Cancer, 1983 Dec 1, 52(11), 2001 - 6 Preradiation chemotherapy for newly diagnosed childhood brain tumors . A modified Phase II trial; Allen JC et al.; A poor-risk population of children with primary malignant central nervous system (CNS) tumors, other than gliomas, can be identified by their young age, by the presence of disease dissemination at diagnosis, and possibly by subtotal resection of the primary tumor . These children require at least neuraxis radiation therapy and possibly chemotherapy for disease control . Unfortunately, once neuraxis radiation is administered, tolerance of subsequent chemotherapy is limited . The authors have explored a multimodal treatment approach in 14 poor-risk patients initially consisting of a modified Phase II chemotherapy trial followed by neuraxis radiation . The diagnoses were medulloblastoma (5), pineoblastoma (3), cerebral primitive neuroectodermal tumor (3), germinoma (2), and choroid plexus carcinoma (1) . Eleven patients had disseminated CNS disease, and two had bone marrow involvement at diagnosis . Nine patients received 2 courses of intravenous cyclophosphamide (80 mg/kg) alone over 8 weeks, and five others received three daily doses of intrathecal Ara-C (50 mg/m2) and oral hydroxyurea (40 mg/kg) with each course of cyclophosphamide . There were four complete responses (two dysgerminomas, one pineoblastoma, and one primitive neuroectodermal tumor), one partial response (medulloblastoma), and three mixed responses (two medulloblastomas, one pineoblastoma) to chemotherapy alone, for a response rate of 57% . Twelve patients subsequently tolerated the planned dose of neuraxis radiation . The median survival of all patients was 11 months, and seven of eight deaths were related to recurrent disease . The hematologic toxicity was appreciable, and one death resulted from gram-negative septicemia . Through the use of this type of Phase II trial, valuable information can be obtained on the response rates to specific chemotherapy agents administered prior to radiation . Although cyclophosphamide alone was an active agent in this context, these treatment regimens did not have an important affect on survival. Clin Lab Med, 1983 Dec, 3(4), 719 - 44 Septicemia and lung injury; Brigham KL et al.; The results of investigations undertaken by the authors which deal with the functional and structural changes in the lungs resulting from gram-negative bacterial endotoxemia and the mechanisms of these changes are analyzed . The authors emphasize the major roles played by granulocytes and metabolites of arachidonic acid in mediating endotoxin-induced lung injury. Experientia, 1983 Nov 15, 39(11), 1271 - 3 Bacterial growth on 1,2-dichloroethane; Stucki G et al.; 1,2-Dichloroethane (5 mM) served as the only carbon and energy source for bacterium DE2, a gram-negative, oxidase-positive, motile rod . The specific growth rate mu of strain DE2 on 1,2-dichloroethane was 0.08 h-1 . A NAD-dependent 2-chloroacetaldehyde dehydrogenase activity and a 2-chloroacetate halidohydrolase activity were detected in extracts of cells grown on 1,2-dichloroethane. Z Hautkr, 1983 Nov 1, 58(21), 1539 - 41 {Volon A shake mix--a promising innovation}; Brinkmann W; Clinical testing of Volon A shake lotion (containing zinc oxide and corticosteroids) showed good results especially with regard to acute dermatoses and, as a surprise, in patients suffering from gram-negative infections of the feet. Endoscopy, 1983 Nov, 15(6), 350 - 2 Disinfection of gastrointestinal fibrescopes--evaluation of the disinfectants Dettox and Gigasept; O'Connor HJ et al.; The disinfectant solutions Dettox (based on a quaternary ammonium compound) and Gigasept (based on succine dialdehyde) were evaluated during disinfection procedures with a new disinfecting apparatus for gastrointestinal fibrescopes . Thorough disinfection was achieved after 2 minutes using Dettox 8% or Gigasept 10%; persistent fibrescope contamination with Gram-negative organisms was found after disinfection with Dettox 4% or Gigasep 5% . No adverse effects in endoscopy staff or damage to fibrescopes were seen . Adequate disinfection of endoscopic equipment prevents endoscopy-related infection and can be readily achieved by trained endoscopy staff using rapidly bactericidal disinfectants. J Cell Sci, 1983 Nov, 64, 137 - 46 Infection of macronuclear anlagen of Paramecium caudatum with the macronucleus-specific symbiont Holospora obtusa; Fujishima M et al.; The gram-negative bacterium Holospora obtusa is an endonuclear symbiont of Paramecium caudatum, which is incorporated into the host cells via the food vacuoles and infects their macronucleus exclusively, but never the micronucleus . Since these two kinds of nuclei originate from a fertilization nucleus, it is assumed that the macronucleus acquires a property necessary for it to be recognized by the bacterium at a certain time during the nuclear differentiation process . We found that this property is acquired by four of the eight postzygotic nuclei as soon as the four nuclei differentiate morphologically into the macronuclear anlagen. Isr J Med Sci, 1983 Nov, 19(11), 982 - 3 Necrotizing enterocolitis--a 5-year experience; Mogilner BM et al.; With the increased survival of very-low-birth-weight neonates, necrotizing enterocolitis (NEC) represents one of the most frequent life-threatening conditions for this population . NEC was diagnosed on 24 occasions during a 5-year period (1977-81) at the Neonatal Intensive Care Unit, Kaplan Hospital, Rehovot . These 24 NEC cases, confirmed by radiological, surgical or pathological findings, were analyzed in a retrospective study . The mean weight was 1,450 g and the mean gestational age 32 weeks . Only one of the affected infants was a full-term newborn . The mean age at onset of symptoms was 9.8 days . In one case, NEC developed before feedings were started . The infectious agents--most frequently gram-negative rods--were isolated from the most seriously ill babies . Cultures from blood and gastric aspirate were positive in 10 of the 12 fatal cases . No bacteria were isolated from the blood among the survivors . Rotavirus, the only viral particle detected, was diagnosed in the bloody stools of two of the infants who recovered completely . Prophylactic therapy with oral kanamycin, administered to all premature infants weighing less than 1,500 g born over a 3-year period, did not appear to have a preventive influence . The overall mortality was 50%, with no sequelae observed among survivors . The high incidence of positive cultures among fatal cases suggests that overwhelming infection played a fundamental role in the outcome. Antonie Van Leeuwenhoek, 1983 Nov, 49(4-5), 429 - 46 Agromonas oligotrophica gen . nov., sp . nov., a nitrogen-fixing oligotrophic bacterium; Ohta H et al.; Phenotypic and chemotaxonomic characteristics of five isolates of acetylene-reducing (nitrogen-fixing) oligotrophic bacteria from a paddy soil were investigated . They showed similar phenotypic characteristics: they were aerobic, asporogenous, gram-negative, motile by a polar flagellum, and irregular rods . On full strength nutrient broth (NB) growth was severely suppressed, but well supported on 10- to 10000-fold diluted NB . They consumed glucose but produced no acid, and also utilized phenolic acids such as ferulic acid or p-coumaric acid . The cellular fatty acid composition, quinone system and DNA base composition of the isolates were investigated . Cellular fatty acids mainly consisted of straight-chain unsaturated C18:1 (62-81% of total fatty acids) . Ubiquinone Q-10 and a high guanine-plus-cytosine content (65.1-66.0 mol%) were found . The taxonomic status of the isolates is discussed and a new genus, Agromonas, with a single species Agromonas oligotrophica sp . nov., is proposed for these isolates . The type strain of A . oligotrophica is JCM 1494. J Clin Microbiol, 1983 Nov, 18(5), 1262 - 3 Isolation of Branhamella catarrhalis from sputum and tracheal aspirate; Aitken JM et al.; Branhamella catarrhalis was suggested by the presence of gram-negative intracellular diplococci and confirmed by quantitative culture of the expectorated sputa of 11 patients with clinical evidence of lower respiratory tract infection . In quantitative culture, more than 20 colonies of B . catarrhalis were seen in each of the liquefied expectorated sputa at a dilution of 10(-7) . Transtracheal aspirations were then performed on these 11 patients, and B . catarrhalis was isolated from the lower respiratory tract secretions of 10 of the patients . Of the 10 isolates, 5 produced beta-lactamase . None of the isolates grew on modified Thayer-Martin medium . The presence of gram-negative intracellular diplococci and the growth of B . catarrhalis on quantitative culture of expectorated sputum reliably indicates the presence of B . catarrhalis in the lower respiratory tract. Arch Otolaryngol, 1983 Nov, 109(11), 772 - 3 Parotitis associated with Eikenella corrodens in a healthy adult; Bissell P et al.; Eikenella corrodens is a gram-negative, facultatively anaerobic rod that is part of the normal oral flora . Although its pathogenicity was uncertain until recently, E corrodens has been implicated in a variety of human infections, usually in mixed culture, and commonly in patients predisposed by virtue of trauma, malignant neoplasms, antecedent surgery, or parenteral drug abuse . Parotitis due to E corrodens occurred in a healthy 72-year-old woman . Therapy with high-dose intravenous oxacillin sodium had been without effect, but surgical drainage plus antibiotic therapy directed against E corrodens produced prompt resolution. Am J Dis Child, 1983 Nov, 137(11), 1055 - 6 Initial antibiotic treatment of purulent meningitis in infants 1 to 2 months of age; Enzenauer RW et al.; The bacterial cause of purulent meningitis in patients younger than 2 months of age was reviewed . Hemophilus influenzae was the most common organism isolated from infants 1 to 2 months of age . Gram-negative enteric organisms were not shown to cause meningitis in this age group in term infants without neonatal complications . Initial antibiotic therapy for infants in this age group should include ampicillin sodium and chloramphenicol sodium succinate. Proc Natl Acad Sci U S A, 1983 Nov, 80(22), 6829 - 33 Structural similarities between the development-specific protein S from a gram-negative bacterium, Myxococcus xanthus, and calmodulin; Inouye S et al.; During differentiation of Myxococcus xanthus, a large amount of protein S is produced and assembled on the surface of the myxospore by a process that specifically requires Ca2+ . The gene for protein S has been cloned, and two tandemly repeated homologous genes have been found to be within a short distance of each other in the M . xanthus chromosome . We determined the DNA sequence of 3,692 bp encompassing both genes and deduced the amino acid sequences of the two gene products . The gene 1 (upstream) product and the gene 2 (downstream) product show extensive amino acid sequence homology (88%) . However, from their structures, protein S was found to be produced from gene 2, indicating that gene 2 is specifically turned on during differentiation . The structure of protein S shows striking similarities with calmodulin: protein S is composed of four internally homologous domains . In particular, the first and the third domains, consisting of 38 residues each, show a high level of homology (79%), and the second and the fourth domains, consisting of 40 residues each, show homology of 65% . In the first and the third domains, there is a common sequence of nine residues, Glu (or Asp)-Asn-Asn-Thr-Ile-Ser-Ser-Val-Lys, which is highly homologous to one of the proposed Ca2+-binding sequences in bovine brain calmodulin, Asp-Gly-Asn-Gly-Thr-Ile-Thr-Thr-Lys. J Immunol, 1983 Nov, 131(5), 2595 - 600 Immunologic dysfunction during viral oncogenesis . I . Nonspecific immunosuppression caused by malignant rabbit fibroma virus; Strayer DS et al.; Malignant rabbit fibroma virus (MV) is a potent oncogenic poxvirus that produces a rapidly progressive syndrome of disseminated myxosarcoma, immunosuppression, and fatal gram-negative infection . MV is probably a recombinant between Shope fibroma virus (SFV) and rabbit myxoma virus, and is capable of preventing or aborting the in vitro proliferative responses of rabbit lymphocytes to B and T lymphocyte mitogens . Proliferative responses to sheep erythrocytes (SRBC) are similarly affected, although MV does not alter ongoing antibody responses to SRBC . Splenic lymphocytes from MV tumor-bearing rabbits suppress antibody and proliferative responses to SRBC when added to lymphocytes from SRBC-primed rabbits . Finally, lysates of cultured splenic lymphocytes from rabbits given MV suppress both proliferative and antibody-forming responses to SRBC . When MV is removed from these lysates by UV inactivation or by centrifugation, the suppressive activity remains . We therefore conclude that MV induces immunologic unresponsiveness in rabbits by at least two mechanisms . First, a direct suppressive effect of added virus on in vitro lymphocyte proliferation is seen . There is no effect in this situation if an antibody response is already in progress . Second, spleen cells exposed to MV in vivo produce one or more soluble factors capable of suppressing both proliferative and antibody responses of normal lymphocytes. Isr J Med Sci, 1983 Oct, 19(10), 894 - 6 Necrotizing enterocolitis associated with rotavirus infection; Mogilner BM et al.; Infection has been widely reported as one of the factors usually incriminated in the development of necrotizing enterocolitis (NEC) in a previously ischemic bowel . Gram-negative bacteria have previously been implicated as pathogens in this dangerous entity, for which neonates are at high risk . However, viral infections have rarely been reported in connection with NEC . Rotavirus was identified in the stools of two premature infants who developed the full-blown picture of NEC in the Neonatal Intensive Care Unit (NICU) at Kaplan Hospital, Rehovot . Both cases occurred within a period of 3 months, during the winter season . During that time, rotavirus was diagnosed in the stools of 10 other infants admitted to the NICU . The detection of rotavirus in the stools of the two premature infants with NEC observed by us strongly suggests that rotavirus should be included in the list of infectious agents associated with the development of NEC. J Wildl Dis, 1983 Oct, 19(4), 349 - 52 Chronic bacterial pneumonia in free-ranging Eastern box turtles (Terrapene carolina carolina); Evans RH; Chronic bacterial pneumonia was diagnosed in two free-ranging Eastern box turtles . Mucoid exudation into the upper respiratory tract and bilateral, caseating pneumonia were seen grossly . Microscopically, chronic, active inflammation with pseudomembrane formation occurred in the nasal sinuses and lungs while caseating granuloma-like structures were also observed in alveoli and associated infundibulae . Since viral, protozoal or fungal agents could neither be demonstrated in tissue sections by light or electronmicroscopy, nor could they be isolated in vitro, the gram-negative bacteria, seen in large numbers within the lesions and easily cultured in vitro, were considered the etiologic agents of this disease. J Am Vet Med Assoc, 1983 Oct 1, 183(7), 786 - 9 Bacterial endotoxin in blood of dysgalactic sows in relation to microbial status of uterus, milk, and intestine; Morkoc A et al.; Clinical cases of lactation failure in sows from 6 swine herds in Illinois were investigated for the presence of bacterial endotoxins in blood and the concurrent microbial status of uterus, milk, and intestine . Twenty-five affected sows were compared with 13 contemporary healthy sows (controls) in the same herds . A higher prevalence of bacterial endotoxin in blood of affected sows than in the controls, although not statistically significant, supported earlier theories of endotoxin involvement in the disease . Further, a positive relationship was noticed between prevalence of solely gram-negative bacteria in ileum and milk and development of dysgalactia and endotoxemia . No such relationship was found for bacterial isolates from the uterus, suggesting lack of association between lactation failure and metritis. Am J Dis Child, 1983 Oct, 137(10), 974 - 6 Septic arthritis caused by Kingella kingae; Powell JM et al.; Kingella kingae is a slow-growing, fastidious gram-negative coccobacillus that is a normal inhabitant of the oropharynx of man, but it has rarely been implicated as a human pathogen . Two cases of septic arthritis caused by this organism are reported along with a review of seven previously reported cases of infections caused by this organism . Bone and joint infections predominate . Gram's-stained smears of pus from bone or joint fluid aspirate have been negative for organisms, and a delay of growth in cultures with initial difficulty in classification of the isolate is characteristic . Kingella kingae organisms have been uniformly sensitive to the penicillins and all other commonly used antibiotics that were tested . Response to treatment was good in all nine patients found to have infections caused by this organism. J Periodontol, 1983 Oct, 54(10), 598 - 617 Scanning and transmission electron microscopic study of tissue-invading microorganisms in localized juvenile periodontitis; Carranza FA Jr et al.; This transmission and scanning electron microscope study documents the invasion of microorganisms into the gingiva and along resorbing alveolar bone surfaces in a 15-year-old patient with localized juvenile periodontitis . The invading bacteria were mainly Gram-negative fusiform, coccobacilli and spirochetes . Microorganisms identified as Mycoplasma were also found to invade in some areas . Polymorphonuclear neutrophils (PMNs) were seen in association with the bacteria . The majority of bacteria were covered by PMNs and enclosed by the phagocyte but did not appear to lie within phagosomes . High numbers of PMNs were found in the gingival connective tissue inflammatory infiltrate and in the pocket epithelium . Invasion into the gingiva and alveolar bone by bacteria and Mycoplasma in localized juvenile periodontitis may be importance in the therapy of this infection. Infect Immun, 1983 Oct, 42(1), 208 - 13 A type-specific antigen of Eikenella corrodens is the major outer membrane protein; Maliszewski CR et al.; Eikenella corrodens released antigenic material in the form of outer membrane fragments during growth . A culture filtrate antigen (AgA) from three strains reacted with antisera to whole bacteria with serotype specificity . A monoclonal antibody to the AgA of strain 1073 reacted with only 2 of 12 strains tested by enzyme-linked immunosorbent assay, immunofluorescence assay, and immunoelectrophoresis assay . The antigenic reactivity was resistant to boiling and to pronase and trypsin treatments . AgA was isolated from an outer membrane preparation after boiling in sodium dodecyl sulfate, radioiodinating the proteins, and precipitating AgA specifically with monoclonal antibody . A single protein band corresponding to the major outer membrane protein of E . corrodens was observed by autoradiography of sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the immunoprecipitate . AgA had a molecular weight of 42,000, and its amino acid content resembled those reported for major outer membrane proteins with similar molecular weights from two other gram-negative organisms. Gene, 1983 Oct, 24(2-3), 299 - 308 Stable cosmid vectors that enable the introduction of cloned fragments into a wide range of gram-negative bacteria; Frey J et al.; A cosmid cloning system has been developed which is useful for the construction of genomic libraries and the introduction of clones into a broad range of bacterial species . The cosmids pMMB33 and pMMB34 allow selective cloning into their unique BamHI site of 36-kb DNA fragments generated by BamHI, Sau3A and MboI partial digestion . This selective cloning is achieved by a strategy that avoids formation of polycosmids without a dephosphorylation step . It uses two unique recognition sites within the vectors for endoncleases that generate blunt-ended DNA fragments for the preparation of left and right cosmid "arms" . An alternative method that uses the unique EcoRI and SstI sites and dephosphorylation of the cosmid arms prior to BamHI digestion is also outlined and discussed . The DNA is first cloned with either vector into a rec- E . coli strain, where clones can be maintained stably, and can then be introduced by mobilization into a wide range of Gram-negative species to permit the study of gene expression and complementation . Because mobilization is much more efficient than transformation, the vector has the advantage that it can be transferred between bacterial species that specify different restriction systems, where transformation appears to be inefficient . The vectors have been used to generate gene libraries from the chromosomal DNA of several Pseudomonas and a Thiobacillus species . The genes specifying myo-inositol transport from Pseudomonas strain JD34 have been cloned with this system. Clin Exp Immunol, 1983 Oct, 54(1), 95 - 102 Human T cell proliferation in response to E . coli presented by autologous macrophages is antigen specific; Mannhalter JW et al.; Interactions of human T cells and macrophages/monocytes (MOs) following stimulation by a Gram negative micro-organism (E . coli) have been investigated . Immunoadsorption studies showed that the E . coli-induced proliferative response of human T cells was antigen specific . The T cell pool could be selectively depleted of E . coli reactive cells by short exposure to autologous E . coli pulsed Mos . This treatment did not remove T cell reactivity directed towards an unrelated antigen (tetanus toxoid) . This demonstrated the antigen specificity of the immunoadsorption step, which was further confirmed by reconstitution of E . coli reactivity after supplementing the adsorbed T cell pool with E . coli specific T cells . The Mo requirement for the E . coli-induced T cell response was confirmed and kinetic studies showed a dose-dependence with respect to the amount of E . coli used for both E . coli-induced T cell proliferation and the efficiency of immunoadsorption. Jpn J Antibiot, 1983 Sep, 36(9), 2431 - 6 {Clinical evaluation of latamoxef in the perinatal period}; Takase Z et al.; Latamoxef (LMOX), a new oxacephem antibiotic with high activity against Gram-negative bacteria has been investigated for use in No . of 58 mothers in perinatal period, and obtained following results . Concentration of LMOX in maternal serum was 43.4 micrograms/ml at the 1 hour after intravenous administration of 1 g . In umbilical cord serum and amniotic fluid, LMOX showed good translation after intravenous administration of 1 g into the mother, but no adverse effect appeared in the neonate . LMOX is highly useful antibiotic in perinatal infections, and the safe dose of LMOX to the mother in perinatal period is 1--2 g per day considerably. Z Naturforsch {C}, 1983 Sep-Oct, 38(9-10), 812 - 4 Immobilization of E . coli cell as an antigen by radiation polymerization method; Kaetsu I et al.; E . coli NIJ cells were immobilized by radiation polymerization of 2-hydroxyethyl methacrylate at low temperatures . The immobilized E . coli cells as an antigen were reacted with peroxidase labeled anti-E . coli in competition with the free E . coli cells . It was found that E . coli cells can be assayed quantitatively with the immobilized E . coli cells in disc form . Microorganisms such as gram negative bacteria had no specific affinity to anti-E . coli . Cross reactivity of the immobilized E . coli cells with the E . coli cells from various strains was examined. Rev Infect Dis, 1983 Sep-Oct, 5 Suppl 4, S733 - 47 Bacterial endotoxins and pathogenesis; Morrison DC; Recent advances in endotoxin biochemistry, cell biology, and immunopathology are reviewed . Discussion is focused on the endotoxin-unresponsive C3H/HeJ mouse and the contributions the studies of this mouse have made to current concepts of the mechanisms of endotoxin action . The extension of the observations documented with this experimental model provide a firm foundation for productive future research into the precise role of bacterial endotoxins in the protection against, and exacerbation of, gram-negative bacterial sepsis. Am J Med, 1983 Aug 29, 75(2A), 90 - 5 Systemic infections treated with amdinocillin in combination with other beta-lactam antibiotics; King JW et al.; Amdinocillin is a semisynthetic derivative of 6-beta-amidinopenicillanic acid, which has bactericidal activity against a broad spectrum of gram-negative bacteria . We report the results of a multicenter study evaluating the safety and efficacy of amdinocillin in combination with other beta-lactam antibiotics in the treatment of 120 serious gram-negative bacterial infections . Amdinocillin was safe and well tolerated and, in combination with other beta-lactam antibiotics, was effective in the treatment of a broad range of gram-negative bacterial infections . Therapy with amdinocillin and other beta-lactam antibiotics was often associated with a demonstrable synergistic effect . Thus, amdinocillin holds promise as an effective antibiotic with synergistic potential when used in combination with penicillins and cephalosporins. Am J Med, 1983 Aug 29, 75(2A), 106 - 12 Efficacy of amdinocillin and lack of nephrotoxicity when combined with a second beta-lactam antibiotic for therapy of serious gram-negative bacillary infections; Sattler FR et al.; Seventy-eight patients with serious gram-negative bacillary infections were assigned at random to receive either amdinocillin or an aminoglycoside . In addition, each patient was also given a broad-spectrum penicillin or cephalosporin antibiotic . The clinical response to treatment was comparable in the two groups . Cures were effected in 35 (92 percent) of 38 patients treated with amdinocillin and a beta-lactam antibiotic, compared with 37 (93 percent) of 40 patients who were treated with an aminoglycoside/beta-lactam combination . For the entire group, only five (7 percent) of the 75 infecting organisms were resistant in vitro to the treatment beta-lactam or amdinocillin combination, and similarly only two (3 percent) organisms were resistant to the treatment aminoglycoside (p = 0.44) . Although drug-related toxicity occurred with equal frequency in the two groups, six patients treated with an aminoglycoside experienced nephrotoxicity compared with none of the patients who received amdinocillin (p = 0.034) . Thus, amdinocillin plus a broad-spectrum beta-lactam antibiotic may provide suitable empiric therapy for many patients with presumed gram-negative infection and so avoid the risk of aminoglycoside-induced nephrotoxicity. Am J Obstet Gynecol, 1983 Aug 15, 146(8), 953 - 7 Pyelonephritis in pregnancy: a prospective randomized trial to prevent recurrent disease evaluating suppressive therapy with nitrofurantoin and close surveillance; Lenke RR et al.; It has been advocated that if a patient develops acute pyelonephritis during pregnancy, she should receive suppressive therapy for the remainder of the gestation to prevent a recurrence of the disease . We have prospectively evaluated 200 patients following an acute episode of pyelonephritis during pregnancy . All patients were followed in a special clinic . Half the patients received nitrofurantoin as suppressive therapy . Recurrent pyelonephritis occurred in 7% of the patients receiving suppressive therapy versus 8% of those patients receiving close surveillance in the clinic . The results cast doubt upon the need for suppressive therapy and instead dramatized the beneficial effects of close surveillance with cultures . The data also suggest, at least in a high-risk population, that patients with gram-negative bacilluria of less than 10(5) colonies/ml may have a substantial risk of developing symptomatic recurrences . Prompt treatment of even low levels of gram-negative bacilluria should be considered in patients at risk for recurrent disease. S Afr Med J, 1983 Aug 6, 64(6), 216 - 7 Ruptured abdominal aortic aneurysm associated with an aorto-enteric fistula . A case report; Du Toit DF et al.; A patient with a ruptured abdominal aortic aneurysm and a primary aortoduodenal fistula is reported on . Treatment included aneurysmectomy, suture of the duodenal fistula, closure of the proximal and distal abdominal aortic stumps, and construction of an axillobifemoral bypass . The postoperative course was complicated by spinal cord ischaemia and pataplegia, Gram-negative septicaemia, secondary intra-abdominal haemorrhage and multiple abscess formation. Nature, 1983 Aug 4-10, 304(5925), 449 - 51 The pyrogenic and mitogenic actions of interleukin-1 are related; Duff GW et al.; Our present understanding of the pathogenesis of fever is that host macrophages, following activation by an appropriate stimulus such as Gram-negative lipopolysaccharide (LPS) immune complexes, or primed lymphocytes in the presence of specific antigen, synthesize and release endogenous pyrogen (EP) . EP is carried in the blood circulation to the hypothalamic area of the brain where its action, involving a protein synthetic step, results in an increase of the level at which body temperature is maintained . Recently, it was shown that EP is very similar and possibly identical to another macrophage mediator previously called lymphocyte activating factor and now known as interleukin-1 (IL-1) which, in conjunction with lectin or specific antigen, induces clonal expansion of T lymphocytes . We show here that murine T-cell proliferation in response to IL-1 in vitro is greatly increased when the cells are exposed to a temperature typical of fever and that injection of the same IL-1 causes fever in mice . If this relationship exists in vivo, the resulting facilitation of a T-cell-dependent immune response may well confer survival value and contribute to the evolutionary conservation of fever--a phylogenetically ancient response to infection. Neurosurgery, 1983 Aug, 13(2), 167 - 9 Colonic complications of ventriculoperitoneal shunts; Abu-Dalu K et al.; Late perforation of the large bowel by the abdominal catheter of a ventriculoperitoneal (VP) shunt is extremely rare . Four of the five reported patients subsequently died . We report here three patients who presented with this complication and were treated successfully . Bowel perforation by a VP shunt catheter should be considered when a shunt infection is secondary to gram-negative enteric organisms . It can occur without evidence of peritonitis, and the abdominal catheter can be removed percutaneously, thus avoiding a laparotomy. Am J Surg, 1983 Aug, 146(2), 194 - 7 Fate of aortic graft removal; Martin-Paredero V et al.; Reoperation to remove an aortic graft was performed in 18 patients . The need for removal was infection in the majority . A changing flora was seen in aortic graft infection with gram-negative organisms predominating . Despite a standardized approach with total graft removal, aortic closure, and extraanatomic reconstruction, amputation and mortality rates remain unacceptably high . A new approach to this problem is needed, and further trials with autogenous reconstruction appear warranted. Jpn J Antibiot, 1983 Aug, 36(8), 2093 - 7 {Experimental and clinical studies of latamoxef in intestinal surgery}; Mori Y et al.; After the intravenous administration of 1.0 g of latamoxef (LMOX), the concentration of LMOX were determined in normal intestinal tissue and serum of 17 patients underwent surgery for intestinal problems, and the results obtained were as follows . At 60 approximately 150 minutes after administration, the levels of LMOX were 37.5 approximately 26.3 micrograms/ml in serum and 14.8 approximately 10.5 micrograms/g in normal intestinal tissues . This values were enough to inhibit the growth of Gram-negative bacteria caused for some postoperative wound infections . For intravenous administration of 1.0 g of LMOX just before operation, no wound infection was observed in 13 patients with large intestinal cancer and 4 patients with benign intestinal disease. Can J Microbiol, 1983 Aug, 29(8), 874 - 80 Morphological and physiological characteristics and lipopolysaccharide composition of N2-fixing (C2H2-reducing) root-associated Pseudomonas sp; Haahtela K et al.; A dinitrogen-fixing Pseudomonas sp . was isolated from the roots of the grass Deschampsia caespitosa . The motile organism, which had 4 to 10 polar flagella, was gram negative, obligately aerobic, oxidase positive, arginine dihydrolase positive, and fluorescent . To verify API20B, API20E, and Oxi-Ferm identifications, as well as results from standard microbiological tests and electron microscopic examinations, which all indicated the organism to be a Pseudomonas, we analyzed its lipopolysaccharide . The lipopolysaccharide contained neutral sugars, phosphorus, heptose, hexosamine, 2-keto-3-deoxyoctonate, and fatty acids, which were dodecanoic, 3-hydroxydecanoic, 2-hydroxydodecanoic, and 3-hydroxydodecanoic acids . Both the qualitative and quantitative compositions resembled known data of the genus Pseudomonas . Dinitrogen fixation, determined as C2H2 reduction in semisolid medium, was supported by several carbon sources including malate and glucose . The N2 fixation activity was decreased if the oxygen concentration of the gas phase was lowered to one-tenth of atmospheric concentration . The highest specific nitrogenase activity recorded was 954 nmol C2H4/mg bacterial protein per hour, which is about 30% of that noted for Azospirillum lipoferum used as reference. J Antibiot (Tokyo), 1983 Aug, 36(8), 1013 - 9 Cephalosporins . VI . Synthesis and structure-activity relationships of new 7 beta-{(Z)-2-alkoxyimino-2-(2-aminothiazol-4-yl)acetamido}cephalosporins with a tetraxolopyridazine at the 3-position; Alpegiani M et al.; The synthesis and in vitro activity of 7 beta-{(Z)-2-alkoxyimino- 2-(2-aminothiazol-4-yl) acetamido}cephalosporins with a tetrazolo{1,5-b}pyridazine at the 3-position are described . These cephalosporins showed excellent activity against Gram-negative bacteria, including beta-lactamase producing strains . The most interesting compound of the series was 7 beta-{(Z)-2-(2-aminothiazol-4-yl)-2-methoxyimino acetamido} -3-(8-carboxytetrazolo{1,5-b}pyridazin-6-yl)- thiomethyl-3-cephem-4-carboxylic acid (9, FCE 20485) because of its extraordinarily long half-life and marked in vivo activity. Resuscitation, 1983 Aug, 10(4), 283 - 90 Acute respiratory failure in patients with generalized peritonitis; Vincent JL et al.; The evolution of acute respiratory failure was studied in 27 patients with generalized peritonitis . The natural history of pulmonary failure indicates an incidence of 74% of atelectasis progressing to pneumonitis in the majority of patients . In 21 patients, similar aerobic microorganisms were recovered from the sputum and abdominal focus of infection . The emergence of gram negative pneumonia by the third day of onset of peritonitis appeared to add significantly to respiratory failure . In the management of respiratory failure, early use of positive and expiratory pressure with mechanical ventilation was associated with improvement or reversal of hypoxia . A high fatality (89%) was attributed to uncontrolled sepsis rather than to respiratory failure. J Infect Dis, 1983 Aug, 148(2), 316 - 21 A model system to demonstrate that beta-lactamase-associated antibiotic trapping could be a potential means of resistance; Gutmann L et al.; Addition of beta-lactamase to cultures of antibiotic-sensitive Escherichia coli protected the bacteria against lysis induced by either a hydrolyzable (cephalothin) or relatively nonhydrolyzable (ceftriaxone) cephalosporin . The later addition of a nonhydrolyzable, non-lysis-inducing beta-lactam antibiotic (oxacillin), which had a higher affinity for the beta-lactamase than ceftriaxone, allowed the reversal of the protection and the onset of lysis . These results suggest that trapping of the antibiotic by the enzyme, without significant hydrolysis, is a reversible process that may play a role in the resistance of some gram-negative bacteria to third-generation cephalosporins. J Immunol Methods, 1983 Jul 29, 61(3), 275 - 81 Removal of gram-negative endotoxin from solutions by affinity chromatography; Issekutz AC; Endotoxins liberated by gram-negative bacteria are frequent contaminants of aqueous and physiological solutions . Because of their potent biological effects in vivo and in vitro, it is often necessary to eliminate even minute quantities of endotoxin from such solutions . A process is described which exploits the high binding affinity of polymyxin B for the lipid A moiety of most endotoxins in order to remove endotoxins from solutions by chromatography on polymyxin B Sepharose 4B . This method was simple, very effective, resulting in essentially complete removal of several endotoxins from heavily contaminated solutions (1-10 micrograms/ml by Limulus amoebocyte lysate assay) and employed mild physiological conditions. Am J Med, 1983 Jul 28, 75(1B), 7 - 18 Pathophysiology of bacteremia; McCabe WR et al.; Despite the frequency and importance of both nosocomial and "community-acquired" bacteremia, definitive information concerning crucial pathophysiologic events in human bacteremia remains sparse . An extensive variety of clinical manifestations, such as fever, rigors, shock, altered circulatory dynamics, cutaneous manifestations changes in the coagulation, complement, and other mediator systems, and effects on the lungs, heart, kidney, liver, and other end organs, have been described, but it is difficult to determine the relative frequency of these events in bacteremia caused by different species . The extensive number of bacterial species capable of producing bacteremia and variations in the type of presentation, such as acute, asymptomatic, and chronic, even when bacteremia is produced by the same species, undoubtedly contribute to this difficulty and suggest that a variety of pathophysiologic mechanisms occur in various bacteremias . In contrast, the relative frequency of various manifestations and some pathophysiologic mechanisms have been better delineated in Gram-negative bacteremia . The development of bacteremia enhances the lethality of most types of localized infection and several studies have demonstrated a relation between the magnitude of bacteremia and the outcome of the disease . Among various pathophysiologic alterations, mechanisms involved in the production of fever have been delineated most clearly . Fever appears to reflect a "common pathway" with almost all infectious agents and results from release of endogenous pyrogen from phagocytic cells . Endogenous pyrogen regulates the thermostatic setting of the body through its effect on the anterior hypothalamus . Endogenous pyrogen seems identical with Interleukin 1 and exerts a variety of other biologic activities . An extensive number of bacterial components have been proposed as "effectors" and an equally large number of endogenous substances proposed as "mediators" of the pathophysiologic events in bacteremia . The importance of many of these effectors and mediators has been postulated largely on the basis of in vitro and animal studies . The lack of critical clinical studies hampers extrapolation of these experimental studies to human bacteremia . The development of more effective therapy for the complications of bacteremia, such as shock, will continue to be hampered until the mechanisms involved in the production of those pathophysiologic events that are crucial determinants of outcome have been delineated more precisely in human disease. Nature, 1983 Jul 21-27, 304(5923), 280 - 2 DNA sequences at the ends of transposon Tn5 required for transposition; Johnson RC et al.; Transposons are a class of genetic elements that can move from one site in a cell's genome to another independently of the cell's general recombination system . Little is known about the mechanism of transposition of compound transposons such as Tn5, but it is thought that a transposon-encoded protein (a transposase) must recognize the outer ends of the element and, together with host factors, catalyse the transfer of the internal DNA into a new site in a manner that may involve replication . It has previously been shown that the synthesis of an IS50R-encoded protein (protein 1) is an essential requirement for Tn5 transposition . Here we demonstrate that a structure containing only the outer 186 base pairs (bp) of both inverted repeats is capable of being efficiently complemented to transpose in Escherichia coli, provided IS50R is located close by on the same replicon . In addition, Bal31-generated deletions indicate that 16-18 bp of the outer end of IS50L are required for transposition . This 16-18-bp sequence contains the 8-9-bp small inverted repeat present at each end of IS50 plus a 9-bp sequence which is homologous to an interrelated sequence present in four copies in the chromosomal origin of replication in a variety of Gram-negative bacteria . This sequence organization suggests that the ends of Tn5 may function to provide a recognition site for the Tn5 transposase adjacent to a sequence recognized by the host replication system. Clin Pharmacol Ther, 1983 Jul, 34(1), 110 - 6 Tobramycin kinetics during continuous ambulatory peritoneal dialysis; Bunke CM et al.; To establish therapeutic guidelines for tobramycin use in patients receiving continuous ambulatory peritoneal dialysis (CAPD), we studied tobramycin single-dose kinetics in CAPD patients . Tobramycin was studied after a 1.5-mg/kg dose given either intravenously (TOB-IV) or intraperitoneally (TOB-IP) . TOB-IV provided a plasma concentration above 3 mg/l at 12 hr with a t 1/2 of 39.5 hr . When tobramycin was given intraperitoneally, 52% of the dose was absorbed; peak plasma concentrations were only 1.8 mg/l, and the t 1/2 was 35 hr . CAPD accounted for only 15% to 20% of total body clearance in both groups . The kinetic principle of superposition was used to predict plasma concentrations after repeated TOB-IP . A model using once-a-day dosing predicted that a loading dose of 4 mg/kg followed by 1.5 mg/kg would achieve steady-state plasma concentrations of 2.8 to 4.2 mg/l . Another model using tobramycin in each exchange predicted that a loading dose of 3 mg/kg followed by 0.3 mg/kg would provide steady-state plasma concentrations of 2.8 to 3.1 mg/l . These data should be useful in treating CAPD patients with tobramycin who have nonperitoneal gram-negative aerobic bacterial infections, as well as those who require the drug for peritonitis. Antimicrob Agents Chemother, 1983 Jul, 24(1), 15 - 7 Moxalactam concentrations in human prostatic tissue; Smith RP et al.; The concentrations of moxalactam in human prostatic tissue, obtained by enucleation or transurethral resection, were measured in 10 patients after the intramuscular administration of two 500-mg doses . The average concentrations of moxalactam in prostatic tissue in the enucleated and transurethral resection specimens were 4.0 micrograms/g and 5.2 micrograms/ml, and the ratios of the moxalactam concentrations in prostate to those in plasma were 0.24 and 0.31, respectively . The concentrations of moxalactam achieved in prostatic tissue after the administration of relatively low doses were greater than the minimum inhibitory concentrations of moxalactam for most common gram-negative pathogens . Concentrations of moxalactam in carefully obtained transurethral resection specimens were similar to those found in the enucleated specimens. Res Vet Sci, 1983 Jul, 35(1), 30 - 4 Clinical findings and pathological changes in Histophilus ovis infections of sheep; Webb RF; The Gram-negative pleomorphic bacterium Histophilus ovis was incriminated as the cause of natural cases of epididymitis in rams, polyarthritis in lambs, mastitis and abortion in ewes . Epididymitis was sporadic in occurrence, unilateral in distribution and varied from acute to chronic in degree . Polyarthritis affected recently born lambs and resulted in acute lameness and subsequent debility . Mastitis was rare in occurrence, unilateral in distribution, acute and gangrenous in type . Abortion was also rare and manifested by a specific haemorrhagic placentitis . These four conditions were reproduced experimentally . The clinical, pathological and histopathological changes associated with field and experimental cases are described. J Clin Pathol, 1983 Jul, 36(7), 793 - 7 Clinical application of a new nephelometric technique to measure complement activation; Vergani D et al.; A new nephelometric technique to measure C3d as an indicator of complement activation, is described . C3d is isolated at high concentration of polyethyleneglycol (PEG), incubated with commercially available anti-C3d antiserum at a final concentration of 2.5% PEG and then measured in a Behring Laser Nephelometer . In contrast to previously available techniques our assay detects the low concentrations of C3d present in all normal subjects, which result from the continuous C3 catabolism occurring in vivo . We have also measured C3d blood concentrations in a large number of patients with diseases associated with complement activation . Raised C3d concentrations were found in 68% of rheumatoid arthritis, 57% of primary biliary cirrhosis, 38% of chronic active hepatitis, 100% of Gram-negative bacteraemia and 100% of malaria . The nephelometric technique has proved to be sensitive, economical and fast, and could be adapted for routine determination of C3d blood concentrations to monitor disease activity and response to treatment. J Bacteriol, 1983 Jul, 155(1), 345 - 50 Isolation of the carotenoid-containing cell wall of three unicellular cyanobacteria; Resch CM et al.; A carotenoid-containing membrane fraction devoid of chlorophyll and phycobiliproteins was isolated from three unicellular cyanobacteria, Synechococcus sp., Synechococcus leopoliensis UTEX 625, and Anacystis nidulans R-2, by aqueous-phase separation, hydrophobic chromatography, and differential centrifugation . The presence of 2-keto-3-deoxyoctonate, muramic acid, and diaminopimelic acid suggests that the preparation is highly enriched in cell wall . Electron micrographs of thin sections of this material showed C-shaped membrane profiles similar to those seen in other gram-negative cell wall preparations . The inactivation of cyanophage AS-1 by this fraction confirmed its identity as cell wall . The cell wall contained approximately equal weights of total carbohydrate and protein . Absorption maxima at 434, 452, and 488 nm indicated the presence of carotenoids . These were in the outer membrane and were not due to contaminating cytoplasmic or thylakoid membranes . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the preparations showed a broad band of approximately 50,000 molecular weight which contained 35% of the total outer membrane protein . This band was resolved into at least two components running at approximately 50,000 and 52,000 molecular weight . The smaller of these polypeptides was a glycoprotein . The polypeptide components were unaffected by protease or detergent treatment in either whole cells or isolated cell wall preparations, indicating that the polypeptide components were not exposed to the surface or easily removed from the hydrophobic environment. Gastroenterology, 1983 Jul, 85(1), 186 - 9 Transient agranulocytosis associated with non-A, non-B hepatitis; Vande Stouwe RA et al.; A 44-yr-old woman with non-A, non-B hepatitis developed agranulocytosis and absence of marrow granulocyte precursor cells with only mild involvement of other blood elements . The agranulocytosis was complicated by gram-negative septicemia, successfully treated with antibiotic therapy . Marrow recovery followed 2 wk of supportive therapy . Before reversal of the agranulocytosis, a future bone marrow transplant was a consideration, making the use of therapeutic granulocyte transfusions, with their ability to sensitize the recipient, potentially harmful . Experience in this case indicates that agranulocytosis associated with non-A, non-B hepatitis may be reversible, and supports the use of supportive care including appropriate antibiotics, and if necessary, granulocyte transfusions, pending marrow recovery. Neurochirurgia (Stuttg) . 1983 Jul;26(4):125. Treatment of Gram negative meningitis with cefotaxime; Glauser MP et al.; The authors report on the successful cefotaxime treatment (one of the newer cephalosporins) of K . pneumoniae meningitis which developed while the patient was under treatment with an older cefalosporin, cephalothin. Res Vet Sci, 1983 Jul, 35(1), 25 - 9 Bacteriological characteristics of Histophilus ovis and its relationship to similar bacteria; Webb RF; Seventeen strains of Histophilus ovis were obtained from a variety of pathological conditions and geographical areas and were examined to determine the bacteriological characteristics of the organism . All were Gram-negative pleomorphic rods which only grew under micro-aerophilic conditions in media enriched with blood, serum or meat particles . All strains were catalase negative, indole positive and nitrate positive while most produced acid from glucose, fructose, galactose, mannose, xylose, mannitol and sorbitol . Eight strains were examined serologically and compared with two strains of Actinobacillus seminis . In agglutination and precipitation tests, all strains of H ovis appeared antigenically identical and showed antigenic relationships to A seminis . Results of complement fixation tests confirmed the close, if not identical, antigenic relationship of H ovis and A seminis . It is suggested that H ovis and A seminis are biochemical variants of the same organism. Science, 1983 Jun 17, 220(4603), 1279 - 81 The genus-specific antigen of Chlamydia: resemblance to the lipopolysaccharide of enteric bacteria; Nurminen M et al.; A strong immunological cross-reaction between a major glycolipid antigen of Chlamydia and the innermost (Re) core of the lipopolysaccharide of enteric bacteria was demonstrated with the aid of mutants in which the Re structure is exposed . The chlamydial glycolipid resembled the Re lipopolysaccharide in molecular size, solubility, and endotoxic properties and may thus be functionally equivalent to lipopolysaccharide, an essential and characteristic component of the outer membrane of Gram-negative bacteria. Can Med Assoc J, 1983 Jun 15, 128(12), 1411 - 4 Pneumonia in renal transplant patients; Bowie DM et al.; Between January 1976 and March 1982, 28 episodes of pneumonia occurred in 26 renal transplant patients . The overall mortality rate was 46% . Of the 16 patients with nosocomial pneumonia 9 (56%) died, whereas of the 12 patients with community-acquired pneumonia 4 (33%) died . In all 9 cases of unknown cause the response to empiric treatment was prompt, whereas in 4 of the 10 cases of monomicrobial pneumonia and 8 of the 9 cases of polymicrobial pneumonia the patient died . Cytomegalovirus was the sole cause of the pneumonia in two patients and a contributing cause, along with aerobic gram-negative bacteria, in another five, four of whom also had a fungal infection . Two patients, both of whom survived, had nosocomial Legionnaires' disease. Nature, 1983 Jun 9-15, 303(5917), 526 - 8 Sensitization of Gram-negative bacteria to antibiotics and complement by a nontoxic oligopeptide; Vaara M et al.; A major virulence factor of bacteria that cause generalized infections is their resistance to the lytic action of the complement cascade, an important defence mechanism of the host . Invasive Gram-negative enteric bacteria, which cause about one-third of all bacteraemic infections, are completely resistant to lysis by complement, even in the presence of hyperimmune serum . The same bacteria are also resistant to many antibiotics that are effective therapeutic agents against other bacteria, as the outermost surface layer (the outer membrane) of the bacteria functions as a permeability barrier . Here we show that it is possible to sensitize such bacteria to both complement and antibiotics by using an agent that binds to the outer membrane . This agent is a nontoxic derivative of polymyxin which by itself has no bactericidal action. Southeast Asian J Trop Med Public Health, 1983 Jun, 14(2), 199 - 203 Heavy metal and disinfectant resistance in clinical isolates of gram-negative rods; Khor SY et al.; Ninety-five clinical strains of Gram-negative bacteria were examined for resistance to mercury, silver and disinfectants . 41% of the strains possessed resistance to mercury, 21% to silver and 7.3% of the strains were resistant to chlorhexidine . Mercury resistance was shown to be plasmid-mediated in 17 strains and silver resistance in 10 strains . Chlorhexidine resistance was not shown to be transferable. NIPH Ann, 1983 Jun, 6(1), 23 - 35 External quality assessment for clinical microbiological laboratories in Norway 1982 . 1 . Evaluation of the identifications of 24 bacterial strains; Lassen J et al.; The first general external quality assessment (EQA) for clinical microbiological laboratories in Norway was carried out in 1982 . Fifteen of 16 county and regional laboratories participated . Twenty-four pure cultures of different bacterial species were distributed by post . The distribution was "open" in the sense that the participants were aware of the cultures being part of the assessment . The strains had to be treated as routine clinical specimens . The bacterial identifications, the identification methods and the antibiotic sensitivity pattern had to be reported . The mean number of erroneous identifications was 2.7 (11.3%) . Eleven strains were correctly identified by all laboratories, whereas four strains were misidentified by four to seven laboratories, accounting for approximately 50% of all misidentifications . All laboratories used "rapid" biochemical methods when identifying Gram-negative rods, mainly the "Three-tube method" and API 20E . Five laboratories used only one method, 10 used a combination of two or three methods . The use of more than one method did not give any substantial advantage . The accuracy of the "rapid" biochemical methods was approximately 88%, contrasting to approximately 96-98% when scientifically evaluated . The necessity of developing a permanent EQA scheme for microbiological laboratories is emphasized and a possible design for this is discussed. J Immunogenet, 1983 Jun, 10(3), 237 - 50 Immune responses to hapten-lipopolysaccharide conjugates in mice . III . Genetics of the antibody response to polysaccharide antigens; Skelly RR et al.; Antibody responses to the polysaccharide antigens of bacterial lipopolysaccharides and their hapten derivatives are herein documented to be under multigenic control . Among the genes responsible for the antibody response to these polysaccharide antigens include those coded for by genes located on the X chromosome and those on chromosome 17 linked to genes in the H-2 and/or Qa loci . The use of B10 congenic mice revealed that two genes on chromosome 17 are involved in the regulation of the antibody response to bacterial polysaccharide antigens . The use of CXB recombinant inbred mice confirmed the multigenic control of the antibody response within their background array of genes . The data clearly demonstrate that immune responses to these polysaccharide antigens are under genetic control, the importance of which may be of significance with regard to humoral protection during gram-negative infection. J Reticuloendothel Soc, 1983 Jun, 33(6), 477 - 83 Endotoxin fails to induce procoagulant in C3H/HeJ exudate macrophages; Shands JW Jr; Monocytes and macrophages from a variety of animal species produce procoagulants upon stimulation with endotoxin in vitro . While C3H/HeJ mice and their cells have exhibited refractoriness to known effects of phenol-water extracted endotoxin, two recent reports indicate that the cells of these mice produce procoagulants in a normal manner in response to endotoxin . This study compares the responsiveness of cells of C3H/HeJ and C3H/HeN mice to phenol-water extracted endotoxin and to disrupted gram-negative cell walls . Phenol-water extracted endotoxin had no mitogenic effect on spleen cells and failed to elicit procoagulant synthesis in exudate macrophages from C3H/HeJ mice . In contrast it was an effective stimulant for spleen cells and exudate macrophages of C3H/HeN mice . Gram-negative cell walls were an effective stimulant for spleen cells and macrophages from both mouse strains . I conclude that exudate macrophages of C3H/HeJ mice do not respond to endotoxin by producing procoagulant. Am J Med Technol, 1983 Jun, 49(6), 437 - 41 Serum aminoglycoside monitoring by enzyme immunoassay, biological, and fluorescence immunoassay procedures; Buchanan AG et al.; Aerobic gram-negative infections are treated with aminoglycosides, but it is difficult to achieve safe yet effective dosages in individual patients using a standard dosing formula . Serum aminoglycoside levels are monitored to determine dosage adjustments . We compared enzyme immunoassay, bioassay, and fluorescence immunoassay procedures for measuring gentamicin and tobramycin levels in patients' sera, and in pooled human sera containing added gentamicin and tobramycin . The enzyme immunoassay procedure provided the most acceptable method for monitoring serum aminoglycoside levels on the bases of precision, cost, and turnaround time. Antimicrob Agents Chemother, 1983 Jun, 23(6), 827 - 30 Pharmacokinetics of amdinocillin in healthy adults; Meyers BR et al.; The pharmacokinetics of amdinocillin (mecillinam) were determined in 10 healthy volunteers . Single doses of 10 and 15 mg/kg of body weight were administered intravenously and intramuscularly in a crossover study . Plasma concentrations of amdinocillin were determined by microbiological assay . Mean peak plasma concentrations were 49 and 87 micrograms/ml after intravenous doses of 10 and 15 mg/kg, respectively . The terminal half-life value of 0.89 h was similar for both doses . After intramuscular injections, the mean concentration of drug in plasma was 26.2 micrograms/ml for the 10-mg/kg dose and 29.6 micrograms/ml for the 15-mg/kg dose, with terminal half-lives of 0.96 and 0.86 h, respectively . The mean apparent volumes of distribution at steady state were 18 and 16 liters/100 kg for the intravenous doses of 10 and 15 mg/kg, respectively . Drug concentrations in plasma at 4 h were above the minimal inhibitory concentrations for gram-negative organisms categorized as susceptible to this drug. Proc Natl Acad Sci U S A, 1983 Jun, 80(12), 3595 - 8 Location and nucleotide sequence of the transfer origin of the broad host range plasmid RK2; Guiney DG et al.; The origin of plasmid DNA transfer, oriT, has been localized on RK2, a conjugative drug-resistance plasmid of the IncP group with a very broad host range in gram-negative bacteria . The transfer origin is contained in a 760-base-pair Hae II restriction fragment that maps in the same region as the single-strand nick made by the RK2 relaxation complex . The functional oriT was subcloned as a 112-base-pair Hpa II fragment, and the DNA sequence of this region was determined . The dominant structural feature of the oriT sequence is a 19-base-pair inverted repeat, with 15 of the 19 bases able to form pairs in a hairpin structure . This inverted repeat may be the recognition site for the relaxation complex proteins, which nick the plasmid DNA molecule and initiate the transfer process. Bioorg Khim, 1983 Jun, 9(6), 725 - 33 {Lipopolysaccharide-protein complexes of the outer membrane of gram-negative bacteria}; Solov'eva TF et al.; The evidence for occurring lipopolysaccharide-protein complexes in the outer membrane of gram-negative bacteria has been summarized . The composition and supramolecular structure of these complexes as well as their functions in microbial envelope and substantial role in membrane organization have been discussed . The biological properties of the complexes as endotoxins and O-specific antigens have been considered. Hepatogastroenterology, 1983 Jun, 30(3), 79 - 82 The relationship between endotoxin and the phagocytic activity of the reticuloendothelial system; Kuratsune H et al.; The frequency of endogenous endotoxemia caused by gram-negative bacteria in the intestine of patients with liver cirrhosis, is attracting much attention in the clinical study of endotoxin . To clarify the reason for such high frequency, the indices of the phagocytic activity of reticuloendothelial system (RES), alpha 2-macroglobulin (alpha 2-M) and endotoxin were studied in patients with chronic liver disease, and in normal controls . In the case of liver cirrhosis, the phagocytic activity of RES (K value) was markedly diminished, and a negative correlation between the K value and alpha 2-M was recognized in endotoxemia . These results suggest that endotoxemia in liver cirrhosis is based on spillover of endotoxins from portal flow. J Biol Chem, 1983 May 25, 258(10), 6524 - 9 Solubilization, isolation, and immunochemical characterization of the major outer membrane protein from Rhodopseudomonas sphaeroides; Deal CD et al.; Solubilization of the major outer membrane protein of Rhodopseudomonas sphaeroides, and subsequent isolation, has been achieved by both non-detergent- and detergent-based methods . The protein was differentially solubilized from other outer membrane proteins in 5 M guanidine thiocyanate which was exchanged by dialysis for 7 M urea . The urea-soluble protein was purified to homogeneity by a combination of DEAE-Sephadex chromatography and preparative electrophoretic techniques . Similar to the peptidoglycan-associated proteins of other Gram-negative bacteria, the protein was also purified by differential temperature extraction of the outer membrane in the presence of sodium dodecyl sulfate (SDS) followed by preparative SDS-polyacrylamide gel electrophoresis . Immunochemical analysis of the proteins isolated by the two techniques established the immunochemical identity and homogeneity of each preparation . Immunoblots of SDS-polyacrylamide gels revealed that antibody directed against the major outer membrane protein reacted with the three high molecular weight aggregates present in the outer membrane which we have previously shown to be composed of the major outer membrane protein and three nonidentical small molecular weight proteins. Lancet, 1983 May 21, 1(8334), 1123 - 6 Randomised, controlled trial of the comparative efficacy, auditory toxicity, and nephrotoxicity of tobramycin and netilmicin; Lerner AM et al.; 254 patients with serious gram-negative bacillary infections were enrolled into a multicentre, randomised, blind clinical trial and treated with tobramycin-ticarcillin or netilmicin-ticarcillin . The two treatment groups were similar as to sex, age, and weight . The mean daily dose of netilmicin (237 mg) was higher than that of tobramycin (211 mg), p less than 0.01, but the mean duration of therapy was longer with tobramycin (9.4 days versus 8.7 days), p less than 0.01 . The netilmicin cohort also had more serious underlying diseases, p less than 0.028 . Clinical (tobramycin, 93% and netilmicin, 91%) and bacteriological responses (tobramycin, 87% and netilmicin, 89%) were similar . 84 tobramycin and 73 netilmicin patients had serial audiograms . Eighth nerve deficits developed in 10 (12%) tobramycin and two (3%) netilmicin patients, p = 0.037 . Drug-related renal dysfunction developed in 5 (4%) of 114 tobramycin patients whose renal function was monitored and in 1 (1%) of 116 netilmicin patients, p = 0.12. Carbohydr Res, 1983 May 16, 116(1), 31 - 7 {Synthesis of a disaccharide with antibiotic activity}; Lockhoff O et al.; The aminodisaccharide glycoside methyl 2,4-diamino-2,4-dideoxy-6-O-(2,6-diamino-2,6-dideoxy-alpha-D-glucopyranosyl)- beta-D-glucopyranoside (4), which exhibits a structural resemblance to neamine, was synthesized via the azido method . Starting from 6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl bromide, the alpha-D-glycosylation of O-6 of methyl 2,4-diazido-3-O-benzyl-2,4-dideoxy-beta-D-glucopyranoside was accomplished stereoselectively at low temperatures in the presence of mercury bromide . Against some gram-negative test-organisms, the activity of 4 was found to be in the same range as neamine, but directed against different germs. Schweiz Med Wochenschr, 1983 May 14, 113(19), 701 - 8 {Causes of death in cases of lymphoma, myeloma and Hodgkin disease . Study of 218 cases}; Trono D et al.; An autopsy study of 218 cases of lymphoproliferative disease was performed to establish the cause of death . It covered 144 cases of malignant nonHodgkin's lymphoma, 23 cases of Hodgkin's disease and 51 cases of myeloma . It was established that infection is by far the most frequent cause (34% of cases) followed by tumor invasion (11.5% of cases), hemorrhage (9% of cases) and other pathologies linked to the basic process (10% of cases) . The proportion of patients who die from intercurrent illness is still considerable (62 cases, 28%) . Infection is most often pulmonary or systemic; gram-negative bacteria play a predominant role . Toxicity of treatment is obvious in causing neutropenia and thrombocytopenia among other side effects with fatal consequences. Minerva Med, 1983 May 12, 74(20), 1187 - 90 {Possibilities and current technics of dialysis in leptospirosis with severe renal damage}; Fiori GP et al.; Three patients with severe liver and renal failure admitted to the Infectious Diseases Department of the Alessandria for suspected leptospirosis in the second half of 1979 are presented . In one case, the agent responsible was Leptospira icterohaemorrhagiae AB Wjnberg strain, in another Gram-negative sepsis, and in the third acute pancreatitis associated with serious Escherichia coli infection . An account is given of the peritoneal dialysis technique that led to successful resolution of the serious liver and renal failure. Pediatr Infect Dis, 1983 May-Jun, 2(3), 187 - 92 Significance of viral infections in severe combined immunodeficiency disease; Jarvis WR et al.; An analysis of a prospective study of viral infections in 12 patients with severe combined immunodeficiency is presented . Infections of viral etiology were common, with pulmonary and gastrointestinal infections being most frequent . Fourteen of 25 infections (56%) were nonsocomially acquired and 10 of 25 (40%) were community-acquired . The period of symptomatology and the duration of viral excretion were usually prolonged beyond those associated with disease in the general pediatric population . Pulmonary infections were associated with considerable morbidity and mortality . Gastrointestinal infections disrupted gastrointestinal function and possibly played a role in enteric Gram-negative bacillary sepsis . The inability of these patients to eradicate these viruses in the absence of immunologic reconstitution resulted in significant morbidity, often with a fatal outcome. Am J Med, 1983 May, 74(5), 902 - 4 Osteomyelitis caused by Veillonella; Barnhart RA et al.; Veillonella parvula and alcalescens are anaerobic gram-negative cocci that, when isolated from anaerobic cultures of clinical specimens, are usually regarded as commensal organisms . Occasionally they play a pathogenic role and require antibiotic therapy . Limited clinical experience and in vitro susceptibility studies suggest that penicillin G is the drug of choice for these organisms and that cephalosporins, clindamycin, chloramphenicol, and metronidazole may be acceptable therapeutic alternatives . Presented herein is a case report of a Veillonella infection, a discussion of the importance of these organisms when they occur in a clinical infection, and a discussion of the appropriate antibiotic therapy. Antimicrob Agents Chemother, 1983 May, 23(5), 738 - 41 Effects of penicillinase on bactericidal and complement activities in normal human serum; Biggs WH 3rd et al.; During routine addition of penicillinase (beta-lactamase) to patients sera, we found that the capacity of some of these sera to kill serum-sensitive gram-negative organisms was significantly decreased . Further controlled studies showed that penicillinase decreased both the bactericidal activity of normal human sera and the total hemolytic activity (CH50) of complement in these sera . The decreased bactericidal activity correlated significantly (r = 0.57, P less than 0.05) with the reduction of CH50 in eight normal sera . These effects of penicillinase were time and temperature dependent . Measurement of individual complement component activities showed that penicillinase decreased the activity of C2, C4, and C3-C9, suggesting that the penicillinase preparation activated the classical pathway . These results cast doubts on the validity of bactericidal determinations when sera are pretreated with penicillinase. AJNR Am J Neuroradiol, 1983 May-Jun, 4(3), 822 - 5 Bacterial meningitis in infants: sonographic features; Rosenberg HK et al.; Twenty-three infants with clinically proven bacterial meningitis were studied with real-time cranial sonography at the time of initial diagnosis and in several cases subsequently . A spectrum of sonographic abnormalities was observed, including bright convolutional markings, focal or diffuse increased and/or decreased parenchymal echoes, ventricular debris, and hydrocephalus . In three infants with virulent Gram-negative meningitis serial sonographic studies showed the development of encephalomalacia . Because clinical neurologic assessment of the infant is limited, a diagnostic imaging method that is sensitive to early structural change and suitable for serial observations is advantageous . Transfontanelle real-time sonographic examination of the brain was found to be a reliable, informative, and relatively inexpensive method of documenting and monitoring complicated bacterial meningitis. AJNR Am J Neuroradiol, 1983 May-Jun, 4(3), 461 - 5 Periventricular white-matter cysts in a murine model of gram-negative ventriculitis; Naidich TP et al.; Hydrocephalic patients with shunt infections frequently develop multiple cerebrospinal-fluid-density cysts that cause midline shift and life-threatening intracranial hypertension and respond poorly, if at all, to shunt diversion of cerebrospinal fluid . These cysts have been considered to represent multiloculation of the ventricular system by ependymal adhesions and veils resulting from ventriculitis . Studies using an experimental model of E . coli meningitis/ventriculitis in the hy-3 mouse suggest these cysts: (1) develop by the coalescence of lakes of white-matter edema, (2) grow to large size entirely within the periventricular white matter, and (3) cause pseudoloculation of the ventricle by compression from without . The so-called intraventricular septa or "veils" are the ependyma displaced inward by subependymal cysts or sheets of residual pericystic white matter . This finding permits better interpretation of computed tomographic images depicting persistent enlargement of the so-called multiloculations despite functioning ventricular shunt catheters, the multiplicity of cysts, and the white-matter location of these cysts. Appl Environ Microbiol, 1983 May, 45(5), 1501 - 5 Levels of gram-negative bacteria, Aspergillus fumigatus, dust, and endotoxin at compost plants; Clark CS et al.; Airborne gram-negative bacteria, endotoxins, dust, and Aspergillus fumigatus were measured in four compost plants in Sweden . At sites where material was processed, the number of airborne A . fumigatus exceeded 10(6)/m3, whereas the number of gram-negative bacteria was usually lower . Dust levels were moderate, and endotoxin levels were well below 0.5 micrograms/m3 . Medical studies to evaluate the effects of this type of microbial exposure are recommended. Infect Immun, 1983 May, 40(2), 847 - 9 Persistence of associated gram-negative bacteria in experimental actinomycotic lesions in mice; Jordan HV et al.; Mixed actinomycotic infections were established in a susceptible weanling mouse model by using combinations of Actinomyces israelii and Eikenella corrodens or A . israelii and Actinobacillus actinomycetemcomitans . Acute lesions caused by either of the gram-negative organisms alone were resolved within a few weeks; however, these organisms persisted up to 3 months in chronic lesions in combination with A . israelii. Arch Surg, 1983 May, 118(5), 636 - 41 Fluorophotometric evaluation of capillary permeability in gram-negative shock; Tom WW et al.; We developed a new method by which capillary permeability changes secondary to gram-negative sepsis can be easily monitored . In a preliminary trial, ten dogs were injected intravenously with live Escherichia coli . Progressive extravasation of fluorescein from the retinal capillary bed was demonstrated by retinal angiography, thus indicating "capillary leak." In a subsequent trial, fluorophotometry facilitated direct quantitation of this leak . Three control and three septic dogs underwent continuous hemodynamic and physiologic monitoring . Hourly retinal fluorophotometric measurements were recorded . The control group demonstrated no capillary leak nor any change in hemodynamic and physiologic status . In the septic group, there was a dramatic increase in extravascular fluorescein concentration two to four hours after E coli infusion, correlating well with hemodynamic and physiologic parameters typical of gram-negative shock. Antibiotiki, 1983 Apr, 28(4), 282 - 5 {R plasmid distribution in S . typhi isolated on the territory of the left coast of the Ukraine in 1970-1982}; Morozova NS et al.; A total of 373 strains of S . typhi isolated in 1970-1982 were tested with respect to their sensitivity to 9 antibiotics active against gram-negative bacteria . It was shown that about 1/3 of the isolates were resistant to 1-3 antibiotics . Among the resistant isolates the number of strains resistant to 4-5 and more antibiotics amounted to 12.5 per cent . The plasmid nature of the antibiotic resistance in the isolated strains of S . typhi was shown . Transmissive R plasmids were detected in 13 per cent of the strains studied . Within the last 5 years there was an increase in the proportion of strains with transmissive R plasmids in patients with sporadic typhoid fever or especially in groups of patients with the disease. J Bacteriol, 1983 Apr, 154(1), 113 - 7 Phthalate pathway of phenanthrene metabolism: formation of 2'-carboxybenzalpyruvate; Barnsley EA; The metabolism of phenanthrene by a gram-negative organism able to use this compound as a sole source of carbon and energy has been examined . 1-Hydroxy-2-naphthoic acid was oxidized by oxygen in a reaction catalyzed by a dioxygenase which was activated by ferrous ions . The stoichiometry of the oxidation and the UV spectrum of the product were consistent with the identification of the product as 2'-carboxybenzalpyruvate . This was confirmed by cleaving the product with a partially purified aldolase to yield 2-carboxybenzaldehyde and pyruvate . A number of enzymes for the metabolism of 1-hydroxy-2-naphthoic acid were induced by growth on phthalate or (less well) by growth on protocatechuate . The latter supported only a slow rate of growth, and this and poor induction may have been due to a slow rate of entry into the cell. Am J Orthod, 1983 Apr, 83(4), 290 - 8 Adjunctive orthodontic therapy in the treatment of juvenile periodontitis: report of a case and review of the literature; McLain JB et al.; Historically, the patient with juvenile periodontitis (periodontosis) presented as somewhat of an unknown entity to the orthodontist . With uncertainties concerning etiology still present, the orthodontist may be hesitant to undertake orthodontic treatment for the juvenile periodontitis patient . The literature pertaining to proposed etiologic factors and treatment modalities for juvenile periodontitis is briefly reviewed . Current evidence indicates that juvenile periodontitis patients have a compromised host response which allows an exaggerated susceptibility to certain gram-negative organisms . The disease is characterized by rapidly progressing bone loss, which is not associated with marked local irritation or gingival inflammation . Early diagnosis and conservative periodontal treatment have demonstrated good results . However, cases of advanced lesions or those cases that also involve malocclusion and potential occlusal traumatism may benefit from adjunctive orthodontic therapy . Successful management of a case involving multiple tooth loss along with a moderate degree of malocclusion is presented, with emphasis on the coordination of periodontic, orthodontic, and prosthodontic care . Orthodontic movement of teeth into previously affected areas was quite successful after a short healing period following extractions . A suggested protocol for the combined orthodontic, periodontic, and fixed prosthodontic management of the juvenile periodontitis patient is presented . Once the disease process has been arrested, the prognosis of each tooth is evaluated and possible rehabilitations, including orthodontic treatment and fixed prostheses, are planned . Periodontal evaluations are scheduled concurrently with orthodontic appointments to monitor the condition as tooth movement occurs. J Bacteriol, 1983 Apr, 154(1), 32 - 40 Differentiation after premature release of intraperiplasmically growing Bdellovibrio bacteriovorous; Ruby EG et al.; Bdellovibrio bacteriovorous attacks and penetrates other gram-negative bacteria, creating a growth chamber termed a bdelloplast . We have found that exposing the bdelloplasts to EDTA, followed by treatment with a lytic enzyme concentrate derived from bdellovirio cultures, prematurely released the intraperiplasmically growing bdellovibrios at any time during their growth cycle . Upon release, the growth-form bdellovibrios terminated any initiated rounds of DNA synthesis and differentiated into motile attack-form cells . The ability of growth-form cells to synthesize DNA appears to depend upon an initiation signal that is not received until about 60 min after attack . Each subsequent round of DNA synthesis by the growing bdellovibrio filaments seems to require an additional initiation signal that is provided by their intraperiplasmic environment . Differentiation included fragmentation into multiple progeny cells to a degree proportional to the extent of intraperiplasmic growth . This differentiation could be performed totally at the expense of cellular reserves . The significance of these data to an understanding of the regulation of differentiation in bdellovibrios is discussed. Lab Invest, 1983 Apr, 48(4), 458 - 70 Acute effects of Escherichia coli endotoxin on the pulmonary microcirculation of anesthetized sheep structure:function relationships; Meyrick B et al.; Infusion of Escherichia coli endotoxin into sheep causes a syndrome analogous to the adult respiratory distress syndrome . Physiologic measurements show an initial phase of marked pulmonary hypertension followed by a phase characterized by the production of large quantities of protein-rich lung lymph . The present study relates the structural changes that occur during endotoxemia to concomitant functional changes . In five anesthetized open-chest sheep, we monitored pulmonary and systemic artery pressure for a 1 hour baseline period and for 4 hours after the start of E . coli endotoxin infusion (1.25 microgram/kg, intravenously) . We also measured cardiac output, arterial blood gases and pH, and number of circulating leukocytes . In addition, we sequentially biopsied random lobes from the lungs of each sheep at baseline and at 15, 30, 60, 120, 180, and 240 minutes after the start of endotoxin . Five control sheep were treated identically except that they received saline instead of endotoxin . By 15 minutes after the start of endotoxin infusion, light microscopy revealed margination and accumulation of leukocytes in the lungs' microcirculation . Counts of the number of peripheral lung granulocytes in biopsy specimens showed a 3-fold increase above baseline by 15 minutes and a 6-fold increase by 4 hours . By electron microscopy, the leukocytes were identified as both granulocytes and lymphocytes, present in approximately equal numbers . Some granulocytes were fragmented, and specific granules were found free in the vessel lumen . By 30 minutes, some leukocytes were migrating into the interstitium . By 60 minutes, interstitial edema was seen, and there was focal endothelial cell damage . Correlation of the structural with the physiologic changes shows that the initial accumulation of leukocytes in the microcirculation occurs when pulmonary hypertension develops . The migration of leukocytes into the interstitium and endothelial cell damage precedes the physiologic changes that we interpret as increased pulmonary vascular permeability . Since gram negative septicemia is a frequent occurrence in the adult respiratory distress syndrome the changes described here may be similar to the alterations that occur early in the development of the syndrome in man. J Bacteriol, 1983 Apr, 154(1), 324 - 9 Absence of siderophore activity in Legionella species grown in iron-deficient media; Reeves MW et al.; Growth of Legionella species in a defined medium deficient in iron did not result in the production of phenolic or hydroxamate siderophores which could be detected by chemical or biological assay methods . Growth of a variety of other gram-negative organisms under the same conditions resulted in the production of both hydroxamate and phenolate siderophores . The iron-deficient medium limited growth of the Legionella species more severely than it did the growth of the other gram-negative organisms . We have concluded that Legionella species do not make the commonly recognized siderophores, probably because they are restricted in their growth to those environments in which inorganic iron is readily available or is supplied in a form bound to an unknown carrier. Nature, 1983 Mar 17-23, 302(5905), 268 - 70 Novel lipid components of the Azotobacter vinelandii cyst membrane; Reusch RN et al.; Phospholipids are ubiquitous components of biological membranes . In the vegetative cells of Azotobacter vinelandii, a Gram-negative free-living aerobic soil bacterium, the membrane lipids are phospholipids with polar head group and fatty acyl compositions similar to those of Escherichia coli . We report here that when A . vinelandii differentiates to form metabolically dormant cysts, the phospholipids in the membranes are replaced by a family of 5-n-alkylresorcinols and 6-n-alkylpyrones . These novel amphiphilic lipids form a unique membrane matrix which may contribute to the physiology and desiccation resistance of the cyst. Burns Incl Therm Inj, 1983 Mar, 9(4), 280 - 3 Burn injuries in Lagos; Sowemimo GO; Eighty-nine cases of burns admitted to the Lagos University Teaching Hospital during an 8-year-period (1968-75) have been studied . The age incidence ranged from 1 day to 54 years . Fifty cases (56.2 per cent) occurred in children below the age of 15 years . Thirty-nine (43.8 per cent) were adults, aged 15 years and above . Sixty-three cases (70.8 per cent) were domestic accidents . There was a mortality rate of 13.5 per cent . There was severe morbidity in the surviving cases, the average admission period in 73 cases being 37 days and the average total healing time in 57 cases being 54 days . The most troublesome late complications were contractures, hypertrophic or keloid scars and failure of repigmentation . Gram-negative bacteria accounted for 64 per cent of the incidence of wound sepsis . Health education has an important role to play in the prevention of burn accidents both in the home and in industry . In particular, it is suggested that cooking above floor level and closer supervision of children should reduce the incidence of domestic burns in younger children, while stricter factory inspection, with rigorous enforcement of industrial safety laws, should reduce the incidence of industrial burn accidents in the working adult population. Infect Immun, 1983 Mar, 39(3), 1385 - 91 Interactions of lipid a and liposome-associated lipid A with Limulus polyphemus amoebocytes; Richardson EC et al.; Lipid A or lipid A fractions and liposomes containing lipid A were tested for the ability to gel Limulus amoebocyte lysates and for effects on intact Limulus amoebocytes . Liposomes having a relatively low concentration of lipid A did not produce coagulation of lysate and were designated as Limulus-negative, but liposomes having a high concentration of lipid A were Limulus-positive . Limulus-negative liposomes had no effect on intact amoebocytes . Limulus-positive liposomes caused a striking transformation in the appearance of amoebocytes in that the cells sent out long filamentous extensions that formed a tangled network of processes between cells . The filamentous projections were similar to those that have been previously observed in the presence of gram-negative bacteria . We conclude that amoebocytes have the ability to recognize Limulus-positive liposomes, but the lack of activation of Limulus lysate or the absence of amoebocyte recognition does not prove the absence of liposomal lipid A . We also found that individual lipid A fractions were heterogeneous in their ability to gel lysate . Of eight fractions tested, one (fraction 1) had no detectable activity above the background, and the seven others had activity that ranged from 10-fold to 10,000-fold above the background . The heterogeneity of lipid A fractions detected in assays with amoebocyte lysate was consistent with the finding of heterogeneity in other functional assays of lipid A fractions. Surgery, 1983 Mar, 93(3), 448 - 54 Immunotherapeutic modification of Escherichia coli--induced experimental peritonitis and bacteremia by glucan; Williams DL et al.; Previous data from our laboratory have demonstrated that glucan administration significantly alters the course of a variety of experimentally induced infectious diseases . In view of the increasing incidence of gram-negative infections, studies were initiated to evaluate the effect of intraperitoneal glucan therapy on Escherichia coli-induced peritonitis and sepsis . Male ICR/Tex mice were injected intraperitoneally with glucan or dextrose on days 5 and 3 prior to intraperitoneal challenge with 1.0 x 10(8) E . coli . Glucan administration resulted in a significant enhancement of survival . Evaluation of the mechanism of protective action of glucan revealed that both the glucan and dextrose control groups showed an equivalent level of blood-borne E . coli at early periods . At 6 hours after challenge the glucan group showed a significant decrease in blood-borne E . coli . In contrast, the dextrose control group demonstrated progressive bacteremia . A significant depression of phagocytic activity occurred in E . coli-infected mice as compared with control mice that were not exposed to the bacterial challenge . The enhancement in phagocytic function observed in glucan-treated control mice was unaltered in E . coli challenged, glucan-treated mice . The possible importance of hyperfunctional macrophages in reduction of mortality from E . coli sepsis was denoted by methyl palmitate-induced reversal of the glucan hyperfunctional state . Methyl palmitate-treated glucan injected mice were not protected against E . coli infection . These data denote that the intraperitoneal administration of glucan significantly modifies the course of E . coli-induced peritonitis and bacteremia due, in part, to glucan-induced enhancement of macrophage function. Presse Med, 1983 Feb 5, 12(5), 287 - 92 {Penetration of netilmicin into respiratory secretions}; Bergogne-Berezin E et al.; Aminoglycosides are often used in the treatment of severe Gram-negative infections, particularly those involving the respiratory tract . The purpose of this study was to evaluate the penetration of netilmicin into bronchial secretions . In 8 tracheostomized patients samples of bronchial secretions were taken at intervals through the tracheostomy cannula after intramuscular injection of netilmicin 2 mg/kg bodyweight . Concentrations of the drug were measured in bronchial secretions and in blood samples taken simultaneously, using the agar diffusion method (Grove and Randall procedure) . The results showed significant penetration of netilmicin, with a mean bronchial peak reaching 3.4 micrograms/ml 1 h after the injection . Elimination was slow, with a mean residual level of 2 micrograms/ml at 6 hours . The bronchial to serum levels ratio was high (greater than 30% at 1 hour) . Individual variations in both serum and bronchial levels were noted; they were unrelated to the underlying pathology . However, changes in bronchial concentrations correlated with changes in serum concentrations, which suggests passive diffusion across the blood-bronchoalveolar barrier . The fluctuations in bronchial levels and the usually low bronchial concentrations of aminoglycosides previously reported are discussed in relation to the methods used. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1983 Feb, 253(4), 476 - 88 Viability and ultrastructure of S . aureus treated with fosfomycin; Schmid EN; Fosfomycin was administered to logarithmic growing cells of S . aureus ATCC 12600 when the number of viable cells (CFU) was about 5 X 10(7) cells/ml . Within 240 min the CFU i) increased for about 70% when 6 micrograms fosfomycin/ml were administered, ii) decreased for about 91% when 25 micrograms glucose-6-phosphate (G-6-P) were administered in addition to 6 micrograms fosfomycin/ml, and iii) decreased for about 98% when 60 micrograms fosfomycin/ml and 25 micrograms G-6-P/ml were added . By means of turbidity measurements mainly a retardation in cell reproduction could be recognized . Contrary to Gram-negative bacteria, the reduction of viable cells for about 90% was not accompanied by a loss of cell integrity in the same range . In addition to the ATCC strain this could be shown for eight further strains of S . aureus. J Bacteriol, 1983 Feb, 153(2), 658 - 64 Purification and properties of Selenomonas ruminantium lysine decarboxylase; Kamio Y et al.; Selenomonas ruminantium, a strictly anaerobic, gram-negative bacterium isolated from sheep rumen, contains lysine decarboxylase (Y . Kamio et al., J . Bacteriol . 145:122-128, 1981) . This report describes the synthesis, purification, and characterization of the enzyme . Lysine decarboxylase was synthesized in cells grown in chemically defined medium without lysine . The enzyme was purified approximately 1,800-fold to electrophoretic homogeneity . The native enzyme of approximate molecular weight 88,000 consisted of two identical subunits, each with a molecular weight of 44,000 . Several properties of the enzyme were determined and compared with those of the lysine decarboxylases from Escherichia coli and Bacterium cadaverisis. Jpn J Exp Med, 1983 Feb, 53(1), 59 - 63 Significance of test for antibody-coated bacteria in biliary tract infection; Iwata K et al.; To detect a biliary tract infection, antibody-coated bacteria (ACB) in bile and duodenal juice was examined in 146 specimens from 111 patients by direct immunofluorescent antibody technique (FA test) . One hundred and forty one of these specimens were also cultured and the results were compared with those of FA test . Organisms were isolated in 77 specimens from 59 patients . Thirty nine (from 31 cases) in these 77 specimens showed ACB . Result of FA test was related to clinical findings such as fever and leucocytosis, but was not to upper abdominal pain, jaundice, liver function test abnormality and the presence of gallstones . Isolates were mainly gram negative rods in ACB positive group (77%) . Classification of immunoglobulin of ACB indicated a predominance of IgG and IgA classes over IgM class. Drug Intell Clin Pharm, 1983 Feb, 17(2), 92 - 9 The management of septic shock; Eskridge RA; Septic shock is a common emergency, most often caused by gram-negative bacteremia . Appearance of gram-negative endotoxin in the systemic circulation sets off a complex reaction involving many physiologic systems . The resultant reduction in microcirculation and subsequent organ dysfunction often lead to death . Early therapy to support the cardiovascular system and rational antibiotic therapy may improve the chance of survival . Careful monitoring of disease and drug effect parameters is essential to therapy. Ann Surg, 1983 Feb, 197(2), 147 - 51 Bacteremia following prosthetic valve replacement; Parker FB Jr et al.; The outcome of patients developing early bacteremia was investigated in 890 patients following cardiac valve replacement over a ten-year period . Thirty-two patients developed bacteremia during the hospital recovery period from valve replacement (3.6%) . Sixty per cent of the organisms involved were gram-negative . Twenty-one of 23 patients had white blood counts greater than 14,000 at the time of positive blood culture . Nine patients died, seven of septic complications . Only two patients developed endocarditis . No patient with bacteremia diagnosed within ten days of surgery developed endocarditis, however two patients developed gram-negative sepsis in this period . The diagnosis and treatment of bacteremia requires continual vigilance if significant mortality and morbidity are to be averted. Dev Biol Stand, 1983, 53, 35 - 40 Cellular immunity in typhoid fever, Legionnaires' disease, amebiasis: role of transfer factor and Levamisole in typhoid fever; Tanphaichitra D; Typhoid fever is an infectious disease commonly seen in the tropics, with multisystem involvement and a high morbidity and mortality rate . Legionnaires' disease: a newly described acute respiratory infection by unusual aerobic gram-negative micro-organisms namely Legionella pneumophila . Cellular immunity: in vitro and in vivo evaluations of cellular immunity using E-rosette formation (E) and 2.4-Dinitrochlorobenzene (D) reaction were made in typhoid fever, amebiasis and Legionnaires' disease . Results will be presented . Three patients with relapsing typhoid fever were given transfer factor and another group with typhoid fever were given Levamisole with sulfamethoxazole-trimethoprim . Up to 90% of the cases receiving immunopotentiating factors/agents improved faster in both general condition, fever and cellular immunity. Eur J Clin Pharmacol, 1983, 24(5), 643 - 7 Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients; Bauer LA et al.; Aminoglycoside pharmacokinetics were determined in 30 normal weight patients and 30 morbidly obese patients (greater than 90% overweight) . All had normal renal function and a gram-negative infection (documented by cultures, fever and elevated white blood cell counts) which was treated only with aminoglycoside antibiotics . The normal weight and morbidly obese patients were matched with respect to the following criterion: age, sex, ideal body weight (IBW), serum creatinine, site of infection, and type of aminoglycoside antibiotic (gentamicin, tobramycin, or amikacin) . The results were similar for all 3 drugs . Average half-life was 2 h for both the morbidly obese and normal weight patients . The mean volumes of distribution and clearances were significantly larger in the morbidly obese (23.3 l and 135.8 ml/min for gentamicin, 29.9 l and 162.4 ml/min for tobramycin, and 26.8 l and 157.3 ml/min for amikacin) than in normal weight patients (17.0 l and 95.9 ml/min for gentamicin, 18.3 l and 101.3 ml/min for tobramycin, and 18.6 l and 99.2 ml/min for amikacin) . As a result of altered aminoglycoside pharmacokinetics, morbidly obese patients required significantly larger mean doses (540 mg/d for gentamicin, 690 mg/d for tobramycin and 1970 mg/d for amikacin) when compared to the normal weight patients (380 mg/d, 420 mg/d and 1420 mg/d, respectively; p less than 0.005) in order to achieve comparable serum concentrations. Eur J Clin Pharmacol, 1983, 24(5), 639 - 42 Influence of age on amikacin pharmacokinetics in patients without renal disease . Comparison with gentamicin and tobramycin; Bauer LA et al.; The influence of age on amikacin pharmacokinetics was examined in 87 patients with normal renal function . All patients had a gram negative infection, were febrile, weighed within 20% of their ideal body weight, did not receive penicillin antibiotics concurrently, had normal hematocrits and had a measured 24 h creatinine clearance greater than 80 ml/min/1.73 m2 . 31 patients were 20-39 years old, 27 patients were between the ages of 40-59 years, and 29 patients were 60-79 years old . These patients were compared to patients in similar previous studies who received gentamicin or tobramycin . No significant differences in clearance, volume of distribution or half-life were found due to age within a single drug group (amikacin, gentamicin, or tobramycin) or among the 3 drug groups . However, a substantial amount of intersubject variability existed in the calculated pharmacokinetic parameters . Patients over 40 years old tended to be underdosed with amikacin and the other 2 aminoglycosides . The average amikacin dose needed to achieve the desired steady-state concentrations was 18.9 mg/kg/day . 52% of the amikacin patients required doses greater than the recommended maximum (15 mg/kg/day) . Since aminoglycoside pharmacokinetics do not change as age increases, doses do not need to be arbitrarily changed in older patients with normal renal function. Microbiol Immunol, 1983, 27(2), 137 - 49 Chemical and biological properties of Lipopolysaccharides from symbiotic luminous bacteria from several luminous marine animals; Kuwae T et al.; The chemical and biological properties of lipopolysaccharides (LPS) in five strains of symbiotic luminous bacteria isolated from four species of luminous marine fishes, Coelorhynchus kishinouyei (CK-1), Chlorophthalmus albatrossis (CA-1), Ventrifossa garmani (VG-1), and Acropoma japonicum (AJ-1b), as well as from a luminous squid, Doryteuthis kensaki (DK-1) were examined . The LPS isolated from these symbiotic luminous bacteria were characterized by the absence of 2-keto-3-deoxyoctonate, known to be a basic component of the usual gram-negative bacterial LPS . All LPS from these symbiotic luminous bacteria upon electrophoresis in sodium dodecylsulfate polyacrylamide gel exhibited one or two clear main bands with high mobility, and one or two obscure minor bands with low mobility when stained with periodate-Schiff reagent . LPS from CA-1 and VG-1 exhibited similar electrophoretic patterns, whereas the electrophoretic patterns of the LPS from CK-1, AJ-1b, and DK-1 were easily distinguishable from each other . All these LPS also had similarly potent and diverse biological activities in regard to their adjuvanticity, immunosuppression, polyclonal effect, B-cell mitogenicity, and activation of the phagocytic function of macrophages. Intensive Care Med, 1983, 9(3), 117 - 22 Endotoxaemia in septic shock: clinical and post mortem correlations; McCartney AC et al.; The Limulus amoebocyte lysate assay was used as one of a series of laboratory and clinical investigations on a group of 31 patients suffering from septic shock in order to assess the clinical significance of this assay for the detection of circulating endotoxin in clinical gram-negative sepsis . Four patients with cardiogenic shock served as controls . Endotoxin was detected in the bloodstream of all patients with septic shock during the 24 h following referral and was not detected in the control patients . Eventual clinical recovery was associated with the disappearance of endotoxin from the peripheral blood . Blood cultures were unhelpful as a prognostic indicator in these critically ill patients . A quantitative assay of endotoxin in blood may allow a more precise relationship with the clinical manifestations of major sepsis. Circ Shock, 1983, 10(3), 205 - 13 Interaction of oxygen free radicals and cardiac sarcoplasmic reticulum: proposed role in the pathogenesis of endotoxin shock; Manson NH et al.; An initial event in gram-negative bacteremia is activation of the complement cascade with production of C5a . C5a, in turn, acts as a chemotactic stimulus for leukocytic aggregation and, in conjunction with bacterial products, stimulates the release of oxygen free radicals from leukocytes . We have hypothesized that these oxygen free radicals (.O2-, superoxide anion; .OH, hydroxyl radical; H2O2, hydrogen peroxide) contribute to the characteristic myocardial dysfunction of endotoxin shock, Isolated canine cardiac sarcoplasmic reticulum (SR) was used as a subcellular determinant of mechanical function . SR was incubated for 20 min at 37 degrees C in the presence of phorbol myristate acetate activated leukocytes (A-L) and calcium uptake and Ca2+-adenosine triphosphatase (ATPase) activities were measured . Activated leukocytes significantly depressed SR Ca2+ uptake rates (C = 1.12 +/- 0.05 mumol CA2+/mg-min; A-L = 0.73 +/- 0.05) . The addition of catalase (CAT; 10 micrograms/ml) or superoxide dismutase (SOD: 10 micrograms/ml) plus CAT reversed the inhibition of SR Ca2+ uptake . SOD further depressed SR Ca2+ uptake (+SOD = 0.55 +/0 0.04 mumol Ca2+/mg-min) . Mannitol had no effect . SR ATPase activity was inhibited with A-L (C = 1.41 +/- 0.04 mumol Pi/mg-min; A-L = 0.84 +/- 0.09) . Neither mannitol, nor SOD nor CAT alone had any effect on the depression of SR ATPase activity . SOD plus CAT reversed the ATPase depression induced by A-L . It is concluded that phorbol myristate acetate activated leukocytes via free radical-mediated mechanisms can directly affect function and activity of the excitation-contraction coupling system of cardiac muscle . Free radical scavengers identified hydrogen peroxide as a major mediator of depressed Ca2+ uptake rates . In conjunction with the superoxide anion, hydrogen peroxide contributes to the depressed ATPase activity. J Bacteriol, 1983 Jan, 153(1), 335 - 9 Contributing carbohydrate catabolic pathways in Cyclobacterium marinus; Raj HD et al.; The primary and secondary pathways of carbohydrate metabolism were determined in a nonfermentative gram-negative ring-forming marine bacterium, Cyclobacterium marinus, by radiorespirometric studies . Whereas glucose is oxidized mainly via the Embden-Meyerhof pathway, gluconate is catabolized mainly via the Entner-Doudoroff pathway, both in conjunction with the tricarboxylic acid cycle as a secondary pathway and with some participation of the pentose phosphate pathway . The operation of these contributing catabolic pathways in this unique marine bacterium was substantiated by assaying the activities of the key enzymes specific to each pathway. Pharmacology, 1983, 26(2), 100 - 9 Endotoxin and low protein diet induced depression of the rat hepatic drug metabolism; Sonawane BR et al.; The effects of the combination of low protein diet feeding and endotoxin (E . coli, serotype 026 B6) upon rat hepatic microsomal mixed function oxidase (MFO) enzymes were investigated . Short-term (7 days) feeding of low protein (8%) diet and acute (single dose) exposure to endotoxin resulted in an additive decrease in MFO enzymes . However, chronic (7 days) endotoxin exposure did not depress liver microsomal MFO enzyme activities except for aniline hydroxylase . Long-term (105 days) feeding of the low protein diet and acute endotoxin exposure further decreased aminopyrine N-demethylase and benzo(a)pyrene hydroxylase activities compared to individual treatments . These results suggest that, under these experimental conditions, the two host-related environmental factors interact and potentiate a decrease in rat hepatic microsomal drug metabolizing enzymes . These observations may be of clinical relevance to explain altered drug reactions in patients with gram-negative infections and endotoxemia under the conditions of malnutrition. Acta Otorhinolaryngol Belg, 1983, 37(6), 842 - 7 {Capnocytophaga sputigena in sinusitis}; Rysselaere M et al.; The genus Capnocytophaga was reported in the literature for the first time in 1979 . Capnocytophaga are fusiform gram-negative, slowly growing bacteria that require a high pCO2 . They belong to the normal buccal flora and they are reported as pathogens in infections of the periodontal region with progressive periodontitis and in septicaemia in patients with immunodeficiencies and buccal ulcerations . The present paper is the first to report Capnocytophaga sputigena as a pathogen in sinusitis . The patient presented a chronic maxillary sinusitis as a complication of a complicated tooth-extraction . The proof for pathogenicity was demonstrated by the presence of Capnocytophaga in the polymorphonucleocytes of the sinusal secretions and by the fact that the bacteria were not easily eradicated despite multiple sinusal irrigations. Ther Drug Monit, 1983, 5(3), 263 - 7 Clinical use of a one-compartment model for determining netilmicin pharmacokinetic parameters and dosage recommendations; Rotschafer JC et al.; To determine netilmicin pharmacokinetic parameters and to evaluate the use of a one-compartment pharmacokinetic model, 32 patients receiving netilmicin for suspected gram-negative sepsis were enrolled in our study protocol . Dose and dosage interval for each patient were determined by one-compartment pharmacokinetic analysis of six postinfusion netilmicin serum samples (0.16, 0.33, 0.5, 1, 2, and 3 h) measured by radioimmunoassay . In patients with a normal serum creatinine, mean (+/- SD) half-life and distribution volume were 1.9 +/- 1.1 h and 0.2 +/- 0.8 L/kg, respectively . The average daily dose and mean days of therapy were 5.1 +/- 1.9 mg/kg/day for 7.3 +/- 2.8 days . Serum creatinine changes of greater than 0.5 mg% occurred in 2 of 28 (7%) patients . Substantial variability in half-life and distribution volume occurred in patients . Initial dosages of 5-7 mg/kg/day in divided dosages seem appropriate for adult patients with normal renal function . Monitoring of serum levels and adjustment of dose and dosage interval are necessary to maintain therapeutic antibiotic concentrations . As with other aminoglycosides, the one-compartment pharmacokinetic model proved to be an acceptable method for measuring netilmicin pharmacokinetic parameters and individualizing therapy. Arzneimittelforschung, 1983, 33(9), 1236 - 9 Comparative stability of first, second and third generation cephalosporins and N-formimidoyl thienamycin against gram-negative beta-lactamases; Vuye A; The susceptibility of cefamandole, cefoxitin, cefotaxime, moxalactam, and N-formimidoyl thienamycin to different gram-negative beta-lactamases was determined by the UV-spectrophotometric method and two microbiological techniques in comparison with that of first generation cephalosporins . In general, the microbiological methods were more sensitive than the UV-assay . Cefamandole was rapidly hydrolyzed by all enzymes tested . The beta-lactamase stability of the other compounds was significantly higher, but clearly proved to be not absolute . With the aid of the "double-disc technique", the most sensitive of the methods used, cefotaxime was shown to be susceptible to all enzymes, whereas cefoxitin, moxalactam and N-formimidoyl thienamycin showed some susceptibility to 6, 3 and 7 enzymes, respectively . Moxalactam appeared to be the most stable of the compounds tested. J Antimicrob Chemother, 1983 Jan, 11 Suppl, 147 - 52 Cefotetan and beta-lactamases . I . An analysis of the affinity of cefotetan for beta-lactamases; Labia R et al.; Cefotetan is a new cephamycin whose interaction with a group of eight beta-lactamases isolated from various Gram-negative bacteria has been studied . Using computerized micro-acidimetry, cefotetan was found to be resistant to the hydrolytic action of various enzymes, including those which actively hydrolyse cefotaxime . Despite this resistance to hydrolysis, cefotetan nevertheless shows a certain affinity for these enzymes . These data were submitted to two statistical procedures consisting of correspondence analysis and ascending hierarchical classification . These techniques revealed that cefotetan behaves very much like cefoxitin (another cephamycin) and also like cefotaxime and moxalactam. Mol Gen Genet, 1983, 192(3), 436 - 8 Homology in the transfer origins of broad host range IncP plasmids: definition of two subgroups of P plasmids; Yakobson E et al.; The transfer systems of broad host range IncP plasmids are increasingly used in the genetic analysis and manipulation of many gram-negative bacteria . We have examined the structural and functional relatedness of the transfer origins of ten different broad host range plasmids which belong to the IncP incompatibility group . The data reported here, together with our results on relatedness of the replication segments of these plasmids, demonstrate that the genomes of all IncP plasmids share extensive sequence homology in the regions specifying the transfer origin and replication functions . The homology results reveal the existence of two subclasses among IncP plasmids, designated here as IncP alpha and IncP beta . Furthermore, a functional analysis of the transfer origins of IncP plasmids suggests strongly that the DNA-nicking relaxation complex (Guiney and Helinski 1979) is required for plasmid transfer during conjugation. Arch Oral Biol, 1983, 28(2), 133 - 43 Architecture of minor salivary gland duct/lymphoid follicle associations and possible antigen-recognition sites in the monkey Macaca fascicularis; Schroeder HE et al.; In Macaca fascicularis, lymphoid follicles with germinal centres related to minor salivary gland ducts are frequently found in the mucosa of lips, cheeks and the soft palate . Three semi-three-dimensional reconstructions, each based on 3 sets of 230-300 serial Epon sections, of such duct/follicle-assemblies (2 in the soft palate and 1 in the lip) and electron microscopic observations were made . These revealed that (1) these structures were about 0.05-0.1 mm3 in size, (2) they were found preferentially at sites where small interlobular ducts fused to form a pelvis-like basin from which blind duct portions protruded into the surrounding lymphoid tissue and (3) they often included a germinal centre which partly embraced blind ducts . The walls of such blind ducts were heavily infiltrated by lymphocytes and in part blast-forming T-cells . Portions of the walls of interlobular and main secretory ducts, passing directly or peripherally through follicles, were also infiltrated with lymphocytes . The duct lumen within the follicles contained clusters of Gram-negative bacteria, probably rods . Based on these findings, it is argued that gland duct/follicle assemblies represent physiological entities, either formed and re-formed temporarily or of long-standing nature, which may provide the locus (i.e . tonsillar microcrypt-like pouches) and the structural matrix necessary for local antigen recognition . The antigens (bacteria, macromolecules in salivary fluid, etc.) might enter the above structure by way of the secretory ducts . Such matrices may also exist in man. Methods Enzymol, 1983, 97, 3 - 11 Genetic analysis of protein export in Escherichia coli; Beckwith J et al.; Genetic studies on the secretion process in gram-negative bacteria have made considerable progress . Within the near future, such studies should lead to a detailed understanding of the important features of signal sequences and how they function . The cloning of the structural gene for an enzyme that cleaves signal sequences from precursors of secreted proteins will allow the genetic characterization of this locus and its function . Finally, the isolation and characterization of mutants that affect components of the cell's secretory apparatus are also under way . These mutants permit the detection of genes and their products that are involved in secretion . A combination of the genetic approaches and in vitro studies should lead to a picture of the details of passage of proteins through a membrane. Adv Nephrol Necker Hosp, 1983, 12, 253 - 75 Comparative nephrotoxicity of four aminoglycosides: biochemical and ultrastructural modifications of lysosomes; Fillastre JP et al.; In 1982, aminoglycosides still are widely prescribed and considered indispensable for the treatment of severe gram-negative infections . All the aminoglycosides are nephrotoxic, but both experimental works and clinical investigations indicate that they do not all have the same nephrotoxic potential . Within the renal tubular cell in several animal species and in man, the initial and the most extensive changes are those that occur in the lysosomes . We compared the effects of gentamicin, tobramycin, netilmicin and, amikacin on (a) lysosomal structural latency, (b) the activity of several enzymes, either lysosomal or those contained in the proximal tubular cell brush border, and (c) the accumulation of myeloid bodies in the lysosomes . From our results, it appears that gentamicin is the aminoglycoside that induces the greatest number of lysosomal changes whereas amikacin induces the least, with the effects of netilmicin and tobramycin quite close to those of amikacin . Other works comparing the nephrotoxicity of aminoglycosides reveal the same high nephrotoxic potential of gentamicin. J Trauma, 1983 Jan, 23(1), 19 - 24 Regulation of granulopoiesis following severe thermal injury; Peterson V et al.; Neutropenia often accompanies septicemia in burned patients . This paradox suggests a defect in the regulation of granulopoiesis . Colony stimulating factor (CSF) produced by the monocyte-macrophage system is an important regulator of granulocyte production . We followed serial serum CSF levels and peripheral blood leukocyte differential counts in 22 patients with greater than 30% burns . Six patients (mean burn, 58%) developed Gram-negative septicemia and died (Group I) . Sixteen patients (mean burn, 38%) had no fatal septicemias (Group II) . Nonsurvivors had initially low levels of CSF and developed persistent monocytopenia . Survivors, in contrast, had prompt rises in CSF and developed monocytosis . The presence of monocytopenia and low CSF levels in Group I suggests an abnormality in the stimulatory arm regulating granulopoiesis . Such a defect may play a role in the development of fatal septicemia following severe thermal injury. Rev Argent Microbiol, 1983, 15(3), 157 - 62 {Azomonas agilis in the surface water of the environs of Buenos Aires}; Alvarez R; In 1941, it was reported the presence of Azomonas agilis in rivers near Buenos Aires City . To our knowledge no other study has been carried out since then, so that the object of this paper was to investigate some characteristics of this organism and i