05 micrograms/ml in CSF and had no bactericidal activity in CSF . Paper chromatography of CSF from cefotaxime-treated rabbits showed that 85.3% (+/- 3.1%) of the antibiotic activity was ascribed to desacetylcefotaxime, a metabolite that is less potent than the parent drug . Neither cefotaxime nor moxalactam was taken up in vitro by rabbit choroid plexus tissue, but cephalothin was taken up at a rate of 9.6 +/- 1.1 microgram/g per hr . Perhaps cefotaxime and moxalactam reached higher concentrations in CSF than did cephalothin because they are not removed from the CSF by the exit pump of the choroid plexus . The fact that levels of cefotaxime in CSF are lower than those of moxalactam could be attributed to the presence of desacetylcefotaxime, a metabolite that is less active than cefotaxime. J Pediatr Orthop, 1982 Aug, 2(3), 255 - 62 Benefits and risks of sequential parenteral--oral cephalosporin therapy for suppurative bone and joint infections; Nelson JD et al.; Seventy-five infants and children with suppurative skeletal infections were managed with a sequential parenteral-oral regimen of cephalosporin antibiotic therapy . Initially, parenteral antibiotics (cefamandole for 48 patients and cefuroxime for 27 patients) were given for a median of 5 days . Oral therapy was with large doses of cefaclor (150 mg/kg/day) or cephalexin (100 mg/kg/day) . Eight patients (11%) had inadequate serum bactericidal activity with cefaclor . Six of them were successfully managed with alternative oral antibiotics, and parenteral therapy resumed in one patient . Chronic disease developed in a child who was continued on oral cloxacillin therapy in spite of absent serum bactericidal activity . It is concluded that oral therapy can be successful for the majority of patients but that it is hazardous and not indicated if careful laboratory monitoring of compliance and serum bactericidal activity cannot be performed. J Lab Clin Med, 1982 Aug, 100(2), 218 - 29 Cerebrospinal fluid prognostic indices in experimental pneumococcal meningitis; Scheld WM et al.; The prognostic value of initial and sequential determinations of quantitative bacterial concentrations, leukocytes, glucose, lactate, lactic acid dehydrogenase, and creatine phosphokinase in CSF was examined in rabbits with experimental pneumococcal meningitis while they were receiving equivalent, rapidly bactericidal antibiotic therapy . The following mean CSF variables correlated with death due to meningitis: (1) an early (day 1) high bacterial titer and lactate concentration with simultaneous low leukocyte count and glucose level and (2) late (day 3) elevated lactate and lactic acid dehydrogenase levels and leukocyte count . A high concentration of bacteria inoculated into the CSF and a high plasma glucose level also adversely influenced prognosis . Careful analysis of these variables may identify high-risk patients with pneumococcal meningitis and ultimately may be useful in gauging the therapeutic response. J Invest Dermatol, 1982 Aug, 79(2), 74 - 8 Neutrophil studies in psoriatics: in vivo migration, phagocytosis and bacterial killing; Dubertret L et al.; A reproducible method for sequential study of migration out of human skin, phagocytosis and bactericidal activity of neutrophils is described . Untreated psoriatics exhibit an early increase of chemotactic activity (0-8 hr, p less than 0.02) and subsequently a strong inhibition of chemotaxis (8-24 hr, p less than 0.01), a slight decrease of phagocytosis and a decrease in bactericidal activity (20 min, p less than 0.02; 30 min, p less than 0.003); 60 min, p less than 0.001; 120 min, p less than 0.001) as compared with controls . After clearing of skin lesions, the early increased chemotactic activity returned to normal values but the subsequent chemotactic inhibition remains as strong as before treatment . Phagocytosis increased to normal values (p less than 0.02) and bactericidal activity also increased but remained significantly low . These abnormalities were more evident in migrating than in circulating neutrophils, underlining the sensitivity of the described method. Am J Med, 1982 Aug, 73(2), 260 - 7 Association between serum inhibitory and bactericidal concentrations and therapeutic outcome in bacterial endocarditis; Coleman DL et al.; Several recent reviews on the therapy of bacterial endocarditis have recommended that a serum inhibitory and/or bactericidal concentration (SIC/SBC) of 1:8 or more be achieved to ensure successful therapeutic outcome . We conducted a methodologic and statistical analysis of the available literature on endocarditis to determine the association between SIC/SBC titers of 1:8 or more and therapeutic outcome . We reviewed 17 studies published between 1948 and 1980 in which both SIC/SBC and therapeutic outcome were available . Factors that affect outcome, such as age, duration of symptoms, organism, and valve status, varied widely among the 226 patients . The methods used to measure SIC/SBC differed with respect to the time of obtaining the blood specimen relative to the antibiotic dose, size of the bacterial inoculum, type of broth, and definition of the bactericidal end-point . None of the 17 studies showed a significant association between SIC/SBC titers of 1:8 or more and survival or bacteriologic cure . Fifteen of the 17 also failed to demonstrate a significant association between SIC/SBC titers of 1:8 or more and medical cure . However, each of the studies that failed to demonstrate an association between SIC/SBC titers of 1:8 or more and improved therapeutic outcome had an insufficient sample size to confidently exclude a false-negative result . Analysis of the published data reveals insufficient evidence to demonstrate that SIC and SBC titers are of prognostic value in the therapy of patients with bacterial endocarditis. Antimicrob Agents Chemother, 1982 Aug, 22(2), 272 - 6 Bactericidal activity of antibiotics against Legionella micdadei (Pittsburgh pneumonia agent); Dowling JN et al.; The bactericidal activity of five antibiotics for Legionella micdadei was determined by the construction of time-kill curves . Erythromycin, rifampin, penicillin G, cephalothin, and gentamicin were bactericidal for L . micdadei at readily achievable concentrations . The minimal bactericidal concentrations, defined as those producing 99.9% killing within 24 h, were: erythromycin, 4.6; rifampin, 0.13; penicillin G, 0.25; cephalothin, 2.5; and gentamicin, 0.25 micrograms/ml . The ratios of the minimal bactericidal to minimal inhibitory concentrations for these antibiotics ranged from 1 to 8 . Thus, the poor in vivo activity of beta-lactam and aminoglycoside antibiotics against L . micdadei cannot be ascribed to a lack of killing by these agents. Antimicrob Agents Chemother, 1982 Aug, 22(2), 262 - 5 Excretion of cephalothin and cefamandole by the normal pancreas and in acute pancreatitis in dogs; Studley JG et al.; Nine mongrel dogs were studied to evaluate the excretion of cefamandole (five dogs) and cephalothin (four dogs) in the pancreatic fluid . Each dog was studied before and after the induction of pancreatitis, with 2 weeks between studies . After intravenous administration of a 25-mg/kg dose of either cephalosporin, serum and pancreatic fluid concentrations were monitored for 6 h . Both cephalothin and cefamandole were excreted in bactericidal concentrations in the normal pancreas and in acute pancreatitis . Clearance of cefamandole (290 ml/min) and cephalothin (348 ml/min) were similar pre- and postinduction of pancreatitis . Serum albumin concentration was less during the post-pancreatitis phase compared with the prepancreatitis phase . Penetration of cephalothin was reduced in pancreatitis, whereas cefamandole penetration increased in pancreatitis. Drugs, 1982 Aug, 24(2), 118 - 32 Short-course therapy for tuberculosis; Aquinas M; The discovery of rifampicin was the turning point away from the standard long term treatment for tuberculosis of 18 to 24 months and towards a 6-month curative programme . Rifampicin has proven to be highly effective and vital to short-course tuberculosis therapy, but its disadvantage is its cost . This makes it relatively unavailable where it is most needed, i.e . in countries where tuberculosis is still rampant, but which are economically underdeveloped . In such areas other needs take precedence over a chronic and non-spectacular medical condition like tuberculosis . During the past 10 years pyrazinamide has been 'rediscovered' and restudied, and when used in combination with rifampicin has been shown to play an important role in short-course chemotherapy . Its contribution to efficacy does not appear to extend beyond the first 2 months of therapy, and it should be discontinued after 2 months . This relatively short administration period helps to minimise adverse reactions to the drug . The main measure of success in short-course chemotherapy is the relapse rate, and this has been higher, sometimes unacceptably so, in regimens where bacteriostatic drugs were substituted for bactericidal ones . In conclusion, isoniazid, rifampicin and pyrazinamide in combination may be deemed essential to an effective short-course regimen of 6 months' duration . Curtailing the duration of treatment to less than 6 months in smear-positive tuberculosis results in high relapse rates and thus is not acceptable . Several studies have been undertaken varying the drug combinations, the dosages and the drug administration routines (i.e . whether daily followed by intermittent or intermittent throughout), in an effort to arrive at the simplest, most effective, least toxic and most economical all-round treatment programme . Such studies are still in progress . When recommended dosage regiments are followed, the incidence of adverse reactions is low with short-course therapy, and in only 5% or less of patients is it necessary to withdraw one or more drugs. J Bacteriol, 1982 Aug, 151(2), 819 - 27 Nucleotide sequence analysis of the complement resistance gene from plasmid R100; Ogata RT et al.; The multiple antibiotic resistance plasmid R100 renders Escherichia coli resistant to the bactericidal action of serum complement . We constructed a plasmid (pOW3) consisting of a 1,900-base-pair-long restriction fragment from R100 joined to a 2,900-base-pair-long fragment of pBR322 carrying ampicillin resistance . E . coli strains carrying pOW3 or R100 were up to 10,000-fold less sensitive to killing by serum complement than were plasmid-free bacteria or bacteria carrying pBR322 . Nucleotide sequencing revealed that 875 of the 1,900 bases from R100 correspond exactly to part of the bacterial insertion sequence IS2 . The remaining 1,075 bases contained only one sizeable open reading frame; it covered 729 base pairs (243 amino acids) and was preceded by nucleotide sequences characteristic of bacterial promoters and ribosome binding sites . The first 20 amino acids of the predicted protein showed features characteristic of a signal sequence . The remainder of the predicted protein showed an amino acid composition almost identical with that determined for the traT protein from the E . coli F factor . Southern blot analysis showed that the resistance gene from R100 does not hybridize to the serum resistance gene from ColV,I-K94 isolated by Binns et al.; we concluded that these genes are distinct. J Clin Pharmacol, 1982 Jul, 22(7), 297 - 300 Selecting drug combinations for treatment of drug-resistant mycobacterial diseases; Nash DR et al.; Mixtures of antituberculosis drugs were evaluated for their in vitro effects on drug-resistant isolates of Mycobacterium tuberculosis and M . avium-intracellulare . The response of individual isolates to representative drug combinations was not always predictable from the results of single-drug sensitivity assays . For the case of M . tuberculosis, combinations of drugs were often bactericidal even under conditions where two or more drugs were without effect when tested singly . The more widely drug-resistant M . avium-intracellulare demonstrated increased growth inhibition when subcultured in the presence of single drugs, particularly rifampin and streptomycin . However, these conditions favored the selection of highly resistant strains . Alternatively, multiple drugs were often bacteriostatic; and under conditions where isolates demonstrated growth inhibition, the selection of highly drug-resistant strains was delayed . These results suggest a role for multiple-drug sensitivity assays in selecting drug combinations to be used in the treatment of drug-resistant mycobacterioses. J Bacteriol, 1982 Jul, 151(1), 262 - 8 Bactericidal effect of 5-azacytidine on Escherichia coli carrying EcoRII restriction-modification enzymes; Friedman S; 5-Azacytidine was found to be bactericidal to Escherichia coli carrying plasmids specifying EcoRII restriction-modification systems, but not to the same strains lacking these plasmids . Of other base analogs tested, only 5(beta-D-ribofuranosyl)isocytidine had similar, although weaker, effects . Plasmids that had lost the EcoRII restriction-modification system did not confer sensitivity to 5-azacytidine . Mutants defective in the restriction function remained sensitive to the toxic effects of the drug; however, a mutant defective in the modification function lost most of the sensitivity to 5-azacytidine . For the bactericidal effect to be seen, the cells had to be growing; cells in the stationary phase of growth were not killed by the drug . The drug inhibited the methylase enzyme, and an inhibitor of the enzyme could be detected in vitro in extracts of cells that had been treated with 5-azacytidine . This nalidixic acid inhibited its formation . Coumermycin but not nalidixic acid antagonized the bactericidal effect of the drug; however, coumermycin was more effective in preventing the inhibition of the methylase by 5-azacytidine than was nalidixic acid. J Clin Immunol, 1982 Jul, 2(3), 237 - 41 Hidradenitis suppurativa: evidence for a bactericidal defect correctable by cholinergic agonist in vitro and in vivo; Ginder PA et al.; Hidradenitis suppurativa (HS) affects the apocrine sweat glands, giving chronic recurrent abscesses of axillary and perineal areas . We report a patient who had a defect in polymorphonuclear leukocyte killing of bacteria associated with low levels of intracellular cyclic GMP . This defect was corrected with a cholinergic agonist in vitro . Treatment of the patient with a cholinergic agonist, bethanechol chloride, resulted in prolonged clinical improvement, normal bactericidal function, and normal levels of intracellular cyclic GMP . The possible mechanisms responsible for the bactericidal defect and for the patient's improvement are discussed. S Afr Med J, 1982 Jun 5, 61(23), 867 - 70 Short-course chemotherapy for pulmonary tuberculosis . Points of interest; Zabow M et al.; A build-up of numbers of tuberculosis patients who default at an early stage from the ambulatory intensive short-course chemotherapy routinely practised in the Combined Health Scheme of the Divisional Council of the Cape is bringing to light the bactericidal power of a four-drug, rifampicin-containing regimen . Within the range of 40-80 daily doses, all is by no means lost if the patient defaults. Lab Invest, 1982 Jun, 46(6), 597 - 604 Characterization of rat polymorphonuclear leukocyte subcellular granules; Calamai EG et al.; The bactericidal subcellular granules of rat peritoneal neutrophils were studied to determine selected physical and biochemical characteristics . Isopycnic centrifugation of these granules resolved them into three subpopulations: specific granules (buoyant density = 1.176) as well as light and heavy azurophil granules (buoyant density = 1.20 and 1.22, respectively) . These buoyant densities corresponded closely to those of similarly isolated human granules . Specific granules of rat peritoneal neutrophil contained 68 per cent of the sedimentable alkaline phosphatase activity and part of the lysozyme of the whole rat peritoneal neutrophil . The light azurophil granules contained the remainder of the lysozyme, as well as a substantial portion of the beta-glucuronidase activity . Peroxidase was detected in both light and heavy azurophil granules, as was neutral protease . Morphologically, the rat specific granules were round or slightly ovoid organelles (0.10 to 0.13 micrometer in diameter) . The azurophil granules were larger (0.3 micrometer) ellipsoid as well as round in shape, and stained strongly for peroxidase . These granules were significantly smaller than the crystal-containing granules of eosinophils. Blood, 1982 Jun, 59(6), 1317 - 29 Human neutrophil-specific granule deficiency: a model to assess the role of neutrophil-specific granules in the evolution of the inflammatory response; Gallin JI et al.; It has been suggested that neutrophil (PMN) specific granules are important in cell aggregation, locomotion, hydroxyl radical formation, and in extracellular functions such as the generation of complement-related inflammatory mediators (C5a) and the feedback regulation of myelopoiesis . In the current studies, a 9-yr-old boy with a history of recurrent infections and specific granule deficiency (absent lactoferrin, B-12 binding proteins, and characteristic specific granules on sucrose gradient centrifugation of cell homogenates) was studied to assess some of these concepts . In vivo, the patient had decreased PMN and monocyte accumulation into Rebuck skin windows but an expected febrile episode with an associated neutropenia (PMN margination) and neutrophilia (mobilization of marrow reserves) in response to intravenous endotoxin . In vitro, the patient's resting PMN showed increased ruffling, increased surface-to-volume ratio, and increased numbers of centriole-associated microtubules . His PMN showed a significant decrease in cell negative surface charge (which may relate to aggregation) in response to several stimuli and adhered better than normally to plastic . In addition, his PMN aggregated normally in response to the chemoattractant f-met-leu-phe, although the subsequent disaggregation normally seen with PMN did not occur with the patient's cells . Chemotaxis of the patient's PMN to several stimuli was abnormal, and specific saturable and displaceable binding of the chemoattractant f-met-leu-{3H}phe was decreased . Similarly, following incubation with secretagogues, there was a less than normal increase in f-met-leu-{3H}phe binding and an absence of the normal increases in PMN surface area . The patient's PMN bactericidal activity, stimulated oxygen metabolism (cytochrome-c reduction, chemiluminescence, and NBT reduction), and elicited changes in membrane potential were also abnormal . Studies assessing the mechanism for the abnormal monocyte accumulation into skin windows indicated the patient's monocyte chemotaxis was better than normal in vitro . However, the patient's PMN homogenates lacked a stimulus of monocyte locomotion and did not generate chemotactic activity normally from serum . Thus, the data indicate that specific granule constituents are not required for neutrophil margination in vivo or aggregation in vitro . However, the data support the concept that PMN-specific granules are important for PMN locomotion and oxidative metabolism . In addition, extracellular release of specific granule constituents appears to be important for amplification of the initial and subsequent phases of the inflammatory response. Am J Clin Nutr, 1982 Jun, 35(6), 1430 - 6 Neutrophil functions during total parenteral nutrition and Intralipid infusion; Palmblad J et al.; Total parenteral nutrition (TPN) has been associated with an increased incidence of infection . To assess the hypothesis that TPN, and in particular one of its constituents, the rat emulsion Intralipid, might impair host defense, we investigated in vitro migration, bactericidal functions, and chemiluminescence of the neutrophil granulocyte in four patients with Crohn's disease, given TPN for up to 12 wk . No abnormal values were found during TPN, but both before and after, impaired migration was noted . Further, 10 volunteers were given 10% Intralipid (85 ml/h), and in blood samples obtained 2 h after discontinuation of the infusion, enhancements were recorded for migration stimulated with serum